Ionis Pharmaceuticals (IONS) 10-K 26 Feb 16 2015 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2015	Feb. 19, 2016	Jun. 30, 2015
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, 2015
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			$ 5,760,508,916
Entity Common Stock, Shares Outstanding		120,658,638
Document Fiscal Year Focus	2,015
Document Fiscal Period Focus	FY

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Current assets:
Cash and cash equivalents	$ 128,797	$ 142,998
Short-term investments	650,386	585,834
Contracts receivable	11,356	3,903
Inventories	6,899	6,290
Investment in Regulus Therapeutics Inc.	24,792	81,881
Other current assets	14,773	15,691
Total current assets	837,003	836,597
Property, plant and equipment, net	90,233	88,958
Patents, net	19,316	17,186
Deposits and other assets	9,553	13,068
Total assets	956,105	955,809
Current liabilities:
Accounts payable	28,355	17,984
Accrued compensation	16,065	12,302
Accrued liabilities	28,105	30,451
Current portion of long-term obligations	9,029	2,882
Current portion of deferred contract revenue	67,322	51,713
Total current liabilities	148,876	115,332
Long-term deferred contract revenue	134,306	127,797
Long-term obligations, less current portion	2,341	7,669
Long-term financing liability for leased facility	72,217	71,731
Total liabilities	755,315	698,029
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 120,351,480 and 118,442,726 shares issued and outstanding at December 31, 2015 and December 31, 2014, respectively	120	118
Additional paid-in capital	1,309,107	1,224,509
Accumulated other comprehensive income (loss)	(13,565)	39,747
Accumulated deficit	(1,094,872)	(1,006,594)
Total stockholders' equity	200,790	257,780
Total liabilities and stockholders' equity	956,105	955,809
1 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes	347,214	327,486
2 3/4 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes	$ 50,361	$ 48,014

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2015	Dec. 31, 2014
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)	120,351,480	118,442,726
Common stock, shares outstanding (in shares)	120,351,480	118,442,726
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.00%	1.00%
Convertible Senior Notes [Member] | 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, 2015	Dec. 31, 2014	Dec. 31, 2013
Revenue:
Research and development revenue under collaborative agreements	$ 281,360	$ 202,514	$ 144,194
Licensing and royalty revenue	2,343	11,647	3,091
Total revenue	283,703	214,161	147,285
Expenses:
Research, development and patent expenses	322,292	241,751	184,033
General and administrative	37,173	20,140	14,918
Total operating expenses	359,465	261,891	198,951
Loss from operations	(75,762)	(47,730)	(51,666)
Other income (expense):
Investment income	4,302	2,682	2,085
Interest expense	(36,732)	(22,209)	(19,355)
Gain on investments, net	75	1,256	2,378
Gain on investment in Regulus Therapeutics Inc.	20,211	19,902	0
Loss on early retirement of debt	0	(8,292)	0
Loss before income tax (expense) benefit	(87,906)	(54,391)	(66,558)
Income tax (expense) benefit	(372)	15,407	5,914
Net loss	$ (88,278)	$ (38,984)	$ (60,644)
Basic and diluted net loss per share (in dollars per share)	$ (0.74)	$ (0.33)	$ (0.55)
Shares used in computing basic and diluted net loss per share (in shares)	119,719	117,691	110,502

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (88,278)	$ (38,984)	$ (60,644)
Unrealized (losses) gains on investments, net of tax	(33,101)	40,079	10,253
Reclassification adjustment for realized (gains) losses included in net loss	(20,211)	(21,412)	(1,653)
Comprehensive loss	$ (141,590)	$ (20,317)	$ (52,044)

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
Balance at Dec. 31, 2012	$ 102	$ 1,077,150	$ 12,480	$ (906,966)	$ 182,766
Balance (in shares) at Dec. 31, 2012	101,481
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(60,644)	(60,644)
Change in unrealized gains (losses), net of tax	0	0	8,600	0	8,600
Issuance of common stock in connection with employee stock plans	$ 5	62,953	0	0	62,958
Issuance of common stock in connection with employee stock plans (in shares)	5,372
Issuance of public common stock	$ 9	173,283	0	0	173,292
Issuance of public common stock (in shares)	9,618
Share-based compensation expense	$ 0	11,418	0	0	11,418
Balance at Dec. 31, 2013	$ 116	1,324,804	21,080	(967,610)	378,390
Balance (in shares) at Dec. 31, 2013	116,471
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(38,984)	(38,984)
Change in unrealized gains (losses), net of tax	0	0	18,667	0	18,667
Issuance of common stock in connection with employee stock plans	$ 2	23,071	0	0	23,073
Issuance of common stock in connection with employee stock plans (in shares)	1,972
2 3/4 percent convertible senior notes redemption, equity portion	$ 0	(326,444)	0	0	(326,444)
1 percent convertible senior notes, equity portion, net of issuance costs	0	170,232	0	0	170,232
Share-based compensation expense	0	31,383	0	0	31,383
Excess tax benefits from shared-based compensation awards	0	1,463	0	0	1,463
Balance at Dec. 31, 2014	$ 118	1,224,509	39,747	(1,006,594)	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)
Change in unrealized gains (losses), net of tax	0	0	(53,312)	0	(53,312)
Issuance of common stock in connection with employee stock plans	$ 2	24,888	0	0	24,890
Issuance of common stock in connection with employee stock plans (in shares)	1,908
Share-based compensation expense	$ 0	59,314	0	0	59,314
Excess tax benefits from shared-based compensation awards	0	396	0	0	396
Balance at Dec. 31, 2015	$ 120	$ 1,309,107	$ (13,565)	$ (1,094,872)	$ 200,790
Balance (in shares) at Dec. 31, 2015	120,351

CONSOLIDATED STATEMENTS OF STO7

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Parenthetical) - Convertible Senior Notes [Member]	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
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%
1 Percent Convertible Senior Notes [Member]
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Interest rate on convertible senior notes	1.00%	1.00%

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Operating activities:
Net loss	$ (88,278)	$ (38,984)	$ (60,644)
Adjustments to reconcile net loss to net cash provided by operating activities:
Depreciation	6,984	6,380	6,591
Amortization of patents	1,381	1,142	1,184
Amortization of licenses	1,873	1,882	2,007
Amortization of premium on investments, net	7,812	7,470	5,572
Amortization of debt issuance costs	1,133	595	415
Amortization of long-term financing liability for leased facility	6,665	6,622	6,567
Share-based compensation expense	59,314	31,383	11,418
Gain on investment in Regulus Therapeutics Inc.	(20,211)	(19,902)	0
Loss on early retirement of debt	0	8,292	0
Gain on investments, net	(75)	(1,256)	(2,378)
Non-cash losses related to patents, licensing and property, plant and equipment	1,881	1,305	6,306
Tax benefit from other unrealized gains on securities	0	(12,835)	(5,914)
Changes in operating assets and liabilities:
Contracts receivable	(7,453)	7,199	(10,580)
Inventories	(609)	1,743	(1,912)
Other current and long-term assets	(4,319)	(1,750)	(1,091)
Accounts payable	9,211	4,824	66
Income taxes	0	(4,034)	0
Accrued compensation	3,763	134	4,290
Deferred rent	205	153	217
Accrued liabilities	(2,345)	8,358	6,691
Deferred contract revenue	22,118	(11,415)	88,344
Net cash provided by operating activities	21,125	6,285	63,493
Investing activities:
Purchases of short-term investments	(493,467)	(391,883)	(425,554)
Proceeds from the sale of short-term investments	419,584	294,727	172,762
Purchases of property, plant and equipment	(7,692)	(7,518)	(1,552)
Acquisition of licenses and other assets, net	(4,056)	(3,586)	(3,810)
Proceeds from the sale of Regulus Therapeutics, Inc.	25,527	22,949	0
Proceeds from the sale of strategic investments	52	2,463	2,428
Net cash used in investing activities	(60,052)	(82,848)	(255,726)
Financing activities:
Proceeds from equity awards	24,888	23,071	62,958
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs	0	487,035	0
Repurchase of $140 million principal amount of the 2 3/4 percent convertible senior notes	0	(441,394)	0
Proceeds from borrowing on line of credit facility	8,500	0	0
Proceeds from public common stock offering	0	0	173,292
Proceeds from equipment financing arrangement	0	0	2,513
Excess tax benefits from share-based compensation awards	396	1,463	0
Principal payments on debt and capital lease obligations	(9,058)	(10,587)	(11,039)
Net cash provided by financing activities	24,726	59,588	227,724
Net (decrease) increase in cash and cash equivalents	(14,201)	(16,975)	35,491
Cash and cash equivalents at beginning of year	142,998	159,973	124,482
Cash and cash equivalents at end of year	128,797	142,998	159,973
Supplemental disclosures of cash flow information:
Interest paid	6,800	6,353	6,000
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	1,162	2,151	704
2 3/4 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Amortization of convertible notes discount	2,347	6,723	6,344
1 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Amortization of convertible notes discount	$ 19,728	$ 2,256	$ 0

CONSOLIDATED STATEMENTS OF CAS9

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Dec. 31, 2015	Dec. 31, 2014	Nov. 30, 2014	Dec. 31, 2013
2 3/4 Percent Convertible Senior Notes [Member]
Financing activities:
Principal amount repurchased		$ 140
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Interest rate on convertible senior notes	1.00%	1.00%
Convertible Senior Notes [Member] | 2 3/4 Percent Convertible Senior Notes [Member]
Adjustments to reconcile net loss to net cash provided by operating activities:
Interest rate on convertible senior notes	2.75%	2.75%		2.75%
Financing activities:
Principal amount repurchased			$ 140

Organization and Significant Ac

Organization and Significant Accounting Policies	12 Months Ended
	Dec. 31, 2015
Organization and Significant Accounting Policies [Abstract]
Organization and Significant Accounting Policies	1. Organization and Significant Accounting Policies Basis of presentation The consolidated financial statements include the accounts of Ionis Pharmaceuticals, Inc. ("we", "us" or "our") and our wholly owned subsidiary, Akcea Therapeutics, Inc., which we formed in December 2014. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc. Organization and business activity We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic drugs using antisense technology. Basic and diluted net loss per share We compute basic net loss per share by dividing the net loss by the weighted-average number of common shares outstanding during the period. As we incurred a net loss for 2015, 2014 and 2013, 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. 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. 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, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI Rx Rx Rx Rx  The exclusive license we granted to Bayer to develop and commercialize IONIS-FXI Rx  The development services we agreed to perform for IONIS-FXI Rx  The initial supply of API. We determined that each of these three units of accounting have stand-alone value. The exclusive license we granted to Bayer has stand-alone value because it is an exclusive license that gives Bayer the right to develop IONIS-FXI 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 collaboration was $100 million and we allocated it based on the relative BESP of each unit of accounting. We engaged a third party, independent valuation expert to assist us with determining BESP. We estimated the selling price of the license granted for IONIS-FXI 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 ongoing 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 ongoing 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 drug product we will use. We determine the selling price of our API consistently for all of our partnerships. On an annual basis, we calculate our fully absorbed cost to manufacture API. We then determine the unit price we will charge our partners by dividing our fully absorbed costs by the quantity of API we expect to produce during the year. For purposes of determining BESP of the services we will perform and the API in our Bayer transaction, accounting guidance required us to include a markup for a reasonable profit margin. Based on the units of accounting under the agreement, we allocated the $100 million upfront payment from Bayer as follows:  $91.2 million to the IONIS-FXI Rx  $4.3 million for ongoing development services; and  $4.5 Assuming a constant selling price for the other elements in the arrangement, if there was an assumed ten percent increase or decrease in the estimated selling price of the IONIS-FXI 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 Rx The following are the periods over which we are recognizing revenue for each of our units of accounting under our Bayer agreement:  We recognized the portion of the consideration attributed to the IONIS-FXI Rx  We are recognizing the amount attributed to the ongoing development services for IONIS-FXI Rx  We will recognize the amount attributed to the API supply when 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 customer. 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, since early 2012, we have entered into four collaboration agreements with Biogen:  In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize nusinersen for spinal muscular atrophy, or SMA. As part of the collaboration, we received a $29 million upfront payment and we are responsible for global development of nusinersen through completion of Phase 2/3 clinical trials.  In June 2012, we entered into a second and separate collaboration agreement with Biogen to develop and commercialize a novel antisense drug targeting DMPK, or dystrophia myotonica-protein kinase. As part of the collaboration, we received a $12 million upfront payment and we are responsible for global development of the drug through the completion of a Phase 2 clinical trial.  In December 2012, we entered into a third and separate collaboration agreement with Biogen to discover and develop antisense drugs against three targets to treat neurological or neuromuscular disorders. As part of the collaboration, we received a $30 million upfront payment and we are responsible for the discovery of a lead antisense drug for each of three targets.  In September 2013, we entered into a fourth and separate collaboration agreement with Biogen to leverage antisense technology to advance the treatment of neurological diseases. We granted Biogen exclusive rights to the use of our antisense technology to develop therapies for neurological diseases as part of this broad collaboration. We received a $100 million upfront payment and we are responsible for discovery and early development through the completion of a Phase 2 clinical trial for each antisense drug identified during the six-year term of this collaboration, while Biogen is responsible for the creation and development of small molecule treatments and biologics. All four of these collaboration agreements give Biogen the option to license one or more drugs resulting from the specific collaboration. If Biogen exercises an option, it will pay us a license fee and will assume future development, regulatory and commercialization responsibilities for the licensed drug. We are also eligible to receive milestone payments associated with the research and/or development of the drugs prior to licensing, milestone payments if Biogen achieves pre-specified regulatory milestones, and royalties on any product sales from any drugs resulting from these collaborations. We evaluated all four of the Biogen agreements to determine whether we should account for them as separate agreements. We determined that we should account for the agreements separately because we conducted the negotiations independently of one another, each agreement focuses on different drugs, there are no interrelated or interdependent deliverables, there are no provisions in any of these agreements that are essential to the other agreement, and the payment terms and fees under each agreement are independent of each other. We also evaluated the deliverables in each of these agreements to determine whether they met 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. For all four of these agreements, we determined that the options did not have stand-alone value because Biogen cannot pursue the development or commercialization of the drugs resulting from these collaborations until it exercises the respective option or options. As such, for each agreement we considered the deliverables to be a single unit of accounting and we are recognizing the upfront payment for each of the agreements over the respective estimated period of our performance. 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 paragraph. 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 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 Phase 1 clinical trials 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 scale studies in patients with the primary intent of determining the efficacy 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. The Phase 3 studies typically involve large numbers of patients and can take up to several years to complete. If the data gathered during the 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 a drug achieves marketing authorization, it moves into the commercialization stage, during which our partner will market and sell the drug to patients. Although our partner will ultimately be responsible for marketing and selling the 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 sold 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.  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 existing 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. We also consider milestones associated with our alliance with Alnylam Pharmaceuticals, Inc. substantive because we provide Alnylam ongoing access to our technology to develop and commercialize RNA interference, or RNAi, therapeutics. 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 Licensing and royalty revenue We often enter into agreements to license our proprietary patent rights on an exclusive or non-exclusive basis in exchange for license fees and/or royalties. We generally recognize as revenue immediately those licensing fees and royalties for which we have no significant future performance obligations and are reasonably assured of collecting the resulting receivable. For example, during 2014, we recognized $9.5 million in revenue from Alnylam related to its license of our technology to one of its partners because we had no performance obligations and collectability was reasonably assured. 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, 2015, 2014 and 2013, research and development expenses were $319.5 million, $238.9 million and $173.7 million, respectively. A portion of the costs included in research and development expenses are costs associated with our collaboration agreements. For the years ended December 31, 2015, 2014 and 2013, research and development costs of approximately $161.7 million, $85.6 million and $51.0 million, respectively, were related to our collaborative 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 10.2 years at December 31, 2015. The cost of our patents capitalized on our consolidated balance sheet at December 31, 2015 and 2014 was $27.5 million and $25.0 million, respectively. Accumulated amortization related to patents was $8.2 million and $7.8 million at December 31, 2015 and 2014, respectively. Based on existing patents, estimated amortization expense related to patents in each of the next five years is as follows: Years Ending December 31, Amortization (in millions) 2016 $ 1.4 2017 $ 1.3 2018 $ 1.2 2019 $ 1.1 2020 $ 1.0 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 2015, 2014 and 2013, patent expenses were $2.8 million, $2.9 million and $10.3 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.1 million, $1.3 million and $6.4 million, respectively. 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 in privately and publicly held biotechnology companies that we have received as part of a technology license or collaboration agreement. At December 31, 2015, we held ownership interests of less than 20 percent in each of the respective companies. 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 of these publicly held companies as a separate component of comprehensive income (loss). We account for 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. We hold one cost method investment in Atlantic Pharmaceuticals Limited. Realization of our equity position in this company is 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 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 deliver the drugs to our partners, or as we provide these drugs for our own clinical trials. 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, 2015, 2014 or 2013. Total inventory was $6.9 million and $6.3 million as of December 31, 2015 and 2014, respectively. 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) 2015 2014 Computer software, laboratory, manufacturing and other equipment 3 to 10 $ 56,822 $ 49,772 Building and building systems 25 to 40 48,163 48,521 Land improvements 20 2,853 2,853 Leasehold improvements 5 to 20 39,061 37,935 Furniture and fixtures 5 to 10 5,842 5,732 152,741 144,813 Less accumulated depreciation (72,706 ) (66,053 ) 80,035 78,760 Land 10,198 10,198 Total $ 90,233 $ 88,958 We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. 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 We evaluate long-lived assets, which include property, plant and equipment, patent costs, and exclusive licenses acquired from third parties, 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 $1.9 million, $1.3 million and $6.4 million for the years ended December 31, 2015, 2014 and 2013, respectively, related primarily to the write-down of intangible assets. 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 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), an entity recognizes 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) is 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 to our Consolidated Statement of Operations. The following table summarizes changes in accumulated other comprehensive income for the years ended December 31, 2015, 2014 and 2013 (in thousands): Year Ended December 31, 2015 2014 2013 Beginning balance accumulated other comprehensive income $ 39,747 $ 21,080 $ 12,480 Unrealized (losses) gains on securities, net of tax (1) (33,101 ) 40,079 10,253 Amounts reclassified from accumulated other comprehensive (loss) income (2) (20,211 ) (21,412 ) (1,653 ) Net other com

Investments

Investments	12 Months Ended
	Dec. 31, 2015
Investments [Abstract]
Investments	2. Investments As of December 31, 2015, we have 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, 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, 2015: One year or less 49 % After one year but within two years 27 % After two years but within three and a half years 24 % Total 100 % As illustrated above, at December 31, 2015, 76 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, 2015, we had an ownership interest of less than 20 percent During The following is a summary of our investments (in thousands): Gross Unrealized December 31, 2015 Cost Gains Losses Estimated Fair Value Available-for-sale securities (1): Corporate debt securities $ 181,670 $ 5 $ (250 ) $ 181,425 Debt securities issued by U.S. government agencies 50,559 1 (19 ) 50,541 Debt securities issued by the U.S. Treasury 2,604 — (3 ) 2,601 Debt securities issued by states of the United States and political subdivisions of the states (2) 79,414 18 (88 ) 79,344 Total securities with a maturity of one year or less 314,247 24 (360 ) 313,911 Corporate debt securities 258,703 3 (1,705 ) 257,001 Debt securities issued by U.S. government agencies 38,956 — (244 ) 38,712 Debt securities issued by states of the United States and political subdivisions of the states 48,552 3 (243 ) 48,312 Total securities with a maturity of more than one year 346,211 6 (2,192 ) 344,025 Total available-for-sale securities $ 660,458 $ 30 $ (2,552 ) $ 657,936 Equity securities: Regulus Therapeutics Inc. $ 7,162 $ 17,630 $ — $ 24,792 Total equity securities $ 7,162 $ 17,630 $ — $ 24,792 Total available-for-sale and equity securities $ 667,620 $ 17,660 $ (2,552 ) $ 682,728 Gross Unrealized December 31, 2014 Cost Gains Losses Estimated Fair Value Available-for-sale securities (1): Corporate debt securities (2) $ 219,856 $ 89 $ (89 ) $ 219,856 Debt securities issued by U.S. government agencies 47,496 7 (27 ) 47,476 Debt securities issued by the U.S. Treasury (2) 19,008 9 — 19,017 Debt securities issued by states of the United States and political subdivisions of the states (2) 45,196 19 (53 ) 45,162 Total securities with a maturity of one year or less 331,556 124 (169 ) 331,511 Corporate debt securities 152,730 16 (600 ) 152,146 Debt securities issued by U.S. government agencies 62,530 — (151 ) 62,379 Debt securities issued by states of the United States and political subdivisions of the states 60,073 32 (234 ) 59,871 Total securities with a maturity of more than one year 275,333 48 (985 ) 274,396 Total available-for-sale securities $ 606,889 $ 172 $ (1,154 ) $ 605,907 Equity securities: Regulus Therapeutics Inc. $ 12,477 $ 69,404 $ — $ 81,881 Total equity securities $ 12,477 $ 69,404 $ — $ 81,881 Total available-for-sale and equity securities $ 619,366 $ 69,576 $ (1,154 ) $ 687,788 (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, 2015 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 397 $ 406,098 $ (1,908 ) $ 16,066 $ (47 ) $ 422,164 $ (1,955 ) Debt securities issued by U.S. government agencies 19 71,842 (262 ) 1,001 (1 ) 72,843 (263 ) Debt securities issued by the U.S. Treasury 2 2,601 (3 ) — — 2,601 (3 ) Debt securities issued by states of the United States and political subdivisions of the states 230 59,882 (173 ) 29,634 (158 ) 89,516 (331 ) Total temporarily impaired securities 648 $ 540,423 $ (2,346 ) $ 46,701 $ (206 ) $ 587,124 $ (2,552 ) We believe that the decline in value of these 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 their amortized cost basis at maturity.

