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EXHIBIT 10.31
PILASITE LICENSE AGREEMENT
This LICENSE AGREEMENT ("Agreement") is made as of the 18th day of
July, 1996 (the "Effective Date") by and between InSite Vision Incorporated, a
Delaware corporation, having offices at 965 Atlantic Avenue, Alameda, California
94501 ("InSite") and Bausch & Lomb Pharmaceuticals, Inc., a Delaware
corporation, having offices at 8500 Hidden River Parkway, Tampa, Florida 33637
("B&L").
WHEREAS, InSite owns certain proprietary rights and know-how relating
to the manufacture, use and sale of PilaSite(R) (as defined herein);
WHEREAS, B&L desires to acquire, and InSite is willing to grant to B&L,
a license under such proprietary rights and know-how under the terms and
conditions set forth herein.
NOW THEREFORE, in consideration of the mutual covenants and obligations
set forth herein, the parties agree as follows:
1. DEFINITIONS
The following terms as used in this Agreement shall have the
meanings set forth in this Section :
1.1 "Affiliate" shall mean all corporations or business entities
which directly or indirectly are controlled by, control or are under common
control with B&L or InSite as the case may be.
1.2 "Agreement Period" shall mean the period commencing upon the
Effective Date and extending until the termination of this Agreement pursuant to
Section 14 hereof.
1.3 "FDA" shall mean the United States Food and Drug Administration
or any successor entity thereto.
1.4 "Know-How" shall mean all technology, formula, trade secrets,
technical data, pre-clinical and clinical data, toxicological and
pharmacological data and any other information or experience owned, controlled
or in the possession of InSite as of the Effective Date relating to or useful in
connection with the development, manufacture, use or sale of PilaSite as well as
any improvements or modifications to such Know-How developed by, or by any third
party for, InSite during the Agreement Period.
1.5 "Major Markets" shall mean those countries listed on Exhibit C.
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1.6 "NDA" shall mean a New Drug Application as defined in the United
States Federal Food, Drug and Cosmetic Act ("FFDCA") and applicable regulations
promulgated thereunder.
1.7 "Net Sales" shall mean the amount invoiced by B&L, its
Affiliates or sublicensees to independent third parties for the sale of
PilaSite, less cash discounts and/or quantity discounts allowed; credit for
customer returns and allowances; charges for freight handling and transportation
as well as freight insurance which are separately billed to B&L; chargebacks;
Medicaid rebates and rebates made or taken in amounts customary in the industry;
and sales and use taxes and other similar taxes incurred by B&L all as
determined in accordance with B&L's standard accounting practices. Net Sales
shall not include product samples or clinical trial supplies.
1.8 "1984 Act" shall mean the United States Drug Price Competition
and Patent Term Restoration Act of 1984 as amended, including 21 USC Section
355, 35 USC Section 155-156, 35 USC Section 271 and applicable regulations
promulgated thereunder.
1.9 "Patent Rights" shall mean all of InSite's right, title and
interest in and to any worldwide patents or patent applications, any claim of
which would cover PilaSite or its manufacture or use which are owned by or
licensed to InSite as of the Effective Date, as set forth on Exhibit D hereto,
and any continuations, continuations in part, divisions, re-examinations,
re-issues or extensions of any of the above described patents or patent
applications.
1.10 "PilaSite" shall mean an ophthalmic formulation containing
pilocarpine as the sole active ingredient in the DuraSite(R) polymer suspension
vehicle.
1.11 "Royalty Period" shall be determined on a country-by-country
basis and shall mean that period beginning on the date of the first commercial
sale of PilaSite by B&L in any country and ending upon the later of the
expiration of all Patent Rights in such country or * * * from the first
commercial sale of PilaSite by B&L in such country. [* INDICATES THAT MATERIAL
HAS BEEN OMITTED AND CONFIDENTIAL TREATMENT HAS BEEN REQUESTED THEREFOR. ALL
SUCH OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE COMMISSION PURSUANT TO
RULE 24b-2.]
1.12 "Secondary Royalty Period" shall be determined on a country-by
country basis and shall mean that period beginning on the date the Royalty
Period for such country expires and ending upon the expiration of this
Agreement, including any extension thereof.
1.13 "Territory" shall mean anywhere in the world.
2. GRANT
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2.1 (a) InSite hereby grants to B&L during the Agreement Period a
license or sublicense, with the right to sublicense, under the Patent Rights and
unpatented Know-How referred to in the following sentence, to manufacture, have
manufactured, use, import and sell PilaSite for eye care. The Patent Rights and
Know-How licensed or sublicensed under this Section 2 shall consist of all of
the Patent Rights and unpatented Know-How already invented, developed or owned
by InSite or licensed to InSite on the Effective Date which may relate to the
manufacture, use, import or sale of PilaSite and any improvements or
modifications thereto developed or obtained by InSite during the Agreement
Period.
(b) In consideration for the license granted in Section 2.1(a)
above, B&L shall pay InSite a license fee in the amount of * * * (the "License
Fee"). The License Fee shall be paid by B&L as follows: (i) * * * within five
(5) days after the Effective Date; and (ii) the remaining * * *, in one or more
installments equal to, and paid on the same day as, any facility expense
payments in excess of * * * due from InSite to B&L (the "Additional Expense
Payments") in accordance with Section 3.2 of that certain BetaSite Supply
Agreement between InSite and B&L of even date herewith (the "Supply Agreement").
In the event that, pursuant to the Supply Agreement, InSite's Additional Expense
Payments are less than * * *, B&L shall pay InSite an amount equal to * * * less
all Additional Expense Payments made by InSite upon the earlier to occur of (x)
January 15, 1997, (y) as determined in the reasonable judgment of B&L, the
successful completion of the Phase III clinical study report for the PilaSite
NDA. All payments provided for in this paragraph shall be made by wire transfer
in immediately available United States dollars to such account as InSite shall
specify in writing to B&L not less than two (2) days prior to the date such
payment is due. [* INDICATES THAT MATERIAL HAS BEEN OMITTED AND CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED THEREFOR. ALL SUCH OMITTED MATERIAL HAS BEEN FILED
SEPARATELY WITH THE COMMISSION PURSUANT TO RULE 24b-2.]
