Exclusive License Agreement

Exhibit 10.46 Execution Copy EXCLUSIVE LICENSE AGREEMENT      This Exclusive License Agreement (this " Agreement ") is made effective as of July 31, 2007 (the " Effective Date "), by and between Archemix Corp, a Delaware corporation with offices at 300 Third Street, Cambridge, MA 02142 (" Archemix "), and Ophthotech Corporation, a Delaware corporation with offices at c/o SV Life Sciences, 60 State Street, Suite 3650, Boston, MA 02109 (" Ophthotech "). Archemix and Ophthotech are each hereinafter referred to individually as a " Party " and together as the " Parties ."      WHEREAS, Archemix is the owner of or otherwise controls, certain patents and proprietary technology;      WHEREAS, Ophthotech desires to obtain an exclusive license from Archemix under such patents and technology to develop and commercialize certain products; and      WHEREAS, Archemix desires to grant such license to Ophthotech on the terms and subject to the conditions of this Agreement.      NOW, THEREFORE, in consideration of the mutual covenants contained herein, and for other good and valuable consideration, the receipt and adequacy of which are hereby acknowledged, the Parties hereby agree as follows: ARTICLE 1 DEFINITIONS      Whenever used in the Agreement with an initial capital letter, the terms defined in this Article 1 shall have the meanings specified.      1.1 " Adverse Event " means any untoward, undesired or unplanned medical occurrence in a human clinical trial subject or a patient, which occurrence has a temporal relationship to administration of a Licensed Product, whether or not considered related to the Licensed Product, including, without limitation, any undesirable sign (including abnormal laboratory findings of clinical concern), symptom or disease that may be associated with the use of such Licensed Product.      1.2 " Acceptance " means, with respect to an IND, [***] days from the date such IND is received by the FDA, if no clinical hold is issued by the FDA with respect thereto or, to the extent issued, such later date on which such IND is no longer subject to that clinical hold.      1.3 " Affiliate " means, with respect to any Person, any other Person that, directly or indirectly, controls or is controlled by or is under common control with, such Person. For purposes of this definition, "control" means (a) ownership of fifty percent (50%) or more of the shares of stock entitled to vote for the election of directors in the case of a corporation or fifty percent (50%) or more of the equity interests in the case of any other type of legal entity, (b) status as a general partner in any partnership, or (c) any other arrangement whereby a Person controls or has the right to control the board of directors of a corporation or equivalent governing body of an entity other than a corporation. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

     1.4 " AMD " means age-related macular degeneration and includes the following separate Indications: wet AMD and dry AMD.      1.5 " Annual Net Sales " means, with respect to any Calendar Year, the aggregate amount of the Net Sales for such Calendar Year.      1.6 " Anti-C5 Aptamer " means an Aptamer that binds to C5 provided by Archemix to, or identified in the Anti-C5 Aptamer-Specific Patent Rights licensed to, Ophthotech under this Agreement, including without limitation any Aptamer that binds to C5 as set out in the issued patents and pending patent applications listed in Exhibit A , and any Aptamer(s) Derived therefrom.      1.7 " Anti-C5 Aptamer-Specific Patent Rights " means any Licensed Patent Rights that specifically claim ARC186, ARC1905 and/or any other Aptamer that binds to C5 or the manufacture, use, offer for sale, sale or importation thereof in the Field.      1.8 " Applicable Laws " means federal, state, local, national and supra-national laws, statutes, rules and regulations, including any rules, regulations guidance, guidelines or requirements of regulatory authorities, national securities exchanges or securities listing organizations, that may be in effect from time to time during the Term and are applicable to a particular activity hereunder.      1.9 " Aptamer " means (a) any naturally or non-naturally occurring oligonucleotide identified through the SELEX Process that binds with high specificity and affinity to a Target, and (b) any oligonucleotide Derived from an oligonucleotide of clause (a) that has such high specificity and affinity to a Target.      1.10 " ARC186 " means an unpegylated Anti-C5 Aptamer having the chemical composition set forth in Schedule 2 attached hereto.      1.11 " ARC1905 " means a pegylated Anti-C5 Aptamer having the chemical composition set forth in Schedule 1 attached hereto.      1.12 " Archemix Collaborative Partner " means any Third Party with whom Archemix is engaged, from time to time, in a collaborative effort to research, develop or commercialize Aptamers, which collaborative effort is evidenced by a written agreement. For purposes of clarity, as used in this definition, a "collaborative effort" includes, without limitation, out-licensing of products developed by Archemix or its Affiliates.      1.13 " Archemix-Gilead License Agreement " means the License Agreement between Gilead Sciences, Inc. and Archemix dated October 21, 2001, as amended.      1.14 " C5 " means complement factor C5.      1.15 " Calendar Quarter " means the period beginning on the Effective Date and ending on the last day of the calendar quarter in which the Effective Date falls, and thereafter each successive period of three (3) consecutive calendar months ending on March 31, June 30, Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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September 30 or December 31.      1.16 " Calendar Year " means the period beginning on the Effective Date and ending on December 31 of the year in which the Effective Date falls and thereafter each successive period of twelve (12) months commencing on January 1 and ending on December 31.      1.17 " Challenge " means any challenge to the validity or enforceability of any Licensed Patent Right, in the absence of a breach of this Agreement by Ophthotech, including, without limitation, by (a) filing a declaratory judgment action in which any Licensed Patent Right is alleged to be invalid or unenforceable; (b) citing prior art pursuant to [***], filing a request for re-examination of any Licensed Patent Right pursuant to [***] and/or [***] or provoking or becoming party to an interference with an application for any Licensed Patent Right pursuant to [***]; or (c) filing or commencing any reexamination, opposition, cancellation, nullity or similar proceedings against any Licensed Patent Right in any country.      