Long-Term Obligations and Commi

Long-Term Obligations and Commitments	12 Months Ended
	Dec. 31, 2015
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, 2015 2014 1 percent convertible senior notes $ 347,214 $ 327,486 2¾ percent convertible senior notes 50,361 48,014 Long-term financing liability for leased facility 72,217 71,731 Equipment financing arrangement 515 3,226 Leases and other obligations 2,341 7,325 Total $ 472,648 $ 457,782 Less: current portion (515 ) (2,882 ) Total Long-Term Obligations $ 472,133 $ 454,900 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 is $61.2 million. We recognized an $8.3 million non-cash loss as a result of the early retirement of a portion of the 2¾ percent notes. At December 31, 2015 we had the following convertible debt outstanding (amounts in millions except price per share data): 1 Percent Convertible Senior Notes 2¾ Percent Convertible Senior Notes Outstanding balance $ 500 $ 61 Issue date November 2014 August 2012 Maturity date November 2021 October 2019 Interest rate 1 percent 2¾ percent Conversion price per share $ 66.81 $ 16.63 Total shares of common stock subject to conversion 7.5 3.7 Interest is payable semi-annually in arrears on May 15 and November 15 of each year for the 1 percent notes and on April 1 and October 1 for the 2 ¾ 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 7.5 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. The 2¾ percent notes are convertible at the option of the note holders prior to July 1, 2019 only under certain conditions. On or after July 1, 2019, the notes are convertible into approximately 3.7 million shares of common stock at a conversion price of approximately $16.63 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 can redeem the 2¾ percent notes at our option, in whole or in part, on or after October 5, 2016 if the last reported sale price of our common stock for at least 20 trading days (whether or not consecutive) during the period of 30 consecutive trading days ending on the trading day immediately preceding the date we provide the redemption notice exceeds 130 percent of the applicable conversion price for the 2¾ percent notes on each such day. The redemption price for the 2¾ percent notes will equal 100 percent of the principal amount being redeemed, plus accrued and unpaid interest, plus $90 per each $1,000 principal amount being redeemed. Holders of the 2¾ percent notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indenture governing these notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest. For the 2¾ percent notes, the price of our common stock exceeded the conversion threshold price during the quarter ended December 31, 2015. As a result, the 2¾ percent notes are convertible at the option of the holders during the quarter ending March 31, 2016. As of December 31, 2015, the if-converted value of the 2¾ percent notes, which assumes that the notes will be converted into shares of our common stock, exceeded the principal amount by $166.9 million. We did not include the potential effect of the conversion of our convertible notes into our common stock in the computation of diluted net loss per share because the effect would have been anti-dilutive. 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 2¾ Percent Convertible Senior Notes Nonconvertible debt borrowing rate 7.4 percent 8.0 percent Effective interest rate 7.8 percent 8.8 percent Amortization period of debt discount 7 years 7 years Interest expense for the year ended December 31, 2015, 2014 and 2013 included $23.2 million, $9.6 million and $6.8 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 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, 2015 2014 2¾ Percent Convertible Senior Notes Fair value of outstanding notes $ 215,320 $ 223,900 Principal amount of convertible notes outstanding $ 61,247 $ 61,247 Unamortized portion of debt discount $ 10,886 $ 13,233 Long-term debt $ 50,361 $ 48,014 Carrying value of equity component $ 18,714 $ 18,714 1 Percent Convertible Senior Notes Fair value of outstanding notes $ 555,000 $ 568,000 Principal amount of convertible notes outstanding $ 500,000 $ 500,000 Unamortized portion of debt discount $ 152,786 $ 172,514 Long-term debt $ 347,214 $ 327,486 Carrying value of equity component $ 174,770 $ 174,770 Financing Arrangements 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 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, we will pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility beginning after June 1, 2016. As of December 31, 2015 we had $8.5 million in outstanding borrowings under the credit facility, which were used to fund our capital equipment needs and is consistent with our historical practice to finance these costs. As of December 31, 2015, our outstanding borrowings under this credit facility were at a weighted average interest rate of 1.67 percent. The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement. In October 2008, we entered into an equipment financing loan agreement. As of December 31, 2015, our outstanding borrowings under this loan agreement were at a weighted average interest rate of 4.39 percent. The carrying balance under this loan agreement at December 31, 2015 and 2014 was $0.5 million and $3.2 million, respectively. Our remaining outstanding balance is due in June 2016 and interest is payable monthly. Maturity Schedules Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2015 are as follows (in thousands): 2016 $ 15,767 2017 6,744 2018 6,744 2019 6,744 2020 66,304 Thereafter 505,960 Subtotal $ 608,263 Less: current portion (9,029 ) Less: fixed and determinable interest (37,655 ) Less: unamortized portion of debt discount (163,672 ) Plus: Deferred rent 2,006 Total $ 399,913 Operating Leases We lease office, laboratory and manufacturing space under non-cancelable operating leases with terms through December 2031. We are located in three buildings in Carlsbad, California, which consists of laboratory, manufacturing and office space. Our facilities include a primary research and development facility, a manufacturing facility and a building adjacent to our manufacturing facility. We account for the lease of our primary research and development facility as a financing obligation as discussed below. Our manufacturing facility is used for our drug development business and was built to meet current Good Manufacturing Practices and the facility adjacent to our manufacturing facility has laboratory and office space that we use to support our manufacturing activities. The lease for our manufacturing facility expires in 2031 and has four five-year options to extend. Under the lease agreement, we have the option to purchase the facility at the end of each year from 2016 through 2020, and at the end of 2026 and 2031. The lease for the facility adjacent to our manufacturing facility has an initial term ending in June 2021 with an option to extend the lease for up to two five-year periods. Additionally, Akcea leases office space in a building in Cambridge, Massachusetts. The lease for Akcea has a three-year term and expires in July 2018. We also lease office equipment under non-cancelable operating leases with terms through June 2017. Annual future minimum payments under operating leases as of December 31, 2015 are as follows (in thousands): Operating Leases 2016 $ 1,879 2017 1,878 2018 1,597 2019 1,474 2020 1,527 Thereafter 16,125 Total minimum payments $ 24,480 Rent expense for the year ended December 31, 2015 was $2.0 million and was $1.8 million each of the years ended December 31, 2014 and 2013. We recognize 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 $2.0 million and $1.8 million at December 31, 2015 and 2014, respectively. Research and Development Facility Lease Obligation In March 2010, we entered into a lease agreement with an affiliate of BioMed Realty, L.P., or BioMed. Under the lease, BioMed constructed our primary research and development facility in Carlsbad, California. The lease expires in 2031 and has four five-year options to extend. Under the lease agreement, we have the option to purchase the facility and land at the end of each year from 2016 through 2020, and at the end of 2026 and 2031. To gain early access to the facility, we agreed to modify our lease with BioMed to accept additional responsibility. As a result, we recorded the costs for the facility as a fixed asset and we also recorded a corresponding liability in our non-current liabilities as a long-term financing obligation. In July 2011, we took possession of the facility and began depreciating the cost of the facility over its economic useful life. At December 31, 2015 and 2014, the facility and associated parcel of land had a net book value of $62.2 million and $64.4 million, respectively, which included $9.9 million and $7.7 million, respectively, of accumulated depreciation. We are applying our rent payments, which began on January 1, 2012, against the liability over the term of the lease. In conjunction with the lease agreement with BioMed, we purchased a parcel of land for $10.1 million and subsequently sold it to BioMed. Since we have the option to purchase the facility, including the land, we have continuing involvement in the land, which requires us to account for the purchase and sale of the land as a financing transaction. As such, our property, plant and equipment at December 31, 2015 and 2014 included the value of the land. Additionally, we have recorded a corresponding amount in our non-current liabilities as a long-term financing obligation. Since land is not a depreciable asset, the value of the land and financing obligation we recorded will not change until we exercise our purchase option or the lease terminates. Annual future rent payments as of December 31, 2015 for our primary research and development facility are as follows (in thousands): Future Rent Payments 2016 $ 6,550 2017 6,550 2018 6,943 2019 6,943 2020 7,359 Thereafter 91,205 Total minimum payments $ 125,550

Stockholders' Equity

Stockholders' Equity	12 Months Ended
	Dec. 31, 2015
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, 2015, 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, 2015. Common Stock At December 31, 2015 and 2014, we had 300,000,000 shares of common stock authorized, of which 120,351,480 and 118,442,726 were issued and outstanding, respectively. As of December 31, 2015, total common shares reserved for future issuance were 18,512,177. During the years ending December 31, 2015, 2014 and 2013, we issued 1,908,000, 1,972,000 and 5,372,000 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 $24.9 million, $23.1 million and $63.0 million in 2015, 2014 and 2013, 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, 2015, a total of 3,619,716 options were outstanding, of which options to purchase 2,927,597 shares were exercisable, and 13,462 shares were available for future grant under the 1989 Plan. 2000 Broad Based Equity Incentive Plan In January 2000, we adopted the 2000 Broad-Based Equity Incentive Plan (the 2000 Plan), which, as amended, provided for the issuance of non-qualified stock options for the purchase of up to 5,990,000 shares of common stock to our employees, directors, and consultants. Typically options expire seven or ten years from the date of grant. Options granted under this plan generally 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. At December 31, 2015, a total of 44,025 options were outstanding and exercisable, and no shares were available for future grant under the 2000 Plan. The 2000 Plan expired on January 5, 2010, so we may no longer grant new options under the 2000 Plan. Change of Control Under 1989 Plan and 2000 Plan With respect to both the 1989 Plan and 2000 Plan, in the event of:  a sale, lease or other disposition of all or substantially all of our assets;  a merger or consolidation in which we are not the surviving corporation; or  reverse merger in which we are the surviving corporation but the shares of common stock outstanding immediately preceding the merger are converted by virtue of the merger into other property, whether in the form of securities, cash or otherwise, then any surviving corporation or acquiring corporation will assume any stock awards outstanding under the 2000 Plan and the 1989 Plan or will substitute similar stock awards (including an award to acquire the same consideration paid to the shareholders in the transaction for those outstanding under the 2000 Plan and the 1989 Plan). In the event any surviving corporation or acquiring corporation refuses to assume such stock awards or to substitute similar stock awards for those outstanding under the 2000 Plan and the 1989 Plan, then with respect to stock awards held by participants whose continuous service has not terminated, such stock awards automatically vest in full and the stock awards will terminate if not exercised (if applicable) at or prior to such event. 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, 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. 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, 2015, a total of 3,832,225 options were outstanding, of which 659,254 were exercisable, 712,034 restricted stock unit awards were outstanding, and 5,989,752 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 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, 2015, a total of 544,812 options were outstanding, of which 309,319 were exercisable, 38,621 restricted stock unit awards were outstanding, and 859,871 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 3,224,596 million shares authorized under the plan as of December 31, 2015. 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 2015, employees purchased and we issued to employees 38,372 shares under the ESPP at a weighted average price of $37.43 per share. At December 31, 2015, there were 481,764 shares available for purchase under the ESPP. Stock Option Activity The following table summarizes the stock option activity for the year ended December 31, 2015 (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, 2014 7,379 $ 19.52 Granted 2,550 $ 61.02 Exercised (1,674 ) $ 14.07 Cancelled/forfeited/expired (214 ) $ 42.43 Outstanding at December 31, 2015 8,041 $ 33.21 4.57 $ 232,581 Exercisable at December 31, 2015 3,940 $ 16.43 3.32 $ 179,273 The weighted-average estimated fair values of options granted were $27.44, $17.54 and $7.10 for the years ended December 31, 2015, 2014 and 2013, respectively. The total intrinsic value of options exercised during the years ended December 31, 2015, 2014 and 2013 were $84.7 million, $62.8 million and $69.6 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $23.6 million, $22.4 million and $62.0 million for the years ended December 31, 2015, 2014 and 2013, respectively. For the year ended December 31, 2015, the weighted-average fair value of options exercised was $64.69. As of December 31, 2015, total unrecognized compensation cost related to non-vested stock-based compensation plans was $45.7 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 1.3 years. Restricted Stock Unit Activity The following table summarizes the RSU activity for the year ended December 31, 2015 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2014 638 $ 30.52 Granted 348 $ 65.69 Vested (196 ) $ 27.40 Cancelled/forfeited (39 ) $ 42.87 Non-vested at December 31, 2015 751 $ 47.47 For the years ended December 31, 2015, 2014 and 2013, the weighted-average grant date fair value of RSUs granted was $65.69, $44.94 and $17.42 per RSU, respectively. As of December 31, 2015, total unrecognized compensation cost related to RSUs was $16.0 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, 2015, 2014 and 2013 (in thousands), which was allocated as follows and includes $6.5 million of stock-based compensation expense for Akcea employees in 2015: Year Ended December 31, 2015 2014 2013 Research, development and patents $ 43,638 $ 25,843 $ 9,673 General and administrative 15,676 5,540 1,745 Total $ 59,314 $ 31,383 $ 11,418 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), an entity recognizes 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, 2015, 2014 and 2013, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: December 31, 2015 2014 2013 Risk-free interest rate 1.5 % 1.7 % 1.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 53.8 % 50.1 % 51.1 % Expected life 4.5 years 4.7 years 5.1 years Board of Director Stock Options: December 31, 2015 2014 2013 Risk-free interest rate 2.1 % 2.2 % 2.2 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 52.2 % 54.2 % 52.7 % Expected life 6.9 years 6.9 years 7.2 years ESPP: December 31, 2015 2014 2013 Risk-free interest rate 0.1 % 0.1 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 51.7 % 60.1 % 62.9 % 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, 2015
Income Taxes [Abstract]
Income Taxes	5. Income Taxes The provisions for income taxes on income from continuing operations were as follows (in thousands): Year Ended December 31, 2015 2014 2013 Current: Federal $ 379 $ 263 $ — State (7 ) (4,295 ) 2 Total current 372 (4,032 ) 2 Deferred: Federal — (8,948 ) (5,082 ) State — (2,427 ) (834 ) Total deferred — (11,375 ) (5,916 ) Income tax expense (benefit) $ 372 $ (15,407 ) $ (5,914 ) In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, intraperiod tax allocation rules require us to allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. During 2015, we recorded unrealized losses on our investments in available-for-sale securities in other comprehensive income, therefore we did not have to allocate our tax provision to our other categories of earnings. However, during 2014 and 2013, we recorded unrealized gains on our investments in available-for-sale securities and had to allocate our tax provision between continuing operations and other comprehensive income. As a result, for the years ended December 31, 2014 and 2013, we recorded a $12.8 million and $5.9 million tax benefit, respectively, in continuing operations and a $12.8 million and $5.9 million tax expense, respectively, in other comprehensive income. In December 2014, we reached an agreement with the State of California Franchise Tax Board with regard to California franchise tax we paid for the tax year ended December 31, 2009. As part of the agreement, we received a franchise tax refund of $4.3 million in 2015 and our research credit carry-forward to December 31, 2010 increased by $4.3 million. We recognized an income tax benefit for the refund in the fourth quarter of 2014. The increase in our research credit carry-forward increased our deferred tax assets but did not impact our consolidated balance sheet as we recorded a full valuation allowance on our deferred tax assets. The reconciliation between our effective tax rate on income from continuing operations and the statutory U.S. tax rate is as follows (in thousands): Year Ended December 31, 2015 2014 2013 Pre-tax loss $ (87,906 ) $ (54,391 ) $ (66,558 ) Statutory rate (30,767 ) 35.0 % (19,035 ) 35.0 % (23,295 ) 35.0 % State income tax net of federal benefit 1 0.0 % (3,125 ) 5.7 % (3,823 ) 5.7 % Net change in valuation allowance 69,499 (79.1 )% 29,547 (54.3 )% 28,850 (43.3 )% Loss on debt extinguishment — 0.0 % 2,406 (4.4 )% — 0.0 % Tax credits (41,284 ) 47.0 % (23,628 ) 43.4 % (15,839 ) 23.8 % California franchise tax refund — 0.0 % (2,795 ) 5.1 % — 0.0 % Deferred tax true-up 1,496 (1.7 )% 977 (1.8 )% 8,023 (12.1 )% Other 1,427 (1.6 )% 246 (0.5 )% 170 (0.2 )% Effective rate $ 372 (0.4 )% $ (15,407 ) 28.2 % $ (5,914 ) 8.9 % Significant components of our deferred tax assets and liabilities as of December 31, 2015 and 2014 are as follows (in thousands): Year Ended December 31, 2015 2014 Deferred Tax Assets: Net operating loss carryovers $ 218,493 $ 231,654 R&D credits 153,601 93,594 Deferred revenue 45,110 58,836 Stock-based compensation 31,093 21,553 Other 19,655 15,549 Total deferred tax assets $ 467,952 $ 421,186 Deferred Tax Liabilities: Convertible debt $ (55,928 ) $ (73,733 ) Unrealized gain in other comprehensive income (5,288 ) (27,878 ) Intangible and capital assets (2,643 ) (3,641 ) Net deferred tax asset $ 404,093 $ 315,934 Valuation allowance (404,093 ) (315,934 ) Net deferreds $ — $ — We have net deferred tax assets relating primarily to net operating loss carryforwards, or NOL’s, and research and development tax credit carryforwards. Subject to certain limitations, we may use these deferred tax assets to offset taxable income in future periods. Since we have a history of losses and the likelihood of future profitability is not assured, we have provided a full valuation allowance for the deferred tax assets in our balance sheet as of December 31, 2015. If we determine that we are able to realize a portion or all of these deferred tax assets in the future, we will record an adjustment to increase their recorded value and a corresponding adjustment to increase income or additional paid in capital, as appropriate, in that same period. We recognize excess tax benefits associated with share-based compensation to stockholders' equity only when realized. We follow 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 share-based compensation. Under this approach, we do not realize our excess tax benefits related to share-based compensation until after we utilize all other our tax benefits available to us. During the year ended December 31, 2015, we realized $0.4 million of such excess tax benefits, and accordingly, we recorded a corresponding credit to additional paid-in capital. As of December 31, 2015, we had $76.9 million of unrealized excess tax benefits associated with share-based compensation. We will account for the tax benefits as a credit to additional paid-in capital, if and when we realize them, rather than a reduction of the provision for income taxes. At December 31, 2015, we had federal and California tax net operating loss carryforwards of approximately $734.7 million and $886.5 million, respectively. Our federal tax loss carryforwards will begin to expire in 2023, unless we use them before then. Our California loss carryforwards continue to expire in 2015. At December 31, 2015, we also had federal and California research and development tax credit carryforwards of approximately $146.8 million and $44.7 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. In 2009, we had a substantial amount of taxable income and we used a portion of our Federal NOL carryforwards to reduce our federal income taxes. We analyze filing positions in all of the federal and state 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): Year Ended December 31, 2015 2014 2013 Beginning balance of unrecognized tax benefits $ 27,365 $ 23,964 $ 10,872 Decrease for prior period tax positions — (1,653 ) — Increase for prior period tax positions 215 — 9,821 Increase for current period tax positions 23,677 5,054 3,271 Ending balance of unrecognized tax benefits $ 51,257 $ 27,365 $ 23,964 At December 31, 2015 we had $33.3 million of tax benefits included in our unrecognized tax benefits that, if we recognized them, would reduce our annual effective tax rate subject to the valuation allowance. 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, 2015. 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 and forward are subject to examination by the U.S. tax authorities and our tax years for 2002 and forward are subject to examination by the California tax authorities.