(c) Under the foregoing license and sublicense, B&L (and B&L's
sublicensees) shall have the exclusive right under the Patent Rights and
Know-How referred to above to manufacture, import, have manufactured, use and
sell PilaSite anywhere in the world.
2.2 (a) InSite shall take all steps necessary, and shall bear all
costs, to complete and submit an NDA for PilaSite with the FDA and shall use its
reasonable efforts (consistent with similarly situated companies) to cause such
NDA to be approved by FDA. Provided, however, that B&L shall be responsible for
performing and shall bear the costs of, except as otherwise provided herein, the
Services (as more fully described on Schedule 2.2(a) attached hereto).
Notwithstanding anything contained herein to the contrary, in the event that
B&L, after five (5) good faith attempts, is unable to successfully manufacture,
stability test and validate three (3) QA/QC-release lots of Product for NDA
registration purposes, B&L and InSite shall equally share all costs incurred in
connection with the manufacture, stability testing and validation of three (3)
additional QA/QC-release lots for
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NDA registration purposes (the "Additional Stability Studies"); and provided,
further, that in the event that the parties are unable to successfully complete
the Additional Stability Studies, B&L's president and InSite's chief executive
officer shall, within ten (10) days, meet to jointly determine the appropriate
action. B&L shall provide InSite with all data and reports from the
aforementioned developmental activities for purposes of InSite's submission of
the NDA.
(b) B&L may develop a drug master file ("DMF") covering its
manufacture of PilaSite. In the event that B&L undertakes to develop a DMF, it
shall not be required to exercise efforts beyond those employed by B&L for other
customers of B&L for contract manufactured product. B&L shall allow InSite to
reference the DMF in the course of seeking and obtaining FDA approval of the
NDA, and shall provide InSite with the DMF reference letter; provided, however,
that B&L's obligations to disclose to InSite the contents of the DMF shall be
limited to those sections which pertain to B&L's manufacture of PilaSite. B&L
shall be responsible for providing InSite with the CMC Section for inclusion in
the NDA.
(c) B&L shall use its best commercial efforts consistent with good
business judgment, and shall bear all costs incurred therefor, to file
applications for regulatory approval of PilaSite in the Major Markets and shall
use reasonable efforts to cause such applications to be approved by all
necessary regulatory authorities in each Major Market. In the event that B&L
elects not to file applications for regulatory approval of PilaSite in any Major
Market within six (6) months of the date the PilaSite NDA is approved, or fails
to use reasonable efforts to cause any such applications to be approved by the
necessary regulatory authorities, or fails to maintain such regulatory
approvals, upon thirty (30) days advanced written notice by InSite, the license
granted by InSite to B&L in Section 2.1(a) above shall no longer be exclusive in
such Major Market. In such event, the royalty paid by B&L on sales of PilaSite
in such Major Market for which the license is no longer exclusive shall continue
to be calculated in accordance with Section 3 below; provided, however, that in
no event shall the royalty paid by B&L exceed the royalties paid by any other
nonexclusive licensee in such Major Market.
2.3 B&L shall use commercially reasonable efforts consistent with good
business judgment, relevant to the country involved, to commercialize and sell
PilaSite in the Territory.
2.4 In the event that, in the course of performing its obligations
hereunder prior to the approval for sale of PilaSite, either party is required
to expend sums or efforts that would render commercially impracticable its
activities to complete such approval, then the parties shall meet and discuss in
good faith, how and whether to proceed toward PilaSite approval.
3. ROYALTIES
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3.1 (a) In consideration of the rights granted in Section 2 above,
during the Royalty Period in any country, B&L shall pay InSite royalties
consisting of * * * of Net Sales of PilaSite in such country. In the event that
during the Royalty Period for any country, any of InSite's Patent Rights expire
or are invalidated, or InSite is unable or elects not to obtain a patent in such
country, and generic versions of PilaSite are being sold in such country (and
such generic sales are not in contravention of any governmental, judicial or
private regulatory rules, regulations, laws, orders or judgments in effect in
such country), the royalty rate paid by B&L for sales in such country shall be
reduced to * * * of Net Sales in such country. During the Secondary Royalty
Period in any country, B&L shall pay InSite the following royalties on Net Sales
of PilaSite: (i) * * * of Net Sales of PilaSite during the first year of the
Secondary Royalty Period; (ii) * * * of Net Sales of PilaSite for the second
year of the Secondary Royalty Period; and (iii) * * * of Net Sales of PilaSite
during the third year of the Secondary Period and during any subsequent year in
which this Agreement or any extension thereof is in effect. In addition, during
the Secondary Royalty Period in any country, B&L shall pay InSite royalties of *
* * of Net Sales of the Generic (as defined below) unless B&L's sale of the
Generic was pursuant to the filing of an ANDA (as hereinafter defined) and
without any cooperation from InSite whatsoever, in which event B&L's obligation
to pay a royalty to InSite in connection with its sales of the Generic shall
exist for * * * years of the Secondary Royalty Period. Notwithstanding anything
contained herein to the contrary, B&L shall not be required to pay InSite any
royalty on Net Sales of the Generic after the end of the * * * of the Secondary
Royalty Period. [* INDICATES THAT MATERIAL HAS BEEN OMITTED AND CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED THEREFOR. ALL SUCH OMITTED MATERIAL HAS BEEN FILED
SEPARATELY WITH THE COMMISSION PURSUANT TO RULE 24b-2.]
