Ionis Pharmaceuticals (IONS) 10-K 28 Feb 18 2017 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2017	Feb. 20, 2018	Jun. 30, 2017
Document and Entity Information [Abstract]
Entity Registrant Name	IONIS PHARMACEUTICALS INC
Entity Central Index Key	874,015
Document Type	10-K
Document Period End Date	Dec. 31, 2017
Amendment Flag	false
Current Fiscal Year End Date	--12-31
Entity Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Filer Category	Large Accelerated Filer
Entity Public Float			$ 5,158,628,572
Entity Common Stock, Shares Outstanding		125,403,219
Document Fiscal Year Focus	2,017
Document Fiscal Period Focus	FY

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Current assets:
Cash and cash equivalents	$ 129,630	$ 84,685
Short-term investments	893,085	580,538
Contracts receivable	62,955	108,043
Inventories	9,982	7,489
Other current assets	72,332	17,177
Total current assets	1,167,984	797,932
Property, plant and equipment, net	121,907	92,845
Patents, net	22,004	20,365
Deposits and other assets	10,129	1,325
Total assets	1,322,024	912,467
Current liabilities:
Accounts payable	24,886	21,120
Accrued compensation	25,151	24,186
Accrued liabilities	66,618	36,013
Current portion of long-term obligations	1,621	1,185
Current portion of deferred contract revenue	106,465	51,280
Total current liabilities	224,741	133,784
Long-term deferred contract revenue	72,708	91,198
1 percent convertible senior notes	533,111	500,511
Long-term obligations, less current portion	12,974	15,050
Long-term financing liability for leased facility	0	72,359
Long-term mortgage debt	59,771	0
Total liabilities	903,305	812,902
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 124,976,373 and 121,636,273 shares issued and outstanding at December 31, 2017 and December 31, 2016, respectively	125	122
Additional paid-in capital	1,549,904	1,311,229
Accumulated other comprehensive income (loss)	(31,759)	(30,358)
Accumulated deficit	(1,187,398)	(1,181,428)
Total Ionis stockholders' equity	330,872	99,565
Noncontrolling interest in Akcea Therapeutics, Inc.	87,847	0
Total stockholders' equity	418,719	99,565
Total liabilities and stockholders' equity	$ 1,322,024	$ 912,467

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2017	Dec. 31, 2016
Stockholders' equity:
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	124,976,373	121,636,273
Common stock, shares outstanding (in shares)	124,976,373	121,636,273
1 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	2.75%	2.75%

CONSOLIDATED STATEMENTS OF OPER

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Commercial revenue:
SPINRAZA royalties	$ 112,540	$ 883	$ 0
Licensing and other royalty revenue	9,519	19,839	2,343
Total commercial revenue	122,059	20,722	2,343
Research and development revenue under collaborative agreements	385,607	325,898	281,360
Total revenue	507,666	346,620	283,703
Expenses:
Research, development and patent	374,644	344,320	322,292
Selling, general and administrative	108,488	48,616	37,173
Total operating expenses	483,132	392,936	359,465
Income (loss) from operations	24,534	(46,316)	(75,762)
Other income (expense):
Investment income	7,805	5,472	4,377
Interest expense	(44,752)	(38,795)	(36,732)
Gain on investment in Regulus Therapeutics Inc.	374	0	20,211
Loss on extinguishment of financing liability for leased facility	(7,689)	0	0
Loss on early retirement of debt	0	(3,983)	0
Other expenses	(3,548)	0	0
Loss before income tax benefit (expense)	(23,276)	(83,622)	(87,906)
Income tax benefit (expense)	5,980	(2,934)	(372)
Net loss	(17,296)	(86,556)	(88,278)
Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.	11,326	0	0
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (5,970)	$ (86,556)	$ (88,278)
Basic net income (loss) per share (in dollars per share)	$ 0.08	$ (0.72)	$ (0.74)
Shares used in computing basic net income (loss) per share (in shares)	124,016	120,933	119,719
Diluted net income (loss) per share (in dollars per share)	$ 0.08	$ (0.72)	$ (0.74)
Shares used in computing diluted net income (loss) per share (in shares)	126,098	120,933	119,719

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (17,296)	$ (86,556)	$ (88,278)
Unrealized losses on investments, net of tax	(960)	(17,219)	(33,101)
Reclassification adjustment for realized (gains) losses included in net loss	(374)	447	(20,211)
Currency translation adjustment	(67)	(21)	0
Comprehensive loss	(18,697)	(103,349)	(141,590)
Comprehensive loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.	11,421	0	0
Comprehensive loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (7,276)	$ (103,349)	$ (141,590)

CONSOLIDATED STATEMENTS OF STOC

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) shares in Thousands, $ in Thousands	Common Stock [Member]	Additional Paid In Capital [Member]	Accumulated Other Comprehensive Income (Loss) [Member]	Accumulated Deficit [Member]	Total Ionis Stockholders' Equity [Member]	Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]	Total
Balance at Dec. 31, 2014	$ 118	$ 1,224,509	$ 39,747	$ (1,006,594)	$ 257,780	$ 0	$ 257,780
Balance (in shares) at Dec. 31, 2014	118,443
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(88,278)	(88,278)	0	(88,278)
Change in unrealized gains (losses), net of tax	0	0	(53,312)	0	(53,312)	0	(53,312)
Foreign currency translation							0
Issuance of common stock in connection with employee stock plans	$ 2	24,888	0	0	24,890	0	24,890
Issuance of common stock in connection with employee stock plans (in shares)	1,908
Stock-based compensation expense	$ 0	59,314	0	0	59,314	0	59,314
Noncontrolling interest in Akcea Therapetuics, Inc.							0
Excess tax benefits from stock-based compensation awards	0	396	0	0	396	0	396
Balance at Dec. 31, 2015	$ 120	1,309,107	(13,565)	(1,094,872)	200,790	0	200,790
Balance (in shares) at Dec. 31, 2015	120,351
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(86,556)	(86,556)	0	(86,556)
Change in unrealized gains (losses), net of tax	0	0	(16,772)	0	(16,772)	0	(16,772)
Foreign currency translation	0	0	(21)	0	(21)	0	(21)
Issuance of common stock in connection with employee stock plans	$ 2	13,706	0	0	13,708	0	13,708
Issuance of common stock in connection with employee stock plans (in shares)	1,285
2 3/4 percent convertible senior notes redemption, equity portion	$ 0	(128,888)	0	0	(128,888)	0	(128,888)
1 percent convertible senior notes, equity portion, net of issuance costs	0	43,335	0	0	43,335	0	43,335
Stock-based compensation expense	0	72,108	0	0	72,108	0	72,108
Noncontrolling interest in Akcea Therapetuics, Inc.							0
Excess tax benefits from stock-based compensation awards	0	1,861	0	0	1,861	0	1,861
Balance at Dec. 31, 2016	$ 122	1,311,229	(30,358)	(1,181,428)	99,565	0	99,565
Balance (in shares) at Dec. 31, 2016	121,636
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(5,970)	(5,970)	0	(5,970)
Change in unrealized gains (losses), net of tax	0	0	(1,334)	0	(1,334)	0	(1,334)
Foreign currency translation	0	0	(67)	0	(67)	0	(67)
Novartis stock purchase	$ 2	71,737	0	0	71,739	0	71,739
Novartis stock purchase (in shares)	1,631
Issuance of common stock in connection with employee stock plans	$ 1	22,931	0	0	22,932	0	22,932
Issuance of common stock in connection with employee stock plans (in shares)	1,709
Stock-based compensation expense	$ 0	85,975	0	0	85,975	0	85,975
Issuance of Akcea common stock in conjunction with intial public offering	$ 0	157,270	0	0	157,270	0	157,270
Issuance of Akcea common stock in conjunction with intial public offering (in shares)	0
Noncontrolling interest in Akcea Therapeutics, Inc. in conjunction with initial public offering	$ 0	(90,351)	0	0	(90,351)	90,381	30
Noncontrolling interest in Akcea Therapetuics, Inc.	0	(8,887)	0	0	(8,887)	(2,534)	(11,421)
Balance at Dec. 31, 2017	$ 125	$ 1,549,904	$ (31,759)	$ (1,187,398)	$ 330,872	$ 87,847	$ 418,719
Balance (in shares) at Dec. 31, 2017	124,976

CONSOLIDATED STATEMENTS OF STO7

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Parenthetical)	Dec. 31, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Dec. 31, 2015
2 3/4 Percent Convertible Senior Notes [Member]
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Interest rate on convertible senior notes	2.75%	2.75%	2.75%	2.75%	2.75%
1 Percent Convertible Senior Notes [Member]
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%	1.00%

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Operating activities:
Net loss	$ (17,296)	$ (86,556)	$ (88,278)
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Depreciation	6,708	7,481	6,984
Amortization of patents	1,641	1,552	1,381
Amortization of licenses	0	0	1,873
Amortization of premium on investments, net	6,752	6,813	7,812
Amortization of debt issuance costs	1,616	1,225	1,133
Amortization of senior convertible notes discount	30,920	23,890	22,075
Amortization of long-term financing liability for leased facility	3,659	6,693	6,665
Stock-based compensation expense	85,975	72,108	59,314
Gain on investment in Regulus Therapeutics, Inc.	(374)	0	(20,211)
Loss on extinguishment of financing liability for leased facility	7,689	0	0
Loss on early retirement of debt	0	3,983	0
Non-cash losses related to patents, licensing, property, plant and equipment and strategic investments	3,302	2,297	1,881
Changes in operating assets and liabilities:
Contracts receivable	45,088	(96,687)	(7,453)
Inventories	(2,493)	(590)	(609)
Other current and long-term assets	(58,367)	1,603	(4,394)
Long-term income tax receivable	(9,114)	0	0
Accounts payable	1,784	(10,677)	9,211
Income taxes	435	1,069	0
Accrued compensation	965	8,121	3,763
Accrued liabilities and deferred rent	28,564	4,720	(2,140)
Deferred contract revenue	36,695	(59,150)	22,118
Net cash (used in) provided by operating activities	174,149	(112,105)	21,125
Investing activities:
Purchases of short-term investments	(877,810)	(300,912)	(493,467)
Proceeds from the sale of short-term investments	557,369	364,572	419,584
Purchases of property, plant and equipment	(34,764)	(7,107)	(7,692)
Acquisition of licenses and other assets, net	(3,093)	(4,421)	(4,056)
Purchase of strategic investments	(2,500)	0	0
Proceeds from the sale of Regulus Therapeutics, Inc.	2,507	4,467	25,527
Proceeds from the sale of strategic investments	0	0	52
Net cash (used in) provided by investing activities	(358,291)	56,599	(60,052)
Financing activities:
Proceeds from equity awards	22,931	13,417	24,888
Proceeds from the issuance of common stock in Akcea Therapeutics, Inc. from its initial public offering, net of underwriters' discount	110,438	0	0
Proceeds from building mortgage debt, net of issuance costs	59,750	0	0
Proceeds from the issuance of common stock to Novartis	71,737	0	0
Proceeds from borrowing on line of credit facility	0	4,000	8,500
Proceeds from sale of Akcea Therapeutics, Inc. common stock to Novartis in a private placement	50,000	0	0
Offering costs paid	(2,037)	(818)	0
Payment to settle financing liability for leased facility	(80,133)	0	0
Excess tax benefits from stock-based compensation awards	0	1,861	396
Principal payments on debt and capital lease obligations	(3,599)	(7,066)	(9,058)
Net cash provided by financing activities	229,087	11,394	24,726
Net increase (decrease) in cash and cash equivalents	44,945	(44,112)	(14,201)
Cash and cash equivalents at beginning of year	84,685	128,797	142,998
Cash and cash equivalents at end of year	129,630	84,685	128,797
Supplemental disclosures of cash flow information:
Interest paid	8,035	7,313	6,800
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	1,983	3,439	1,162
1 percent convertible senior notes principal issued related to our December 2016 debt exchange	0	185,450	0
2 3/4 percent convertible senior notes principal extinguished related to our December 2016 debt exchange	0	61,099	0
Unpaid deferred offering costs	$ 0	$ 291	$ 0

CONSOLIDATED STATEMENTS OF CAS9

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical)	Dec. 31, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Dec. 31, 2015
1 Percent Convertible Senior Notes [Member]
Supplemental disclosures of non-cash investing and financing activities:
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Supplemental disclosures of non-cash investing and financing activities:
Interest rate on convertible senior notes	2.75%	2.75%	2.75%	2.75%	2.75%

Organization and Significant Ac

Organization and Significant Accounting Policies	12 Months Ended
	Dec. 31, 2017
Organization and Significant Accounting Policies [Abstract]
Organization and Significant Accounting Policies	1. Organization and Significant Accounting Policies Basis of Presentation In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. ("we", "us" or "our") and the consolidated results of our majority-owned affiliate, Akcea Therapeutics, Inc., which we formed in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, and therefore beginning in July 2017, we no longer own 100 percent of Akcea. As of July 19, 2017, the closing of the IPO, we owned approximately 68 percent of Akcea. Refer to the noncontrolling interest in Akcea section in this note for further information related to our accounting for our investment in Akcea. Organization and Business Activity We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic drugs using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc. Basic and Diluted Net Income (Loss) per Share We compute basic net income (loss) per share by dividing the net income (loss) attributable to our common stockholders by our weighted average number of common shares outstanding during the period. The calculation of total net income (loss) attributable to our common stockholders for 2017 considered our net income for Ionis on a stand-alone basis plus our share of Akcea’s net loss. To calculate the portion of Akcea’s net loss attributable to our ownership, we multiplied Akcea’s loss per share by the weighted average shares we owned in Akcea during the year. Prior to Akcea’s IPO, we owned Akcea Series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea’s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. For 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the year. The two-class method required Akcea to calculate its net income (loss) per share six percent total net income available to Ionis common stockholders for the calculation of net income per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations. We calculated our basic net income per share for 2017 as follows (in thousands, except per share amounts): Year Ended December 31, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Loss Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 20,669 $ (2.82 ) $ (58,332 ) Preferred shares 15,748 (1.55 ) (24,344 ) Akcea’s net loss attributable to our ownership $ (82,676 ) Ionis’ stand-alone net income 92,336 Net income available to Ionis common stockholders $ 9,661 Weighted average shares outstanding 124,016 Basic net income per share $ 0.08 For 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. Diluted common equivalent shares for 2017 consisted of the following (in thousands except per share amounts): Year Ended December 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Net income available to Ionis common stockholders $ 9,661 124,016 $ 0.08 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,619 Shares issuable upon restricted stock award issuance — 459 Shares issuable related to our ESPP — 4 Income available to Ionis common stockholders, plus assumed conversions $ 9,661 126,098 $ 0.08 For 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. As we incurred a net loss for 2016 and 2015, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:    2¾ percent convertible senior notes;  Dilutive stock options;  Unvested restricted stock units; and  Employee Stock Purchase Plan, or ESPP. Revenue Recognition We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet. Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue We often enter into agreements to license and sell our technology on an exclusive or non-exclusive basis in exchange for upfront fees, license fees, milestone payments and/or royalties. We generally recognize as revenue immediately license payments with stand-alone value when the license is delivered and we are reasonably assured of collecting the resulting receivable. We recognize royalty revenue in the period in which the counterparty sells the related product, unless we are unable to obtain information to estimate the royalty. For example, in 2017 we recorded SPINRAZA royalty revenue of $112.5 million. Research and development revenue under collaborative agreements Arrangements with multiple deliverables Our collaboration agreements typically contain multiple elements, or deliverables, including technology licenses or options to obtain technology licenses, research and development services, and in certain cases manufacturing services, and we allocate the consideration to each unit of accounting based on the relative selling price of each deliverable. Amendments to agreements From time to time we amend our collaboration agreements. For these agreements, before we identify our deliverables and allocate consideration to each unit of accounting, we must determine if the amendment should be accounted for as a separate agreement, or if the amendment and any undelivered elements for the original agreement should be accounted for as a single new arrangement. For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI Rx Rx Rx Rx Rx Rx Under the 2017 amendment, there was a substantial increase in the consideration we are eligible to receive and a significant change in the deliverables we will provide to Bayer. As a result, we concluded that the amendment should be evaluated with the undelivered elements of the original agreement as a single new arrangement. Therefore, we evaluated our original and 2017 amended agreements with Bayer together to determine our deliverables. We concluded that the 2017 amendment did not impact the items we already delivered to Bayer. Identifying deliverables and units of accounting We evaluate the deliverables in our collaboration agreements to determine whether they meet the criteria to be accounted for as separate units of accounting or whether they should be combined with other deliverables and accounted for as a single unit of accounting. When the delivered items in an arrangement have "stand-alone value" to our customer, we account for the deliverables as separate units of accounting. Delivered items have stand-alone value if they are sold separately by any vendor or the customer could resell the delivered items on a stand-alone basis. For example, our 2017 amended agreement with Bayer has multiple elements. We evaluated the deliverables in this arrangement when we entered into the 2017 amended agreement and determined that certain of the deliverables have stand-alone value. Below is a list of the three units of accounting under our 2017 amended agreement: ● The exclusive license we granted to Bayer to develop and commercialize IONIS-FXI-L Rx ● The development services we agreed to perform for IONIS-FXI-L Rx Rx ● The remaining undelivered IONIS-FXI Rx We determined that each of these three units of accounting have stand-alone value. The license we granted to Bayer has stand-alone value because it gives Bayer the exclusive right to develop IONIS-FXI-L Rx Measurement and allocation of arrangement consideration Our collaborations may provide for various types of payments to us including upfront payments, funding of research and development, milestone payments, licensing fees and royalties on product sales. We initially allocate the amount of consideration that is fixed and determinable at the time the agreement is entered into and exclude contingent consideration. We allocate the consideration to each unit of accounting based on the relative selling price of each deliverable. We use the following hierarchy of values to estimate the selling price of each deliverable: (i) vendor-specific objective evidence of fair value; (ii) third-party evidence of selling price; and (iii) best estimate of selling price, or BESP. BESP reflects our best estimate of what the selling price would be if we regularly sold the deliverable on a stand-alone basis. We recognize the revenue allocated to each unit of accounting as we deliver the related goods or services. If we determine that we should treat certain deliverables as a single unit of accounting, then we recognize the revenue ratably over our estimated period of performance. We determined that the allocable arrangement consideration for the Bayer 2017 amended agreement was $76.3 million, comprised of the $75 million we received as part of the amendment and the remaining amount of the $100 million upfront payment we had not yet recognized into revenue, related to the undelivered API. We allocated the consideration based on the relative BESP of each unit of accounting. We engaged a third party, independent valuation specialist to assist us with determining BESP. We estimated the selling price of the license granted for IONIS-FXI-L Rx Rx ● Estimated future product sales; ● Estimated royalties on future product sales; ● Contractual milestone payments; ● Expenses we expect to incur; ● Income taxes; and ● An appropriate discount rate. We estimated the selling price of the development services by using our internal estimates of the cost to perform the specific services and estimates of expected cash outflows to third parties for services and supplies over the expected period that we will perform the development services. The significant inputs we used to determine the selling price of the development services included: ● The number of internal hours we will spend performing these services; ● The estimated cost of work we will perform; ● The estimated cost of work that we will contract with third parties to perform; and ● The estimated cost of API we will use. For purposes of determining BESP of the services we will perform and the API we will deliver in our 2017 amended Bayer transaction, accounting guidance required us to include a markup for a reasonable profit margin. Based on the units of accounting under the 2017 amended agreement, we allocated the $76.3 million of allocable consideration as follows: ● $64.9 million to the IONIS-FXI-L Rx ● $11.0 million for development services for IONIS-FXI-L Rx Rx ● $0.4 IONIS-FXI Rx Assuming a constant selling price for the other elements in the arrangement, if there was an assumed 10 percent increase or decrease in the estimated selling price of the IONIS-FXI-L Rx Rx Timing of revenue recognition We recognize revenue as we deliver each item under the arrangement and the related revenue is realizable and earned. For example, we recognized revenue for the exclusive license we granted Bayer for IONIS-FXI-L Rx The following are the periods over which we are recognizing revenue for each of our units of accounting under our 2017 amended Bayer agreement: ● We recognized the portion of the consideration attributed to the IONIS-FXI-L Rx ● We are recognizing the amount attributed to the development services for IONIS-FXI-L Rx Rx ● We are recognizing the amount attributed to the remaining API supply as we deliver it to Bayer. Multiple agreements From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether they should be accounted for individually as distinct arrangements or whether the separate agreements are, in substance, a single multiple element arrangement. We evaluate whether the negotiations are conducted jointly as part of a single negotiation, whether the deliverables are interrelated or interdependent, whether fees in one arrangement are tied to performance in another arrangement, and whether elements in one arrangement are essential to another arrangement. Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that they are, in effect, part of a single arrangement. For example, in the first quarter of 2017, we and Akcea entered into two separate agreements with Novartis at the same time: a collaboration agreement and a stock purchase agreement, or SPA. Akcea entered into a collaboration agreement with Novartis to develop and commercialize AKCEA-APO(a)-L Rx and AKCEA-APOCIII-L Rx . Under the collaboration agreement, Akcea received a $75 million upfront payment. For each drug, Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the Food and Drug Administration, or FDA, and delivering API. Under the collaboration agreement, Novartis has an exclusive option to develop and commercialize AKCEA-APO(a)-L Rx and AKCEA-APOCIII-L Rx . If Novartis exercises an option for one of these drugs, Novartis will pay Akcea a million license fee and will assume all further global development, regulatory and commercialization activities and costs for the licensed drug. Akcea is also eligible to receive a development milestone payment, milestone payments if Novartis achieves pre-specified regulatory milestones, commercial milestones and tiered royalties on net sales from each drug under the collaboration. Under the SPA, Novartis purchased 1.6 million shares of Ionis’ common stock for $100 million in the first quarter of 2017 and paid a premium over the weighted average trading price at the time of purchase. Additionally, the SPA required Novartis to purchase $50 million of Akcea’s common stock in a concurrent private placement with Akcea’s IPO in July 2017. We evaluated the Novartis agreements to determine whether we should treat the agreements separately or as a single arrangement. We considered that the agreements were negotiated concurrently and in contemplation of one another. Additionally, the same individuals were involved in the negotiations of both agreements. Based on these facts and circumstances, we concluded that we should treat both agreements as a single arrangement and evaluate the provisions of the agreements on a combined basis. Refer to Note 6, Collaborative Arrangements and Licensing Agreements Milestone payments Our collaborations often include contractual milestones, which typically relate to the achievement of pre-specified development, regulatory and/ or commercialization events. These three categories of milestone events reflect the three stages of the life-cycle of our drugs, which we describe in more detail in the following paragraphs. Prior to the first stage in the life-cycle of our drugs, we perform a significant amount of work using our proprietary antisense technology to design chemical compounds that interact with specific genes that are good targets for drug discovery. From these research efforts, we hope to identify a development candidate. The designation of a development candidate is the start of the development stage, which is the first stage in the life-cycle of our drugs. A development candidate is a chemical compound that has demonstrated the necessary safety and efficacy in preclinical animal studies to warrant further study in humans. During the first step of the development stage, we or our partners study our drugs in Investigational New Drug, or IND,-enabling studies, which are animal studies intended to support an IND application and/or the foreign equivalent. An approved IND allows us or our partners to study our development candidate in humans. If the regulatory agency approves the IND, we or our partners initiate a Phase 1 clinical trial in which we typically enroll a small number of healthy volunteers to ensure the development candidate is safe for use in patients. If we or our partners determine that a development candidate is safe based on the Phase 1 data, we or our partners initiate Phase 2 studies that are generally larger studies in patients with the primary intent of determining the preliminary efficacy and safety of the development candidate. The final step in the development stage is Phase 3 studies to gather the necessary safety and efficacy data to request marketing authorization from the FDA and/or foreign equivalents. Phase 3 studies typically involve larger numbers of patients and can take up to several years to complete. If the data gathered during the Phase 3 trials demonstrates acceptable safety and efficacy results, we or our partner will submit an application to the FDA and/or its foreign equivalents for marketing authorization. This stage of the drug’s life-cycle is the regulatory stage. If the FDA or a foreign equivalent grants marketing authorization for a drug, it moves into the commercialization stage. During this stage we or our partner will market and sell the drug to patients. Although our partner may ultimately be responsible for marketing and selling a partnered drug, our efforts to discover and develop a drug that is safe, effective and reliable contributes significantly to our partner’s ability to successfully sell the drug. The FDA and its foreign equivalents have the authority to impose significant restrictions on an approved drug through the product label and on advertising, promotional and distribution activities. Therefore, our efforts designing and executing the necessary animal and human studies are critical to obtaining claims in the product label from the regulatory agencies that would allow us or our partner to successfully commercialize our drug. Further, the patent protection afforded our drugs as a result of our initial patent applications and related prosecution activities in the United States and foreign jurisdictions are critical to our partner’s ability to sell our drugs without competition from generic drugs. The potential sales volume of an approved drug is dependent on several factors including the size of the patient population, market penetration of the drug, and the price charged for the drug. Generally, the milestone events contained in our partnership agreements coincide with the progression of our drugs from development, to marketing authorization and then to commercialization. The process of successfully discovering a new development candidate, having it approved and ultimately selling it for a profit is highly uncertain. As such, the milestone payments we may earn from our partners involve a significant degree of risk to achieve. Therefore, as a drug progresses through the stages of its life-cycle, the value of the drug generally increases. Development milestones in our partnerships may include the following types of events: ● Designation of a development candidate. Following the designation of a development candidate, IND-enabling animal studies for a new development candidate generally take 12 to 18 months to complete. ● Initiation of a Phase 1 clinical trial. Generally, Phase 1 clinical trials take one to two years to complete. ● Initiation or completion of a Phase 2 clinical trial. Generally, Phase 2 clinical trials take one to three years to complete. ● Initiation or completion of a Phase 3 clinical trial. Generally, Phase 3 clinical trials take two to four years to complete. Regulatory milestones in our partnerships may include the following types of events: ● Filing of regulatory applications for marketing authorization such as a New Drug Application, or NDA, in the United States or a Marketing Authorization Application, or MAA, in Europe. Generally, it takes six to twelve months to prepare and submit regulatory filings. ● Obtaining marketing authorization in a major market, such as the United States, Europe or Japan. Generally it takes one to two years after an application is submitted to obtain authorization from the applicable regulatory agency. Commercialization milestones in our partnerships may include the following types of events: ● First commercial sale in a particular market, such as in the United States or Europe. ● Product sales in excess of a pre-specified threshold, such as annual sales exceeding $1 billion. The amount of time to achieve this type of milestone depends on several factors including but not limited to the dollar amount of the threshold, the pricing of the product and the pace at which customers begin using the product. We assess whether a substantive milestone exists at the inception of our agreements. When a substantive milestone is achieved, we recognize revenue related to the milestone payment immediately. For our licensing and collaboration agreements in which we are involved in the discovery and/or development of the related drug or provide the partner with access to new technologies we discover, we have determined that the majority of future development, regulatory and commercialization milestones are substantive. For example, we consider most of the milestones associated with our strategic alliance with Biogen substantive because we are using our antisense drug discovery platform to discover and develop new drugs against targets for neurological diseases. In evaluating if a milestone is substantive we consider whether: ● Substantive uncertainty exists as to the achievement of the milestone event at the inception of the arrangement; ● The achievement of the milestone involves substantive effort and can only be achieved based in whole or in part on our performance or the occurrence of a specific outcome resulting from our performance; ● The amount of the milestone payment appears reasonable either in relation to the effort expended or to the enhancement of the value of the delivered items; ● There is no future performance required to earn the milestone; and ● The consideration is reasonable relative to all deliverables and payment terms in the arrangement. If any of these conditions are not met, we do not consider the milestone to be substantive and we defer recognition of the milestone payment and recognize it as revenue over our estimated period of performance, if any. Further information about our collaborative arrangements can be found in Note 6, Collaborative Arrangements and Licensing Agreements Option to license In several of our collaboration agreements, we provide our partner with an option to obtain a license to one or more of our drugs. When we have a multiple element arrangement that includes an option to obtain a license, we evaluate if the option is a deliverable at the inception of the arrangement. We do not consider the option to be a deliverable if we conclude that it is substantive and not priced at a significant and incremental discount. We consider an option substantive if, at the inception of the arrangement, we are at risk as to whether our collaboration partner will choose to exercise its option to obtain the license. In those circumstances, we do not include the associated license fee in the allocable consideration at the inception of the agreement. Rather, we account for the license fee when our partner exercises its option. For example, during 2017, we earned license fee revenue when three of our partners, Bayer, Janssen and Roche, exercised their options to license three of our drugs, which under the respective agreements we concluded to be substantive options at inception. As a result, in 2017 we recognized the related revenue immediately in research and development revenue under collaborative agreements on our statement of operations as these amounts relate to drugs in development under research and development collaboration arrangements. Research, Development and Patent Expenses Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2017, 2016 and 2015, research and development expenses were $372.5 million, $340.4 million and $319.5 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2017, 2016 and 2015, research and development costs of approximately $59.5 million, $187.1 million and $161.7 million, respectively, were related to our partner agreements. We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.1 years at December 31, 2017. The cost of our patents capitalized on our consolidated balance sheet at December 31, 2017 and 2016 was $30.8 million and $28.8 million, respectively. Accumulated amortization related to patents was $8.8 million and $8.4 million at December 31, 2017 and 2016, respectively. Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following: Years Ending December 31, Amortization (in millions) 2018 $ 1.6 2019 $ 1.4 2020 $ 1.3 2021 $ 1.3 2022 $ 1.2 We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2017, 2016 and 2015, patent expenses were $2.1 million, $3.9 million and $2.8 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $0.4 million, $2.3 million and $1.1 million, respectively. Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): December 31, 2017 2016 Clinical expenses $ 16,347 $ 23,428 In-licensing expenses 33,790 6,430 Other miscellaneous expenses 16,481 6,155 Total accrued liabilities $ 66,618 $ 36,013 Noncontrolling Interest in Akcea Therapeutics, Inc. In July 2017, Akcea completed an IPO. Akcea raised $193.8 million of aggregate gross proceeds from the IPO, including $50.0 million from a private placement by Novartis. Akcea’s net proceeds were $182.4 million. As part of Akcea’s IPO, we invested $25.0 million. In conjunction with the IPO, the shares of Akcea’s series A convertible preferred stock we owned converted into shares of Akcea’s common stock. Additionally, the amount outstanding under Akcea’s line of credit with us converted into shares of Akcea’s common stock. Prior to Akcea’s IPO in July 2017, we owned 100 percent of Akcea’s stock and consolidated 100 percent of Akcea’s results in our financial statements. In connection with Akcea’s IPO, shares of Akcea’s common stock were sold to third parties. We owned approximately 68 percent of Akcea after the IPO and at December 31, 2017. The shares third parties own represent an interest in Akcea’s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our consolidated financial statements. The noncontrolling interest attributable to other owners of Akcea’s common stock is reflected in a separate line on the statement of operations and a separate line within stockholders’ equity in our consolidated financial statements. In addition, we recorded a noncontrolling interest adjustment to account for the stock options that Akcea grants for its common stock, which if exercised, will dilute our ownership in Akcea. This adjustment was reflected as a reclassification within stockholders’ equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized from inception through the IPO. Going forward, each period we will reclassify Akcea’s stock-based compensation expense in a similar fashion. Concentration of Credit Risk Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody’s, Standard & Poor’s, or S&P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity. Cash, Cash Equivalents and Short-Term Investments We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term investments as “available-for-sale” and carry them at fair market value based upon prices for identical or similar items on the last day of the fiscal period. We record unrealized gains and losses as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold. We have equity investments of less than 20 percent in privately and publicly held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2017, we held equity investments in one publicly held company, Antisense Therapeutics Limited, or ATL. Furthermore, we held cost method investments in five companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Kastle Therapeutics, Seventh Sense Biosystems and Suzhou Ribo Life Science Co., Ltd. We account for our equity investments in publicly held companies at fair value and record unrealized gains and losses related to temporary increases and decreases in the stock as a separate component of comprehensive income (loss). We account for our equity investments in privately held companies under the cost method of accounting because we own less than 20 percent and do not have significant influence over their operations. Realization of our equity position in these private companies is usually uncertain. When realization of our investment is uncertain, we record a full valuation allowance. In determining if and when a decrease in market value below our cost in our equity positions is temporary or other-than-temporary, we examine historical trends in the stock price, the financial condition of the company, near term prospects of the company and our current need for cash. If we determine that a decline in value in either a public or private investment is other-than-temporary, we recognize an impairment loss in the period in which the other-than-temporary decline occurs. Inventory Valuation We capitalize the costs of raw materials that we purchase for use in producing our drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs th