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	12 Months Ended
	Dec. 31, 2015
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 a preclinical program and the option to license a drug for each target advanced under this research collaboration. Upon acceptance of a drug development candidate, AstraZeneca will be responsible for all further global development, regulatory and commercialization activities for such drug. 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, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. We will earn the next milestone payment of $25 million under this collaboration upon identification of the first drug candidate to move into development. In addition, we are eligible to receive tiered royalties up to the low teens on sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. Oncology Collaboration In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs for cancer. As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize IONIS-STAT3-2.5 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 are recognizing the remaining $7.6 million related to the option to license three drugs under the research program through December 2016. 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 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 2015, 2014 and 2013 we earned revenue of $6.4 million, $27.7 million and $29.1 million, respectively, from our relationship with AstraZeneca, which represented two percent, 13 percent and 20 percent, respectively, of our total revenue for those periods. Our balance sheets at December 31, 2015 and 2014 included deferred revenue of $63.3 million and $4.4 million, respectively, related to our relationship with AstraZeneca. Biogen We have established four strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological and neuromuscular disorders. These collaborations combine our expertise in creating antisense drugs with Biogen's expertise in developing therapies for neurological disorders. We and Biogen are currently developing six drugs to treat neurological diseases under these collaborations, including nusinersen, IONIS-DMPK-2.5 Rx Rx Rx Rx Rx Rx Nusinersen In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize nusinersen for the treatment of SMA. We are currently conducting a Phase 3 study evaluating nusinersen in infants with SMA, which we expect to be fully enrolled in the second quarter of 2016. We are also conducting a Phase 3 study evaluating nusinersen in children with SMA, for which we have completed target enrollment. In addition, we are evaluating nusinersen in two Phase 2 open-label studies, one in children with SMA and one in infants with SMA. Patients from all of these studies continue to have access to nusinersen through open-label extension dosing. We are responsible for completing the studies we are currently conducting. Biogen has the option to license nusinersen. If Biogen exercises its option, it will pay us a license fee and will assume all other global development, regulatory and commercialization responsibilities. Biogen may exercise this option upon completion of and data review of the first successful Phase 2/3 trial or completion of both Phase 2/3 trials. An amendment in December 2014 provided for additional opt-in scenarios, based on the filing or the acceptance of a new drug application or marketing authorization application with the FDA or EMA. In June 2015, we and Biogen amended the development plan for nusinersen to include conducting the open-label extension study for the Phase 3 studies in infants and children. As a result of the change to the development plan, we earned an $11 million milestone payment when we initiated the Phase 3 open-label extension study and we are eligible to earn additional milestone and other payments. Under the terms of the agreement, we received an upfront payment of $29 million, which we are amortizing through February 2017. We are also eligible to receive a license fee, milestone payments and tiered royalties up to the mid-teens on any sales of nusinersen. Over the term of the collaboration, we are eligible to receive up to $346 million in a license fee and payments, including up to $121 million in substantive milestone and other payments associated with the clinical development of nusinersen prior to licensing and up to $150 million in substantive milestone payments if Biogen achieves pre-specified regulatory milestones. From inception through December 2015, we have received more than $130 million in milestone payments and upfront fees for advancing nusinersen. In 2015, we earned $40 million for advancing the studies we are conducting in infants and children with SMA. In addition we earned a $2 million milestone payment in February 2016 for further advancing the Phase 3 study of nusinersen in infants. We will earn the next milestone payment of $2 million if we further advance the Phase 3 study of nusinersen in infants. IONIS-DMPK-2.5 Rx In June 2012, we and Biogen entered into a second and separate collaboration agreement to develop and commercialize a novel antisense drug, IONIS-DMPK-2.5 Rx, Rx Rx Rx Rx Rx Rx Rx Neurology In December 2012, we and Biogen entered into a third and separate collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurological or neuromuscular 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-BIIB4 Rx Rx, Rx Strategic Neurology In September 2013, we and Biogen entered into a fourth and separate collaboration agreement, which is a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurological 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 being pursued 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. We are currently advancing three drugs, IONIS-SOD1 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 2015, we have received $135 million in milestone payments and upfront fees under this collaboration. In December 2015, we earned a $5 million milestone payment for validating a fifth target under this collaboration. We will earn the next milestone payment of up to $10 million if we choose another target to advance 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 2015, 2014 and 2013, we earned revenue of $106.2 million, $123.2 million and $37.0 million, respectively, from our relationship with Biogen, which represented 37 percent, 58 percent and 25 percent, respectively, of our total revenue for those periods. Our balance sheets at December 31, 2015 and 2014 included deferred revenue of $91.6 million and $118.1 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 Under the terms of the agreement, we are eligible to receive $155 million in near-term payments, including a $100 million upfront payment we received in the second quarter of 2015 and a $55 million milestone payment that we are eligible to receive upon advancement of the program following the Phase 2 study in patients with end-stage renal disease on hemodialysis. We recorded revenue of $91.2 million related to the license for IONIS-FXI Rx Rx Over the term of the agreement, we are eligible to receive up to $375 million in license fees, substantive milestone payments and other payments, including up to $120 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 IONIS-FXI Rx Rx 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 2015 we earned revenue of $93.4 million, from our relationship with Bayer, which represented 33 percent of our total revenue for the period. Our consolidated balance sheet at December 31, 2015 included deferred revenue of $6.7 million related to our relationship with Bayer. Genzyme Corporation, a Sanofi company In January 2008, we entered into an alliance with Genzyme focused on the licensing and co-development of Kynamro. The license and co-development agreement provided Genzyme with exclusive worldwide rights for all therapeutic purposes to our patents and know-how related to Kynamro. The transaction included a $175 million licensing fee and a $150 million equity investment by Genzyme in our stock. From inception through December 2015, we have received $375 million in a license fee, milestone payments and an equity investment for advancing Kynamro in development. In January 2016, we terminated our license agreement with Genzyme. During 2015 and 2014, we did not earn any revenue from our relationship with Genzyme. During 2013, we earned revenue of $32.5 million from our relationship with Genzyme, which represented 22 percent of our total revenue for that year. 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. Our alliance currently comprises five drugs in development, including our Phase 3 drug IONIS-TTR Rx In October 2012, we and GSK amended the original agreement to reflect an accelerated clinical development plan for IONIS-TTR Rx. Rx Rx Rx Rx Rx In addition to IONIS-TTR Rx Rx Rx Rx Rx, Under our agreement, if GSK successfully develops all five drugs for one or more indications and achieves pre-agreed sales targets, we could receive license fees and substantive milestone payments of more than $1.0 billion, including up to $183.5 million for the achievement of development milestones, up to $363.5 million for the achievement of regulatory milestones and up to $348 million for the achievement of commercialization milestones. Through December 2015, we have received $135 million in milestone payments and upfront fees under this alliance with GSK, not including a $1.5 million payment we earned in January 2016 when GSK further advanced IONIS-HBV-L Rx 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, other than the IONIS-TTR Rx ● GSK may terminate the IONIS-TTR Rx ● 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 2015, 2014 and 2013, we earned revenue of $33.3 million, $37.3 million and $35.3 million, respectively, from our relationship with GSK, which represented 12 percent, 17 percent and 24 percent, respectively, of our total revenue for those years. Our balance sheets at December 31, 2015 and 2014 included deferred revenue of $4.9 million and $10.0 million, respectively, related to our relationship with GSK. Janssen Biotech, Inc., a pharmaceutical company of Johnson & Johnson 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 are amortizing through December 2018. We are eligible to receive nearly $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 $420 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the near teens on sales from any drugs resulting from this collaboration. We will earn the next milestone payment of $5 million if Janssen chooses another target to advance under this collaboration. 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 2015 we earned revenue of $8.9 million from our relationship with Janssen. During 2014 and 2013 we did not earn any revenue from our relationship with Janssen. Our balance sheet at December 31, 2015 included deferred revenue of $26.3 million related to our relationship with Janssen. 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 are currently evaluating a drug targeting HTT, IONIS-HTT 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; ● 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; and ● Either we or Roche may terminate the brain shuttle program if at least one development candidate is not designated under such program by a mutually agreed deadline. During 2015, 2014 and 2013, we earned revenue of $31.2 million, $8.7 million and $5.1 million, respectively from our relationship with Roche, which represented 11 percent, four percent and three percent, respectively, of our total revenue for those years. Our balance sheet at December 31, 2015 and 2014 included deferred revenue of $8.8 million and $17.0 million, respectively related to our relationship with Roche. Satellite Company Collaborations Achaogen, Inc. In 2006, we exclusively licensed to Achaogen, Inc. specific know-how, patents and patent applications relating to aminoglycosides. In exchange, Achaogen agreed to certain payment obligations related to aminoglycosides Achaogen developed. Achaogen is developing plazomicin, an aminoglycoside Achaogen discovered based on the technology we licensed to Achaogen. In connection with the license, Achaogen issued to us $1.5 million of Achaogen Series A Preferred Stock. 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. Through December 2015, we have earned $7 million in milestone payments from Achaogen, including a $4 million milestone payment we earned in September 2014 when Achaogen initiated a Phase 3 study of plazomicin in patients with serious multi-drug resistant, gram-negative bacterial infections. 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 royalties on sales of drugs resulting from the program. Achaogen is solely responsible for the continued development of plazomicin. During 2015 and 2013, we did not earn any revenue from our relationship with Achaogen. During 2014 we earned revenue of $4 million from our relationship with Achaogen and we sold all of the Achaogen stock we owned resulting in net proceeds of $1.3 million. 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 $0.4 million if Alnylam initiates a Phase 1 study for a drug in Alnylam’s 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. 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 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 May 2014 through April 2019 for double-stranded RNAi therapeutics. Through December 2015, we have received nearly $70 million from Alnylam. During 2015, 2014 and 2013, we earned revenue from our relationship with Alnylam totaling $1.3 million, $9.9 million and $1.5 million, respectively. Antisense Therapeutics Limited In 2001 we licensed ATL1102 and ATL1103 to ATL, an Australian company publicly traded on the Australian Stock Exchange. ATL is currently undertaking a chronic toxicology study in primates to support a potential Phase 2b trial of ATL1102 in patients with multiple sclerosis, or MS. In addition, ATL is currently developing ATL1103 for growth and sight disorders. We are eligible to receive royalties on sales of ATL1102 and ATL1103. We may also receive a portion of the fees ATL receives if it licenses ATL1102 or ATL1103. At December 31, 2015 and 2014, we owned less than ten percent of ATL’s equity. During 2015, 2014 and 2013, we did not earn any revenue from our relationship with ATL. Atlantic Pharmaceuticals Limited In March 2007, we licensed alicaforsen to Atlantic Pharmaceuticals, a UK-based specialty pharmaceutical company founded in 2006. Atlantic Pharmaceuticals is developing alicaforsen for the treatment of ulcerative colitis, or UC, and other inflammatory diseases. Atlantic Pharmaceuticals is initially developing alicaforsen for pouchitis, a UC indication, followed by UC and other inflammatory diseases. In exchange for the exclusive, worldwide license to alicaforsen, we received a $2 million upfront payment from Atlantic Pharmaceuticals in the form of equity. Under the agreement, we could receive milestone payments totaling up to $1.4 million for the achievement of regulatory milestones for multiple indications. We will earn the next milestone payment of $0.6 million if Atlantic Pharmaceuticals submits an NDA for alicaforsen with the FDA. In 2010, Atlantic Pharmaceuticals began supplying alicaforsen under international named patient supply regulations for patients with inflammatory bowel disease, or IBD, for which we receive royalties. In 2010 and 2013, we agreed to sell Atlantic Pharmaceuticals alicaforsen drug substance in return for shares of Atlantic Pharmaceuticals’ common stock. Additionally, in 2013 we received an advance payment in the form of equity for the initial royalties that we will earn from Atlantic Pharmaceuticals. We recorded a full valuation allowance for all of the equity we received from Atlantic Pharmaceuticals, including the upfront payment, because realization of value from the equity is uncertain. At December 31, 2015 and 2014, we owned approximately 11 percent and 12 percent, respectively, of Atlantic Pharmaceuticals’ equity. We earned $0.7 million related to royalties and sales of drug substance in 2013. Because the payments were made in equity, we did not record any revenue. During 2015 and 2014, our revenue was negligible from our relationship with Atlantic Pharmaceuticals. OncoGenex Technologies Inc., a subsidiary of OncoGenex Pharmaceuticals Inc. Custirsen In November 2001, we established a drug development collaboration with OncoGenex, a biotechnology company committed to the development of cancer therapeutics for patients with drug resistant and metastatic cancers, to co-develop and commercialize custirsen, an anti-cancer antisense drug that targets clusterin. OncoGenex is currently evaluating custirsen in two Phase 3 studies. In July 2008, we and OncoGenex amended the co-development agreement pursuant to which OncoGenex became solely responsible for the costs, development and commercialization of custirsen. In exchange, OncoGenex agreed to pay us royalties on sales of custirsen and to share consideration it receives from licensing custirsen to a third party, except for consideration OncoGenex receives for the fair market value of equity and reimbursement of research and development expenses. Under the amended agreement, we assigned to OncoGenex our rights in the patents claiming the composition and therapeutic methods of using custirsen and granted OncoGenex a worldwide, nonexclusive license to our know-how and patents covering our core antisense technology and manufacturing technology solely for use with custirsen. In addition, we agreed that so long as OncoGenex or its commercialization partner is using commercially reasonable efforts to develop and commercialize custirsen, we will not research, develop or commercialize an antisense compound designed to modulate clusterin. The amended agreement will continue until OncoGenex or its commercialization partner is no longer developing or commercializing custirsen or until we terminate the agreement for OncoGenex’s uncured failure to make a payment required under the agreement. OGX-225 In August 2003, we and OncoGenex entered into a second and separate agreement for the development of an antisense anti-cancer drug, OGX-225. OncoGenex is responsible for all development costs and activities. OncoGenex issued to us $0.8 million of OncoGenex securities as payment for an upfront fee. In addition, OncoGenex will pay us milestone payments totaling up to $3.5 million for the achievement of key development and regulatory milestones, including up to $1.5 million for the achievement of development milestones and up to $2 million for the achievement of regulatory milestones. In addition, we are eligible to receive royalties on future product sales of OGX-225. As of December 31, 2015, OncoGenex had not achieved any milestone events related to OGX-225. We will earn the next milestone payment of $0.5 million if OncoGenex initiates a Phase 2 study for OGX-225. Apatorsen In January 2005, we entered into a third and separate agreement with OncoGenex to allow for the development of an additional antisense anti-cancer drug, apatorsen. OncoGenex and collaborators ar

Segment Information and Concent

Segment Information and Concentration of Business Risk	12 Months Ended
	Dec. 31, 2015
Segment Information and Concentration of Business Risk [Abstract]
Segment Information and Concentration of Business Risk	In 2015, we began reporting our financial results in two reportable segments, Ionis Core, previously referred to as Drug Discovery and Development, and Akcea Therapeutics, our wholly owned subsidiary. Segment 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 or best-in-class drugs for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy. We formed Akcea to develop and commercialize drugs for cardiometabolic disorders. Moving our lipid drugs into a company that we own and control ensures that our core focus at Ionis remains on innovation while allowing us to maintain control over and retain more value from our lipid drugs. To date, Akcea has not earned any revenue. The following is our segment information for 2015 (in thousands): 2015 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Research and development $ 285,608 $ — $ (4,248 ) $ 281,360 Licensing and royalty 2,343 — — 2,343 Total segment revenue $ 287,951 $ — $ (4,248 ) $ 283,703 Loss from operations $ (21,378 ) $ (54,384 ) $ — $ (75,762 ) Total assets $ 1,004,150 $ 55,354 $ (103,399 ) $ 956,105 The following is our segment information for 2014 and 2013 (in thousands) revised for comparative purposes to show operating expense for Akcea-related projects in 2014 and 2013: 2014 Ionis Core Akcea Therapeutics Total Revenue: Research and development $ 202,514 $ — $ 202,514 Licensing and royalty 11,647 — 11,647 Total segment revenue $ 214,161 $ — $ 214,161 Loss from operations $ (26,033 ) $ (21,697 ) $ (47,730 ) 2013 Ionis Core Akcea Therapeutics Total Revenue: Research and development $ 147,380 $ — $ 144,194 Licensing and royalty 3,091 — 3,091 Total segment revenue $ 150,471 $ — $ 147,285 Loss from operations $ (38,764 ) $ (12,902 ) $ (51,666 ) 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: 2015 2014 2013 Partner A 37 % 58 % 25 % Partner B 33 % 0 % 0 % Partner C 12 % 17 % 24 % Partner D 11 % 4 % 3 % Partner E 2 % 13 % 20 % Partner F 0 % 0 % 22 % Contracts receivables at December 31, 2015 and December 31, 2014 were comprised of approximately 99 percent for each year from two and three significant partners, respectively.

Employment Benefits

Employment Benefits	12 Months Ended
	Dec. 31, 2015
Employment Benefits [Abstract]
Employment Benefits	8. Employment Benefits We have an employee 401(k) salary deferral plan, covering all employees. Employees may make contributions by withholding a percentage of their salary up to the IRS annual limit ($18,000 and $24,000 in 2015 for employees under 50 years old and employees 50 years old or over, respectively). We made approximately $1.5 million, $1.0 million and $0.6 million in matching contributions for the years ended December 31, 2015, 2014 and 2013, respectively.

Legal Proceedings

Legal Proceedings	12 Months Ended
	Dec. 31, 2015
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. We do not believe, relative to our current legal proceedings, that a loss is both probable and estimable. As such, as of December 31, 2015, we did not have a liability related to any of our current legal proceedings, including the following matters. Gilead Litigation In August 2013, Gilead Sciences Inc. filed a suit in the United States District Court of the Northern District of California related to United States Patent Nos. 7,105,499 and 8,481,712 that are jointly owned by Merck Sharp & Dohme Corp. and Ionis Pharmaceuticals, Inc. In the suit Gilead is asking 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. Under our agreement with Merck, Merck is responsible for the costs of this suit. Gilead filed a motion for summary judgment alleging invalidity of the asserted patents. In February 2016, the court denied the motion. In the same order, the court granted our motion for summary judgement for a finding of infringement, but noted that Gilead may still pursue its invalidity defenses at trial. The trial for this case is scheduled to begin March 7, 2016.

Quarterly Financial Data (Unaud

Quarterly Financial Data (Unaudited)	12 Months Ended
	Dec. 31, 2015
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, 2015 and 2014 are as follows (in thousands, except per share data). 2015 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 62,583 $ 120,428 $ 49,121 $ 51,571 Operating expenses $ 71,913 $ 75,782 $ 97,259 $ 114,511 Income (loss) from operations $ (9,330 ) $ 44,646 $ (48,138 ) $ (62,940 ) Net income (loss) $ (16,717 ) $ 35,648 $ (35,776 ) $ (71,433 ) Basic net income (loss) per share (1) $ (0.14 ) $ 0.30 $ (0.30 ) $ (0.59 ) Diluted net income (loss) per share (1) (2) $ (0.14 ) $ 0.29 $ (0.30 ) $ (0.59 ) 2014 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 28,161 $ 57,076 $ 44,063 $ 84,861 Operating expenses $ 57,828 $ 63,726 $ 65,556 $ 74,781 Income (loss) from operations $ (29,667 ) $ (6,650 ) $ (21,493 ) $ 10,080 Net income (loss) $ (31,280 ) $ (12,081 ) $ (26,676 ) $ 31,053 Basic net income (loss) per share (1) $ (0.27 ) $ (0.10 ) $ (0.23 ) $ 0.26 Diluted net income (loss) per share (1) (3) $ (0.27 ) $ (0.10 ) $ (0.23 ) $ 0.25 (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) For the three months ended June 30, 2015, 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 June 30, 2015 consisted of the following (in thousands): Three Months Ended June 30, 2015 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 35,648 119,742 $ 0.30 Effect of diluted securities: Shares issuable upon exercise of stock options 3,974 Shares issuable upon restricted stock award issuance 376 Shares issuable related to our ESPP 4 Shares issuable related to our 2¾ percent notes 1,047 3,683 Income available to common shareholders, plus assumed conversions $ 36,695 127,779 $ 0.29 For the three months ended June 30, 2015, the calculation excludes the 1 percent notes because the effect on diluted earnings per share was anti-dilutive. (3) For the three months ended December 31, 2014, 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, 2014 consisted of the following (in thousands): Three Months Ended December 31, 2014 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 31,053 118,223 $ 0.26 Effect of diluted securities: Shares issuable upon exercise of stock options 4,189 Shares issuable upon restricted stock award issuance 418 Shares issuable related to our ESPP 9 Income available to common shareholders, plus assumed conversions $ 31,053 122,839 $ 0.25 For the three months ended December 31, 2014, the calculation excludes the 1 percent and 2¾ percent convertible senior notes because the effect on diluted earnings per share was anti-dilutive.

