Document:

exv10w45

Exhibit 10.45

C
O N F I D E N
T I A L

LICENSE AGREEMENT

     THIS LICENSE AGREEMENT (“Agreement”) is made and entered into effective as of July 23, 2007
(the “Effective Date”), by and between Archemix Corp., having principal offices at 300 Third
Street, Cambridge, Massachusetts 02142 (“Archemix”), and Isis Pharmaceuticals, Inc., having
principal offices at 1896 Rutherford Road, Carlsbad, California 92008 (“Isis”). Archemix and Isis
each may be referred to herein individually as a “Party,” or collectively as the “Parties.”

     WHEREAS, Isis is a recognized leader in the development of antisense oligonucleotides, and
Archemix is a recognized leader in the development of Aptamers (as defined below);

     WHEREAS, Isis has developed proprietary chemistries and know-how that may accelerate the
successful commercialization of Aptamers, and Archemix is developing know-how that may reciprocally
inform the development of other oligonucleotides (including antisense); and

     WHEREAS, this Agreement establishes a strategic alliance between Isis and Archemix which
enables the Parties to benefit from Isis’ proprietary chemistries and their mutual proprietary
expertise to facilitate their respective discovery, development, and commercialization efforts;

     NOW, THEREFORE, the Parties do hereby agree as follows:

ARTICLE 1

DEFINITIONS

Capitalized terms used in this Agreement and not otherwise defined herein have the meanings set
forth in Appendix 1.

ARTICLE 2

GRANT OF RIGHTS

     Section 2.1 License Grants.

          2.1.1 Subject to the terms and conditions of this Agreement, Isis hereby grants to Archemix
for use outside of the Excluded Field:

	 	(x)	 	a worldwide, royalty-bearing, non-exclusive license under the
Isis Analytical Patents solely to research, make (but not have made), use,
import, offer to sell and sell and otherwise discover, develop, and
commercialize Licensed Products;

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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	 	(y)	 	a worldwide, royalty-bearing, nonexclusive license under the
Isis Manufacturing Patents solely to research, make (but not have made), use,
import, offer to sell and sell and otherwise discover, develop, and
commercialize Licensed Products; and
	 
	 	(z)	 	a worldwide, royalty-bearing, exclusive (subject to Section
2.1.2) license under the Isis Chemistry Patents, with the right to grant
sublicenses subject to Section 4.4, to research, make, have made, use, import,
offer to sell and sell and otherwise discover, develop, and commercialize
Licensed Products.

Archemix will have no right to sublicense or otherwise transfer to any Third Party any rights in or
to the licenses to the Isis Analytical Patents or to the Isis Manufacturing Patents granted to
Archemix under Section 2.1.1(x) or 2.1.1(y), respectively. For the avoidance of doubt, and subject
to the field restriction set forth in the first sentence of Section 2.1.1, Archemix’s conduct
through its own employees or consultants of in-house tests on Aptamer Products made by Third
Parties shall be deemed to fall within Archemix’s rights to “make” Licensed Products under Sections
2.1.1(x) and 2.1.1(y) as applicable, and shall not constitute “having made.”

          2.1.2 Upon the occurrence of any Conversion Event, the exclusive license granted to Archemix
under Section 2.1.1(z) will automatically become non-exclusive, subject to the following:

(a) Such license will remain exclusive with respect to any Target and any
Licensed Product that binds to such Target for which Archemix (or an
Archemix Affiliate or Archemix Sublicensee) has achieved the [***] milestone
and has timely paid Isis the applicable milestone payment under Section 5.2
below prior to the occurrence of the first Conversion Event.

(b) If, following the occurrence of the first Conversion Event, such
exclusive license converts to a non-exclusive license pursuant to this
Section 2.1.2, such license will convert back to an exclusive license
(regardless of the intervening period of non-exclusivity) with respect to
any Target and any Licensed Product that binds to such Target for which
Archemix (or an Archemix Affiliate or Archemix Sublicensee) has achieved the
[***] milestone and has timely paid Isis the applicable milestone payment
under Section 5.2 below; provided, that Isis has not, after the first
Conversion Event but prior to Archemix’s (or an Archemix Affiliate’s or
Archemix Sublicensee’s) achievement of the [***] Milestone and payment of
the applicable milestone payment, granted a license to a Third Party that
would prevent Isis from granting an exclusive license with respect to such
Target and Licensed Product to Archemix.

(c) Any license that remains or becomes exclusive pursuant to clauses (a) or
(b) above following a Conversion Event will remain exclusive as long as
Archemix (or an Archemix Affiliate or Archemix Sublicensee) is

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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actively researching, developing or commercializing the Licensed Product
that is the subject of the license, or another Aptamer for such Target. For
the avoidance of doubt, if Archemix (or an Archemix Affiliate or Archemix
Sublicensee) discontinues its activities with respect to a Licensed Product
that is the subject of an exclusive license pursuant to clause (a) or (b)
above, Archemix (or an Archemix Affiliate or Archemix Sublicensee) will
still be deemed to be actively researching or developing a Licensed Product
for such Target if it begins research or development activities relating to
a back-up product that is intended to be a Licensed Product for such Target
within [***] days thereafter.

          2.1.3 Notwithstanding the foregoing, Isis retains the right under the license granted to
Archemix under Section 2.1.1(z) above to fulfill its obligations under any licenses granted by Isis
prior to the Effective Date, and to grant Permitted Licenses, and the exclusivity of the license
granted to Archemix under Section 2.1.1(z) is limited by any such licenses granted prior to and
after the Effective Date. For the avoidance of doubt, no Permitted License shall grant any Third
Party exclusive rights under the Isis Patents to research, make, have made, use, import, offer to
sell or sell, or otherwise discover, develop, or commercialize Licensed Products.

     Section 2.2 Know-How License Grants.

          2.2.1 License Grant to Archemix. Subject to the terms and conditions of this
Agreement, Isis grants to Archemix a worldwide, fully paid, royalty-free, non-exclusive license,
with the right to sublicense subject to the last two sentences of this Section 2.2.1, under all
Know-How disclosed by Isis to Archemix under this Agreement, to use such Know-How solely to
research, make, have made, use, import, offer to sell and sell and otherwise discover, develop and
commercialize Aptamer Products. Archemix will have no right to sublicense or otherwise transfer any
rights in or to the license granted to Archemix under this Section 2.2.1 to any Know-How covering
information related to Isis’ manufacturing or analytical technology. Any Sublicense granted under
this Section 2.2.1 will (i) be subject to Section 4.4 below, and (ii) require the Archemix
Sublicensee to maintain the confidentiality of the sublicensed Know-How in accordance with
confidentiality provisions at least as protective as those set forth in Article 7 herein.

          2.2.2 License Grant to Isis. Subject to the terms and conditions of this Agreement,
Archemix grants to Isis a worldwide, fully paid, royalty-free, non-exclusive license, with the
right to sublicense subject to the last sentence of this Section 2.2.2, under all Know-How
disclosed by Archemix to Isis under this Agreement, to use such Know-How solely to research, make,
have made, use, import, offer to sell and sell and otherwise discover, develop and commercialize
products other than Aptamer Products. Any sublicense granted under this Section 2.2.2 will require
the sublicensee to maintain the confidentiality of the sublicensed Know-How in accordance with
confidentiality provisions at least as protective as those set forth in Article 7 herein.

          2.2.3 Additional Licenses. In addition to the licenses granted in Sections 2.1.1 and
2.2.1, Isis agrees, at Archemix’s request, to negotiate in good faith with Archemix for the

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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grant of a license to Archemix under any Patents not licensed to Archemix hereunder, or
additional rights under Patents that are licensed hereunder, that are, at the time of such request,
owned or Controlled by Isis, to research, make, have made, use, import, offer to sell and sell and
otherwise discover, develop, and commercialize Licensed Products, subject to any Third Party rights
or other contractual limitations.

ARTICLE 3

SCOPE OF COLLABORATION; COLLABORATION ACTIVITIES

     Section 3.1 Scope of Collaboration; Research Management Committee. To assist the development
of each Party’s commercial focus, representatives from Isis and Archemix will meet regularly, as
mutually agreed, to share Know-How and coordinate basic research efforts that have the potential to
impact each Party’s development efforts (the “Collaboration”). In particular, a jointly composed
research management committee (“RMC”) will meet at least [***] per [***] during the term of the
Collaboration, alternating venues between the vicinities of Cambridge, Massachusetts and Carlsbad,
California, to coordinate the exchange of know-how and research planning. Meetings of the RMC will
be by telephone or by video conference if desired by either Party. Intellectual property
representatives of each Party may participate in RMC meetings and such meetings will provide a
forum to discuss intellectual property issues relevant to the Collaboration.

     Section 3.2 Collaboration Activities. To the extent that the Parties agree to conduct any
joint activities under the Collaboration, the Parties will use Commercially Reasonable Efforts to
conduct their respective Collaboration research and development activities in a good scientific
manner, and in compliance in all material respects with all Applicable Law, and will cooperate
reasonably with the other Party to achieve the goals of the Collaboration. Each Party will bear
the sole responsibility for funding its own Collaboration research and development activities,
unless otherwise agreed by the Parties.

     Section 3.3 Term of Collaboration Activities. The Collaboration will remain in effect for a
period [***] years following the Effective Date, and may be continued thereafter with the mutual
agreement of both Parties.

     Section 3.4 Consulting Activities. Archemix may request Isis to perform certain research and
development activities to aid in the advancement of Licensed Products. Isis will be under no
obligation to perform such consulting activities requested by Archemix. Any mutually agreed upon
consulting work will be performed under an agreed upon work plan, which will include estimates of
Isis’ FTE time to be expended. Isis will be compensated by Archemix for the performance of any such
consulting work by Isis at the FTE Rate.

ARTICLE 4

LICENSED PRODUCT DEVELOPMENT; CONDITIONS TO LICENSES

     Section 4.1 Development/Commercialization/Regulatory Responsibilities. Archemix is solely
responsible for the development and commercialization of Licensed Products.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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Archemix will comply with all Applicable Laws in connection with the development and
commercialization of the Licensed Products.

     Section 4.2 Reports. Archemix will provide to Isis [***] reports (each an “R&D Report”)
summarizing which Isis chemistries and analytical methods are actively being used in Archemix’s
programs, subject to Archemix’s confidentiality obligations to Third Parties. Archemix will not be
required to disclose specific Targets in any R&D Report. The R&D Reports will be the Confidential
Information of Archemix.

     Section 4.3 Safety Reporting and Notification. Subject to confidentiality obligations to Third
Parties, each Party will notify the other Party as soon as practicable (and, if possible, provide
as much advance notice as possible) of any event or other information of which such Party becomes
aware that is materially related to the safety of the Licensed Products (such as serious adverse
events). Notwithstanding the foregoing, regardless of whether Isis provides such safety-related
information to Archemix, in no event will Isis have any liability under this Agreement with respect
to any Licensed Product.

     Section 4.4 Conditions to Sublicenses.

          4.4.1 Prior to the first Conversion Event, Archemix may enter into Sublicenses of the rights
under Section 2.1.1(z).

          4.4.2 Following the first Conversion Event, Archemix may enter into Sublicenses of the rights
under Section 2.1.1(z) with respect to (i) any Target that remains exclusive, without limitation,
and (ii) any Target that is non-exclusive, solely in connection with development and
commercialization of a Licensed Product to such Target.

          4.4.3 For purposes of clarification, the Sublicenses described in Section 4.4.1 and Section
4.4.2 may be entered into with (i) any licensee or sublicensee of Archemix under any Patents of
Archemix or a Third Party that Archemix is entitled to sublicense, including any Third Party
licensee of Archemix’s SELEX or other technology, or (ii) an Affiliate of Archemix. Further, for
the avoidance of doubt, Archemix will have the right to offer, but shall not be obliged to grant, a
Sublicense to any entity that is a development or commercialization partner or licensee of Archemix
as of the Effective Date (each, a “Legacy Licensee”) that desires to take a license to any of the
Isis Chemistry Patents and/or the Isis Know-How. Any Sublicense granted to a Legacy Licensee will
be consistent with, and expressly made subject to, this Agreement. [***]

ARTICLE 5

FINANCIAL PROVISIONS

     Section 5.1 Warrant Grant. On the Effective Date of this Agreement, Archemix will grant to
Isis a seven-year warrant to acquire 600,000 shares of Archemix’s common stock at a purchase price
of twenty-five cents ($0.25) per share (subject to adjustment in the event of a stock split,
reverse stock split or other similar events), by executing the warrant attached hereto as Appendix
5 (the “Warrant”).

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     Section 5.2 Milestone Payments by Archemix. Archemix will pay to Isis each milestone payment
not more than [***] days after first achievement, by Archemix, its Affiliates or an Archemix
Sublicensee, of each of the events for each Licensed Product as follows:

	 	 	 
	Event	 	Payment
	[***]

	 	$[***] (U.S.)
	[***]

	 	$[***] (U.S.)
	[***]

	 	$[***] (U.S.)
	[***]

	 	$[***] (U.S.)

          5.2.1 Any milestone payments paid by Archemix to Isis for a particular Licensed Product are
creditable against Sublicense Revenue payable to Isis for such Licensed Product, subject to Section
5.4.1 and will be accompanied by a statement to Isis indicating to which Licensed Product and
Target such milestone payment applies. For purposes of illustration, (a) if Archemix has paid a
milestone payment to Isis for a Licensed Product prior to sublicensing such Licensed Product, such
milestone payment will not also be payable by the Archemix Sublicensee, and such milestone payment
will be creditable against the portion of Sublicense Revenue payable to Isis for such Licensed
Product (subject to Section 5.4.1 ). [***] milestone will be [***] for any Target, [***] Licensed
Product is [***] that binds to such Target.

     Section 5.3 Sublicense Revenue Sharing.

          5.3.1 Sublicenses Involving Licensed Product(s). In the event that Archemix enters into a
Sublicense for any Licensed Product, Archemix will pay Isis the following percentages of all
Sublicense Revenue received:

(a) [***]% of all Sublicense Revenue from any Sublicense of any Licensed
Product entered into [***] the [***] a [***] for such Licensed Product;

(b) [***]% of all Sublicense Revenue from any Sublicense of any Licensed
Product entered into [***] the [***] a [***] for such Licensed Product but
[***] the [***] a [***] for such Licensed Product; and

(c) [***]% of all Sublicense Revenue from any Sublicense of any Licensed
Product entered into [***] the [***] a [***] for such Licensed Product.

          5.3.2 Sublicenses Prior to a Licensed Product. In the event that Archemix enters into a
Sublicense that does not involve any Licensed Products at the time of such Sublicense, Archemix
will pay Isis [***] percent ([***]%) of all Sublicense Revenue received from such Sublicense.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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Notwithstanding the foregoing, in cases where Archemix enters into a Sublicense with a Legacy
Licensee that does not involve any Licensed Products at the time of such Sublicense, in addition to
payment of the applicable percentage of Sublicense Revenue (excluding up-front consideration) under
either of Sections 5.3.1 or 5.3.2 above, Archemix will pay Isis [***] percent ([***]%) of any
up-front consideration received by Archemix from any such Sublicense for the extension of such
license.

          5.3.2 Any payment to Isis for its portion of Sublicense Revenue due under this Section 5.3
will be due within [***] days of the date such Sublicense Revenue is earned; provided, however,
within [***] days after any calendar quarter in which Sublicense Revenue is earned, Archemix will
send Isis a written statement of the amount of Isis’ portion of such Sublicense Revenue.

     Section 5.4 Royalty Payments by Archemix.

          5.4.1 In consideration of Isis’ collaborative efforts and the licenses granted hereunder,
Archemix will pay Isis a royalty of [***]% of Net Sales of each Archemix-Marketed Licensed Product.
For any Licensed Products sold by an Archemix Sublicensee pursuant to a Sublicense, in
consideration of Isis’ collaborative efforts and the licenses granted hereunder, Archemix will pay
Isis a royalty on Net Sales of such Licensed Products equal to the greater of (i) the applicable
Sublicense Revenue rate set forth in Section 5.3.1 or 5.3.2 above multiplied by the [***] Archemix
is [***] under such Sublicense, or (ii) [***]% of Net Sales of such Licensed Products.
Notwithstanding the foregoing, in the event that of all of the Isis Patent Rights licensed
hereunder the only Patent used with respect to a particular Licensed Product is an Isis
Manufacturing Patent, then the Parties will negotiate in good faith a [***] Net Sales of such
Licensed Product.

          5.4.2 Reduction of Royalties. If the exclusive license granted to Archemix under Section
2.1.1(z) becomes non-exclusive with respect to a Licensed Product, during the period of
non-exclusivity the otherwise applicable royalty rate on Net Sales for such Licensed Product
payable to Isis under Section 5.4.1 will be reduced by [***]%; provided, however, that in no event
will the royalty payable to Isis on Net Sales of Licensed Products be reduced to less than [***]%.

          5.4.3 Royalty Term for Licensed Products. Archemix will pay Isis a royalty on Net Sales of
Licensed Products, in each country in which the Licensed Products are manufactured, used or sold,
from the date of first commercial sale of the Licensed Products until the expiration of the
last-to-expire Valid Claim within an Isis Patent in such country that covers (a) the manufacture,
use, or sale of the Licensed Product, and/or (b) a method used in the discovery, identification or
characterization of the Licensed Product. For purposes of clarity, notwithstanding the immediately
preceding sentence, if a Licensed Product is made in a country where, but for the licenses granted
hereunder, it would infringe a Valid Claim of an Isis Patent, then Archemix will be obligated to
pay a royalty on Net Sales of such Licensed Product in any country.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     Section 5.5 Timing of Royalty Payments. The royalties from Archemix to Isis set forth in
Section 5.4 are due and payable within [***] days after each respective Royalty Due Date and will
be calculated based on the Net Sales in the calendar quarter immediately preceding the applicable
Royalty Due Date.

     Section 5.6 Payment Method. Any amounts due to Isis under this Agreement will be paid in U.S.
dollars, by wire transfer in immediately available funds to an account designated by Isis. Any
payments or portions thereof due hereunder which are not paid on the date such payments are due
under this Agreement will bear simple interest at a rate of [***]% per month, or the maximum rate
permitted by Applicable Law, whichever is lower, calculated on the number of days such payment is
delinquent.

     Section 5.7 Currency; Foreign Payments. If any currency conversion will be required in
connection with any payment hereunder, such conversion will be made by using the exchange rate for
the purchase of U.S. dollars as published in The Wall Street Journal, Eastern Edition, on the last
Business Day of the calendar quarter to which such payments relate. If at any time legal
restrictions prevent the prompt remittance of any payments in any jurisdiction, Archemix may notify
Isis and make such payments by depositing the amount thereof in local currency in a bank account or
other depository in such country in the name of Isis or its designee, and Archemix will have no
further obligations under this Agreement with respect thereto.

     Section 5.8 Taxes. Archemix may deduct from any amounts it is required to pay to Isis
pursuant to this Agreement an amount equal to that withheld for or due on account of any taxes
(other than taxes imposed on or measured by net income) or similar governmental charge imposed by a
jurisdiction based on such payments to Isis (“Withholding Taxes”). Archemix will provide Isis a
certificate evidencing payment of any Withholding Taxes hereunder within [***] days of such payment
and will reasonably assist Isis, at Isis’ expense, to obtain the benefit of any applicable tax
treaty.

     Section 5.9 Records Retention; Audit.

          5.9.1 Record Retention. Archemix will maintain (and will contractually require that the
Archemix Sublicensees maintain) complete and accurate books, records and accounts that fairly
reflect Net Sales with respect to the Licensed Products, in each case in sufficient detail to
confirm the accuracy of any payments required hereunder and in accordance with GAAP, which books,
records and accounts will be retained by Archemix until the later of (i) [***] years after the end
of the period to which such books, records and accounts pertain, and (ii) the expiration of the
applicable tax statute of limitations (or any extensions thereof), or for such longer period as may
be required by Applicable Law.

          5.9.2 Audit. Isis will have the right to have an independent certified public accounting firm
of nationally recognized standing, reasonably acceptable to Archemix, have access during normal
business hours, and upon reasonable prior written notice, to Archemix’s records as may be
reasonably necessary to verify the accuracy of Net Sales or Sublicense Revenue, as applicable, for
any calendar quarter or calendar year ending not more than [***] months prior to the date of such
request; provided, however, that Isis will not have the right to

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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conduct more than one such audit in any Calendar Year except as provided below or more than
one such audit covering any given time period. Isis will require such accounting firm to enter
into a confidentiality agreement with Archemix in a form reasonably acceptable to Archemix prior to
the conduct of any audit. The accounting firm will disclose to Isis only whether the Net Sales
and/or Sublicense Revenue has been correctly reported, the specific detail concerning any
discrepancies, and the corrected amount of Net Sales and/or Sublicense Revenue payments. Isis will
bear the cost of such audit unless the audit reveals an underpayment to Isis of more than [***]%,
in which case Archemix will bear the cost of the audit. In any agreement for a Sublicense granted
by Archemix hereunder, Archemix will use Commercially Reasonable Efforts to secure a similar right
on the part of Archemix to audit its Archemix Sublicensee, and, if reasonably requested in writing
by Isis, will enforce such audit right and disclose its audit report to Isis’s auditors.

          5.9.3 Payment of Additional Amounts. If, based on the results of such audit, additional
payments are owed by Archemix under this Agreement, Archemix will make such additional payments,
with interest as set forth in Section 5.6, within [***] days after the date on which such
accounting firm’s written report is delivered to such Party.

          5.9.4 Confidentiality. Isis will treat the financial information subject to review under this
Section 5.9 in accordance with the confidentiality provisions of Article 7.

ARTICLE 6

PRESS RELEASES & PUBLICATIONS

     Section 6.1 Press Releases.

          6.1.1 Press Releases — Generally. Each provision of this Section 6.1.1 is subject to Section
6.1.2 below. Press releases or other similar public communication by either Party relating to this
Agreement, will be approved in advance by the other Party, which approval will not be unreasonably
withheld or delayed, except for those communications required by Applicable Law, disclosures of
information for which consent has previously been obtained, and information of a similar nature to
that which has been previously disclosed publicly with respect to this Agreement, each of which
will not require advance approval, but will be provided to the other Party as soon as practicable
after the release or communication thereof.