(b) Notwithstanding anything in this Agreement to the contrary, if any
of the Patent Rights expire or are invalidated, or if InSite is unable or elects
not to obtain a patent in such country, and generic versions of PilaSite are
being sold in such country (and such generic sales are not in contravention of
any governmental, judicial or private regulatory rules, regulations, laws,
orders or judgments in effect in such country), B&L shall have the right to
manufacture, use, import, sell and distribute a generic equivalent to PilaSite
by either submitting and receiving approval of an abbreviated new drug
application, and, in countries other than the United States, an equivalent
abbreviated application ("ANDA") or obtaining from InSite the right to
supplement or amend the NDA, or foreign equivalent, to introduce a generic form
of PilaSite (the "Generic"). If B&L submits an ANDA for the Generic, it shall
notify InSite in writing at least ninety (90) days prior to the date of
submission and InSite shall cooperate with B&L in the preparation of such
submission. Alternatively, if B&L elects to submit a supplement to the NDA, or
foreign equivalent, with respect to the Generic, B&L may request from InSite,
and InSite shall grant B&L, such specific rights to the NDA, or foreign
equivalent, as are necessary to enable B&L to submit such supplement to
introduce and sell the Generic. If B&L elects to launch the Generic in any
country prior to the end of the Royalty Period in such country, in anticipation
of the entry of a third party generic competitor, the royalty due on sales of
such Generic by B&L shall be * * * of Net Sales until the end of the
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Royalty Period. InSite hereby covenants not to sue B&L for patent infringement
relating to sales of the Generic which are in accordance with this Section
3.1(b) during the Royalty Period in such country. [* INDICATES THAT MATERIAL
HAS BEEN OMITTED AND CONFIDENTIAL TREATMENT HAS BEEN REQUESTED THEREFOR. ALL
SUCH OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE COMMISSION PURSUANT TO
RULE 24b-2.]
3.2 Sales of PilaSite between or among B&L, its Affiliates and
sublicensees shall not be subject to any royalty hereunder, and in such cases
royalties shall be calculated upon B&L or its Affiliates' or sublicensees' Net
Sales to an independent third party. B&L shall be responsible for payment of any
royalty accrued on Net Sales of PilaSite to such independent third party through
B&L's Affiliates or sublicenses. Royalties shall accrue hereunder only once in
respect of the same unit of the PilaSite.
4. TIMING OF ROYALTY PAYMENTS; RECORDS
4.1 Within 45 days after the end of each calendar quarter, B&L shall
pay to InSite the royalty payment due for such quarter in U.S. dollars. Such
royalty shall be converted, where applicable, from the currency of the country
in which the sale was made into U.S. dollars at the average month-end exchange
rates for such quarter as calculated based on the daily exchange rate published
in the Wall Street Journal.
4.2 Together with each quarterly royalty payment, B&L shall submit
to InSite a written accounting showing its computation of royalties due under
this Agreement for such quarter. Said accounting shall set forth gross sales,
Net Sales, the exchange rate applied, if any, and the total royalties due for
the quarter in question.
4.3 B&L shall keep full and accurate books and records reflecting
the sales of PilaSite and the data used in arriving at Net Sales and the amount
of royalties payable to InSite hereunder for no less than one year after the end
of each such quarter. B&L shall permit InSite, at InSite's expense, to have such
books and records examined by independent certified public accountants retained
by InSite and reasonably acceptable to B&L, during regular business hours upon
reasonable advance notice, but not later than one year following the rendering
of any such reports, accounting and payments, and no more often than one time
per year. Such independent accountants shall keep confidential (under a written
confidentiality agreement reasonably acceptable to B&L) any information obtained
during such examination and shall report to InSite only the amounts of royalties
which the independent accountant believes to be due and payable hereunder. If
such examination discloses a discrepancy of 5% or more in any amount due InSite
under this Agreement, B&L shall reimburse InSite for the out-of-pocket cost of
such examination, including any reasonable professional fees and expenses
incurred by InSite.
5. WARRANTIES
5.1 InSite warrants and represents that:
(a) it is the owner of the Patent Rights and Know-How and has
the right to license or sublicense, in the manner set forth in this Agreement,
said Patent Rights and Know-How free of any lien or encumbrance in the
Territory;
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(b) it has not assigned or conveyed any interest in the Patent
Rights or Know-How which may be inconsistent with the rights granted hereunder;
(c) to the best of its knowledge and after a diligent search,
the practice of the Patent Rights and Know-How in the Territory does not
infringe any rights of third parties;
(d) it is not aware that any third party is infringing the
Patent Rights;
(e) it is a corporation duly incorporated and in good standing
in its state of incorporation and has all requisite power to enter into and
perform this Agreement. Upon execution by the parties hereto, this Agreement
shall constitute a valid and legally binding obligation of InSite, enforceable
in accordance with its terms; and
(f) it has prosecuted all patent applications within the
Patent Rights in good faith and has no reason to believe that any patent
included within the Patent Rights would be invalid or would be held to be
unenforceable by a court of competent jurisdiction.
6. TRANSFER AND OWNERSHIP OF KNOW-HOW; MAINTENANCE OF NDA
6.1 As part of the license granted in Section 2, and in order to
enable B&L to develop, make, have made, use and sell PilaSite, InSite shall
provide B&L with all Know-How within thirty (30) days after signing this
Agreement. In addition, all improvements or modifications to such Know-How
generated or obtained by InSite during the Agreement Period shall be transferred
to B&L within thirty (30) days of its generation or receipt by InSite. Such
Know-How is provided to B&L subject to the confidentiality restrictions set
forth in this Agreement.
6.2 (a) Following FDA approval of the NDA, B&L agrees to take any
and all action necessary to ensure that the NDA is maintained and all statutory
obligations associated therewith are fulfilled. To facilitate B&L's ability to
assume responsibility for maintaining the NDA, contemporaneously with the
execution of this Agreement, InSite shall execute and deliver a letter
substantially in the form of Exhibit A to this Agreement, authorizing B&L to act
on InSite's behalf as the responsible agent. Such letter shall be updated and
modified as necessary, but no less frequently than annually at the reasonable
request of B&L.
(b) InSite hereby grants to B&L a right of reference with
respect to all information contained in the NDA, and any supplements or
amendments to such NDA. This right of reference shall include a right of
reference for purposes of Section 505(b)(2) of the FFDCA and its implementing
regulations. Contemporaneously with the execution of this Agreement, InSite
shall execute a letter substantially in the form of Exhibit B to this Agreement
(a "Right of Reference Letter").