Organization and Significant 20

Organization and Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2015
Organization and Significant Accounting Policies [Abstract]
Basis of Presentation	Basis of presentation The consolidated financial statements include the accounts of Ionis Pharmaceuticals, Inc. ("we", "us" or "our") and our wholly owned subsidiary, Akcea Therapeutics, Inc., which we formed in December 2014. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.
Organization and Business Activity	Organization and business activity We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic drugs using antisense technology.
Basic and Diluted Net Loss per Share	Basic and diluted net loss per share We compute basic net loss per share by dividing the net loss by the weighted-average number of common shares outstanding during the period. As we incurred a net loss for 2015, 2014 and 2013, 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. 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. 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, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI Rx Rx Rx Rx  The exclusive license we granted to Bayer to develop and commercialize IONIS-FXI Rx  The development services we agreed to perform for IONIS-FXI Rx  The initial supply of API. We determined that each of these three units of accounting have stand-alone value. The exclusive license we granted to Bayer has stand-alone value because it is an exclusive license that gives Bayer the right to develop IONIS-FXI 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 collaboration was $100 million and we allocated it based on the relative BESP of each unit of accounting. We engaged a third party, independent valuation expert to assist us with determining BESP. We estimated the selling price of the license granted for IONIS-FXI 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 ongoing 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 ongoing 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 drug product we will use. We determine the selling price of our API consistently for all of our partnerships. On an annual basis, we calculate our fully absorbed cost to manufacture API. We then determine the unit price we will charge our partners by dividing our fully absorbed costs by the quantity of API we expect to produce during the year. For purposes of determining BESP of the services we will perform and the API in our Bayer transaction, accounting guidance required us to include a markup for a reasonable profit margin. Based on the units of accounting under the agreement, we allocated the $100 million upfront payment from Bayer as follows:  $91.2 million to the IONIS-FXI Rx  $4.3 million for ongoing development services; and  $4.5 Assuming a constant selling price for the other elements in the arrangement, if there was an assumed ten percent increase or decrease in the estimated selling price of the IONIS-FXI 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 Rx The following are the periods over which we are recognizing revenue for each of our units of accounting under our Bayer agreement:  We recognized the portion of the consideration attributed to the IONIS-FXI Rx  We are recognizing the amount attributed to the ongoing development services for IONIS-FXI Rx  We will recognize the amount attributed to the API supply when 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 customer. 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, since early 2012, we have entered into four collaboration agreements with Biogen:  In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize nusinersen for spinal muscular atrophy, or SMA. As part of the collaboration, we received a $29 million upfront payment and we are responsible for global development of nusinersen through completion of Phase 2/3 clinical trials.  In June 2012, we entered into a second and separate collaboration agreement with Biogen to develop and commercialize a novel antisense drug targeting DMPK, or dystrophia myotonica-protein kinase. As part of the collaboration, we received a $12 million upfront payment and we are responsible for global development of the drug through the completion of a Phase 2 clinical trial.  In December 2012, we entered into a third and separate collaboration agreement with Biogen to discover and develop antisense drugs against three targets to treat neurological or neuromuscular disorders. As part of the collaboration, we received a $30 million upfront payment and we are responsible for the discovery of a lead antisense drug for each of three targets.  In September 2013, we entered into a fourth and separate collaboration agreement with Biogen to leverage antisense technology to advance the treatment of neurological diseases. We granted Biogen exclusive rights to the use of our antisense technology to develop therapies for neurological diseases as part of this broad collaboration. We received a $100 million upfront payment and we are responsible for discovery and early development through the completion of a Phase 2 clinical trial for each antisense drug identified during the six-year term of this collaboration, while Biogen is responsible for the creation and development of small molecule treatments and biologics. All four of these collaboration agreements give Biogen the option to license one or more drugs resulting from the specific collaboration. If Biogen exercises an option, it will pay us a license fee and will assume future development, regulatory and commercialization responsibilities for the licensed drug. We are also eligible to receive milestone payments associated with the research and/or development of the drugs prior to licensing, milestone payments if Biogen achieves pre-specified regulatory milestones, and royalties on any product sales from any drugs resulting from these collaborations. We evaluated all four of the Biogen agreements to determine whether we should account for them as separate agreements. We determined that we should account for the agreements separately because we conducted the negotiations independently of one another, each agreement focuses on different drugs, there are no interrelated or interdependent deliverables, there are no provisions in any of these agreements that are essential to the other agreement, and the payment terms and fees under each agreement are independent of each other. We also evaluated the deliverables in each of these agreements to determine whether they met 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. For all four of these agreements, we determined that the options did not have stand-alone value because Biogen cannot pursue the development or commercialization of the drugs resulting from these collaborations until it exercises the respective option or options. As such, for each agreement we considered the deliverables to be a single unit of accounting and we are recognizing the upfront payment for each of the agreements over the respective estimated period of our performance. 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 paragraph. 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 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 Phase 1 clinical trials 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 scale studies in patients with the primary intent of determining the efficacy 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. The Phase 3 studies typically involve large numbers of patients and can take up to several years to complete. If the data gathered during the 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 a drug achieves marketing authorization, it moves into the commercialization stage, during which our partner will market and sell the drug to patients. Although our partner will ultimately be responsible for marketing and selling the 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 sold 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.  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 existing 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. We also consider milestones associated with our alliance with Alnylam Pharmaceuticals, Inc. substantive because we provide Alnylam ongoing access to our technology to develop and commercialize RNA interference, or RNAi, therapeutics. 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 Licensing and royalty revenue We often enter into agreements to license our proprietary patent rights on an exclusive or non-exclusive basis in exchange for license fees and/or royalties. We generally recognize as revenue immediately those licensing fees and royalties for which we have no significant future performance obligations and are reasonably assured of collecting the resulting receivable. For example, during 2014, we recognized $9.5 million in revenue from Alnylam related to its license of our technology to one of its partners because we had no performance obligations and collectability was reasonably assured.
Research, Development and Patent Expenses	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, 2015, 2014 and 2013, research and development expenses were $319.5 million, $238.9 million and $173.7 million, respectively. A portion of the costs included in research and development expenses are costs associated with our collaboration agreements. For the years ended December 31, 2015, 2014 and 2013, research and development costs of approximately $161.7 million, $85.6 million and $51.0 million, respectively, were related to our collaborative 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 10.2 years at December 31, 2015. The cost of our patents capitalized on our consolidated balance sheet at December 31, 2015 and 2014 was $27.5 million and $25.0 million, respectively. Accumulated amortization related to patents was $8.2 million and $7.8 million at December 31, 2015 and 2014, respectively. Based on existing patents, estimated amortization expense related to patents in each of the next five years is as follows: Years Ending December 31, Amortization (in millions) 2016 $ 1.4 2017 $ 1.3 2018 $ 1.2 2019 $ 1.1 2020 $ 1.0 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 2015, 2014 and 2013, patent expenses were $2.8 million, $2.9 million and $10.3 million, respectively, and included non-cash charges related to the write-down of our patent costs to their estimated net realizable values of $1.1 million, $1.3 million and $6.4 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 in privately and publicly held biotechnology companies that we have received as part of a technology license or collaboration agreement. At December 31, 2015, we held ownership interests of less than 20 percent in each of the respective companies. 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 of these publicly held companies as a separate component of comprehensive income (loss). We account for 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. We hold one cost method investment in Atlantic Pharmaceuticals Limited. Realization of our equity position in this company is 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 deliver the drugs to our partners, or as we provide these drugs for our own clinical trials. 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, 2015, 2014 or 2013. Total inventory was $6.9 million and $6.3 million as of December 31, 2015 and 2014, 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) 2015 2014 Computer software, laboratory, manufacturing and other equipment 3 to 10 $ 56,822 $ 49,772 Building and building systems 25 to 40 48,163 48,521 Land improvements 20 2,853 2,853 Leasehold improvements 5 to 20 39,061 37,935 Furniture and fixtures 5 to 10 5,842 5,732 152,741 144,813 Less accumulated depreciation (72,706 ) (66,053 ) 80,035 78,760 Land 10,198 10,198 Total $ 90,233 $ 88,958 We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term.
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, patent costs, and exclusive licenses acquired from third parties, 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 $1.9 million, $1.3 million and $6.4 million for the years ended December 31, 2015, 2014 and 2013, 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), an entity recognizes 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 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 to our Consolidated Statement of Operations. The following table summarizes changes in accumulated other comprehensive income for the years ended December 31, 2015, 2014 and 2013 (in thousands): Year Ended December 31, 2015 2014 2013 Beginning balance accumulated other comprehensive income $ 39,747 $ 21,080 $ 12,480 Unrealized (losses) gains on securities, net of tax (1) (33,101 ) 40,079 10,253 Amounts reclassified from accumulated other comprehensive (loss) income (2) (20,211 ) (21,412 ) (1,653 ) Net other comprehensive (loss) income for the period (53,312 ) 18,667 8,600 Ending balance accumulated other comprehensive (loss) income $ (13,565 ) $ 39,747 $ 21,080 (1) Other comprehensive income includes income tax expense of $12.8 million and $5.9 million for the years ended December 31, 2014 and 2013, respectively. There was no tax expense for other comprehensive income for the year ended December 31, 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. For 2014, $19.9 million is included in a separate line called “Gain on investment in Regulus Therapeutics Inc.”, with the remaining amount included in a separate line called “Gain on investments, net” on our Consolidated Statement of Operations. Amounts for 2013 are included in a separate line called “Gain on investments, net” 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 assign 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 the 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 In 2015, we began operating as two segments, our Ionis Core segment, previously referred to as Drug Discovery and Development, and Akcea Therapeutics, which consists of the operations of our wholly owned subsidiary, Akcea Therapeutics, Inc. We formed Akcea to develop and commercialize drugs for cardiometabolic 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 use judgments and estimates in determining the allocation of shared expenses to the two segments.
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. Our Level 3 investments include our investments in the equity securities of publicly held biotechnology companies for which we calculated a lack of marketability discount because there were restrictions on when we could trade the securities. Historically, we have determined the lack of marketability discount by using a Black-Scholes model to value a hypothetical put option to approximate the cost of hedging the stock until the restriction ends. The majority of our securities have been classified 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 2015 and 2014, there were no transfers between our Level 1 and Level 2 investments. We recognize transfers between levels of the fair value hierarchy on the date of the event or change in circumstances that caused the transfer. We measure the following major security types at fair value on a recurring basis. The following summary breaks down the fair-value hierarchy that we valued each security with at December 31, 2015 and 2014 (in thousands): At December 31, 2015 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents (1) $ 88,902 $ 88,902 $ — $ — Corporate debt securities (2) 438,426 — 438,426 — Debt securities issued by U.S. government agencies (2) 89,253 — 89,253 — Debt securities issued by the U.S. Treasury (2) 2,601 2,601 — — Debt securities issued by states of the United States and political subdivisions of the states (3) 127,656 — 127,656 — Investment in Regulus Therapeutics Inc. 24,792 24,792 — — Total $ 771,630 $ 116,295 $ 655,335 $ — At December 31, 2014 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents (1) $ 104,680 $ 104,680 $ — $ — Corporate debt securities (4) 372,002 — 372,002 — Debt securities issued by U.S. government agencies (2) 109,855 — 109,855 — Debt securities issued by the U.S. Treasury (5) 19,017 19,017 — — Debt securities issued by states of the United States and political subdivisions of the states (6) 105,033 — 105,033 — Investment in Regulus Therapeutics Inc. 81,881 — — 81,881 Total $ 792,468 $ 123,697 $ 586,890 $ 81,881 (1) Included in cash and cash equivalents on our consolidated balance sheet. (2) Included in short-term investments on our consolidated balance sheet. (3) $7.5 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. (4) $0.8 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) $10 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. (6) $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. In the first quarter of 2014, Achaogen completed an initial public offering. As a result, we stopped using the cost method of accounting for our equity investment in Achaogen and instead we began accounting for it at fair value. Until September 2014, the fair value of our investment in Achaogen included a lack of marketability discount because there were restrictions on when we could trade the securities. As such, we classified our Achaogen stock as a Level 3 investment. In September 2014, we reclassified our investment in Achaogen to a Level 1 investment because the contractual trading restrictions on the shares we owned ended and we subsequently sold all of our shares in 2014. In November 2014, Regulus completed a public offering. As part of the offering, we sold shares of Regulus' common stock and became subject to trading restrictions on our remaining shares through January 2015. Therefore, at December 31, 2014, we recorded a lack of marketability discount on our investment in Regulus and classified it as a Level 3 investment. At the end of January 2015, we reclassified our investment in Regulus to a Level 1 investment because the contractual trading restrictions on the shares we owned ended. The following is a summary of our investments measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the years ended December 31, 2015 and 2014 (in thousands): Year Ended December 31, 2015 2014 Beginning balance of Level 3 investments $ 81,881 $ — Transfers into Level 3 investments — 108,009 Total gains (losses) included in accumulated other comprehensive income (loss) 22,377 (24,897 ) Transfers out of Level 3 investments (104,258 ) (1,231 ) Ending balance of Level 3 investments $ — $ 81,881
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 promised goods or services to customers in an amount that reflects what the entity expects in exchange for the goods or services. This guidance also requires more detailed disclosures to enable users of the financial statements to understand the nature, amount, timing and uncertainty of revenue and cash flows arising from contracts with customers. The guidance as originally issued is effective for fiscal years, and interim periods within that year, beginning after December 15, 2016. In July 2015, the FASB issued updated accounting guidance to allow for an optional one year deferral from the original effective date. As a result, we will adopt this guidance beginning on January 1, 2018. The guidance allows us to select one of two methods of adoption, either the full retrospective approach, meaning the guidance would be applied to all periods presented, or modified retrospective, meaning the cumulative effect of applying the guidance would be recognized as an adjustment to our opening retained earnings balance. We are currently determining the adoption method and timing as well as the effects the adoption will have on our consolidated financial statements and disclosures. In August 2014, the FASB issued accounting guidance on how and when to disclose going-concern uncertainties in the financial statements. This guidance will require us to perform interim and annual assessments to determine our ability to continue as a going concern within one year from the date that we issue our financial statements. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2016. We will adopt this guidance in our fiscal year beginning January 1, 2017. We do not expect this guidance to have any effect on our consolidated financial statements. In February 2015, the FASB issued accounting guidance which amends existing consolidation guidance for entities that are required to evaluate whether they should consolidate certain legal entities. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2015. We will adopt this guidance in our fiscal year beginning January 1, 2016. We do not expect this guidance to have any effect on our consolidated financial statements. In April 2015, the FASB issued accounting guidance to simplify the presentation of debt issuance costs. The amended guidance requires us to present debt issuance costs as a direct deduction from the carrying amount of the related debt liability rather than as an asset. The guidance does not require us to change how we recognize and measure our debt issuance costs. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2015, with early adoption permitted. We will adopt this guidance in our fiscal year beginning January 1, 2016. We do not expect this guidance to have a material impact on our consolidated financial statements. In April 2015, the FASB issued accounting guidance to clarify the accounting for fees paid in cloud computing arrangements. The amendment provides guidance to customers about whether a cloud computing arrangement includes a software license element consistent with the acquisition of other software licenses or if the arrangement excludes a software license and should be accounted for as a service contract. The guidance does not change the accounting for service contracts. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2015. We will adopt this guidance in our fiscal year beginning January 1, 2016 on a prospective basis. We do not expect this guidance to have a material impact on our consolidated financial statements. In July 2015, the FASB issued accounting guidance to simplify the remeasurement of inventory. The amended guidance applies to entities that value inventory under methods other than last-in first-out (LIFO) or the retail inventory method and applies to us because we value our inventory under the FIFO method. The amended guidance requires us to measure our inventory at the lower of cost and net realizable value. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2015 on a prospective basis. We will adopt this guidance in our fiscal year beginning January 1, 2016. We do not expect this guidance to have any effect on our consolidated financial statements. In November 2015, the FASB issued accounting guidance to simplify the classification of deferred income tax assets and liabilities to always be classified as current, compared to the previous treatment, which required us to allocate our deferred tax assets between current and noncurrent. The guidance is effective for fiscal years, and interim periods within that year, beginning after December 15, 2016 on a prospective or retrospective basis, with early adoption permitted. We adopted this guidance on a prospective basis and reflected it in our consolidated balance sheet at December 31, 2015. 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 changes in value 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 will adopt this guidance on January 1, 2018 and we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We are currently determining the effects the adoption will have on our consolidated financial statements and disclosures.