          6.1.2 Press Releases – Licensed Product Safety. Subject to any confidentiality obligations to
Third Parties, each Party will notify the other Party within the time frames required by Applicable
Law of any event of which it becomes aware materially related to the safety of Licensed Products
(including any Regulatory Approval) so that the Parties may analyze the need to or desirability of
publicly disclosing or reporting such event; provided, that, Archemix will be required to so notify
Isis only if such event is reasonably determined by Archemix to be related to the Isis Chemistries.
Archemix will have the right to disclose any such safety information supplied by Isis to any of
the Archemix Sublicensees that are Researching, developing or commercializing Licensed Products,
and to any Third Party as required by Applicable Law. Notwithstanding Section 6.1.1 above, (a) any
press release or other similar public communication by either Party related to a Licensed Product’s
safety, except for those

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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communications required by Applicable Law, will be submitted to the other Party for review and
approval at least [***] hours in advance (if reasonably practicable) of such proposed public
disclosure, which approval will not be unreasonably withheld, conditioned or delayed and (b)
Archemix will have the sole right to issue any press release or other similar public communication
related to a Licensed Product’s safety unrelated to the Isis Chemistries.

     Section 6.2 Publications. At least [***] days prior to a Party’s submission of any material
related to any Collaboration research or development activities conducted hereunder pursuant to
Section 3.2 for publication or presentation, such Party (the “Submitting Party”) will provide to
the other Party (the “Commenting Party”) a draft of such material for its review and comment. Such
drafts will be subject to Article 7. The Commenting Party will provide any comments to the
Submitting Party within [***] days of receipt of such materials. No publication or presentation
with respect to any such Collaboration research or development activities hereunder will be made
unless and until any information determined by the Commenting Party to be the Commenting Party’s
Confidential Information has been removed. If requested in writing by the Commenting Party, the
Submitting Party will withhold material from submission for publication or presentation for a
reasonable time, but no more than [***] days, to allow for the filing of a patent application.

ARTICLE 7

CONFIDENTIALITY

     Section 7.1 Disclosure and Use Restriction. Except pursuant to an Authorized Disclosure, the
Parties agree that, for the Term and for [***] years thereafter, each Party will keep completely
confidential and will not publish, submit for publication or otherwise disclose, and will not use
for any purpose, except for the purposes contemplated by this Agreement, any Confidential
Information received from the other Party.

     Section 7.2 Terms of Agreement. Either Party may disclose (i) an unredacted copy of this
Agreement on a confidential basis to its Affiliates, prospective and actual sublicensees, its
legal, business and financial advisors, bankers and accountants, and its prospective lenders,
investors, or acquirers, and (ii) the terms of this Agreement as required under applicable
securities laws or regulations (including without limitation under rules or regulations of any
securities exchange or NASDAQ). Except as set forth in the preceding sentence, neither Party will
disclose the terms of this Agreement or any part thereof to any Third Party.

     Section 7.3 Sublicensing. In the case of any Sublicense permitted under this Agreement, or
other permitted transfers to a Third Party by Archemix of any Confidential Information received by
Archemix under this Agreement, the following conditions apply: (A) Archemix will obtain an
agreement from any such Archemix Sublicensee or Third Party that receives Isis’ Confidential
Information from Archemix that such Archemix Sublicensee or Third Party will be bound by
confidentiality and non-use provisions at least as protective of Isis’ Confidential Information as
the provisions of this Agreement, and (B) in the event of a conflict between the non-use or
confidentiality provisions in this Agreement and the non-use or confidentiality provisions of a
Sublicense properly granted hereunder, such Sublicense provisions will prevail.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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ARTICLE 8

INTELLECTUAL PROPERTY

     Section 8.1 Ownership of Intellectual Property. In the event the Parties agree to conduct
research and/or development activities under the Collaboration, such activities will be performed
in accordance with a mutually agreed upon written Collaboration plan, which will include, among
other relevant things, provisions regarding ownership of any intellectual property arising under
the Collaboration, and the Parties’ respective rights and responsibilities regarding the filing,
prosecution, and maintenance of any Patents coving such intellectual property. This Agreement will
be understood to be a joint research agreement to discover Licensed Products and associated uses in
accordance with 35 U.S.C. § 103(c)(3).

     Section 8.2 Prosecution of Patents. Each Party will have the [***] right, [***] cost and
expense and [***] discretion, to obtain, prosecute and maintain throughout the world any Patents
solely owned or Controlled by such Party, including with respect to Isis, the Isis Chemistry
Patents, the Isis Manufacturing Patents and the Isis Analytical Patents.

     Section 8.3 Enforcement of Patents.

          8.3.1 Rights and Procedures. If Isis or Archemix determines that any Patent licensed
hereunder is being infringed by a Third Party’s activities and that such infringement could affect
the exercise by the Parties of their respective rights and obligations under this Agreement, it
will promptly notify the other Party in writing, unless doing so would constitute a breach of a
duty of confidentiality to such Third Party that arose prior to the date that Isis or Archemix, as
applicable, became aware of the infringing activities. The Party controlling the Patent(s) which
are allegedly being infringed will have the sole right, but not the obligation, to remove such
infringement, including with respect to Isis, the Isis Chemistry Patents, the Isis Manufacturing
Patents, and the Isis Analytical Patents, and Archemix, as the exclusive licensee to the license
granted under Section 2.1.1(z) above, agrees to cooperate with and assist Isis in the resolution
and removal of any such infringement, including, without limitation, negotiating in good-faith with
such Third Party with respect to the rights granted to Archemix under Section 2.1.1(z) above.

ARTICLE 9

TERM; CONSEQUENCES OF TERMINATION

     Section 9.1 Term. Unless earlier terminated in accordance with the provisions of Article 10,
the term of this Agreement (the “Term”) commences upon the Effective Date and will continue until
the expiration of all obligations to pay royalties on all Licensed Products.

     Section 9.2 Rights in Bankruptcy. All rights and licenses granted under or pursuant to this
Agreement by Isis or Archemix are, and will otherwise be deemed to be, for purposes of Section
365(n) of the United States Bankruptcy Code, licenses of rights to “intellectual property” as
defined under Section 101 of the United States Bankruptcy Code. The Parties agree that the
Parties, as licensees of such rights under this Agreement, will retain and may fully exercise all
of their rights and elections under the United States Bankruptcy Code. The Parties further agree

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

11

 

that, in the event of the commencement of a bankruptcy proceeding by or against a Party under
the United States Bankruptcy Code, the Party hereto that is not a Party to such proceeding will be
entitled to a complete duplicate of (or complete access to, as appropriate) any such intellectual
property and all embodiments of such intellectual property, which, if not already in the
non-subject Party’s possession, will be promptly delivered to it (a) upon any such commencement of
a bankruptcy proceeding upon the non-subject Party’s written request therefor, unless the Party
subject to such proceeding elects to continue to perform all of its obligations under this
Agreement or (b) if not delivered under clause (a) above, following the rejection of this Agreement
by or on behalf of the Party subject to such proceeding upon written request therefor by the
non-subject Party.

     Section 9.3 Consequences of Termination.

          9.3.1 Licenses. Upon early termination of this Agreement in its entirety pursuant to Article
10, the licenses granted hereunder will terminate.

          9.3.2 Return of Information and Materials. Upon early termination of this Agreement in its
entirety pursuant to Article 10, each Party will return all data, files, records and other
materials in its possession or control relating to the other Party’s Patents or otherwise
containing or comprising the other Party’s Confidential Information (except one copy of which may
be retained for archival purposes).

          9.3.3 Transfer of Sublicenses. Any sublicenses granted by Archemix in accordance with Section
2.1.1 and/or 2.2.1 prior to the date of the corresponding notice of termination under Section 10
issued by Isis will survive if the relevant Sublicensee agrees in writing to be bound by the terms
of this Agreement as such terms apply to such Sublicensee (in which event, such Sublicensee will be
deemed a direct licensee of Isis); provided, further, that any such Sublicensee will only be
responsible for any payments that become due as a result solely of such Sublicensee’s activities
after the effective date of any such termination.

     Section 9.4 Accrued Liabilities; Surviving Obligations.

          9.4.1 Accrued Rights & Liabilities. Termination or expiration of this Agreement for any
reason will be without prejudice to any liabilities, rights, or financial compensation that will
have accrued to the benefit of a Party prior to such termination or expiration. Such termination
or expiration will not relieve a Party from obligations that are expressly indicated to survive the
termination or expiration of this Agreement.

          9.4.2 Survival. Articles and Sections 1, 6, 7, 8.1, 8.2, 9, 10, 12 and 14 of this Agreement
will survive expiration or termination of this Agreement for any reason. Section 5.1 (Warrant
Grant) will survive any permitted termination of this Agreement by Isis.

ARTICLE 10

MATERIAL BREACH OF THIS AGREEMENT

     Section 10.1 Material Breach. If a Party materially breaches this Agreement and such breach
is not cured within [***] days after the receipt of a notice of such breach from the other

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

12

 

Party (or, if such breach cannot be cured within such [***]-day period, if the defaulting
Party does not commence actions to cure within such period and diligently continues such actions),
the Party not in default may, without limiting any of its other rights under this Agreement, invoke
Section 14.4 below; provided, however, that in the event of a good faith dispute with respect to
the existence of a default, the [***]-day cure period will be stayed until the dispute is resolved
under Section 14.4. Notwithstanding anything to the contrary in this Agreement, in the event
Archemix breaches its obligations under Article 5, and such breach is not cured within [***] days
after Archemix’s receipt of notice of such breach, Isis may terminate this Agreement by providing
written notice to Archemix; provided, however, that in the event of a good faith dispute with
respect to the existence of a default, the [***]-day cure period will be stayed until the dispute
is resolved under Section 14.4. If either Party materially breaches this Agreement, the other
Party shall be entitled to suspend the obligations of the Parties under Sections 3.1, 3.2 and 3.3
and any Collaboration plans then in effect pursuant to Section 12.5. Such suspension shall be
without prejudice to any rights or remedies of a Party under such Collaboration plan(s) accruing
prior to the date of the suspension.

ARTICLE 11

[RESERVED]

ARTICLE 12

INDEMNIFICATION AND INSURANCE

     Section 12.1 Indemnification of Isis. Archemix will indemnify Isis, its Affiliates, and each
of their respective directors, officers, employees and agents (“Isis Parties”) and defend and hold
each of them harmless, from and against any and all losses, damages, liabilities, costs and
expenses (including reasonable attorneys’ fees and expenses) to the extent arising from or
occurring as a result of any and all liability suits, investigations, claims or demands by a Third
Party (collectively, “Losses”) arising from or occurring as a result of or in connection with (a)
any use by Archemix, its Affiliates, agents or Archemix Sublicensees of any information, technology
(including Know-How) of Isis, or Isis Patent Rights, or (b) whether or not negligence is found or
alleged, the manufacture, use, handling, storage, sale or other disposition of a Licensed Product
or other compound by Archemix, its Affiliates, agents or Archemix Sublicensees. Notwithstanding
the foregoing, Archemix will have no obligations under this Section 12.1 to the extent a Loss is
covered by an Isis indemnification obligation under Section 12.2 below.

     Section 12.2 Indemnification of Archemix. Isis will indemnify Archemix, its Affiliates, and
each of their respective directors, officers, employees and agents (“Archemix Parties”) and defend
and hold each of them harmless, from and against any and all Losses arising from or occurring as a
result of or in connection with any use by Isis, its Affiliates, agents or sublicensees of any
information or technology (including Know-How) of Archemix. Notwithstanding the foregoing, Isis
will have no obligations under this Section 12.2 to the extent a Loss is covered by an Archemix
indemnification obligation under Section 12.1 above.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

13

 

     Section 12.3 Conditions to Indemnity. Each of Isis’ and Archemix’s agreement to indemnify,
defend and hold the Archemix Parties or the Isis Parties respectively (each, an “Indemnitee”)
harmless is conditioned in each case upon the Indemnitee (i) providing written notice to the
indemnifying Party (the “Indemnitor”) of any claim, demand or action arising out of the indemnified
activities within [***] days after the Indemnitee has knowledge of such claim, demand or action,
(ii) permitting the Indemnitor to assume full responsibility for and control over the
investigation, preparation and defense of any such claim or demand, (iii) assisting the Indemnitor,
at the Indemnitor’s reasonable expense, in the investigation, preparation and defense of any such
claim or demand; and (iv) not compromising or settling such claim or demand without the
Indemnitor’s prior written consent; provided that, if the Indemnitee entitled to indemnification
fails to promptly notify the Indemnitor pursuant to the foregoing clause (i), the Indemnitor will
only be relieved of its indemnification obligation to the extent prejudiced by such failure.

     Section 12.4 Insurance. Archemix will have and maintain such types and amounts of liability
insurance as is normal and customary in the industry generally for parties similarly situated,
including product liability insurance and clinical trials insurance for Licensed Products (each of
which will name Isis as an additional insured), and will upon request provide Isis with a
certificate of insurance. Archemix will promptly notify Isis of any material change in insurance
coverage or lapse in coverage in that regard.

     Section 12.5 Collaboration Activities. In the event the Parties agree to conduct research
and/or development activities under the Collaboration, such activities will be performed in
accordance with a mutually agreed upon written Collaboration plan, which will include, to the
extent deemed appropriate by the Parties, additional indemnification obligations relevant to such
Collaboration activities.

ARTICLE 13

REPRESENTATIONS AND WARRANTIES

     Section 13.1 Representations, Warranties, and Covenants. Each Party hereby represents,
warrants, and covenants to the other Party as of the Effective Date as follows:

          13.1.1 Corporate Authority. Such Party (a) has the power and authority and the legal right to
enter into this Agreement (including the Warrant) and perform its obligations hereunder, and (b)
has taken all necessary action on its part required to authorize the execution and delivery of this
Agreement (including the Warrant) and the performance of its obligations hereunder. This Agreement
(including the Warrant) has been duly executed and delivered on behalf of such Party and
constitutes a legal, valid and binding obligation of such Party and is enforceable against it in
accordance with its terms subject to the effects of bankruptcy, insolvency or other laws of general
application affecting the enforcement of creditor rights and judicial principles affecting the
availability of specific performance and general principles of equity, whether enforceability is
considered a proceeding at law or equity.

          13.1.2 Consents, Approvals, etc. All necessary consents, approvals and authorizations of all
Regulatory Authorities and other parties required to be obtained by such

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

14

 

Party in connection with the execution and delivery of this Agreement (including the Warrant),
and the performance of its obligations hereunder have been obtained.

          13.1.3 Conflicts. The execution and delivery of this Agreement (including the Warrant) and
the performance of such Party’s obligations hereunder (a) do not conflict with or violate any
requirement of Applicable Law or any provision of the articles of incorporation, bylaws or any
similar instrument of such Party, as applicable, in any material way, and (b) do not conflict with,
violate, or breach or constitute a default or require any consent not already obtained under, any
contractual obligation or court or administrative order by which such Party is bound.

     Section 13.2 Isis Representations, Warranties, and Covenants. Isis hereby represents,
warrants, and covenants to Archemix as of the Effective Date as follows:

          13.2.1 IP Ownership. To the best of Isis’ knowledge, Isis has sufficient legal and/or
beneficial title and ownership of the Isis Patent Rights as is necessary to fulfill its obligations
under this Agreement and to grant the licenses (or sublicenses as the case may be) to Archemix
pursuant to this Agreement;

          13.2.2 Third Party Actions. To the best of Isis’ knowledge, no actions, suits, claims,
disputes, or proceedings concerning the Isis Patent Rights licensed hereunder are currently pending
or are threatened in writing, that if determined adversely to Isis would have a material adverse
effect on the Licensed Product or would impair Isis’ ability to perform its obligations under this
Agreement.

          13.2.3 Third Party Rights. To the best of Isis’ knowledge, except as disclosed in writing to
Archemix, Isis has not granted to any Third Party any right to use, license or otherwise exploit
the Isis Patent Rights in a manner which would conflict with the rights granted to Archemix under
Section 2.2.1.

          13.2.4 No Additional Royalties. To the best of Isis’ knowledge, Archemix will have no
obligation to make any royalty or other payment to any Third Party as a result of the grant by Isis
to Archemix of the licenses set forth in Section 2.1.1 or 2.2.1.

          13.2.5 No Judgments. To the best of Isis’ knowledge, there are no judgments, decrees or
orders of any court or administrative agency that affect the use by Archemix, as contemplated by
this Agreement, of the Isis Patent Rights licensed hereunder.

          13.2.6 Compliance with Third Party Licenses. To the best of Isis’ knowledge, Isis is in
compliance in all material respects with the material terms of all licenses and other agreements
with Third Parties under which it has the right to use any Isis Patent Rights, all such agreements
are in full force and effect, and no Third Party has given Isis written notice that an event has
occurred which with notice or lapse of time would constitute a breach or default or permit
termination, modification or acceleration under any such agreements.

          13.2.7 Isis Patent Rights. Appendix 2 (Isis Analytical Patents), Appendix 3 (Isis
Manufacturing Patents), and Appendix 4 (Isis Chemistry Patents) contain all Patents Controlled

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

15

 

by Isis that are believed, to the best of Isis’ knowledge, to be necessary to research,
develop and commercialize Licensed Products. To the extent a Patent Controlled by Isis as of the
Effective Date is inadvertently omitted from Appendix 2, Appendix 3, or Appendix 4, Isis agrees in
good faith to add such omitted Patent to the appropriate appendix.

     Section 13.3
Archemix Representations, Warranties, and Covenants.

     Archemix hereby represents, warrants, and covenants to Isis that:

          13.3.1 Capabilities. Archemix has the requisite personnel, expertise, experience and skill to
perform its obligations under this Agreement; and Archemix, its Affiliates, and its Archemix
Sublicensees will at all times comply with all Applicable Laws in connection with this Agreement;

          13.3.2 Capitalization. Archemix has, prior to or on the Effective Date, supplied to Isis a
table accurately showing the capitalization of Archemix as of the Effective Date, on a
fully-diluted basis. Such table will be deemed to be the Confidential Information of Archemix.
Except as set forth in such table, there are no outstanding shares of capital stock of Archemix or
warrants, options, agreements, convertible securities or other commitments pursuant to which
Archemix is or may become obligated to issue any shares of its capital stock or other securities.
Archemix understands and agrees that Isis is relying upon these representations and warranties when
accepting the issuance of the Warrant under Section 5.1 above.

     Section 13.4 DISCLAIMER OF WARRANTY. NEITHER PARTY WARRANTS THAT THE COLLABORATION WILL BE
SUCCESSFUL OR RESULT IN ANY LICENSED PRODUCTS. EXCEPT FOR THE EXPRESS WARRANTIES SET FORTH IN THIS
ARTICLE 13, ARCHEMIX AND ISIS MAKE NO REPRESENTATIONS AND GRANT NO WARRANTIES, EXPRESS OR IMPLIED,
EITHER IN FACT OR BY OPERATION OF LAW, BY STATUTE OR OTHERWISE, AND ARCHEMIX AND ISIS EACH
SPECIFICALLY DISCLAIM ANY OTHER WARRANTIES, WHETHER WRITTEN OR ORAL, OR EXPRESS OR IMPLIED,
INCLUDING ANY WARRANTY OF QUALITY, MERCHANTABILITY OR FITNESS FOR A PARTICULAR USE OR PURPOSE OR
ANY WARRANTY AS TO THE VALIDITY OF ANY PATENTS OR THE NON-INFRINGEMENT OF ANY INTELLECTUAL PROPERTY
RIGHTS OF THIRD PARTIES.

ARTICLE 14

MISCELLANEOUS

     Section 14.1 Assignment. Without the prior written consent of the other Party hereto, neither
Party will sell, transfer, assign, delegate, pledge or otherwise dispose of, this Agreement or any
of its rights or duties hereunder; provided, however, that (i) either Party hereto may assign or
transfer this Agreement or any of its rights or obligations hereunder without the consent of the
other Party to any Third Party successor in interest with which it has merged or consolidated, or
to which it has transferred all or substantially all of its assets or stock to which this Agreement
relates if in any such event the Third Party assignee or surviving entity assumes in writing all of

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

16

 

the assigning Party’s obligations under this Agreement or (ii) Isis may assign or transfer its
rights under Article 5 (but not liabilities) to a Third Party in connection with a royalty
factoring transaction. Any purported assignment or transfer in violation of this Section 14.1 will
be void ab initio and of no force or effect.

     Section 14.2 Severability. If any provision of this Agreement is held to be illegal, invalid
or unenforceable by a court of competent jurisdiction, such adjudication will not affect or impair,
in whole or in part, the validity, enforceability, or legality of any remaining portions of this
Agreement. All remaining portions will remain in full force and effect as if the original
Agreement had been executed without the invalidated, unenforceable or illegal part. The Parties
agree to use good faith, reasonable efforts to replace the illegal, invalid or unenforceable
provision with a legal, valid and enforceable provision that achieves similar economic and
non-economic effects as the severed provision.

     Section 14.3 Governing Law. This Agreement will be governed by and construed in accordance
with the laws of the State of New York, USA without reference to any rules of conflicts of laws.

     Section 14.4 Dispute Resolution.

          14.4.1 General. Any dispute, controversy or claim arising from or related to this Agreement
or the breach thereof will first be referred to the attention of the Chief Executive Officer of
Archemix and the Executive Vice President and CFO of Isis (the “Executive Officers”) by notice in
writing in accordance with the terms of this Agreement. The Executive Officers (or their
respective designees) will meet as soon as reasonably possible thereafter, and use their good faith
efforts to mutually agree upon the resolution of the dispute, controversy or claim. If any
dispute, controversy or claim is not resolved by the designated officers of the Parties (or their
designees) within [***] days after such dispute is referred to them, then the Parties agree that
such dispute will be referred to mediation, and if the dispute remains unresolved after mediation,
either Party will have the right to arbitrate such dispute in accordance with Section 14.4.3;
provided, however, that any dispute relating to the construction or validity of any Patent will not
be subject to arbitration.

          14.4.2 Mediation. If the Parties pursue mediation proceedings the Parties will attempt to
resolve such dispute in accordance with the Commercial Mediation Procedures of the American
Arbitration Association (“AAA”), before resorting to arbitration in accordance with Section 14.4.3
below. The mediation will be conducted by a single mediator experienced in the business and
technology that is the subject of this Agreement. The place of mediation will be in Denver,
Colorado. Either Party may apply to a court of competent jurisdiction for interim injunctive
relief until the mediation decision is rendered or the dispute, controversy or claim is otherwise
resolved.

          14.4.3 Arbitration. If the Parties do not fully settle any dispute, controversy or claim
pursuant to Section 14.4.1 or 14.4.2 and a Party wishes to pursue the matter further, each such
dispute, controversy or claim will be finally resolved by binding arbitration in accordance with
the Commercial Arbitration Rules of the AAA, and judgment on the arbitration award may

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

17

 

be entered in any court having jurisdiction thereof. The arbitration will be conducted by
three arbitrators, one chosen by each Party and the third chosen by the other two arbitrators. If
the two arbitrators selected by the Parties cannot agree upon an arbitrator, the arbitrator will be
appointed by the AAA. No individual will be appointed to arbitrate a dispute pursuant to this
Agreement unless he or she agrees in writing to be bound by the provisions of Section 14.4. The
place of arbitration will be Denver, Colorado. Either Party may apply to a court of competent
jurisdiction for interim injunctive relief until the arbitration award is rendered or the
controversy is otherwise resolved.