1.18 " Commercially Reasonable Efforts " means, with respect to activities of Ophthotech under this Agreement, the efforts and resources customarily used by similarly sized biotechnology companies in the performance of such activities for other products owned by such companies which are of similar market potential and at a similar stage of development, taking into account the competitiveness of the market place, the regulatory structure involved and other relevant and material factors.      1.19 " Complement Cascade " means the following plasma proteins which are part of a cascade of reactions by which pathogen recognition is converted into an effective host defense against initial infection: [***].      1.20 " Completion " means, with respect to a clinical trial, the closing of the database with respect to that applicable clinical trial.      1.21 " Confidential Information " means all information and Technology disclosed or provided by, or on behalf of a Party (the " Disclosing Party ") to the other Party (the " Receiving Party ") or to any of the Receiving Party’s employees, consultants, Affiliates or sublicensees pursuant to or in connection with this Agreement; provided , that , none of the foregoing shall be Confidential Information if: (a) as of the date of disclosure, it is known to the Receiving Party or its Affiliates, as demonstrated by credible written documentation, other than by virtue of a prior confidential disclosure to such Receiving Party; (b) as of the date of disclosure it is in the public domain or it subsequently enters the public domain other than through a breach by the Receiving Party or its Affiliates of a contractual obligation; (c) it is obtained by the Receiving Party from a Third Party having a lawful right to make such disclosure free from any obligation of confidentiality to the Disclosing Party or its Affiliates; or (d) it is independently developed by or for the Receiving Party or its Affiliates without reference to or use of any Confidential Information of the Disclosing Party or its Affiliates as demonstrated by credible written documentation. For purposes of clarity, unless excluded from Confidential Information pursuant to the provisos of the preceding sentence, any scientific, technical or financial information Controlled by a Disclosing Party and disclosed at any meeting of the Parties or disclosed through an audit report shall constitute Confidential Information of the Disclosing Party. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     1.22 " Control " or " Controlled " means with respect to Technology or Patent Rights, the possession by a Party of the right to grant a license or sublicense to such Technology or Patent Rights as provided herein solely to the extent that such grant does not (a) violate the terms of any agreement or arrangement with any Third Party or (b) violate any Applicable Laws. Notwithstanding the foregoing, with respect to Technology or Patent Rights licensed by Archemix from a Third Party after the Effective Date (i.e., with respect to Technology or Patent Rights that are not Licensed Technology or Licensed Patent Rights as of the Effective Date), where the grant of a license or sublicense to Ophthotech to such Technology or Patent Rights as provided herein would require a payment of additional consideration by Archemix to such Third Party licensor, Control by Archemix shall be deemed to exist only if Ophthotech agrees to reimburse Archemix for such additional payment of consideration.      1.23 " Derived " means identified, obtained, developed, created, synthesized, designed or resulting from, based upon, containing or incorporating or generated from or conjugated to or complexed with (whether directly or indirectly or in whole or in part).      1.24 " Development " and " Develop " means, with respect to any Licensed Product, all activities with respect to such Licensed Product relating to research and development in connection with seeking, obtaining and/or maintaining any regulatory approval (including without limitation any Regulatory Approval) for such Licensed Product in the Field in the Territory, including, without limitation, all pre-clinical research and development activities, all human clinical studies, all activities relating to developing the ability to manufacture any Licensed Product or any component thereof (including, without limitation, process development work), and all other activities relating to seeking, obtaining and/or maintaining any regulatory approvals for Licensed Products (including without limitation any Regulatory Approvals) from the FDA and/or any Foreign Regulatory Authority.      1.25 " Diagnosis " means (a) the determination or monitoring of (i) the presence or absence of a disease, (ii) the stage, progression or severity of a disease or (iii) the effect on a disease of a particular treatment; and/or (b) the selection of patients for a particular treatment with respect to a disease.      1.26 " Diagnostics " means In Vitro Diagnostics, In Vivo Diagnostics and any Aptamer product used for Diagnosis.      1.27 " Field " means the prevention, treatment, cure or control of all Indications of the eye, adnexa of the eye, orbit and optic nerve, but excluding Diagnostics.      1.28 " First Commercial Sale " means, on a country-by-country basis, the date of the first arm’s length transaction, transfer or disposition for value to a Third Party of a Licensed Product by or on behalf of, Ophthotech, its Affiliate or Sublicensee in such country. For purposes of clarity, the use of any Licensed Product in clinical trials, pre-clinical studies or other research or development activities or the disposal or transfer of a Licensed Product for a bona fide charitable purpose or for purposes of a commercially reasonable sampling program shall not be deemed to be an arm’s length transaction, transfer or disposition for value for purposes of this definition. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     1.29 " FDA " means the United States Food and Drug Administration and any successor agency or authority thereto.      