Investments

Investments	12 Months Ended
	Dec. 31, 2017
Investments [Abstract]
Investments	2. Investments As of December 31, 2017, we had primarily invested our excess cash in debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody’s, Standard & Poor’s, or S&P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity. The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2017: One year or less 71 % After one year but within two years 23 % After two years but within three and one half years 6 % Total 100 % As illustrated above, at December 31, 2017, 94 percent of our available-for-sale securities had a maturity of less than two years. All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. At December 31, 2017, we had an ownership interest of less than 20 percent During The following is a summary of our investments (in thousands): Gross Unrealized Estimated December 31, 2017 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (2) $ 500,599 $ 2 $ (752 ) $ 499,849 Debt securities issued by U.S. government agencies 83,926 — (212 ) 83,714 Debt securities issued by the U.S. Treasury 29,428 — (17 ) 29,411 Debt securities issued by states of the U.S. and political subdivisions of the states (2) 29,240 4 (122 ) 29,122 Total securities with a maturity of one year or less 643,193 6 (1,103 ) 642,096 Corporate debt securities 148,663 8 (1,059 ) 147,612 Debt securities issued by U.S. government agencies 52,779 — (168 ) 52,611 Debt securities issued by the U.S. Treasury 1,409 — (2 ) 1,407 Debt securities issued by states of the U.S. and political subdivisions of the states 65,550 — (740 ) 64,810 Total securities with a maturity of more than one year 268,401 8 (1,969 ) 266,440 Total available-for-sale securities $ 911,594 $ 14 $ (3,072 ) $ 908,536 Gross Unrealized Estimated December 31, 2016 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities $ 195,087 $ 25 $ (161 ) $ 194,951 Debt securities issued by U.S. government agencies 26,548 — (10 ) 26,538 Debt securities issued by the U.S. Treasury 29,298 2 (14 ) 29,286 Debt securities issued by states of the U.S. and political subdivisions of the states (2) 72,775 2 (134 ) 72,643 Total securities with a maturity of one year or less 323,708 29 (319 ) 323,418 Corporate debt securities 202,408 36 (1,174 ) 201,270 Debt securities issued by U.S. government agencies 28,807 1 (167 ) 28,641 Debt securities issued by states of the U.S. and political subdivisions of the states 36,816 1 (349 ) 36,468 Total securities with a maturity of more than one year 268,031 38 (1,690 ) 266,379 Total available-for-sale securities $ 591,739 $ 67 $ (2,009 ) $ 589,797 Equity securities: Regulus Therapeutics Inc. $ 2,133 $ 281 $ — $ 2,414 Total equity securities $ 2,133 $ 281 $ — $ 2,414 Total available-for-sale and equity securities $ 593,872 $ 348 $ (2,009 ) $ 592,211 (1) Our available-for-sale securities are held at amortized cost. (2) Includes investments classified as cash equivalents on our consolidated balance sheet. Investments we consider to be temporarily impaired at December 31, 2017 are as follows (in thousands): Less than 12 Months of Temporary Impairment More than 12 Months of Temporary Impairment Total Temporary Impairment Number of Investments Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Corporate debt securities 476 $ 551,446 $ (1,236 ) $ 74,987 $ (575 ) $ 626,433 $ (1,811 ) Debt securities issued by U.S. government agencies 45 107,788 (262 ) 27,538 (118 ) 135,326 (380 ) Debt securities issued by the U.S. Treasury 7 30,818 (19 ) — — 30,818 (19 ) Debt securities issued by states of the U.S. and political subdivisions of the states 60 62,519 (545 ) 24,572 (317 ) 87,091 (862 ) Total temporarily impaired securities 588 $ 752,571 $ (2,062 ) $ 127,097 $ (1,010 ) $ 879,668 $ (3,072 ) We believe that the decline in value of our debt securities is temporary and primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold these securities to maturity. Therefore, we anticipate full recovery of our debt securities’ amortized cost basis at maturity.

Long-Term Obligations and Commi

Long-Term Obligations and Commitments	12 Months Ended
	Dec. 31, 2017
Long-Term Obligations and Commitments [Abstract]
Long-Term Obligations and Commitments	3. Long-Term Obligations and Commitments The carrying value of our long-term obligations was as follows (in thousands): December 31, 2017 2016 1 percent convertible senior notes $ 533,111 $ 500,511 Long-term mortgage debt 59,771 — Long-term financing liability for leased facility — 72,359 Principal balance of fixed rate note with Morgan Stanley 12,500 12,500 Leases and other obligations 2,095 3,735 Total $ 607,477 $ 589,105 Less: current portion (1,621 ) (1,185 ) Total Long-Term Obligations $ 605,856 $ 587,920 Convertible Notes In November 2014, we completed a $500 million offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. We raised $487 million of proceeds, net of issuance costs. We used a substantial portion of the net proceeds from the issuance of the 1 percent convertible senior notes to repurchase $140 million in principal of our 2¾ percent convertible senior notes at a price of $441.9 million, including accrued interest. As a result, the new principal balance of the 2¾ percent notes was $61.2 million. In December 2016, we issued an additional $185.5 million of 1 percent convertible senior notes in exchange for the redemption of $61.1 million of our 2¾ percent convertible senior notes. As a result of the debt exchange we completed in December 2016, we recorded a $4.0 million non-cash loss on early retirement of debt, reflecting the early retirement of the majority of our remaining 2¾ percent convertible notes in December 2016. At December 31, 2017, we had a nominal amount of our 2¾ percent convertible senior notes outstanding. At December 31, 2017 we had the following 1 percent convertible senior notes outstanding (amounts in millions except price per share data): 1 Percent Convertible Senior Notes Outstanding balance $ 685.5 Original issue date ($500 million of principal) November 2014 Additional issue date ($185.5 million of principal) December 2016 Maturity date November 2021 Interest rate 1 percent Conversion price per share $ 66.81 Total shares of common stock subject to conversion 10.3 Interest is payable semi-annually in arrears on May 15 and November 15 of each year for the 1 percent notes. The 1 percent notes are convertible at the option of the note holders prior to July 1, 2021 only under certain conditions. On or after July 1, 2021, the notes are initially convertible into approximately 10.3 million shares of common stock at a conversion price of approximately $66.81 per share. We will settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the 1 percent notes prior to maturity, and no sinking fund is provided for them. If we undergo a fundamental change, holders may require us to purchase for cash all or any portion of their 1 percent notes at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest to, but excluding, the fundamental change purchase date. We account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt’s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes: 1 Percent Convertible Senior Notes Issued in November 2014 1 Percent Convertible Senior Notes Issued in December 2016 Nonconvertible debt borrowing rate 7.4 percent 6.8 percent Effective interest rate 7.8 percent 7.2 percent Amortization period of debt discount 7 years 5 years Interest expense for the year ended December 31, 2017, 2016 and 2015 included $32.5 million, $25.1 million and $23.2 million, respectively, of non-cash interest expense related to the amortization of the debt discount and debt issuance costs for our convertible notes. The following table summarizes information about the equity and liability components of our outstanding 1 percent convertible notes (in thousands). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement: December 31, 2017 2016 Fair value of outstanding notes $ 727,420 $ 700,969 Principal amount of convertible notes outstanding $ 685,450 $ 685,450 Unamortized portion of debt discount $ 144,112 $ 175,699 Long-term debt $ 533,111 $ 500,511 Carrying value of equity component $ 219,011 $ 219,011 Financing Arrangements Line of Credit Arrangement In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley. We amended the credit agreement in February 2016 to increase the amount available for us to borrow. Under the amended credit agreement, we can borrow up to a maximum of $30 million of revolving credit for general working capital purposes. Under the credit agreement interest is payable monthly in arrears on the outstanding principal at a borrowing rate based on our option of: (i) a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum; (ii) a fixed rate equal to LIBOR plus 1.25 percent for a period of one, two, three, four, six, or twelve months as elected by us; or (iii) a fixed rate equal to the LIBOR swap rate during the period of the loan. Additionally, after June 1, 2016, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of December 31, 2017, we had $12.5 million in outstanding borrowings under the credit facility with a 2.31 percent fixed interest rate and a maturity date of September 2019, which we used to fund our capital equipment needs and is consistent with our historical practice to finance these costs. The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement. Research and Development and Manufacturing Facilities In July 2017, we purchased the building that houses our primary R&D facility for $79.4 million. As a result of the purchase, we extinguished the financing liability we had previously recorded on our balance sheet. The difference between the purchase price of the facility and the carrying value of our financing liability at the time of the purchase was $7.7 million. We recognized this amount as a non-cash loss on extinguishment of financing liability for leased facility in our consolidated results of operations in the third quarter of 2017. We also purchased our manufacturing facility in July 2017 for $14.0 million. We previously accounted for the lease on this facility as an operating lease. We capitalized the purchase price of the building as a fixed asset in the third quarter of 2017. We financed the purchase of our primary R&D facility and our manufacturing facility, with mortgage debt of $51.3 million and $9.1 million, respectively. Our primary R&D facility mortgage has an interest rate of 3.88 percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages we are only required to make interest payments. Both mortgages mature in August 2027. Maturity Schedules Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2017 are as follows (in thousands): 2018 $ 9,617 2019 22,082 2020 9,330 2021 694,774 2022 2,809 Thereafter 71,603 Subtotal $ 810,215 Less: current portion (53 ) Less: fixed and determinable interest (51,465 ) Less: unamortized portion of debt discount (144,791 ) Plus: Deferred rent 165 Total $ 614,071 Operating Leases We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two five-year periods. Additionally, Akcea leases office space in a building in Cambridge, Massachusetts. A portion of Akcea's operating lease expires in July 2018, with the other portion expiring in April 2020. We also lease office equipment under non-cancelable operating leases with terms through January 2021. Annual future minimum payments under operating leases as of December 31, 2017 are as follows (in thousands): Operating Leases 2018 $ 864 2019 636 2020 477 2021 147 Total minimum payments $ 2,124 Rent expense was $1.7 million for the year ended December 31, 2017. Rent expense was $2.0 million for each of the years ended December 31, 2016 and 2015. We recognized rent expense on a straight line basis over the lease term for the lease on our manufacturing facility, the lease on our building adjacent to our manufacturing facility and Akcea’s office space, which resulted in a deferred rent balance of $0.1 million and $2.1 million at December 31, 2017 and 2016, respectively.