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(c) InSite hereby grants B&L the right to receive, upon written
request and at the expense of InSite, complete copies of the NDA, including any
supplements or amendments thereto, all correspondence with the FDA regarding the
NDA or PilaSite in general, all minutes of meetings held between the FDA and
InSite to discuss the NDA or PilaSite in general, all memoranda of conversations
between InSite and the FDA that relate to the NDA or PilaSite in general, and
all of InSite's Know-How. From and after the date hereof, InSite agrees that it
shall not transfer ownership of the NDA or any Know-How to any person or entity
other than B&L without the prior written consent of B&L, which consent shall not
be unreasonably withheld; provided, however, that B&L's prior written consent
shall not be required for InSite to transfer nonexclusive rights to the NDA or
Know-How to any third party for the purpose of manufacturing, marketing and
distributing PilaSite in any Major Market in which B&L no longer has an
exclusive license pursuant to the operation of Section 2.2(b) above.
(d) B&L agrees to provide InSite with (i) fifteen (15) days'
notice prior to submission to the FDA of any routine submissions or
insignificant amendments such as minor labeling changes or minor manufacturing
changes and (ii) forty-five (45) days' notice prior to submission to the FDA of
any submission, supplement or amendment not referred to in Section 6.2(d)(i)
hereof. B&L shall provide complete copies of all proposed supplements,
submissions and amendments to InSite upon giving notice to InSite of such
proposed submission. From and after the date hereof, B&L agrees that it shall
not submit to the FDA any NDA supplement or amendment with respect to PilaSite
without the consent of InSite, which consent shall not be unreasonably withheld
and B&L may assume that InSite consents to any proposed submission that InSite
does not object to by the end of the relevant notice period. B&L further agrees
to promptly provide InSite with copies of all correspondence with and reports to
the FDA or any other agency regarding PilaSite or the NDA, all minutes of
meetings held between the FDA and B&L to discuss PilaSite or the NDA, and all
memoranda of any conversations between B&L and the FDA that relate to PilaSite
or the NDA.
7. CONFIDENTIALITY
7.1 InSite and B&L shall keep any Know-How or business information
provided or made available by the other party or its Affiliates hereunder
confidential, and neither InSite nor B&L shall, without the prior written
consent of the other party or its Affiliates, as the case may be, use (except as
expressly permitted by this Agreement or for the purposes of this Agreement), or
disclose to any third party, any Know-How or business information provided or
made available by the other party or its Affiliates hereunder; provided,
however, that the foregoing shall not apply to information which the party
receiving such information can establish by written documentation to (i) have
been publicly known at the time of disclosure by the other party or its
Affiliates, as the case may be, (ii) have become publicly known, without fault
on its part, subsequent to such disclosure, (iii) have been otherwise known by
it from a source (other than the other party or its agents or
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Affiliates), lawfully having possession of such information, or (v) have been
developed by it or its Affiliates independently of the disclosure by the other
party or its Affiliates.
The foregoing shall not preclude the disclosure of information by
InSite or B&L:
(a) to its legal representatives, Affiliates, consultants, outside
contractors and (if it has the right to grant the license or sublicense) its
licensees and sublicensees, under like confidentiality obligations on the part
of the recipients, or
(b) to the extent required by law or regulation, provided that, to
the extent reasonably possible, it shall give prompt written notice of the
proposed disclosure to the other party or its Affiliates, as the case may be, so
as to allow the other party or its Affiliates, as the case may be, an
opportunity to object to such requirement and, if applicable, assure that
confidential treatment will be accorded to such information, or
(c) to the extent that such information is reasonably required to be
disclosed for the purpose of securing necessary governmental authorization for
the clinical testing or marketing of products or for the purpose of conducting
clinical testing or marketing of products, or of prosecuting or defending
litigation.
7.2 The terms of this Agreement shall not be disclosed by either
party to any third party (other than as provided in Subsections 7.1(a), (b) and
(c) above) or be published unless both parties expressly agree otherwise in
writing. Furthermore, neither party shall use the name of the other party or its
Affiliates without their prior written consent. However, the foregoing
restrictions shall not apply to the disclosure of information set forth in the
form of an agreed-upon press release, if any, which may be prepared in mutually
agreeable format and substance for release when this Agreement becomes
effective, or to disclosures required by law or regulation.
8. PATENTS
8.1 InSite shall undertake and shall bear all costs of the
prosecution and maintenance of the Patent Rights in the Territory. InSite shall
employ reasonable efforts to keep B&L fully and timely informed with respect to
the course and conduct of patent application prosecution matters within the
scope of Patent Rights.
8.2 If InSite elects to terminate either the prosecution or
maintenance of the Patent Rights prior to the completion of normal prosecution
before the patent examiner or prior to the end of the term for maintenance, as
the case may be, it will give B&L sixty (60) days prior written notice of such
election prior to any time limit on any action due. B&L, upon receipt of such
notice, shall have the option to undertake the continuation of such prosecution
or maintenance and InSite will transfer title to B&L for such patent application
or patent.
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9. ENFORCEMENT OF PATENT RIGHTS
9.1 If either party shall become aware of any infringement or
threatened infringement of any Patent Rights, including that contained in a
notice provided under the 1984 Act by a party filing an NDA for PilaSite, then
the party having such knowledge shall give notice to the other within ten (10)
days of becoming aware of such infringement or threatened infringement.
9.2 InSite shall have the first right but not an obligation to bring
an enforcement action or to take any other reasonable steps to defend the Patent
Rights against infringement and B&L shall in such event give all reasonable
assistance to InSite with respect to patent and legal questions. The costs of
such patent enforcement shall be borne by InSite. If InSite does not commence a
particular infringement action within ninety (90) days after it has received
notice of such infringement, B&L, after notifying InSite in writing, shall be
entitled to bring such infringement action or other appropriate action or claim
at its own expense but shall request in writing that InSite fund 50% of such
expenses. If InSite declines to pursue such action or fails to respond to B&L
within sixty (60) days after receipt of B&L's notice that it will do so, B&L
shall have the right to undertake such action and if InSite fails to fund 50% of
B&L's expenses in pursuing such action, then B&L shall be entitled to 100% of
all recoveries and B&L shall no longer be required to pay royalties to InSite
for PilaSite in the country in which such action was prosecuted. Recovery from
any settlement or judgment from any such action in the Territory either pursued
by InSite or co-funded by InSite shall go first to reimburse the expenses of the
parties and the remainder shall be shared by the parties on a 50%/50% basis.