1.30 " Foreign Regulatory Authorities " means any applicable supranational, national, federal, state or local regulatory agency, department, bureau or other governmental entity of any country or jurisdiction in the Territory (other than the FDA in the United States), having responsibility in such country or jurisdiction for any Regulatory Approvals of any kind in such country or jurisdiction, and any successor agency or authority thereto.      1.31 " FTE " means [***] hours of work devoted to, or in support of, the Archemix technology transfer activities performed pursuant to Section 3.5.4 hereof carried out by one or more appropriately trained employees of Archemix, measured in accordance with Archemix’s time allocation practices from time to time.      1.32 " FTE Costs " means the sum of [***] Dollars ($[***]) multiplied by the number of FTEs in such period.      1.33 " IND " means an investigational new drug application (as defined in Title 21 of the United States Code of Federal Regulations, as amended from time to time) filed or to be filed with the FDA with regard to any Licensed Product.      1.34 " Indication " means any human indication, disease, disorder or condition in the Field, which can be treated, controlled, prevented, cured or the progression of which can be delayed. For purposes of clarity, whether any such indication, disease, disorder or condition constitutes a separate Indication shall be determined by reference to the applicable ICD-9 codes, with each separate code constituting a separate Indication; provided , that , with respect to AMD, wet AMD and dry AMD, and only wet AMD and dry AMD, shall constitute separate Indications. "ICD-9" means the World Health Organization International Classification of Diseases, version 9, and excludes any other versions of the ICD.      1.35 " In Vitro Diagnostics " means the use of the SELEX Process or Aptamers in the assay, testing or determination, outside of a living organism, of a substance in a test material. In Vitro Diagnostics shall include, among other things, the use of the SELEX Process or Aptamers in the assay, testing or determination: (a) outside of a living organism, (i) of a human substance in a test material, often to identify or follow the progression of a disease or disorder or to select a patient for treatment; (ii) of a plant substance, animal substance or other substance in a test material, often to identify or follow the progression of a disease, process or disorder in a human or non-human organism; and (iii) of environmental substances (as in water quality testing); (b) of a substance on a test material such as cells (as in FACS analysis or other measurements of pathogens within biological samples); and (c) any other in vitro diagnostic use of the SELEX Process or Aptamers in drug development processes, including target identification, pre-clinical and clinical testing, and the following more specific examples of uses of Aptamer technology: (i) to observe, through protein profiling, protein levels moving up or down in diseases or models of diseases, and to evaluate whether such proteins are sensible targets for the development of therapeutic agents; (ii) to observe coordinated expression of protein pathways in a variety of biological states in various systems; (iii) to study protein or metabolite levels during pre-clinical Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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drug candidate evaluation in response to putative therapeutic agents during clinical trials ( e.g. , as markers of efficacy or response); and (iv) to study human protein or metabolite levels in response to putative therapeutic agents during clinical trials ( e.g. , as markers of efficacy or response). Notwithstanding the above, In Vitro Diagnostics shall exclude any of the above-described uses in this Section 1.34 conducted in the Development of Anti-C5 Aptamers under this Agreement.      1.36 " In Vivo Diagnostics " means the use of any product containing one or more Aptamers for any human in vivo diagnostic purpose related to ( inter alia ) the identification, quantification or monitoring of the propensity toward or actual existence of, any disease state.      1.37 " Knowledge " means, with respect to Archemix, the actual knowledge of the chief executive officer, any vice president or the chief legal officer of Archemix.      1.38 " Legal Exclusivity Period " means, with respect to a Licensed Product and a country in the Territory, the period (a) beginning on the earlier of the commencement of the Patent-Based Exclusivity Period or of the Non Patent-Based Exclusivity Period and (b) expiring on the later of the expiration of the Patent-Based Exclusivity Period or the Non Patent-Based Exclusivity Period.      1.39 " Licensed Patent Rights " means all Patent Rights Controlled by Archemix or any of its Affiliates during the Term that cover or claim Licensed Products in the Field, including without limitation the Development, manufacture, use, offer for sale, sale or importation thereof. For purposes of clarity, the Licensed Patent Rights, as of the Effective Date, include without limitation the Patent Rights listed on Exhibit A attached hereto.      1.40 " Licensed Product " means any pharmaceutical product comprised of or Derived from, in whole or in part, ARC1905, ARC186 and/or any other Anti-C5 Aptamer.      1.41 " Licensed Technology " means any Technology Controlled by Archemix or any of its Affiliates during the Term that is necessary or useful for the Development, manufacture, use, offer for sale, sale or importation of Licensed Products in the Field.      1.42 " Material EU Country " means each of the United Kingdom, Germany, France, Italy and Spain.      