Stockholders' Equity

Stockholders' Equity	12 Months Ended
	Dec. 31, 2017
Stockholders' Equity [Abstract]
Stockholders' Equity	4. Stockholders’ Equity Preferred Stock We are authorized to issue up to 15,000,000 shares of “blank check” Preferred Stock. As of December 31, 2017, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2017. Common Stock At December 31, 2017 and 2016, we had 300,000,000 shares of common stock authorized, of which 124,976,373 and 121,636,273 were issued and outstanding, respectively. As of December 31, 2017, total common shares reserved for future issuance were 18,419,727. During the years ended December 31, 2017, 2016 and 2015, we issued 1,706,000, 1,285,000 and 1,908,000 shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net proceeds from these transactions of $22.9 million, $13.7 million and $24.9 million in 2017, 2016 and 2015, respectively. Stock Plans 1989 Stock Option Plan In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for the issuance of non-qualified and incentive stock options for the purchase of up to 20,000,000 shares of common stock to our employees, directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the repricing. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2017, a total of 1,603,403 options were outstanding, of which options to purchase 1,553,252 shares were exercisable, and 31,878 shares were available for future grant under the 1989 Plan. 2011 Equity Incentive Plan In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015 and in May 2017, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan to increase the total number of shares reserved for issuance. We increased the shares available under our 2011 Equity Incentive Plan from 5,500,000 to 11,000,000 in June 2015 and from 11,000,000 to 16,000,000 in May 2017. The plan expires in June 2021. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only options and restricted stock unit awards to our employees, directors and consultants. Under the 2011 Plan, stock options cannot vest in a period of less than two years and restricted stock unit awards cannot vest in a period of less than three years. We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2017, a total of 7,120,643 options were outstanding, of which 3,201,717 were exercisable, 821,771 restricted stock unit awards were outstanding, and 6,822,389 shares were available for future grant under the 2011 Plan. Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in control. In the absence of such provisions, no such acceleration will occur. The stock options and restricted stock unit awards we issue to our chief executive officer and issued to B. Lynne Parshall in her former role as chief operating officer will accelerate upon a change of control, as defined in the 2011 Plan. Corporate Transactions and Change in Control under 2011 Plan In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following actions with respect to outstanding stock awards under the 2011 Plan:  arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);  arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or acquiring corporation (or its parent company);  accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;  arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;  cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and  arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise. 2002 Non-Employee Directors’ Stock Option Plan In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee Directors’ Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors’ Stock Option Plan (the 2002 Plan). In June 2015, after receiving approval from our stockholders, we amended our 2002 Non-Employee Directors Stock Option Plan to increase the total number of shares reserved for issuance. We increased the shares available under our 2002 Non-Employee Directors Stock Option Plan from 1,200,000 to 2,000,000. Options under this plan expire ten years from the date of grant. Options granted become exercisable in four equal annual installments beginning one year after the date of grant. At December 31, 2017, a total of 672,750 options were outstanding, of which 427,125 were exercisable, 40,933 restricted stock unit awards were outstanding, and 635,867 shares were available for future grant under the 2002 Plan. Employee Stock Purchase Plan In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years, we reserved an additional 150,000 shares of common stock for the ESPP resulting in a total of 3,524,596 shares authorized under the plan as of December 31, 2017. The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee’s compensation) at the lower of 85 percent of fair market value at the beginning of the purchase period or the end of each six-month purchase period. Under the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2017, employees purchased and we issued to employees 67,481 shares under the ESPP at a weighted average price of $27.51 per share. At December 31, 2017, there were 668,232 shares available for purchase under the ESPP. Stock Option Activity The following table summarizes the stock option activity for the year ended December 31, 2017 (in thousands, except per share and contractual life data): Number of Shares Weighted Average Exercise Price Per Share Average Remaining Contractual Term (Years) Aggregate Intrinsic Value Outstanding at December 31, 2016 9,178 $ 40.48 Granted 3,274 $ 47.76 Exercised (1,345 ) $ 15.74 Cancelled/forfeited/expired (1,710 ) $ 51.71 Outstanding at December 31, 2017 9,397 $ 44.52 4.42 $ 92,288 Exercisable at December 31, 2017 5,182 $ 39.10 3.33 $ 80,167 The weighted-average estimated fair values of options granted were $25.42, $26.72 and $27.44 for the years ended December 31, 2017, 2016 and 2015, respectively. The total intrinsic value of options exercised during the years ended December 31, 2017, 2016 and 2015 were $49.5 million, $28.0 million and $84.7 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $21.2 million, $12.6 million and $23.6 million for the years ended December 31, 2017, 2016 and 2015, respectively. For the year ended December 31, 2017, the weighted-average fair value of options exercised was $52.53. As of December 31, 2017, total unrecognized compensation cost related to non-vested stock-based compensation plans was $75.2 million. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures. We expect to recognize this cost over a weighted average period of 1.2 years. Restricted Stock Unit Activity The following table summarizes the RSU activity for the year ended December 31, 2017 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2016 778 $ 47.68 Granted 420 $ 48.88 Vested (296 ) $ 43.79 Cancelled/forfeited (39 ) $ 48.90 Non-vested at December 31, 2017 863 $ 49.55 For the years ended December 31, 2017, 2016 and 2015, the weighted-average grant date fair value of RSUs granted was $48.88, $41.79 and $65.69 per RSU, respectively. As of December 31, 2017, total unrecognized compensation cost related to RSUs was $16.5 million. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures. We expect to recognize this cost over a weighted average period of 1.2 years. Stock-based Compensation Expense and Valuation Information The following table summarizes stock-based compensation expense for the years ended December 31, 2017, 2016 and 2015 (in thousands), which was allocated as follows and includes $17.5 million, $10.1 million and $6.5 million of stock-based compensation expense for Akcea employees in 2017, 2016 and 2015, respectively: Years Ended December 31, 2017 2016 2015 Research, development and patent $ 64,521 $ 55,099 $ 43,638 Selling, general and administrative 21,454 17,009 15,676 Total $ 85,975 $ 72,108 $ 59,314 Determining Fair Value Valuation. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on actual and projected exercise patterns. We recognize compensation expense for stock options granted, RSUs, and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period. For the years ended December 31, 2017, 2016 and 2015, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: December 31, 2017 2016 2015 Risk-free interest rate 1.8 % 1.5 % 1.5 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 65.9 % 58.7 % 53.8 % Expected life 4.5 years 4.5 years 4.5 years Board of Director Stock Options: December 31, 2017 2016 2015 Risk-free interest rate 2.2 % 1.3 % 2.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 61.2 % 53.1 % 52.2 % Expected life 6.6 years 6.5 years 6.9 years ESPP: December 31, 2017 2016 2015 Risk-free interest rate 0.8 % 0.4 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 59.9 % 86.4 % 51.7 % Expected life 6 months 6 months 6 months Risk-Free Interest Rate. Dividend Yield. Volatility. Expected Life. Forfeitures.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2017
Income Taxes [Abstract]
Income Taxes	5. Income Taxes Loss before income tax (benefit) expense is comprised of (in thousands): Years Ended December 31, 2017 2016 2015 United States $ (11,802 ) $ (83,622 ) $ (87,906 ) Foreign (11,474 ) — — Loss before income tax (benefit) expense $ (23,276 ) $ (83,622 ) $ (87,906 ) Our income tax (benefit) expense was as follows (in thousands): Years Ended December 31, 2017 2016 2015 Current: Federal $ (7,460 ) $ 1,067 $ 379 State 1,246 1,867 (7 ) Foreign 234 — — Total current income tax (benefit) expense (5,980 ) 2,934 372 Deferred: Federal — — — State — — — Total deferred income tax (benefit) expense — — — Total income tax (benefit) expense $ (5,980 ) $ 2,934 $ 372 The reconciliation between our effective tax rate on loss from continuing operations and the statutory U.S. tax rate is as follows (in thousands): Years Ended December 31, 2017 2016 2015 Pre-tax loss $ (23,276 ) $ (83,622 ) $ (87,906 ) Statutory rate (8,147 ) 35.0 % (29,268 ) 35.0 % (30,767 ) 35.0 % State income tax net of federal benefit 722 (3.1 )% (276 ) 0.3 % 1 0.0 % Foreign 4,299 (18.3 )% — 0.0 % — 0.0 % Net change in valuation allowance (76,409 ) 328.3 % 55,927 (66.9 )% 69,499 (79.1 )% Net operating loss expiration 3,987 (17.0 )% — 0.0 % — 0.0 % Tax credits (32,769 ) 140.8 % (26,954 ) 32.2 % (41,284 ) 47.0 % Deferred tax true-up 4,848 (20.6 )% 2,591 (3.1 )% 1,496 (1.7 )% Tax Cuts and Jobs Act 107,323 (461.1 )% — — 0.0 % Nondeductible items 4,123 (17.9 )% 1,149 (1.4 )% 1,055 (1.2 )% Akcea deconsolidation adjustment at IPO 469 (2.0 )% — 0.0 % — 0.0 % Excess stock-based compensation (14,337 ) 61.0 % — 0.0 % — 0.0 % Other (89 ) 0.6 % (235 ) 0.4 % 372 (0.4 )% Effective rate $ (5,980 ) 25.7 % $ 2,934 (3.5 )% $ 372 (0.4 )% Significant components of our deferred tax assets and liabilities as of December 31, 2017 and 2016 are as follows (in thousands): Years Ended December 31, 2017 2016 Deferred Tax Assets: Net operating loss carryovers $ 153,575 $ 194,372 R&D credits 240,290 193,845 Deferred revenue 42,055 54,203 Stock-based compensation 40,090 48,209 Intangible and capital assets 672 — Other 12,164 26,228 Total deferred tax assets $ 488,846 $ 516,857 Deferred Tax Liabilities: Convertible debt $ (32,391 ) $ (62,669 ) Intangible and capital assets — (2,030 ) Net deferred tax asset $ 456,455 $ 452,158 Valuation allowance (456,455 ) (452,158 ) Total net deferred tax assets and liabilities $ — $ — In accordance with the SEC guidance, we provided our best estimate of the impact of the Tax Act in the period ended December 31, 2017 based on our understanding of the Tax Act and guidance available as of the date of this filing. We remeasured our existing net U.S. deferred tax assets using the enacted rate and other known existing changes to the tax code. This resulted in a total decrease in these assets by $107.3 million which was fully offset by a decrease in the valuation allowance. In addition, we recorded a $7.7 million tax benefit related to our cumulative prior year AMT tax credit carryovers, which are now reflected as part of a long-term income tax receivable because under the Tax Act, AMT credits are refundable from 2018 through 2021.We also assessed the impact of the deemed repatriation of foreign earnings and the impact of the limitation on tax deductions for executive compensation under the applicable section of the tax code. We have recognized provisional amounts in our financial statements for these and other items. The ultimate impact may differ materially from these provisional amounts due to, among other things, additional analysis, changes in our interpretations and assumptions, additional regulatory guidance that may be issued, and other actions we may take as a result of the Tax Act. At December 31, 2017, we had federal and California tax net operating loss carryforwards of approximately $561.1 million and $887.1 million, respectively. Our federal tax loss carryforwards will begin to expire in 2024, unless we use them before then. Our California loss carryforwards continued to expire in 2017. At December 31, 2017 we also had federal and California research and development tax credit carryforwards of approximately $233.3 million and $56.2 million, respectively. Our Federal research and development tax credit carryforwards begin to expire in 2018. Our California research and development tax credit carryforwards are available indefinitely. Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized. We have incurred historical financial statement losses since inception and as a result we have a full valuation allowance recorded against our net deferred tax assets. We regularly assess the future realization of our net deferred tax assets and will reduce the valuation allowance in any such period in which we determine that all, or a portion, of our deferred tax assets are more-likely-than-not to be realized. Our valuation allowance increased by $4.3 million from December 31, 2016 to December 31, 2017. The net increase relates to increases from current year activity, offset by a decrease related to the remeasurement of our net deferred tax assets as required by the Tax Act. Historically, we recognized excess tax benefits associated with stock-based compensation to stockholders' equity only when realized. We followed the with-and-without approach excluding any indirect effects of the excess tax deductions to determine when we should realize excess tax benefits relating to stock-based compensation. Under this approach, we did not realize our excess tax benefits related to stock-based compensation until after we utilize all our other tax benefits available to us. During the year ended December 31, 2016, we realized $1.9 million of such excess tax benefits, and accordingly, we recorded a corresponding credit to additional paid-in capital. In March 2016, the FASB issued amended guidance to simplify certain aspects of accounting for stock-based payments. We adopted this amended guidance on January 1, 2017. Under the amended guidance, we recognize all excess tax benefits and tax deficiencies as income tax expense or benefit in the period in which they occur. We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position. The following table summarizes our gross unrecognized tax benefits (in thousands): Years Ended December 31, 2017 2016 2015 Beginning balance of unrecognized tax benefits $ 66,999 $ 51,257 $ 27,365 Settlement of prior period tax positions — (4,033 ) — Increase for prior period tax positions 1,520 7,928 215 Increase for current period tax positions 9,495 11,847 23,677 Ending balance of unrecognized tax benefits $ 78,014 $ 66,999 $ 51,257 Included in the balance of unrecognized tax benefits at December 31, 2017, is $63.6 million that could impact our effective tax rate, if recognized. None of the unrecognized tax benefits currently impact our effective tax rate due to the full valuation allowance we have recorded against our deferred tax assets. We do not foresee any material changes to our gross unrecognized tax benefits within the next twelve months. We recognize interest and/or penalties related to income tax matters in income tax expense. We did not recognize any accrued interest and penalties related to gross unrecognized tax benefits during the year ended December 31, 2017. Due to the carryforward of unutilized net operating losses and research and development credits, we are subject to taxation in the United States and various state jurisdictions. Our tax years for 1998 through 2016 are subject to examination by the U.S. tax authorities and our tax years for 2003 through 2016 are subject to examination by the California tax authorities. We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	12 Months Ended
	Dec. 31, 2017
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	6. Collaborative Arrangements and Licensing Agreements Strategic Partnerships AstraZeneca Cardiometabolic and Renal Diseases Collaboration In July 2015, we and AstraZeneca formed a strategic collaboration to discover and develop antisense therapies for treating cardiovascular and metabolic diseases primarily focused on targets in the kidney and renal diseases. As part of the agreement, we granted AstraZeneca an exclusive license to IONIS-AZ4-2.5-L Rx , a drug we designed to treat cardiovascular disease and our first LIgand-Conjugated Antisense, or LICA, technology. We also granted AstraZeneca the option to license a drug for each additional target advanced under this research collaboration. In February 2018, AstraZeneca licensed a second drug under our collaboration, IONIS-AZ5-2.5 Rx , a drug we designed to . AstraZeneca is responsible for all further global development, regulatory and commercialization activities and costs for IONIS-AZ4-2.5-L Rx and IONIS-AZ5-2.5 Rx and any other future drug development candidates AstraZeneca accepts. Under the terms of the agreement, we received a $65 million upfront payment. Since this agreement has multiple elements, we evaluated the deliverables in this arrangement and determined that none of the deliverables have stand-alone value because of the early stage of research for this collaboration. Therefore, we concluded there is one unit of accounting and we are amortizing the $65 million upfront payment through August 2021. We are eligible to receive license fees and substantive milestone payments of up to more than $4 billion as drugs under this collaboration advance, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. From inception through December 2017, we have received $93 million in upfront fees, milestone payments, and other payments under this cardiometabolic and renal diseases collaboration, including a $25 million milestone payment we received when we moved the first development candidate into preclinical development, IONIS-AZ4-2.5-L Rx Rx cardiometabolic research program with AstraZeneca. Oncology Collaboration In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs to treat cancer. As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize IONIS-STAT3-2.5 Rx Rx Rx Rx Rx Rx Under the terms of the agreement, we received $31 million in upfront payments. We recorded revenue of $11.5 million upon receipt of these payments and we have amortized $11.9 million into revenue as we have performed development activities under this collaboration. We recognized the remaining $7.6 million related to the option to license three drugs under the research program through February 2018. In January 2016, we and AstraZeneca amended the agreement for the research program. We are eligible to receive milestone payments and license fees from AstraZeneca as programs advance in development. In addition, we are eligible to receive tiered royalties up to the low to mid-teens on sales from any drugs resulting from these programs. If AstraZeneca successfully develops IONIS-STAT3-2.5 Rx Rx if we advance a drug under our cancer research program with AstraZeneca. Each of our agreements with AstraZeneca will continue until the expiration of all payment obligations under the applicable agreement. In addition, the agreement, or any program under the applicable agreement, may terminate early under the following situations: ● AstraZeneca may terminate the agreement or any program at any time by providing written notice to us; ● AstraZeneca may terminate the agreement or any program by providing written notice if we undergo a change of control with a third party; and ● Either we or AstraZeneca may terminate the agreement or any program by providing written notice to the other party upon the other party's uncured failure to perform a material obligation under the agreement, or the entire agreement if the other party becomes insolvent. During 2017, 2016 and 2015 we earned revenue of $13.8 million, $64.9 million and $6.4 million, respectively, from our relationship with AstraZeneca, which represented three percent, 19 percent and two percent, respectively, of our total revenue for those periods. Our balance sheets at December 31, 2017 and 2016 included deferred revenue of $41.8 million and $51.5 million, respectively, related to our relationship with AstraZeneca. Biogen We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense drugs with Biogen's expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved drug to treat people with spinal muscular atrophy, or SMA. Additionally, we and Biogen are currently developing six other drugs to treat neurodegenerative diseases under these collaborations, including IONIS-SOD1 Rx for ALS, IONIS-MAPT Rx (formerly IONIS-BIIB4 Rx ) for Alzheimer’s disease and IONIS-C9 Rx (formerly IONIS-BIIB5 Rx ), IONIS-BIIB6 Rx , IONIS-BIIB7 Rx and IONIS-BIIB8 Rx to treat undisclosed neurodegenerative diseases. In addition to these drugs, we and Biogen are evaluating numerous additional targets to develop drugs to treat neurological diseases. new antisense drugs for the treatment of SMA From inception through December 2017, we have received nearly $745 million from our Biogen collaborations. SPINRAZA In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. In December 2016, the FDA approved SPINRAZA for the treatment of SMA in pediatric and adult patients. In January 2018, Biogen reported that SPINRAZA was available in over 30 global markets. Our 2017 revenue included $112.5 million in commercial revenue from SPINRAZA royalties. In addition to SPINRAZA royalties, from inception through December 2017, we have received $436 million in payments for advancing SPINRAZA, including $90 million of milestone payments for the approval of SPINRAZA in the EU and Japan we earned during 2017. We are receiving tiered royalties up to the mid-teens on any sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We paid Cold Spring Harbor Laboratory and the University of Massachusetts nominal amounts for license fees and milestone payments we received in 2017. We also pay a low single digit royalty on sales of SPINRAZA. Additionally, we owe a low single digit royalty on future sales of SPINRAZA. Biogen is responsible for all further global development, regulatory and commercialization activities and costs for SPINRAZA. New antisense drugs for the treatment of SMA In December 2017, we entered into a collaboration agreement with Biogen to new antisense drugs for the treatment of SMA . Biogen will have the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen will be responsible for all further global development, regulatory and commercialization activities and costs for such therapies . Under the collaboration agreement, we received a upfront payment in December 2017, which we plan to amortize through December 2019. We will earn development and regulatory substantive milestone payments from Biogen if new drugs advance towards marketing approval. In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, substantive milestone payments and other payments, including up to $80 million for the achievement of development milestones, up to $180 million for the achievement of commercialization milestones and $800 million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties from the mid-teens to mid-20 percent range on net sales. We will earn the next milestone payment of up to $45 million for the initiation of a Phase 3 study for a drug under this collaboration. Neurology In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurodegenerative diseases. We are responsible for the development of each of the drugs through the completion of the initial Phase 2 clinical study for such drug. Biogen has the option to license a drug from each of the three programs through the completion of the first Phase 2 study for each program. We are currently advancing IONIS-MAPT Rx Rx Under the terms of the agreement, we received an upfront payment of $30 million, which we are amortizing through December 2020. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and substantive milestone payments per program, plus a mark-up of the cost estimate of the Phase 1 and 2 studies. We are eligible to receive up to $10 million in development milestone payments to support research and development of each program, plus a mark-up of the cost estimate of the Phase 1 and 2 studies. We are also eligible to receive up to $130 million in milestone payments per program if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any drugs resulting from each of the three programs. From inception through December 2017, we have received $56 million in milestone payments and upfront fees under this collaboration, including $10 million milestone payment we received in 2017 for the initiation of a Phase 1/2a study of IONIS-MAPT Rx . We will earn the next milestone payment of $7.5 Rx Strategic Neurology In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license drugs resulting from this collaboration. The exclusivity for neurological diseases will last through September 2019, and may be extended for any drug development programs Biogen is pursuing under the collaboration. We will usually be responsible for drug discovery and early development of antisense drugs and Biogen will have the option to license antisense drugs after Phase 2 proof of concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug. We are currently advancing five drugs, IONIS-SOD1 Rx Rx Rx Rx Rx Rx Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all drugs developed through this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. If we have a change of control during the first six years of the collaboration, we may be required to refund Biogen a portion of the $100 million upfront payment, with the amount of the potential refund decreasing ratably as we progress through the initial six-year term of the collaboration. We are amortizing the $100 million upfront payment through September 2019. Because the amortization period for the upfront payment will never be less than the initial six-year term of the collaboration, the amount of revenue we recognize from the upfront payment will never exceed the amount that Biogen could potentially require us to refund. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and substantive milestone payments. We are eligible to receive up to approximately $60 million for the achievement of research and development milestones, including amounts related to the cost of clinical trials, and up to $130 million for the achievement of regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any antisense drugs developed under this collaboration. If other modalities are chosen, such as small molecules or monoclonal antibodies, we are eligible to receive up to $90 million in substantive milestone payments, including up to $35 million for the achievement of research and development milestones and up to $55 million for the achievement of regulatory milestones. In addition, we are eligible to receive tiered single-digit royalties on sales from any drugs using non-antisense modalities developed under this collaboration. From inception through December 2017, we have received $165 million in upfront fees, milestone payments and other payments under this collaboration, including $15 million in milestone payments we received in 2017 for . We will earn the next milestone payment of up to $10 million if we advance a program under this collaboration. Each of our agreements with Biogen will continue until the earlier of the date all of Biogen's options to obtain the exclusive licenses under the applicable agreement expire unexercised or, if Biogen exercises its option, until the expiration of all payment obligations under the applicable agreement. In addition, each agreement, or any program under an agreement, may terminate early under the following situations: ● Biogen may terminate the agreement or any program at any time by providing written notice to us; ● Under specific circumstances, if we are acquired by a third party with a product that directly competes with a compound being developed under the agreement, Biogen may terminate the affected program by providing written notice to us; ● If, within a specified period of time, any required clearance of a transaction contemplated by an agreement under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, is not received, then either we or Biogen may terminate the affected program by providing written notice to the other party; and ● Either we or Biogen may terminate any program by providing written notice to the other party upon the other party's uncured failure to perform a material obligation under the agreement with respect to the affected program, or the entire agreement if the other party becomes insolvent. During 2017, 2016 and 2015, we earned revenue of $259.8 million, $207.9 million and $106.2 million, respectively, from our relationship with Biogen, which represented 51 percent, 60 percent and 37 percent, respectively, of our total revenue for those periods. Our balance sheets at December 31, 2017 and 2016 included deferred revenue of $69.3 million and $67.5 million, respectively, related to our relationship with Biogen. Research, Development and Commercialization Partners Bayer In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI Rx Rx Rx Rx In February 2017, we amended our agreement with Bayer to advance IONIS-FXI Rx and to initiate development of IONIS-FXI-L Rx , which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. We recorded revenue of $64.9 million related to the license for IONIS-FXI-L Rx in February 2017, and we are recognizing the remaining amount over the period we are performing the ongoing development activities for IONIS-FXI-L Rx and IONIS-FXI Rx through May 2019. We are conducting a Phase 2b study evaluating IONIS-FXI Rx in people with end-stage renal disease on hemodialysis to finalize dose selection . Additionally, we plan to develop IONIS-FXI-L Rx through Phase 1. Following these studies and Bayer's decision to further advance these programs, Bayer will be responsible for all global development, regulatory and commercialization activities and costs for both drugs. We are eligible to receive additional milestone payments as each drug advances toward the market. In total over the term of our collaboration, we are eligible to receive up to $385 million in license fees, substantive milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both drugs combined. From inception through December 2017, we have received over $175 million from our Bayer collaboration. We will earn the next milestone payment of $10 million if we advance a program under this collaboration. Our agreement with Bayer will continue until the expiration of all payment obligations under the agreement. In addition, the agreement, or any program under the agreement, may terminate early under the following situations: ● Bayer may terminate the agreement or any program at any time by providing written notice to us; ● Either we or Bayer may terminate the agreement or any program by providing written notice to the other party upon the other party’s uncured failure to perform a material obligation under the agreement, or the entire agreement if the other party becomes insolvent. During 2017, 2016 and 2015 we earned revenue of $69.2 million, $5.4 million and $93.4 million, respectively, from our relationship with Bayer, which represented 14 percent, two percent and 33 percent, respectively, of our total revenue for those periods. Our consolidated balance sheet at December 31, 2017 and 2016 included deferred revenue of $7.3 million and $1.4 million, respectively, related to our relationship with Bayer. GSK In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received $38 million in upfront and expansion payments, which we amortized through September 2017. In August 2017, as part of a reprioritization of its pipeline and strategic review of its Rare Diseases business, GSK declined its options for inotersen, our Phase 3 drug to treat people with TTR amyloidosis and IONIS-FB-L Rx Rx GSK, consistent with its focus on treatments for infectious diseases, continues to advance two drugs targeting hepatitis B virus, or HBV, under our collaboration: IONIS-HBV Rx Rx Rx Under our agreement, if GSK successfully develops these drugs and achieves pre-agreed sales targets, we could receive license fees and substantive milestone payments of $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. From inception through December 2017, we have received more than $162 million in payments under this alliance with GSK. We will earn the next milestone payment of up to $15 million for the initiation of a Phase 3 study for the HBV program. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any product that GSK successfully commercializes under this alliance. Our alliance with GSK will continue until the earlier of the date that all of GSK's options to obtain the exclusive licenses under the agreement expire unexercised or, if GSK exercises its option, until the expiration of all payment obligations under the agreement. In addition, the agreement, or any program under the agreement, may terminate early under the following situations: ● GSK may terminate any program, at any time by providing written notice to us; and ● Either we or GSK may terminate any program by providing written notice to the other party upon the other party's uncured failure to perform a material obligation under the agreement with respect to the affected program, or the entire agreement if the other party becomes insolvent. During 2017, 2016 and 2015, we earned revenue of $8.6 million, $12.3 million and $33.3 million respectively, from our relationship with GSK, which represented two percent, four percent and 12 percent, respectively, of our total revenue for those years. Our balance sheet at December 31, 2016 included deferred revenue of $2.1 million, related to our relationship with GSK. Janssen Biotech, Inc. In December 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract. Janssen has the option to license drugs from us through the designation of a development candidate for up to three programs. Prior to option exercise we are responsible for the discovery activities to identify a development candidate. If Janssen exercises an option for one of the programs, it will be responsible for the global development, regulatory and commercial activities under that program. Under the terms of the agreement, we received $35 million in upfront payments, which we amortized through November 2017. We are eligible to receive up to more than $800 million in license fees and substantive milestone payments for these programs, including up to $175 million for the achievement of development milestones, up to $440 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. From inception through December 2017, we have received $61.8 million, including $15 million in license fees when Janssen licensed IONIS-JBI1-2.5 Rx Rx Rx Our agreement with Janssen will continue until the earlier of the date that all of Janssen’s options to obtain the exclusive licenses under the agreement expire unexercised or, if Janssen exercises its option, until the expiration of all payment obligations under the agreement. In addition, the agreement, or any program under the agreement, may terminate early under the following situations: ● Janssen may terminate the agreement or any program at any time by providing written notice to us; and ● Either we or Janssen may terminate any program by providing written notice to the other party upon the other party’s uncured failure to perform a material obligation under the agreement, or the entire agreement if the other party becomes insolvent. During 2017, 2016 and 2015 we earned revenue of $33.5 million, $27.3 million and $8.9 million, respectively, from our relationship with Janssen. Our balance sheet at December 31, 2016 included deferred revenue of $17.5 million related to our relationship with Janssen. Novartis In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L Rx Rx Rx Rx Akcea received a $75 million upfront payment in the first quarter of 2017, of which it retained $60 million and paid us $15 million as a sublicense fee. If Novartis exercises its option for a drug, Novartis will pay Akcea a license fee equal to $150 million for each drug it licenses. In addition, for AKCEA-APO(a)-L Rx Rx Rx Rx The agreement with Novartis will continue until the earlier of the date that all of Novartis’ options to obtain the exclusive licenses under the agreement expire unexercised or, if Novartis exercises its options, until the expiration of all payment obligations under the agreement. In addition, the agreement as a whole or with respect to any drug under the agreement, may terminate early under the following situations: ● Novartis may terminate the agreement as a whole or with respect to any drug at any time by providing written notice to us; ● Either we or Novartis may terminate the agreement with respect to any drug by providing written notice to the other party in good faith that we or Novartis has determined that the continued development or commercialization of the drug presents safety concerns that pose an unacceptable risk or threat of harm in humans or would violate any applicable law, ethical principles, or principles of scientific integrity; ● Either we or Novartis may terminate the agreement for a drug by providing written notice to the other party upon the other party’s uncured failure to perform a material obligation related to the drug under the agreement, or the entire agreement if the other party becomes insolvent; and ● We may terminate the agreement if Novartis disputes or assists a third party to dispute the validity of any of our patents. In conjunction with this collaboration, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea’s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. To determine the amount of revenue to recognize under our agreements with Novartis, we first concluded that we would account for the collaboration and SPA agreements as a single multiple element arrangement. We next identified four separate units of accounting under the arrangement, each with stand-alone value: ● Development services for AKCEA-APO(a)-L Rx ● Development services for AKCEA-APOCIII-L Rx ● API for AKCEA-APO(a)-L Rx ● API for AKCEA-APOCIII-L Rx We then determined the total consideration under the arrangement was $180.0 million, which included the following: ● $75 million from the upfront payment; ● $100 million from our common stock Novartis purchased under the SPA, including $28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and ● $5.0 million for the potential premium Novartis would have paid if they purchased our common stock in the future. We first allocated $71.6 million of the consideration to equity based on the fair value of our common stock Novartis purchased. Next, we allocated the remaining consideration of $108.4 million based on the relative stand-alone selling price of each unit of accounting as follows: ● $64.0 million for the development services for AKCEA-APO(a)-L Rx ; ● $40.1 million for the development services for AKCEA-APOCIII-L Rx ● $1.5 Rx ● $2.8 Rx We are recognizing the amount attributed to the development services for AKCEA-APO(a)-L Rx Rx Rx Rx During 2017, we earned revenue of $55.2 million from our relationship with Novartis, which represented 11 percent of our total revenue for 2017. Our balance sheet at December 31, 2017 included deferred revenue of $58.9 million related to our relationship with Novartis. Roche In April 2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for Huntington's disease, or HD, based on our antisense technology. Roche has the option to license the drugs from us through the completion of the first Phase 1 trial. Under the agreement, we are responsible for the discovery and development of an antisense drug targeting huntingtin, or HTT, protein. We evaluated a drug targeting HTT, IONIS-HTT Rx In December 2017, upon completion of the Phase 1/2a study, Roche exercised its option to license IONIS-HTT Rx Rx Rx Rx Rx Our alliance with Roche will continue until the earlier of the date Roche's option to obtain the exclusive license under the agreement expires unexercised or, if Roche exercises its option, until the expiration of all payment obligations under the agreement. In addition, the agreement may terminate early under the following situations: ● Roche may terminate the agreement at any time by providing written notice to us; and ● Either we or Roche may terminate the agreement by providing written notice to the other party upon the other party's uncured failure to perform a material obligation under the agreement or if the other party becomes insolvent. During 2017, 2016 and 2015, we earned revenue of $53.0 million, $7.1 million and $31.2 million, respectively from our relationship with Roche, which represented 10 percent, two percent and 11 percent, respectively, of our total revenue for those years. Our balance sheet at December 31, 2016 included deferred revenue of $1.7 million related to our relationship with Roche. Satellite Company Partnerships Achaogen, Inc. In 2006, we exclusively licensed to Achaogen, Inc. specific know-how, patents and patent applications relating to aminoglycosides. In connection with the license, Achaogen issued to us $1.5 million of Achaogen stock. Achaogen is developing plazomicin, an aminoglycoside Achaogen discovered based on the technology we licensed to Achaogen. If Achaogen successfully develops and commercializes two drugs under our agreement, we will receive payments totaling up to $49.3 million for the achievement of key clinical, regulatory and sales events. The FDA set a Prescription Drug User Fee Act, or PDUFA, date of June 25, 2018 for plazomicin. Achaogen also plans to submit an MAA to the EMA in 2018. From inception through December 2017, we have earned $7 million in milestone payments from Achaogen. We will earn the next milestone payment of $7.5 million if Achaogen obtains regulatory approval for plazomicin in a major market. We are also eligible to receive low single digit royalties on sales of drugs resulting from the program. Achaogen is solely responsible for the continued development, regulatory and commercialization activities of plazomicin. During 2017, 2016 and 2015, we did not earn any revenue from our relationship with Achaogen. Alnylam Pharmaceuticals, Inc. In March 2004, we entered into an alliance with Alnylam to develop and commercialize RNAi therapeutics. Under the terms of the agreement, we exclusively licensed to Alnylam our patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics in exchange for a $5 million technology access fee, participation in fees from Alnylam’s partnering programs, as well as future milestone and royalty payments from Alnylam. For each drug Alnylam develops under this alliance, we may receive up to $3.4 million in milestone payments, including up to $1.1 million for the achievement of development milestones and $2.3 million for regulatory milestones. We will earn the next milestone payment of $0.8 million if Alnylam advances a drug in its pipeline. We also have the potential to earn royalties on drug sales and a portion of payments that Alnylam receives from licenses of our technology it grants to its partners, plus royalties. We retained rights to a limited number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi drugs targeting a limited number of therapeutic targets on a nonexclusive basis. If we develop or commercialize an RNAi-based drug using Alnylam’s technology, we will pay Alnylam up to $3.4 million in milestone payments for specified development and regulatory events, plus royalties. To date, we do not have an RNAi-based drug in development. In 2015, we and Alnylam entered into an alliance in which we formed an intellectual property cross-license under which we and Alnylam each obtained exclusive license rights to four therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four targets, including FXI and Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from

Segment Information and Concent

Segment Information and Concentration of Business Risk	12 Months Ended
	Dec. 31, 2017
Segment Information and Concentration of Business Risk [Abstract]
Segment Information and Concentration of Business Risk	7. Segment Information and Concentration of Business Risk We have two reportable segments Ionis Core and Akcea Therapeutics. Prior to Akcea’s IPO in July 2017, we owned 100 percent of Akcea’s stock and consolidated 100 percent of Akcea’s results in our financial statements. After Akcea’s IPO, we owned approximately 68 percent of Akcea. As a result, beginning in the third quarter of 2017, we began adjusting our financial statements to reflect the noncontrolling interest that we no longer own in Akcea. Our reportable segments remain unchanged as a result of Akcea’s IPO. Segment income (loss) from operations includes revenue less operating expenses attributable to each segment. In our Ionis Core segment we are exploiting a novel drug discovery platform we created to generate a broad pipeline of first-in-class and/or best-in-class drugs for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy and includes multiple streams of revenue including license fees, milestone payments and royalties, among others. Akcea is people . The following tables show our segment revenue and income (loss) from operations for (in thousands), respectively. 2017 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Commercial revenue: SPINRAZA royalties $ 112,540 $ — $ — $ 112,540 Licensing and other royalty revenue 9,519 — — 9,519 Total commercial revenue 122,059 — — 122,059 R&D revenue under collaborative agreements 384,805 55,209 (54,407 ) 385,607 Total segment revenue $ 506,864 $ 55,209 $ (54,407 ) $ 507,666 Total operating expenses $ 373,788 $ 163,871 $ (54,527 ) $ 483,132 Income (loss) from operations $ 133,076 $ (108,662 ) $ 120 $ 24,534 2016 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Commercial revenue: SPINRAZA royalties $ 883 $ — $ — $ 883 Licensing and other royalty revenue 19,839 — — 19,839 Total commercial revenue 20,722 — — 20,722 R&D revenue under collaborative agreements 338,546 — (12,648 ) 325,898 Total segment revenue $ 359,268 $ — $ (12,648 ) $ 346,620 Total operating expenses $ 322,192 $ 83,512 $ (12,768 ) $ 392,936 Income (loss) from operations $ 37,076 $ (83,512 ) $ 120 $ (46,316 ) 2015 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: R&D revenue under collaborative agreements $ 284,015 $ — $ (2,655 ) $ 281,360 Licensing and other royalty revenue 2,343 — — 2,343 Total segment revenue $ 286,358 $ — $ (2,655 ) $ 283,703 Total operating expenses $ 309,492 $ 52,748 $ (2,775 ) $ 359,465 Income (loss) from operations $ (23,134 ) $ (52,748 ) $ 120 $ (75,762 ) The following table shows our total assets by segment at December 31, 2017 and 2016 (in thousands), respectively. Total Assets Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total December 31, 2017 $ 1,341,828 $ 268,804 $ (288,608 ) $ 1,322,024 December 31, 2016 $ 1,067,770 $ 10,684 $ (165,987 ) $ 912,467 We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as 10 percent or more of our total revenue, was as follows: 2017 2016 2015 Partner A 51 % 60 % 37 % Partner B 14 % 2 % 33 % Partner C 10 % 2 % 11 % Partner D 11 % 0 % 0 % Partner E 3 % 19 % 2 % Partner F 2 % 4 % 12 % Contracts receivables at December 31, 2017 and December 31, 2016 were comprised of approximately 84 percent and 92 percent for each year from two significant partners, respectively.