Notwithstanding the foregoing, if the monetary recovery is less than the
out-of-pocket expenses of InSite and B&L, reimbursement shall be on a pro rata
basis, based upon cost incurred. In any event, InSite and B&L shall assist one
another and reasonably cooperate in any such litigation at the other's request
without expense to the requesting party.
9.3 If InSite and B&L, after consultation with each other, elect not
to bring individually or jointly, or if InSite and B&L, as the case may be,
are/is not able to stop such infringing activities in any country, the
applicable royalty for such country shall be adjusted as set forth in Section
3.1, if applicable.
10. INDEMNIFICATION
10.1 Indemnification of B&L. InSite shall indemnify, defend, save
and hold B&L and each of its Affiliates, officers, directors, employees and
agents harmless from and against any liability, loss, damage, cost or expense
including reasonable attorneys' fees and expenses, excluding consequential or
special damages ("Loss" or "Losses") resulting from or arising out of (a) any
material breach of any warranty hereunder or material non-fulfillment or
non-performance by InSite of any agreement, covenant or obligation of InSite
under this Agreement; (b) any actual or alleged defect in PilaSite manufactured
by B&L, other than any actual or alleged defect arising out of B&L's failure to
manufacture PilaSite in accordance with the terms of this Agreement and except
as otherwise provided in Sections 10.2 and 10.3 below; (c) FDA enforcement
action, inspection or product recalls or market withdrawals relating to
PilaSite, except where arising out of or resulting from B&L's failure to
manufacture PilaSite in
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accordance with the terms of this Agreement or B&L's labeling, packaging,
promotion, distribution, or marketing of finished units of PilaSite and except
as provided in Sections 10.2 and 10.3 below; and (d) any actual or alleged
infringement or violation by the Patent Rights or Know-How of any patent, trade
secret or other proprietary right of any third party.
10.2 Indemnification of InSite. B&L shall indemnify, defend, save
and hold InSite and each of its Affiliates, officers, directors, employees and
agents harmless from and against Loss or Losses resulting from, or arising out
of (a) a material breach of any warranty hereunder or material non-fulfillment
or non-performance by B&L of any agreement, covenant or obligation of B&L under
this Agreement; (b) any actual or alleged defect in PilaSite manufactured
hereunder arising out of B&L's failure to manufacture PilaSite in accordance
with the terms of this Agreement, including without limitation, defects due to
tampering with PilaSite during the manufacturing process; (c) B&L's acts
relating to the promotion, marketing, labeling, packaging and/or distribution of
PilaSite; and (d) FDA enforcement action, inspection, product recalls or market
withdrawals relating to PilaSite resulting from B&L's failure to manufacture
PilaSite in accordance with the terms of this Agreement or arising out of the
labeling or packaging of finished units of PilaSite.
10.3 Joint Obligations. InSite and B&L shall equally share any
Losses, and shall jointly defend any actions related thereto, resulting from or
arising out of acts, actions, defects, product recalls or market withdrawals for
which responsibility is not specifically apportioned by Sections 10.1 and 10.2
above. Such joint obligations shall include, without limitation, product recalls
or market withdrawals due to any tampering with PilaSite after manufacture and
distribution by B&L. Any such product recalls or market withdrawals shall be
controlled and conducted by B&L.
10.4 Survival. The provisions of this Section 10 shall survive any
termination of this Agreement.
10.5 Indemnification Procedures. Upon the occurrence of an event
which requires indemnification under this Agreement (an "Indemnification
Event"), the indemnified party shall give prompt written notice to the
indemnifying party providing reasonable details of the nature of the event and
the basis of the indemnity claim. The indemnifying party shall then have the
right, at its expense and with counsel of its choice, to defend, contest or
otherwise protect against any such action. The indemnified party shall also have
the right, but not the obligation, to participate at its own expense in the
defense thereof with counsel of its choice. The indemnified party shall
cooperate to the extent reasonably necessary to assist the indemnifying party in
defending, contesting or otherwise protesting against any such action provided
that the reasonable out-of-pocket cost in doing so shall be paid by the
indemnifying party. If the indemnified party fails to promptly notify
11.
12
the indemnifying party of the occurrence of an Indemnification Event and such
failure has a material adverse effect on the indemnifying party, the indemnified
party shall not be entitled to indemnification with respect to such
Indemnification Event. If the indemnifying party fails within thirty (30) days
after receipt of such notice (a) to notify the indemnified party of its intent
to defend, or (b) to defend, contest or otherwise protect against such suit,
action, investigation, claim or proceeding, or fails to diligently continue to
provide such defense after undertaking to do so, the indemnified party shall
have the right, upon ten (10) days' prior written notice to the indemnifying
party, to defend, settle and satisfy any such suit, action, claim, investigation
or proceeding and recover the reasonable costs of the same from the indemnifying
party.
11. PATENT TERM EXTENSION
Within sixty (60) days after approval of an NDA for PilaSite, and
at B&L's option, B&L shall have the right to file at its own cost and expense an
application for an extension of any United States patent falling within the
Patent Rights, and, where applicable, for extension of Patent Rights in any
other country of the Territory under similar laws permitting patent term
extension. InSite designates B&L as its agent with respect to such filing and
prosecution for patent term extension, and agrees to cooperate with B&L in
providing any information required under the relevant United States laws or
similar laws outside the United States. Such action by B&L may be undertaken in
the name of InSite, if deemed necessary or appropriate by B&L, and InSite agrees
to cooperate with B&L, and execute any documents reasonably necessary relating
to such action.
12. TRADEMARK
InSite shall grant B&L an exclusive license to the trademark
PilaSite; provided, however, that such license shall be nonexclusive in any
Major Market for which the general technology license granted hereunder becomes
nonexclusive pursuant to Section 2.2(b).
13. NOTICES
All notices required or permitted hereunder shall by given in
writing and sent by facsimile transmission, or mailed postage prepaid by first
class certified or registered mail, or sent by a nationally recognized express
courier service, or hand delivered at the following addresses:
Bausch & Lomb Pharmaceuticals, Inc.