1.43 " Net Sales " means the gross amount billed or invoiced by Ophthotech or any of its Affiliates or Sublicensees to Third Parties throughout the Territory for sales or other dispositions or transfers for value of Licensed Products less (i) allowances for normal and customary trade, quantity and cash discounts actually allowed and taken, and inventory management fees paid to wholesalers and distributors, (ii) transportation, insurance and postage charges, if paid by Ophthotech or any Affiliate or Sublicensee and included on any such Third Party’s bill or invoice as a separate item, (iii) credits, chargebacks, retroactive price reductions, rebates and returns, to the extent actually allowed, (iv) negotiated payments made to private sector and government Third Party payors (e.g., PBMs, HMOs and PPOs) and purchasers/providers (e.g., staff model HMOs, hospitals and clinics), regardless of the payment Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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mechanism, including without limitation off-invoice, rebate, chargeback and credit mechanisms, (v) discounts paid under discount prescription drug programs and reductions for coupon and voucher programs; (vi) any tax, tariff, customs duty, excise or other duty or other governmental charge (other than a tax on income) levied on the sale, transportation or delivery of Licensed Product and actually paid by Ophthotech or any of its Affiliates or Sublicensees; and (vii) portions of gross amounts billed or invoiced that are written off as uncollectible, not to exceed [***] percent ([***]%) of Annual Net Sales in any Calendar Year. In addition, Net Sales are subject to the following:           (a) If Ophthotech or any of its Affiliates or Sublicensees effects a sale, disposition or transfer of a Licensed Product to a customer in a particular country as part of a package of Licensed Products and services (but not in a Combination Product), the Net Sales of such Licensed Product to such customer shall be deemed to be "the fair market value" of such Licensed Product less applicable discounts pursuant to this definition of Net Sales. For purposes of this subsection (a), "fair market value" shall mean the fraction (A/A+B), where A equals the value that would have been derived had such Licensed Product been sold as a separate Licensed Product to another customer in the country concerned on customary commercial terms and B equals the aggregate value that would have been derived had the other components of such package been sold as separate products to another customer in the country concerned on customary commercial terms.           (b) In the case of pharmacy incentive programs, hospital performance incentive program chargebacks, disease management programs, similar programs or discounts on "bundles" of Licensed Products, all discounts and the like shall be allocated among Licensed Products on the basis of which such discounts and the like were actually granted or, if such basis cannot be determined, in proportion to the respective list prices of such Licensed Products.           (c) For purposes of clarity, use of any Licensed Product in clinical trials, pre-clinical studies or other research or development activities or disposal or transfer of Licensed Products for a bona fide charitable purpose or purposes of a commercially reasonable sampling program shall not give rise to any Net Sales.           (d) Sales or transfers of Licensed Product among Ophthotech, its Affiliates and Sublicensees for the purpose of subsequent resale to Third Parties shall not be included in Net Sales; with respect to such sales or transfers, the gross amounts billed or invoiced in connection with the subsequent resale to Third Parties will be included in the calculation of Net Sales.      In the event that a Licensed Product under this Agreement is sold in combination (" Combination Product ") with another ingredient or component having independent, supplementary or enabling therapeutic effect (e.g., as a catalyst or adjuvant) or diagnostic utility or that has independent function as a medical device or means of administration (a " Supplemental Component "), then "Net Sales," for purposes of determining royalty payments on the Combination Product, shall be calculated using one of the following methods: Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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          (y) By multiplying the Net Sales of the Combination Product (calculated prior to the application of this formula) by the fraction C/C+D, where C is the average gross selling price, during the applicable Calendar Quarter in the country concerned, of the Licensed Product when sold separately, and D is the average gross selling price, during the applicable Calendar Quarter in the country concerned, of the Supplemental Component(s) when sold separately; or           (z) In the event that no such separate sales are made of the Licensed Product or any of Supplemental Components in such Combination Product during the applicable Calendar Quarter in the country concerned, Net Sales, for the purposes of determining royalty payments shall be calculated using the above formula where C is the reasonably estimated commercial value of the Licensed Product sold separately and D is the reasonably estimated commercial value of the Supplemental Components sold separately. Any such estimates shall be determined using criteria to be mutually agreed upon by the Parties. Such estimates shall be reported to Archemix in the reports to be provided pursuant to Section 4.5.1 hereof. If the Parties are unable to agree on the criteria for determining such estimates, either Party may submit such dispute for resolution pursuant to the provisions of Section 10.2.2 (Accelerated Arbitration).      1.44 " Non Patent-Based Exclusivity Period " means, with respect to a Licensed Product in a country in the Territory, that period of time during which no Third Party has been granted the legal right by the FDA or any Foreign Regulatory Authority, as applicable, in such country to market and sell the Licensed Product in such country.      1.45 " Non-Royalty Term " means, with respect to each Licensed Product, the period commencing on the Effective Date and continuing on a product-by-product, and country-by-country basis until the date on which no further payments of Sublicense Income are received by Ophthotech.      1.46 " Patent-Based Exclusivity Period " means, with respect to a Licensed Product and a country in the Territory, that period of time during which at least one Valid Claim of the Licensed Patent Rights covers the Licensed Product.      1.47 " Patent Rights " means all rights and interests in and to issued patents and pending patent applications including, without limitation, provisional and non-provisional patent applications, and all divisions, continuations and continuations-in-part thereof, patents issuing on any of the foregoing, all reissues, reexaminations, renewals and extensions thereof, and supplementary protection certificates therefor, as well as any certificates of invention or applications therefor, and all foreign equivalents of any of the foregoing.      