          14.4.4 Disputes Regarding Material Breach. If the Parties are in dispute as to whether one
party is in material breach of this Agreement, then the mediator or arbitrators will first
determine if material breach has in fact occurred, and if so, will grant the defaulting Party the
cure period provided pursuant to Section 10.1. If the material breach is not cured within the time
period provided pursuant to Section 10.1, the mediation or arbitration will continue and the
mediator or arbitrators will, as part of the same mediation or arbitration, award actual direct
damages to the non-defaulting Party.

          14.4.5 Costs and Expenses. Except as expressly provided herein, each Party will bear its own
costs and expenses and attorneys’ fees and an equal share of the mediator’s and/or arbitrators’ and
any administrative fees of mediation and arbitration. Notwithstanding the foregoing, in the case of
arbitration, if a Party has been found to be in material and willful breach of this Agreement, the
defaulting Party will be responsible for both Parties’ costs and expenses (including the costs of
the arbitrators and any administrative fees of arbitration) and the reasonable attorneys’ fees of
the non-defaulting Party; provided, however, that the total amount of such fees and expenses the
defaulting Party is required to reimburse the non-defaulting Party will not exceed the total amount
of monetary damages awarded to the non-defaulting Party as a result of such material breach.

          14.4.6 Procedure. Except to the extent necessary to confirm an award or as may be required by
Applicable Law, neither a Party, a mediator, nor an arbitrator may disclose the existence, content,
or results of a mediation or an arbitration without the prior written consent of both Parties. In
no event will an arbitration be initiated after the date when commencement of a legal or equitable
proceeding based on the dispute, controversy or claim would be barred by the applicable New York
statute of limitations.

          14.4.7 Speedy Resolution. The Parties intend, and will take all reasonable action as is
necessary or desirable to ensure, that there be a speedy resolution to any dispute which becomes
the subject of mediation or arbitration, and the mediator and arbitrators will conduct the
mediation or arbitration so as to resolve the dispute as expeditiously as possible.

          14.4.8 Awards. In any mediation, a decision or opinion issued by the mediator regarding the
dispute between the Parties is non-binding. The arbitrators may award monetary damages and
injunctive relief. Monetary damages may be in the form of off-set royalties or otherwise, to
account for the damages to the non-defaulting Party from the breach, and to account for the
defaulting Party’s contribution to the Licensed Product in view of the breach. All awards will be
in writing and will state reasons. Executed copies of all awards will be delivered

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

18

 

by the arbitrators to the Parties as soon as is reasonably possible. All awards of the
arbitrators will be final and binding on the Parties. The Parties undertake to satisfy any award
without delay.

     Section 14.5 Notices. All notices or other communications that are required or permitted
hereunder will be in writing and delivered personally with acknowledgement of receipt, sent by
facsimile (and promptly confirmed by personal delivery, registered or certified mail or overnight
courier as provided herein), sent by nationally-recognized overnight courier or sent by registered
or certified mail, postage prepaid, return receipt requested, addressed as follows:

     If to Archemix, to:

Archemix Corp.

300 Third Street

Cambridge, Massachusetts 02142

Attention: Legal Department

Telephone: (617) 617-621-7700

Facsimile: (617) 921-9300

with a copy to:

Mintz Levin PC

One Financial Center

Boston, MA 02111

Attention: John Cheney

Telephone: (617) 542-6000

Facsimile: (617) 542-2241

     If to Isis, to:

Isis Pharmaceuticals, Inc.

1896 Rutherford Road

Carlsbad, California 92008

Attention: Executive Vice President and CFO

Telephone: (760) 931-9200

Facsimile: (760) 603-4650

with a copy to:

Attention: General Counsel

Facsimile: (760) 268-4922

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

19

 

or to such other address as the Party to whom notice is to be given may have furnished to the other
Party in writing in accordance herewith. Any such communication will be deemed to have been given
(i) when delivered, if personally delivered or sent by facsimile on a Business Day, with
confirmation of receipt, (ii) on the Business Day after dispatch, if sent by nationally-recognized
overnight courier, and (iii) on the third Business Day following the date of mailing, if sent by
mail. It is understood and agreed that this Section 14.5 is not intended to govern the day-to-day
business communications necessary between the Parties in performing their duties, in due course,
under the terms of this Agreement.

     Section 14.6 Entire Agreement; Modifications. The Mutual Confidential Disclosure Agreement by
and between the Parties dated April 11, 2005 and amended as of September 15, 2006, and the Mutual
Confidential Disclosure Agreement by and between the Parties dated April 11, 2003 (collectively,
the “Prior CDAs”) are hereby terminated by the mutual consent of the Parties. As of the Effective
Date, all information disclosed under the Prior CDAs will be deemed to be Confidential Information
disclosed under this Agreement and subject to the terms hereof. Neither Party will thereby be
relieved of any liability accruing prior to the Effective Date under the Prior CDAs. This Agreement
sets forth and constitutes the entire agreement and understanding between the Parties with respect
to the subject matter hereof and all prior agreements, understanding, promises and representations,
whether written or oral, with respect thereto are superseded hereby. Each Party confirms that it
is not relying on any representations or warranties of the other Party except as specifically set
forth herein. No amendment, modification, release or discharge will be binding upon the Parties
unless in writing and duly executed by authorized representatives of both Parties.

     Section 14.7 Relationship of the Parties. The Parties hereto understand and agree that the
Collaboration is limited to the activities, rights and obligations as set forth in this Agreement.
Nothing in this Agreement will be construed (a) to create or imply a general partnership between
the Parties, (b) to make either Party the employee or agent of the other for any purpose, (c) to
alter, amend, supersede or vitiate any other arrangements between the Parties with respect to any
subject matters not covered hereunder, except for the Prior CDAs as expressly set forth in Section
14.6, (d) to give either Party the right to bind the other, (e) to create any duties or obligations
between the Parties except as expressly set forth herein, or (f) to grant any direct or implied
licenses or any other right other than as expressly set forth herein.

     Section 14.8 Waiver. Any term or condition of this Agreement may be waived at any time by the
Party that is entitled to the benefit thereof, but no such waiver will be effective unless set
forth in a written instrument duly executed by or on behalf of the Party waiving such term or
condition. Any such waiver will not be deemed a waiver of any other right or breach hereunder.

     Section 14.9 Counterparts. This Agreement may be executed in two (2) or more counterparts,
each of which will be deemed an original, but all of which together will constitute one and the
same instrument.

     Section 14.10 No Benefit to Third Parties. The representations, warranties, covenants and
agreements set forth in this Agreement are for the sole benefit of the Parties hereto and their

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

20

 

successors and permitted assigns, and they will not be construed as conferring any rights on
any other parties.

     Section 14.11 Further Assurance. Each Party will duly execute and deliver, or cause to be
duly executed and delivered, such further instruments and do and cause to be done such further acts
and things, including the filing of such assignments, agreements, documents and instruments, as may
be necessary to carry out the provisions and purposes of this Agreement.

     Section 14.12 Interpretation. Each Party has had the opportunity to consult with counsel in
connection with the review, drafting and negotiation of this Agreement. Accordingly, the rule of
construction that any ambiguity in this Agreement will be construed against the drafting party will
not apply. The captions to the several Articles and Sections hereof are not a part of this
Agreement, but are merely a convenience to assist in locating the several Articles and Sections
hereof. In this Agreement: (a) the word “including” and its variants will be deemed to be followed
by the phrase “without limitation”; (b) the singular will include the plural and vice versa; and
(c) masculine, feminine and neuter pronouns will be interchangeable.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed by their duly
authorized representatives as of the Effective Date.

	 	 	 	 	 	 	 	 	 	 	 
	Archemix Corp.	 	 	 	Isis Pharmaceuticals, Inc.	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	Per:

	 	/s/ Gregg Beloff
 

	 	 
	 	Per:
	 	/s/ Lynne Parshall
 

	 	 
	Gregg Beloff	 	 	 	B. Lynne Parshall	 	 
	Chief Financial Officer	 	 	 	Executive Vice President and CFO	 	 

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

22

 

APPENDIX
1

Definitions

     “Affiliate” of a Party means any other entity that, directly or indirectly, through one or
more intermediaries, controls, is controlled by, or is under common control with such first Party.
For purposes of this definition only, “control” and, with correlative meanings, the terms
“controlled by” and “under common control with” mean the possession, directly or indirectly, of the
power to direct the management or policies of an entity, whether through the ownership of voting
securities or by contract relating to voting rights or corporate governance.

     “Applicable Law” means the applicable laws, rules, and regulations, including any rules,
regulations, guidelines, or other requirements of the Regulatory Authorities that may be in effect
from time to time.

     “Aptamer” means an oligonucleotide that (i) specifically binds to a target protein, and (ii)
is covered by a claim within U.S. Patent [***] or, but for the expiration, earlier termination, or
decision of a court or other governmental agency of competent jurisdiction holding all claims
permanently revoked, unenforceable or invalid of U.S. Patent [***], would have been covered by a
claim within U.S. Patent [***].

     “Aptamer Product” means any product comprising an Aptamer.

     “Archemix-Marketed Licensed Product” means a Licensed Product that is manufactured (either by
Archemix or on its behalf) and marketed or sold solely by Archemix or any of its Affiliates in
accordance with this Agreement.

     “Archemix Sublicensee” or “Sublicensee” means a Third Party recipient of a Sublicense,
including any Legacy Licensee, but excluding sublicensed Archemix Affiliates.

     “ASO” means a [***] or [***] or [***], [***] or [***] having a [***] that is [***] and that
[***] via the [***], of such [***] to a [***].

     “Authorized Disclosure” means a disclosure of the other Party’s Confidential Information to
the extent that such disclosure is:

          (a) made in response to a valid order of a court of competent jurisdiction; provided, however,
that the Party subject to such order will first have given notice to the other Party and given the
other Party a reasonable opportunity to quash such order and to obtain a protective order requiring
that the Confidential Information and documents that are the subject of such order be held in
confidence by such court or agency or, if disclosed, be used only for the purposes for which the
order was issued; and provided, further, that if a disclosure order is not quashed or a protective
order is not

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

obtained, the Confidential Information disclosed in response to such court or governmental
order will be limited to that information which is legally required to be disclosed in response to
such court or governmental order;

          (b) otherwise required by law; provided, however, that the disclosing Party will provide the
other Party with notice of such disclosure in advance thereof to the extent practicable;

          (c) made by the disclosing Party to the Regulatory Authorities as necessary for the
development or commercialization of a Licensed Product in a country, as required in connection with
any filing, application or request for Regulatory Approval, to obtain Patents, or as required by
applicable securities laws and regulations; provided, however, that reasonable measures will be
taken to assure confidential treatment of such information;

          (d) made by the disclosing Party, to Affiliates, permitted sublicensees, licensors, directors,
officers, employees, consultants, representatives or agents, in connection with the performance of
this Agreement or otherwise for the licensing, development, manufacturing and/or marketing of
actual or potential Licensed Products (or for such parties to determine their interest in
performing such activities) in accordance with this Agreement on the condition that such Third
Parties agree to be bound by confidentiality and non-use obligations at least as protective as
those contained in this Agreement; or

          (e) made by the disclosing Party to existing or potential acquirers; existing or potential
pharmaceutical collaborators (to the extent contemplated hereunder); investment bankers; existing
or potential investors, merger candidates, partners, venture capital firms or other financial
institutions or investors for purposes of obtaining financing; or, bona fide strategic potential
partners; each of whom prior to disclosure must be bound by obligations of confidentiality and
non-use at least equivalent in scope to those set forth in this Agreement;

     “Business Day” means any day, other than Saturday, Sunday or any statutory holiday in the
United States.

     “Calendar Year” means each successive period of 12 months commencing on January 1 and ending
on December 31.

     “Commercially Reasonable Efforts” means with respect to any objective by an entity,
reasonable, diligent, good faith efforts to accomplish such objective as such entity (together with
its Affiliates as a group) would normally use in the ordinary course of business and research to
accomplish a similar objective under similar circumstances.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

     “Confidential Information” means all information and Know-How and any tangible embodiments
thereof provided by or on behalf of one Party to the other Party either in connection with the
discussions and negotiations pertaining to this Agreement or in the course of performing this
Agreement, which may include data; knowledge; practices; processes; ideas; research plans;
engineering designs and drawings; research data; manufacturing processes and techniques;
scientific, manufacturing, marketing and business plans; and financial and personnel matters
relating to the disclosing Party or to its present or future products, sales, suppliers, customers,
employees, investors or business.

     Exceptions. Notwithstanding the foregoing, information or know-how of a Party will not be
deemed Confidential Information of such Party for purposes of this Agreement if such information or
know-how:

          (a) was already known to the receiving Party, as evidenced by their written records, other
than under an obligation of confidentiality or non-use, at the time of disclosure to such receiving
Party;

          (b) was generally available or known to parties reasonably skilled in the field to which such
information or know-how pertains, or was otherwise part of the public domain, at the time of its
disclosure to such receiving Party;

          (c) became generally available or known to parties reasonably skilled in the field to which
such information or know-how pertains, or otherwise became part of the public domain, after its
disclosure to such receiving Party through no fault of the receiving Party;

          (d) was disclosed to such receiving Party, other than under an obligation of confidentiality
or non-use, by a Third Party who had no obligation to the disclosing Party not to disclose such
information or know-how to others; or

          (e) was independently discovered or developed by such receiving Party, as evidenced by their
written records, without the use of Confidential Information belonging to the disclosing Party and
prior to any subsequent disclosure by the receiving Party.

     “Control” means possession of the ability to grant a license or sublicense hereunder without
violating the terms of any agreement with any Third Party and without any compensation to such
Third Party; provided, however, that if a Party has a right to grant a license or sublicense, with
respect to an item of intellectual property to the other Party only upon payment of compensation
(including milestones or royalties) to a Third Party (“Third Party Reimbursement”), then the first
Party will be deemed to have “Control” of the relevant item only if the other Party agrees to bear
the cost of such Third Party Reimbursement.

     “Conversion Event” means the occurrence of any one of the following:

       1. [***] Initiation of a [***]l has occurred [***]; or

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

       2. The earlier to occur of (i) the date of expiration of all claims of U.S. Patent [***], and
(ii) the date all claims of U.S. Patent [***] have been donated to the public, disclaimed,
permanently revoked, or held invalid or unenforceable by a court or other governmental agency of
competent jurisdiction in an unappealed or unappealable decision.

     “Excluded Field” means the making, using, or selling of any product containing OSI
Pharmaceuticals, Inc.’s (successor in interest to Eyetech Pharmaceuticals, Inc.) [***] product (or
any product containing [***]) (also known as [***]), in each case (i) including any minor chemical
modifications to [***] and (ii) for the treatment of [***] conditions.

     “FDA” means the United States Food and Drug Administration and any successor agency thereto.

     “FTE” means [***] ([***]) hours of work per year (excluding vacations and holidays).

     “FTE Rate” means $[***] per Isis FTE; provided, however, that each year ([***]), the foregoing
FTE rate will be modified for such year by a factor that reflects the annual salary increase
multiplier approved by the Compensation Committee of Isis’ Board of Directors for Isis’ employees
for the applicable year.

     “GAAP” means generally accepted accounting principles of the United States, consistently
applied.

     “IND” means an investigational new drug application with the FDA for authorization to commence
human clinical trials, and its equivalent in other countries or regulatory jurisdictions.

     “Initiation of a Phase 1 Clinical Trial” means the first administration of a Licensed Product
to the first human for the initial clinical testing of a Licensed Product in humans (first-in-human
study).

     “Initiation of a Phase 2 Clinical Trial” means the first visit by the first human patient in a
Phase 2 Clinical Trial during which dosing of a Licensed Product occurs.

     “Initiation of a Pivotal Quality Clinical Trial” means the first visit by the first patient in
a Pivotal Quality Clinical Trial during which dosing of a Licensed Product occurs.

     “Isis Analytical Patents” means the Patents set forth on Appendix 2 to this Agreement.

     “Isis Chemistries” means any chemical compositions covered by one or more claims of the Isis
Chemistry Patents.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

     “Isis Chemistry Patents” means the Patents set forth on Appendix 4 to this Agreement.

     “Isis Manufacturing Patents” means the Patents set forth on Appendix 3 to this Agreement.

     “Isis Patent Rights” means the Isis Chemistry Patents, the Isis Manufacturing Patents, and the
Isis Analytical Patents.

     “Know-How” means technical information and materials, including without limitation,
technology, data, results, biological materials, assays, constructs, compounds, practices, methods,
knowledge, trade secrets, skill and experience, in each case disclosed by one Party to the other
Party hereunder.

     “Legacy Licensee” has the meaning set forth in Section 4.4.3.

     “Licensed Product” means an Aptamer Product (a) the sale, use, or manufacture of which is
covered by one or more Valid Claims within the Isis Patent Rights, and/or (b) that was discovered,
identified, or characterized using a method covered by one or more Valid Claims within the Isis
Patent Rights, and includes Archemix-Marketed Licensed Products.

     “Losses” has the meaning set forth in Section 12.1.

     “Major Market Country” means each of the United States, Japan, the United Kingdom, France, and
Germany.

     “NDA” means a New Drug Application filed with the FDA after completion of clinical trials to
obtain marketing approval for commercial product in the United States or equivalent application for
regulatory approval in other Major Market Countries.

   “Net Sales” means the gross invoiced price charged by Archemix, its Affiliates or any
Archemix Sublicensees, as appropriate, for the sale of a Licensed Product to a Third Party by
Archemix, its Affiliates or Archemix Sublicensees, as appropriate, less the following
deductions:

(i) Trade and quantity discounts actually granted;

(ii) Credits, allowances, rebates, and returns (including product recalls), to the extent
actually allowed and taken;

(iii) Transportation, insurance and postage charges, if prepaid by Archemix or its
Affiliates or Archemix Sublicensees and included on any such party’s bill or invoice as a
separate item;

(iv) The amount of any sales tax or other taxes assessed directly on the sale of such
Licensed Product which is not refunded; and

(v) Charge back payments or rebates granted to managed health care organizations or
federal, state and local governments, their agencies, purchasers

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

and reimbursers, including without limitation, with respect to any Net Sales in Japan, any
sales-based contribution for “Drug Induced Suffering” and any sales-based contribution for
“Contribution for Measure for Drug Safety,” in the amount determined by and payable to the
Pharmaceuticals and Medical Devices Agency (so-called “KIKO”).

For purposes of clarity, use of any Licensed Product in clinical trials, pre-clinical studies or
other research or development activities, or disposal or transfer of Licensed Products for a bona
fide charitable purpose or a commercially reasonable sampling program, will not give rise to any
Net Sales. The Parties agree that any reasonable definition of “Net Sales,” customarily used in
pharmaceutical industry technology licensing contracts, that is agreed to by Archemix and an
Archemix Sublicensee in an arms-length transaction under a particular Sublicense will be used in
calculating the royalty payment to Isis on sales of Licensed Products sold pursuant to such
Sublicense.

     “Patents” includes (a) all U.S. patents and patent applications, (b) any substitutions,
divisions, continuations, continuations-in-part, reissues, renewals, registrations, confirmations,
re-examinations, extensions, supplementary protection certificates and the like, and any
provisional applications, of any such patents or patent applications, and (c) any foreign or
international equivalent of any of the foregoing.

     “Permitted License” means a license granted by Isis during the term of this Agreement to any
manufacturer for the manufacture, sale, and export of drug compounds, research reagents, or raw
materials, including the manufacture of oligonucleotides, oligonucleotide research reagents, or
oligonucleotide raw materials for the manufacture, sale, and export of drug compounds, research
reagents, or raw materials, including the manufacture, sale, and export of oligonucleotides,
oligonucleotide research reagents, or oligonucleotide raw materials.

     “Phase 1 Clinical Trial” means the initial clinical testing of a Licensed Product in humans
(first-in-human study).

     “Phase 2 Clinical Trial” means a Phase 2a Clinical Trial or a Phase 2b Clinical Trial.

     “Phase 2a Clinical Trial” means a controlled clinical trial of a Licensed Product that
utilizes the pharmacokinetic and pharmacodynamic information obtained from one (1) or more
previously conducted Phase 1 Clinical Trial(s) and/or other Phase 2a Clinical Trial(s) in order to
confirm the optimal manner of use of such Licensed Product (dose and dose regimens) and to better
determine safety and efficacy.

     “Phase 2b Clinical Trial” means a clinical trial of a Licensed Product on sufficient numbers
of patients that is designed to provide a preliminary determination of safety and efficacy of such
Licensed Product in the target patient population over a range of doses and dose regimens.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

     “Pivotal Quality Clinical Trial” means a human clinical trial of a Licensed Product designed
to be of a [***] to support [***] or [***] with other studies. If it is unclear whether or not a
study design will be sufficient to support [***] (other than by virtue of the uncertainty of safety
and efficacy data from that trial) the study will be deemed to be a Pivotal Quality Clinical Trial
on the initiation of activities to support an NDA filing. A [***] clinical study will be deemed to
be a Pivotal Quality Clinical Trial.

     “Regulatory Approval” means (a) in the United States, approval by the FDA of an NDA, or
similar application for marketing approval, and satisfaction of any related applicable FDA
registration and notification requirements (if any), and (b) in a market other than the United
States, approval by regulatory authorities having jurisdiction over such country of a single
application or set of applications comparable to an NDA, and satisfaction of any related applicable
regulatory and notification requirements (if any).

     “Regulatory Authority” means any applicable government entities regulating or otherwise
exercising authority with respect to the development and commercialization of a Licensed Product.

     “Royalty Due Dates” means March 31, June 30, September 30 and December 31 of each and every
year during which this Agreement remains in full force and effect.

     “Sublicense” means a sublicense from Archemix to a Third Party (including any Archemix
Sublicensee) under the Isis Chemistry Patents and/or Isis’s Know-How, in accordance with the terms
and conditions of this Agreement. A series of Sublicenses to the same Archemix Sublicensee or
related Archemix Sublicensees will be aggregated to constitute a single Sublicense.