Employment Benefits

Employment Benefits	12 Months Ended
	Dec. 31, 2017
Employment Benefits [Abstract]
Employment Benefits	8. Employment Benefits We have an employee 401(k) salary deferral plan, covering all employees. Employees could make contributions by withholding a percentage of their salary up to the IRS annual limit $18,000 and $24,000 in 2017 for employees under 50 years old and employees 50 years old or over, respectively. We made approximately $3.0 million, $1.7 million and $1.5 million in matching contributions for the years ended December 31, 2017, 2016 and 2015, respectively.

Legal Proceedings

Legal Proceedings	12 Months Ended
	Dec. 31, 2017
Legal Proceedings [Abstract]
Legal Proceedings	9. Legal Proceedings From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If the potential loss from any legal proceeding is considered probable and the amount can be reasonably estimated, we accrue a liability for the estimated loss. Significant judgment is required to determine the probability of a loss and whether the amount of the loss is reasonably estimable. The outcome of any proceeding is not determinable in advance. As a result, the assessment of a potential liability and the amount of accruals recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding, and may revise our estimates. Gilead Litigation In August 2013, Gilead Sciences Inc. filed a suit in the United States District Court of Northern District of California related to United States Patent Nos. 7,105,499 and 8,481,712, which are jointly owned by Merck Sharp & Dohme Corp. and Ionis Pharmaceuticals, Inc. In the suit Gilead asked the court to determine that Gilead's activities do not infringe any valid claim of the named patents and that the patents are not valid. We and Merck Sharp & Dohme Corp. filed our answer denying Gilead's noninfringement and invalidity contentions, contending that Gilead's commercial sale and offer for sale of sofosbuvir prior to the expiration of the '499 and '712 patents infringes those patents, and requesting monetary damages to compensate for such infringement. In the trial for this case held in March 2016, the jury upheld all ten four percent of $5 two

Quarterly Financial Data (Unaud

Quarterly Financial Data (Unaudited)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Data (Unaudited) [Abstract]
Quarterly Financial Data (Unaudited)	10. Quarterly Financial Data (Unaudited) The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a fair statement of the results of the interim periods. Summarized quarterly data for the years ended December 31, 2017 and 2016 are as follows (in thousands, except per share data). 2017 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 110,304 $ 104,152 $ 120,911 $ 172,299 Operating expenses $ 96,315 $ 105,823 $ 107,002 $ 173,992 Income (loss) from operations $ 13,989 $ (1,671 ) $ 13,909 $ (1,693 ) Net income (loss) $ 3,468 $ (11,206 ) $ (4,896 ) $ (4,662 ) Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders $ 3,468 $ (11,206 ) $ (976 ) $ 2,744 Basic net income (loss) per share (1) (2) $ 0.03 $ (0.09 ) $ 0.00 $ 0.02 Diluted net income (loss) per share (1) (3) $ 0.03 $ (0.09 ) $ 0.00 $ 0.02 2016 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 36,874 $ 38,470 $ 110,927 $ 160,349 Operating expenses $ 91,526 $ 87,397 $ 94,819 $ 119,194 Income (loss) from operations $ (54,652 ) $ (48,927 ) $ 16,108 $ 41,155 Net income (loss) $ (62,917 ) $ (56,855 ) $ 7,351 $ 25,865 Basic net income (loss) per share (1) $ (0.52 ) $ (0.47 ) $ 0.06 $ 0.21 Diluted net income (loss) per share (1) (4) (5) $ (0.52 ) $ (0.47 ) $ 0.06 $ 0.21 (1) We computed net income (loss) per share independently for each of the quarters presented. Therefore, the sum of the quarterly net income (loss) per share will not necessarily equal the total for the year. (2) As discussed in Note 1, Organization and Significant Accounting Policies, Our basic net income (loss) per share for the three months ended December 31, 2017, was calculated as follows (in thousands, except per share amounts): Three Months Ended December 31, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Loss Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 45,448 $ (0.35 ) $ (15,955 ) Akcea’s net loss attributable to our ownership $ (15,955 ) Ionis’ stand-alone net income 18,672 Net income available to Ionis common stockholders $ 2,717 Weighted average shares outstanding 124,818 Basic net income per share $ 0.02 For the three months ended December 31, 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. Diluted common equivalent shares for the three months ended December 31, 2017 consisted of the following (in thousands except per share amounts): Three Months Ended December 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 2,717 124,818 $ 0.02 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,532 Shares issuable upon restricted stock award issuance — 507 Shares issuable related to our ESPP — 5 Income available to common shareholders, plus assumed conversions $ 2,717 126,862 $ 0.02 For the three months ended December 31, 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. Prior to Akcea’s IPO, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea’s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. During the three months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the six percent cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares which we owned in our calculation of basic and diluted net income (loss) per share for three months ended September 30, 2017. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations. Our basic net income (loss) per share for the three months ended September 30, 2017, was calculated as follows (in thousands, except per share amounts): Three Months Ended September 30, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Income (Loss) Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 36,556 $ (0.27 ) $ (9,870 ) Preferred shares 5,651 0.05 283 Akcea’s net loss attributable to our ownership $ (9,587 ) Ionis’ stand-alone net income 9,168 Net loss available to Ionis common stockholders $ (419 ) Weighted average shares outstanding 124,370 Basic net income per share $ 0.00 (3) For the three months ended March 31, 2017 we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended March 31, 2017 consisted of the following (in thousands): Three Months Ended March 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 3,468 122,861 $ 0.03 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,674 Shares issuable upon restricted stock award issuance — 377 Shares issuable related to our ESPP — 60 Income available to common shareholders, plus assumed conversions $ 3,468 124,972 $ 0.03 For the three months ended March 31, 2017, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. (4) For the three months ended December 31, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended December 31, 2016 consisted of the following (in thousands): Three Months Ended December 31, 2016 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 25,865 121,340 $ 0.21 Effect of diluted securities: Shares issuable upon exercise of stock options — 2,189 Shares issuable upon restricted stock award issuance — 403 Shares issuable related to our ESPP — 21 Income available to common shareholders, plus assumed conversions $ 25,865 123,953 $ 0.21 For the three months ended December 31, 2016, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share would be anti-dilutive. (5) For the three months ended September 30, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended September 30, 2016 consisted of the following (in thousands): Three Months Ended September 30, 2016 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 7,351 120,989 $ 0.06 Effect of diluted securities: Shares issuable upon exercise of stock options — 2,129 Shares issuable upon restricted stock award issuance — 202 Shares issuable related to our ESPP — 58 Income available to common shareholders, plus assumed conversions $ 7,351 123,378 $ 0.06 For the three months ended September 30, 2016, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share would be anti-dilutive.

Organization and Significant 20

Organization and Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2017
Organization and Significant Accounting Policies [Abstract]
Basis of Presentation	Basis of Presentation In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. ("we", "us" or "our") and the consolidated results of our majority-owned affiliate, Akcea Therapeutics, Inc., which we formed in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, and therefore beginning in July 2017, we no longer own 100 percent of Akcea. As of July 19, 2017, the closing of the IPO, we owned approximately 68 percent of Akcea. Refer to the noncontrolling interest in Akcea section in this note for further information related to our accounting for our investment in Akcea.
Basic and Diluted Net Income (Loss) per Share	Basic and Diluted Net Income (Loss) per Share We compute basic net income (loss) per share by dividing the net income (loss) attributable to our common stockholders by our weighted average number of common shares outstanding during the period. The calculation of total net income (loss) attributable to our common stockholders for 2017 considered our net income for Ionis on a stand-alone basis plus our share of Akcea’s net loss. To calculate the portion of Akcea’s net loss attributable to our ownership, we multiplied Akcea’s loss per share by the weighted average shares we owned in Akcea during the year. Prior to Akcea’s IPO, we owned Akcea Series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea’s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. For 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the year. The two-class method required Akcea to calculate its net income (loss) per share six percent total net income available to Ionis common stockholders for the calculation of net income per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations. We calculated our basic net income per share for 2017 as follows (in thousands, except per share amounts): Year Ended December 31, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Loss Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 20,669 $ (2.82 ) $ (58,332 ) Preferred shares 15,748 (1.55 ) (24,344 ) Akcea’s net loss attributable to our ownership $ (82,676 ) Ionis’ stand-alone net income 92,336 Net income available to Ionis common stockholders $ 9,661 Weighted average shares outstanding 124,016 Basic net income per share $ 0.08 For 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. Diluted common equivalent shares for 2017 consisted of the following (in thousands except per share amounts): Year Ended December 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Net income available to Ionis common stockholders $ 9,661 124,016 $ 0.08 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,619 Shares issuable upon restricted stock award issuance — 459 Shares issuable related to our ESPP — 4 Income available to Ionis common stockholders, plus assumed conversions $ 9,661 126,098 $ 0.08 For 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. As we incurred a net loss for 2016 and 2015, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:    2¾ percent convertible senior notes;  Dilutive stock options;  Unvested restricted stock units; and  Employee Stock Purchase Plan, or ESPP.
Revenue Recognition	Revenue Recognition We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet. Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue We often enter into agreements to license and sell our technology on an exclusive or non-exclusive basis in exchange for upfront fees, license fees, milestone payments and/or royalties. We generally recognize as revenue immediately license payments with stand-alone value when the license is delivered and we are reasonably assured of collecting the resulting receivable. We recognize royalty revenue in the period in which the counterparty sells the related product, unless we are unable to obtain information to estimate the royalty. For example, in 2017 we recorded SPINRAZA royalty revenue of $112.5 million. Research and development revenue under collaborative agreements Arrangements with multiple deliverables Our collaboration agreements typically contain multiple elements, or deliverables, including technology licenses or options to obtain technology licenses, research and development services, and in certain cases manufacturing services, and we allocate the consideration to each unit of accounting based on the relative selling price of each deliverable. Amendments to agreements From time to time we amend our collaboration agreements. For these agreements, before we identify our deliverables and allocate consideration to each unit of accounting, we must determine if the amendment should be accounted for as a separate agreement, or if the amendment and any undelivered elements for the original agreement should be accounted for as a single new arrangement. For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI Rx Rx Rx Rx Rx Rx Under the 2017 amendment, there was a substantial increase in the consideration we are eligible to receive and a significant change in the deliverables we will provide to Bayer. As a result, we concluded that the amendment should be evaluated with the undelivered elements of the original agreement as a single new arrangement. Therefore, we evaluated our original and 2017 amended agreements with Bayer together to determine our deliverables. We concluded that the 2017 amendment did not impact the items we already delivered to Bayer. Identifying deliverables and units of accounting We evaluate the deliverables in our collaboration agreements to determine whether they meet the criteria to be accounted for as separate units of accounting or whether they should be combined with other deliverables and accounted for as a single unit of accounting. When the delivered items in an arrangement have "stand-alone value" to our customer, we account for the deliverables as separate units of accounting. Delivered items have stand-alone value if they are sold separately by any vendor or the customer could resell the delivered items on a stand-alone basis. For example, our 2017 amended agreement with Bayer has multiple elements. We evaluated the deliverables in this arrangement when we entered into the 2017 amended agreement and determined that certain of the deliverables have stand-alone value. Below is a list of the three units of accounting under our 2017 amended agreement: ● The exclusive license we granted to Bayer to develop and commercialize IONIS-FXI-L Rx ● The development services we agreed to perform for IONIS-FXI-L Rx Rx ● The remaining undelivered IONIS-FXI Rx We determined that each of these three units of accounting have stand-alone value. The license we granted to Bayer has stand-alone value because it gives Bayer the exclusive right to develop IONIS-FXI-L Rx Measurement and allocation of arrangement consideration Our collaborations may provide for various types of payments to us including upfront payments, funding of research and development, milestone payments, licensing fees and royalties on product sales. We initially allocate the amount of consideration that is fixed and determinable at the time the agreement is entered into and exclude contingent consideration. We allocate the consideration to each unit of accounting based on the relative selling price of each deliverable. We use the following hierarchy of values to estimate the selling price of each deliverable: (i) vendor-specific objective evidence of fair value; (ii) third-party evidence of selling price; and (iii) best estimate of selling price, or BESP. BESP reflects our best estimate of what the selling price would be if we regularly sold the deliverable on a stand-alone basis. We recognize the revenue allocated to each unit of accounting as we deliver the related goods or services. If we determine that we should treat certain deliverables as a single unit of accounting, then we recognize the revenue ratably over our estimated period of performance. We determined that the allocable arrangement consideration for the Bayer 2017 amended agreement was $76.3 million, comprised of the $75 million we received as part of the amendment and the remaining amount of the $100 million upfront payment we had not yet recognized into revenue, related to the undelivered API. We allocated the consideration based on the relative BESP of each unit of accounting. We engaged a third party, independent valuation specialist to assist us with determining BESP. We estimated the selling price of the license granted for IONIS-FXI-L Rx Rx ● Estimated future product sales; ● Estimated royalties on future product sales; ● Contractual milestone payments; ● Expenses we expect to incur; ● Income taxes; and ● An appropriate discount rate. We estimated the selling price of the development services by using our internal estimates of the cost to perform the specific services and estimates of expected cash outflows to third parties for services and supplies over the expected period that we will perform the development services. The significant inputs we used to determine the selling price of the development services included: ● The number of internal hours we will spend performing these services; ● The estimated cost of work we will perform; ● The estimated cost of work that we will contract with third parties to perform; and ● The estimated cost of API we will use. For purposes of determining BESP of the services we will perform and the API we will deliver in our 2017 amended Bayer transaction, accounting guidance required us to include a markup for a reasonable profit margin. Based on the units of accounting under the 2017 amended agreement, we allocated the $76.3 million of allocable consideration as follows: ● $64.9 million to the IONIS-FXI-L Rx ● $11.0 million for development services for IONIS-FXI-L Rx Rx ● $0.4 IONIS-FXI Rx Assuming a constant selling price for the other elements in the arrangement, if there was an assumed 10 percent increase or decrease in the estimated selling price of the IONIS-FXI-L Rx Rx Timing of revenue recognition We recognize revenue as we deliver each item under the arrangement and the related revenue is realizable and earned. For example, we recognized revenue for the exclusive license we granted Bayer for IONIS-FXI-L Rx The following are the periods over which we are recognizing revenue for each of our units of accounting under our 2017 amended Bayer agreement: ● We recognized the portion of the consideration attributed to the IONIS-FXI-L Rx ● We are recognizing the amount attributed to the development services for IONIS-FXI-L Rx Rx ● We are recognizing the amount attributed to the remaining API supply as we deliver it to Bayer. Multiple agreements From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether they should be accounted for individually as distinct arrangements or whether the separate agreements are, in substance, a single multiple element arrangement. We evaluate whether the negotiations are conducted jointly as part of a single negotiation, whether the deliverables are interrelated or interdependent, whether fees in one arrangement are tied to performance in another arrangement, and whether elements in one arrangement are essential to another arrangement. Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that they are, in effect, part of a single arrangement. For example, in the first quarter of 2017, we and Akcea entered into two separate agreements with Novartis at the same time: a collaboration agreement and a stock purchase agreement, or SPA. Akcea entered into a collaboration agreement with Novartis to develop and commercialize AKCEA-APO(a)-L Rx and AKCEA-APOCIII-L Rx . Under the collaboration agreement, Akcea received a $75 million upfront payment. For each drug, Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the Food and Drug Administration, or FDA, and delivering API. Under the collaboration agreement, Novartis has an exclusive option to develop and commercialize AKCEA-APO(a)-L Rx and AKCEA-APOCIII-L Rx . If Novartis exercises an option for one of these drugs, Novartis will pay Akcea a million license fee and will assume all further global development, regulatory and commercialization activities and costs for the licensed drug. Akcea is also eligible to receive a development milestone payment, milestone payments if Novartis achieves pre-specified regulatory milestones, commercial milestones and tiered royalties on net sales from each drug under the collaboration. Under the SPA, Novartis purchased 1.6 million shares of Ionis’ common stock for $100 million in the first quarter of 2017 and paid a premium over the weighted average trading price at the time of purchase. Additionally, the SPA required Novartis to purchase $50 million of Akcea’s common stock in a concurrent private placement with Akcea’s IPO in July 2017. We evaluated the Novartis agreements to determine whether we should treat the agreements separately or as a single arrangement. We considered that the agreements were negotiated concurrently and in contemplation of one another. Additionally, the same individuals were involved in the negotiations of both agreements. Based on these facts and circumstances, we concluded that we should treat both agreements as a single arrangement and evaluate the provisions of the agreements on a combined basis. Refer to Note 6, Collaborative Arrangements and Licensing Agreements Milestone payments Our collaborations often include contractual milestones, which typically relate to the achievement of pre-specified development, regulatory and/ or commercialization events. These three categories of milestone events reflect the three stages of the life-cycle of our drugs, which we describe in more detail in the following paragraphs. Prior to the first stage in the life-cycle of our drugs, we perform a significant amount of work using our proprietary antisense technology to design chemical compounds that interact with specific genes that are good targets for drug discovery. From these research efforts, we hope to identify a development candidate. The designation of a development candidate is the start of the development stage, which is the first stage in the life-cycle of our drugs. A development candidate is a chemical compound that has demonstrated the necessary safety and efficacy in preclinical animal studies to warrant further study in humans. During the first step of the development stage, we or our partners study our drugs in Investigational New Drug, or IND,-enabling studies, which are animal studies intended to support an IND application and/or the foreign equivalent. An approved IND allows us or our partners to study our development candidate in humans. If the regulatory agency approves the IND, we or our partners initiate a Phase 1 clinical trial in which we typically enroll a small number of healthy volunteers to ensure the development candidate is safe for use in patients. If we or our partners determine that a development candidate is safe based on the Phase 1 data, we or our partners initiate Phase 2 studies that are generally larger studies in patients with the primary intent of determining the preliminary efficacy and safety of the development candidate. The final step in the development stage is Phase 3 studies to gather the necessary safety and efficacy data to request marketing authorization from the FDA and/or foreign equivalents. Phase 3 studies typically involve larger numbers of patients and can take up to several years to complete. If the data gathered during the Phase 3 trials demonstrates acceptable safety and efficacy results, we or our partner will submit an application to the FDA and/or its foreign equivalents for marketing authorization. This stage of the drug’s life-cycle is the regulatory stage. If the FDA or a foreign equivalent grants marketing authorization for a drug, it moves into the commercialization stage. During this stage we or our partner will market and sell the drug to patients. Although our partner may ultimately be responsible for marketing and selling a partnered drug, our efforts to discover and develop a drug that is safe, effective and reliable contributes significantly to our partner’s ability to successfully sell the drug. The FDA and its foreign equivalents have the authority to impose significant restrictions on an approved drug through the product label and on advertising, promotional and distribution activities. Therefore, our efforts designing and executing the necessary animal and human studies are critical to obtaining claims in the product label from the regulatory agencies that would allow us or our partner to successfully commercialize our drug. Further, the patent protection afforded our drugs as a result of our initial patent applications and related prosecution activities in the United States and foreign jurisdictions are critical to our partner’s ability to sell our drugs without competition from generic drugs. The potential sales volume of an approved drug is dependent on several factors including the size of the patient population, market penetration of the drug, and the price charged for the drug. Generally, the milestone events contained in our partnership agreements coincide with the progression of our drugs from development, to marketing authorization and then to commercialization. The process of successfully discovering a new development candidate, having it approved and ultimately selling it for a profit is highly uncertain. As such, the milestone payments we may earn from our partners involve a significant degree of risk to achieve. Therefore, as a drug progresses through the stages of its life-cycle, the value of the drug generally increases. Development milestones in our partnerships may include the following types of events: ● Designation of a development candidate. Following the designation of a development candidate, IND-enabling animal studies for a new development candidate generally take 12 to 18 months to complete. ● Initiation of a Phase 1 clinical trial. Generally, Phase 1 clinical trials take one to two years to complete. ● Initiation or completion of a Phase 2 clinical trial. Generally, Phase 2 clinical trials take one to three years to complete. ● Initiation or completion of a Phase 3 clinical trial. Generally, Phase 3 clinical trials take two to four years to complete. Regulatory milestones in our partnerships may include the following types of events: ● Filing of regulatory applications for marketing authorization such as a New Drug Application, or NDA, in the United States or a Marketing Authorization Application, or MAA, in Europe. Generally, it takes six to twelve months to prepare and submit regulatory filings. ● Obtaining marketing authorization in a major market, such as the United States, Europe or Japan. Generally it takes one to two years after an application is submitted to obtain authorization from the applicable regulatory agency. Commercialization milestones in our partnerships may include the following types of events: ● First commercial sale in a particular market, such as in the United States or Europe. ● Product sales in excess of a pre-specified threshold, such as annual sales exceeding $1 billion. The amount of time to achieve this type of milestone depends on several factors including but not limited to the dollar amount of the threshold, the pricing of the product and the pace at which customers begin using the product. We assess whether a substantive milestone exists at the inception of our agreements. When a substantive milestone is achieved, we recognize revenue related to the milestone payment immediately. For our licensing and collaboration agreements in which we are involved in the discovery and/or development of the related drug or provide the partner with access to new technologies we discover, we have determined that the majority of future development, regulatory and commercialization milestones are substantive. For example, we consider most of the milestones associated with our strategic alliance with Biogen substantive because we are using our antisense drug discovery platform to discover and develop new drugs against targets for neurological diseases. In evaluating if a milestone is substantive we consider whether: ● Substantive uncertainty exists as to the achievement of the milestone event at the inception of the arrangement; ● The achievement of the milestone involves substantive effort and can only be achieved based in whole or in part on our performance or the occurrence of a specific outcome resulting from our performance; ● The amount of the milestone payment appears reasonable either in relation to the effort expended or to the enhancement of the value of the delivered items; ● There is no future performance required to earn the milestone; and ● The consideration is reasonable relative to all deliverables and payment terms in the arrangement. If any of these conditions are not met, we do not consider the milestone to be substantive and we defer recognition of the milestone payment and recognize it as revenue over our estimated period of performance, if any. Further information about our collaborative arrangements can be found in Note 6, Collaborative Arrangements and Licensing Agreements Option to license In several of our collaboration agreements, we provide our partner with an option to obtain a license to one or more of our drugs. When we have a multiple element arrangement that includes an option to obtain a license, we evaluate if the option is a deliverable at the inception of the arrangement. We do not consider the option to be a deliverable if we conclude that it is substantive and not priced at a significant and incremental discount. We consider an option substantive if, at the inception of the arrangement, we are at risk as to whether our collaboration partner will choose to exercise its option to obtain the license. In those circumstances, we do not include the associated license fee in the allocable consideration at the inception of the agreement. Rather, we account for the license fee when our partner exercises its option. For example, during 2017, we earned license fee revenue when three of our partners, Bayer, Janssen and Roche, exercised their options to license three of our drugs, which under the respective agreements we concluded to be substantive options at inception. As a result, in 2017 we recognized the related revenue immediately in research and development revenue under collaborative agreements on our statement of operations as these amounts relate to drugs in development under research and development collaboration arrangements.
Research and Development Expenses	Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our consolidated balance sheet and we expense them as the services are provided. For the years ended December 31, 2017, 2016 and 2015, research and development expenses were $372.5 million, $340.4 million and $319.5 million, respectively. A portion of the costs included in research and development expenses are costs associated with our partner agreements. For the years ended December 31, 2017, 2016 and 2015, research and development costs of approximately $59.5 million, $187.1 million and $161.7 million, respectively, were related to our partner agreements.
Patent Expenses	We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the United States Patent and Trademark Office, or foreign equivalent, issues the patent. The weighted average remaining amortizable life of our issued patents was 10.1 years at December 31, 2017. The cost of our patents capitalized on our consolidated balance sheet at December 31, 2017 and 2016 was $30.8 million and $28.8 million, respectively. Accumulated amortization related to patents was $8.8 million and $8.4 million at December 31, 2017 and 2016, respectively. Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following: Years Ending December 31, Amortization (in millions) 2018 $ 1.6 2019 $ 1.4 2020 $ 1.3 2021 $ 1.3 2022 $ 1.2 We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs. In 2017, 2016 and 2015, patent expenses were $2.1 million, $3.9 million and $2.8 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $0.4 million, $2.3 million and $1.1 million, respectively.
Concentration of Credit Risk	Concentration of Credit Risk Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody’s, Standard & Poor’s, or S&P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.
Cash, Cash Equivalents and Short-Term Investments	Cash, Cash Equivalents and Short-Term Investments We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term investments as “available-for-sale” and carry them at fair market value based upon prices for identical or similar items on the last day of the fiscal period. We record unrealized gains and losses as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments. We use the specific identification method to determine the cost of securities sold. We have equity investments of less than 20 percent in privately and publicly held biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2017, we held equity investments in one publicly held company, Antisense Therapeutics Limited, or ATL. Furthermore, we held cost method investments in five companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Kastle Therapeutics, Seventh Sense Biosystems and Suzhou Ribo Life Science Co., Ltd. We account for our equity investments in publicly held companies at fair value and record unrealized gains and losses related to temporary increases and decreases in the stock as a separate component of comprehensive income (loss). We account for our equity investments in privately held companies under the cost method of accounting because we own less than 20 percent and do not have significant influence over their operations. Realization of our equity position in these private companies is usually uncertain. When realization of our investment is uncertain, we record a full valuation allowance. In determining if and when a decrease in market value below our cost in our equity positions is temporary or other-than-temporary, we examine historical trends in the stock price, the financial condition of the company, near term prospects of the company and our current need for cash. If we determine that a decline in value in either a public or private investment is other-than-temporary, we recognize an impairment loss in the period in which the other-than-temporary decline occurs.
Inventory Valuation	Inventory Valuation We capitalize the costs of raw materials that we purchase for use in producing our drugs because until we use these raw materials they have alternative future uses. We include in inventory raw material costs for drugs that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single drug. For example, if one of our drugs failed, we could use the raw materials for that drug to manufacture our other drugs. We expense these costs when we begin to manufacture API for a particular drug. We reflect our inventory on the balance sheet at the lower of cost or market value under the first-in, first-out method, or FIFO. We review inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value. We consider several factors in estimating the net realizable value, including shelf life of raw materials, alternative uses for our drugs and clinical trial materials, and historical write-offs. We did not record any inventory write-offs for the years ended December 31, 2017, 2016 or 2015. Total inventory was $10.0 million and $7.5 million as of December 31, 2017 and 2016, respectively.
Property, Plant and Equipment	Property, Plant and Equipment We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands): Estimated Useful Lives December 31, (in years) 2017 2016 Computer software, laboratory, manufacturing and other equipment 3 to 10 $ 66,558 $ 63,287 Building, building improvements and building systems 15 to 40 92,770 48,909 Land improvements 20 2,853 2,853 Leasehold improvements 5 to 15 26,748 41,736 Furniture and fixtures 5 to 10 6,161 5,937 195,090 162,722 Less accumulated depreciation (87,676 ) (80,075 ) 107,414 82,647 Land 14,493 10,198 Total $ 121,907 $ 92,845 We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. As a result of the purchase of our primary manufacturing facility in 2017, we reclassed previously capitalized leasehold improvements to building, building improvements and building systems. Additionally, during 2017 we made additional improvements and expansions of our buildings to accommodate the growth in our business.
Fair Value of Financial Instruments	Fair Value of Financial Instruments We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.
Long-Lived Assets	Long-Lived Assets We evaluate long-lived assets, which include property, plant and equipment and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets. We recorded charges of $0.8 million, $2.3 million and $1.9 million for the years ended December 31, 2017, 2016 and 2015, respectively, related primarily to the write-down of intangible assets.
Use of Estimates	Use of Estimates The preparation of consolidated financial statements in conformity with accounting principles generally accepted in the United States requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements and accompanying notes. Actual results could differ from those estimates.
Stock-Based Compensation Expense	Stock-Based Compensation Expense We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our Consolidated Statements of Operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model as our method of valuing option awards and stock purchase rights under our ESPP. On the grant date, we use our stock price and assumptions regarding a number of highly complex and subjective variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors. Option-pricing models were developed for use in estimating the value of traded options that have no vesting or hedging restrictions and are fully transferable. Because our employee stock options have certain characteristics that are significantly different from traded options, and because changes in the subjective assumptions can materially affect the estimated value, in management’s opinion, the existing valuation models may not provide an accurate measure of the fair value of our employee stock options. Although we determine the estimated fair value of employee stock options using an option-pricing model, that value may not be indicative of the fair value observed in a willing buyer/willing seller market transaction. We recognize compensation expense for option awards using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period. The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted vest annually over a four-year period. See Note 4, Stockholders’ Equity,
Accumulated Other Comprehensive Income (Loss)	Accumulated other comprehensive income (loss) Accumulated other comprehensive income (loss) is primarily comprised of unrealized gains and losses on investments, net of taxes and adjustments we made to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our Consolidated Statement of Operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the years ended December 31, 2017, 2016 and 2015 (in thousands): Years Ended December 31, 2017 2016 2015 Beginning balance accumulated other comprehensive (loss) income $ (30,358 ) $ (13,565 ) $ 39,747 Unrealized losses on securities, net of tax (1) (960 ) (17,219 ) (33,101 ) Amounts reclassified from accumulated other comprehensive (loss) income (2) (374 ) 447 (20,211 ) Currency translation adjustment (67 ) (21 ) — Net other comprehensive loss for the period (1,401 ) (16,793 ) (53,312 ) Ending balance accumulated other comprehensive loss $ (31,759 ) $ (30,358 ) $ (13,565 ) (1) There was no tax expense for other comprehensive loss for the years ended December 31, 2017, 2016 or 2015. (2) Amounts for 2015 and 2017 are included in the separate line called “Gain on investment in Regulus Therapeutics Inc.” on our Consolidated Statement of Operations.
Convertible Debt	Convertible Debt We account for convertible debt instruments, including our 1 percent and 2¾ percent notes that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. Determining the fair value of the debt component requires the use of accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense. We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method. For additional information, see Note 3, Long-Term Obligations and Commitments
Segment Information	Segment Information We have two operating segments, our Ionis Core segment and Akcea Therapeutics. Prior to Akcea’s IPO in July 2017, we owned 100 percent of Akcea’s stock. After Akcea’s IPO, we owned approximately 68 percent of Akcea. We did not change our reportable segments as a result of Akcea’s IPO. Akcea is a late-stage biopharmaceutical company focused on developing and commercializing drugs to treat people with serious cardiometabolic diseases caused by lipid disorders. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis’ development, R&D support expenses and general and administrative expenses to Akcea for work we performed on behalf of Akcea.
Fair Value Measurements	Fair Value Measurements We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify the majority of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices. During 2017 and 2016, there were no transfers between our Level 1 and Level 2 investments. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs. During 2017 and 2016 we did not have any investments that were classified as Level 3 investments. The following tables present the major security types we held at December 31, 2017 and 2016 that are regularly measured and carried at fair value. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities’ fair value (in thousands): At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 86,262 $ 86,262 $ — Corporate debt securities (2) 647,461 — 647,461 Debt securities issued by U.S. government agencies (3) 136,325 — 136,325 Debt securities issued by the U.S. Treasury (3) 30,818 30,818 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 93,932 — 93,932 Total $ 994,798 $ 117,080 $ 877,718 At December 31, 2016 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 54,137 $ 54,137 $ — Corporate debt securities (3) 396,221 — 396,221 Debt securities issued by U.S. government agencies (3) 55,179 — 55,179 Debt securities issued by the U.S. Treasury (3) 29,286 29,286 — Debt securities issued by states of the U.S. and political subdivisions of the states (5) 109,111 — 109,111 Investment in Regulus Therapeutics Inc. 2,414 2,414 — Total $ 646,348 $ 85,837 $ 560,511 (1) Included in cash and cash equivalents on our consolidated balance sheet. (2) $11.9 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet. (3) Included in short-term investments on our consolidated balance sheet. (4) $3.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet. (5) $9.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet. Novartis Future Stock Purchase In January 2017, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis was required to purchase $50 million of Akcea’s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Therefore, at the inception of the SPA, we recorded a $5.0 million asset representing the fair value of the potential future premium we could have received if Novartis purchased our common stock. We determined the fair value of the future premium by calculating the value based on the stated premium in the SPA and estimating the probability of an Akcea IPO. We also included a lack of marketability discount when we determined the fair value of the premium because we would have issued unregistered shares to Novartis if they had purchased our common stock. We measured this asset using Level 3 inputs and recorded it in other assets on our consolidated balance sheet. Because Akcea completed its IPO before April 2018, Novartis will not purchase additional shares of Ionis stock. Therefore, this asset no longer had any value and we wrote-off the remaining balance to other expenses on our third quarter 2017 consolidated statement of operations. The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for 2017 (in thousands): Year Ended December 31, 2017 Beginning balance of Level 3 instruments $ — Value of the potential premium we will receive from Novartis at inception of the SPA (January 2017) 5,035 Write-off of premium to other expenses (5,035 ) Ending balance of Level 3 instruments $ —
Income Taxes	Income Taxes On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act makes broad and complex changes to the U.S. tax code. The changes include, but are not limited to, reducing the U.S. federal corporate tax rate from 35 percent to 21 percent, imposing a mandatory one-time transition tax on certain unrepatriated earnings of foreign subsidiaries, introducing bonus depreciation that will allow for full expensing of qualified property, eliminating the corporate alternative minimum tax, or AMT, and changing how existing AMT credits can be realized, and modifying or repealing many business tax deductions and credits. The SEC staff issued guidance to address the application of U.S. GAAP in situations when a registrant does not have the necessary information available, prepared, or analyzed (including computations) in reasonable detail to complete the accounting for certain income tax effects of the Tax Act. We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. Valuation allowances are provided when necessary to reduce deferred tax assets to the amount expected to be realized. We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation settlement. The second step is to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement. We recognize interest and penalties related to unrecognized tax benefits within the income tax expense line in the accompanying consolidated statements of operations. Accrued interest and penalties are included within other long-term liabilities in the consolidated balance sheets. We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, no assurance can be given that the final tax outcome of these matters will not be different from that which is reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which such determination is made. We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. Estimates of future taxable income are based on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized. We have incurred historical financial statement losses and as a result we had a full valuation allowance recorded against our net deferred tax assets for each of the years in these financial statements. We regularly assess the future realization of our net deferred tax assets and will reduce the valuation allowance in any such period in which we determine that all, or a portion, of our deferred tax assets are more-likely-than-not to be realized. We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.
Impact of Recently Issued Accounting Standards	Impact of Recently Issued Accounting Standards In May 2014, the FASB issued accounting guidance on the recognition of revenue from customers. Under this guidance, an entity will recognize revenue when it transfers control of promised goods or services to customers in an amount that reflects what the entity expects to receive in exchange for the goods or services. Further an entity will recognize revenue upon satisfying the performance obligation(s) under the related contract. Our performance obligation under our collaboration agreements is typically the research and development activities associated with the delivery of a drug candidate or drug to our partner. Under the current accounting guidance, we recognize revenue from milestone payments we earn under the milestone method from our collaboration agreements. Under the new guidance, the milestone method of revenue recognition is eliminated. Specifically, certain R&D milestone payments we previously recognized in full when we achieved a milestone will now be recognized over a period of time. If we achieve an R&D milestone payment related to activities we are performing under a collaboration agreement, we will recognize the associated revenue from the milestone payment over our estimated performance obligation period. Rx milestone payment over the period we are providing R&D services for Biogen. For milestones achieved for which we do not have a continuing performance obligation, we will continue to recognize the milestone payment in its entirety as revenue in the period in which our partner achieves the milestone. For example, in 2017, we earned a $50 million milestone payment from Biogen for the EU approval of SPINRAZA. Under both the new and old standard, we account for this milestone payment the same by recognizing the entire amount upon achievement of the event. This guidance does not change our recognition of commercial revenue from SPINRAZA royalties. We adopted this guidance on January 1, 2018 under the full retrospective approach, which requires us to recast our prior period amounts in the period of adoption. Our adoption of the standard in 2018 will result in the recognition of additional revenue of approximately $17 million and approximately $27 million for 2017 and 2016, respectively. In addition, our adoption of the standard will result in an increase in our deferred revenue balance of approximately $39 million at December 31, 2017 and a corresponding adjustment to our accumulated deficit for the same amount. Since our collaboration revenue has no associated cost of sales, the impact to our net loss (income) is equal to our revenue adjustment for each period. Additionally, as a result of adopting this new guidance there is no impact to our income tax expense because we have a full valuation allowance. This new guidance also requires additional disclosures about the attributes of our revenue and balances associated with our contracts, which we will include in our first quarter of 2018 financial statements. In January 2016, the FASB issued amended accounting guidance related to the recognition, measurement, presentation, and disclosure of certain financial instruments. The amended guidance requires us to measure and record equity investments, except those accounted for under the equity method of accounting that have a readily determinable fair value, at fair value and for us to recognize the changes in fair value in our net income (loss), instead of recognizing unrealized gains and losses through accumulated other comprehensive income, as we currently do under the existing guidance. The amended guidance also changes several disclosure requirements for financial instruments, including the methods and significant assumptions we use to estimate fair value. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2017. We adopted this guidance on January 1, 2018. The adoption of this guidance did not have an impact on our financial results. In February 2016, the FASB issued amended accounting guidance related to lease accounting, which will require us to record all leases with a term longer than one year on our balance sheet. When we record leases on our balance sheet under the new guidance, we will record a liability with a value equal to the present value of payments we will make over the life of the lease and an asset representing the underlying leased asset. The new accounting guidance requires us to determine if our leases are operating or financing leases. We will record expense for operating type leases on a straight-line basis as an operating expense. If we determine a lease is a financing lease, we will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. The new lease standard is effective for annual and interim periods beginning after December 15, 2018, with early adoption permitted. We must adopt the new standard on a modified retrospective basis, which requires us to reflect our leases on our consolidated balance sheet for the earliest comparative period presented. We plan to adopt this guidance on January 1, 2019. We are currently assessing the effects the new guidance will have on our consolidated financial statements and disclosures. In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. This change will result in us remeasuring our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We are currently assessing the timing of adoption as well as the effects it will have on our consolidated financial statements and disclosures. In May 2017, the FASB issued clarifying guidance related to the accounting for modifications of stock-based payment awards. The new guidance is meant to clarify when modification accounting is required. We early adopted this guidance in our financial statements for the quarter ended June 30, 2017 and it did not have an effect on our consolidated financial statements and disclosures.