1.48 " Permitted Activities " means any activity conducted by or on behalf of Archemix or any Third Party licensee or sublicensee of Archemix with respect to (a) applications of aptamers that bind to C5 (including Anti-C5 Aptamers) outside of the Field and/or (b) the use of aptamers that bind to C5 (including Anti-C5 Aptamers) against Targets (including C5) outside of the Field.      1.49 " Person " means an individual, sole proprietorship, partnership, limited partnership, limited liability partnership, corporation, limited liability company, business trust, Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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joint stock company, trust, incorporated association, joint venture or similar entity or organization, including a government or political subdivision, department or agency of a government.      1.50 " Phase I Clinical Trial " means a clinical trial conducted in healthy humans or in patients with a particular disease or condition, which clinical trial is designed to initially explore the safety, drug-drug interactions and/or pharmacokinetics of an investigational drug given its intended use, and to support continued testing of such drug in Phase II Clinical Trials. For purposes of clarity, a Phase I Clinical Trial may also initially explore efficacy if a safety endpoint for such trial coincides with an initial indication of efficacy.      1.51 " Phase II Clinical Trial " means a clinical trial conducted in patients with a particular disease or condition, which clinical trial is designed to establish the safety, appropriate dosage and pharmacological activity of an investigational drug given its intended use, and to initially explore its efficacy for such disease or condition.      1.52 " Phase III Clinical Trial " means a pivotal clinical trial conducted in patients with a particular disease or condition, which clinical trial is designed to ascertain efficacy and safety of an investigational drug for its intended use and to define warnings, precautions and Adverse Events that are associated with the investigational drug in the dosage range intended to be prescribed, with the purpose of preparing and submitting applications for Regulatory Approval or label expansion to the FDA in the United States or pertinent Foreign Regulatory Authority in a country outside the United States.      1.53 " Regulatory Approval " means any and all approvals (including pricing and reimbursement approvals), product and establishment licenses, registrations or authorizations of any kind of the FDA or any Foreign Regulatory Authority necessary for the marketing and commercial sale of a Licensed Product (or any component thereof) for use in the Field in any country or other jurisdiction in the Territory.      1.54 " Royalty Term " means, with respect to each Licensed Product, the period commencing on the Effective Date and continuing on a product-by-product, and country-by-country basis until the later of (a) the last to expire Valid Claim covering the Licensed Product in such country or (b) twelve (12) years from the date of First Commercial Sale of such Licensed Product in such country.      1.55 " SELEX Portfolio " means those Patent Rights licensed by Gilead to Archemix pursuant to the Archemix-Gilead License Agreement.      1.56 " SELEX Process " means any means used for the identification or generation of a nucleic acid that binds to a Target by means other than Watson-Crick base-pairing, including, without limitation, any process that (a) is covered by the SELEX Portfolio, including, without limitation, U.S. Patent Nos. [***] or [***], (b) is covered by any other Patent Rights Controlled by Archemix, or (c) is covered by any continuation, divisional, continuation-in-part, substitution, renewal, reissue, re-examination or extension, or any foreign equivalent of, the foregoing Patent Rights. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     1.57 " SELEX Technology " means any process for modifying, optimizing and/or stabilizing an Aptamer, wherein such modification, optimization or stabilization includes, without limitation, minimization, truncation, conjugation, pegylation, complexation, substitution, deletion and/or incorporation of modified nucleotides.      1.58 " Serious Adverse Event " means an Adverse Event occurring at any dose that (a) results in death, (b) is life-threatening, (c) requires inpatient hospitalization or prolongation of an existing hospitalization, (d) results in a persistent or significant disability or incapacity or (e) results in a congenital anomaly or birth defect. Additionally, important medical events that are not described in the immediately preceding sentence shall be considered Serious Adverse Events when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in the immediately preceding sentence.      1.59 " Sublicensee " means any Third Party to whom Ophthotech grants a sublicense of some or all of the rights granted to Ophthotech under this Agreement.      1.60 " Sublicense Income " means [***] payments received by Ophthotech or its Affiliates from its Sublicensees in connection with sublicenses granted hereunder excluding (a) payments [***] a Sublicensee to [***] or [***] to be [***] by such Ophthotech or its Affiliates [***] to a [***] for [***] which has been agreed to with the Sublicensee and based on full-time equivalent or other cost-accounting methodologies that are consistent with then current industry practices, (b) payments [***] of the [***] of Ophthotech to the extent that the [***] for [***] does not [***] the then [***] thereof, as [***] of Ophthotech; provided , that , if requested by Archemix, Ophthotech shall [***] Archemix with [***] for any [***] and any [***] any [***] may be submitted by either Party to arbitration pursuant to Section 10.2.2, and (c) [***] to Ophthotech by such Sublicensee on [***] (or, in the case of a [***] with a Sublicensee, [***] to Ophthotech by such Sublicensee) pursuant to the applicable sublicense agreement.      1.61 " Sustained Drug Delivery Product " means any Licensed Product comprising or incorporating Sustained Drug Delivery Technology.      1.62 " Sustained Drug Delivery Technology " means any Technology including, without limitation, any modifications to a Licensed Product and/or its formulation, designed to significantly prolong local effects relative to intravitreal injection of the Licensed Product.      1.63 " Target " means a protein, cytokine, enzyme, receptor, transducer, transcription factor, antigen or any other non-nucleic acid molecule.      