8500 Hidden River Parkway
Tampa, Florida 33637
Attn: President
12.
13
With a copy to:
Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester, New York 14604
Attn: General Counsel
InSite Vision Incorporated
965 Atlantic Avenue
Alameda, California 94501
Attn: Chief Executive Officer
With a copy to:
Brobeck, Phleger & Harrison LLP
Two Embarcadero Place
2200 Geng Road
Palo Alto, California 94303
Attn: J. Stephan Dolezalek, Esq.
Any notice, if mailed properly addressed, postage prepaid, shall be deemed made
three days after the date of mailing as indicated on the certified or registered
mail receipt, or on the next business day if sent by express courier service or
on the date of delivery or transmission if hand delivered or sent by facsimile
transmission.
14. TERM AND TERMINATION
14.1 The term of this Agreement shall begin as of the date hereof
and shall remain in effect until the later of the expiration of the last to
expire Patent Rights, or ten (10) years from the first commercial sale of
PilaSite in the last country in which it is commercially exploited, unless
earlier terminated as permitted hereunder. B&L shall have the right, upon 180
days written notice to InSite, to renew this Agreement for an unlimited number
of five (5) year terms (each a "Renewal Term"). B&L shall have the right to
terminate any Renewal Term only upon 180 days prior written notice to InSite.
Upon the termination of this Agreement for any reason, B&L shall have the right,
consistent with past practice, to market, distribute, and sell any finished
units of PilaSite in B&L's possession at the time of such termination.
14.2 In the event of a breach or default of this Agreement by
either party which is not cured within ninety (90) days after the receipt of
notice thereof from the other party, the party not in breach or default shall be
entitled (without prejudice to any of its other rights) to terminate this
Agreement by giving notice to take effect immediately.
14.3 B&L may terminate this Agreement and the licenses granted
hereunder at any time, without cause, upon 180 days written notice to InSite, at
which time B&L, and
13.
14
its Affiliates and sublicensees, as applicable, shall return to InSite all
documented or written Know-How previously provided to B&L by InSite pursuant to
Section 6 of this Agreement.
14.4 The termination of this Agreement shall not release either
party from any obligation which matured prior to the effective date of the
termination.
14.5 The confidentiality obligations set forth in Section 7 shall
survive the termination or expiration of this Agreement.
15. FORCE MAJEURE
Neither party shall be responsible or liable to the other
hereunder for failure or delay in performance of this Agreement due to any war,
fire, accident or other casualty, or any labor disturbance or act of God or the
public enemy, or any other contingency beyond such party's reasonable control.
In addition, in the event of the applicability of this Section , the party
affected by such force majeure shall use reasonable efforts, consistent with
good business judgment, to eliminate, cure and overcome any of such causes and
resume performance of its obligations.
16. ASSIGNMENT
This Agreement and all rights and obligation hereunder are personal
to the parties hereto, and may not be assigned without the express prior written
consent of the other, which consent shall not be unreasonably withheld. Any
assignment or attempt at same in the absence of such prior written consent shall
be void and without effect.
17. GOVERNING LAW
This Agreement shall be governed by, and construed in accordance
with, the laws of the State of California as though made and to be fully
performed in said State.
18. SEVERABILITY
If any one or more of the provisions of this Agreement shall be
held to be invalid, illegal or unenforceable, the validity, legality or
enforceability of the remaining provisions hereof shall not in any way be
affected or impaired thereby. In the event any provision shall be held invalid,
illegal or unenforceable, the parties shall use best efforts to substitute a
valid, legal and enforceable provision which, insofar as possible, implements
the purposes hereof.
14.
15
19. NO WAIVER
The failure of any party hereto at any time or times to require
performance of any provisions hereof shall in no manner affect its rights to
enforce such provision at a later time.
20. ENTIRE AGREEMENT
This Agreement constitutes the entire understanding between the
parties relating to the subject matter thereof, and no amendment or modification
to this Agreement shall be valid or binding upon the parties unless made in
writing and signed by the representatives of such parties.
21. DISPUTE RESOLUTION
Except that either party may seek equitable relief from a court, if
any dispute arises between InSite and B&L with respect to the interpretation or
breach of this Agreement, either party shall notify the other of the dispute in
writing and shall attempt to resolve the dispute through discussions between
INSITE'S Chief Executive Officer and B&L's President. If such officers are
unable to resolve the dispute within thirty (30) days after the date written
notice of the dispute is delivered, the parties shall seek to resolve the
dispute by initiating an Alternative Dispute Resolution ("ADR") in which the
Judicial Arbitration and Mediation Services ("JAMS"), Oakland, California shall
select the mediator. Such mediator shall hold a hearing to resolve the dispute
within sixty (60) days of his or her selection. The location of the hearing
shall be Oakland, California. Each party may be represented by counsel and shall
have the right to make a presentation of evidence at such hearing. The mediator
shall render a disposition on the proposed rulings as expeditiously as possible
but not later than fifteen (15) days after the conclusion of the hearing. If the
parties are unable to resolve the dispute, the dispute may, upon the agreement
of the parties, be settled by arbitration. If the parties agree to arbitrate the
dispute, such arbitration shall take place in Alameda County, California in
accordance with the then current commercial arbitration rules of the American
Arbitration Association and judgment upon the award rendered by the
Arbitrator(s) shall be binding on the parties and may be entered by either party
in the court or forum, state or federal, having jurisdiction. Notwithstanding
anything to the contrary, nothing in this Agreement shall be deemed as
preventing either party from seeking injunctive relief (or any other provisional
remedy) from any court having jurisdiction over the parties and the subject
matter of the dispute as necessary to protect either party's name, proprietary
information, trade secrets, know-how or any other proprietary rights. Further,
in the event the parties do not agree to arbitrate any dispute hereunder, either
party may seek such other remedy, at law or in equity, as it may deem necessary
or appropriate.
15.
16
IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their duly authorized representatives as of the day and year first
above written.
BAUSCH & LOMB PHARMACEUTICALS, INSITE VISION INCORPORATED
INC.