Organization and Significant 21

Organization and Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2017
Organization and Significant Accounting Policies [Abstract]
Basic Net Income per Share	We calculated our basic net income per share for 2017 as follows (in thousands, except per share amounts): Year Ended December 31, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Loss Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 20,669 $ (2.82 ) $ (58,332 ) Preferred shares 15,748 (1.55 ) (24,344 ) Akcea’s net loss attributable to our ownership $ (82,676 ) Ionis’ stand-alone net income 92,336 Net income available to Ionis common stockholders $ 9,661 Weighted average shares outstanding 124,016 Basic net income per share $ 0.08
Basic and Diluted Net Income Per Share	For 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. Diluted common equivalent shares for 2017 consisted of the following (in thousands except per share amounts): Year Ended December 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Net income available to Ionis common stockholders $ 9,661 124,016 $ 0.08 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,619 Shares issuable upon restricted stock award issuance — 459 Shares issuable related to our ESPP — 4 Income available to Ionis common stockholders, plus assumed conversions $ 9,661 126,098 $ 0.08
Amortization Expense for Patents	Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following: Years Ending December 31, Amortization (in millions) 2018 $ 1.6 2019 $ 1.4 2020 $ 1.3 2021 $ 1.3 2022 $ 1.2
Accrued Liabilities	Our accrued liabilities consisted of the following (in thousands): December 31, 2017 2016 Clinical expenses $ 16,347 $ 23,428 In-licensing expenses 33,790 6,430 Other miscellaneous expenses 16,481 6,155 Total accrued liabilities $ 66,618 $ 36,013
Property, Plant and Equipment	We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands): Estimated Useful Lives December 31, (in years) 2017 2016 Computer software, laboratory, manufacturing and other equipment 3 to 10 $ 66,558 $ 63,287 Building, building improvements and building systems 15 to 40 92,770 48,909 Land improvements 20 2,853 2,853 Leasehold improvements 5 to 15 26,748 41,736 Furniture and fixtures 5 to 10 6,161 5,937 195,090 162,722 Less accumulated depreciation (87,676 ) (80,075 ) 107,414 82,647 Land 14,493 10,198 Total $ 121,907 $ 92,845
Changes in Accumulated Other Comprehensive Income (Loss)	Accumulated other comprehensive income (loss) is primarily comprised of unrealized gains and losses on investments, net of taxes and adjustments we made to reclassify realized gains and losses on investments from other accumulated comprehensive income (loss) to our Consolidated Statement of Operations. The following table summarizes changes in accumulated other comprehensive income (loss) for the years ended December 31, 2017, 2016 and 2015 (in thousands): Years Ended December 31, 2017 2016 2015 Beginning balance accumulated other comprehensive (loss) income $ (30,358 ) $ (13,565 ) $ 39,747 Unrealized losses on securities, net of tax (1) (960 ) (17,219 ) (33,101 ) Amounts reclassified from accumulated other comprehensive (loss) income (2) (374 ) 447 (20,211 ) Currency translation adjustment (67 ) (21 ) — Net other comprehensive loss for the period (1,401 ) (16,793 ) (53,312 ) Ending balance accumulated other comprehensive loss $ (31,759 ) $ (30,358 ) $ (13,565 ) (1) There was no tax expense for other comprehensive loss for the years ended December 31, 2017, 2016 or 2015. (2) Amounts for 2015 and 2017 are included in the separate line called “Gain on investment in Regulus Therapeutics Inc.” on our Consolidated Statement of Operations.
Assets Measured at Fair Value on a Recurring Basis	The following tables present the major security types we held at December 31, 2017 and 2016 that are regularly measured and carried at fair value. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities’ fair value (in thousands): At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 86,262 $ 86,262 $ — Corporate debt securities (2) 647,461 — 647,461 Debt securities issued by U.S. government agencies (3) 136,325 — 136,325 Debt securities issued by the U.S. Treasury (3) 30,818 30,818 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 93,932 — 93,932 Total $ 994,798 $ 117,080 $ 877,718 At December 31, 2016 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 54,137 $ 54,137 $ — Corporate debt securities (3) 396,221 — 396,221 Debt securities issued by U.S. government agencies (3) 55,179 — 55,179 Debt securities issued by the U.S. Treasury (3) 29,286 29,286 — Debt securities issued by states of the U.S. and political subdivisions of the states (5) 109,111 — 109,111 Investment in Regulus Therapeutics Inc. 2,414 2,414 — Total $ 646,348 $ 85,837 $ 560,511 (1) Included in cash and cash equivalents on our consolidated balance sheet. (2) $11.9 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet. (3) Included in short-term investments on our consolidated balance sheet. (4) $3.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet. (5) $9.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
Reconciliation of Assets Measured at Fair Value on a Recurring Basis Using Significant Unobservable Inputs (Level 3)	The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for 2017 (in thousands): Year Ended December 31, 2017 Beginning balance of Level 3 instruments $ — Value of the potential premium we will receive from Novartis at inception of the SPA (January 2017) 5,035 Write-off of premium to other expenses (5,035 ) Ending balance of Level 3 instruments $ —

Investments (Tables)

Investments (Tables)	12 Months Ended
	Dec. 31, 2017
Investments [Abstract]
Contract Maturity of Available-for-Sale Securities	The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2017: One year or less 71 % After one year but within two years 23 % After two years but within three and one half years 6 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Gross Unrealized Estimated December 31, 2017 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (2) $ 500,599 $ 2 $ (752 ) $ 499,849 Debt securities issued by U.S. government agencies 83,926 — (212 ) 83,714 Debt securities issued by the U.S. Treasury 29,428 — (17 ) 29,411 Debt securities issued by states of the U.S. and political subdivisions of the states (2) 29,240 4 (122 ) 29,122 Total securities with a maturity of one year or less 643,193 6 (1,103 ) 642,096 Corporate debt securities 148,663 8 (1,059 ) 147,612 Debt securities issued by U.S. government agencies 52,779 — (168 ) 52,611 Debt securities issued by the U.S. Treasury 1,409 — (2 ) 1,407 Debt securities issued by states of the U.S. and political subdivisions of the states 65,550 — (740 ) 64,810 Total securities with a maturity of more than one year 268,401 8 (1,969 ) 266,440 Total available-for-sale securities $ 911,594 $ 14 $ (3,072 ) $ 908,536 Gross Unrealized Estimated December 31, 2016 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities $ 195,087 $ 25 $ (161 ) $ 194,951 Debt securities issued by U.S. government agencies 26,548 — (10 ) 26,538 Debt securities issued by the U.S. Treasury 29,298 2 (14 ) 29,286 Debt securities issued by states of the U.S. and political subdivisions of the states (2) 72,775 2 (134 ) 72,643 Total securities with a maturity of one year or less 323,708 29 (319 ) 323,418 Corporate debt securities 202,408 36 (1,174 ) 201,270 Debt securities issued by U.S. government agencies 28,807 1 (167 ) 28,641 Debt securities issued by states of the U.S. and political subdivisions of the states 36,816 1 (349 ) 36,468 Total securities with a maturity of more than one year 268,031 38 (1,690 ) 266,379 Total available-for-sale securities $ 591,739 $ 67 $ (2,009 ) $ 589,797 Equity securities: Regulus Therapeutics Inc. $ 2,133 $ 281 $ — $ 2,414 Total equity securities $ 2,133 $ 281 $ — $ 2,414 Total available-for-sale and equity securities $ 593,872 $ 348 $ (2,009 ) $ 592,211 (1) Our available-for-sale securities are held at amortized cost. (2) Includes investments classified as cash equivalents on our consolidated balance sheet.
Temporarily Impaired Investments	Investments we consider to be temporarily impaired at December 31, 2017 are as follows (in thousands): Less than 12 Months of Temporary Impairment More than 12 Months of Temporary Impairment Total Temporary Impairment Number of Investments Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Corporate debt securities 476 $ 551,446 $ (1,236 ) $ 74,987 $ (575 ) $ 626,433 $ (1,811 ) Debt securities issued by U.S. government agencies 45 107,788 (262 ) 27,538 (118 ) 135,326 (380 ) Debt securities issued by the U.S. Treasury 7 30,818 (19 ) — — 30,818 (19 ) Debt securities issued by states of the U.S. and political subdivisions of the states 60 62,519 (545 ) 24,572 (317 ) 87,091 (862 ) Total temporarily impaired securities 588 $ 752,571 $ (2,062 ) $ 127,097 $ (1,010 ) $ 879,668 $ (3,072 )

Long-Term Obligations and Com23

Long-Term Obligations and Commitments (Tables)	12 Months Ended
	Dec. 31, 2017
Long-Term Obligations and Commitments [Abstract]
Long-Term Obligations	The carrying value of our long-term obligations was as follows (in thousands): December 31, 2017 2016 1 percent convertible senior notes $ 533,111 $ 500,511 Long-term mortgage debt 59,771 — Long-term financing liability for leased facility — 72,359 Principal balance of fixed rate note with Morgan Stanley 12,500 12,500 Leases and other obligations 2,095 3,735 Total $ 607,477 $ 589,105 Less: current portion (1,621 ) (1,185 ) Total Long-Term Obligations $ 605,856 $ 587,920
Convertible Notes	At December 31, 2017, we had a nominal amount of our 2¾ percent convertible senior notes outstanding. At December 31, 2017 we had the following 1 percent convertible senior notes outstanding (amounts in millions except price per share data): 1 Percent Convertible Senior Notes Outstanding balance $ 685.5 Original issue date ($500 million of principal) November 2014 Additional issue date ($185.5 million of principal) December 2016 Maturity date November 2021 Interest rate 1 percent Conversion price per share $ 66.81 Total shares of common stock subject to conversion 10.3 We account for our convertible notes using an accounting standard that requires us to assign a value to our convertible debt equal to the estimated fair value of similar debt instruments without the conversion feature and to record the remaining portion in equity. As a result, we recorded our convertible notes at a discount, which we are amortizing as additional non-cash interest expense over the expected life of the respective debt. We determined our nonconvertible debt borrowing rate using a combination of the present value of the debt’s cash flows and a Black-Scholes valuation model. The following table summarizes the nonconvertible borrowing rate, effective interest rate and amortization period of our debt discount for our convertible notes: 1 Percent Convertible Senior Notes Issued in November 2014 1 Percent Convertible Senior Notes Issued in December 2016 Nonconvertible debt borrowing rate 7.4 percent 6.8 percent Effective interest rate 7.8 percent 7.2 percent Amortization period of debt discount 7 years 5 years The following table summarizes information about the equity and liability components of our outstanding 1 percent convertible notes (in thousands). We measured the fair values of the convertible notes outstanding based on quoted market prices, which is a Level 2 measurement: December 31, 2017 2016 Fair value of outstanding notes $ 727,420 $ 700,969 Principal amount of convertible notes outstanding $ 685,450 $ 685,450 Unamortized portion of debt discount $ 144,112 $ 175,699 Long-term debt $ 533,111 $ 500,511 Carrying value of equity component $ 219,011 $ 219,011
Maturity Schedules	Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2017 are as follows (in thousands): 2018 $ 9,617 2019 22,082 2020 9,330 2021 694,774 2022 2,809 Thereafter 71,603 Subtotal $ 810,215 Less: current portion (53 ) Less: fixed and determinable interest (51,465 ) Less: unamortized portion of debt discount (144,791 ) Plus: Deferred rent 165 Total $ 614,071
Future Minimum Payments Under Operating Leases	Annual future minimum payments under operating leases as of December 31, 2017 are as follows (in thousands): Operating Leases 2018 $ 864 2019 636 2020 477 2021 147 Total minimum payments $ 2,124

Stockholders' Equity (Tables)

Stockholders' Equity (Tables)	12 Months Ended
	Dec. 31, 2017
Stockholders' Equity [Abstract]
Stock Option Activity	The following table summarizes the stock option activity for the year ended December 31, 2017 (in thousands, except per share and contractual life data): Number of Shares Weighted Average Exercise Price Per Share Average Remaining Contractual Term (Years) Aggregate Intrinsic Value Outstanding at December 31, 2016 9,178 $ 40.48 Granted 3,274 $ 47.76 Exercised (1,345 ) $ 15.74 Cancelled/forfeited/expired (1,710 ) $ 51.71 Outstanding at December 31, 2017 9,397 $ 44.52 4.42 $ 92,288 Exercisable at December 31, 2017 5,182 $ 39.10 3.33 $ 80,167
RSU Activity	The following table summarizes the RSU activity for the year ended December 31, 2017 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2016 778 $ 47.68 Granted 420 $ 48.88 Vested (296 ) $ 43.79 Cancelled/forfeited (39 ) $ 48.90 Non-vested at December 31, 2017 863 $ 49.55
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the years ended December 31, 2017, 2016 and 2015 (in thousands), which was allocated as follows and includes $17.5 million, $10.1 million and $6.5 million of stock-based compensation expense for Akcea employees in 2017, 2016 and 2015, respectively: Years Ended December 31, 2017 2016 2015 Research, development and patent $ 64,521 $ 55,099 $ 43,638 Selling, general and administrative 21,454 17,009 15,676 Total $ 85,975 $ 72,108 $ 59,314
Weighted-Average Assumptions for Stock Options	For the years ended December 31, 2017, 2016 and 2015, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: December 31, 2017 2016 2015 Risk-free interest rate 1.8 % 1.5 % 1.5 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 65.9 % 58.7 % 53.8 % Expected life 4.5 years 4.5 years 4.5 years Board of Director Stock Options: December 31, 2017 2016 2015 Risk-free interest rate 2.2 % 1.3 % 2.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 61.2 % 53.1 % 52.2 % Expected life 6.6 years 6.5 years 6.9 years
Weighted-Average Assumptions for ESPP	ESPP: December 31, 2017 2016 2015 Risk-free interest rate 0.8 % 0.4 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 59.9 % 86.4 % 51.7 % Expected life 6 months 6 months 6 months

