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.

9









 







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.

21









 








     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.

 









 








	 	 	 	 	 	 	 	 	 	 	 
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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.

 









 






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

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

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

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




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

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




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

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




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

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

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

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

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





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

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

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

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

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

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





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

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

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

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

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





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
	[***]

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

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

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

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

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

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

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

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

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

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

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

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







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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	 	[***]
	 	[***]





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.




 









 





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.