By: /s/ ALAN P. DOZIER By: /s/ S.K. CHANDRASEKARAN
-------------------------------- ------------------------------
Title: President Title: Chief Executive Officer
16.
17
EXHIBIT A
TRANSFER OF RESPONSIBILITY FROM
INSITE AND BLP
Center for Drug Evaluation
and Research
Food and Drug Administration
To Whom It May Concern:
InSite Vision Incorporated ("InSite") hereby appoints Bausch & Lomb
Pharmaceuticals, Inc. ("BLP") as the agent of InSite to perform all duties and
obligations with respect to maintaining regulatory compliance for
________________ [name of product and NDA number] to BLP as Responsible Agent.
These duties may include, but not be limited to, the submission of annual
reports, the submission of supplements and amendments, the submission of adverse
event reports, the submission of annual drug lists, and the payment of any fees
due under the Prescription Drug User Fee Act.
18
EXHIBIT B
RIGHT OF REFERENCE
Center for Drug Evaluation
and Research
Food and Drug Administration
To Whom It May Concern:
InSite Vision International hereby confers upon Bausch & Lomb Pharmaceuticals,
Inc. a right of reference for all statutory purposes under the Federal Food,
Drug and Cosmetic Act, including 21 U.S.C. Section 355(b)(2), and implementing
regulations with respect to all information contained in [name of new drug
application and NDA number].
19
EXHIBIT C
MAJOR MARKETS
France
Germany
Italy
Spain
United Kingdom
China
India
Japan
South Korea
Taiwan
Canada
Mexico
20
EXHIBIT D
PilaSite Patents
INSITE LICENSED PATENTS Patent/Application Date Filed/Issued/Allowed
* J. ROBINSON, BIOADHESIVE COMPOSITION 4,615,697 P 10/07/86 1
AND TREATMENT THEREWITH 4,983,392 P 01/08/91 1
5,225,196 P 07/06/93 1
INSITE PATENTS
* OPHTHALMIC SUSPENSIONS 5,192,535 P 03/09/93 1
21
STATUS OF USSN 07/544,518 AND FOREIGN COUNTERPARTS
COUNTRY SERIAL NO. FILING DATE PATENT NO. ISSUE DATE STATUS
United States 07/544,518 June 27, 1990 5,192,535 March 9, 1993 Issued
* * * * * *
* * * * * *
New Zealand 238757 June 27, 1991 238,756 March 16, 1993 Issued
South Africa 914971 June 27, 1991 914971 September 30, 1992 Issued
* * * *
* * * *
* * * *
* * * *
[* INDICATES THAT MATERIAL HAS BEEN OMITTED AND CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED THEREFOR. ALL SUCH OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO RULE 24b-2.]
22
SUMMARY
Columbia Patents 1
USA: USSN 551,295 filed 11/14/83 Abandoned
USA: USSN 690,483 filed 12/20/84 US 4,615,697 issued 10/07/86 Priority: WO 84US1827; USSN 551,295
USA: USSN 909,960 filed 09/22/86 US 4,795,436 issued 01/03/89 Priority: USSNs 551,295; 690,483
USA: USSN 287,464 filed 12/20/88 US 4,983,392 issued 01/08/91 Priority: USSNs 551,295; 690,483; 909,960
USA: USSN 638,184 filed 01/07/91 US 5,225,196 issued 07/06/93 Priority: USSNs 551,295; 690,483; 909,960;
287,464
Canada: CA 495209 filed 11/13/85 CA 1260832 issued 09/26/89 Priority: USSN 690,483
PCT: WO 84US1827 filed 11/09/84 WO 8502092 issued 09/26/89 Priority: USSN 551,195
Designated States (national): AU, JP, US
Designated States (regional): AT, BE, CH, DE, FR, GB, LU, NL,
SE
Australia: AU 8436184 filed 11/09/84 AU 565354 issued 06/03/85 Priority: WO 84US1827; USSN 551,295
Japan: JP 84504250 filed 11/09/84 JP 61500612 issued 04/03/86 Priority: WO 84US1827; USSN 551,295
Europe: EP 84904286 A filed 11/09/84 EP 163696 A1 issued 11/25/92 Priority: WO 84US1827; USSN 551,295
Designated States: AT, BE,
CH, DE, FR, GB, LI, LU, NL, SE
Germany: EP 84904286 A filed 11/09/84 DE 3485995 issued 01/07/93 Priority: WO 84US1827; USSN 551,295
Austria: EP 84904286 A filed 11/09/84 AT 82667 issued 12/15/92 Priority: Wo 84US1827; USSN 551,295
Europe: EP 92105052 A filed 11/09/84 EP 501523 A1 issued 09/02/92 Priority: USSN 551,295
Unknown-divisional of EP 84904286
probably
23
Columbia Patents 2
* * *
* * *
* * *
* * *
Europe: EP 90300327 filed 01/11/90 EP 429156 issued 05/29/91 Priority: USSN 429,770
Europe: EP 90300340 filed 01/11/90 EP 431719 issued 06/12/91 Priority: USSN 429,755
Europe: EP 91901558 filed 10/24/90 EP 500807 issued 09/02/92 Priority: USSNs 429,770; 429,755
Designated States (same for all three): AT, BE, CH, DE, DK ES, FR, GB, GR,
IT, LI, LU, NL,SE
PCT: WO 90US6087 filed 10/24/90 WO 9106283 issued 05/16/91 Priority USSNs 429,770; 429,755
Designated States (national): AT, AU, BB, BG, BR, CA, CH, DE, DK,
ES, FI, GB, HU, JP, KP, KR, LK, LU,
MC, MG, MW, NL, NO, RO, SD, SE,
SU, US
Designated States (regional): AT, BE, CH, DE, DK, ES, FR, GB, GR,
IT, LU, NL, SE
Australia: AU 9170331 filed 10/24/90 AU 639,069 issued 07/15/93 Priority: 90US6087; USSNs 429,770;
429,755
Brazil: BR 907807 filed 10/24/90 BR 9007807 issued 09/29/92 Priority: 90US6087; USSNs 429,770;
429,755
Canada: CA 2072148 filed 10/24/90 CA 2072148 issued 05/01/91 Priority: USSNs 429,770; 429,755
Spain: EP 90300340 filed 01/11/90 ES 2050096 issued 05/16/94 Priority: USSN 429,755
Finland: FL 921932 filed 04/29/92 FI 9201932 issued 04/29/92 Priority: US6087; USSNs 429,770;
429,755
Hungary: HU 921465 filed 10/24/90 HU 9201465 issued 07/28/92 Priority: USSNs 429,770; 429,755
Israel: IL 96148 filed 10/29/90 IL 964148 issued 07/18/91 Priority: USSNs 429,770; 429,755
Japan: JP 91501917 filed 10/24/90 JP 5504338 issued 07/08/93 Priority: 90US6087; USSNs 429,770;
429,755
Monaco: MC 6087 filed 10/24/90 MC 2204 issued 11/26/94 Priority: USSNs 429,770; 429,755
Norway: NO 921686 filed 04/29/92 NO 9201686 issued 04/29/92 Priority: 90US6087; USSNs 429,770;
429,755
Portugal: PT 95729 filed 10/29/90 PT 95729 issued 09/13/91 Priority: USSNs 429,770; 429,755
S. Africa: ZA 908603 filed 10/26/90 ZA 9008603 issued 08/28/91 Priority: USSN 429,770
[* INDICATES THAT MATERIAL HAS BEEN OMITTED AND CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED THEREFOR. ALL SUCH OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE
COMMISSION PURSUANT TO RULE 24b-2.]