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2017
Income Taxes [Abstract]
Loss Before Income Tax (Benefit) Expense	Loss before income tax (benefit) expense is comprised of (in thousands): Years Ended December 31, 2017 2016 2015 United States $ (11,802 ) $ (83,622 ) $ (87,906 ) Foreign (11,474 ) — — Loss before income tax (benefit) expense $ (23,276 ) $ (83,622 ) $ (87,906 )
Income Tax (Benefit) Expense	Our income tax (benefit) expense was as follows (in thousands): Years Ended December 31, 2017 2016 2015 Current: Federal $ (7,460 ) $ 1,067 $ 379 State 1,246 1,867 (7 ) Foreign 234 — — Total current income tax (benefit) expense (5,980 ) 2,934 372 Deferred: Federal — — — State — — — Total deferred income tax (benefit) expense — — — Total income tax (benefit) expense $ (5,980 ) $ 2,934 $ 372
Reconciliation of Statutory to Effective Tax Rate	The reconciliation between our effective tax rate on loss from continuing operations and the statutory U.S. tax rate is as follows (in thousands): Years Ended December 31, 2017 2016 2015 Pre-tax loss $ (23,276 ) $ (83,622 ) $ (87,906 ) Statutory rate (8,147 ) 35.0 % (29,268 ) 35.0 % (30,767 ) 35.0 % State income tax net of federal benefit 722 (3.1 )% (276 ) 0.3 % 1 0.0 % Foreign 4,299 (18.3 )% — 0.0 % — 0.0 % Net change in valuation allowance (76,409 ) 328.3 % 55,927 (66.9 )% 69,499 (79.1 )% Net operating loss expiration 3,987 (17.0 )% — 0.0 % — 0.0 % Tax credits (32,769 ) 140.8 % (26,954 ) 32.2 % (41,284 ) 47.0 % Deferred tax true-up 4,848 (20.6 )% 2,591 (3.1 )% 1,496 (1.7 )% Tax Cuts and Jobs Act 107,323 (461.1 )% — — 0.0 % Nondeductible items 4,123 (17.9 )% 1,149 (1.4 )% 1,055 (1.2 )% Akcea deconsolidation adjustment at IPO 469 (2.0 )% — 0.0 % — 0.0 % Excess stock-based compensation (14,337 ) 61.0 % — 0.0 % — 0.0 % Other (89 ) 0.6 % (235 ) 0.4 % 372 (0.4 )% Effective rate $ (5,980 ) 25.7 % $ 2,934 (3.5 )% $ 372 (0.4 )%
Deferred Tax Assets and Liabilities	Significant components of our deferred tax assets and liabilities as of December 31, 2017 and 2016 are as follows (in thousands): Years Ended December 31, 2017 2016 Deferred Tax Assets: Net operating loss carryovers $ 153,575 $ 194,372 R&D credits 240,290 193,845 Deferred revenue 42,055 54,203 Stock-based compensation 40,090 48,209 Intangible and capital assets 672 — Other 12,164 26,228 Total deferred tax assets $ 488,846 $ 516,857 Deferred Tax Liabilities: Convertible debt $ (32,391 ) $ (62,669 ) Intangible and capital assets — (2,030 ) Net deferred tax asset $ 456,455 $ 452,158 Valuation allowance (456,455 ) (452,158 ) Total net deferred tax assets and liabilities $ — $ —
Gross Unrecognized Tax Benefits	The following table summarizes our gross unrecognized tax benefits (in thousands): Years Ended December 31, 2017 2016 2015 Beginning balance of unrecognized tax benefits $ 66,999 $ 51,257 $ 27,365 Settlement of prior period tax positions — (4,033 ) — Increase for prior period tax positions 1,520 7,928 215 Increase for current period tax positions 9,495 11,847 23,677 Ending balance of unrecognized tax benefits $ 78,014 $ 66,999 $ 51,257

Segment Information and Conce26

Segment Information and Concentration of Business Risk (Tables)	12 Months Ended
	Dec. 31, 2017
Segment Information and Concentration of Business Risk [Abstract]
Segment Information	2017 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Commercial revenue: SPINRAZA royalties $ 112,540 $ — $ — $ 112,540 Licensing and other royalty revenue 9,519 — — 9,519 Total commercial revenue 122,059 — — 122,059 R&D revenue under collaborative agreements 384,805 55,209 (54,407 ) 385,607 Total segment revenue $ 506,864 $ 55,209 $ (54,407 ) $ 507,666 Total operating expenses $ 373,788 $ 163,871 $ (54,527 ) $ 483,132 Income (loss) from operations $ 133,076 $ (108,662 ) $ 120 $ 24,534 2016 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Commercial revenue: SPINRAZA royalties $ 883 $ — $ — $ 883 Licensing and other royalty revenue 19,839 — — 19,839 Total commercial revenue 20,722 — — 20,722 R&D revenue under collaborative agreements 338,546 — (12,648 ) 325,898 Total segment revenue $ 359,268 $ — $ (12,648 ) $ 346,620 Total operating expenses $ 322,192 $ 83,512 $ (12,768 ) $ 392,936 Income (loss) from operations $ 37,076 $ (83,512 ) $ 120 $ (46,316 ) 2015 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: R&D revenue under collaborative agreements $ 284,015 $ — $ (2,655 ) $ 281,360 Licensing and other royalty revenue 2,343 — — 2,343 Total segment revenue $ 286,358 $ — $ (2,655 ) $ 283,703 Total operating expenses $ 309,492 $ 52,748 $ (2,775 ) $ 359,465 Income (loss) from operations $ (23,134 ) $ (52,748 ) $ 120 $ (75,762 ) The following table shows our total assets by segment at December 31, 2017 and 2016 (in thousands), respectively. Total Assets Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total December 31, 2017 $ 1,341,828 $ 268,804 $ (288,608 ) $ 1,322,024 December 31, 2016 $ 1,067,770 $ 10,684 $ (165,987 ) $ 912,467
Revenue from Significant Partners	We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as 10 percent or more of our total revenue, was as follows: 2017 2016 2015 Partner A 51 % 60 % 37 % Partner B 14 % 2 % 33 % Partner C 10 % 2 % 11 % Partner D 11 % 0 % 0 % Partner E 3 % 19 % 2 % Partner F 2 % 4 % 12 %

Quarterly Financial Data (Una27

Quarterly Financial Data (Unaudited) (Tables)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Data (Unaudited) [Abstract]
Quarterly Financial Data	The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a fair statement of the results of the interim periods. Summarized quarterly data for the years ended December 31, 2017 and 2016 are as follows (in thousands, except per share data). 2017 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 110,304 $ 104,152 $ 120,911 $ 172,299 Operating expenses $ 96,315 $ 105,823 $ 107,002 $ 173,992 Income (loss) from operations $ 13,989 $ (1,671 ) $ 13,909 $ (1,693 ) Net income (loss) $ 3,468 $ (11,206 ) $ (4,896 ) $ (4,662 ) Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders $ 3,468 $ (11,206 ) $ (976 ) $ 2,744 Basic net income (loss) per share (1) (2) $ 0.03 $ (0.09 ) $ 0.00 $ 0.02 Diluted net income (loss) per share (1) (3) $ 0.03 $ (0.09 ) $ 0.00 $ 0.02 2016 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 36,874 $ 38,470 $ 110,927 $ 160,349 Operating expenses $ 91,526 $ 87,397 $ 94,819 $ 119,194 Income (loss) from operations $ (54,652 ) $ (48,927 ) $ 16,108 $ 41,155 Net income (loss) $ (62,917 ) $ (56,855 ) $ 7,351 $ 25,865 Basic net income (loss) per share (1) $ (0.52 ) $ (0.47 ) $ 0.06 $ 0.21 Diluted net income (loss) per share (1) (4) (5) $ (0.52 ) $ (0.47 ) $ 0.06 $ 0.21 (1) We computed net income (loss) per share independently for each of the quarters presented. Therefore, the sum of the quarterly net income (loss) per share will not necessarily equal the total for the year. (2) As discussed in Note 1, Organization and Significant Accounting Policies, Our basic net income (loss) per share for the three months ended December 31, 2017, was calculated as follows (in thousands, except per share amounts): Three Months Ended December 31, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Loss Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 45,448 $ (0.35 ) $ (15,955 ) Akcea’s net loss attributable to our ownership $ (15,955 ) Ionis’ stand-alone net income 18,672 Net income available to Ionis common stockholders $ 2,717 Weighted average shares outstanding 124,818 Basic net income per share $ 0.02 For the three months ended December 31, 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. Diluted common equivalent shares for the three months ended December 31, 2017 consisted of the following (in thousands except per share amounts): Three Months Ended December 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 2,717 124,818 $ 0.02 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,532 Shares issuable upon restricted stock award issuance — 507 Shares issuable related to our ESPP — 5 Income available to common shareholders, plus assumed conversions $ 2,717 126,862 $ 0.02 For the three months ended December 31, 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. Prior to Akcea’s IPO, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea’s IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. During the three months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the six percent cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares which we owned in our calculation of basic and diluted net income (loss) per share for three months ended September 30, 2017. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations. Our basic net income (loss) per share for the three months ended September 30, 2017, was calculated as follows (in thousands, except per share amounts): Three Months Ended September 30, 2017 Weighted Average Shares Owned in Akcea Akcea’s Net Income (Loss) Per Share Ionis’ Portion of Akcea’s Net Loss Common shares 36,556 $ (0.27 ) $ (9,870 ) Preferred shares 5,651 0.05 283 Akcea’s net loss attributable to our ownership $ (9,587 ) Ionis’ stand-alone net income 9,168 Net loss available to Ionis common stockholders $ (419 ) Weighted average shares outstanding 124,370 Basic net income per share $ 0.00 (3) For the three months ended March 31, 2017 we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended March 31, 2017 consisted of the following (in thousands): Three Months Ended March 31, 2017 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 3,468 122,861 $ 0.03 Effect of dilutive securities: Shares issuable upon exercise of stock options — 1,674 Shares issuable upon restricted stock award issuance — 377 Shares issuable related to our ESPP — 60 Income available to common shareholders, plus assumed conversions $ 3,468 124,972 $ 0.03 For the three months ended March 31, 2017, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive. (4) For the three months ended December 31, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended December 31, 2016 consisted of the following (in thousands): Three Months Ended December 31, 2016 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 25,865 121,340 $ 0.21 Effect of diluted securities: Shares issuable upon exercise of stock options — 2,189 Shares issuable upon restricted stock award issuance — 403 Shares issuable related to our ESPP — 21 Income available to common shareholders, plus assumed conversions $ 25,865 123,953 $ 0.21 For the three months ended December 31, 2016, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share would be anti-dilutive. (5) For the three months ended September 30, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. Diluted common equivalent shares for the three months ended September 30, 2016 consisted of the following (in thousands): Three Months Ended September 30, 2016 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 7,351 120,989 $ 0.06 Effect of diluted securities: Shares issuable upon exercise of stock options — 2,129 Shares issuable upon restricted stock award issuance — 202 Shares issuable related to our ESPP — 58 Income available to common shareholders, plus assumed conversions $ 7,351 123,378 $ 0.06 For the three months ended September 30, 2016, the calculation excludes the 1 percent and 2¾ percent notes because the effect on diluted earnings per share would be anti-dilutive.

Organization and Significant 28

Organization and Significant Accounting Policies, Basis of Presentation (Details)	5 Months Ended	7 Months Ended
	Dec. 31, 2017	Jul. 18, 2017
Organization and Significant Accounting Policies [Abstract]
Percentage ownership before IPO		100.00%
Percentage ownership after IPO	68.00%

Organization and Significant 29

Organization and Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended																12 Months Ended
	Dec. 31, 2017		Sep. 30, 2017		Jun. 30, 2017		Mar. 31, 2017		Dec. 31, 2016		Sep. 30, 2016		Jun. 30, 2016	[2]	Mar. 31, 2016	[2]	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Basic Net Income (Loss) per Share [Abstract]
Basic net income (loss) per share (in dollars per share)	$ 0.02	[1],[2]	$ 0	[1],[2]	$ (0.09)	[2]	$ 0.03	[2]	$ 0.21	[2]	$ 0.06	[2]	$ (0.47)		$ (0.52)		$ 0.08	$ (0.72)	$ (0.74)
Net income (loss)	$ 2,744		$ (976)		$ (11,206)		$ 3,468										$ (5,970)	$ (86,556)	$ (88,278)
Net income available to Ionis common stockholders	$ 2,717		$ (419)				$ 3,468		$ 25,865		$ 7,351						$ 9,661
Shares used in computing basic net income per share (in shares)	124,818		124,370				122,861		121,340		120,989						124,016	120,933	119,719
Income available to Ionis common shareholders, plus assumed conversions	$ 2,717						$ 3,468		$ 25,865		$ 7,351						$ 9,661
Shares issuable related to our ESPP																	4
Shares used in computing diluted net income per share (in shares)	126,862						124,972		123,953		123,378						126,098	120,933	119,719
Diluted net income per share (in dollars per share)	$ 0.02	[2]	$ 0	[2]	$ (0.09)	[2]	$ 0.03	[2],[3]	$ 0.21	[2],[4]	$ 0.06	[2],[5]	$ (0.47)		$ (0.52)		$ 0.08	$ (0.72)	$ (0.74)
1 Percent Convertible Senior Notes [Member]
Basic Net Income (Loss) per Share [Abstract]
Interest rate on convertible senior notes	1.00%						1.00%		1.00%		1.00%						1.00%	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Basic Net Income (Loss) per Share [Abstract]
Interest rate on convertible senior notes	2.75%						2.75%		2.75%		2.75%						2.75%	2.75%	2.75%
Stock Options [Member]
Basic Net Income (Loss) per Share [Abstract]
Shares issuable related to stock-based compensation (in shares)	1,532						1,674		2,189		2,129						1,619
Restricted Stock Awards [Member]
Basic Net Income (Loss) per Share [Abstract]
Shares issuable related to stock-based compensation (in shares)	507						377		403		202						459
Ionis [Member]
Basic Net Income (Loss) per Share [Abstract]
Net income (loss)	$ 18,672		$ 9,168														$ 92,336
Akcea [Member]
Basic Net Income (Loss) per Share [Abstract]
Net income (loss)	$ (15,955)		$ (9,587)														$ (82,676)
Akcea [Member] | Common Stock [Member]
Basic Net Income (Loss) per Share [Abstract]
Weighted average shares owned in Akcea (in shares)	45,448		36,556														20,669
Basic net income (loss) per share (in dollars per share)	$ (0.35)		$ (0.27)														$ (2.82)
Net income (loss)	$ (15,955)		$ (9,870)														$ (58,332)
Akcea [Member] | Series A Convertible Preferred Stock [Member]
Basic Net Income (Loss) per Share [Abstract]
Dividend rate																	6.00%
Conversion ratio																	converted into common stock on a 1:1 basis
Weighted average shares owned in Akcea (in shares)			5,651														15,748
Basic net income (loss) per share (in dollars per share)			$ 0.05														$ (1.55)
Net income (loss)			$ 283														$ (24,344)
[1]	As discussed in Note 1, Organization and Significant Accounting Policies, we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. The calculation of total net income (loss) attributable to our common stockholders for the three months ended December 31, 2017 and September 30, 2017 considered our net income for Ionis on a stand-alone basis plus our share of Akcea's net loss for the periods. To calculate the portion of Akcea's net loss attributable to our ownership, we multiplied Akcea's income (loss) per share by the weighted average shares we owned in Akcea during the period. For the three months ended December 31, 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. For the three months ended December 31, 2017, the calculation excluded the 1 percent and 2.75 percent notes because the effect on diluted earnings per share was anti-dilutive. Prior to Akcea's IPO, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea's IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. During the three months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the six percent cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares which we owned in our calculation of basic and diluted net income (loss) per share for three months ended September 30, 2017. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.
[2]	We computed net income (loss) per share independently for each of the quarters presented. Therefore, the sum of the quarterly net income (loss) per share will not necessarily equal the total for the year.
[3]	For the three months ended March 31, 2017 we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended March 31, 2017, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share was anti-dilutive.
[4]	For the three months ended December, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended December 31, 2016, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share would be anti-dilutive.
[5]	For the three months ended September 30, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended September 30, 2016, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share would be anti-dilutive.

Organization and Significant 30

Organization and Significant Accounting Policies, Revenue Recognition (Details) $ in Thousands, shares in Millions	1 Months Ended		3 Months Ended			12 Months Ended
	Feb. 28, 2017USD ($)AccountingUnit	May 31, 2015USD ($)	Dec. 31, 2017USD ($)Agreement	Mar. 31, 2017USD ($)AccountingUnitDrugshares	Jun. 30, 2015USD ($)	Dec. 31, 2017USD ($)DrugCategoryStagePartner	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Jan. 31, 2017USD ($)
Revenue Recognition [Abstract]
SPINRAZA royalties						$ 112,540	$ 883	$ 0
Number of categories of milestone events | Category						3
Number of stages of life-cycle of drugs | Stage						3
Number of partners that exercised option to license drugs | Partner						3
Number of drugs licensed under option in collaboration agreements | Drug						3
Minimum [Member]
Revenue Recognition [Abstract]
Period to complete IND-enabling animal studies						12 months
Period to complete Phase 1 clinical trial						1 year
Period to complete Phase 2 clinical trial						1 year
Period to complete Phase 3 clinical trial						2 years
Period to prepare and submit regulatory filings						6 months
Period to obtain marketing authorization from applicable regulatory agency						1 year
Pre-specified product sales threshold included in commercialization milestones						$ 1,000,000
Maximum [Member]
Revenue Recognition [Abstract]
Period to complete IND-enabling animal studies						18 months
Period to complete Phase 1 clinical trial						2 years
Period to complete Phase 2 clinical trial						3 years
Period to complete Phase 3 clinical trial						4 years
Period to prepare and submit regulatory filings						12 months
Period to obtain marketing authorization from applicable regulatory agency						2 years
Novartis [Member]
Revenue Recognition [Abstract]
Number of agreements | Agreement			2
Bayer [Member]
Revenue Recognition [Abstract]
Upfront payment received	$ 75,000	$ 100,000			$ 100,000
Bayer [Member]
Revenue Recognition [Abstract]
Payment received for advancing programs	$ 75,000
Number of units of accounting | AccountingUnit	3
Allocable arrangement consideration	$ 76,300
Consideration allocated to exclusive license	64,900
Consideration allocated to development activities	11,000
Consideration allocated to delivery of API	$ 400
Assumed percentage change in estimated selling price	10.00%
Percentage change in earned revenue based on assumed change in estimated selling price	1.00%
Amount by which earned revenue would change based on assumed change in estimated selling price	$ 700
Novartis [Member]
Revenue Recognition [Abstract]
Number of units of accounting | AccountingUnit				4
Number of drugs with exclusive option that could be exercised | Drug				1
Shares issued (in shares) | shares				1.6
Proceeds from sale of common stock, including premium paid				$ 100,000
Additional amount of common stock required to be purchased				50,000					$ 50,000
Akcea [Member] | Novartis [Member]
Revenue Recognition [Abstract]
Upfront payment received				$ 75,000
License fee receivable per drug			$ 150,000			$ 150,000

Organization and Significant 31

Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Research, Development and Patent Expenses [Abstract]
Research and development expenses	$ 372.5	$ 340.4	$ 319.5
Patents [Member]
Patents [Abstract]
Estimated useful life	10 years 1 month 6 days
Cost	$ 30.8	28.8
Accumulated amortization	8.8	8.4
Estimated Amortization Expense [Abstract]
2,018	1.6
2,019	1.4
2,020	1.3
2,021	1.3
2,022	1.2
Patent expenses	2.1	3.9	2.8
Non-cash charges related to write-down	0.4	2.3	1.1
Collaborative Agreements [Member]
Research, Development and Patent Expenses [Abstract]
Research and development expenses	$ 59.5	$ 187.1	$ 161.7

Organization and Significant 32

Organization and Significant Accounting Policies, Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Organization and Significant Accounting Policies [Abstract]
Clincial expenses	$ 16,347	$ 23,428
In-licensing expenses	33,790	6,430
Other miscellanous accruals	16,481	6,155
Total accrued liabilities	$ 66,618	$ 36,013

Organization and Significant 33

Organization and Significant Accounting Policies, Noncontrolling Interest in Akcea Therapeutics, Inc. (Details) - USD ($) $ in Thousands	1 Months Ended	5 Months Ended	7 Months Ended	12 Months Ended
	Jul. 31, 2017	Dec. 31, 2017	Jul. 18, 2017	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Akcea IPO [Abstract]
Proceeds from sale of common stock to Novartis in a private placement				$ 50,000	$ 0	$ 0
Investment in subsidiary	$ 25,000
Percentage ownership before IPO			100.00%
Percentage of results included in consolidation			100.00%
Percentage ownership after IPO		68.00%
Akcea [Member]
Akcea IPO [Abstract]
Gross proceeds from IPO	193,800
Proceeds from sale of common stock to Novartis in a private placement	50,000
Net proceeds from IPO	$ 182,400

Organization and Significant 34

Organization and Significant Accounting Policies, Cash, Cash Equivalents and Short-Term Investments (Details)	Dec. 31, 2017Company
Cash, Cash Equivalents and Investments [Abstract]
Number of publicly-held companies in which there is an equity ownership interest of less than 20%	1
Number of privately-held companies in which there is an equity ownership interest of less than 20%	5

Organization and Significant 35

Organization and Significant Accounting Policies, Inventory Valuation (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Inventory Valuation [Abstract]
Inventory write-off	$ 0	$ 0	$ 0
Inventories	$ 9,982	$ 7,489

Organization and Significant 36

Organization and Significant Accounting Policies, Property, Plant and Equipment (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
Property, Plant and Equipment [Abstract]
Less accumulated depreciation	$ (87,676)	$ (80,075)
Property, plant and equipment, net	121,907	92,845
Property, Plant and Equipment, Excluding Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	195,090	162,722
Property, plant and equipment, net	107,414	82,647
Computer Software, Laboratory, Manufacturing and Other Equipment [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 66,558	63,287
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	3 years
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	10 years
Building, Building Improvements and Building Systems [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 92,770	48,909
Building, Building Improvements and Building Systems [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	15 years
Building, Building Improvements and Building Systems [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	40 years
Land Improvements [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 2,853	2,853
Estimated useful lives	20 years
Leasehold Improvements [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 26,748	41,736
Leasehold Improvements [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	5 years
Leasehold Improvements [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	15 years
Furniture and Fixtures [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 6,161	5,937
Furniture and Fixtures [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	5 years
Furniture and Fixtures [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful lives	10 years
Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 14,493	$ 10,198

Organization and Significant 37

Organization and Significant Accounting Policies, Long-Lived Assets (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Long-Lived Assets [Abstract]
Charges related to write-down of intangible assets	$ 0.8	$ 2.3	$ 1.9

Organization and Significant 38

Organization and Significant Accounting Policies, Stock-based Compensation Expense (Details)	12 Months Ended
	Dec. 31, 2017
RSUs [Member]
Stock-Based Compensation [Abstract]
Vesting period	4 years

Organization and Significant 39

Organization and Significant Accounting Policies, Accumulated Other Comprehensive Income (Loss) (Details) - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Balance		$ 99,565	$ 200,790	$ 257,780
Net other comprehensive loss for the period		(1,401)	(16,793)	(53,312)
Balance		418,719	99,565	200,790
Income tax expense included in other comprehensive income		0	0	0
Accumulated Other Comprehensive (Loss) Income [Member]
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Balance		(30,358)	(13,565)	39,747
Balance		(31,759)	(30,358)	(13,565)
Unrealized Losses on Securities [Member]
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Other comprehensive loss before reclassifications, net of tax	[1]	(960)	(17,219)	(33,101)
Amounts reclassified from accumulated other comprehensive (loss) income	[2]	(374)	447	(20,211)
Currency Translation Adjustment [Member]
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Other comprehensive loss before reclassifications, net of tax		$ (67)	$ (21)	$ 0
[1]	There was no tax expense for other comprehensive loss for the years ended December 31, 2017, 2016 or 2015.
[2]	Amounts for 2015 are included in the separate line called "Gain on investment in Regulus Therapeutics Inc." on our Consolidated Statement of Operations.

Organization and Significant 40

Organization and Significant Accounting Policies, Convertible Debt (Details)	Dec. 31, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Dec. 31, 2015
1 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	2.75%	2.75%	2.75%	2.75%	2.75%

Organization and Significant 41

Organization and Significant Accounting Policies, Segment Information (Details) - Segment	5 Months Ended	7 Months Ended	12 Months Ended
	Dec. 31, 2017	Jul. 18, 2017	Dec. 31, 2017
Segment Information [Abstract]
Number of operating segments			2
Percentage ownership before IPO		100.00%
Percentage ownership after IPO	68.00%

Organization and Significant 42

Organization and Significant Accounting Policies, Fair Value Measurements on a Recurring Basis (Details) - USD ($) $ in Thousands		Dec. 31, 2017		Dec. 31, 2016
Organization and Significant Accounting Policies [Abstract]
Transfers from Level 1 to Level 2		$ 0		$ 0
Transfers from Level 2 to Level 1		0		0
Fair Value Measurements [Abstract]
Available-for-sale securities				592,211
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	86,262		54,137
Investment in Regulus Therapeutics Inc.				2,414
Total		994,798		646,348
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		647,461	[2]	396,221	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		11,900
Recurring Basis [Member] | Debt Securities issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[3]	136,325		55,179
Recurring Basis [Member] | Debt Securities issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[3]	30,818		29,286
Recurring Basis [Member] | Debt Securities issued by the U.S. Treasury [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		3,500		9,300
Recurring Basis [Member] | Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		93,932	[4]	109,111	[5]
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		86,262		54,137
Investment in Regulus Therapeutics Inc.				2,414
Total		117,080		85,837
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		30,818		29,286
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Investment in Regulus Therapeutics Inc.				0
Total		877,718		560,511
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		647,461		396,221
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		136,325		55,179
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		93,932		109,111
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]
Fair Value Measurements [Abstract]
Total		$ 0		$ 0
[1]	Included in cash and cash equivalents on our consolidated balance sheet.
[2]	$11.9 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
[3]	Included in short-term investments on our consolidated balance sheet.
[4]	$3.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
[5]	$9.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.