     “Sublicense Revenue” means [***] cash consideration and non-cash consideration that Archemix
receives from an Archemix Sublicensee on or following the date of the Sublicense in consideration
of the grant of any Sublicense, including, but not limited to, license fees, up-front payments,
milestone payments, and license maintenance fees, but excluding: (i) [***] of Licensed Products,
(ii) payments made in consideration of [***] of Archemix at [***], and (iii) payments specifically
committed to reimburse Archemix for the direct cost of research and development for Licensed
Products. If Archemix receives any non-cash Sublicense Revenue, Archemix will pay Isis, at
Archemix’s election, either (x) a [***] equal to the [***] of such Sublicense Revenue or (y) the
[***], of such Sublicense Revenue. The [***] of [***] relating to [***] in a [***] company will be
determined by the valuation of such company’s [***]. For purposes of calculating Sublicense
Revenue, a series of Sublicenses to the same Archemix Sublicensee or related Archemix Sublicensees
will be aggregated to constitute a single Sublicense.

     “Target” means a protein, cytokine, enzyme, receptor, transducer, transcription factor,
antigen or any other non-nucleic acid molecule.

     “Term” has the meaning set forth in Section 9.1.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

     “Third Party” means any party other than Isis or Archemix or their respective Affiliates.

     “Valid Claim” means a claim of a Patent which (i) in the case of any granted, unexpired United
States Patent or foreign Patent, will not have been donated to the public, disclaimed or held
invalid or unenforceable by a court of competent jurisdiction in an unappealed or unappealable
decision, or (ii) in the case of any United States or foreign patent application, is being
prosecuted in good faith and will not have been permanently cancelled, withdrawn, or abandoned,
provided that (x) no more than [***] years have passed since the earliest date of filing for such
application in the United States (unless and until such claim is granted), and (y) no more than
[***] years have passed since the earliest date of filing for such application outside of the
United States (unless and until such claim is granted).

     “Withholding Taxes” has the meaning set forth in Section 5.8.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

APPENDIX 2

ISIS ANALYTICAL PATENTS

	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]

APPENDIX 3

ISIS MANUFACTURING PATENTS

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Patent/	 	 	 	 
	Technology	 	Docket #	 	Country/Treaty	 	Application #	 	Title	 	Filing Date
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	 	 	 	 	 	 	Patent/	 	 	 	 
	Technology	 	Docket #	 	Country/Treaty	 	Application #	 	Title	 	Filing Date
	[***]

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Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	 	 	Patent/	 	 	 	 
	Technology	 	Docket #	 	Country/Treaty	 	Application #	 	Title	 	Filing Date
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	Technology	 	Docket #	 	Country/Treaty	 	Application #	 	Title	 	Filing Date
	 

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	Technology	 	Docket #	 	Country/Treaty	 	Application #	 	Title	 	Filing Date
	 

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Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

APPENDIX 4

ISIS CHEMISTRY PATENTS

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	 [***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	 [***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	 [***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
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	 	[***]
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	 	[***]
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the
Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
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	 	[***]
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	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
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	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 
	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	[***]

	 	[***]
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	[***]

	 	[***]
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	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	Docket	 	 	 	 	 	Serial	 	Filing	 	Patent	 	Grant	 	 
	Number	 	Country	 	Status	 	Number	 	Date	 	Number	 	Date	 	Title
	[***]

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	[***]

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	[***]

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	[***]

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	[***]

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	[***]

	 	[***]
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	[***]

	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]
	 	[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the
Commission pursuant to the Company’s application requesting confidential treatment under Rule 406
of the Securities Act.

 

 

APPENDIX 5

Warrant

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the
Commission pursuant to the Company’s application requesting confidential treatment under Rule 406
of the Securities Act.exv10w46

Exhibit 10.46

Execution
Copy

EXCLUSIVE LICENSE AGREEMENT

     This Exclusive License Agreement (this “Agreement”) is made effective as of July 31,
2007 (the “Effective Date”), by and between Archemix Corp, a Delaware corporation with
offices at 300 Third Street, Cambridge, MA 02142 (“Archemix”), and Ophthotech Corporation,
a Delaware corporation with offices at c/o SV Life Sciences, 60 State Street, Suite 3650, Boston,
MA 02109 (“Ophthotech”). Archemix and Ophthotech are each hereinafter referred to
individually as a “Party” and together as the “Parties.”

     WHEREAS, Archemix is the owner of or otherwise controls, certain patents and proprietary
technology;

     WHEREAS, Ophthotech desires to obtain an exclusive license from Archemix under such patents
and technology to develop and commercialize certain products; and

     WHEREAS, Archemix desires to grant such license to Ophthotech on the terms and subject to the
conditions of this Agreement.

     NOW, THEREFORE, in consideration of the mutual covenants contained herein, and for other good
and valuable consideration, the receipt and adequacy of which are hereby acknowledged, the Parties
hereby agree as follows:

ARTICLE 1 DEFINITIONS

     Whenever used in the Agreement with an initial capital letter, the terms defined in this
Article 1 shall have the meanings specified.

     1.1 “Adverse Event” means any untoward, undesired or unplanned medical
occurrence in a human clinical trial subject or a patient, which occurrence has a temporal
relationship to administration of a Licensed Product, whether or not considered related to the
Licensed Product, including, without limitation, any undesirable sign (including abnormal
laboratory findings of clinical concern), symptom or disease that may be associated with the use of
such Licensed Product.

     1.2 “Acceptance” means, with respect to an IND, [***] days from the date such IND is
received by the FDA, if no clinical hold is issued by the FDA with respect thereto or, to the
extent issued, such later date on which such IND is no longer subject to that clinical hold.

     1.3 “Affiliate” means, with respect to any Person, any other Person that, directly or
indirectly, controls or is controlled by or is under common control with, such Person. For
purposes of this definition, “control” means (a) ownership of fifty percent (50%) or more of the
shares of stock entitled to vote for the election of directors in the case of a corporation or
fifty percent (50%) or more of the equity interests in the case of any other type of legal entity,
(b) status as a general partner in any partnership, or (c) any other arrangement whereby a Person
controls or has the right to control the board of directors of a corporation or equivalent
governing body of an entity other than a corporation.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

 

 

     1.4 “AMD” means age-related macular degeneration and includes the following separate
Indications: wet AMD and dry AMD.

     1.5 “Annual Net Sales” means, with respect to any Calendar Year, the aggregate amount
of the Net Sales for such Calendar Year.

     1.6 “Anti-C5 Aptamer” means an Aptamer that binds to C5 provided by Archemix to, or
identified in the Anti-C5 Aptamer-Specific Patent Rights licensed to, Ophthotech under this
Agreement, including without limitation any Aptamer that binds to C5 as set out in the issued
patents and pending patent applications listed in Exhibit A, and any Aptamer(s) Derived
therefrom.

     1.7 “Anti-C5 Aptamer-Specific Patent Rights” means any Licensed Patent Rights that
specifically claim ARC186, ARC1905 and/or any other Aptamer that binds to C5 or the manufacture,
use, offer for sale, sale or importation thereof in the Field.

     1.8 “Applicable Laws” means federal, state, local, national and supra-national laws,
statutes, rules and regulations, including any rules, regulations guidance, guidelines or
requirements of regulatory authorities, national securities exchanges or securities listing
organizations, that may be in effect from time to time during the Term and are applicable to a
particular activity hereunder.

     1.9 “Aptamer” means (a) any naturally or non-naturally occurring oligonucleotide
identified through the SELEX Process that binds with high specificity and affinity to a Target, and
(b) any oligonucleotide Derived from an oligonucleotide of clause (a) that has such high
specificity and affinity to a Target.

     1.10 “ARC186” means an unpegylated Anti-C5 Aptamer having the chemical composition set
forth in Schedule 2 attached hereto.

     1.11 “ARC1905” means a pegylated Anti-C5 Aptamer having the chemical composition set
forth in Schedule 1 attached hereto.

     1.12 “Archemix Collaborative Partner” means any Third Party with whom Archemix is
engaged, from time to time, in a collaborative effort to research, develop or commercialize
Aptamers, which collaborative effort is evidenced by a written agreement. For purposes of clarity,
as used in this definition, a “collaborative effort” includes, without limitation, out-licensing of
products developed by Archemix or its Affiliates.

     1.13 “Archemix-Gilead License Agreement” means the License Agreement between Gilead
Sciences, Inc. and Archemix dated October 21, 2001, as amended.

     1.14 “C5” means complement factor C5.

     1.15 “Calendar Quarter” means the period beginning on the Effective Date and ending on
the last day of the calendar quarter in which the Effective Date falls, and thereafter each
successive period of three (3) consecutive calendar months ending on March 31, June 30,

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

2

 

September 30 or December 31.

     1.16 “Calendar Year” means the period beginning on the Effective Date and ending on
December 31 of the year in which the Effective Date falls and thereafter each successive period of
twelve (12) months commencing on January 1 and ending on December 31.

     1.17 “Challenge” means any challenge to the validity or enforceability of any Licensed
Patent Right, in the absence of a breach of this Agreement by Ophthotech, including, without
limitation, by (a) filing a declaratory judgment action in which any Licensed Patent Right is
alleged to be invalid or unenforceable; (b) citing prior art pursuant to [***], filing a request
for re-examination of any Licensed Patent Right pursuant to [***] and/or [***] or provoking or
becoming party to an interference with an application for any Licensed Patent Right pursuant to
[***]; or (c) filing or commencing any reexamination, opposition, cancellation, nullity or similar
proceedings against any Licensed Patent Right in any country.

     1.18 “Commercially Reasonable Efforts” means, with respect to activities of Ophthotech
under this Agreement, the efforts and resources customarily used by similarly sized biotechnology
companies in the performance of such activities for other products owned by such companies which
are of similar market potential and at a similar stage of development, taking into account the
competitiveness of the market place, the regulatory structure involved and other relevant and
material factors.

     1.19 “Complement Cascade” means the following plasma proteins which are part of a
cascade of reactions by which pathogen recognition is converted into an effective host defense
against initial infection: [***].

     1.20 “Completion” means, with respect to a clinical trial, the closing of the database
with respect to that applicable clinical trial.

     1.21 “Confidential Information” means all information and Technology disclosed or
provided by, or on behalf of a Party (the “Disclosing Party”) to the other Party (the
“Receiving Party”) or to any of the Receiving Party’s employees, consultants, Affiliates or
sublicensees pursuant to or in connection with this Agreement; provided, that, none
of the foregoing shall be Confidential Information if: (a) as of the date of disclosure, it is
known to the Receiving Party or its Affiliates, as demonstrated by credible written documentation,
other than by virtue of a prior confidential disclosure to such Receiving Party; (b) as of the date
of disclosure it is in the public domain or it subsequently enters the public domain other than
through a breach by the Receiving Party or its Affiliates of a contractual obligation; (c) it is
obtained by the Receiving Party from a Third Party having a lawful right to make such disclosure
free from any obligation of confidentiality to the Disclosing Party or its Affiliates; or (d) it is
independently developed by or for the Receiving Party or its Affiliates without reference to or use
of any Confidential Information of the Disclosing Party or its Affiliates as demonstrated by
credible written documentation. For purposes of clarity, unless excluded from Confidential
Information pursuant to the provisos of the preceding sentence, any scientific, technical or
financial information Controlled by a Disclosing Party and disclosed at any meeting of the Parties
or disclosed through an audit report shall constitute Confidential Information of the Disclosing
Party.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

3

 

     1.22 “Control” or “Controlled” means with respect to Technology or Patent
Rights, the possession by a Party of the right to grant a license or sublicense to such Technology
or Patent Rights as provided herein solely to the extent that such grant does not (a) violate the
terms of any agreement or arrangement with any Third Party or (b) violate any Applicable Laws.
Notwithstanding the foregoing, with respect to Technology or Patent Rights licensed by Archemix
from a Third Party after the Effective Date (i.e., with respect to Technology or Patent Rights that
are not Licensed Technology or Licensed Patent Rights as of the Effective Date), where the grant of
a license or sublicense to Ophthotech to such Technology or Patent Rights as provided herein would
require a payment of additional consideration by Archemix to such Third Party licensor, Control by
Archemix shall be deemed to exist only if Ophthotech agrees to reimburse Archemix for such
additional payment of consideration.

     1.23 “Derived” means identified, obtained, developed, created, synthesized, designed
or resulting from, based upon, containing or incorporating or generated from or conjugated to or
complexed with (whether directly or indirectly or in whole or in part).

     1.24 “Development” and “Develop” means, with respect to any Licensed Product,
all activities with respect to such Licensed Product relating to research and development in
connection with seeking, obtaining and/or maintaining any regulatory approval (including without
limitation any Regulatory Approval) for such Licensed Product in the Field in the Territory,
including, without limitation, all pre-clinical research and development activities, all human
clinical studies, all activities relating to developing the ability to manufacture any Licensed
Product or any component thereof (including, without limitation, process development work), and all
other activities relating to seeking, obtaining and/or maintaining any regulatory approvals for
Licensed Products (including without limitation any Regulatory Approvals) from the FDA and/or any
Foreign Regulatory Authority.

     1.25 “Diagnosis” means (a) the determination or monitoring of (i) the presence or
absence of a disease, (ii) the stage, progression or severity of a disease or (iii) the effect on a
disease of a particular treatment; and/or (b) the selection of patients for a particular treatment
with respect to a disease.

     1.26 “Diagnostics” means In Vitro Diagnostics, In Vivo Diagnostics and any Aptamer
product used for Diagnosis.

     1.27 “Field” means the prevention, treatment, cure or control of all Indications of
the eye, adnexa of the eye, orbit and optic nerve, but excluding Diagnostics.

     1.28 “First Commercial Sale” means, on a country-by-country basis, the date of the
first arm’s length transaction, transfer or disposition for value to a Third Party of a Licensed
Product by or on behalf of, Ophthotech, its Affiliate or Sublicensee in such country. For purposes
of clarity, the use of any Licensed Product in clinical trials, pre-clinical studies or other
research or development activities or the disposal or transfer of a Licensed Product for a bona
fide charitable purpose or for purposes of a commercially reasonable sampling program shall not be
deemed to be an arm’s length transaction, transfer or disposition for value for purposes of this
definition.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

4

 

     1.29 “FDA” means the United States Food and Drug Administration and any successor
agency or authority thereto.

     1.30 “Foreign Regulatory Authorities” means any applicable supranational, national,
federal, state or local regulatory agency, department, bureau or other governmental entity of any
country or jurisdiction in the Territory (other than the FDA in the United States), having
responsibility in such country or jurisdiction for any Regulatory Approvals of any kind in such
country or jurisdiction, and any successor agency or authority thereto.

     1.31 “FTE” means [***] hours of work devoted to, or in support of, the Archemix
technology transfer activities performed pursuant to Section 3.5.4 hereof carried out by one or
more appropriately trained employees of Archemix, measured in accordance with Archemix’s time
allocation practices from time to time.

     1.32 “FTE Costs” means the sum of [***] Dollars ($[***]) multiplied by the number of
FTEs in such period.

     1.33 “IND” means an investigational new drug application (as defined in Title 21 of
the United States Code of Federal Regulations, as amended from time to time) filed or to be filed
with the FDA with regard to any Licensed Product.

     1.34 “Indication” means any human indication, disease, disorder or condition in the
Field, which can be treated, controlled, prevented, cured or the progression of which can be
delayed. For purposes of clarity, whether any such indication, disease, disorder or condition
constitutes a separate Indication shall be determined by reference to the applicable ICD-9 codes,
with each separate code constituting a separate Indication; provided, that, with
respect to AMD, wet AMD and dry AMD, and only wet AMD and dry AMD, shall constitute separate
Indications. “ICD-9” means the World Health Organization International Classification of Diseases,
version 9, and excludes any other versions of the ICD.

     1.35 “In Vitro Diagnostics” means the use of the SELEX Process or Aptamers in the
assay, testing or determination, outside of a living organism, of a substance in a test material.
In Vitro Diagnostics shall include, among other things, the use of the SELEX Process or Aptamers in
the assay, testing or determination: (a) outside of a living organism, (i) of a human substance in
a test material, often to identify or follow the progression of a disease or disorder or to select
a patient for treatment; (ii) of a plant substance, animal substance or other substance in a test
material, often to identify or follow the progression of a disease, process or disorder in a human
or non-human organism; and (iii) of environmental substances (as in water quality testing); (b) of
a substance on a test material such as cells (as in FACS analysis or other measurements of
pathogens within biological samples); and (c) any other in vitro diagnostic use of the SELEX
Process or Aptamers in drug development processes, including target identification, pre-clinical
and clinical testing, and the following more specific examples of uses of Aptamer technology: (i)
to observe, through protein profiling, protein levels moving up or down in diseases or models of
diseases, and to evaluate whether such proteins are sensible targets for the development of
therapeutic agents; (ii) to observe coordinated expression of protein pathways in a variety of
biological states in various systems; (iii) to study protein or metabolite levels during
pre-clinical

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

5

 

drug candidate evaluation in response to putative therapeutic agents during clinical trials
(e.g., as markers of efficacy or response); and (iv) to study human protein or metabolite levels in
response to putative therapeutic agents during clinical trials (e.g., as markers of efficacy or
response). Notwithstanding the above, In Vitro Diagnostics shall exclude any of the
above-described uses in this Section 1.34 conducted in the Development of Anti-C5 Aptamers under
this Agreement.

     1.36 “In Vivo Diagnostics” means the use of any product containing one or more
Aptamers for any human in vivo diagnostic purpose related to (inter alia) the identification,
quantification or monitoring of the propensity toward or actual existence of, any disease state.

     1.37 “Knowledge” means, with respect to Archemix, the actual knowledge of the chief
executive officer, any vice president or the chief legal officer of Archemix.

     1.38 “Legal Exclusivity Period” means, with respect to a Licensed Product and a
country in the Territory, the period (a) beginning on the earlier of the commencement of the
Patent-Based Exclusivity Period or of the Non Patent-Based Exclusivity Period and (b) expiring on
the later of the expiration of the Patent-Based Exclusivity Period or the Non Patent-Based
Exclusivity Period.

     1.39 “Licensed Patent Rights” means all Patent Rights Controlled by Archemix or any of
its Affiliates during the Term that cover or claim Licensed Products in the Field, including
without limitation the Development, manufacture, use, offer for sale, sale or importation thereof.
For purposes of clarity, the Licensed Patent Rights, as of the Effective Date, include without
limitation the Patent Rights listed on Exhibit A attached hereto.

     1.40 “Licensed Product” means any pharmaceutical product comprised of or Derived from,
in whole or in part, ARC1905, ARC186 and/or any other Anti-C5 Aptamer.

     1.41 “Licensed Technology” means any Technology Controlled by Archemix or any of its
Affiliates during the Term that is necessary or useful for the Development, manufacture, use, offer
for sale, sale or importation of Licensed Products in the Field.

     1.42 "Material EU Country” means each of the United Kingdom, Germany, France, Italy
and Spain.

     1.43 “Net Sales” means the gross amount billed or invoiced by Ophthotech or any of its
Affiliates or Sublicensees to Third Parties throughout the Territory for sales or other
dispositions or transfers for value of Licensed Products less (i) allowances for normal and
customary trade, quantity and cash discounts actually allowed and taken, and inventory management
fees paid to wholesalers and distributors, (ii) transportation, insurance and postage charges, if
paid by Ophthotech or any Affiliate or Sublicensee and included on any such Third Party’s bill or
invoice as a separate item, (iii) credits, chargebacks, retroactive price reductions, rebates and
returns, to the extent actually allowed, (iv) negotiated payments made to private sector and
government Third Party payors (e.g., PBMs, HMOs and PPOs) and purchasers/providers (e.g., staff
model HMOs, hospitals and clinics), regardless of the payment

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

6

 

mechanism, including without limitation off-invoice, rebate, chargeback and credit mechanisms,
(v) discounts paid under discount prescription drug programs and reductions for coupon and voucher
programs; (vi) any tax, tariff, customs duty, excise or other duty or other governmental charge
(other than a tax on income) levied on the sale, transportation or delivery of Licensed Product and
actually paid by Ophthotech or any of its Affiliates or Sublicensees; and (vii) portions of gross
amounts billed or invoiced that are written off as uncollectible, not to exceed [***] percent
([***]%) of Annual Net Sales in any Calendar Year. In addition, Net Sales are subject to the
following:

          (a) If Ophthotech or any of its Affiliates or Sublicensees effects a sale, disposition or
transfer of a Licensed Product to a customer in a particular country as part of a package of
Licensed Products and services (but not in a Combination Product), the Net Sales of such Licensed
Product to such customer shall be deemed to be “the fair market value” of such Licensed Product
less applicable discounts pursuant to this definition of Net Sales. For purposes of this
subsection (a), “fair market value” shall mean the fraction (A/A+B), where A equals the value that
would have been derived had such Licensed Product been sold as a separate Licensed Product to
another customer in the country concerned on customary commercial terms and B equals the aggregate
value that would have been derived had the other components of such package been sold as separate
products to another customer in the country concerned on customary commercial terms.

          (b) In the case of pharmacy incentive programs, hospital performance incentive program
chargebacks, disease management programs, similar programs or discounts on “bundles” of Licensed
Products, all discounts and the like shall be allocated among Licensed Products on the basis of
which such discounts and the like were actually granted or, if such basis cannot be determined, in
proportion to the respective list prices of such Licensed Products.

          (c) For purposes of clarity, use of any Licensed Product in clinical trials, pre-clinical
studies or other research or development activities or disposal or transfer of Licensed Products
for a bona fide charitable purpose or purposes of a commercially reasonable sampling program shall
not give rise to any Net Sales.

          (d) Sales or transfers of Licensed Product among Ophthotech, its Affiliates and Sublicensees
for the purpose of subsequent resale to Third Parties shall not be included in Net Sales; with
respect to such sales or transfers, the gross amounts billed or invoiced in connection with the
subsequent resale to Third Parties will be included in the calculation of Net Sales.

     In the event that a Licensed Product under this Agreement is sold in combination
(“Combination Product”) with another ingredient or component having independent,
supplementary or enabling therapeutic effect (e.g., as a catalyst or adjuvant) or diagnostic
utility or that has independent function as a medical device or means of administration (a
“Supplemental Component”), then “Net Sales,” for purposes of determining royalty payments
on the Combination Product, shall be calculated using one of the following methods:

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

7

 

          (y) By multiplying the Net Sales of the Combination Product (calculated prior to the
application of this formula) by the fraction C/C+D, where C is the average gross selling price,
during the applicable Calendar Quarter in the country concerned, of the Licensed Product when sold
separately, and D is the average gross selling price, during the applicable Calendar Quarter in the
country concerned, of the Supplemental Component(s) when sold separately; or

          (z) In the event that no such separate sales are made of the Licensed Product or any of
Supplemental Components in such Combination Product during the applicable Calendar Quarter in the
country concerned, Net Sales, for the purposes of determining royalty payments shall be calculated
using the above formula where C is the reasonably estimated commercial value of the Licensed
Product sold separately and D is the reasonably estimated commercial value of the Supplemental
Components sold separately. Any such estimates shall be determined using criteria to be mutually
agreed upon by the Parties. Such estimates shall be reported to Archemix in the reports to be
provided pursuant to Section 4.5.1 hereof. If the Parties are unable to agree on the criteria for
determining such estimates, either Party may submit such dispute for resolution pursuant to the
provisions of Section 10.2.2 (Accelerated Arbitration).