24
CONTAINER PATENT SUMMARY
INSITE PATENTS Patent/Application Date Filed/Issued/Allowed
1. LIQUID DROPLET DISPENSING APPARATUS 5,040,706 P 08/20/91 1
(UTILITY)
2. LIQUID DROPLET DISPENSING APPARATUS D322,313 P 12/10/91 1
(DESIGN)
25
STATUS OF LIQUID DROPLET DISPENSER FOR THE EYE (Design)
INVENTORS: Nicholas F. Talesfore
COUNTRY SERIAL NO. FILING DATE PATENT NO. ISSUE DATE STATUS
United States 07/366,029 June 14, 1989 D322,313 December 10, 1991 Issued
Australia 196490 June 21, 1990 111102 May 23, 1991 Issued
Benelux 6528600 February 28, 1990 1995800 February 28, 1990 Issued
Canada 0504902 April 5, 1990 67311 October 25, 1990 Issued
Switzerland 118158 March 1, 1990 118158 March 1, 1990 Issued
Germany M90016076 March 1, 1990 M90016076 December 20, 1990 Issued
Spain 122487 June 28, 1990 122487 February 22, 1991 Issued
France 901578 March 8, 1990 901578 March 8, 1990 Issued
United Kingdom 2005079 March 1, 1990 2005079 July 24, 1990 Issued
Ireland 29690 March 8, 1990 D8969 June 20, 1990 Issued
Israel 16630 June 20, 1990 16630 January 7, 1991 Issued
Italy 20837B90 March 16, 1990 58334 February 24, 1993 Issued
Japan 0086691990 March 14, 1990 849012 June 26, 1992 Issued
New Zealand 23332 June 16, 1990 23332 November 28, 1990 Issued
Phillipines D7713 October 2, 1990 D5176 November 5, 1991 Issued
Sweden 900452 March 1, 1990 49069 January 23, 1991 Issued
26
STATUS OF LIQUID DROPLET DISPENSER FOR THE EYE (Utility)
INVENTORS: Jeffrey P. Davis, Roy D. Archibald, Christa D. Nicholas,
S.K. Chandrasekaran
COUNTRY SERIAL NO. FILING DATE PATENT NO. ISSUE DATE STATUS
United States 07/324,793 March 17, 1989 5,040,706 August 20, 1991 Issued
Austria 90958158 March 2, 1990 E85761 February 17, 1993 Issued
Australia 5773390 June 21, 1990 619989 June 9, 1992 Issued
Belgium 90958158 March 2, 1990 0447496 February 17, 1993 Issued
Canada 2011734 March 8, 1990 2011734 May 24, 1994 Issued
Switzerland 909058158 March 2, 1990 0447496 February 17, 1993 Issued
Germany 90858158 March 2, 1990 69000356 February 17, 1993 Issued
Denmark 909058158 March 2, 1990 0447496 February 17, 1993 Issued
European Patent Convent 909058158 March 2, 1990 0447496 February 17, 1993 Issued
Spain 909058158 March 2, 1990 0447496 February 17, 1993 Issued
Spain 9002045 June 29, 1990 9002045 January 23, 1992 Issued
France 909058158 March 2, 1990 0447496 February 17, 1993 Issued
United Kingdom 90958158 March 2, 1990 0447496 February 17, 1993 Issued
Italy 909058158 March 2, 1990 0447496 February 17, 1993 Issued
Japan 2505442 March 2, 1990 1922786 April 7, 1995 Issued
Luxembourg 909058158 March 2, 1990 0447496 February 17, 1993 Issued
Netherlands 90958158 March 2, 1990 0447496 February 17, 1993 Issued
New Zealand 234140 June 19, 1990 234140 May 24, 1993 Issued
Phillipines 41324 October 5, 1990 26430 July 15, 1992 Issued
Sweden 909058158 March 2, 1990 0447496 February 17, 1993 Issued
27
SCHEDULE 2.2(a)
SERVICES
* Preparation of protocols governing stability testing of product and drug
substance.
* Develop specifications for drug substance and drug product (and components
thereof) and analytical assays methods validation.
* Stability testing of drug substance and product, and validation thereof.
* Response to FDA questions/comments on NDA filed by InSite relating to data
and information provided by B&P.
* Supervision of pre-approval inspection by FDA and provision of such other
regulatory support and assistance as is reasonably requested by InSite and
necessary to obtain FDA approval of the NDA.
* Validation of product manufacturing process before submission of NDA by
InSite.
* Manufacture of three (3) QA/QC-released lots for NDA registration purposes
and stability studies to support NDA submission and approval.
* Validation of sterilization of drug product.