Organization and Significant 43

Organization and Significant Accounting Policies, Fair Value Measurements - Novartis Future Stock Purchase (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Mar. 31, 2017	Jan. 31, 2017
Novartis [Member]
Novartis Future Stock Purchase [Abstract]
Additional amount of common stock required to be purchased		$ 50,000	$ 50,000
Fair value of potential future premium			$ 5,000
Equity Securities [Member]
Unobservable Inputs (Level 3) [Roll Forward]
Beginning balance of Level 3 instruments	$ 0
Value of the potential premium we will receive from Novartis at inception of the SPA (January 2017)	5,035
Write-off of premium to other expenses	(5,035)
Ending balance of Level 3 instruments	$ 0

Organization and Significant 44

Organization and Significant Accounting Policies, Income Taxes (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Income Taxes [Abstract]
U.S. federal corporate tax rate		35.00%	35.00%	35.00%
Plan [Member]
Income Taxes [Abstract]
U.S. federal corporate tax rate	21.00%

Organization and Significant 45

Organization and Significant Accounting Policies, Impact of Recently Issued Accounting Standards (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Impact of Recently Issued Accounting Standards [Abstract]
Revenue	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Accumulated deficit	(1,187,398)				(1,181,428)				(1,187,398)	(1,181,428)
Income tax expense									(5,980)	2,934	372
Biogen [Member]
Impact of Recently Issued Accounting Standards [Abstract]
Milestone payment earned									50,000
Revenue									259,800	207,900	$ 106,200
Deferred revenue	69,300				$ 67,500				69,300	67,500
Biogen [Member] | IONIS-MAPT [Member]
Impact of Recently Issued Accounting Standards [Abstract]
Milestone payment earned									10,000
Revenue									10,000
Recognition of Revenue from Customers [Member] | Plan [Member]
Impact of Recently Issued Accounting Standards [Abstract]
Revenue									17,000	27,000
Deferred revenue	39,000								39,000
Accumulated deficit	$ 39,000								39,000
Income tax expense									$ 0	$ 0

Investments, Contract Maturity

Investments, Contract Maturity of Available-for-Sale Securities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)Company	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	71.00%
After one year but within two years	23.00%
After two years but within three and a half years	6.00%
Total	100.00%
Percentage of available-for-sale securities with a maturity of less than two years	94.00%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months
Ownership Interests in Private and Public Companies [Abstract]
Number of privately-held companies in which there is an equity ownership interest of less than 20%	5
Number of publicly-held companies in which there is an equity ownership interest of less than 20%	1
Gain on investment in Regulus Therapeutics Inc. | $	$ 374	$ 0	$ 20,211

Investments, Summary of Investm

Investments, Summary of Investments (Details) - USD ($) $ in Thousands		Dec. 31, 2017		Dec. 31, 2016
Summary of Investments [Abstract]
Cost				$ 593,872
Gross unrealized gains				348
Gross unrealized losses				(2,009)
Estimated fair value				592,211
Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	$ 643,193		323,708
Gross unrealized gains		6		29
Gross unrealized losses		(1,103)		(319)
Estimated fair value		642,096		323,418
Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	268,401		268,031
Gross unrealized gains		8		38
Gross unrealized losses		(1,969)		(1,690)
Estimated fair value		266,440		266,379
Available-for-sale Securities [Member]
Summary of Investments [Abstract]
Cost	[1]	911,594		591,739
Gross unrealized gains		14		67
Gross unrealized losses		(3,072)		(2,009)
Estimated fair value		908,536		589,797
Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	500,599	[2]	195,087
Gross unrealized gains		2		25
Gross unrealized losses		(752)		(161)
Estimated fair value		499,849		194,951
Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	148,663		202,408
Gross unrealized gains		8		36
Gross unrealized losses		(1,059)		(1,174)
Estimated fair value		147,612		201,270
Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	83,926		26,548
Gross unrealized gains		0		0
Gross unrealized losses		(212)		(10)
Estimated fair value		83,714		26,538
Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	52,779		28,807
Gross unrealized gains		0		1
Gross unrealized losses		(168)		(167)
Estimated fair value		52,611		28,641
Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	29,428		29,298
Gross unrealized gains		0		2
Gross unrealized losses		(17)		(14)
Estimated fair value		29,411		29,286
Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	1,409
Gross unrealized gains		0
Gross unrealized losses		(2)
Estimated fair value		1,407
Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1],[2]	29,240		72,775
Gross unrealized gains		4		2
Gross unrealized losses		(122)		(134)
Estimated fair value		29,122		72,643
Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	65,550		36,816
Gross unrealized gains		0		1
Gross unrealized losses		(740)		(349)
Estimated fair value		$ 64,810		36,468
Equity Securities [Member]
Summary of Investments [Abstract]
Cost				2,133
Gross unrealized gains				281
Gross unrealized losses				0
Estimated fair value				2,414
Regulus Therapeutics Inc. [Member]
Summary of Investments [Abstract]
Cost				2,133
Gross unrealized gains				281
Gross unrealized losses				0
Estimated fair value				$ 2,414
[1]	Our available-for-sale securities are held at amortized cost.
[2]	Includes investments classified as cash equivalents on our consolidated balance sheet.

Investments, Investments Tempor

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Dec. 31, 2017USD ($)Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	588
Estimated fair value, less than 12 months of temporary impairment	$ 752,571
Unrealized losses, less than 12 months of temporary impairment	(2,062)
Estimated fair value, more than 12 months of temporary impairment	127,097
Unrealized losses, more than 12 months of temporary impairment	(1,010)
Estimated fair value, total temporary impairment	879,668
Unrealized losses, total temporary impairment	$ (3,072)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	476
Estimated fair value, less than 12 months of temporary impairment	$ 551,446
Unrealized losses, less than 12 months of temporary impairment	(1,236)
Estimated fair value, more than 12 months of temporary impairment	74,987
Unrealized losses, more than 12 months of temporary impairment	(575)
Estimated fair value, total temporary impairment	626,433
Unrealized losses, total temporary impairment	$ (1,811)
Debt Securities issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	45
Estimated fair value, less than 12 months of temporary impairment	$ 107,788
Unrealized losses, less than 12 months of temporary impairment	(262)
Estimated fair value, more than 12 months of temporary impairment	27,538
Unrealized losses, more than 12 months of temporary impairment	(118)
Estimated fair value, total temporary impairment	135,326
Unrealized losses, total temporary impairment	$ (380)
Debt Securities issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	7
Estimated fair value, less than 12 months of temporary impairment	$ 30,818
Unrealized losses, less than 12 months of temporary impairment	(19)
Estimated fair value, more than 12 months of temporary impairment	0
Unrealized losses, more than 12 months of temporary impairment	0
Estimated fair value, total temporary impairment	30,818
Unrealized losses, total temporary impairment	$ (19)
Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	60
Estimated fair value, less than 12 months of temporary impairment	$ 62,519
Unrealized losses, less than 12 months of temporary impairment	(545)
Estimated fair value, more than 12 months of temporary impairment	24,572
Unrealized losses, more than 12 months of temporary impairment	(317)
Estimated fair value, total temporary impairment	87,091
Unrealized losses, total temporary impairment	$ (862)

Long-Term Obligations and Com49

Long-Term Obligations and Commitments, Long-Term Obligations (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	$ 607,477	$ 589,105
Less: current portion	(1,621)	(1,185)
Total Long-Term Obligations	605,856	587,920
1 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	533,111	500,511
Long-term Mortgage Debt [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	59,771	0
Long-term Financing Liability for Leased Facility [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	0	72,359
Fixed Rate Note with Morgan Stanley [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	12,500	12,500
Leases and Other Obligations [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	$ 2,095	$ 3,735

Long-Term Obligations and Com50

Long-Term Obligations and Commitments, Convertible Notes (Details) $ / shares in Units, $ in Thousands	1 Months Ended		12 Months Ended
	Dec. 31, 2016USD ($)	Nov. 30, 2014USD ($)	Dec. 31, 2017USD ($)shares$ / shares	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Mar. 31, 2017	Sep. 30, 2016
Convertible Notes [Abstract]
Loss on early retirement of debt			$ 0	$ (3,983)	$ 0
Amortization of debt discount and debt issuance costs			32,500	25,100	$ 23,200
Long-term debt	$ 500,511		$ 533,111	$ 500,511
1 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Maturity date			Nov. 30, 2021
Interest rate	1.00%		1.00%	1.00%	1.00%	1.00%	1.00%
Conversion price per share (in dollars per share) | $ / shares			$ 66.81
Total shares of common stock subject to conversion (in shares) | shares			10,300,000
Percentage of principal amount used a purchase price upon occurrence of fundamental change			100.00%
Principal amount of convertible notes outstanding	$ 685,450		$ 685,450	$ 685,450
Unamortized portion of debt discount	175,699		144,112	175,699
Long-term debt	500,511		533,111	500,511
Carrying value of equity component	219,011		219,011	219,011
1 Percent Convertible Senior Notes [Member] | Level 2 [Member]
Convertible Notes [Abstract]
Fair value of outstanding notes	700,969		$ 727,420	700,969
1 Percent Convertible Senior Notes Issued in November 2014 [Member]
Convertible Notes [Abstract]
Face amount of offering		$ 500,000
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs		487,000
Issue date			Nov. 30, 2014
Nonconvertible debt borrowing rate			7.40%
Effective interest rate			7.80%
Amortization period of debt discount			7 years
1 Percent Convertible Senior Notes Issued in December 2016 [Member]
Convertible Notes [Abstract]
Face amount of offering	185,500			185,500
Issue date			Dec. 31, 2016
Nonconvertible debt borrowing rate			6.80%
Effective interest rate			7.20%
Amortization period of debt discount			5 years
2 3/4 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Principal amount repurchased	61,100	140,000		$ 61,100
Repurchase of convertible senior notes		441,900
Loss on early retirement of debt	$ 3,983
Interest rate	2.75%		2.75%	2.75%	2.75%	2.75%	2.75%
Principal amount of convertible notes outstanding		$ 61,200

Long-Term Obligations and Com51

Long-Term Obligations and Commitments, Financing Arrangements (Details) $ in Millions	12 Months Ended
	Dec. 31, 2017USD ($)
Fixed Rate Note with Morgan Stanley [Member]
Financing Arrangements [Abstract]
Outstanding borrowings	$ 12.5
Interest rate	2.31%
Maturity date	Sep. 30, 2019
Morgan Stanley [Member] | Revolving Line of Credit [Member]
Financing Arrangements [Abstract]
Term of agreement	5 years
Maximum borrowing capacity	$ 30
Commitment fee percentage on unused capacity	0.25%
Morgan Stanley [Member] | Revolving Line of Credit [Member] | LIBOR [Member]
Financing Arrangements [Abstract]
Term of variable rate	1 month
Basis spread on variable rate	1.25%
Term of fixed rate elected	one, two, three, four, six, or twelve months

Long-Term Obligations and Com52

Long-Term Obligations and Commitments, Research and Development and Manufacturing Facilities (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended	12 Months Ended
	Jul. 31, 2017	Sep. 30, 2017	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Research and Development and Manufacturing Facilities [Abstract]
Loss on extinguishment of financing liability for leased facility			$ (7,689)	$ 0	$ 0
Primary R&D Facility [Member]
Research and Development and Manufacturing Facilities [Abstract]
Payment to acquire building	$ 79,400
Loss on extinguishment of financing liability for leased facility		$ (7,689)
Proceeds from mortgage loan	$ 51,300
Interest rate	3.88%
Period to make interest only payments on mortgage loan			5 years
Manufacturing Facility [Member]
Research and Development and Manufacturing Facilities [Abstract]
Payment to acquire building	$ 14,000
Proceeds from mortgage loan	$ 9,100
Interest rate	4.20%
Period to make interest only payments on mortgage loan			5 years

Long-Term Obligations and Com53

Long-Term Obligations and Commitments, Maturity Schedules (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Annual Debt and Other Obligation Maturities [Abstract]
Less: current portion	$ (1,621)	$ (1,185)
Total	605,856	$ 587,920
Long-Term Obligations, Excluding Financing Liability for Leased Facility [Member]
Annual Debt and Other Obligation Maturities [Abstract]
2,018	9,617
2,019	22,082
2,020	9,330
2,021	694,774
2,022	2,809
Thereafter	71,603
Total minimum payments	810,215
Less: current portion	(53)
Less: fixed and determinable interest	(51,465)
Less: unamortized portion of debt discount	(144,791)
Plus: Deferred rent	165
Total	$ 614,071

Long-Term Obligations and Com54

Long-Term Obligations and Commitments, Operating Leases (Details) - Office and Laboratory Space [Member] $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)Option	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Annual Future Minimum Payments Under Operating Leases [Abstract]
2,018	$ 864
2,019	636
2,020	477
2,021	147
Total minimum payments	2,124
Rent expense	1,700	$ 2,000	$ 2,000
Deferred rent	$ 100	$ 2,100
Building [Member]
Operating Leases [Abstract]
Number of options to extend lease | Option	2
Term of lease extension	5 years

Stockholders' Equity, Preferred

Stockholders' Equity, Preferred and Common Stock (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Common Stock [Abstract]
Common stock, shares authorized to issue (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	124,976,373	121,636,273
Common stock, shares outstanding (in shares)	124,976,373	121,636,273
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 22,931	$ 13,417	$ 24,888
Preferred Stock [Member]
Preferred Stock [Abstract]
Preferred stock, shares authorized (in shares)	15,000,000
Preferred stock, shares outstanding (in shares)	0
Series C Junior Participating Preferred Stock [Member]
Preferred Stock [Abstract]
Preferred stock, shares issued (in shares)	0
Preferred stock, shares outstanding (in shares)	0
Common Stock [Member]
Common Stock [Abstract]
Common stock, shares authorized to issue (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	124,976,373	121,636,273
Common stock, shares outstanding (in shares)	124,973,373	121,636,273
Common shares reserved for future issuance (in shares)	18,419,727
Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)	1,706,000	1,285,000	1,908,000
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 22,900	$ 13,700	$ 24,900

Stockholders' Equity, Stock Pla

Stockholders' Equity, Stock Plans (Details)	1 Months Ended	12 Months Ended
	Jun. 30, 2009shares	Dec. 31, 2017Installment$ / sharesshares	May 31, 2017shares	Apr. 30, 2017shares	Dec. 31, 2016shares	Jun. 30, 2015shares	May 31, 2015shares
Stock Options [Member]
Stock Plans [Abstract]
Number of options outstanding (in shares)		9,397,000			9,178,000
Number of options exercisable (in shares)		5,182,000
Restricted Stock Units [Member]
Stock Plans [Abstract]
Vesting period		4 years
1989 Stock Option Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)		20,000,000
Vesting period		4 years
Award term		7 years
Number of options outstanding (in shares)		1,603,403
Number of options exercisable (in shares)		1,553,252
Number of shares available for grant (in shares)		31,878
1989 Stock Option Plan [Member] | One Year from Date of Grant [Member]
Stock Plans [Abstract]
Vesting percentage		25.00%
2011 Equity Incentive Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)			16,000,000	11,000,000		11,000,000	5,500,000
Number of options outstanding (in shares)		7,120,643
Number of options exercisable (in shares)		3,201,717
Number of shares available for grant (in shares)		6,822,389
Number of awards outstanding (in shares)		821,771
2011 Equity Incentive Plan [Member] | Stock Options [Member] | Minimum [Member]
Stock Plans [Abstract]
Vesting period		2 years
2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member]
Stock Plans [Abstract]
Vesting period		4 years
2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member] | Minimum [Member]
Stock Plans [Abstract]
Vesting period		3 years
2002 Non-Employee Directors' Stock Option Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)						2,000,000	1,200,000
Award term		10 years
Number of options outstanding (in shares)		672,750
Number of options exercisable (in shares)		427,125
Number of shares available for grant (in shares)		635,867
Number of awards outstanding (in shares)		40,933
2002 Non-Employee Directors' Stock Option Plan [Member] | One Year from Date of Grant [Member]
Stock Plans [Abstract]
Number of equal annual installments over which options become exercisable | Installment		4
Employee Stock Purchase Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)		3,524,596
Number of shares available for grant (in shares)		668,232
Number of additional shares reserved for issuance (in shares)	150,000	150,000
Maximum percentage of employee compensation used to purchase shares		10.00%
Percentage of fair market value used to determine purchase price of stock		85.00%
Purchase period		6 months
Holding period for purchased stock		6 months
Shares purchased and issued under ESPP (in shares)		67,481
Purchase price (in dollars per share) | $ / shares		$ 27.51

Stockholders' Equity, Stock Opt

Stockholders' Equity, Stock Option Activity (Details) - Stock Options [Member] - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Number of Shares [Abstract]
Outstanding at beginning of period (in shares)	9,178
Granted (in shares)	3,274
Exercised (in shares)	(1,345)
Cancelled/forfeited/expired (in shares)	(1,710)
Outstanding at end of period (in shares)	9,397	9,178
Exercisable at end of period (in shares)	5,182
Weighted Average Exercise Price Per Share [Abstract]
Outstanding at beginning of period (in dollars per share)	$ 40.48
Granted (in dollars per share)	47.76
Exercised (in dollars per share)	15.74
Cancelled/forfeited/expired (in dollars per share)	51.71
Outstanding at end of period (in dollars per share)	44.52	$ 40.48
Exercisable at end of period (in dollars per share)	$ 39.10
Average Remaining Contractual Term, Aggregate Intrinsic Value and Other [Abstract]
Average remaining contractual term, outstanding at end of period	4 years 5 months 1 day
Average remaining contractual term, exercisable at end of period	3 years 3 months 29 days
Aggregate intrinsic value, outstanding at end of period	$ 92,288
Aggregate intrinsic value, exercisable at end of period	$ 80,167
Weighted average fair value of options granted (in dollars per share)	$ 25.42	$ 26.72	$ 27.44
Intrinsic value of options exercised	$ 49,500	$ 28,000	$ 84,700
Cash received from exercise of stock options	$ 21,200	$ 12,600	$ 23,600
Weighted-average fair value of options exercised (in dollars per share)	$ 52.53
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	$ 75,200
Weighted average period for recognition	1 year 2 months 12 days

Stockholders' Equity, Restricte

Stockholders' Equity, Restricted Stock Unit Activity (Details) - Restricted Stock Units [Member] - USD ($) $ / shares in Units, shares in Thousands, $ in Millions	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Number of Shares [Abstract]
Non-vested at beginning of period (in shares)	778
Granted (in shares)	420
Vested (in shares)	(296)
Cancelled/forfeited (in shares)	(39)
Non-vested at end of period (in shares)	863	778
Weighted Average Grant Date Fair Value per Share [Abstract]
Non-vested at beginning of period (in dollars per share)	$ 47.68
Granted (in dollars per share)	48.88	$ 41.79	$ 65.69
Vested (in dollars per share)	43.79
Cancelled/forfeited (in dollars per share)	48.90
Non-vested at end of period (in dollars per share)	$ 49.55	$ 47.68
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested RSUs	$ 16.5
Weighted average period for recognition	1 year 2 months 12 days

Stockholders' Equity, Stock-bas

Stockholders' Equity, Stock-based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 85,975	$ 72,108	$ 59,314
Research, Development and Patent [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	64,521	55,099	43,638
Selling, General and Administrative [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	21,454	17,009	15,676
Akcea Therapeutics [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 17,500	$ 10,100	$ 6,500

Stockholders' Equity, Stock-b60

Stockholders' Equity, Stock-based Valuation Information (Details)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Employee Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	1.80%	1.50%	1.50%
Dividend yield	0.00%	0.00%	0.00%
Volatility	65.90%	58.70%	53.80%
Expected life	4 years 6 months	4 years 6 months	4 years 6 months
Board of Director Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	2.20%	1.30%	2.10%
Dividend yield	0.00%	0.00%	0.00%
Volatility	61.20%	53.10%	52.20%
Expected life	6 years 7 months 6 days	6 years 6 months	6 years 10 months 24 days
Employee Stock Purchase Plan (ESPP) [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	0.80%	0.40%	0.10%
Dividend yield	0.00%	0.00%	0.00%
Volatility	59.90%	86.40%	51.70%
Expected life	6 months	6 months	6 months

Income Taxes, Loss Before Incom

Income Taxes, Loss Before Income Tax (Benefit) Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Income Taxes [Abstract]
United States	$ (11,802)	$ (83,622)	$ (87,906)
Foreign	(11,474)	0	0
Loss before income tax benefit (expense)	$ (23,276)	$ (83,622)	$ (87,906)

Income Taxes, Income Tax (Benef

Income Taxes, Income Tax (Benefit) Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Current [Abstract]
Federal	$ (7,460)	$ 1,067	$ 379
State	1,246	1,867	(7)
Foreign	234	0	0
Total current income tax (benefit) expense	(5,980)	2,934	372
Deferred [Abstract]
Federal	0	0	0
State	0	0	0
Total deferred income tax (benefit) expense	0	0	0
Income tax (benefit) expense	$ (5,980)	$ 2,934	$ 372

Income Taxes, Reconciliation of

Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre-tax loss	$ (23,276)	$ (83,622)	$ (87,906)
Statutory rate	(8,147)	(29,268)	(30,767)
State income tax net of federal benefit	722	(276)	1
Foreign	4,299	0	0
Net change in valuation allowance	(76,409)	55,927	69,499
Net operating loss expiration	3,987	0	0
Tax credits	(32,769)	(26,954)	(41,284)
Deferred tax true-up	4,848	2,591	1,496
Tax Cuts and Jobs Act	107,323	0	0
Nondeductible items	4,123	1,149	1,055
Akcea deconsolidation adjustment at IPO	469	0	0
Excess stock-based compensation	(14,337)	0	0
Other	(89)	(235)	372
Income tax (benefit) expense	$ (5,980)	$ 2,934	$ 372
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	35.00%	35.00%	35.00%
State income tax net of federal benefit	(3.10%)	0.30%	0.00%
Foreign	(18.30%)	0.00%	0.00%
Net change in valuation allowance	328.30%	(66.90%)	(79.10%)
Net operating loss expiration	(17.00%)	0.00%	0.00%
Tax credits	140.80%	32.20%	47.00%
Deferred tax true-up	(20.60%)	(3.10%)	(1.70%)
Tax Cuts and Jobs Act	(461.10%)	0.00%	0.00%
Nondeductible items	(17.90%)	(1.40%)	(1.20%)
Akcea deconsolidation adjustment at IPO	(2.00%)	0.00%	0.00%
Excess stock-based compensation	61.00%	0.00%	0.00%
Other	0.60%	0.40%	(0.40%)
Effective rate	25.70%	(3.50%)	(0.40%)

Income Taxes, Deferred Tax Asse

Income Taxes, Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
Deferred Tax Assets [Abstract]
Net operating loss carryovers	$ 153,575	$ 194,372
R&D credits	240,290	193,845
Deferred revenue	42,055	54,203
Stock-based compensation	40,090	48,209
Intangible and capital assets	672	0
Other	12,164	26,228
Total deferred tax assets	488,846	516,857
Deferred Tax Liabilities [Abstract]
Convertible debt	(32,391)	(62,669)
Intangible and capital assets	0	(2,030)
Net deferred tax asset	456,455	452,158
Valuation allowance	(456,455)	(452,158)
Total net deferred tax assets and liabilities	0	$ 0
Impact of change in tax rate on deferred tax assets under the Tax Act	107,300
Tax benefit related to cumulative prior year AMT tax credit carryovers under the Tax Act	$ (7,700)

Income Taxes, Tax Credit Carryf

Income Taxes, Tax Credit Carryforwards (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Income Taxes [Abstract]
Excess tax benefits from stock-based compensation awards		$ 1,861	$ 396
Deferred Tax Assets [Member]
Income Taxes [Abstract]
Increase in valuation allowance	$ 4,300
Research and Development [Member] | Federal [Member]
Tax Credit Carryforwards [Abstract]
Tax credit carryforwards	233,300
Research and Development [Member] | California [Member]
Tax Credit Carryforwards [Abstract]
Tax credit carryforwards	56,200
Federal [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	561,100
California [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	$ 887,100

Income Taxes, Gross Unrecognize

Income Taxes, Gross Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Gross Unrecognized Tax Benefits [Roll Forward]
Beginning balance of unrecognized tax benefits	$ 66,999	$ 51,257	$ 27,365
Settlement of prior period tax positions	0	(4,033)	0
Increase for prior period tax positions	1,520	7,928	215
Increase for current period tax positions	9,495	11,847	23,677
Ending balance of unrecognized tax benefits	78,014	$ 66,999	$ 51,257
Unrecognized tax benefits that could impact effective tax rate, if recognized	63,600
Interest and penalties on unrecognized tax benefits	$ 0

Collaborative Arrangements an67

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	1 Months Ended				3 Months Ended								12 Months Ended
	Feb. 27, 2018USD ($)	Dec. 31, 2016USD ($)	Jul. 31, 2015USD ($)	Dec. 31, 2012USD ($)	Dec. 31, 2017USD ($)Drug	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)AccountingUnitDrugProgram	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned					$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Deferred revenue		$ 51,500			41,800				$ 51,500				41,800	51,500
Revenue earned													$ 13,800	$ 64,900	$ 6,400
AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage													3.00%	19.00%	2.00%
Cardiometabolic and Renal Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received			$ 65,000
Number of units of accounting | AccountingUnit													1
Minimum potential amount of payments receivable for license fees and substantive milestones					4,000,000								$ 4,000,000
Maximum amount of payments receivable for development milestones					1,100,000								1,100,000
Maximum amount of payments receivable for regulatory milestones					2,900,000								2,900,000
Cumulative payments received					93,000								93,000
Milestone payment earned		$ 25,000
Next prospective milestone					10,000								10,000
Cardiometabolic and Renal Diseases [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned	$ 30,000
Oncology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Minimum potential amount of payments receivable for license fees and substantive milestones					750,000								750,000
Maximum amount of payments receivable for development milestones					226,000								226,000
Maximum amount of payments receivable for regulatory milestones					485,000								485,000
Cumulative payments received					97,800								97,800
Milestone payment earned				$ 11,500
Next prospective milestone					17,500								$ 17,500
Number of drugs that can be licensed under option in collaboration agreement | Drug													3
Number of anti-cancer research programs covered by collaboration agreement | Program													3
Cumulative upfront fees received					31,000								$ 31,000
Upfront fee amortized into revenue					11,900								11,900
Deferred revenue					7,600								7,600
Milestone payment to be earned					$ 5,000								$ 5,000
Number of additional drugs that can be developed under research programs covered by collaboration agreement | Drug					2								2