     1.44
“Non Patent-Based Exclusivity Period” means, with respect to a Licensed Product
in a country in the Territory, that period of time during which no Third Party has been granted the
legal right by the FDA or any Foreign Regulatory Authority, as applicable, in such country to
market and sell the Licensed Product in such country.

     1.45 “Non-Royalty Term” means, with respect to each Licensed Product, the period
commencing on the Effective Date and continuing on a product-by-product, and country-by-country
basis until the date on which no further payments of Sublicense Income are received by Ophthotech.

     1.46 “Patent-Based Exclusivity Period” means, with respect to a Licensed Product and
a country in the Territory, that period of time during which at least one Valid Claim of the
Licensed Patent Rights covers the Licensed Product.

     1.47 “Patent Rights” means all rights and interests in and to issued patents and
pending patent applications including, without limitation, provisional and non-provisional patent
applications, and all divisions, continuations and continuations-in-part thereof, patents issuing
on any of the foregoing, all reissues, reexaminations, renewals and extensions thereof, and
supplementary protection certificates therefor, as well as any certificates of invention or
applications therefor, and all foreign equivalents of any of the foregoing.

     1.48
“Permitted Activities” means any activity conducted by or on behalf of Archemix
or any Third Party licensee or sublicensee of Archemix with respect to (a) applications of aptamers
that bind to C5 (including Anti-C5 Aptamers) outside of the Field and/or (b) the use of aptamers
that bind to C5 (including Anti-C5 Aptamers) against Targets (including C5) outside of the Field.

     1.49 “Person” means an individual, sole proprietorship, partnership, limited
partnership, limited liability partnership, corporation, limited liability company, business trust,

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

8

 

joint stock company, trust, incorporated association, joint venture or similar entity or
organization, including a government or political subdivision, department or agency of a
government.

     1.50 “Phase I Clinical Trial” means a clinical trial conducted in healthy humans or in
patients with a particular disease or condition, which clinical trial is designed to initially
explore the safety, drug-drug interactions and/or pharmacokinetics of an investigational drug given
its intended use, and to support continued testing of such drug in Phase II Clinical Trials. For
purposes of clarity, a Phase I Clinical Trial may also initially explore efficacy if a safety
endpoint for such trial coincides with an initial indication of efficacy.

     1.51 “Phase II Clinical Trial” means a clinical trial conducted in patients with a
particular disease or condition, which clinical trial is designed to establish the safety,
appropriate dosage and pharmacological activity of an investigational drug given its intended use,
and to initially explore its efficacy for such disease or condition.

     1.52 “Phase III Clinical Trial” means a pivotal clinical trial conducted in patients
with a particular disease or condition, which clinical trial is designed to ascertain efficacy and
safety of an investigational drug for its intended use and to define warnings, precautions and
Adverse Events that are associated with the investigational drug in the dosage range intended to be
prescribed, with the purpose of preparing and submitting applications for Regulatory Approval or
label expansion to the FDA in the United States or pertinent Foreign Regulatory Authority in a
country outside the United States.

     1.53 “Regulatory Approval” means any and all approvals (including pricing and
reimbursement approvals), product and establishment licenses, registrations or authorizations of
any kind of the FDA or any Foreign Regulatory Authority necessary for the marketing and commercial
sale of a Licensed Product (or any component thereof) for use in the Field in any country or other
jurisdiction in the Territory.

     1.54 “Royalty Term” means, with respect to each Licensed Product, the period
commencing on the Effective Date and continuing on a product-by-product, and country-by-country
basis until the later of (a) the last to expire Valid Claim covering the Licensed Product in such
country or (b) twelve (12) years from the date of First Commercial Sale of such Licensed Product in
such country.

     1.55 “SELEX Portfolio” means those Patent Rights licensed by Gilead to Archemix
pursuant to the Archemix-Gilead License Agreement.

     1.56 “SELEX Process” means any means used for the identification or generation of a
nucleic acid that binds to a Target by means other than Watson-Crick base-pairing, including,
without limitation, any process that (a) is covered by the SELEX Portfolio, including, without
limitation, U.S. Patent Nos. [***] or [***], (b) is covered by any other Patent Rights Controlled
by Archemix, or (c) is covered by any continuation, divisional, continuation-in-part, substitution,
renewal, reissue, re-examination or extension, or any foreign equivalent of, the foregoing Patent
Rights.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

9

 

     1.57 “SELEX Technology” means any process for modifying, optimizing and/or stabilizing
an Aptamer, wherein such modification, optimization or stabilization includes, without limitation,
minimization, truncation, conjugation, pegylation, complexation, substitution, deletion and/or
incorporation of modified nucleotides.

     1.58 “Serious Adverse Event” means an Adverse Event occurring at any dose that (a)
results in death, (b) is life-threatening, (c) requires inpatient hospitalization or prolongation
of an existing hospitalization, (d) results in a persistent or significant disability or incapacity
or (e) results in a congenital anomaly or birth defect. Additionally, important medical events
that are not described in the immediately preceding sentence shall be considered Serious Adverse
Events when, based upon appropriate medical judgment, they may jeopardize the patient or subject
and may require medical or surgical intervention to prevent one of the outcomes listed in the
immediately preceding sentence.

     1.59 “Sublicensee” means any Third Party to whom Ophthotech grants a sublicense of
some or all of the rights granted to Ophthotech under this Agreement.

     1.60 "Sublicense Income” means [***] payments received by Ophthotech or its Affiliates
from its Sublicensees in connection with sublicenses granted hereunder excluding (a) payments [***]
a Sublicensee to [***] or [***] to be [***] by such Ophthotech or its Affiliates [***] to a [***]
for [***] which has been agreed to with the Sublicensee and based on full-time equivalent or other
cost-accounting methodologies that are consistent with then current industry practices, (b)
payments [***] of the [***] of Ophthotech to the extent that the [***] for [***] does not [***] the
then [***] thereof, as [***] of Ophthotech; provided, that, if requested by
Archemix, Ophthotech shall [***] Archemix with [***] for any [***] and any [***] any [***] may be
submitted by either Party to arbitration pursuant to Section 10.2.2, and (c) [***] to Ophthotech by
such Sublicensee on [***] (or, in the case of a [***] with a Sublicensee, [***] to Ophthotech by
such Sublicensee) pursuant to the applicable sublicense agreement.

     1.61 “Sustained Drug Delivery Product” means any Licensed Product comprising or
incorporating Sustained Drug Delivery Technology.

     1.62 “Sustained Drug Delivery Technology” means any Technology including, without
limitation, any modifications to a Licensed Product and/or its formulation, designed to
significantly prolong local effects relative to intravitreal injection of the Licensed Product.

     1.63 “Target” means a protein, cytokine, enzyme, receptor, transducer, transcription
factor, antigen or any other non-nucleic acid molecule.

     1.64 “Technology” means, collectively, inventions, discoveries, improvements, trade
secrets and proprietary methods, whether or not patentable, including, without limitation: (a)
methods of production or use of, and structural and functional information pertaining to, chemical
compounds and (b) compositions of matter, data, formulations, processes, techniques, know-how and
results (including any negative results).

     1.65 “Territory” means all countries and jurisdictions of the world.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

10

 

     1.66 “Third Party” means any person or entity other than Ophthotech, Archemix and
their respective Affiliates.

     1.67 “ULEHI” means University License Equity Holdings, Inc., formerly known as UTC.

     1.68 “Unexpected Adverse Event” means an Adverse Event, the specificity or severity of
which is not consistent with the current package insert or investigator’s brochure for the Licensed
Product. An Unexpected Adverse Event includes any event that may be symptomatically and
pathophysiologically related to an event listed in the current package insert or investigator’s
brochure, but differs from the listed event because of greater severity or specificity.

     1.69 “URC License Agreement” means the Restated Assignment and License Agreement,
dated July 17, 1991, by and between University Research Corporation and Gilead Sciences, Inc. as
successor in interest to NeXstar Pharmaceuticals, Inc.

     1.70 “UTC” means University Technology Corporation, the successor to the University
Research Corporation.

     1.71 “Valid Claim” means any claim of a pending patent application or an issued,
unexpired patent covered under the Licensed Patent Rights that (a) has not been finally cancelled,
withdrawn, abandoned or rejected by any administrative agency or other body of competent
jurisdiction, (b) has not been permanently revoked, held invalid or declared unpatentable or
unenforceable in a decision of a court or other body of competent jurisdiction that is unappealable
or unappealed within the time allowed for appeal, (c) has not been rendered unenforceable through
disclaimer or otherwise, (d) is not lost through an interference proceeding and (e) in the case any
claim of a pending patent application, is not pending more than [***] years from filing date of the
earliest patent application from which such pending patent application claims priority.

     Additional Definitions. In addition, each of the following definitions shall have the
respective meanings set forth in the section of this Agreement indicated below:

	 	 	 
	Definition	 	Section
	AAA
	 	10.2.1
	Agreement
	 	Recitals
	Archemix
	 	Recitals
	Archemix Indemnitees
	 	8.1
	Claims
	 	8.1
	Development Plan
	 	3.2
	Disclosing Party
	 	1.21
	Dispute
	 	10.2.1
	Effective Date
	 	Recitals
	Expert
	 	10.2.2(a)
	Generic Product
	 	4.2.2

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

11

 

	 	 	 
	Definition	 	Section
	Gilead Indemnitee
	 	8.3
	Indemnified Party
	 	8.2
	Infringement
	 	6.3.1
	Infringement Notice
	 	6.3.1
	[***]
	 	4.2.3
	Licensed Patent Right Fees
	 	6.2
	Mandatory Jurisdiction
	 	6.2
	Negotiation Period
	 	2.3.2
	[***]
	 	2.3.2
	Ophthotech
	 	Recitals
	Option
	 	2.3.2
	Option Period
	 	2.3.2
	Optional Jurisdiction
	 	6.2
	Party
	 	Recitals
	Parties
	 	Recitals
	[***]
	 	3.2
	Receiving Party
	 	1.21
	Series A Financing
	 	4.1.2
	Series A Investors
	 	4.1.2
	Series A Rights
	 	4.1.2
	Shares
	 	4.1.2
	Sirna Materials
	 	3.5.1
	Stock Purchase Agreement
	 	4.1.2
	Sublicense Income Payments
	 	4.3.2
	Term
	 	9.1
	Third Party Payments
	 	4.2.3

ARTICLE 2 GRANT OF RIGHTS

     2.1 License to Ophthotech.

          2.1.1 Grant of License. Archemix hereby grants to Ophthotech an exclusive,
royalty-bearing license, including the right to grant sublicenses in accordance with Section 2.1.3,
under the Licensed Patent Rights and Licensed Technology, to Develop, have Developed, make, have
made, use, have used, sell, offer for sale, distribute for sale, have sold, import, have imported,
export and have exported, Licensed Products in the Territory, for any and all uses within the
Field, subject to the terms and conditions of this Agreement. For purposes of clarity, (a)
Ophthotech shall have the right under this license to use SELEX Technology for the sole purpose of
modifying Anti-C5 Aptamers for use in the Field, (b) Ophthotech shall have no right under this
license to practice the SELEX Process for any reason, including to identify or modify aptamers, and
(c) subject to Section 2.3, Archemix shall retain the right to use the Licensed Technology and
practice the Licensed Patent Rights to (i) research, develop, have developed, make, have made, use,
have used, sell, offer for sale, have sold, distribute for sale, import, have imported, export and
have exported any product that is not a Licensed Product in the Field and (ii) research, develop,
have developed, make, have made, use, have used, sell, offer for sale,

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

12

 

have sold, distribute for sale, import, have imported, export and have exported any Licensed
Product outside the Field.

          2.1.2 Negative Covenant. Ophthotech is not granted the right to, and hereby agrees
that it will not (a) practice any inventions covered by a Valid Claim under the Licensed Patent
Rights or the SELEX Process, except as expressly permitted under this Agreement, (b) research,
develop, make, have made, use, have used, sell, offer for sale, have sold, distribute for sale,
import, have imported, export or have exported Diagnostics or (c) perform any research or
development on ARC1905, ARC186 and/or Anti C5 Aptamer for any use outside of the Field.
Notwithstanding the foregoing provisions of this Section 2.1.2, (i) Ophthotech shall not be
restricted by Section 2.1.2(a) or (b) from engaging in any activity that, in the absence of a
license from Archemix, would not infringe a Valid Claim Controlled by Archemix, and the foregoing
covenant by Ophthotech shall not apply to any such non-infringing activities and (ii) Ophthotech
shall not be restricted by Section 2.1.2(a) or (b) from engaging in any activity in which Opthotech
is permitted to engage pursuant to a license, sublicense or other right granted to Ophthotech in
any agreement other than this Agreement with respect to the SELEX Portfolio, the SELEX Process,
SELEX Technology or Aptamers, whether granted by Archemix, Gilead or any other Person having the
right to grant such license, sublicense or other right.

          2.1.3 Right to Sublicense. Ophthotech shall have the right to grant sublicenses to
all or any portion of its rights under the license granted pursuant to Section 2.1.1;
provided, that, (a) Archemix shall be notified of the grant of each such
sublicense; (b) each such sublicense shall be subject to, and consistent with, the terms and
conditions of this Agreement; (c) each such sublicense shall contain and include the following
provisions of this Agreement (with appropriate modifications to account for the identities of the
parties to such sublicense): Sections 2.1.2 (Negative Covenant), 2.1.4 (Reversion of License
Rights), 2.1.5 (Gilead-Archemix License Agreement), 6.3.3 (Effect of Challenge) and 9.2.2
(Termination for Challenge); (d) each such sublicense shall contain and include provisions
substantially similar to, and consistent with, the language provided in Sections 2.1.1 (Grant of
License), 3.1.2 (Diligence), 4.3.1 (Royalties), and Article 5 (Treatment of Confidential
Information); (e) upon termination of this Agreement, any such sublicense shall be considered a
direct license from Archemix as provided in Section 9.3 hereof; and (f) Ophthotech shall provide
Archemix with a copy of each sublicense agreement within thirty (30) days of execution. If
requested by a Sublicensee in connection with the negotiation of a sublicense, Archemix shall enter
into a “stand-by” license agreement directly with such Sublicensee to further document the
provisional license described in the foregoing clause (e); provided, that, as a
condition to Archemix’s execution of any such “stand-by” license, Ophthotech shall (i) provide to
Archemix, at least ten (10) days prior to the anticipated date of execution, a copy of the proposed
form of such “stand-by” license and any material information reasonably necessary for Archemix to
ensure that the sublicense agreement conforms to all terms and conditions of sublicensing under
this Agreement and (ii) reimburse Archemix for the reasonable legal fees and expenses incurred by
Archemix in connection with its review and execution of such “stand-by” license.

          2.1.4 Reversion of License Rights. Ophthotech acknowledges and agrees that each of
the URC License Agreement and the Gilead-Archemix License Agreement provide that the Archemix
rights in the SELEX Process or the SELEX Technology and the SELEX Portfolio may revert to Gilead or
ULEHI if Archemix, its Affiliates and all assignees and sublicensees

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

13

 

cease to exercise reasonable efforts to develop the commercial applications of products and
services utilizing the SELEX Process or the SELEX Technology. Ophthotech further acknowledges and
agrees that the URC License Agreement provides that in the event of any termination of the URC
License Agreement, the SELEX License granted to Ophthotech hereunder shall remain in full force and
effect in accordance with Section 3.4 of the URC License Agreement; provided, that,
Ophthotech is not then in breach of this Agreement and Ophthotech agrees to be bound to ULEHI as
the licensor under the terms and conditions of this Agreement. Archemix shall inform Ophthotech of
such event immediately after the Archemix rights revert to Gilead or ULEHI.

          2.1.5 Gilead-Archemix License Agreement. Ophthotech acknowledges and agrees that the
Gilead-Archemix License Agreement provides that in the event of any termination of the
Gilead-Archemix License Agreement, the SELEX License granted to Ophthotech hereunder shall remain
in full force and effect in accordance with Section 2.3 of the Gilead-Archemix License Agreement;
provided, that, Ophthotech agrees to be bound to Gilead as the licensor under the
terms and conditions of this Agreement; provided, that, if the termination of the
Gilead-Archemix License Agreement arises out of the action or inaction of Ophthotech, Gilead, at
its option, may terminate such license.

     2.2 No Other Rights. Ophthotech is not granted any rights to use or otherwise exploit
Licensed Patent Rights or Licensed Technology except as set forth in this Agreement.

     2.3 Exclusivity and Right of First Negotiation.

          2.3.1 Exclusivity. During the Term, neither Archemix nor any of its Affiliates will,
alone or with a Third Party, conduct any activity, for the purpose of researching, developing or
commercializing any aptamer that binds to C5 (including any Anti-C5 Aptamer) in the Field in the
Territory. For purposes of clarity, the restrictions set forth in this Section 2.3.1 shall not
apply to Permitted Activities.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

14

 

          2.3.2 Right of First Negotiation. Archemix shall notify Ophthotech in writing if
Archemix or an Affiliate of Archemix seeks to license [***] the [***] to any[***] for [***] the
[***] in the [***], for [***] the [***] and shall grant Ophthotech an option to initiate
negotiation of a license under Archemix’s interest in such rights (the “Option”).
Concurrently with such notice, Archemix shall supply to Ophthotech a summary of such information in
Archemix’s possession concerning [***], subject to Archemix’s confidentiality obligations to Third
Parties. Such Option shall be in effect for a period of [***] days from the date of notice of the
[***] pursuant to this Section 2.3.2 (the “Option Period”). Ophthotech may exercise the
Option by providing written notice to Archemix within the Option Period of its intent to exercise
such Option, at which time the Parties shall in good faith negotiate for up to [***] days (the
“Negotiation Period”) an agreement for the commercial exploitation of such rights, which
agreement shall contain commercially reasonable terms and conditions. If Ophthotech does not
exercise the Option during the Option Period, provides written notice that it chooses not to
exercise the Option, or the Negotiation Period expires without execution of an agreement between
the Parties, then (i) neither Party shall have any further obligation to enter into or continue any
negotiations with respect to the subject matter of the Option, and (ii) Archemix may license such
rights to a Third Party without any further obligation to Ophthotech. For purposes of clarity, no
Option shall arise if the rights that Archemix seeks to license [***] of the [***] of the [***].

ARTICLE
3 DEVELOPMENT AND COMMERCIALIZATION OF LICENSED PRODUCTS AND PROVISION OF MATERIALS.

     3.1 Development and Commercialization.

          3.1.1 Responsibility. From and after the Effective Date, Ophthotech shall have full
control and authority over the Development and commercialization of Licensed Products in the Field
in the Territory, including, without limitation, (a) all pre-clinical Development activities
(including any pharmaceutical development work on formulations or process development relating to
any Licensed Product), (b) all activities related to human clinical trials, (c) all activities
relating to manufacture and supply of all Licensed Products (including all required process
development and scale up work with respect thereto), (d) all marketing, promotion, sales,
distribution, import and export activities relating to any Licensed Product, and (e) all activities
relating to any regulatory filings, registrations, applications and Regulatory Approvals relating
to any of the foregoing. Ophthotech shall own all data, results and all other information arising
from any such activities under this Agreement, including, without limitation, all regulatory
filings, registrations, applications and Regulatory Approvals relating to Licensed Products, and
all of the foregoing information, documentation and materials shall be considered Confidential
Information and Technology solely owned by Ophthotech. All activities relating to Development and
commercialization under this Agreement shall be undertaken at Ophthotech’s sole cost and expense,
except as otherwise expressly provided in this Agreement.

          3.1.2 Diligence.

                    (a) General Diligence Obligations. Ophthotech will exercise Commercially Reasonable
Efforts in Developing and commercializing at least one Licensed

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

15

 

Product in the Field and in undertaking investigations and actions required to obtain
Regulatory Approvals necessary to market such Licensed Product in the Field in the United States,
the European Union, and Japan, and in such ex-United States markets, in addition to the European
Union and Japan, where Ophthotech determines, in the exercise of Commercially Reasonable Efforts,
that it is commercially reasonable to do so. In the event that Ophthotech fails to use Commercially
Reasonable Efforts as required hereunder, then on a Licensed Product-by-Licensed Product and
country-by-country basis as to such Licensed Product in such country, Archemix may, in its sole
discretion (i) terminate the licenses granted under Article 2 of this Agreement for breach under
Section 9.2.3 below, or (ii) convert the licenses granted under Article 2 of this Agreement from
exclusive licenses to non-exclusive licenses, in either case only as such licenses apply to such
Licensed Product in such country(ies); provided that, if Ophthotech is exercising
Commercially Reasonable Efforts in each Material EU Country, then Archemix may not so terminate or
convert such licenses as to any country in the European Union. The foregoing provisions of this
Section 3.1.2(a) shall constitute Archemix’s sole and exclusive remedies and Ophthotech’s sole and
exclusive liabilities for any failure by Ophthotech to exercise Commercially Reasonable Efforts to
Develop or commercialize any Licensed Product in any country or in the European Union pursuant to
this Section 3.12(a). In satisfying its obligation to use Commercially Reasonable Efforts with
respect to such Licensed Product, Ophthotech may engage in Development and commercialization
activities in various markets in a reasonably sequenced manner, it being understood that
Development and commercialization in the United States, the European Union, Japan and other markets
likely will not be pursued by Ophthotech on concurrent Development and commercialization schedules.

                    (b) Specific Diligence Obligations. Without limiting the generality of the provision
of Section 3.1.2 above, Ophthotech hereby agrees that it will:

                         (i) file an [***] for a Licensed Product for an [***] within [***] within [***] years of the
Effective Date;

                         (ii) complete a [***] of a Licensed Product for an [***] within [***] within [***] years of
the Effective Date; and

                         (iii) complete a [***] of a Licensed Product for an [***] within [***] within [***] years of
the Effective Date.