1.64 " Technology " means, collectively, inventions, discoveries, improvements, trade secrets and proprietary methods, whether or not patentable, including, without limitation: (a) methods of production or use of, and structural and functional information pertaining to, chemical compounds and (b) compositions of matter, data, formulations, processes, techniques, know-how and results (including any negative results).      1.65 " Territory " means all countries and jurisdictions of the world. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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     1.66 " Third Party " means any person or entity other than Ophthotech, Archemix and their respective Affiliates.      1.67 " ULEHI " means University License Equity Holdings, Inc., formerly known as UTC.      1.68 " Unexpected Adverse Event " means an Adverse Event, the specificity or severity of which is not consistent with the current package insert or investigator’s brochure for the Licensed Product. An Unexpected Adverse Event includes any event that may be symptomatically and pathophysiologically related to an event listed in the current package insert or investigator’s brochure, but differs from the listed event because of greater severity or specificity.      1.69 " URC License Agreement " means the Restated Assignment and License Agreement, dated July 17, 1991, by and between University Research Corporation and Gilead Sciences, Inc. as successor in interest to NeXstar Pharmaceuticals, Inc.      1.70 " UTC " means University Technology Corporation, the successor to the University Research Corporation.      1.71 " Valid Claim " means any claim of a pending patent application or an issued, unexpired patent covered under the Licensed Patent Rights that (a) has not been finally cancelled, withdrawn, abandoned or rejected by any administrative agency or other body of competent jurisdiction, (b) has not been permanently revoked, held invalid or declared unpatentable or unenforceable in a decision of a court or other body of competent jurisdiction that is unappealable or unappealed within the time allowed for appeal, (c) has not been rendered unenforceable through disclaimer or otherwise, (d) is not lost through an interference proceeding and (e) in the case any claim of a pending patent application, is not pending more than [***] years from filing date of the earliest patent application from which such pending patent application claims priority.       Additional Definitions . In addition, each of the following definitions shall have the respective meanings set forth in the section of this Agreement indicated below:

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 2 GRANT OF RIGHTS      2.1 License to Ophthotech .           2.1.1 Grant of License . Archemix hereby grants to Ophthotech an exclusive, royalty-bearing license, including the right to grant sublicenses in accordance with Section 2.1.3, under the Licensed Patent Rights and Licensed Technology, to Develop, have Developed, make, have made, use, have used, sell, offer for sale, distribute for sale, have sold, import, have imported, export and have exported, Licensed Products in the Territory, for any and all uses within the Field, subject to the terms and conditions of this Agreement. For purposes of clarity, (a) Ophthotech shall have the right under this license to use SELEX Technology for the sole purpose of modifying Anti-C5 Aptamers for use in the Field, (b) Ophthotech shall have no right under this license to practice the SELEX Process for any reason, including to identify or modify aptamers, and (c) subject to Section 2.3, Archemix shall retain the right to use the Licensed Technology and practice the Licensed Patent Rights to (i) research, develop, have developed, make, have made, use, have used, sell, offer for sale, have sold, distribute for sale, import, have imported, export and have exported any product that is not a Licensed Product in the Field and (ii) research, develop, have developed, make, have made, use, have used, sell, offer for sale, Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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have sold, distribute for sale, import, have imported, export and have exported any Licensed Product outside the Field.           2.1.2 Negative Covenant . Ophthotech is not granted the right to, and hereby agrees that it will not (a) practice any inventions covered by a Valid Claim under the Licensed Patent Rights or the SELEX Process, except as expressly permitted under this Agreement, (b) research, develop, make, have made, use, have used, sell, offer for sale, have sold, distribute for sale, import, have imported, export or have exported Diagnostics or (c) perform any research or development on ARC1905, ARC186 and/or Anti C5 Aptamer for any use outside of the Field. Notwithstanding the foregoing provisions of this Section 2.1.2, (i) Ophthotech shall not be restricted by Section 2.1.2(a) or (b) from engaging in any activity that, in the absence of a license from Archemix, would not infringe a Valid Claim Controlled by Archemix, and the foregoing covenant by Ophthotech shall not apply to any such non-infringing activities and (ii) Ophthotech shall not be restricted by Section 2.1.2(a) or (b) from engaging in any activity in which Opthotech is permitted to engage pursuant to a license, sublicense or other right granted to Ophthotech in any agreement other than this Agreement with respect to the SELEX Portfolio, the SELEX Process, SELEX Technology or Aptamers, whether granted by Archemix, Gilead or any other Person having the right to grant such license, sublicense or other right.           