Organization and Significant 21

Organization and Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2015
Organization and Significant Accounting Policies [Abstract]
Amortization Expense for Patents	Based on existing patents, estimated amortization expense related to patents in each of the next five years is as follows: Years Ending December 31, Amortization (in millions) 2016 $ 1.4 2017 $ 1.3 2018 $ 1.2 2019 $ 1.1 2020 $ 1.0
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) 2015 2014 Computer software, laboratory, manufacturing and other equipment 3 to 10 $ 56,822 $ 49,772 Building and building systems 25 to 40 48,163 48,521 Land improvements 20 2,853 2,853 Leasehold improvements 5 to 20 39,061 37,935 Furniture and fixtures 5 to 10 5,842 5,732 152,741 144,813 Less accumulated depreciation (72,706 ) (66,053 ) 80,035 78,760 Land 10,198 10,198 Total $ 90,233 $ 88,958
Changes in Accumulated Other Comprehensive Income (Loss)	Accumulated other comprehensive income (loss) is 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 to our Consolidated Statement of Operations. The following table summarizes changes in accumulated other comprehensive income for the years ended December 31, 2015, 2014 and 2013 (in thousands): Year Ended December 31, 2015 2014 2013 Beginning balance accumulated other comprehensive income $ 39,747 $ 21,080 $ 12,480 Unrealized (losses) gains on securities, net of tax (1) (33,101 ) 40,079 10,253 Amounts reclassified from accumulated other comprehensive (loss) income (2) (20,211 ) (21,412 ) (1,653 ) Net other comprehensive (loss) income for the period (53,312 ) 18,667 8,600 Ending balance accumulated other comprehensive (loss) income $ (13,565 ) $ 39,747 $ 21,080 (1) Other comprehensive income includes income tax expense of $12.8 million and $5.9 million for the years ended December 31, 2014 and 2013, respectively. There was no tax expense for other comprehensive income for the year ended December 31, 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. For 2014, $19.9 million is included in a separate line called “Gain on investment in Regulus Therapeutics Inc.”, with the remaining amount included in a separate line called “Gain on investments, net” on our Consolidated Statement of Operations. Amounts for 2013 are included in a separate line called “Gain on investments, net” on our Consolidated Statement of Operations.
Assets Measured at Fair Value on a Recurring Basis	We measure the following major security types at fair value on a recurring basis. The following summary breaks down the fair-value hierarchy that we valued each security with at December 31, 2015 and 2014 (in thousands): At December 31, 2015 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents (1) $ 88,902 $ 88,902 $ — $ — Corporate debt securities (2) 438,426 — 438,426 — Debt securities issued by U.S. government agencies (2) 89,253 — 89,253 — Debt securities issued by the U.S. Treasury (2) 2,601 2,601 — — Debt securities issued by states of the United States and political subdivisions of the states (3) 127,656 — 127,656 — Investment in Regulus Therapeutics Inc. 24,792 24,792 — — Total $ 771,630 $ 116,295 $ 655,335 $ — At December 31, 2014 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents (1) $ 104,680 $ 104,680 $ — $ — Corporate debt securities (4) 372,002 — 372,002 — Debt securities issued by U.S. government agencies (2) 109,855 — 109,855 — Debt securities issued by the U.S. Treasury (5) 19,017 19,017 — — Debt securities issued by states of the United States and political subdivisions of the states (6) 105,033 — 105,033 — Investment in Regulus Therapeutics Inc. 81,881 — — 81,881 Total $ 792,468 $ 123,697 $ 586,890 $ 81,881 (1) Included in cash and cash equivalents on our consolidated balance sheet. (2) Included in short-term investments on our consolidated balance sheet. (3) $7.5 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. (4) $0.8 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) $10 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. (6) $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 summary of our investments measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the years ended December 31, 2015 and 2014 (in thousands): Year Ended December 31, 2015 2014 Beginning balance of Level 3 investments $ 81,881 $ — Transfers into Level 3 investments — 108,009 Total gains (losses) included in accumulated other comprehensive income (loss) 22,377 (24,897 ) Transfers out of Level 3 investments (104,258 ) (1,231 ) Ending balance of Level 3 investments $ — $ 81,881

Investments (Tables)

Investments (Tables)	12 Months Ended
	Dec. 31, 2015
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, 2015: One year or less 49 % After one year but within two years 27 % After two years but within three and a half years 24 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Gross Unrealized December 31, 2015 Cost Gains Losses Estimated Fair Value Available-for-sale securities (1): Corporate debt securities $ 181,670 $ 5 $ (250 ) $ 181,425 Debt securities issued by U.S. government agencies 50,559 1 (19 ) 50,541 Debt securities issued by the U.S. Treasury 2,604 — (3 ) 2,601 Debt securities issued by states of the United States and political subdivisions of the states (2) 79,414 18 (88 ) 79,344 Total securities with a maturity of one year or less 314,247 24 (360 ) 313,911 Corporate debt securities 258,703 3 (1,705 ) 257,001 Debt securities issued by U.S. government agencies 38,956 — (244 ) 38,712 Debt securities issued by states of the United States and political subdivisions of the states 48,552 3 (243 ) 48,312 Total securities with a maturity of more than one year 346,211 6 (2,192 ) 344,025 Total available-for-sale securities $ 660,458 $ 30 $ (2,552 ) $ 657,936 Equity securities: Regulus Therapeutics Inc. $ 7,162 $ 17,630 $ — $ 24,792 Total equity securities $ 7,162 $ 17,630 $ — $ 24,792 Total available-for-sale and equity securities $ 667,620 $ 17,660 $ (2,552 ) $ 682,728 Gross Unrealized December 31, 2014 Cost Gains Losses Estimated Fair Value Available-for-sale securities (1): Corporate debt securities (2) $ 219,856 $ 89 $ (89 ) $ 219,856 Debt securities issued by U.S. government agencies 47,496 7 (27 ) 47,476 Debt securities issued by the U.S. Treasury (2) 19,008 9 — 19,017 Debt securities issued by states of the United States and political subdivisions of the states (2) 45,196 19 (53 ) 45,162 Total securities with a maturity of one year or less 331,556 124 (169 ) 331,511 Corporate debt securities 152,730 16 (600 ) 152,146 Debt securities issued by U.S. government agencies 62,530 — (151 ) 62,379 Debt securities issued by states of the United States and political subdivisions of the states 60,073 32 (234 ) 59,871 Total securities with a maturity of more than one year 275,333 48 (985 ) 274,396 Total available-for-sale securities $ 606,889 $ 172 $ (1,154 ) $ 605,907 Equity securities: Regulus Therapeutics Inc. $ 12,477 $ 69,404 $ — $ 81,881 Total equity securities $ 12,477 $ 69,404 $ — $ 81,881 Total available-for-sale and equity securities $ 619,366 $ 69,576 $ (1,154 ) $ 687,788 (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, 2015 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 397 $ 406,098 $ (1,908 ) $ 16,066 $ (47 ) $ 422,164 $ (1,955 ) Debt securities issued by U.S. government agencies 19 71,842 (262 ) 1,001 (1 ) 72,843 (263 ) Debt securities issued by the U.S. Treasury 2 2,601 (3 ) — — 2,601 (3 ) Debt securities issued by states of the United States and political subdivisions of the states 230 59,882 (173 ) 29,634 (158 ) 89,516 (331 ) Total temporarily impaired securities 648 $ 540,423 $ (2,346 ) $ 46,701 $ (206 ) $ 587,124 $ (2,552 )

Long-Term Obligations and Com23

Long-Term Obligations and Commitments (Tables)	12 Months Ended
	Dec. 31, 2015
Long-Term Obligations and Commitments [Abstract]
Long-Term Obligations	The carrying value of our long-term obligations was as follows (in thousands): December 31, 2015 2014 1 percent convertible senior notes $ 347,214 $ 327,486 2¾ percent convertible senior notes 50,361 48,014 Long-term financing liability for leased facility 72,217 71,731 Equipment financing arrangement 515 3,226 Leases and other obligations 2,341 7,325 Total $ 472,648 $ 457,782 Less: current portion (515 ) (2,882 ) Total Long-Term Obligations $ 472,133 $ 454,900
Convertible Notes	At December 31, 2015 we had the following convertible debt outstanding (amounts in millions except price per share data): 1 Percent Convertible Senior Notes 2¾ Percent Convertible Senior Notes Outstanding balance $ 500 $ 61 Issue date November 2014 August 2012 Maturity date November 2021 October 2019 Interest rate 1 percent 2¾ percent Conversion price per share $ 66.81 $ 16.63 Total shares of common stock subject to conversion 7.5 3.7 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 2¾ Percent Convertible Senior Notes Nonconvertible debt borrowing rate 7.4 percent 8.0 percent Effective interest rate 7.8 percent 8.8 percent Amortization period of debt discount 7 years 7 years The following table summarizes information about the equity and liability components of our outstanding 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, 2015 2014 2¾ Percent Convertible Senior Notes Fair value of outstanding notes $ 215,320 $ 223,900 Principal amount of convertible notes outstanding $ 61,247 $ 61,247 Unamortized portion of debt discount $ 10,886 $ 13,233 Long-term debt $ 50,361 $ 48,014 Carrying value of equity component $ 18,714 $ 18,714 1 Percent Convertible Senior Notes Fair value of outstanding notes $ 555,000 $ 568,000 Principal amount of convertible notes outstanding $ 500,000 $ 500,000 Unamortized portion of debt discount $ 152,786 $ 172,514 Long-term debt $ 347,214 $ 327,486 Carrying value of equity component $ 174,770 $ 174,770
Maturity Schedules	Annual debt and other obligation maturities, including fixed and determinable interest, at December 31, 2015 are as follows (in thousands): 2016 $ 15,767 2017 6,744 2018 6,744 2019 6,744 2020 66,304 Thereafter 505,960 Subtotal $ 608,263 Less: current portion (9,029 ) Less: fixed and determinable interest (37,655 ) Less: unamortized portion of debt discount (163,672 ) Plus: Deferred rent 2,006 Total $ 399,913
Future Minimum Payments Under Operating Leases	Annual future minimum payments under operating leases as of December 31, 2015 are as follows (in thousands): Operating Leases 2016 $ 1,879 2017 1,878 2018 1,597 2019 1,474 2020 1,527 Thereafter 16,125 Total minimum payments $ 24,480
Future Rent Payments for Research and Development Facility Lease Obligation	Annual future rent payments as of December 31, 2015 for our primary research and development facility are as follows (in thousands): Future Rent Payments 2016 $ 6,550 2017 6,550 2018 6,943 2019 6,943 2020 7,359 Thereafter 91,205 Total minimum payments $ 125,550

Stockholders' Equity (Tables)

Stockholders' Equity (Tables)	12 Months Ended
	Dec. 31, 2015
Stockholders' Equity [Abstract]
Stock Option Activity	The following table summarizes the stock option activity for the year ended December 31, 2015 (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, 2014 7,379 $ 19.52 Granted 2,550 $ 61.02 Exercised (1,674 ) $ 14.07 Cancelled/forfeited/expired (214 ) $ 42.43 Outstanding at December 31, 2015 8,041 $ 33.21 4.57 $ 232,581 Exercisable at December 31, 2015 3,940 $ 16.43 3.32 $ 179,273
Restricted Stock Unit Activity	The following table summarizes the RSU activity for the year ended December 31, 2015 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2014 638 $ 30.52 Granted 348 $ 65.69 Vested (196 ) $ 27.40 Cancelled/forfeited (39 ) $ 42.87 Non-vested at December 31, 2015 751 $ 47.47
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the years ended December 31, 2015, 2014 and 2013 (in thousands), which was allocated as follows and includes $6.5 million of stock-based compensation expense for Akcea employees in 2015: Year Ended December 31, 2015 2014 2013 Research, development and patents $ 43,638 $ 25,843 $ 9,673 General and administrative 15,676 5,540 1,745 Total $ 59,314 $ 31,383 $ 11,418
Weighted-Average Assumptions - ESPP	ESPP: December 31, 2015 2014 2013 Risk-free interest rate 0.1 % 0.1 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 51.7 % 60.1 % 62.9 % Expected life 6 months 6 months 6 months
Employee Stock Options [Member]
Stockholders' Equity [Abstract]
Weighted-Average Assumptions	For the years ended December 31, 2015, 2014 and 2013, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: December 31, 2015 2014 2013 Risk-free interest rate 1.5 % 1.7 % 1.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 53.8 % 50.1 % 51.1 % Expected life 4.5 years 4.7 years 5.1 years
Board of Director Stock Options [Member]
Stockholders' Equity [Abstract]
Weighted-Average Assumptions	Board of Director Stock Options: December 31, 2015 2014 2013 Risk-free interest rate 2.1 % 2.2 % 2.2 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 52.2 % 54.2 % 52.7 % Expected life 6.9 years 6.9 years 7.2 years

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2015
Income Taxes [Abstract]
Provision for Income Taxes	The provisions for income taxes on income from continuing operations were as follows (in thousands): Year Ended December 31, 2015 2014 2013 Current: Federal $ 379 $ 263 $ — State (7 ) (4,295 ) 2 Total current 372 (4,032 ) 2 Deferred: Federal — (8,948 ) (5,082 ) State — (2,427 ) (834 ) Total deferred — (11,375 ) (5,916 ) Income tax expense (benefit) $ 372 $ (15,407 ) $ (5,914 )
Reconciliation Between Effective and Statutory Tax Rate	The reconciliation between our effective tax rate on income from continuing operations and the statutory U.S. tax rate is as follows (in thousands): Year Ended December 31, 2015 2014 2013 Pre-tax loss $ (87,906 ) $ (54,391 ) $ (66,558 ) Statutory rate (30,767 ) 35.0 % (19,035 ) 35.0 % (23,295 ) 35.0 % State income tax net of federal benefit 1 0.0 % (3,125 ) 5.7 % (3,823 ) 5.7 % Net change in valuation allowance 69,499 (79.1 )% 29,547 (54.3 )% 28,850 (43.3 )% Loss on debt extinguishment — 0.0 % 2,406 (4.4 )% — 0.0 % Tax credits (41,284 ) 47.0 % (23,628 ) 43.4 % (15,839 ) 23.8 % California franchise tax refund — 0.0 % (2,795 ) 5.1 % — 0.0 % Deferred tax true-up 1,496 (1.7 )% 977 (1.8 )% 8,023 (12.1 )% Other 1,427 (1.6 )% 246 (0.5 )% 170 (0.2 )% Effective rate $ 372 (0.4 )% $ (15,407 ) 28.2 % $ (5,914 ) 8.9 %
Deferred Tax Assets and Liabilities	Significant components of our deferred tax assets and liabilities as of December 31, 2015 and 2014 are as follows (in thousands): Year Ended December 31, 2015 2014 Deferred Tax Assets: Net operating loss carryovers $ 218,493 $ 231,654 R&D credits 153,601 93,594 Deferred revenue 45,110 58,836 Stock-based compensation 31,093 21,553 Other 19,655 15,549 Total deferred tax assets $ 467,952 $ 421,186 Deferred Tax Liabilities: Convertible debt $ (55,928 ) $ (73,733 ) Unrealized gain in other comprehensive income (5,288 ) (27,878 ) Intangible and capital assets (2,643 ) (3,641 ) Net deferred tax asset $ 404,093 $ 315,934 Valuation allowance (404,093 ) (315,934 ) Net deferreds $ — $ —
Gross Unrecognized Tax Benefits	The following table summarizes our gross unrecognized tax benefits (in thousands): Year Ended December 31, 2015 2014 2013 Beginning balance of unrecognized tax benefits $ 27,365 $ 23,964 $ 10,872 Decrease for prior period tax positions — (1,653 ) — Increase for prior period tax positions 215 — 9,821 Increase for current period tax positions 23,677 5,054 3,271 Ending balance of unrecognized tax benefits $ 51,257 $ 27,365 $ 23,964

Segment Information and Conce26

Segment Information and Concentration of Business Risk (Tables)	12 Months Ended
	Dec. 31, 2015
Segment Information and Concentration of Business Risk [Abstract]
Segment Information	The following is our segment information for 2015 (in thousands): 2015 Ionis Core Akcea Therapeutics Elimination of Intercompany Activity Total Revenue: Research and development $ 285,608 $ — $ (4,248 ) $ 281,360 Licensing and royalty 2,343 — — 2,343 Total segment revenue $ 287,951 $ — $ (4,248 ) $ 283,703 Loss from operations $ (21,378 ) $ (54,384 ) $ — $ (75,762 ) Total assets $ 1,004,150 $ 55,354 $ (103,399 ) $ 956,105 The following is our segment information for 2014 and 2013 (in thousands) revised for comparative purposes to show operating expense for Akcea-related projects in 2014 and 2013: 2014 Ionis Core Akcea Therapeutics Total Revenue: Research and development $ 202,514 $ — $ 202,514 Licensing and royalty 11,647 — 11,647 Total segment revenue $ 214,161 $ — $ 214,161 Loss from operations $ (26,033 ) $ (21,697 ) $ (47,730 ) 2013 Ionis Core Akcea Therapeutics Total Revenue: Research and development $ 147,380 $ — $ 144,194 Licensing and royalty 3,091 — 3,091 Total segment revenue $ 150,471 $ — $ 147,285 Loss from operations $ (38,764 ) $ (12,902 ) $ (51,666 )
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: 2015 2014 2013 Partner A 37 % 58 % 25 % Partner B 33 % 0 % 0 % Partner C 12 % 17 % 24 % Partner D 11 % 4 % 3 % Partner E 2 % 13 % 20 % Partner F 0 % 0 % 22 %

Quarterly Financial Data (Una27

Quarterly Financial Data (Unaudited) (Tables)	12 Months Ended
	Dec. 31, 2015
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, 2015 and 2014 are as follows (in thousands, except per share data). 2015 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 62,583 $ 120,428 $ 49,121 $ 51,571 Operating expenses $ 71,913 $ 75,782 $ 97,259 $ 114,511 Income (loss) from operations $ (9,330 ) $ 44,646 $ (48,138 ) $ (62,940 ) Net income (loss) $ (16,717 ) $ 35,648 $ (35,776 ) $ (71,433 ) Basic net income (loss) per share (1) $ (0.14 ) $ 0.30 $ (0.30 ) $ (0.59 ) Diluted net income (loss) per share (1) (2) $ (0.14 ) $ 0.29 $ (0.30 ) $ (0.59 ) 2014 Quarters First Quarter Second Quarter Third Quarter Fourth Quarter Revenue $ 28,161 $ 57,076 $ 44,063 $ 84,861 Operating expenses $ 57,828 $ 63,726 $ 65,556 $ 74,781 Income (loss) from operations $ (29,667 ) $ (6,650 ) $ (21,493 ) $ 10,080 Net income (loss) $ (31,280 ) $ (12,081 ) $ (26,676 ) $ 31,053 Basic net income (loss) per share (1) $ (0.27 ) $ (0.10 ) $ (0.23 ) $ 0.26 Diluted net income (loss) per share (1) (3) $ (0.27 ) $ (0.10 ) $ (0.23 ) $ 0.25 (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) For the three months ended June 30, 2015, 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 June 30, 2015 consisted of the following (in thousands): Three Months Ended June 30, 2015 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 35,648 119,742 $ 0.30 Effect of diluted securities: Shares issuable upon exercise of stock options 3,974 Shares issuable upon restricted stock award issuance 376 Shares issuable related to our ESPP 4 Shares issuable related to our 2¾ percent notes 1,047 3,683 Income available to common shareholders, plus assumed conversions $ 36,695 127,779 $ 0.29 For the three months ended June 30, 2015, the calculation excludes the 1 percent notes because the effect on diluted earnings per share was anti-dilutive. (3) For the three months ended December 31, 2014, 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, 2014 consisted of the following (in thousands): Three Months Ended December 31, 2014 Income (Numerator) Shares (Denominator) Per-Share Amount Income available to common shareholders $ 31,053 118,223 $ 0.26 Effect of diluted securities: Shares issuable upon exercise of stock options 4,189 Shares issuable upon restricted stock award issuance 418 Shares issuable related to our ESPP 9 Income available to common shareholders, plus assumed conversions $ 31,053 122,839 $ 0.25 For the three months ended December 31, 2014, the calculation excludes the 1 percent and 2¾ percent convertible senior notes because the effect on diluted earnings per share was anti-dilutive.