                    (c) Effect of Failure to Meet Obligations. If Ophthotech fails to meet any of the
milestones set forth above in Section 3.1.2(b) by the applicable deadline, but is otherwise in
compliance with the provisions of Section 3.1.2(a) during the applicable diligence period specified
above, then Archemix and Ophthotech will negotiate in good faith an extension of these milestone
deadlines. If Ophthotech (i) fails to meet any of the milestones set forth above in Section
3.1.2(b) by such extended deadline, or (ii) fails to meet any of the milestones set forth above in
Section 3.1.2(b) by the applicable deadline, and is not otherwise in compliance with the provisions
of Section 3.1.2(a) during the applicable diligence period specified above, Archemix may, in its
sole discretion (i) terminate the licenses granted under Article 2 of this Agreement for breach
under Section 9.2.3 below or (ii) convert the licenses granted under Article 2 of this Agreement
from exclusive licenses to non-exclusive licenses. The foregoing provisions of this

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

16

 

Section 3.1.2(c) shall constitute Archemix’s sole and exclusive remedies and Ophthotech’s sole
and exclusive liabilities for any failure by Ophthotech to meet any of the milestones set forth
above in Section 3.1.2(b) by the applicable deadline, as such deadline may be extended pursuant to
this Section 3.1.2(c).

     3.2 Development Plan. Ophthotech shall submit to Archemix for approval, which
approval will not be unreasonably withheld, conditioned or delayed, a development plan
(“Development Plan”) for each Licensed Product that Ophthotech intends to Develop and
commercialize in the Field, which shall include, without limitation, detailed [***] criteria
(“[***]”) for each Indication and the schedule for demonstrating such [***]. Attached
hereto as Exhibit B is the Development Plan, including [***] and [***] [***] criteria,
prepared by Ophthotech and approved by Archemix for the Development of a Licensed Product for the
treatment of one or more [***] within [***]. Amendments to the Development Plan attached hereto as
Exhibit B and all subsequent Development Plans shall be submitted to Archemix for its
review and approval, which shall not be unreasonably withheld, conditioned or delayed. Archemix
shall provide Ophthotech with notice of its approval or rejection of any such amendment or
Development Plan within [***] days of receipt. If the Parties are unable to agree on any such
amendment or Development Plan, either Party may submit such dispute for resolution pursuant to the
provisions of Article 10.

     3.3 Progress Reports. Ophthotech shall provide Archemix with written reports every
[***] months during the Term that shall include, at minimum, information reasonably sufficient to
enable Archemix to satisfy its reporting obligations to Gilead under the Gilead-Archemix License
Agreement with respect to this Agreement and to assess the progress made by Ophthotech toward
meeting the diligence requirements of Section 3.1 above.

     3.4 Notice of Certain Events; Pharmacovigilance. In addition to the progress reports
required pursuant to Section 3.3 above, Ophthotech shall provide Archemix with written notice
within [***] days of the occurrence of (a) the [***] in each country, (b) the Completion of each
[***], [***] and [***] of a Licensed Product, and the final reports thereof, (c) each milestone set
forth in Section 4.4 below, (d) any Regulatory Approval in any country, and (e) any other material
event other than as set forth in the foregoing clauses (a)-(d) related to the Development or
commercialization of Licensed Products. Ophthotech and, to the extent Archemix Develops and/or
commercializes any Licensed Product, Archemix, shall notify one another in writing of all
information coming to their attention regarding Adverse Events, Serious Adverse Events and/or
Unexpected Adverse Events related to, or reasonably likely to be related to, any Licensed Product,
regardless of the origin of such information and, for the avoidance of doubt, including such
information coming to their attention through journal publications and other media. Notifications
of Serious Adverse Events and Unexpected Adverse Events shall be given contemporaneously with
notifications of such Serious Adverse Events or Unexpected Adverse Events to any regulatory
authority, including the FDA or any Foreign Regulatory Authority. In addition, Ophthotech shall
provide Archemix with periodic (not more frequently than [***] per [***]) telephone updates as to
Adverse Events, Serious Adverse Events and/or Unexpected Adverse Events related to any Licensed
Product, to the extent reasonably requested by Archemix. Notifications of all other Adverse Events
shall be provided [***], with the information provided in each [***] notification to be current to
within [***] days prior to the

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

17

 

date of such notification.

     3.5 Material Supply.

          3.5.1 Initial Supply. Within [***] days of the Effective Date, Archemix will make
available for pickup by Ophthotech’s designated carrier, at no additional cost to Ophthotech, [***]
of [***] manufactured at Sirna from GMP [***] (the “Sirna Materials”). Ophthotech shall
provide Archemix with written notice when it has a GMP-compliant facility available for receipt of
the Sirna Materials. Title, possession, risk of loss and all [***] costs and expenses (including
the costs of Ophthotech’s designated carrier) shall [***] by [***] [***] the Sirna Materials [***]
Ophthotech’s designated carrier.

          3.5.2 Additional Supply. For a period of [***] days from the Effective Date,
Ophthotech shall have the right to purchase from Archemix up to [***] of the Sirna Materials, in
addition to the initial [***] supply of Sirna Materials to be provided pursuant to Section 3.5.1
above, at a price of $[***].

          3.5.3 No Warranties. Ophthotech hereby agrees and acknowledges that (a) THE SIRNA
MATERIALS WILL BE SUPPLIED “AS IS,” (b) ARCHEMIX MAKES NO REPRESENTATIONS, AND EXTENDS NO
WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, WITH RESPECT TO THE SIRNA MATERIALS, (c) THERE
ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR THAT
THE USE OF THE SIRNA MATERIALS WILL NOT INFRINGE ANY PATENT RIGHTS OF OTHERS, AND (d) ARCHEMIX
MAKES NO WARRANTIES AS TO THE IDENTITY, PURITY or ACTIVITY OF A PARTICULAR SAMPLE.

          3.5.4 Manufacturing Documentation. On or before [***] days from the Effective Date,
Archemix shall provide Ophthotech with a copy of Item 7 (entitled “Chemistry, Manufacturing &
Control”) of the IND application prepared by Archemix for ARC1905 dated December 15, 2005. Upon
Ophthotech’s request, Archemix shall provide Ophthotech with copies of the supporting documents or
records for such Item 7. Ophthotech shall be responsible for paying all costs including, without
limitation, Archemix’s FTE Costs and any external expenses incurred by Archemix, associated with
the transfer of any such documents or records to Ophthotech under this Section 3.5.4;
provided, that, Archemix may redact any portion of such documentation and records
as it reasonably determines contains Confidential Information of a Third Party.

          3.5.5 Manufacturing. Ophthotech shall be solely responsible, at its expense, for the
conduct of all chemistry, manufacture and control activities with respect to Licensed Products.

ARTICLE 4  PAYMENTS AND ROYALTIES

     4.1  Initial Fees.

          4.1.1 License Fee. In consideration for the rights granted to Ophthotech hereunder,
Ophthotech hereby agrees to pay Archemix an upfront license fee in the amount of

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

18

 

One Million Dollars (U.S. $1,000,000) payable within thirty (30) days of the Effective Date by
wire transfer of immediately available funds, which payment shall be non-refundable and
non-creditable.

          4.1.2 Equity. In consideration for the rights granted to Ophthotech hereunder,
Ophthotech hereby agrees to deliver to Archemix, concurrently with the closing by Ophthotech of its
equity financing involving the issuance of shares of Series A Preferred Stock, $.001 par value per
share (the “Series A Financing”), that number of shares of Junior Preferred Stock, $.001
par value per share (the “Shares”) as shall equal the result obtained by dividing [***]
Dollars (U.S. $[***]) by the purchase price per share of the shares issued to the Series A
Investors in the Series A Financing, on the terms and subject to the conditions set forth in the
stock purchase agreement (the “Stock Purchase Agreement”) to be negotiated and executed by
the investors in the Series A Preferred Financing (the “Series A Investors”). In
connection therewith, Ophthotech acknowledges and agrees that Archemix, as a holder of Shares,
shall receive all of the rights and preferences granted by Ophthotech to the Series A Investors in
the Series A Financing (the “Series A Rights”); provided, that,
notwithstanding anything to the contrary in this Agreement or in the Stock Purchase Agreement or in
any other agreement among Ophthotech and the Series A Investors, (a) Archemix shall not be
obligated, in connection with its purchase of the Shares, to provide any additional funding to
Ophthotech, whether through a mandatory participation right in subsequent financings or similar
obligation, in order to retain the benefit of all of the Series A Rights, (b) Archemix shall not be
entitled to designate a representative to serve on Ophthotech’s board of directors or to attend
board of directors meeting as an observer and (c) at any time when the Shares are outstanding,
Ophthotech shall not amend, waive, alter or repeal any provision of its certificate of
incorporation in a manner that adversely affects the powers, preferences or rights of the Shares
without the approval of a majority of the then outstanding Shares consenting or voting separately
as a class; except as otherwise stated in this clause (c) the Shares shall be voted in the same
manner as the majority of shares of Series A Preferred Stock voting on any such decision on which
the Shares are entitled to vote.

     4.2  Payment of Royalties; Royalty Rates; Minimum Royalties

          4.2.1 Royalty Payments.

                    (a) In consideration for the rights granted to Ophthotech hereunder, Ophthotech shall pay
Archemix a royalty during the Royalty Term based on Annual Net Sales of all Licensed Products sold
by Ophthotech and its Affiliates, at the following rates:

	 	 	 	 	 
	Annual Net Sales (US$)	 	Royalty (%)
	$[***]- $[***]
	 	 	[***]	%
	Greater than $[***]
	 	 	[***]	%

By way of example, if Annual Net Sales were equal to $[***], the royalty due would be equal $[***],
which is calculated as $[***] ($[***] * [***]%) + $[***] ([***] * [***]%).

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

19

 

                    (b) On a Licensed Product-by-Licensed Product and country-by-country basis, the royalty rate
applicable to Net Sales of a Licensed Product made in any country during any portion of the Royalty
Term outside of the Legal Exclusivity Period for such Licensed Product in such country shall be
reduced to [***] percent ([***]%) of the royalty rates otherwise applicable to such Net Sales under
Section 4.2.1(a).

          4.2.2 Competitive Generic Licensed Product. In the event that one or more Third
Parties sells a Generic Product (as defined below) in a country in which a Licensed Product is then
being sold, then during any Calendar Quarter in which sales of Generic Products by all such Third
Parties are equal to at least [***] percent ([***]%) of Ophthotech’s volume-based market share of
the Licensed Product in such country (as measured by prescriptions or other similar information
available in such country), the applicable payments in effect with respect to such Licensed Product
in such country as specified in Sections 4.2.1 and/or 4.3.1 shall be reduced to [***] percent
([***]%) of the rates otherwise applicable under Sections 4.2.1(a) and/or 4.3.1(a). Notwithstanding
the foregoing, the royalty rate reductions specified in the foregoing sentence shall cease, and the
otherwise applicable royalty rates shall be reinstated, on the first day of the Calendar Quarter
immediately following the Calendar Quarter in which sales of such Generic Products account for less
than [***] percent ([***]%) of Ophthotech’s volume-based market share in such country. For purposes
of this Section 4.2.2, a “Generic Product” means a pharmaceutical product that is a
“pharmaceutical equivalent” or “pharmaceutical alternative” (as those terms are used in the
Approved Drug Products with Therapeutic Equivalence Evaluations (a.k.a. the Orange Book) published
by the FDA Center for Drug Evaluation and Research or any successor publication) with respect to
the Licensed Product.

          4.2.3 Third Party License Fee Offset. In the event that in any Royalty Term,
Ophthotech, in order to exploit the license granted to it under Section 2.1 of this Agreement in
any country, actually makes royalty, milestone or other license fee payments to one or more Third
Parties (“Third Party Payments”) as consideration for a license to Patent Rights, in
settlement of litigation or arbitration regarding the infringement of such Patent Rights, or in
satisfaction of a litigation or arbitration judgment or award for infringement of such Patent
Rights, that cover the use, offer for sale, sale or importation in such country of the Anti-C5
Aptamer portion of the Licensed Product or that cover the [***] of ARC 1905 (as set forth in
Schedule 1) or the use of such [***] in the manufacture of ARC 1905, then Ophthotech shall
have the right to reduce the royalty payments otherwise due to Archemix pursuant to Sections 4.2.1
and 4.3.1 for such Licensed Product by [***] percent ([***]%) of such Third Party Payments.
Notwithstanding the foregoing provisions of this Section 4.2.3, in no event will the royalties due
for any Licensed Product in any country be reduced to less than [***] percent ([***]%) of the
royalties otherwise payable pursuant to Section 4.2.1 and 4.3.1; provided that if
in any Calendar Quarter this sentence prevents Ophthotech from reducing any royalty payment by the
full amount of the reduction to which Ophthotech is otherwise entitled under this Section 4.2.3,
Ophthotech shall be entitled to carry forward any amount that it was prevented from deducting in
such Calendar Quarter for deduction in the [***] Calendar Quarter. Notwithstanding the foregoing,
Ophthotech shall be solely responsible for, and the royalties payable to Archemix pursuant to
Section 4.2.1 and Section 4.3.1 shall not be reduced by, the amounts set forth on Schedule
3, which Ophthotech shall pay (subject to, in the case of milestone payments, the achievement
of corresponding milestones and, in the case of royalties,

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

20

 

the occurrence of applicable net sales) in consideration of a sublicense, under Archemix’s
license from [***] (“[***]”), with respect to Patent Rights owned or Controlled by [***]
and licensed to Archemix, to be granted by Archemix to Ophthotech. For purposes of clarity,
Ophthotech shall be obliged to accept such a sublicense under Patent Rights owned or Controlled by
[***], and Ophthotech and Archemix shall enter into an agreement granting Ophthotech such
sublicense promptly after the Effective Date.

          4.2.4 Maximum Offset. Notwithstanding the provisions of the foregoing Sections
4.2.1(b), 4.2.2 and 4.2.3, in no event will the royalties due for any Licensed Product in any
country be reduced to less than [***] percent ([***]%) of the rates specified in Sections 4.2.1(a)
or 4.3.1(a).

     4.3 Sublicense Royalties; Sublicense Income.

          4.3.1 Royalties.

                    (a) In consideration for the rights granted to Ophthotech hereunder, Ophthotech shall pay
Archemix a royalty during the Royalty Term equal to [***] percent ([***]%) of Net Sales of all
Licensed Products sold by Sublicensees.

                    (b) On a Licensed Product-by-Licensed Product and country-by-country basis, the royalty rate
applicable to Net Sales of a Licensed Product sold by a Sublicensee made during any portion of the
Royalty Term outside of the Legal Exclusivity Period for such Licensed Product in such country
shall be reduced to [***] percent ([***]%) of the royalty rate otherwise applicable to such Net
Sales under Section 4.3.1(a).

          4.3.2 Non-Royalty Income. Subject to the crediting of milestone payments made by
Opthotech permitted under clause (a) of Section 4.4.2, in consideration for the rights granted to
Ophthotech hereunder, during the Non-Royalty Term, Ophthotech shall pay Archemix an amount equal to
[***] percent ([***]%) of all Sublicense Income (“Sublicense Income Payments”);
provided, that, on a Licensed Product-by-Licensed Product and country-by-country
basis, such obligation shall continue after the end of the applicable Royalty Term unless
Ophthotech is able to reasonably demonstrate to Archemix in writing that such Sublicense Income was
paid to Ophthotech solely in consideration for sublicenses under Technology and/or Patent Rights
other than the Licensed Technology and/or the Licensed Patent Rights.

     4.4 Milestone Payments.

          4.4.1 Payment. In consideration for the rights granted to Ophthotech and/or its
Sublicensees hereunder, Ophthotech, shall make the following payments to Archemix on a Licensed
Product-by Licensed Product basis within [***] ([***]) days of the initial occurrence of each of
the following events by Ophthotech, its Affiliates and/or its Sublicensees:

          4.4.2
Regulatory Milestones:

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

21

 

	 	 	 	 	 
	 	 	Payment
	Event	 	(US$)
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 
	 
	[***]
	 	$	[***]	 

The foregoing milestone payment obligations under this Section 4.4.2 shall be subject to the
following: (a) [***] milestone payments paid by Ophthotech under this Section 4.4.2 as a result of
the achievement of a milestone event by any Sublicensee of Ophthotech shall be [***] by Ophthotech
against any Sublicense Income Payments payable by Ophthotech pursuant to Section 4.3.2 with respect
to such Sublicensee and (b) if a Licensed Product that was being Developed for a [***] Indication
fails such that Ophthotech and its Affiliates cease further Development of such Licensed Product
for such Indication, then, to the extent that Ophthotech Develops such Licensed Product for [***]
Indication, (i) that [***] Indication shall be deemed to be [***] Indication solely for purposes of
determining the applicable milestones set forth in Section 4.4.2 and (ii) [***] milestone payments
previously paid by Ophthotech for such Licensed Product for such [***] Indication shall be [***] if
such milestone events are achieved for such Licensed Product for [***] Indication but [***]
milestone payments for [***] milestone events shall be due and payable by Ophthotech.

          4.4.3 Sales Milestones. In addition to the milestone payments contemplated by Section
4.4.2 above, Ophthotech shall make each of the following one-time payments during the

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

22

 

Royalty Term to Archemix within [***] days after the first occurrence of the corresponding
milestone event for Annual Net Sales of all Licensed Product for all Indications sold by
Ophthotech, its Affiliates or Sublicensees, in the aggregate in any Calendar Year:

	 	 	 	 	 
	 	 	Milestone Payment
	Milestone Event (US$)	 	(US$)
	Annual Net Sales greater than $[***]
	 	$	[***]	 
	 
	Annual Net Sales greater than $[***]
	 	$	[***]	 

For purposes of determining when sales milestones are achieved under this Section 4.4.3, Net Sales
shall be calculated each Calendar Quarter in the currency in which such Net Sales were achieved by
Ophthotech, its Affiliates or Sublicensees and will be translated quarterly into United States
dollars in accordance with Section 4.5.3 hereof. Each Calendar Quarter’s calculated Net Sales in
United States dollars will then be added to cumulative Net Sales total for all previous Calendar
Quarter(s) during such Calendar Year. When such a sales milestone has been achieved will be
determined as of the last day of each Calendar Quarter, and payment of sales milestone payments
will be made within [***] calendar days following such date. For the avoidance of doubt, the
maximum aggregate amount payable by Ophthotech to Archemix pursuant to this Section 4.4.3 shall be
$[***]. If the aggregate Annual Net Sales of all Licensed Products as set forth above exceeds, for
the first time, both the $[***] and the $[***] milestones in a single Calendar Year, both milestone
payments shall be due (i.e., a total payment of $[***] shall be due).

          4.4.4 Skipped Milestones. If at the time any given milestone payment set forth in
Section 4.4.2 is due, one or more preceding milestone payments for logically antecedent milestones
have not been paid, then such unpaid antecedent milestone payments shall be paid at such time as
well. For example, if at the time a [***] milestone payment is due for [***] Indication, a [***]
milestone payment has not been paid for [***] Indication, then such [***] milestone payment shall
be paid at such time as well.

          4.4.5 Determination that Payments are Due. In the event that Archemix reasonably
believes any milestone payment is due pursuant to Section 4.4.1 or 4.4.3 in spite of not having
received notice from Ophthotech, it shall so notify Ophthotech and shall provide to Ophthotech the
data and information supporting its belief that the conditions for payment have been achieved. If
Ophthotech does not acknowledge that such milestone payment is due within [***] days of receipt of
the data and information from Archemix, then either Party may submit such dispute for resolution
pursuant to the provisions of Section 10.2.2 by providing written notice to the other Party.

     4.5 Payment Terms.

          4.5.1 Payment of Royalties, Milestones and Sublicense Income Payments. Unless
otherwise expressly provided, Ophthotech shall make any milestone, license, royalty payments and
Sublicense Income Payments owed to Archemix hereunder in arrears, within [***] days from the end of
the Calendar Quarter in which such payment accrues. For purposes of determining when a sale of any
Licensed Product occurs under this Agreement, the sale shall

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

23

 

be deemed to occur in accordance with generally accepted accounting principles. Each royalty
payment shall be accompanied by a report for each country in the Territory in which sales of
Licensed Products occurred in the Calendar Quarter covered by such statement, specifying: (v) the
gross sales (if available) and Net Sales in each country’s currency; (w) the applicable royalty
rate under this Agreement; (x) an accounting of deductions taken in the calculation of Net Sales
made in the United States and in any other country in which such accounting is reasonably
available; (y) the applicable exchange rate to convert from each currency other than United States
dollars to United States dollars under this Section 4.5; and (z) the royalties payable in United
States dollars. Each Sublicense Income Payment shall be accompanied by a report specifying: (x)
the aggregate amount of all payments received by Ophthotech or its Affiliates from sublicenses
granted hereunder; (y) all exclusions of such payment amounts from Sublicense Income made pursuant
to Section 1.60; and (z) the Sublicense Income Payments payable in United States dollars.

          4.5.2 Overdue Payments. Subject to the other terms of this Agreement, any payments
not paid within the time period set forth in this Article 4 shall bear interest at a rate of [***]
percent ([***]%) per month from the due date until paid in full; provided, that, in
no event shall said annual rate exceed the maximum interest rate permitted by law in regard to such
payments. Any such overdue payment shall, when made, be accompanied by, and credited first to, all
interest so accrued. Said interest and the payment and acceptance thereof shall not negate or
waive the right of Archemix to any other remedy, legal or equitable, to which it may be entitled
because of the delinquency of the payment.

          4.5.3 Accounting. All references to “dollars” or “$” herein mean United States
dollars. All payments hereunder shall be made in the United States in United States dollars.
Conversion of foreign currency to United States dollars shall be made at the conversion rate
existing in the United States (as reported in The Wall Street Journal) on the last business day of
the applicable Calendar Quarter. If The Wall Street Journal ceases to be published or if the
Parties agree otherwise, then the rate of exchange to be used shall be that reported in such other
business publication of national circulation in the United States as the Parties reasonably agree.

          4.5.4 Withholding Taxes; Restrictions on Payment. All payments hereunder shall be
made free and clear of any taxes, duties, levies, fees or charges, except for withholding taxes (to
the extent applicable). Ophthotech shall make any applicable withholding payments due on behalf of
Archemix and shall provide Archemix upon request with such written documentation regarding any such
payment available to Ophthotech relating to an application by Archemix for a foreign tax credit for
such payment with the United States Internal Revenue Service.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

24

 

          4.5.5 Blocked Payments. In the event that, by reason of applicable laws or
regulations in any country, it becomes impossible or illegal for Ophthotech or its Affiliates or
Sublicensees, to transfer, or have transferred on its behalf, royalties or other payments to
Archemix, such royalties or other payments shall be deposited in local currency in the relevant
country to the credit of Archemix in a recognized banking institution designated by Archemix or, if
none is designated by Archemix within a period of [***] days, in a recognized banking institution
selected by Ophthotech or its Affiliate or Sublicensee, as the case may be, and identified in a
notice in writing given to Archemix.