2.1.3 Right to Sublicense . Ophthotech shall have the right to grant sublicenses to all or any portion of its rights under the license granted pursuant to Section 2.1.1; provided , that , (a) Archemix shall be notified of the grant of each such sublicense; (b) each such sublicense shall be subject to, and consistent with, the terms and conditions of this Agreement; (c) each such sublicense shall contain and include the following provisions of this Agreement (with appropriate modifications to account for the identities of the parties to such sublicense): Sections 2.1.2 (Negative Covenant), 2.1.4 (Reversion of License Rights), 2.1.5 (Gilead-Archemix License Agreement), 6.3.3 (Effect of Challenge) and 9.2.2 (Termination for Challenge); (d) each such sublicense shall contain and include provisions substantially similar to, and consistent with, the language provided in Sections 2.1.1 (Grant of License), 3.1.2 (Diligence), 4.3.1 (Royalties), and Article 5 (Treatment of Confidential Information); (e) upon termination of this Agreement, any such sublicense shall be considered a direct license from Archemix as provided in Section 9.3 hereof; and (f) Ophthotech shall provide Archemix with a copy of each sublicense agreement within thirty (30) days of execution. If requested by a Sublicensee in connection with the negotiation of a sublicense, Archemix shall enter into a "stand-by" license agreement directly with such Sublicensee to further document the provisional license described in the foregoing clause (e); provided , that , as a condition to Archemix’s execution of any such "stand-by" license, Ophthotech shall (i) provide to Archemix, at least ten (10) days prior to the anticipated date of execution, a copy of the proposed form of such "stand-by" license and any material information reasonably necessary for Archemix to ensure that the sublicense agreement conforms to all terms and conditions of sublicensing under this Agreement and (ii) reimburse Archemix for the reasonable legal fees and expenses incurred by Archemix in connection with its review and execution of such "stand-by" license.           2.1.4 Reversion of License Rights . Ophthotech acknowledges and agrees that each of the URC License Agreement and the Gilead-Archemix License Agreement provide that the Archemix rights in the SELEX Process or the SELEX Technology and the SELEX Portfolio may revert to Gilead or ULEHI if Archemix, its Affiliates and all assignees and sublicensees Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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cease to exercise reasonable efforts to develop the commercial applications of products and services utilizing the SELEX Process or the SELEX Technology. Ophthotech further acknowledges and agrees that the URC License Agreement provides that in the event of any termination of the URC License Agreement, the SELEX License granted to Ophthotech hereunder shall remain in full force and effect in accordance with Section 3.4 of the URC License Agreement; provided , that , Ophthotech is not then in breach of this Agreement and Ophthotech agrees to be bound to ULEHI as the licensor under the terms and conditions of this Agreement. Archemix shall inform Ophthotech of such event immediately after the Archemix rights revert to Gilead or ULEHI.           2.1.5 Gilead-Archemix License Agreement . Ophthotech acknowledges and agrees that the Gilead-Archemix License Agreement provides that in the event of any termination of the Gilead-Archemix License Agreement, the SELEX License granted to Ophthotech hereunder shall remain in full force and effect in accordance with Section 2.3 of the Gilead-Archemix License Agreement; provided , that , Ophthotech agrees to be bound to Gilead as the licensor under the terms and conditions of this Agreement; provided , that , if the termination of the Gilead-Archemix License Agreement arises out of the action or inaction of Ophthotech, Gilead, at its option, may terminate such license.      2.2 No Other Rights . Ophthotech is not granted any rights to use or otherwise exploit Licensed Patent Rights or Licensed Technology except as set forth in this Agreement.      2.3 Exclusivity and Right of First Negotiation .           2.3.1 Exclusivity . During the Term, neither Archemix nor any of its Affiliates will, alone or with a Third Party, conduct any activity, for the purpose of researching, developing or commercializing any aptamer that binds to C5 (including any Anti-C5 Aptamer) in the Field in the Territory. For purposes of clarity, the restrictions set forth in this Section 2.3.1 shall not apply to Permitted Activities. Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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          2.3.2 Right of First Negotiation . Archemix shall notify Ophthotech in writing if Archemix or an Affiliate of Archemix seeks to license [***] the [***] to any[***] for [***] the [***] in the [***], for [***] the [***] and shall grant Ophthotech an option to initiate negotiation of a license under Archemix’s interest in such rights (the " Option "). Concurrently with such notice, Archemix shall supply to Ophthotech a summary of such information in Archemix’s possession concerning [***], subject to Archemix’s confidentiality obligations to Third Parties. Such Option shall be in effect for a period of [***] days from the date of notice of the [***] pursuant to this Section 2.3.2 (the " Option Period "). Ophthotech may exercise the Option by providing written notice to Archemix within the Option Period of its intent to exercise such Option, at which time the Parties shall in good faith negotiate for up to [***] days (the " Negotiation Period ") an agreement for the commercial exploitation of such rights, which agreement shall contain commercially reasonable terms and conditions. If Ophthotech does not exercise the Option during the Option Period, provides written notice that it chooses not to exercise the Option, or the Negotiation Period expires without execution of an agreement between the Parties, then (i) neither Party shall have any further obligation to enter into or continue any negotiations with respect to the subject matter of the Option, and (ii) Archemix may license such rights to a Third Party without any further obligation to Ophthotech. For purposes of clarity, no Option shall arise if the rights that Archemix seeks to license [***] of the [***] of the [***]. ARTICLE 3 DEVELOPMENT AND COMMERCIALIZATION OF LICENSED PRODUCTS AND PROVISION OF MATERIALS .      3.1 Development and Commercialization .           