Collaborative Arrangements an68

Collaborative Arrangements and Licensing Agreements, Biogen (Details) $ in Thousands	1 Months Ended			3 Months Ended								12 Months Ended
	Dec. 31, 2017USD ($)DrugMarket	Sep. 30, 2013USD ($)	Dec. 31, 2012USD ($)ProgramTarget	Dec. 31, 2017USD ($)DrugMarket	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)DrugMarket	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
SPINRAZA royalties												$ 112,540	$ 883	$ 0
Revenue earned				$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	346,620	283,703
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of additional drugs in clinical development to treat neurodegenerative diseases | Drug												6
Cumulative payments received	$ 745,000			745,000								$ 745,000
Cumulative payments received	745,000			745,000								745,000
Revenue earned												259,800	207,900	$ 106,200
Deferred revenue	69,300			69,300				$ 67,500				$ 69,300	$ 67,500
Biogen [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage												51.00%	60.00%	37.00%
SPINRAZA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 436,000			$ 436,000								$ 436,000
Number of global markets were SPINRAZA is available | Market	30			30								30
SPINRAZA royalties												$ 112,540
Milestone payments received												90,000
Cumulative payments received	$ 436,000			$ 436,000								436,000
News Antisense Drugs for Treatment of SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	800,000			800,000								800,000
Upfront payment recorded as deferred revenue	25,000
Maximum amount of payments receivable for license fees and substantive milestones	1,200,000			1,200,000								1,200,000
Maximum amount of payments receivable for development milestones	80,000			80,000								80,000
Maximum amount of payments receivable for commercialization milestones	180,000			180,000								180,000
Cumulative payments received	800,000			800,000								$ 800,000
Royalty percentage received on net sales of drug												20.00%
Next prospective milestone	45,000			45,000								$ 45,000
Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	56,000			56,000								56,000
Milestone payments received												10,000
Upfront payment recorded as deferred revenue			$ 30,000
Cumulative payments received	56,000			56,000								56,000
Next prospective milestone	7,500			7,500								7,500
Number of targets | Target			3
Number of programs under which drugs are to be developed and commercialized | Program			3
Maximum amount of payments receivable per program for license fee and substantive milestone payments	210,000			210,000								210,000
Maximum amount of payments receivable per program for development milestones	10,000			10,000								10,000
Maximum amount of payments receivable per program for regulatory milestones	130,000			130,000								130,000
Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	165,400			165,400								165,400
Milestone payments received												15,000
Upfront payment recorded as deferred revenue		$ 100,000
Cumulative payments received	165,400			165,400								165,400
Next prospective milestone	$ 10,000			$ 10,000								$ 10,000
Number of drugs currently being advanced | Drug	5			5								5
Term of collaboration agreement												6 years
Strategic Neurology [Member] | Antisense Molecule [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable for license fees and substantive milestones	$ 260,000			$ 260,000								$ 260,000
Maximum amount of payments receivable for development milestones	60,000			60,000								60,000
Maximum amount of payments receivable for regulatory milestones	130,000			130,000								130,000
Strategic Neurology [Member] | Other Modalities [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable for license fees and substantive milestones	90,000			90,000								90,000
Maximum amount of payments receivable for development milestones	35,000			35,000								35,000
Maximum amount of payments receivable for regulatory milestones	$ 55,000			$ 55,000								$ 55,000

Collaborative Arrangements an69

Collaborative Arrangements and Licensing Agreements, Bayer (Details) - USD ($) $ in Thousands	1 Months Ended			3 Months Ended									12 Months Ended
	Feb. 28, 2017	Jun. 30, 2015	May 31, 2015	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Jun. 30, 2015	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned				$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874		$ 507,666	$ 346,620	$ 283,703
Bayer [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received	$ 75,000		$ 100,000									$ 100,000
Revenue earned	$ 64,900	$ 91,200											69,200	5,400	$ 93,400
Maximum amount of payments receivable for license fees and substantive milestones				385,000									385,000
Maximum amount of payments receivable for development milestones				125,000									125,000
Maximum amount of payments receivable for commercialization milestones				110,000									110,000
Cumulative payments received				175,000									175,000
Next prospective milestone				10,000									10,000
Deferred revenue				$ 7,300				$ 1,400					$ 7,300	$ 1,400
Bayer [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage													14.00%	2.00%	33.00%
Bayer [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on gross margins of both drugs combined													20.00%

Collaborative Arrangements an70

Collaborative Arrangements and Licensing Agreements, GSK (Details) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Mar. 31, 2010USD ($)	Dec. 31, 2017USD ($)Drug	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)Drug	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
GSK [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently being advanced | Drug		2								2
Cumulative payments received		$ 162,000								$ 162,000
Upfront payment received	$ 38,000
Maximum amount of payments receivable for license fees and substantive milestones		262,000								262,000
Maximum amount of payments receivable for development milestones		47,500								47,500
Maximum amount of payments receivable for regulatory milestones		120,000								120,000
Maximum amount of payments receivable for commercialization milestones		70,000								70,000
Next prospective milestone		$ 15,000								15,000
Revenue earned										$ 8,600	12,300	$ 33,300
Deferred revenue						$ 2,100					$ 2,100
GSK [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage										2.00%	4.00%	12.00%

Collaborative Arrangements an71

Collaborative Arrangements and Licensing Agreements, Janssen Biotech, Inc. (Details) $ in Thousands	1 Months Ended		3 Months Ended								12 Months Ended			24 Months Ended
	Jan. 31, 2018USD ($)	Dec. 31, 2014USD ($)	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)Program	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Dec. 31, 2017USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned			$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Janssen Biotech, Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of programs under which drugs are to be developed and commercialized | Program											3
Upfront payment recorded as deferred revenue		$ 35,000
Minimum amount of payments receivable for license fees and substantive milestones			800,000								$ 800,000			$ 800,000
Maximum amount of payments receivable for development milestones			175,000								175,000			175,000
Maximum amount of payments receivable for regulatory milestones			440,000								440,000			440,000
Maximum amount of payments receivable for commercialization milestones			180,000								180,000			180,000
Cumulative payments received			61,800								61,800			61,800
License fee received														15,000
Next prospective milestone			$ 5,000								5,000			$ 5,000
Revenue earned											$ 33,500	27,300	$ 8,900
Deferred revenue							$ 17,500					$ 17,500
Janssen Biotech, Inc. [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Payment received for advancing programs	$ 5,000

Collaborative Arrangements an72

Collaborative Arrangements and Licensing Agreements, Novartis (Details) $ in Thousands, shares in Millions	3 Months Ended								12 Months Ended
	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)AccountingUnitshares	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Jan. 31, 2017USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Novartis [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Shares issued (in shares) | shares				1.6
Proceeds from sale of common stock, including premium paid				$ 100,000
Additional amount of common stock required to be purchased				$ 50,000								$ 50,000
Number of units of accounting | AccountingUnit				4
Total consideration under collaboration				$ 180,000
Premium received on shares issued				28,400
Potential premium received if common stock is purchased in the future at a premium				5,000
Consideration allocated to equity				71,600
Consideration allocated to development services and delivery of API for AKCEA-APO(a)-L and AKCEA-APOCIII-L				108,400
Revenue earned									55,200
Deferred revenue	58,900								$ 58,900
Novartis [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage									11.00%
Akcea [Member] | Novartis [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received				75,000
Portion of upfront payment retained				60,000
Portion of upfront payment paid as a sublicense fee				$ 15,000
License fee receivable per drug	150,000								$ 150,000
Next prospective milestone	25,000								$ 25,000
Percentage of license fees, milestone payments and royalties paid as sublicense fee									50.00%
Akcea [Member] | Novartis [Member] | AKCEA-APO(a)-L [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable for milestones	600,000								$ 600,000
Maximum amount of payments receivable for development milestones	25,000								25,000
Maximum amount of payments receivable for regulatory milestones	290,000								290,000
Maximum amount of payments receivable for commercialization milestones	285,000								$ 285,000
Royalty percentage received on sales of drug									20.00%
Consideration allocated to development activities	64,000								$ 64,000
Consideration allocated to delivery of API	1,500								1,500
Akcea [Member] | Novartis [Member] | AKCEA-APOCIII-L [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable for milestones	530,000								530,000
Maximum amount of payments receivable for development milestones	25,000								25,000
Maximum amount of payments receivable for regulatory milestones	240,000								240,000
Maximum amount of payments receivable for commercialization milestones	265,000								$ 265,000
Royalty percentage received on sales of drug									20.00%
Consideration allocated to development activities	40,100								$ 40,100
Consideration allocated to delivery of API	$ 2,800								$ 2,800

Collaborative Arrangements an73

Collaborative Arrangements and Licensing Agreements, Roche (Details) - USD ($) $ in Thousands	1 Months Ended		3 Months Ended								12 Months Ended
	Jan. 31, 2018	Apr. 30, 2013	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned			$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Roche [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment recorded as deferred revenue		$ 30,000
Milestone payments received											3,000
Maximum amount of payments receivable for license fees and substantive milestones			365,000								365,000
Maximum amount of payments receivable for development milestones			70,000								70,000
Maximum amount of payments receivable for regulatory milestones			170,000								170,000
Maximum amount of payments receivable for commercialization milestones			80,000								80,000
Maximum amount of payment receivable for each additional drug developed			136,500								136,500
Cumulative payments received			60,000								60,000
Next prospective milestone			$ 10,000								10,000
Revenue earned											$ 53,000	7,100	$ 31,200
Deferred revenue							$ 1,700					$ 1,700
Roche [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage											10.00%	2.00%	11.00%
Roche [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
License fee received	$ 45,000

Collaborative Arrangements an74

Collaborative Arrangements and Licensing Agreements, Achaogen, Inc. (Details) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)Drug	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Dec. 31, 2006USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Achaogen, Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee in the form of equity securities												$ 1,500
Number of drugs to be developed and commercialized | Drug									2
Maximum amount of payments receivable for development, regulatory and commercialization milestones	49,300								$ 49,300
Cumulative payments received	7,000								7,000
Next prospective milestone	$ 7,500								7,500
Revenue earned									$ 0	$ 0	$ 0

Collaborative Arrangements an75

Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Mar. 31, 2004USD ($)	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)ProgramTarget
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Alnylam Pharmaceuticals, Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment recorded as deferred revenue	$ 5,000
Maximum amount of payments receivable per drug for milestone payments		3,400								3,400
Maximum amount of payments receivable per drug for development milestones		1,100								1,100
Maximum amount of payments receivable per drug for regulatory milestones		2,300								2,300
Next prospective milestone		800								800
Maximum amount of payments payable for development and regulatory milestones		3,400								3,400
Number of therapeutic programs | Program												4
Number of therapeutic targets granted to Ionis | Target												4
Number of other unnamed therapeutic targets granted to Ionis | Target												2
Number of therapeutic targets granted by Ionis | Target												4
Cumulative payments received		$ 70,000								70,000
Revenue earned										$ 3,300	$ 1,100	$ 1,300

Collaborative Arrangements an76

Collaborative Arrangements and Licensing Agreements, Antisense Therapeutics Limited (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Antisense Therapeutics Limited [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Ownership interest percentage	10.00%				10.00%				10.00%	10.00%
Antisense Therapeutics Limited [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned									$ 0	$ 0	$ 0

Collaborative Arrangements an77

Collaborative Arrangements and Licensing Agreements, Atlantic Pharmaceuticals Limited (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Mar. 31, 2007	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Atlantic Pharmaceuticals Limited [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Ownership interest percentage		9.00%				9.00%				9.00%	9.00%
Atlantic Pharmaceuticals Limited [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee in the form of equity securities	$ 2,000
Maximum amount of payments receivable for regulatory milestones		$ 1,400								$ 1,400
Next prospective milestone		$ 600								600
Revenue earned										$ 0	$ 0	$ 0	[1]
[1]	Revenue from this relationship was negligible for the year.

Collaborative Arrangements an78

Collaborative Arrangements and Licensing Agreements, Dynacure, SAS (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Dynacure, SAS [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Ownership interest percentage	15.00%								15.00%
Maximum amount of payments receivable for license fees and substantive milestones	$ 210,000								$ 210,000
Maximum amount of payments receivable for development milestones	34,500								34,500
Maximum amount of payments receivable for regulatory milestones	111,000								111,000
Maximum amount of payments receivable for commercialization milestones	$ 60,000								60,000
Revenue earned									$ 0	$ 0

Collaborative Arrangements an79

Collaborative Arrangements and Licensing Agreements, Regulus Therapeutics Inc. (Details) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)Drug	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Regulus Therapeutics Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug									2
Revenue earned									$ 0	0	0
Gain on sale of stock											20,211
Proceeds from sale of stock									$ 2,507	$ 4,467	$ 25,527

Collaborative Arrangements an80

Collaborative Arrangements and Licensing Agreements, Suzhou Ribo Life Science Co., Ltd. (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Apr. 30, 2017	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
Suzhou Ribo Life Science Co., Ltd. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment recorded as deferred revenue	$ 2,000
Ownership interest percentage		9.00%								9.00%
Maximum amount of payments receivable for license fees and substantive milestones		$ 152,900								$ 152,900
Maximum amount of payments receivable for development milestones		13,300								13,300
Maximum amount of payments receivable for commercialization milestones		138,400								$ 138,400
Royalty percentage received on sales of drug										20.00%
Cumulative payments received		2,000								$ 2,000
Next prospective milestone		3,300								3,300
Revenue earned										700
Deferred revenue		$ 1,700								$ 1,700

Collaborative Arrangements an81

Collaborative Arrangements and Licensing Agreements, The University of Texas MD Anderson Cancer Center (Details)	12 Months Ended
	Dec. 31, 2017
The University of Texas MD Anderson Cancer Center [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Term of collaboration agreement	5 years

Collaborative Arrangements an82

Collaborative Arrangements and Licensing Agreements, External Project Funding (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Aug. 31, 2016	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874	$ 507,666	$ 346,620	$ 283,703
CHDI Foundation, Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments made		19,300								19,300
Revenue earned										0	0	$ 0	[1]
Cystic Fibrosis Foundation [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment recorded as deferred revenue	$ 1,000
Maximum amount of payments receivable		2,000								2,000
Maximum costs specific to collaboration to be shared evenly with partner		3,000								3,000
Maximum amount of payments payable for regulatory and commercialization milestones		18,000								18,000
Next prospective milestone		800								800
Cumulative payments received		$ 2,700								2,700
Milestone payments received										1,000
Revenue earned										$ 1,900	$ 600
[1]	Revenue from this relationship was negligible for the year.

Collaborative Arrangements an83

Collaborative Arrangements and Licensing Agreements, In-Licensing Agreements (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
Collaborative Arrangement and Licensing Agreement [Abstract]
Accrued liability	$ 66,618	$ 36,013
University of Massachusetts [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Payments for license fees, milestone payments received and royalty on sales of SPINRAZA	9,700	400
Accrued liability	12,900
Cold Spring Harbor Laboratory [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Payments for license fees, milestone payments received and royalty on sales of SPINRAZA	$ 13,100	$ 3,400

Segment Information and Conce84

Segment Information and Concentration of Business Risk, Segment Information (Details) $ in Thousands	3 Months Ended								5 Months Ended	7 Months Ended	12 Months Ended
	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Jun. 30, 2017USD ($)	Mar. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Sep. 30, 2016USD ($)	Jun. 30, 2016USD ($)	Mar. 31, 2016USD ($)	Dec. 31, 2017USD ($)	Jul. 18, 2017	Dec. 31, 2017USD ($)Segment	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)
Segment Information [Abstract]
Number of reportable segments | Segment											2
Percentage ownership before IPO										100.00%
Percentage of results included in consolidation										100.00%
Percentage ownership after IPO									68.00%
Commercial Revenue [Abstract]
SPINRAZA royalties											$ 112,540	$ 883	$ 0
Licensing and other royalty revenue											9,519	19,839	2,343
Total commercial revenue											122,059	20,722	2,343
R&D revenue under collaborative agreements											385,607	325,898	281,360
Total segment revenue	$ 172,299	$ 120,911	$ 104,152	$ 110,304	$ 160,349	$ 110,927	$ 38,470	$ 36,874			507,666	346,620	283,703
Total operating expenses	173,992	107,002	105,823	96,315	119,194	94,819	87,397	91,526			483,132	392,936	359,465
Income (loss) from operations	(1,693)	$ 13,909	$ (1,671)	$ 13,989	41,155	$ 16,108	$ (48,927)	$ (54,652)			24,534	(46,316)	(75,762)
Total assets	1,322,024				912,467				$ 1,322,024		1,322,024	912,467
Operating Segments [Member] | Ionis Core [Member]
Commercial Revenue [Abstract]
SPINRAZA royalties											112,540	883
Licensing and other royalty revenue											9,519	19,839	2,343
Total commercial revenue											122,059	20,722
R&D revenue under collaborative agreements											384,805	338,546	284,015
Total segment revenue											506,864	359,268	286,358
Total operating expenses											373,788	322,192	309,492
Income (loss) from operations											133,076	37,076	(23,134)
Total assets	1,341,828				1,067,770				1,341,828		1,341,828	1,067,770
Operating Segments [Member] | Akcea Therapeutics [Member]
Commercial Revenue [Abstract]
SPINRAZA royalties											0	0
Licensing and other royalty revenue											0	0	0
Total commercial revenue											0	0
R&D revenue under collaborative agreements											55,209	0	0
Total segment revenue											55,209	0	0
Total operating expenses											163,871	83,512	52,748
Income (loss) from operations											(108,662)	(83,512)	(52,748)
Total assets	268,804				10,684				268,804		268,804	10,684
Elimination of Intercompany Activity [Member]
Commercial Revenue [Abstract]
SPINRAZA royalties											0	0
Licensing and other royalty revenue											0	0	0
Total commercial revenue											0	0
R&D revenue under collaborative agreements											(54,407)	(12,648)	(2,655)
Total segment revenue											(54,407)	(12,648)	(2,655)
Total operating expenses											(54,527)	(12,768)	(2,775)
Income (loss) from operations											120	120	$ 120
Total assets	$ (288,608)				$ (165,987)				$ (288,608)		$ (288,608)	$ (165,987)

Segment Information and Conce85

Segment Information and Concentration of Business Risk, Revenue from Significant Partners (Details) - Partner	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Revenue [Member] | Customer Concentration [Member] | Partner A [Member]
Significant Partners [Abstract]
Concentration percentage	51.00%	60.00%	37.00%
Revenue [Member] | Customer Concentration [Member] | Partner B [Member]
Significant Partners [Abstract]
Concentration percentage	14.00%	2.00%	33.00%
Revenue [Member] | Customer Concentration [Member] | Partner C [Member]
Significant Partners [Abstract]
Concentration percentage	10.00%	2.00%	11.00%
Revenue [Member] | Customer Concentration [Member] | Partner D [Member]
Significant Partners [Abstract]
Concentration percentage	11.00%	0.00%	0.00%
Revenue [Member] | Customer Concentration [Member] | Partner E [Member]
Significant Partners [Abstract]
Concentration percentage	3.00%	19.00%	2.00%
Revenue [Member] | Customer Concentration [Member] | Partner F [Member]
Significant Partners [Abstract]
Concentration percentage	2.00%	4.00%	12.00%
Contracts Receivables [Member] | Credit Concentration [Member] | Significant Partners [Member]
Significant Partners [Abstract]
Concentration percentage	84.00%	92.00%
Number of significant partners	2	2

Employment Benefits (Details)

Employment Benefits (Details) - USD ($)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Employment Benefits [Abstract]
Employee contribution limit per calendar year for employees under 50 years of age	$ 18,000
Employee contribution limit per calendar year for employees over 50 years of age	24,000
Matching contributions	$ 3,000,000	$ 1,700,000	$ 1,500,000

Legal Proceedings (Details)

Legal Proceedings (Details) - Suit Related to U.S. Patent Nos. 7,105,499 and 8,481,712 [Member] $ in Billions	1 Months Ended
	Mar. 31, 2016USD ($)ClaimDefense
Legal Proceedings [Abstract]
Number of asserted claims | Claim	10
Percentage of entitled past sales of sofosbuvir included in award	4.00%
Past sales of sofosbuvir included in award | $	$ 5
Number of additional non-jury defenses asserted | Defense	2

Quarterly Financial Data (Una88

Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended																12 Months Ended
	Dec. 31, 2017		Sep. 30, 2017		Jun. 30, 2017		Mar. 31, 2017		Dec. 31, 2016		Sep. 30, 2016		Jun. 30, 2016		Mar. 31, 2016		Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Quarterly Financial Data (Unaudited) [Abstract]
Revenue	$ 172,299		$ 120,911		$ 104,152		$ 110,304		$ 160,349		$ 110,927		$ 38,470		$ 36,874		$ 507,666	$ 346,620	$ 283,703
Operating expenses	173,992		107,002		105,823		96,315		119,194		94,819		87,397		91,526		483,132	392,936	359,465
Income (loss) from operations	(1,693)		13,909		(1,671)		13,989		41,155		16,108		(48,927)		(54,652)		24,534	(46,316)	(75,762)
Net income (loss)	(4,662)		(4,896)		(11,206)		3,468		$ 25,865		$ 7,351		$ (56,855)		$ (62,917)		(17,296)	(86,556)	(88,278)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ 2,744		$ (976)		$ (11,206)		$ 3,468										$ (5,970)	$ (86,556)	$ (88,278)
Basic net income (loss) per share (in dollars per share)	$ 0.02	[1],[2]	$ 0	[1],[2]	$ (0.09)	[2]	$ 0.03	[2]	$ 0.21	[2]	$ 0.06	[2]	$ (0.47)	[2]	$ (0.52)	[2]	$ 0.08	$ (0.72)	$ (0.74)
Diluted net income (loss) per share (in dollars per share)	$ 0.02	[2]	$ 0	[2]	$ (0.09)	[2]	$ 0.03	[2],[3]	$ 0.21	[2],[4]	$ 0.06	[2],[5]	$ (0.47)	[2]	$ (0.52)	[2]	$ 0.08	$ (0.72)	$ (0.74)
Income (Numerator) [Abstract]
Income (loss) available to Ionis common stockholders	$ 2,717		$ (419)				$ 3,468		$ 25,865		$ 7,351						$ 9,661
Income available to Ionis common shareholders, plus assumed conversions	$ 2,717						$ 3,468		$ 25,865		$ 7,351						$ 9,661
Shares (Denominator) [Abstract]
Shares used in computing basic net income (loss) per share (in shares)	124,818		124,370				122,861		121,340		120,989						124,016	120,933	119,719
Effect of Diluted Securities [Abstract]
Shares issuable related to our ESPP (in shares)	5						60		21		58
Shares used in computing diluted net income per share (in shares)	126,862						124,972		123,953		123,378						126,098	120,933	119,719
1 Percent Convertible Senior Notes [Member]
Convertible Senior Notes [Abstract]
Interest rate on convertible senior notes	1.00%						1.00%		1.00%		1.00%						1.00%	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Convertible Senior Notes [Abstract]
Interest rate on convertible senior notes	2.75%						2.75%		2.75%		2.75%						2.75%	2.75%	2.75%
Stock Options [Member]
Effect of Diluted Securities [Abstract]
Shares issuable related to stock-based compensation (in shares)	1,532						1,674		2,189		2,129						1,619
Restricted Stock Awards [Member]
Effect of Diluted Securities [Abstract]
Shares issuable related to stock-based compensation (in shares)	507						377		403		202						459
Ionis [Member]
Quarterly Financial Data (Unaudited) [Abstract]
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ 18,672		$ 9,168														$ 92,336
Akcea [Member]
Quarterly Financial Data (Unaudited) [Abstract]
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	(15,955)		(9,587)														(82,676)
Akcea [Member] | Common Stock [Member]
Quarterly Financial Data (Unaudited) [Abstract]
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (15,955)		$ (9,870)														$ (58,332)
Basic net income (loss) per share (in dollars per share)	$ (0.35)		$ (0.27)														$ (2.82)
Weighted average shares owned in Akcea (in shares)	45,448		36,556														20,669
Akcea [Member] | Series A Convertible Preferred Stock [Member]
Quarterly Financial Data (Unaudited) [Abstract]
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders			$ 283														$ (24,344)
Basic net income (loss) per share (in dollars per share)			$ 0.05														$ (1.55)
Dividend rate																	6.00%
Conversion ratio																	converted into common stock on a 1:1 basis
Weighted average shares owned in Akcea (in shares)			5,651														15,748
[1]	As discussed in Note 1, Organization and Significant Accounting Policies, we compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period. The calculation of total net income (loss) attributable to our common stockholders for the three months ended December 31, 2017 and September 30, 2017 considered our net income for Ionis on a stand-alone basis plus our share of Akcea's net loss for the periods. To calculate the portion of Akcea's net loss attributable to our ownership, we multiplied Akcea's income (loss) per share by the weighted average shares we owned in Akcea during the period. For the three months ended December 31, 2017, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during those periods. For the three months ended December 31, 2017, the calculation excluded the 1 percent and 2.75 percent notes because the effect on diluted earnings per share was anti-dilutive. Prior to Akcea's IPO, we owned Akcea series A convertible preferred stock, which included a six percent cumulative dividend. Upon completion of Akcea's IPO in July 2017, our preferred stock was converted into common stock on a 1:1 basis. The preferred stock dividend was not paid at the IPO because it was not a liquidation event or a change in control. During the three months ended September 30, 2017, Akcea used a two-class method to compute its net income (loss) per share because it had both common and preferred shares outstanding during the periods. The two-class method required Akcea to calculate its net income (loss) per share for each class of stock by dividing total distributable losses applicable to preferred and common stock, including the six percent cumulative dividend contractually due to series A convertible preferred shareholders, by the weighted-average of preferred and common shares outstanding during the requisite period. Since Akcea used the two-class method, accounting rules required us to include our portion of Akcea's net income (loss) per share for both Akcea's common and preferred shares which we owned in our calculation of basic and diluted net income (loss) per share for three months ended September 30, 2017. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the consolidated statements of operations.
[2]	We computed net income (loss) per share independently for each of the quarters presented. Therefore, the sum of the quarterly net income (loss) per share will not necessarily equal the total for the year.
[3]	For the three months ended March 31, 2017 we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended March 31, 2017, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share was anti-dilutive.
[4]	For the three months ended December, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended December 31, 2016, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share would be anti-dilutive.
[5]	For the three months ended September 30, 2016, we had net income. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period. For the three months ended September 30, 2016, the calculation excludes the 1 percent and 2 3/4 percent notes because the effect on diluted earnings per share would be anti-dilutive.