Organization and Significant 28

Organization and Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - Convertible Senior Notes [Member]	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
1 Percent Convertible Senior Notes [Member]
Basic and Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Basic and Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	2.75%	2.75%	2.75%

Organization and Significant 29

Organization and Significant Accounting Policies, Revenue Recognition (Details)	1 Months Ended					3 Months Ended	12 Months Ended
	Jun. 30, 2015USD ($)	Sep. 30, 2013USD ($)	Dec. 31, 2012USD ($)Target	Jun. 30, 2012USD ($)	Jan. 31, 2012USD ($)	Jun. 30, 2015USD ($)	Dec. 31, 2015USD ($)AccountingUnitAgreementCategoryStage	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Revenue Recognition [Abstract]
Licensing and royalty revenue							$ 2,343,000	$ 11,647,000	$ 3,091,000
Collaborations and Licensing Agreements [Member]
Revenue Recognition [Abstract]
Number of categories of milestone events | Category							3
Number of stages of life-cycle of drugs | Stage							3
Collaborations and Licensing Agreements [Member] | Development Milestones - New Development Candidate [Member] | Minimum [Member]
Revenue Recognition [Abstract]
Completion period							12 months
Collaborations and Licensing Agreements [Member] | Development Milestones - New Development Candidate [Member] | Maximum [Member]
Revenue Recognition [Abstract]
Completion period							18 months
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 1 [Member] | Minimum [Member]
Revenue Recognition [Abstract]
Completion period							1 year
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 1 [Member] | Maximum [Member]
Revenue Recognition [Abstract]
Completion period							2 years
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 2 [Member] | Minimum [Member]
Revenue Recognition [Abstract]
Completion period							1 year
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 2 [Member] | Maximum [Member]
Revenue Recognition [Abstract]
Completion period							3 years
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 3 [Member] | Minimum [Member]
Revenue Recognition [Abstract]
Completion period							2 years
Collaborations and Licensing Agreements [Member] | Development Milestones - Phase 3 [Member] | Maximum [Member]
Revenue Recognition [Abstract]
Completion period							4 years
Collaborations and Licensing Agreements [Member] | Regulatory Milestones [Member] | Minimum [Member]
Revenue Recognition [Abstract]
Time to prepare and submit regulatory filings							6 months
Time to obtain approval							1 year
Collaborations and Licensing Agreements [Member] | Regulatory Milestones [Member] | Maximum [Member]
Revenue Recognition [Abstract]
Time to prepare and submit regulatory filings							12 months
Time to obtain approval							2 years
Collaborations and Licensing Agreements [Member] | Commercialization Milestones [Member]
Revenue Recognition [Abstract]
Example of sales threshold as milestone event							$ 1,000,000,000
Bayer [Member] | Agreement Entered into in May 2015 [Member]
Revenue Recognition [Abstract]
Upfront fee received						$ 100,000,000
Number of units of accounting | AccountingUnit							3
Bayer [Member] | Agreement Entered into in May 2015 [Member] | IONIS-FXI [Member]
Revenue Recognition [Abstract]
Upfront fee recognized						91,200,000
Upfront fee recorded as deferred revenue	$ 8,800,000					$ 4,300,000
Assumed change in estimated selling price						10.00%
Percentage by which earned revenue would change 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						$ 900,000
Bayer [Member] | Agreement Entered into in May 2015 [Member] | IONIS-FXI Active Pharmaceutical Ingredient [Member]
Revenue Recognition [Abstract]
Upfront fee recorded as deferred revenue						$ 4,500,000
Biogen [Member] | Collaborations and Licensing Agreements [Member]
Revenue Recognition [Abstract]
Number of collaborative agreements | Agreement							4
Biogen [Member] | Agreement Entered into in January 2012 [Member] | Nusinersen [Member]
Revenue Recognition [Abstract]
Upfront fee recorded as deferred revenue					$ 29,000,000
Biogen [Member] | Agreement Entered into in June 2012 [Member] | IONIS-DMPK-2.5 [Member]
Revenue Recognition [Abstract]
Upfront fee recorded as deferred revenue				$ 12,000,000
Biogen [Member] | Agreement Entered into in December 2012 [Member] | Neurology [Member]
Revenue Recognition [Abstract]
Upfront fee recorded as deferred revenue			$ 30,000,000
Number of targets | Target			3
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Strategic Neurology [Member]
Revenue Recognition [Abstract]
Upfront fee recorded as deferred revenue		$ 100,000,000
Term of collaboration agreement							6 years
Alnylam [Member]
Revenue Recognition [Abstract]
Licensing and royalty revenue								$ 9,500,000

Organization and Significant 30

Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Research, Development and Patent Expenses [Abstract]
Research and development expenses	$ 319.5	$ 238.9	$ 173.7
Estimated Amortization Expense [Abstract]
Non-cash charges related to write-down	$ 1.9	1.3	6.4
Patents [Member]
Patents [Abstract]
Estimated useful life	10 years 2 months 12 days
Cost	$ 27.5	25
Accumulated amortization	8.2	7.8
Estimated Amortization Expense [Abstract]
2,016	1.4
2,017	1.3
2,018	1.2
2,019	1.1
2,020	1
Patent expenses	2.8	2.9	10.3
Non-cash charges related to write-down	1.1	1.3	6.4
Collaborations and Licensing Agreements [Member]
Research, Development and Patent Expenses [Abstract]
Research and development expenses	$ 161.7	$ 85.6	$ 51

Organization and Significant 31

Organization and Significant Accounting Policies, Inventory Valuation (Details) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Inventory Valuation [Abstract]
Inventories	$ 6,899	$ 6,290

Organization and Significant 32

Organization and Significant Accounting Policies, Property, Plant and Equipment (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014
Property, Plant and Equipment [Abstract]
Less accumulated depreciation	$ (72,706)	$ (66,053)
Property, plant and equipment, net	90,233	88,958
Property, Plant and Equipment, Excluding Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	152,741	144,813
Property, plant and equipment, net	80,035	78,760
Computer Software, Laboratory, Manufacturing and Other Equipment [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 56,822	49,772
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	3 years
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	10 years
Building and Building Systems [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 48,163	48,521
Building and Building Systems [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	25 years
Building and Building Systems [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	40 years
Land Improvements [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 2,853	2,853
Estimated useful life	20 years
Leasehold Improvements [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 39,061	37,935
Leasehold Improvements [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	5 years
Leasehold Improvements [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	20 years
Furniture and Fixtures [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 5,842	5,732
Furniture and Fixtures [Member] | Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	5 years
Furniture and Fixtures [Member] | Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	10 years
Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 10,198	$ 10,198

Organization and Significant 33

Organization and Significant Accounting Policies, Long-Lived Assets (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Long-Lived Assets [Abstract]
Impairment charges	$ 1.9	$ 1.3	$ 6.4

Organization and Significant 34

Organization and Significant Accounting Policies, Stock-based Compensation (Details)	12 Months Ended
	Dec. 31, 2015
RSUs [Member]
Stock-Based Compensation [Abstract]
Vesting period	4 years

Organization and Significant 35

Organization and Significant Accounting Policies, Accumulated Other Comprehensive Income (Loss) (Details) - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Beginning balance		$ 257,780
Amounts reclassified from accumulated other comprehensive (loss) income		(20,211)	$ (21,412)	$ (1,653)
Ending balance		200,790	257,780
Income tax expense included in other comprehensive income		0	12,800	5,900
Gain on investment in Regulus Therapeutics Inc.		20,211	19,902	0
Accumulated Other Comprehensive (Loss) Income [Member]
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Beginning balance		39,747	21,080	12,480
Ending balance		(13,565)	39,747	21,080
Unrealized (Losses) Gains on Securities [Member]
Accumulated Other Comprehensive Income (Loss) [Roll Forward]
Other comprehensive (loss) income before reclassifications, net of tax	[1]	(33,101)	40,079	10,253
Amounts reclassified from accumulated other comprehensive (loss) income	[2]	(20,211)	(21,412)	(1,653)
Net other comprehensive (loss) income for the period		$ (53,312)	$ 18,667	$ 8,600
[1]	Other comprehensive income includes income tax expense of $12.8 million and $5.9 million for the years ended December 31, 2014 and 2013, respectively. There was no tax expense for other comprehensive income for the year ended December 31, 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. For 2014, $19.9 million is included in a separate line called "Gain on investment in Regulus Therapeutics Inc.", with the remaining amount included in a separate line called "Gain on investments, net" on our Consolidated Statement of Operations. Amounts for 2013 are included in a separate line called "Gain on investments, net" on our Consolidated Statement of Operations.

Organization and Significant 36

Organization and Significant Accounting Policies, Convertible Debt and Segment Information (Details) - Segment	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Segment Information [Abstract]
Number of operating segments	2
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%
Convertible Senior Notes [Member] | 2 3/4 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	2.75%	2.75%	2.75%

Organization and Significant 37

Organization and Significant Accounting Policies, Fair Value Measurements on a Recurring Basis (Details) - USD ($) $ in Thousands		Dec. 31, 2015		Dec. 31, 2014
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		682,728		687,788
Investment in Regulus Therapeutics Inc.		24,792		81,881
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	88,902		104,680
Investment in Regulus Therapeutics Inc.		24,792		81,881
Total assets		771,630		792,468
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		438,426	[2]	372,002	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				800
Recurring Basis [Member] | Debt Securities issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]	89,253		109,855
Recurring Basis [Member] | Debt Securities issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		2,601	[2]	19,017	[4]
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				10,000
Recurring Basis [Member] | Debt Securities issued by States of the United States and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		127,656	[5]	105,033	[6]
Recurring Basis [Member] | Debt Securities issued by States of the United States and Political Subdivisions of the States [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		7,500		9,300
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		88,902		104,680
Investment in Regulus Therapeutics Inc.		24,792		0
Total assets		116,295		123,697
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		2,601		19,017
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by States of the United States 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		0
Total assets		655,335		586,890
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		438,426		372,002
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		89,253		109,855
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 United States and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		127,656		105,033
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Investment in Regulus Therapeutics Inc.		0		81,881
Total assets		0		81,881
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities issued by States of the United States and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 0		$ 0
[1]	Included in cash and cash equivalents on our consolidated balance sheet.
[2]	Included in short-term investments on our consolidated balance sheet.
[3]	$0.8 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.
[4]	$10 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]	$7.5 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.
[6]	$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 38

Organization and Significant Accounting Policies, Fair Value Measurements Using Significant Unobservable Inputs (Level 3) (Details) - Equity Securities [Member] - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014
Unobservable Inputs (Level 3) [Roll Forward]
Beginning balance of Level 3 investments	$ 81,881	$ 0
Transfers into Level 3 investments	0	108,009
Total gains (losses) included in accumulated other comprehensive income (loss)	22,377	(24,897)
Transfers out of Level 3 investments	(104,258)	(1,231)
Ending balance of Level 3 investments	$ 0	$ 81,881

Investments, Contract Maturity

Investments, Contract Maturity of Available-for-Sale Securities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2015USD ($)Company	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	49.00%
After one year but within two years	27.00%
After two years but within three and a half years	24.00%
Total	100.00%
Percentage of available-for-sale securities with a maturity of less than two years	76.00%
Ownership Interests in Private and Public Companies [Abstract]
Number of privately-held companies in which the entity has an equity ownership interest of less than 20% | Company	1
Number of publicly-held companies in which the entity has an equity ownership interest of less than 20% | Company	2
Gain on investments, net	$ 20,300	$ 21,200	$ 2,400
Gain on investment in Regulus Therapeutics Inc.	20,211	19,902	$ 0
Investment in Regulus Therapeutics Inc.	$ 24,792	$ 81,881
Regulus Therapeutics Inc. [Member]
Ownership Interests in Private and Public Companies [Abstract]
Ownership interest percentage	5.00%

Investments, Summary of Investm

Investments, Summary of Investments and Investments Temporarily Impaired (Details) $ in Thousands		Dec. 31, 2015USD ($)Investment	Dec. 31, 2014USD ($)
Summary of Investments [Abstract]
Cost	[1]	$ 660,458	$ 606,889
Gross unrealized gains	[1]	30	172
Gross unrealized losses	[1]	(2,552)	(1,154)
Estimated fair value	[1]	657,936	605,907
Cost		667,620	619,366
Gross unrealized gains		17,660	69,576
Gross unrealized losses		(2,552)	(1,154)
Estimated fair value		$ 682,728	687,788
Temporarily Impaired Investments [Abstract]
Number of investments | Investment		648
Estimated fair value, less than 12 months of temporary impairment		$ 540,423
Unrealized losses, less than 12 months of temporary impairment		(2,346)
Estimated fair value, more than 12 months of temporary impairment		46,701
Unrealized losses, more than 12 months of temporary impairment		(206)
Estimated fair value, total temporary impairment		587,124
Unrealized losses, total temporary impairment		(2,552)
Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	314,247	331,556
Gross unrealized gains	[1]	24	124
Gross unrealized losses	[1]	(360)	(169)
Estimated fair value	[1]	313,911	331,511
Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	346,211	275,333
Gross unrealized gains	[1]	6	48
Gross unrealized losses	[1]	(2,192)	(985)
Estimated fair value	[1]	$ 344,025	274,396
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment		397
Estimated fair value, less than 12 months of temporary impairment		$ 406,098
Unrealized losses, less than 12 months of temporary impairment		(1,908)
Estimated fair value, more than 12 months of temporary impairment		16,066
Unrealized losses, more than 12 months of temporary impairment		(47)
Estimated fair value, total temporary impairment		422,164
Unrealized losses, total temporary impairment		(1,955)
Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	181,670	219,856	[2]
Gross unrealized gains	[1]	5	89	[2]
Gross unrealized losses	[1]	(250)	(89)	[2]
Estimated fair value	[1]	181,425	219,856	[2]
Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	258,703	152,730
Gross unrealized gains	[1]	3	16
Gross unrealized losses	[1]	(1,705)	(600)
Estimated fair value	[1]	$ 257,001	152,146
Debt Securities issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment		19
Estimated fair value, less than 12 months of temporary impairment		$ 71,842
Unrealized losses, less than 12 months of temporary impairment		(262)
Estimated fair value, more than 12 months of temporary impairment		1,001
Unrealized losses, more than 12 months of temporary impairment		(1)
Estimated fair value, total temporary impairment		72,843
Unrealized losses, total temporary impairment		(263)
Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	50,559	47,496
Gross unrealized gains	[1]	1	7
Gross unrealized losses	[1]	(19)	(27)
Estimated fair value	[1]	50,541	47,476
Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	38,956	62,530
Gross unrealized gains	[1]	0	0
Gross unrealized losses	[1]	(244)	(151)
Estimated fair value	[1]	$ 38,712	62,379
Debt Securities issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment		2
Estimated fair value, less than 12 months of temporary impairment		$ 2,601
Unrealized losses, less than 12 months of temporary impairment		(3)
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		2,601
Unrealized losses, total temporary impairment		(3)
Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1]	2,604	19,008	[2]
Gross unrealized gains	[1]	0	9	[2]
Gross unrealized losses	[1]	(3)	0	[2]
Estimated fair value	[1]	$ 2,601	19,017	[2]
Debt Securities issued by States of the United States and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment		230
Estimated fair value, less than 12 months of temporary impairment		$ 59,882
Unrealized losses, less than 12 months of temporary impairment		(173)
Estimated fair value, more than 12 months of temporary impairment		29,634
Unrealized losses, more than 12 months of temporary impairment		(158)
Estimated fair value, total temporary impairment		89,516
Unrealized losses, total temporary impairment		(331)
Debt Securities issued by States of the United States and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]
Summary of Investments [Abstract]
Cost	[1],[2]	79,414	45,196
Gross unrealized gains	[1],[2]	18	19
Gross unrealized losses	[1],[2]	(88)	(53)
Estimated fair value	[1],[2]	79,344	45,162
Debt Securities issued by States of the United States and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]
Summary of Investments [Abstract]
Cost	[1]	48,552	60,073
Gross unrealized gains	[1]	3	32
Gross unrealized losses	[1]	(243)	(234)
Estimated fair value	[1]	48,312	59,871
Equity Securities [Member]
Summary of Investments [Abstract]
Cost		7,162	12,477
Gross unrealized gains		17,630	69,404
Gross unrealized losses		0	0
Estimated fair value		24,792	81,881
Equity Securities [Member] | Regulus Therapeutics Inc. [Member]
Summary of Investments [Abstract]
Cost		7,162	12,477
Gross unrealized gains		17,630	69,404
Gross unrealized losses		0	0
Estimated fair value		$ 24,792	$ 81,881
[1]	Our available-for-sale securities are held at amortized cost.
[2]	Includes investments classified as cash equivalents on our consolidated balance sheet.

Long-Term Obligations and Com41

Long-Term Obligations and Commitments, Long-Term Obligations (Details) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	$ 472,648	$ 457,782
Less: current portion	(515)	(2,882)
Total Long-Term Obligations	472,133	454,900
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	347,214	327,486
Convertible Senior Notes [Member] | 2 3/4 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	50,361	48,014
Long-term Financing Liability for Leased Facility [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	72,217	71,731
Equipment Financing Arrangement [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	515	3,226
Leases and Other Obligations [Member]
Long-Term Obligations [Abstract]
Total long-term obligations, including current portion	$ 2,341	$ 7,325

Long-Term Obligations and Com42

Long-Term Obligations and Commitments, Convertible Notes (Details)	1 Months Ended	12 Months Ended
	Nov. 30, 2014USD ($)	Dec. 31, 2015USD ($)sharesd$ / shares	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Convertible Notes [Abstract]
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs		$ 0	$ 487,035,000	$ 0
Loss on early retirement of debt		0	(8,292,000)	0
Amortization of debt discount and debt issuance costs		23,200,000	9,600,000	$ 6,800,000
1 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Long-term debt		347,214,000	327,486,000
2 3/4 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Principal amount repurchased			140,000,000
Long-term debt		50,361,000	48,014,000
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Face amount of offering	$ 500,000,000
Proceeds from issuance of 1 percent convertible senior notes, net of issuance costs	487,000,000
Principal amount of convertible notes outstanding		$ 500,000,000	$ 500,000,000
Issue date		Nov. 30, 2014
Maturity date		Nov. 30, 2021
Interest rate		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		7,500,000
Percentage of principal amount used a purchase price upon occurrence of fundamental change		100.00%
Nonconvertible debt borrowing rate		7.40%
Effective interest rate		7.80%
Amortization period of debt discount		7 years
Fair value of outstanding notes		$ 555,000,000	$ 568,000,000
Unamortized portion of liability component		152,786,000	172,514,000
Long-term debt		347,214,000	327,486,000
Carrying value of equity component		174,770,000	174,770,000
Convertible Senior Notes [Member] | 2 3/4 Percent Convertible Senior Notes [Member]
Convertible Notes [Abstract]
Principal amount repurchased	140,000,000
Repurchase of convertible senior notes	441,900,000
Principal amount of convertible notes outstanding	61,200,000	$ 61,247,000	$ 61,247,000
Loss on early retirement of debt	$ 8,300,000
Issue date		Aug. 31, 2012
Maturity date		Oct. 31, 2019
Interest rate		2.75%	2.75%	2.75%
Conversion price per share (in dollars per share) | $ / shares		$ 16.63
Total shares of common stock subject to conversion (in shares) | shares		3,700,000
Percentage of principal amount used a purchase price upon occurrence of fundamental change		100.00%
If-converted value of notes in excess of principal		$ 166,900,000
Nonconvertible debt borrowing rate		8.00%
Effective interest rate		8.80%
Amortization period of debt discount		7 years
Fair value of outstanding notes		$ 215,320,000	$ 223,900,000
Unamortized portion of liability component		10,886,000	13,233,000
Long-term debt		50,361,000	48,014,000
Carrying value of equity component		$ 18,714,000	$ 18,714,000
Convertible Senior Notes [Member] | 2 3/4 Percent Convertible Senior Notes [Member] | On or after October 5, 2016 [Member]
Convertible Notes [Abstract]
Threshold number of trading days to trigger redemption | d		20
Threshold number of consecutive trading days to trigger redemption		30 days
Threshold percentage of conversion price to trigger redemption		130.00%
Percentage of principal amount used as redemption price		100.00%
Additional payment per $1,000 principal amount being redeemed		$ 90
Principal amount being redeemed		$ 1,000

Long-Term Obligations and Com43

Long-Term Obligations and Commitments, Financing Arrangements (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Feb. 25, 2016	Dec. 31, 2014
Financing Arrangements [Abstract]
Carrying balance of loan	$ 472,648		$ 457,782
Equipment Financing Arrangement [Member]
Financing Arrangements [Abstract]
Weighted average interest rate	4.39%
Carrying balance of loan	$ 515		$ 3,226
Morgan Stanley [Member] | Revolving Line of Credit [Member]
Financing Arrangements [Abstract]
Term of agreement	5 years
Commitment fee percentage on unused capacity	0.25%
Outstanding borrowings	$ 8,500
Weighted average interest rate	1.67%
Morgan Stanley [Member] | Revolving Line of Credit [Member] | Subsequent Event [Member]
Financing Arrangements [Abstract]
Maximum borrowing capacity		$ 30,000
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 Com44

Long-Term Obligations and Commitments, Maturity Schedules (Details) - USD ($) $ in Thousands	Dec. 31, 2015	Dec. 31, 2014
Annual Debt and Other Obligation Maturities [Abstract]
Less: current portion	$ (515)	$ (2,882)
Total	472,133	$ 454,900
Long-Term Obligations, Excluding Financing Liability for Leased Facility [Member]
Annual Debt and Other Obligation Maturities [Abstract]
2,016	15,767
2,017	6,744
2,018	6,744
2,019	6,744
2,020	66,304
Thereafter	505,960
Total minimum payments	608,263
Less: current portion	(9,029)
Less: fixed and determinable interest	(37,655)
Less: unamortized portion of debt discount	(163,672)
Plus: Deferred rent	2,006
Total	$ 399,913

Long-Term Obligations and Com45

Long-Term Obligations and Commitments, Operating Leases (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2015USD ($)BuildingOption	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Annual Future Minimum Payments Under Operating Leases [Abstract]
2,016	$ 1,879
2,017	1,878
2,018	1,597
2,019	1,474
2,020	1,527
Thereafter	16,125
Total minimum payments	24,480
Office and Laboratory Space [Member]
Annual Future Minimum Payments Under Operating Leases [Abstract]
Rent expense	2,000	$ 1,800	$ 1,800
Deferred rent	$ 2,000	$ 1,800
Office and Laboratory Space [Member] | Akcea Therapeutics [Member]
Operating Leases [Abstract]
Number of buildings in Carlsbad, California | Building	3
Office and Laboratory Space [Member] | Manufacturing Facility [Member]
Operating Leases [Abstract]
Number of options to extend lease | Option	4
Term of lease extension	5 years
Office and Laboratory Space [Member] | Building [Member]
Operating Leases [Abstract]
Number of options to extend lease | Option	2
Term of lease extension	5 years
Office and Laboratory Space [Member] | Building [Member] | Akcea Therapeutics [Member]
Operating Leases [Abstract]
Term of lease	3 years