3.1.1 Responsibility . From and after the Effective Date, Ophthotech shall have full control and authority over the Development and commercialization of Licensed Products in the Field in the Territory, including, without limitation, (a) all pre-clinical Development activities (including any pharmaceutical development work on formulations or process development relating to any Licensed Product), (b) all activities related to human clinical trials, (c) all activities relating to manufacture and supply of all Licensed Products (including all required process development and scale up work with respect thereto), (d) all marketing, promotion, sales, distribution, import and export activities relating to any Licensed Product, and (e) all activities relating to any regulatory filings, registrations, applications and Regulatory Approvals relating to any of the foregoing. Ophthotech shall own all data, results and all other information arising from any such activities under this Agreement, including, without limitation, all regulatory filings, registrations, applications and Regulatory Approvals relating to Licensed Products, and all of the foregoing information, documentation and materials shall be considered Confidential Information and Technology solely owned by Ophthotech. All activities relating to Development and commercialization under this Agreement shall be undertaken at Ophthotech’s sole cost and expense, except as otherwise expressly provided in this Agreement.           3.1.2 Diligence .                     (a)  General Diligence Obligations . Ophthotech will exercise Commercially Reasonable Efforts in Developing and commercializing at least one Licensed Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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Product in the Field and in undertaking investigations and actions required to obtain Regulatory Approvals necessary to market such Licensed Product in the Field in the United States, the European Union, and Japan, and in such ex-United States markets, in addition to the European Union and Japan, where Ophthotech determines, in the exercise of Commercially Reasonable Efforts, that it is commercially reasonable to do so. In the event that Ophthotech fails to use Commercially Reasonable Efforts as required hereunder, then on a Licensed Product-by-Licensed Product and country-by-country basis as to such Licensed Product in such country, Archemix may, in its sole discretion (i) terminate the licenses granted under Article 2 of this Agreement for breach under Section 9.2.3 below, or (ii) convert the licenses granted under Article 2 of this Agreement from exclusive licenses to non-exclusive licenses, in either case only as such licenses apply to such Licensed Product in such country(ies); provided that , if Ophthotech is exercising Commercially Reasonable Efforts in each Material EU Country, then Archemix may not so terminate or convert such licenses as to any country in the European Union. The foregoing provisions of this Section 3.1.2(a) shall constitute Archemix’s sole and exclusive remedies and Ophthotech’s sole and exclusive liabilities for any failure by Ophthotech to exercise Commercially Reasonable Efforts to Develop or commercialize any Licensed Product in any country or in the European Union pursuant to this Section 3.12(a). In satisfying its obligation to use Commercially Reasonable Efforts with respect to such Licensed Product, Ophthotech may engage in Development and commercialization activities in various markets in a reasonably sequenced manner, it being understood that Development and commercialization in the United States, the European Union, Japan and other markets likely will not be pursued by Ophthotech on concurrent Development and commercialization schedules.                     (b)  Specific Diligence Obligations . Without limiting the generality of the provision of Section 3.1.2 above, Ophthotech hereby agrees that it will:                          (i) file an [***] for a Licensed Product for an [***] within [***] within [***] years of the Effective Date;                          (ii) complete a [***] of a Licensed Product for an [***] within [***] within [***] years of the Effective Date; and                          (iii) complete a [***] of a Licensed Product for an [***] within [***] within [***] years of the Effective Date.                     (c)  Effect of Failure to Meet Obligations . If Ophthotech fails to meet any of the milestones set forth above in Section 3.1.2(b) by the applicable deadline, but is otherwise in compliance with the provisions of Section 3.1.2(a) during the applicable diligence period specified above, then Archemix and Ophthotech will negotiate in good faith an extension of these milestone deadlines. If Ophthotech (i) fails to meet any of the milestones set forth above in Section 3.1.2(b) by such extended deadline, or (ii) fails to meet any of the milestones set forth above in Section 3.1.2(b) by the applicable deadline, and is not otherwise in compliance with the provisions of Section 3.1.2(a) during the applicable diligence period specified above, Archemix may, in its sole discretion (i) terminate the licenses granted under Article 2 of this Agreement for breach under Section 9.2.3 below or (ii) convert the licenses granted under Article 2 of this Agreement from exclusive licenses to non-exclusive licenses. The foregoing provisions of this Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.

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Section 3.1.2(c) shall constitute Archemix’s sole and exclusive remedies and Ophthotech’s sole and exclusive liabilities for any failure by Ophthotech to meet any of the milestones set forth above in Section 3.1.2(b) by the applicable deadline, as such deadline may be extended pursuant to this Section 3.1.2(c).      3.2 Development Plan . Ophthotech shall submit to Archemix for approval, which approval will not be unreasonably withheld, conditioned or delayed, a development plan (" Development Plan ") for each Licensed Product that Ophthotech intends to Develop and commercialize in the Field, which shall include, without limitation, detailed [***] criteria (" [***] ") for each Indication and the schedule for demonstrating such [***]. Attached hereto as Exhibit B is the Development Plan, including [***] and [***] [***] criteria, prepared by Ophthotech and approved by Archemix for the Development of a Licensed Product for the treatment of one or more [***] within [***]. Amendments to the Development Plan attached hereto as Exhibit B and all subsequent Development Plans shall be submitted to Archemix for its review and approval, which shall not be unreasonably withheld, conditioned or delayed. Archemix shall provide Ophthotech with notice of its approval or rejection of any such amendment or Development Plan within [***] days of receipt. If the Parties are unable to agree on any such amendment or Development Plan, either Party may submit such dispute for resolution pursuant to the provisions of Article 10.      3.3 Progress Reports . Ophthotech shall provide Archemix with written rep