     4.6 Records Retention; Review.

          4.6.1 Records; Audit. Ophthotech and its Affiliates and Sublicensees shall keep and
maintain for [***] years from the date of each payment of royalties and Sublicense Income Payments
hereunder complete and accurate records of gross sales, Net Sales, and Sublicense Income received
by Ophthotech and its Affiliates and Sublicensees of each Licensed Product, in sufficient detail to
allow royalties to be determined accurately. Archemix shall have the right for a period of [***]
years after receiving any such royalty payment to appoint at its expense an independent certified
public accountant reasonably acceptable to Ophthotech to audit the relevant records of Ophthotech
and its Affiliates and Sublicensees to verify that the amount of such payment was correctly
determined. Ophthotech and its Affiliates and Sublicensees shall each make its records available
for audit by such independent certified public accountant during regular business hours at such
place or places where such records are customarily kept, upon [***] days written notice from
Archemix, solely to verify that payments hereunder were correctly determined. Such audit right
shall not be exercised by Archemix more than once in any Calendar Year or more than once with
respect to sales of a particular Licensed Product in a particular period. All records made
available for audit shall be deemed to be Confidential Information of Ophthotech or its Affiliates
or Sublicensees, as applicable. In the event there was an underpayment by Ophthotech hereunder,
Ophthotech shall promptly (but in any event no later than [***] days after such shortfall is
finally determined) make payment to Archemix of any shortfall. Archemix shall bear the full cost
of such audit unless such audit discloses an underreporting by Ophthotech of more than [***]
percent ([***]%) of the aggregate amount of royalties or Sublicense Income Payments payable in any
Calendar Year, in which case Ophthotech shall reimburse Archemix for all costs incurred by Archemix
in connection with such audit. If either Party disputes the results of any such audit, then it may
submit such matter for resolution pursuant to Section 10.2.2; provided that the
Party not prevailing in such arbitration shall reimburse the other Party for [***] percent ([***]%)
of the costs and expenses (including attorneys’ fees) incurred by such other Party in connection
with the conduct of such arbitration (including without limitation the Expert’s fees and any
administrative fees of such arbitration).

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

25

 

          4.6.2 Other Parties. Ophthotech shall include in any agreement with its Affiliates or
Sublicensees terms requiring such party to retain records as required in this Section 4.6 and to
permit Archemix to audit such records as required by this Section 4.6.

ARTICLE 5 TREATMENT OF CONFIDENTIAL INFORMATION

     5.1 Confidentiality Obligations. Archemix and Ophthotech each recognizes that the
other Party’s Confidential Information constitutes highly valuable assets of such other Party.
Archemix and Ophthotech each agrees that, subject to the remainder of this Article 5, it will not
disclose, and will cause its Affiliates and sublicensees not to disclose, any Confidential
Information of the other Party and it will not use, and will cause its Affiliates and sublicensees
not to use, any Confidential Information of the other Party except as expressly permitted
hereunder; provided, that, such obligations shall apply during the Term and for an
additional [***] years thereafter.

     5.2 Limited Disclosure and Use. Archemix and Ophthotech each agrees that disclosure
of its Confidential Information may be made by the other Party to any employee, consultant,
contractor, Affiliate or Sublicensee of such other Party to enable such other Party to exercise its
rights or to carry out its responsibilities under this Agreement; provided, that,
any such disclosure or transfer shall only be made to Persons who are bound by written obligations
as described in Section 5.3. In addition, Archemix and Ophthotech each agrees that the other Party
may disclose its Confidential Information (a) on a need-to-know basis to such other Party’s legal
and financial advisors, (b) as reasonably necessary in connection with an actual or potential (i)
permitted sublicense of such other Party’s rights hereunder, (ii) collaboration with an Archemix
Collaborative Partner, subject to written obligations of confidentiality substantially similar to
those of Archemix hereunder, (iii) debt or equity financing of such other Party or (iv) transfer or
sale of all or substantially all of such Party’s assets or business or in the event of its merger,
consolidation, change in control or similar transaction and (c) for any other purpose with the
other Party’s written consent, not to be unreasonably withheld, conditioned or delayed. In
addition, each Party agrees that the other Party may disclose such Party’s Confidential Information
as required by Applicable Laws; provided, that, in the case of any such disclosure,
the disclosing Party shall (1) if practicable, provide the other Party with reasonable advance
notice of and an opportunity to comment on any such required disclosure and (2) if requested by the
other Party, cooperate in all reasonable respects with the other Party’s efforts to obtain
confidential treatment or a protective order with respect to any such disclosure, at the other
Party’s expense.

     5.3 Employees and Consultants. Ophthotech and Archemix each hereby represent that all
of its employees, consultants and contractors, and all of the employees, consultants and
contractors of its Affiliates and sublicensees (including, without limitation, Sublicensees), who
have access to Confidential Information of the other Party are or will, prior to their
participation or access, be bound by written obligations to maintain such Confidential Information
in confidence and not to use such information except as expressly permitted hereunder. Each Party
agrees to use, and to cause its Affiliates and sublicensees (including, without limitation,
Sublicensees) to use, reasonable efforts to enforce such obligations.

     5.4 Publicity. The Parties acknowledge and agree that (a) the terms of this

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

26

 

Agreement constitute Confidential Information of each Party and may only be disclosed (i) as
permitted by Section 5.2, (ii) to investment bankers, investors, and potential investors, lenders
and potential lenders and other sources and other potential sources of financing, licensees and
potential licensees, acquirers or merger partners and potential acquirers or merger partners, and
(iii) or in the case of Archemix, Gilead and University License Equity Holdings, Inc.; and (b) a
copy of this Agreement may be filed by either Party with the Securities and Exchange Commission if
such filing is required by Applicable Laws; provided, that, in connection with any
such filing, such Party shall endeavor to obtain confidential treatment of economic and trade
secret information, and shall provide the other Party with the proposed confidential treatment
request with reasonable time for such other Party to provide comments, which comments shall be
reasonably considered by the filing Party. Notwithstanding anything to the contrary in Section
5.1, except as required by Applicable Laws, neither Party shall issue a press or news release or
make any similar public announcement related to this Agreement without the prior written consent of
the other Party; provided, that, notwithstanding the foregoing, (w) the Parties
shall issue a press release in a mutually agreed form as soon as practicable after the Effective
Date, (x) Ophthotech, its Affiliates and Sublicensees shall be expressly permitted to publicly
announce at any time the status of their Development and commercialization activities relating to
Licensed Products; provided, that, prior to the filing of an application for
Regulatory Approval for a Licensed Product, Ophthotech has given [***] days’ written notice to
Archemix of any such announcement relating to such Licensed Product and, after the filing of an
application for Regulatory Approval for a Licensed Product, Ophthotech has given advance notice to
Archemix of any such announcement relating to such Licensed Product that contains significant
(i.e., label amendments for new safety or efficacy data; Dear Doctor Letters, medical product
safety alerts; Class I, II, or III product recalls; market withdrawals; or public health advisories
) regulatory information about such Licensed Product not previously publicly disclosed, (y)
Archemix may publicly announce the occurrence of any milestone event described in Section 4.4 upon
[***] days’ prior written notice to Ophthotech, and (z) either Party shall be entitled to include
in press and news releases and other public announcements information related to this Agreement
that has previously been publicly announced in accordance with this Section 5.4.

ARTICLE 6 INTELLECTUAL PROPERTY RIGHTS AND PROVISIONS CONCERNING THE FILING, PROSECUTION, MAINTENANCE AND ENFORCEMENT OF PATENT RIGHTS

     6.1 Archemix Intellectual Property Rights. Archemix shall have sole and exclusive
ownership of all right, title and interest on a worldwide basis in and to any and all Licensed
Technology and Licensed Patent Rights.

     6.2 Licensed Patent Rights. Archemix, acting through patent counsel or agents of its
choice, shall be solely responsible for the preparation, filing, prosecution and maintenance of the
Licensed Patent Rights; provided, that, Ophthotech will reimburse Archemix for all
of its out-of-pocket and attorneys fees, expenses, official fees and all other charges accumulated
on or after the Effective Date incident to the preparation, filing, prosecution and maintenance of
the Anti-C5 Aptamer-Specific Patent Rights, including any interference or opposition proceedings,
in the jurisdictions set forth on Exhibit C (each, a “Mandatory Jurisdiction”) and
in any other jurisdictions mutually agreed by the Parties in advance (each, an “Optional
Jurisdiction”), such

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

27

 

agreement not to be unreasonably withheld, conditioned or delayed (collectively, “Licensed
Patent Right Fees”), within [***] days after Ophthotech’s receipt of invoices from Archemix
and/or Archemix’s outside patent counsel for Licensed Patent Right Fees; provided
further, that, Ophthotech may elect not to pay such amounts with respect to (a) any
particular Anti-C5 Aptamer-Specific Patent Rights in any Optional Jurisdiction upon [***] days
prior written notice to Archemix and (b) any particular Anti-C5 Aptamer-Specific Patent Rights in
any Mandatory Jurisdiction that are not listed on Exhibit A as of the Effective Date
(subject to the next sentence of this Section 6.2) upon [***] days prior written notice to
Archemix, in which event such Anti-C5 Aptamer-Specific Patent Rights shall thereafter be excluded
from the Licensed Patent Rights. For purposes of clarity, the Anti-C5 Aptamer-Specific Patent
Rights listed on Exhibit A as of the Effective Date shall be deemed to include, for
purposes of the immediately preceding sentence of this Section 6.2, the Patent Rights listed on
Exhibit A attached hereto and all divisionals, nationalization filings, continuations
(excluding continuations-in-part) thereof, all reissues, reexaminations, renewals and extensions
thereof, and supplementary protection certificates therefor, and all foreign equivalents of any of
the foregoing filed with respect to such Patent Rights during the Term, in each case in any
Mandatory Jurisdiction. In the event that Archemix determines not to file or to abandon any of the
Anti-C5 Aptamer Specific Patent Rights, Archemix shall notify Ophthotech sufficiently in advance so
that Ophthotech can, without any loss of rights, and Ophthotech shall have the right to file,
prosecute and maintain such Patent Rights in Archemix’ name at Ophthotech’s expense. Archemix
shall provide Ophthotech with a reasonable opportunity to review and comment in advance on all
filings and correspondence with patent offices regarding such Anti-C5 Aptamer-Specific Patent
Rights and shall consider in good faith any comments thereon that Ophthotech provides.
Notwithstanding the foregoing, to the extent Anti-C5 Aptamer-Specific Patent Rights are licensed to
Third Parties for use outside the Field in accordance with this Agreement and such Third Parties
are obligated to reimburse Archemix for Licensed Patent Right Fees, the Parties will negotiate in
good faith a proportional reduction of Ophthotech’s obligation for Licensed Patent Right Fees
hereunder.

     6.3 Infringement.

          6.3.1 Notice. In the event during the Term that either Party becomes aware of (i) any
possible infringement of any Licensed Patent Rights or (ii) the submission by any Third Party of an
abbreviated new drug application under the Hatch-Waxman Act for a product that includes an aptamer
covered by Anti-C5 Aptamer-Specific Patent Rights (each, an “Infringement”), that Party shall
promptly notify the other Party and provide it with all details of such Infringement of which it is
aware (each, an “Infringement Notice”).

          6.3.2 Infringement Action. Ophthotech shall have the first right, at its own expense
and with legal counsel of its own choice, to bring suit (or take other appropriate legal action)
against any actual, alleged or threatened Infringement of the Anti-C5 Aptamer-Specific Patent
Rights in the Field. Ophthotech shall determine whether to exercise such first right in its
discretion, which discretion Ophthotech shall exercise in a manner consistent with Ophthotech’s
obligations under Section 3.1.2(a). Archemix shall have the right, at its own expense, to be
represented in any such action by Ophthotech by counsel of Archemix’s own choice; provided,
that, under no circumstances shall the foregoing affect the right of Ophthotech to control
the suit as described in the first sentence of this Section 6.3.2. If Ophthotech does not file any
action or

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting
confidential treatment under Rule 406 of the Securities Act.

28

 

proceeding against any such Infringement within [***] months after the later of (i)
Ophthotech’s notice to Archemix under Section 6.3.1 above, (ii) Archemix’s notice to Ophthotech
under Section 6.3.1 above or (iii) a written request from Archemix to take action with respect to
such infringement, then Archemix shall have the right (but not the obligation), at its own expense,
to bring suit (or take other appropriate legal action) against such actual, alleged or threatened
infringement, with legal counsel of its own choice. Any damages, monetary awards or other amounts
recovered, whether by judgment or settlement, pursuant to any suit, proceeding or other legal
action taken under this Section 6.3.2, shall be applied as follows:

               (a) first, to reimburse the Parties for their respective costs and expenses (including
reasonable attorneys’ fees and costs) incurred in prosecuting such enforcement action; and

               (b) second, [***] percent ([***]%) of any remaining amount shall be retained by the Party
bringing such suit or proceeding or taking such other legal action and [***] percent ([***]%) shall
be paid to the other Party.

          If a Party brings any such action or proceeding hereunder, the other Party agrees to be joined
as party plaintiff if necessary to prosecute such action or proceeding, and to give the Party
bringing such action or proceeding reasonable assistance and authority to file and prosecute the
suit; provided, that, neither Party shall be required to transfer any right, title
or interest in or to any property to the other Party or any Third Party to confer standing on a
Party hereunder. Notwithstanding the foregoing, if Ophthotech declines to bring any such action or
proceeding hereunder, Ophthotech may decline to be joined as a party plaintiff or to assist
Archemix in any such action or proceeding if Ophthotech reasonably determines that being joined to
or assisting in such action or proceeding presents a significant risk of liability under applicable
antitrust laws.

          6.3.3 Effect of Challenge. In further consideration of Archemix’s grant of the
licenses hereunder and except to the extent the following is unenforceable under the Applicable
Laws of a particular jurisdiction where a patent application within the Licensed Patent Rights is
pending or a patent within the Licensed Patent Rights issued, in the event that Ophthotech, its
Affiliates and/or Sublicensees (a) determines to initiate a Challenge or Ophthotech, its Affiliates
and/or Sublicensees determines to assist a Third Party in initiating a Challenge, Ophthotech will
provide written notice to Archemix at least [***] days prior thereto, which notice will include an
identification of all prior art it believes invalidates any claim of the Licensed Patent Rights;
and (b) initiates a Challenge or assists a Third Party in initiating a Challenge, (i) the exclusive
licenses granted by Archemix to Ophthotech hereunder shall, at the option of the Archemix and upon
written notice to Ophthotech, be converted into non-exclusive licenses as of the date of such
notice, (ii) should the outcome of such Challenge determine that any claim of the Licensed Patent
Rights that is the subject of the Challenge is valid or enforceable, the royalty rates set forth in
Sections 4.2 and 4.3 shall be increased by [***] percentage points (e.g., a royalty rate of [***]
percent ([***]%) shall be increased to [***] percent ([***]%)) and (iii) should the outcome of any
Challenge determine no claim of the Licensed Patent Rights Challenged by Ophthotech, its Affiliates
and/or Sublicensees is valid or enforceable, Ophthotech, its Affiliates and/or Sublicensees shall
continue to pay royalties based on Net Sales of Licensed Products sold

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

29

 

in the Territory at the rate of [***] percent ([***]%) until the last day of the Royalty Term
for such Licensed Product notwithstanding such determination. For the avoidance of doubt, a
Challenge shall not constitute a breach of this Agreement.

	
	ARTICLE 7  REPRESENTATIONS AND WARRANTIES; COVENANT REGARDING THIRD PARTY AGREEMENTS

     7.1 Mutual Representations and Warranties. Archemix and Ophthotech each represents
and warrants to the other, as of the Effective Date, as follows:

          7.1.1 Organization. It is a corporation duly organized, validly existing and in good
standing under the laws of the jurisdiction of its organization, and has all requisite power and
authority, corporate or otherwise, to execute, deliver and perform this Agreement.

          7.1.2 Authorization. The execution and delivery of this Agreement and the performance
by it of the transactions contemplated hereby have been duly authorized by all necessary corporate
action and will not violate (a) such Party’s certificate of incorporation or bylaws, (b) any
agreement, instrument or contractual obligation to which such Party is bound in any material
respect, (c) any requirement of any Applicable Laws, or (d) any order, writ, judgment, injunction,
decree, determination or award of any court or governmental agency presently in effect applicable
to such Party.

          7.1.3 Binding Agreement. This Agreement is a legal, valid and binding obligation of
such Party enforceable against it in accordance with its terms and conditions.

          7.1.4 No Inconsistent Obligation. It is not under any obligation, contractual or
otherwise, to any Person that conflicts with or is inconsistent in any respect with the terms of
this Agreement or that would impede the diligent and complete fulfillment of its obligations
hereunder.

     7.2 Acknowledgment of Ophthotech. Ophthotech acknowledges that the licenses granted
to Ophthotech hereunder are subject to certain limitations and restrictions set forth in the
Archemix-Gilead License Agreement as provided by Archemix to Ophthotech prior to the Effective
Date and agrees that Ophthotech shall comply with such limitations and restrictions.

     7.3 Additional Representations and Warranties.

          7.3.1 Archemix represents and warrants to Ophthotech that Archemix has the right to grant the
license granted to Ophthotech on the terms set forth herein;

          7.3.2 Archemix represents and warrants to Ophthotech that, except as previously disclosed to
Ophthotech, as of the Effective Date and with no further duty to update (except as otherwise
stated):

               (a) to its Knowledge, there is no litigation pending or threatened that alleges that (i) the
practice of the SELEX Process and/or the use of SELEX Technology as contemplated by this Agreement
infringes the Patent Rights of any Third Party, or (ii) the

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

30

 

Licensed Patent Rights are invalid or unenforceable; or (iii) the use of the Licensed Patent
Rights or Licensed Technology as contemplated by this Agreement infringes the Patent Rights of any
Third Party; and

               (b) the Archemix-Gilead License Agreement, as heretofore delivered by Archemix to Ophthotech,
represents the complete agreement and understanding between Gilead Sciences, Inc. and Archemix
relating to the Licensed Patent Rights which are the subject of the Archemix-Gilead License
Agreement; the Archemix-Gilead License Agreement has not been modified, supplemented or amended,
other than by amendments thereto provided to Ophthotech prior to the Effective Date; the
Archemix-Gilead License Agreement is in full force and effect, all payments to date required to be
made thereunder by Archemix have been made, and Archemix is in compliance in all material respects
with its obligations thereunder.

     7.4 Archemix Covenants Regarding Archemix-Gilead Agreement. Archemix hereby covenants
to promptly notify Ophthotech upon receipt by Archemix or its Affiliates of any notice from Gilead
Sciences, Inc. of such party’s intent to terminate Archemix’s rights under the Archemix-Gilead
License Agreement or otherwise take any action that would adversely affect Ophthotech’s rights
under this Agreement.

ARTICLE 8 INDEMNIFICATION AND INSURANCE

     8.1 Indemnification of Archemix by Ophthotech. Ophthotech shall indemnify, defend and
hold harmless Archemix, its Affiliates, their respective directors, officers, employees and agents,
and their respective successors, heirs and assigns (the “Archemix Indemnitees”), against
any liability, damage, loss or expense (including reasonable attorneys’ fees and expenses of
litigation) incurred by or imposed upon the Archemix Indemnitees, or any one of them, as a direct
result of Third Party claims, suits, actions or demands (collectively, the “Claims”)
arising out of (a) the research, development, testing, production, manufacture, supply, promotion,
import, sale or use by any Person of any Licensed Product (or any component thereof) manufactured
or sold by Ophthotech or any of its Affiliates or Sublicensees or (b) the gross negligence or
willful misconduct of Ophthotech or any of its Affiliates or Sublicensees; provided,
that, Ophthotech shall have no obligation to indemnify any Archemix Indemnitee for any
Claim arising out of the gross negligence or willful misconduct of Archemix or any of its
Affiliates.

     8.2 Conditions to Indemnification. An Archemix Indemnitee seeking recovery under this
Article 8 (the “Indemnified Party”) in respect of a Claim shall give prompt notice of such
Claim to Ophthotech and provided that Ophthotech is not contesting its obligation under this
Article 8, shall permit Ophthotech to control any litigation relating to such Claim and the
disposition of such Claim (including without limitation any settlement thereof); provided,
that, Ophthotech shall not settle or otherwise resolve such Claim without the prior written
consent of such Indemnified Party, which consent shall not be unreasonably withheld, conditioned or
delayed, unless such settlement includes a full release of the Indemnified Party, in which case
Ophthotech may settle or otherwise resolve such Claim without the prior written consent of such
Indemnified Party. Each Indemnified Party shall cooperate with Ophthotech in its defense of any
such Claim in all reasonable respects and shall have the right to be present in person or

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

31

 

through counsel at all legal proceedings with respect to such Claim.

     8.3 Indemnification of Gilead and UTC by Ophthotech. If and solely to the extent,
legally required by the Archemix-Gilead License Agreement, Ophthotech shall indemnify, defend and
hold harmless Gilead, its Affiliates and UTC and any of their respective directors, officers,
employees and agents (each, a “Gilead Indemnitee”), from and against any losses that are
incurred by a Gilead Indemnitee as a result of any Claims, to the extent such Claims arise out of
the possession, research, development, manufacture, use, offer for sale, sale or other
commercialization, distribution, administration, storage or transport, by Ophthotech or its
Affiliates or Sublicensees of (a) any Aptamers or Licensed Products, or (b) any other products,
services or activities developed by Ophthotech relating to the Licensed Patent Rights, including
any Licensed Products or Aptamers.

     8.4 Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT,
NEITHER PARTY MAKES ANY WARRANTY WITH RESPECT TO ANY TECHNOLOGY, GOODS, SERVICES, RIGHTS OR OTHER
SUBJECT MATTER OF THIS AGREEMENT AND EACH PARTY HEREBY DISCLAIMS ALL WARRANTIES, EXPRESS OR
IMPLIED, INCLUDING, WITHOUT LIMITATION, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR
PURPOSE AND NONINFRINGEMENT. NEITHER PARTY MAKES ANY WARRANTIES AS TO THE VALIDITY OR
ENFORCEABILITY OF THE PATENT RIGHTS LICENSED BY SUCH PARTY TO THE OTHER PARTY.