Long-Term Obligations and Com46

Long-Term Obligations and Commitments, Research and Development Facility Lease Obligation (Details) $ in Thousands	1 Months Ended	12 Months Ended
	Mar. 31, 2010USD ($)	Dec. 31, 2015USD ($)Option	Dec. 31, 2014USD ($)
Research and Development Facility Lease Obligation [Abstract]
Net book value of facility and associated parcel of land		$ 90,233	$ 88,958
Accumulated depreciation of facility		$ 72,706	66,053
Purchase price of land	$ 10,100
Primary Research and Development Facility [Member]
Research and Development Facility Lease Obligation [Abstract]
Number of options to extend lease | Option		4
Term of lease extension		5 years
Net book value of facility and associated parcel of land		$ 62,200	64,400
Accumulated depreciation of facility		9,900	$ 7,700
Annual Future Rent Payments [Abstract]
2,016		6,550
2,017		6,550
2,018		6,943
2,019		6,943
2,020		7,359
Thereafter		91,205
Total minimum payments		$ 125,550

Stockholders' Equity, Preferred

Stockholders' Equity, Preferred and Common Stock (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Common Stock [Abstract]
Common stock, shares authorized to issue (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	120,351,480	118,442,726
Common stock, shares outstanding (in shares)	120,351,480	118,442,726
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 24,888	$ 23,071	$ 62,958
Preferred Stock [Member]
Preferred Stock [Abstract]
Preferred stock, shares authorized to issue (in shares)	15,000,000
Preferred stock, shares issued (in shares)		0
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)	120,351,480	118,442,726
Common stock, shares outstanding (in shares)	120,351,480	118,442,726
Common shares reserved for future issuance (in shares)	18,512,177
Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)	1,908,000	1,972,000	5,372,000
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 24,900	$ 23,100	$ 63,000

Stockholders' Equity, Stock Pla

Stockholders' Equity, Stock Plans (Details)	1 Months Ended	12 Months Ended
	Jun. 30, 2009shares	Dec. 31, 2015Installment$ / sharesshares	Jun. 30, 2015shares	May. 31, 2015shares	Dec. 31, 2014shares
Stock Options [Member]
Stock Plans [Abstract]
Number of options outstanding (in shares)		8,041,000			7,379,000
Number of options exercisable (in shares)		3,940,000
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)		3,619,716
Number of options exercisable (in shares)		2,927,597
Number of shares available for grant (in shares)		13,462
1989 Stock Option Plan [Member] | One Year from Date of Grant [Member]
Stock Plans [Abstract]
Vesting percentage		25.00%
2000 Broad Based Equity Incentive Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)		5,990,000
Vesting period		4 years
Number of options outstanding (in shares)		44,025
Number of options exercisable (in shares)		44,025
Number of shares available for grant (in shares)		0
2000 Broad Based Equity Incentive Plan [Member] | One Year from Date of Grant [Member]
Stock Plans [Abstract]
Vesting percentage		25.00%
2000 Broad Based Equity Incentive Plan [Member] | Minimum [Member]
Stock Plans [Abstract]
Award term		7 years
2000 Broad Based Equity Incentive Plan [Member] | Maximum [Member]
Stock Plans [Abstract]
Award term		10 years
2011 Equity Incentive Plan [Member]
Stock Plans [Abstract]
Number of shares authorized (in shares)			11,000,000	5,500,000
Number of options outstanding (in shares)		3,832,225
Number of options exercisable (in shares)		659,254
Number of shares available for grant (in shares)		5,989,752
Number of awards outstanding (in shares)		712,034
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)		544,812
Number of options exercisable (in shares)		309,319
Number of shares available for grant (in shares)		859,871
Number of awards outstanding (in shares)		38,621
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)		3,224,596
Number of shares available for grant (in shares)		481,764
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)		38,372
Purchase price (in dollars per share) | $ / shares		$ 37.43

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, 2015	Dec. 31, 2014	Dec. 31, 2013
Number of Shares [Abstract]
Outstanding at beginning of period (in shares)	7,379
Granted (in shares)	2,550
Exercised (in shares)	(1,674)
Cancelled/forfeited/expired (in shares)	(214)
Outstanding at end of period (in shares)	8,041	7,379
Exercisable at end of period (in shares)	3,940
Weighted Average Exercise Price Per Share [Abstract]
Outstanding at beginning of period (in dollars per share)	$ 19.52
Granted (in dollars per share)	61.02
Exercised (in dollars per share)	14.07
Cancelled/forfeited/expired (in dollars per share)	42.43
Outstanding at end of period (in dollars per share)	33.21	$ 19.52
Exercisable at end of period (in dollars per share)	$ 16.43
Average Remaining Contractual Term, Aggregate Intrinsic Value and Other [Abstract]
Average remaining contractual term, outstanding at end of period	4 years 6 months 25 days
Average remaining contractual term, exercisable at end of period	3 years 3 months 25 days
Aggregate intrinsic value, outstanding at end of period	$ 232,581
Aggregate intrinsic value, exercisable at end of period	$ 179,273
Weighted average fair value of options granted (in dollars per share)	$ 27.44	$ 17.54	$ 7.10
Intrinsic value of options exercised	$ 84,700	$ 62,800	$ 69,600
Cash received from exercise of stock options	$ 23,600	$ 22,400	$ 62,000
Weighted-average fair value of options exercised (in dollars per share)	$ 64.69
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	$ 45,700
Weighted average period for recognition	1 year 3 months 18 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, 2015	Dec. 31, 2014	Dec. 31, 2013
Number of Shares [Abstract]
Non-vested at beginning of period (in shares)	638
Granted (in shares)	348
Vested (in shares)	(196)
Cancelled/forfeited (in shares)	(39)
Non-vested at end of period (in shares)	751	638
Weighted Average Grant Date Fair Value per Share [Abstract]
Non-vested at beginning of period (in dollars per share)	$ 30.52
Granted (in dollars per share)	65.69	$ 44.94	$ 17.42
Vested (in dollars per share)	27.40
Cancelled/forfeited (in dollars per share)	42.87
Non-vested at end of period (in dollars per share)	$ 47.47	$ 30.52
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested RSUs	$ 16
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, 2015	Dec. 31, 2014	Dec. 31, 2013
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 59,314	$ 31,383	$ 11,418
Research, Development and Patents [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	43,638	25,843	9,673
General and Administrative [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	15,676	$ 5,540	$ 1,745
Akcea Therapeutics [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 6,500

Stockholders' Equity, Stock-b52

Stockholders' Equity, Stock-based Valuation Information (Details)	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Employee Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	1.50%	1.70%	1.10%
Dividend yield	0.00%	0.00%	0.00%
Volatility	53.80%	50.10%	51.10%
Expected life	4 years 6 months	4 years 8 months 12 days	5 years 1 month 6 days
Board of Director Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	2.10%	2.20%	2.20%
Dividend yield	0.00%	0.00%	0.00%
Volatility	52.20%	54.20%	52.70%
Expected life	6 years 10 months 24 days	6 years 10 months 24 days	7 years 2 months 12 days
Employee Stock Purchase Plan (ESPP) [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	0.10%	0.10%	0.10%
Dividend yield	0.00%	0.00%	0.00%
Volatility	51.70%	60.10%	62.90%
Expected life	6 months	6 months	6 months

Income Taxes, Provision for Inc

Income Taxes, Provision for Income Taxes (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Dec. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Current [Abstract]
Federal		$ 379	$ 263	$ 0
State		(7)	(4,295)	2
Total current		372	(4,032)	2
Deferred [Abstract]
Federal		0	(8,948)	(5,082)
State		0	(2,427)	(834)
Total deferred		0	(11,375)	(5,916)
Income tax expense (benefit)		372	(15,407)	(5,914)
Tax benefit related to unrealized gains on investments in available-for-sale securities recorded in continuing operations			(12,800)	(5,900)
Tax expense related to unrealized gains on investments in available-for-sale securities recorded in other comprehensive income			$ 12,800	$ 5,900
State Jurisdiction [Member] | California Franchise Tax Board [Member] | Tax Year 2009 [Member]
Income Taxes [Abstract]
Franchise tax refund		$ 4,300
Research Tax Credit Carryforward [Member] | California Franchise Tax Board [Member] | Tax Year 2009 [Member]
Income Taxes [Abstract]
Increase in research credit carry over	$ 4,300

Income Taxes, Reconciliation of

Income Taxes, Reconciliation of Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre tax loss	$ (87,906)	$ (54,391)	$ (66,558)
Statutory rate	(30,767)	(19,035)	(23,295)
State income tax net of federal benefit	1	(3,125)	(3,823)
Net change in valuation allowance	69,499	29,547	28,850
Loss on debt extinguishment	0	2,406	0
Tax credits	(41,284)	(23,628)	(15,839)
California franchise tax refund	0	(2,795)	0
Deferred tax true-up	1,496	977	8,023
Other	1,427	246	170
Income tax expense (benefit)	$ 372	$ (15,407)	$ (5,914)
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	35.00%	35.00%	35.00%
State income tax net of federal benefit	0.00%	5.70%	5.70%
Net change in valuation allowance	(79.10%)	(54.30%)	(43.30%)
Loss on debt extinguishment	0.00%	(4.40%)	0.00%
Tax credits	47.00%	43.40%	23.80%
California franchise tax refund	0.00%	5.10%	0.00%
Deferred tax true-up	(1.70%)	(1.80%)	(12.10%)
Other	(1.60%)	(0.50%)	(0.20%)
Effective rate	(0.40%)	28.20%	8.90%

Income Taxes, Deferred Tax Asse

Income Taxes, Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014
Deferred Tax Assets [Abstract]
Net operating loss carryovers	$ 218,493	$ 231,654
R&D credits	153,601	93,594
Deferred revenue	45,110	58,836
Stock-based compensation	31,093	21,553
Other	19,655	15,549
Total deferred tax assets	467,952	421,186
Deferred Tax Liabilities [Abstract]
Convertible debt	(55,928)	(73,733)
Unrealized gain in other comprehensive income	(5,288)	(27,878)
Intangible and capital assets	(2,643)	(3,641)
Net deferred tax asset	404,093	315,934
Valuation allowance	(404,093)	(315,934)
Net deferreds	0	0
Excess tax benefits from shared-based compensation awards	396	$ 1,463
Unrealized excess tax benefits associated with share-based compensation	$ 76,900

Income Taxes, Tax Credit Carryf

Income Taxes, Tax Credit Carryforward (Details) $ in Millions	Dec. 31, 2015USD ($)
Research and Development [Member] | Federal [Member]
Tax Credit Carryforward [Abstract]
Tax credit carryforwards	$ 146.8
Research and Development [Member] | California [Member]
Tax Credit Carryforward [Abstract]
Tax credit carryforwards	44.7
Federal [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	734.7
California [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	$ 886.5

Income Taxes, Gross Unrecognize

Income Taxes, Gross Unrecognized Tax Benefits (Details) - USD ($)	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Gross Unrecognized Tax Benefits [Roll Forward]
Beginning balance of unrecognized tax benefits	$ 27,365,000	$ 23,964,000	$ 10,872,000
Decrease for prior period tax positions	0	(1,653,000)	0
Increase for prior period tax positions	215,000	0	9,821,000
Increase for current period tax positions	23,677,000	5,054,000	3,271,000
Ending balance of unrecognized tax benefits	51,257,000	$ 27,365,000	$ 23,964,000
Unrecognized tax benefits that would reduce effective tax rate	33,300,000
Interest and penalties on unrecognized tax benefits	$ 0

Collaborative Arrangements an58

Collaborative Arrangements and Licensing Agreements, Strategic Partnerships - AstraZeneca (Details) $ in Thousands	1 Months Ended	3 Months Ended								7 Months Ended	12 Months Ended
	Jul. 31, 2015USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Jun. 30, 2013USD ($)	Dec. 31, 2015USD ($)AccountingUnit	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)	Dec. 31, 2012Drug	Jan. 31, 2016USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161		$ 283,703	$ 214,161	$ 147,285
AstraZeneca [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned											6,400	27,700	$ 29,100
Deferred revenue		63,300				$ 4,400					$ 63,300	$ 4,400
AstraZeneca [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage											2.00%	13.00%	20.00%
AstraZeneca [Member] | Agreement Entered into in December 2012 [Member] | Oncology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		750,000									$ 750,000
Next potential milestone		15,000									15,000
Number of drugs the collaborative partner may license under a separate research program | Drug														3
Cumulative upfront fees received		31,000									31,000
Revenue earned										$ 11,500
Upfront fee amortized into revenue		11,900									11,900
Deferred revenue		7,600									7,600
Cumulative payments and/or fees received		63,500									63,500
AstraZeneca [Member] | Agreement Entered into in December 2012 [Member] | Oncology [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		226,000									226,000
AstraZeneca [Member] | Agreement Entered into in December 2012 [Member] | Oncology [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		485,000									485,000
AstraZeneca [Member] | Amended Agreement Entered into in January 2016 [Member] | Oncology [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment to be earned															$ 5,000
AstraZeneca [Member] | Agreement Entered into in July 2015 [Member] | Cardiometabolic and Renal Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee received	$ 65,000
Next potential milestone		25,000									$ 25,000
Number of units of accounting | AccountingUnit											1
AstraZeneca [Member] | Agreement Entered into in July 2015 [Member] | Cardiometabolic and Renal Diseases [Member] | License Fee and Substantive Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Minimum amount of payments receivable		4,000,000									$ 4,000,000
AstraZeneca [Member] | Agreement Entered into in July 2015 [Member] | Cardiometabolic and Renal Diseases [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		1,100,000									1,100,000
AstraZeneca [Member] | Agreement Entered into in July 2015 [Member] | Cardiometabolic and Renal Diseases [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		$ 2,900,000									$ 2,900,000

Collaborative Arrangements an59

Collaborative Arrangements and Licensing Agreements, Strategic Partnerships - Biogen (Nusinersen) (Details) - Biogen [Member] $ in Millions	1 Months Ended			12 Months Ended
	Feb. 29, 2016USD ($)	Jun. 30, 2015USD ($)	Jan. 31, 2012USD ($)	Dec. 31, 2015USD ($)AgreementDrugStudy
Nusinersen [Member] | Studies in Infants and Children with SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned				$ 40
Nusinersen [Member] | Open-Label Extension Study for Phase 3 Studies in Infants and Children with SMA [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned	$ 2
Nusinersen [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable				121
Nusinersen [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable				150
Nusinersen [Member] | License Fee and Substantive Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable				$ 346
Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of strategic collaboration agreements | Agreement				4
Collaborations and Licensing Agreements [Member] | Drugs to Treat Neurological Disorders Under Collaborations [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug				6
Collaborations and Licensing Agreements [Member] | Drugs to Treat Undisclosed Neurodegenerative Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug				3
Agreement Entered into in January 2012 [Member] | Phase 2 Studies in Infants and Children with SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of Phase 2 open-label, multiple-dose, dose-escalation studies in which drug is being evaluated | Study				2
Agreement Entered into in January 2012 [Member] | Phase 2 Studies in Infants with SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of Phase 2 open-label, multiple-dose, dose-escalation studies in which drug is being evaluated | Study				1
Agreement Entered into in January 2012 [Member] | Phase 2 Studies in Children with SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of Phase 2 open-label, multiple-dose, dose-escalation studies in which drug is being evaluated | Study				1
Agreement Entered into in January 2012 [Member] | Nusinersen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee recorded as deferred revenue			$ 29
Milestone payment earned		$ 11
Next potential milestone				$ 2
Agreement Entered into in January 2012 [Member] | Nusinersen [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments and/or fees received				$ 130

Collaborative Arrangements an60

Collaborative Arrangements and Licensing Agreements, Strategic Partnerships - Biogen (IONIS-DMPK-2.5) (Details) - Biogen [Member] - USD ($) $ in Millions	1 Months Ended
	Nov. 30, 2015	Jun. 30, 2012	Dec. 31, 2015
Agreement Entered into in June 2012 [Member] | IONIS-DMPK-2.5 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee recorded as deferred revenue		$ 12
Next potential milestone			$ 35
Agreement Entered into in June 2012 [Member] | IONIS-DMPK-2.5 [Member] | License Fee and Substantive Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			263
Cumulative payments and/or fees received			39
Agreement Entered into in June 2012 [Member] | IONIS-DMPK-2.5 [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			63
Agreement Entered into in June 2012 [Member] | IONIS-DMPK-2.5 [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			130
Agreement Amended in June 2015 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned	$ 2.8
Agreement Amended in June 2015 [Member] | IONIS-DMPK-2.5 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			4.2
Next potential milestone			$ 1.4

Collaborative Arrangements an61

Collaborative Arrangements and Licensing Agreements, Strategic Partnerships - Biogen (Neurology) (Details) - Biogen [Member] - Agreement Entered into in December 2012 [Member] - Neurology [Member] $ in Millions	1 Months Ended
	Feb. 29, 2016USD ($)	Feb. 28, 2015USD ($)	Dec. 31, 2012USD ($)TargetDrug	Dec. 31, 2015USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of targets | Target			3
Number of programs under which drugs are to be developed and commercialized | Drug			3
Upfront fee recorded as deferred revenue			$ 30
Milestone payment earned		$ 10
Cumulative payments and/or fees received				$ 40
Next potential milestone				10
Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned	$ 3
License Fee and Substantive Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per program				259
Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per program				59
Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per program				$ 130

Collaborative Arrangements an62

Collaborative Arrangements and Licensing Agreements, Strategic Partnerships - Biogen (Strategic Neurology) (Details) $ in Thousands	1 Months Ended		3 Months Ended								12 Months Ended
	Dec. 31, 2015USD ($)	Sep. 30, 2013USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Drug	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned			$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
Biogen [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned											106,200	123,200	$ 37,000
Deferred revenue	$ 91,600		91,600				$ 118,100				$ 91,600	$ 118,100
Biogen [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage											37.00%	58.00%	25.00%
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently being advanced | Drug											3
Upfront fee recorded as deferred revenue		$ 100,000
Term of collaboration agreement											6 years
Cumulative payments and/or fees received	135,000		135,000								$ 135,000
Milestone payment earned	5,000
Next potential milestone	10,000		10,000								10,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Antisense Molecule [Member] | License Fee and Substantive Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	260,000		260,000								260,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Antisense Molecule [Member] | Research and Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	60,000		60,000								60,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Antisense Molecule [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	130,000		130,000								130,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Other Modalities [Member] | Pre-Specified Events [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	90,000		90,000								90,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Other Modalities [Member] | Research and Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	35,000		35,000								35,000
Biogen [Member] | Agreement Entered into in September 2013 [Member] | Other Modalities [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug	$ 55,000		$ 55,000								$ 55,000

Collaborative Arrangements an63

Collaborative Arrangements and Licensing Agreements, Research, Development and Commercialization Partners - Bayer (Details) - USD ($) $ in Thousands

1 Months Ended

3 Months Ended

12 Months Ended

Jun. 30, 2015

May. 31, 2015

Dec. 31, 2015

Sep. 30, 2015

Jun. 30, 2015

Mar. 31, 2015

Dec. 31, 2014

Sep. 30, 2014

Jun. 30, 2014

Mar. 31, 2014

Dec. 31, 2015

Dec. 31, 2014

Dec. 31, 2013

Collaborative Arrangement and Licensing Agreement [Abstract]

Revenue earned

$ 51,571

$ 49,121

$ 120,428

$ 62,583

$ 84,861

$ 44,063

$ 57,076

$ 28,161

$ 283,703

$ 214,161

$ 147,285

Agreement Entered into in May 2015 [Member] | License Fees, Substantive Milestone Payments and Other Payments [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

$ 375,000

Agreement Entered into in May 2015 [Member] | Development Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

120,000

Agreement Entered into in May 2015 [Member] | Commercialization Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

110,000

Bayer HealthCare [Member] | Collaborations and Licensing Agreements [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Revenue earned

93,400

Deferred revenue

6,700

$ 6,700

Bayer HealthCare [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member] | Strategic Partner [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Concentration percentage

33.00%

Bayer HealthCare [Member] | Agreement Entered into in May 2015 [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Near-term payments

$ 155,000

Upfront fee received

100,000

Next potential milestone

$ 55,000

$ 55,000

Revenue earned

$ 91,200

Bayer HealthCare [Member] | Agreement Entered into in May 2015 [Member] | Minimum [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Percentage of gross margins of sales received as royalties

20.00%

Bayer HealthCare [Member] | Agreement Entered into in May 2015 [Member] | IONIS-FXI [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Upfront fee recorded as deferred revenue