     8.5 Limited Liability. NOTWITHSTANDING ANYTHING TO THE CONTRARY IN THIS AGREEMENT,
NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY OR ANY OF ITS AFFILIATES FOR (I) ANY SPECIAL,
PUNITIVE, INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES, INCLUDING, WITHOUT LIMITATION, LOST
PROFITS OR LOST REVENUES, OR (II) COST OF PROCUREMENT OF SUBSTITUTE GOODS, TECHNOLOGY OR SERVICES,
WHETHER UNDER ANY CONTRACT, WARRANTY, NEGLIGENCE, STRICT LIABILITY OR OTHER LEGAL OR EQUITABLE
THEORY. NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 8.5 SHALL LIMIT EITHER PARTY’S
INDEMNIFICATION OBLIGATIONS HEREUNDER WITH RESPECT TO THIRD PARTY CLAIMS.

     8.6 Insurance. Ophthotech will, at Ophthotech’s expense, obtain and maintain in full
force and effect insurance with respect to the Development and commercialization of Licensed
Products in such amount as U.S.-based biopharmaceutical companies customarily maintain with respect
to the research, development and commercialization of similar products. Such insurance policy or
policies shall name Archemix as an additional named insured, shall be non-cancelable except upon
[***] days prior written notice to Archemix, and shall provide that as to any loss covered thereby
and also by any policies obtained by Archemix itself, Ophthotech’s policies shall provide primary
coverage for Archemix and Archemix’ policies shall be considered excess coverage for Archemix.
Ophthotech will forthwith after the obtaining of such insurance required by this Section 8.6,
obtain and deliver to Archemix certificates of and copies of, and at all times thereafter deliver
without further demand replacement certificates and copies of, all such insurance policies that are
in force and effect. Ophthotech’s obligation under this Section 8.6

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

32

 

may be delegated by Ophthotech to a Third Party collaborator of Ophthotech with Archemix’s
prior written consent, which shall not be unreasonably withheld, conditioned or delayed;
provided, that, (i) such Third Party collaborator has worldwide annual revenue of
at least [***] dollars ($[***]), (ii) such Third Party collaborator maintains either insurance
policy(-ies) or a program of self-insurance in such amount as U.S.-based biopharmaceutical
companies customarily maintain with respect to the research, development and commercialization of
similar products and, if such Third Party collaborator maintains insurance policy(-ies), the
insurance policy(-ies) maintained by such Third Party collaborator names Archemix and Ophthotech as
additional insureds, (iii) such insurance policy or self-insurance covers (or, if there is more
than one such policy, collectively covers) all Licensed Products Developed and/or commercialized by
Ophthotech and (iv) in the case of such a self-insurance program, Ophthotech notifies Archemix that
such Third Party collaborator has represented the existence of such self-insurance program to
Ophthotech, that is consistent with the requirements of this Section 8.6. Any such delegation by
Ophthotech to a Third Party collaborator shall not relieve Ophthotech of its obligations under
Sections 8.1 and 8.3.

ARTICLE 9 TERM AND TERMINATION

     9.1 Term; Expiration. The term (“Term”) of this Agreement shall commence on
the Effective Date and continue, unless earlier terminated as provided herein, until such time as
all Royalty Terms and Non-Royalty Terms for all Licensed Products have ended. Upon expiration (but
not upon termination prior to the expiration) of the Royalty Term and Non-Royalty Term applicable
to a Licensed Product in a country, Ophthotech’s rights and licenses hereunder with respect to such
Licensed Product in such country shall become fully paid-up, non-royalty bearing, perpetual rights
and licenses.

     9.2 Termination.

          9.2.1 Unilateral Right to Terminate. Ophthotech shall have the right to terminate
this Agreement, for any reason, upon (a) at least ninety (90) days’ prior written notice to
Archemix, such notice to state the date at least ninety (90) days following the date of receipt of
such notice by Archemix upon which termination is to be effective, and (b) the payment by
Ophthotech of all amounts due to Archemix through such termination effective date.

          9.2.2 Termination for Challenge. In the event Ophthotech, its Affiliates and/or
Sublicensees initiates a Challenge or assists a Third Party in initiating a Challenge, Archemix
shall have the right to terminate this Agreement, effective immediately upon written notice to
Ophthotech.

          9.2.3 Termination for Breach. Except as set forth herein, either Party may terminate
this Agreement, effective immediately upon written notice to the other Party, for a material breach
by the other Party of this Agreement that, if curable, remains uncured for [***] days ([***] days
in the event that the breach is a failure of a Party to make any payment required hereunder) after
the non-breaching Party first gives written notice to the other Party of such breach and its intent
to terminate this Agreement if such breach is not cured.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

33

 

          9.2.4 Termination for Insolvency. Each Party shall give the other Party reasonable
prior notice of the filing with respect to itself of any voluntary petition, and prompt notice of
the filing with respect to itself of any involuntary petition, under any bankruptcy laws. In the
event that either Party: (a) files for protection under bankruptcy laws; (b) makes an assignment of
all or substantially all of its assets for the benefit of creditors; (c) appoints or suffers
appointment of a receiver or trustee over all or substantially all of its assets; and (d) files a
petition under any bankruptcy or insolvency act or has any such petition filed against it which is
not discharged within [***] days of the filing thereof, then the other Party may terminate this
Agreement effective immediately upon written notice to such Party. All rights and licenses granted
under or pursuant to this Agreement are, and shall otherwise be deemed to be, for purposes of
Section 365(n) of the U.S. Bankruptcy Code, licenses of right to “intellectual property” as defined
under Section 101 of the U.S. Bankruptcy Code.

          9.3 Consequences of Termination of Agreement. In the event of the termination of this
Agreement pursuant to this Article 9, the following provisions shall apply:

          9.3.1 If this Agreement is terminated by Ophthotech pursuant to Section 9.2.1 or by Archemix
pursuant to Sections 9.2.2, 9.2.3 or 9.2.4:

               (a) all licenses granted by Archemix to Ophthotech shall immediately terminate;

               (b) Ophthotech shall promptly return all Confidential Information of Archemix;
provided, that Ophthotech may retain one (1) copy of Confidential Information of
Archemix in its archives solely for the purpose of establishing the contents thereof and ensuring
compliance with its obligations hereunder; and

               (c) each Sublicensee of Ophthotech shall be considered a direct licensee of Archemix;
provided, that, (i) such Sublicensee is then in material compliance with all terms
and conditions of its sublicense, (ii) all accrued payments obligations of such Sublicensee to
Archemix have been paid, and (iii) such Sublicensee agrees in writing to remain in compliance with
all terms and conditions of the sublicense (subject to any notice and cure period provisions
contained in any such sublicense agreement with such Sublicensee).

          9.3.2 If this Agreement is terminated by Ophthotech pursuant to Sections 9.2.3 or 9.2.4, all
licenses granted by Archemix to Ophthotech shall survive subject to Ophthotech’s continued payment
of all royalties, milestones, Sublicense Income and other payments pursuant to Article 4; and
Ophthotech shall promptly return all Confidential Information of Archemix that is not subject to a
continuing license hereunder; provided, that Ophthotech may retain one (1) copy of
each such Confidential Information of Archemix in it archives solely for the purpose of
establishing the contents thereof and ensuring compliance with its obligations hereunder.

     9.4 Remedies. Except as otherwise expressly set forth in this Agreement, the
termination provisions of this Article 9 are in addition to any other relief and remedies available
to either Party at law.

     9.5 Surviving Provisions. Notwithstanding any provision herein to the contrary, the
rights and obligations of the Parties set forth in Articles 5 and 8 and Sections 4.6 and 9.1, as
well

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

34

 

as any rights or obligations otherwise accrued hereunder (including any accrued payment
obligations), shall survive the expiration or termination of the Term.

ARTICLE 10 DISPUTES

     10.1 Negotiation. The Parties recognize that a bona fide dispute as to certain
matters may from time to time arise during the Term that relates to either Party’s rights and/or
obligations hereunder. In the event of the occurrence of such a dispute, either Party may, by
written notice to the other Party, have such dispute referred to their respective senior officials
designated below or their successors or designees, for attempted resolution by good faith
negotiations within [***] days after such notice is received. Said designated senior officials are
as follows:

     For Ophthotech: [***]

     For Archemix: [***]

In the event the designated senior officials or their successors or designees are not able to
resolve such dispute within the [***] day period, either Party may invoke the provisions of Section
10.2.

     10.2 Arbitration.

          10.2.1 Full Arbitration. Subject to Section 10.1, any dispute, controversy or claim
initiated by either Party arising out of, resulting from or relating to this Agreement or the
performance by either Party of its obligations under this Agreement (other than bona fide Third
Party actions or proceedings filed or instituted in an action or proceeding by a Third Party
against a Party (a “Dispute”)), whether before or after termination of this Agreement,
shall be finally resolved by binding arbitration. Whenever a Party shall decide to institute
arbitration proceedings, it shall give written notice to that effect to the other Party. Any such
arbitration shall be conducted under the Commercial Arbitration Rules of the American Arbitration
Association (the “AAA”) by a panel of three arbitrators appointed in accordance with such
rules. Any such arbitration shall be held in Boston, Massachusetts. The method and manner of
discovery in any such arbitration proceeding shall be governed by the laws of the Commonwealth of
Massachusetts. The arbitrator shall have the authority to grant injunctions and/or specific
performance and to allocate between the Parties the costs of arbitration in such equitable manner
as they determine. Judgment upon the award so rendered may be entered in any court having
jurisdiction or application may be made to such court for judicial acceptance of any award and an
order of enforcement, as the case may be. In no event shall a demand for arbitration be made after
the date when institution of a legal or equitable proceeding based upon such claim, dispute or
other matter in question would be barred by the applicable statute of limitations. Notwithstanding
the foregoing, either Party shall have the right, without waiving any right or remedy available to
such Party under this Agreement or otherwise, to seek and obtain from any court of competent
jurisdiction any interim or provisional relief that is necessary or desirable to protect the rights
or property of such Party, pending the selection of the arbitrator hereunder or pending the
arbitrators’ determination of any dispute, controversy or claim hereunder.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

35

 

          10.2.2 Accelerated Arbitration. Disputes submitted to arbitration by a Party under
Section 10.2.1 relating to a matter set forth in Section 1.43(z), 1.60(b), 4.4.5 or 4.6.1, the
following procedures shall apply:

               (a) The Parties shall mutually select a single independent, conflict-free arbitrator (the
“Expert”), who shall have sufficient scientific background and experience to resolve the
Dispute. If the Parties are unable to reach agreement on the selection of an Expert within [***]
business days after submission to arbitration, then either or both Parties shall immediately
request that the AAA select an arbitrator with the requisite scientific background, experience and
expertise. The place of arbitration shall be New York, New York.

               (b) Each Party shall prepare and submit a written summary of such Party’s position and any
relevant evidence in support thereof to the Expert within [***]) days of the selection of the
Expert. Upon receipt of such summaries from each Party, the Expert shall provide copies of the
same to the other Party. Within [***] days of the delivery of such summaries by the Expert, each
Party shall submit a written rebuttal of the other Party’s summary and may also amend and re-submit
its original summary. Oral presentations shall not be permitted unless otherwise requested by the
Expert. The Expert shall make a final decision with respect to the Dispute within [***] days
following receipt of the last of such rebuttal statements submitted by the Parties. Each Party
shall bear its own costs and expenses and attorneys’ fees, and the Party that does not prevail in
the arbitration proceeding shall pay the Expert’s fees and any administrative fees of arbitration.

ARTICLE 11 MISCELLANEOUS

     11.1 Notification. All notices, requests and other communications hereunder shall be
in writing, shall be addressed to the receiving Party’s address set forth below or to such other
address as a Party may designate by notice hereunder, and shall be either (i) delivered by hand,
(ii) made by facsimile transmission, (iii) sent by private courier service providing evidence of
receipt or (iv) sent by registered or certified mail, return receipt requested, postage prepaid.
The addresses and other contact information for the parties are as follows:

	 	 	 	 	 
	 

	 	If to Ophthotech:
	 	If to Archemix:
	 
	 	 	 	 
	 

	 	Ophthotech Corporation
	 	Archemix Corp.
	 

	 	c/o SV Life Sciences
	 	300 Third Street
	 

	 	60 State Street, Ste. 3650
	 	Cambridge, MA 02142
	 

	 	Boston, MA 02109
	 	Tel: (617) 621-7700
	 

	 	Tel: (617) 367-8100
	 	Fax: (617) 621-9300
	 

	 	Fax: (617) 367-1590
	 	Attention: Chief Executive Officer
	 

	 	Attention: President
	 	Attention: Legal Department
	 
	 	 	 	 
	 

	 	With a copy to:
	 	With a copy to:
	 
	 	 	 	 
	 

	 	Wilmer Cutler Pickering Hale and Dorr LLP	 	Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
	 

	 	60 State Street
	 	One Financial Center
	 

	 	Boston, Massachusetts 02109
	 	Boston, Massachusetts 02111

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

36

 

	 	 	 	 	 
	 

	 	Attention: David E. Redlick, Esq.
	 	Attention: John J. Cheney, Esq.
	 

	 	Tel: (617) 526-6000
	 	Tel: (617) 542-6000
	 

	 	Fax: (617) 526-5000
	 	Fax: (617) 542-2241

     All notices, requests and other communications hereunder shall be deemed to have been given
either (i) if by hand, at the time of the delivery thereof to the receiving Party at the address of
such Party set forth above, (ii) if made by facsimile transmission, at the time that confirmation
of receipt thereof has been received by the Party delivering such notice, (iii) if sent by private
courier, on the day such notice is delivered to the recipient or (iv) if sent by registered or
certified mail, on the fifth (5th) business day following the day such mailing is made.

     11.2 Governing Law. This Agreement will be construed, interpreted and applied in
accordance with the laws of the Commonwealth of Massachusetts (excluding its body of law
controlling conflicts of law).

     11.3 Limitations. Except as expressly set forth in this Agreement, neither Party
grants to the other Party any right or license to any of its intellectual property.

     11.4 Entire Agreement. This is the entire Agreement between the Parties with respect
to the subject matter hereof and supersedes all prior representations, understandings and
agreements between the Parties with respect to the subject matter hereof. No modification or
amendment shall be effective unless in writing with specific reference to this Agreement and signed
by the Parties.

     11.5 Waiver. The terms or conditions of this Agreement may be waived only by a
written instrument executed by the Party waiving compliance. The failure of either Party at any
time or times to require performance of any provision hereof shall in no manner affect its rights
at a later time to enforce the same. No waiver by either Party of any condition or term shall be
deemed as a continuing waiver of such condition or term or of another condition or term.

     11.6 Headings. Section and subsection headings are inserted for convenience of
reference only and do not form part of this Agreement.

     11.7 Assignment. Neither this Agreement nor any right or obligation hereunder may be
assigned, delegated or otherwise transferred, in whole or part, by either Party without the prior
express written consent of the other; provided, that, either Party may, without the
written consent of the other, assign this Agreement and its rights and delegate its obligations
hereunder to its Affiliates or in connection with the transfer or sale of all or substantially all
of such Party’s assets or business or in the event of its merger, consolidation, change in control
or similar transaction. Any permitted assignee shall assume all obligations of its assignor under
this Agreement. Any purported assignment in violation of this Section 11.7 shall be void. The
terms and conditions of this Agreement shall be binding upon and inure to the benefit of the
permitted successors and assigns of the parties.

     11.8 Force Majeure. Neither Party shall be liable for failure of or delay in
performing obligations set forth in this Agreement, and neither shall be deemed in breach of its
obligations, if such failure or delay is due to natural disasters or any causes beyond the
reasonable control of

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

37

 

such Party. In event of such force majeure, the Party affected thereby shall use reasonable
efforts to cure or overcome the same and resume performance of its obligations hereunder.

     11.9 Construction. The Parties hereto acknowledge and agree that: (i) each Party and
its counsel reviewed and negotiated the terms and provisions of this Agreement and have contributed
to its revision; (ii) the rule of construction to the effect that any ambiguities are resolved
against the drafting Party shall not be employed in the interpretation of this Agreement; and (iii)
the terms and provisions of this Agreement shall be construed fairly as to all Parties hereto and
not in favor of or against any Party, regardless of which Party was generally responsible for the
preparation of this Agreement.

     11.10 Severability. If any provision(s) of this Agreement are or become invalid, are
ruled illegal by any court of competent jurisdiction or are deemed unenforceable under then current
applicable law from time to time in effect during the Term hereof, it is the intention of the
Parties that the remainder of this Agreement shall not be affected thereby; provided,
that, a Party’s rights under this Agreement are not materially affected. The Parties
hereto covenant and agree to renegotiate any such term, covenant or application thereof in good
faith in order to provide a reasonably acceptable alternative to the term, covenant or condition of
this Agreement or the application thereof that is invalid, illegal or unenforceable, it being the
intent of the Parties that the basic purposes of this Agreement are to be effectuated.

     11.11 Status. Nothing in this Agreement is intended or shall be deemed to constitute
a partner, agency, employer-employee or joint venture relationship between the Parties.

     11.12 Further Assurances. Each Party agrees to execute, acknowledge and deliver such
further instructions, and to do all such other acts, as may be necessary or appropriate in order to
carry out the purposes and intent of this Agreement.

     11.13 Counterparts. This Agreement may be executed simultaneously in one or more
counterparts, each of which shall be deemed an original, but all of which together shall constitute
one and the same instrument.

[Remainder of page intentionally left blank.]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

38

 

     IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed by their respective
duly authorized representative in two (2) originals.

	 	 	 	 	 	 	 	 	 	 	 
	OPHTHOTECH CORPORATION	 	 	 	ARCHEMIX CORP.	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	By: 

Name:

	 	/s/ Samir Patel
 

Samir Patel
	 	 	 	By:

Name:
	 	/s/ John A. Harre
 

John A. Harre
	 	 
	Title:

	 	CEO
	 	 	 	Title:
	 	Vice President	 	 

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

39

 

Schedule 1

Chemical Composition of ARC 1905

ARC1905 is a [***] oligonucleotide having the following sequence:

[***]

The composition of the Aptamer is as follows: [***]

The chemical name for the sodium salt of ARC1905 is:

[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Schedule 1-1

 

     [***]

Molecular Structure of ARC1905

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Schedule 1-2

 

Schedule 2

Chemical Composition of ARC 186

ARC 186
corresponds to the [***] oligonucleotide portion of ARC1905 (set forth in Schedule 1)

 with a [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Schedule 2-1

 

Schedule 3

Financial Parameters for [***] Sublicense

Upfront (one-time fee):

$[***] upfront

Milestones (each payable [***] licensed product covered by patent rights sublicensed pursuant to
the [***] sublicense and developed by Ophthotech or any of its Affiliates or Sublicensees):

$[***] [***]

$[***] [***]

$[***] [***]

$[***] [***] by the [***] in the [***] of the [***] or [***]

Royalties:

[***]% of net sales of licensed product covered by patent rights sublicensed pursuant to the [***]
sublicense, which sales are made by Ophthotech or any of its Affiliates or Sublicensees

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Schedule 3-1

 

Exhibit A

Licensed Patent Rights

1. U.S. Patent Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

2. U.S. Patent Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

3. E.P Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

4. Japan Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

5. U.S. Patent Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

6. PCT Application Serial No.: [***]

Archemix file: [***]

Filed: [***]

Entitled: [***]

7. U.S. Patent [***]

Serial No.: [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

8. U.S. Provisional Patent Application. Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit A-1

 

9. U.S. Provisional Patent Application Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

10. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

11. U.S. Application Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

12. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

13. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

14. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

15. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

16. U.S. Patent Application Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

17. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit A-2

 

18. U.S. Patent Application Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

19. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

20. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

21. U.S. Patent Application Serial No.: [***]

Filed: [***]

Archemix file: [***]

Entitled: [***]

22. U.S. Patent [***]

Issued: [***]

Archemix file: [***]

Entitled: [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit A-3

 

Exhibit B

Development Plan — Treatment of Age-Related Macular Degeneration

Draft timeline through 2009 for [***] Studies. Diamonds indicate approximate times of milestone
events as indicated below.

[***]

	 	1)	 	[***] of [***] for a [***] for a [***]
	 
	 	2)	 	[***] of [***] of [***], the [***] for which [***] by the [***], for a [***] for a
[***]
	 
	 	3)	 	[***] of the [***] that [***] and [***] for a [***] as described on Exhibit D
	 
	 	4)	 	[***] of [***] of [***] (as defined in [***]) for a [***] for a [***], defined as a
[***] of the [***] in [***] OR [***] described on Exhibit D.
	 
	 	5)	 	[***] of [***] of [***], the [***] for which [***] by the [***], for a [***] for a
[***].

Descriptions of [***] are set forth in Exhibit D.

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit B-1

 

Exhibit C

Mandatory Jurisdictions for Patent Prosecution

[***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit C-1

 

Exhibit D

Phase I Clinical Program

[***]

	•	 	Goal: [***] the [***] and [***] of an [***]
	 
	•	 	Design:

	 	o	 	[***], [***]
	 
	 	o	 	[***]
	 
	 	o	 	[***]

	•	 	Endpoints:

	 	o	 	[***]
	 
	 	o	 	[***]
	 
	 	o	 	[***] ([***])

	 	Ø 	 	[***] and [***]
	 
	 	Ø	 	[***] any [***]
	 
	 	Ø	 	[***]
	 
	 	Ø	 	[***]
	 
	 	Ø	 	[***]

	 	o	 	[***]

	 	Ø	 	[***]

	 	o	 	[***] and [***]

	 	Ø	 	[***] and [***] of [***]

[***]

	•	 	Goal: Demonstrate preliminary safety and [***] of an [***] in [***]

	 	o	 	Design:

	 	Ø	 	[***]
	 
	 	Ø	 	[***] from the [***]
	 
	 	Ø	 	[***] on [***]

	•	 	Endpoints

	 	o	 	Safety Endpoints

	 	Ø	 	[***] as in [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit D-1

 

	 	o	 	Efficacy Endponts

	 	Ø	 	[***] — [***] of [***] with [***]
	 
	 	Ø	 	[***]

	 	§	 	[***]
	 
	 	§	 	[***] in [***]
	 
	 	§	 	[***] in [***] and [***]
	 
	 	§	 	[***] in [***]

[***]

	•	 	Goal: [***] and [***] of an [***] with an [***] in [***]

	•	 	Design:

	 	o	 	[***] with an [***]
	 
	 	o	 	[***]

	•	 	Efficacy Endpoints

	 	o	 	[***] — [***] of [***] with [***]
	 
	 	o	 	[***]

	 	Ø	 	[***]
	 
	 	Ø	 	[***] in [***]
	 
	 	Ø	 	[***] in [***] and [***]
	 
	 	Ø	 	[***] in [***]

	•	 	Safety Endpoints

	 	o	 	[***] as in [***]

Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant
to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

Exhibit D-2

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00151-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00151-of-00352.parquet"}]]