$ 8,800

$ 4,300

Collaborative Arrangements an64

Collaborative Arrangements and Licensing Agreements, Research, Development and Commercialization Partners - Genzyme Corporation (Details) - USD ($)	1 Months Ended	3 Months Ended								12 Months Ended
	Jan. 31, 2008	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangement and Licensing Agreement [Abstract]
Equity investment in common stock										$ 0	$ 0	$ 173,292,000
Revenue earned		$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	283,703,000	214,161,000	147,285,000
Genzyme Corporation [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee recorded as deferred revenue	$ 175,000,000
Equity investment in common stock	$ 150,000,000
Cumulative payments, fees and equity investment received		$ 375,000,000								375,000,000
Revenue earned										$ 0	$ 0	$ 32,500,000
Genzyme Corporation [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage												22.00%

Collaborative Arrangements an65

Collaborative Arrangements and Licensing Agreements, Research, Development and Commercialization Partners - GSK (Details) $ in Thousands	1 Months Ended		3 Months Ended								12 Months Ended
	Jan. 31, 2016USD ($)	Mar. 31, 2010USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Drug	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned			$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
GSK [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug											5
Upfront fee received		$ 38,000
Cumulative payments and/or fees received			135,000								$ 135,000
Next potential milestone			5,000								5,000
Revenue earned											33,300	37,300	$ 35,300
Deferred revenue			4,900				$ 10,000				$ 4,900	$ 10,000
GSK [Member] | Collaborations and Licensing Agreements [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned	$ 1,500
GSK [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage											12.00%	17.00%	24.00%
GSK [Member] | Collaborations and Licensing Agreements [Member] | Pre Specified Events [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Minimum amount of payments receivable			1,000,000								$ 1,000,000
GSK [Member] | Collaborations and Licensing Agreements [Member] | Pre-Licensing Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			10,000								10,000
GSK [Member] | Collaborations and Licensing Agreements [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			183,500								183,500
GSK [Member] | Collaborations and Licensing Agreements [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			363,500								363,500
GSK [Member] | Collaborations and Licensing Agreements [Member] | Commercialization Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			348,000								348,000
GSK [Member] | Collaborations and Licensing Agreements [Member] | IONIS-TTR [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments and/or fees received			$ 60,000								$ 60,000
GSK [Member] | Collaborations and Licensing Agreements [Member] | IONIS-HBV, IONIS-HBV-L, IONIS-GSK4-L, and IONIS-RHO-2.5 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug											4
GSK [Member] | Collaborations and Licensing Agreements [Member] | IONIS-HBV and IONIS-HBV-L [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug											2

Collaborative Arrangements an66

Collaborative Arrangements and Licensing Agreements, Research, Development and Commercialization Partners - Janssen Biotech, Inc. (Details)	3 Months Ended								12 Months Ended
	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Drug	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	$ 283,703,000	$ 214,161,000	$ 147,285,000
Janssen Biotech, Inc. [Member] | Agreement Entered Into in December 2014 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of programs under which drugs are to be developed and commercialized | Drug									3
Cumulative payments and/or fees received	35,000,000								$ 35,000,000
Maximum amount of payments receivable	800,000,000								800,000,000
Next potential milestone	5,000,000								5,000,000
Revenue earned									8,900,000	$ 0	$ 0
Deferred revenue	26,300,000								26,300,000
Janssen Biotech, Inc. [Member] | Agreement Entered Into in December 2014 [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable	175,000,000								175,000,000
Janssen Biotech, Inc. [Member] | Agreement Entered Into in December 2014 [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable	420,000,000								420,000,000
Janssen Biotech, Inc. [Member] | Agreement Entered Into in December 2014 [Member] | Commercialization Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable	$ 180,000,000								$ 180,000,000

Collaborative Arrangements an67

Collaborative Arrangements and Licensing Agreements, Research, Development and Commercialization Partners - Roche (Details) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Apr. 30, 2013USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Candidate	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
Roche [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned										31,200	8,700	$ 5,100
Deferred revenue		8,800				$ 17,000				$ 8,800	$ 17,000
Roche [Member] | Collaborations and Licensing Agreements [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage										11.00%	4.00%	3.00%
Roche [Member] | Agreement Entered into in April 2013 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee recorded as deferred revenue	$ 30,000
Maximum amount of payments receivable	362,000
Cumulative payments and/or fees received		52,000								$ 52,000
Next potential milestone	$ 10,000
Roche [Member] | Agreement Entered into in April 2013 [Member] | Development, Regulatory and Commercial Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug		136,500								136,500
Roche [Member] | Agreement Entered into in April 2013 [Member] | HTT [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		67,000								67,000
Roche [Member] | Agreement Entered into in April 2013 [Member] | HTT [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		170,000								170,000
Roche [Member] | Agreement Entered into in April 2013 [Member] | HTT [Member] | Commercialization Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		80,000								80,000
Roche [Member] | Agreement Entered into in April 2013 [Member] | Brain Shuttle Program [Member] | Commercialization Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		$ 50,000								$ 50,000
Number of development candidates that must be generated for brain shuttle program | Candidate										1

Collaborative Arrangements an68

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - Achaogen, Inc. (Details)	1 Months Ended	3 Months Ended								12 Months Ended
	Sep. 30, 2014USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Drug	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)	Dec. 31, 2006USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	$ 283,703,000	$ 214,161,000	$ 147,285,000
Achaogen Inc [Member] | Satellite Company Collaboration and Licensing Agreement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments and/or fees received		7,000,000								$ 7,000,000
Milestone payment earned	$ 4,000,000
Number of drugs to be developed and commercialized | Drug										2
Next potential milestone		7,500,000								$ 7,500,000
Revenue earned										0	4,000,000	$ 0
Net proceeds from sale of stock											$ 1,300,000
Achaogen Inc [Member] | Satellite Company Collaboration and Licensing Agreement [Member] | Pre Specified Events [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable		$ 49,300,000								$ 49,300,000
Achaogen Inc [Member] | Satellite Company Collaboration and Licensing Agreement [Member] | Series A preferred stock [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee in the form of equity securities													$ 1,500,000

Collaborative Arrangements an69

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - Alnylam Pharmaceuticals, Inc. (Details) $ in Thousands	1 Months Ended	3 Months Ended								12 Months Ended
	Mar. 31, 2004USD ($)	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)TargetProgram	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
Alnylam Pharmaceuticals, Inc. [Member] | Satellite Company Collaboration and Licensing Agreement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee recorded as deferred revenue	$ 5,000
Next potential milestone		400								$ 400
Number of therapeutic targets granted to Ionis | Target										4
Number of therapeutic targets granted by Ionis | Target										4
Number of therapeutic programs | Program										4
Cumulative payments and/or fees received		70,000								$ 70,000
Revenue earned										1,300	$ 9,900	$ 1,500
Alnylam Pharmaceuticals, Inc. [Member] | Satellite Company Collaboration and Licensing Agreement [Member] | Pre Specified Events [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug		3,400								3,400
Maximum amount of milestone payments payable		$ 3,400								$ 3,400
Alnylam Pharmaceuticals, Inc. [Member] | Satellite Company Collaboration and Licensing Agreement [Member] | Development Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug			1,100
Alnylam Pharmaceuticals, Inc. [Member] | Satellite Company Collaboration and Licensing Agreement [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable per drug			$ 2,300

Collaborative Arrangements an70

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - Antisense Therapeutics Limited (Details) - USD ($)	3 Months Ended								12 Months Ended
	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	$ 283,703,000	$ 214,161,000	$ 147,285,000
Antisense Therapeutics Limited [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned									$ 0	$ 0	$ 0
Antisense Therapeutics Limited [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Ownership interest percentage	10.00%				10.00%				10.00%	10.00%

Collaborative Arrangements an71

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - Atlantic Pharmaceuticals Limited (Details) - USD ($) $ in Thousands		1 Months Ended	3 Months Ended								12 Months Ended
		Mar. 31, 2007	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned			$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
Atlantic Pharmaceuticals Limited [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront fee in the form of equity securities		$ 2,000
Next potential milestone			$ 600								$ 600
Ownership interest percentage			11.00%				12.00%				11.00%	12.00%
Royalties earned and paid in equity													$ 700
Revenue earned	[1]
Atlantic Pharmaceuticals Limited [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Regulatory Milestones [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable			$ 1,400								$ 1,400
[1]	Revenue from this relationship was negligible for the year.

Collaborative Arrangements an72

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - OncoGenex Technologies Inc. (Details)

1 Months Ended

3 Months Ended

12 Months Ended

Aug. 31, 2003USD ($)

Dec. 31, 2015USD ($)

Sep. 30, 2015USD ($)

Jun. 30, 2015USD ($)

Mar. 31, 2015USD ($)

Dec. 31, 2014USD ($)

Sep. 30, 2014USD ($)

Jun. 30, 2014USD ($)

Mar. 31, 2014USD ($)

Dec. 31, 2015USD ($)Study

Dec. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Collaborative Arrangement and Licensing Agreement [Abstract]

Revenue earned

$ 51,571,000

$ 49,121,000

$ 120,428,000

$ 62,583,000

$ 84,861,000

$ 44,063,000

$ 57,076,000

$ 28,161,000

$ 283,703,000

$ 214,161,000

$ 147,285,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Revenue earned

$ 0

$ 0

$ 0

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Custirsen [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Number of Phase 3 studies in which drug is being evaluated | Study

2

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | OGX-225 [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Upfront fee in the form of equity securities

$ 800,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | OGX-225 [Member] | Phase 2 Study [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Next potential milestone

500,000

$ 500,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | OGX-225 [Member] | Development and Regulatory Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

3,500,000

3,500,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | OGX-225 [Member] | Development Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

1,500,000

1,500,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | OGX-225 [Member] | Regulatory Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

2,000,000

2,000,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Apatorsen [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

5,800,000

5,800,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Apatorsen [Member] | Phase 3 Study [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Next potential milestone

1,300,000

1,300,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Apatorsen [Member] | Development Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

1,300,000

1,300,000

OncoGenex Technologies Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Apatorsen [Member] | Regulatory Milestones [Member]

Collaborative Arrangement and Licensing Agreement [Abstract]

Maximum amount of payments receivable

$ 4,500,000

$ 4,500,000

Collaborative Arrangements an73

Collaborative Arrangements and Licensing Agreements, Satellite Company Collaborations - Regulus Therapeutics Inc. (Details) shares in Millions	3 Months Ended								12 Months Ended
	Dec. 31, 2015USD ($)shares	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)Drugshares	Dec. 31, 2014USD ($)	Dec. 31, 2013USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned	$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	$ 283,703,000	$ 214,161,000	$ 147,285,000
Net carrying value	$ 24,792,000				$ 81,881,000				$ 24,792,000	81,881,000
Regulus Therapeutics Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of drugs currently in development | Drug									3
Revenue earned									$ 0	0	$ 0
Gain from sale of common stock									20,200,000	19,900,000
Total proceeds from sale of common stock									$ 25,500,000	$ 22,900,000
Common stock owned (in shares) | shares	2.8								2.8
Net carrying value	$ 24,800								$ 24,800
Regulus Therapeutics Inc. [Member] | Satellite Company Collaborative Arrangement and Licensing Agreement [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Ownership interest percentage	5.00%								5.00%

Collaborative Arrangements an74

Collaborative Arrangements and Licensing Agreements, External Project Funding (Details) - USD ($)	3 Months Ended								12 Months Ended
	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangement and Licensing Agreement [Abstract]
Research and development expense									$ 319,500,000	$ 238,900,000	$ 173,700,000
Revenue earned	$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	283,703,000	214,161,000	147,285,000
Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Research and development expense									161,700,000	85,600,000	51,000,000
CHDI Foundation Inc [Member] | Collaborations and Licensing Agreements [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Research and development expense									5,000,000	3,000,000
Maximum amount of milestone payments payable	$ 4,000,000								4,000,000
Revenue earned									$ 0	$ 0	$ 400,000

Collaborative Arrangements an75

Collaborative Arrangements and Licensing Agreements, Intellectual Property Sale and Licensing Agreements (Details) - USD ($)	1 Months Ended	3 Months Ended								12 Months Ended
	Jan. 31, 2009	Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015	Mar. 31, 2015	Dec. 31, 2014	Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue earned		$ 51,571,000	$ 49,121,000	$ 120,428,000	$ 62,583,000	$ 84,861,000	$ 44,063,000	$ 57,076,000	$ 28,161,000	$ 283,703,000	$ 214,161,000	$ 147,285,000
Abbott Molecular Inc. [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Sales price of interest owned in subsidiary	$ 215,000,000
Revenue earned										0	$ 0	$ 0
Abbott Molecular Inc. [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative net sales threshold used to calculate earn out payments										$ 140,000,000
Percentage of cumulative net sales used to calculate earn out payments, over $140 million and up to $2.1 billion										2.50%
Percentage of cumulative net sales used to calculate earn out payments, over $2.1 billion										1.50%
Abbott Molecular Inc. [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative net sales threshold used to calculate earn out payments										$ 2,100,000,000
Revenue threshold used to calculate earn out payments										$ 50,000,000
Percentage of cumulative net sales used to calculate earn out payments, over $140 million and up to $2.1 billion										5.00%
Percentage of cumulative net sales used to calculate earn out payments, over $2.1 billion										3.00%
University of Massachusetts [Member] | In-Licensing Arrangement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of milestone payments payable		300,000								$ 300,000
Verva Pharmaceuticals Ltd. [Member] | In-Licensing Arrangement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of milestone payments payable		6,100,000								6,100,000
Cold Spring Harbor Laboratory [Member] | In-Licensing Arrangement [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of sublicense revenue and post licensing milestone payments payable under in-licensing arrangement		$ 11,300,000								$ 11,300,000

Segment Information and Conce76

Segment Information and Concentration of Business Risk (Details) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2015USD ($)	Sep. 30, 2015USD ($)	Jun. 30, 2015USD ($)	Mar. 31, 2015USD ($)	Dec. 31, 2014USD ($)	Sep. 30, 2014USD ($)	Jun. 30, 2014USD ($)	Mar. 31, 2014USD ($)	Dec. 31, 2015USD ($)SegmentPartner	Dec. 31, 2014USD ($)Partner	Dec. 31, 2013USD ($)
Segment Information and Concentration of Business Risk [Abstract]
Number of reportable segments | Segment									2
Revenue [Abstract]
Research and development									$ 281,360	$ 202,514	$ 144,194
Licensing and royalty									2,343	11,647	3,091
Total revenue	$ 51,571	$ 49,121	$ 120,428	$ 62,583	$ 84,861	$ 44,063	$ 57,076	$ 28,161	283,703	214,161	147,285
Loss from operations	(62,940)	$ (48,138)	$ 44,646	$ (9,330)	10,080	$ (21,493)	$ (6,650)	$ (29,667)	(75,762)	(47,730)	(51,666)
Total assets	956,105				$ 955,809				956,105	955,809
Operating Segments [Member] | Ionis Core [Member]
Revenue [Abstract]
Research and development									285,608	202,514	147,380
Licensing and royalty									2,343	11,647	3,091
Total revenue									287,951	214,161	150,471
Loss from operations									(21,378)	(26,033)	(38,764)
Total assets	1,004,150								1,004,150
Operating Segments [Member] | Akcea Therapeutics [Member]
Revenue [Abstract]
Research and development									0	0	0
Licensing and royalty									0	0	0
Total revenue									0	0	0
Loss from operations									(54,384)	$ (21,697)	$ (12,902)
Total assets	55,354								55,354
Elimination of Intercompany Activity [Member]
Revenue [Abstract]
Research and development									(4,248)
Licensing and royalty									0
Total revenue									(4,248)
Loss from operations									0
Total assets	$ (103,399)								$ (103,399)
Revenue [Member] | Partner A [Member]
Significant Partners [Abstract]
Concentration percentage									37.00%	58.00%	25.00%
Revenue [Member] | Partner B [Member]
Significant Partners [Abstract]
Concentration percentage									33.00%	0.00%	0.00%
Revenue [Member] | Partner C [Member]
Significant Partners [Abstract]
Concentration percentage									12.00%	17.00%	24.00%
Revenue [Member] | Partner D [Member]
Significant Partners [Abstract]
Concentration percentage									11.00%	4.00%	3.00%
Revenue [Member] | Partner E [Member]
Significant Partners [Abstract]
Concentration percentage									2.00%	13.00%	20.00%
Revenue [Member] | Partner F [Member]
Significant Partners [Abstract]
Concentration percentage									0.00%	0.00%	22.00%
Contracts Receivables [Member] | Significant Partners [Member]
Significant Partners [Abstract]
Concentration percentage									99.00%	99.00%
Number of significant partners | Partner									2	3

Employment Benefits (Details)

Employment Benefits (Details) - USD ($)	12 Months Ended
	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
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	$ 1,500,000	$ 1,000,000	$ 600,000

Quarterly Financial Data (Una78

Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands		3 Months Ended										12 Months Ended
		Dec. 31, 2015	Sep. 30, 2015	Jun. 30, 2015		Mar. 31, 2015	Dec. 31, 2014		Sep. 30, 2014	Jun. 30, 2014	Mar. 31, 2014	Dec. 31, 2015	Dec. 31, 2014	Dec. 31, 2013
Quarterly Financial Data (Unaudited) [Abstract]
Revenue		$ 51,571	$ 49,121	$ 120,428		$ 62,583	$ 84,861		$ 44,063	$ 57,076	$ 28,161	$ 283,703	$ 214,161	$ 147,285
Operating expenses		114,511	97,259	75,782		71,913	74,781		65,556	63,726	57,828	359,465	261,891	198,951
Loss from operations		(62,940)	(48,138)	44,646		(9,330)	10,080		(21,493)	(6,650)	(29,667)	(75,762)	(47,730)	(51,666)
Net income (loss)		$ (71,433)	$ (35,776)	$ 35,648		$ (16,717)	$ 31,053		$ (26,676)	$ (12,081)	$ (31,280)	$ (88,278)	$ (38,984)	$ (60,644)
Basic net income (loss) per share (in dollars per share)	[1]	$ (0.59)	$ (0.30)	$ 0.30		$ (0.14)	$ 0.26		$ (0.23)	$ (0.10)	$ (0.27)
Diluted net income (loss) per share (in dollars per share)	[1]	(0.59)	(0.30)	$ 0.29	[2]	(0.14)	$ 0.25	[3]	(0.23)	(0.10)	(0.27)
Income (Numerator) [Abstract]
Income available to common shareholders				$ 35,648			$ 31,053
Dilutive effect of 2 3/4 percent notes				1,047
Income available to common shareholders, plus assumed conversions				$ 36,695			$ 31,053
Shares (Denominator) [Abstract]
Shares used in computing basic net income per share (in shares)				119,742			118,223
Effect of Diluted Securities [Abstract]
Shares issuable related to our ESPP				4			9
Shares issuable related to our 2 3/4 percent notes (in shares)				3,683
Shares used in computing diluted net income per share (in shares)				127,779			122,839
Per-Share Amount [Abstract]
Basic net income per share (in dollars per share)	[1]	(0.59)	(0.30)	$ 0.30		(0.14)	$ 0.26		(0.23)	(0.10)	(0.27)
Diluted net income per share (in dollars per share)	[1]	$ (0.59)	$ (0.30)	$ 0.29	[2]	$ (0.14)	$ 0.25	[3]	$ (0.23)	$ (0.10)	$ (0.27)
Convertible Senior Notes [Member] | 1 Percent Convertible Senior Notes [Member]
Convertible Senior Notes [Abstract]
Interest rate on convertible senior notes		1.00%					1.00%					1.00%	1.00%
Convertible Senior Notes [Member] | 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%
Stock Options [Member]
Effect of Diluted Securities [Abstract]
Shares issuable related to stock-based compensation (in shares)				3,974			4,189
Restricted Stock Awards [Member]
Effect of Diluted Securities [Abstract]
Shares issuable related to stock-based compensation (in shares)				376			418
[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]	For the three months ended June 30, 2015, 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 June 30, 2015, the calculation excludes the 1 percent notes because the effect on diluted earnings per share would be anti-dilutive.
[3]	For the three months ended December 31, 2014, 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, 2014, the calculation excludes the 1 percent and 2.75 percent convertible senior notes because the effect on diluted earnings per share would be anti-dilutive.