Research License And Option Agreement BY And Between Archemix Corp. And Ribomic, Inc., Date

Exhibit 10.49 Execution Copy RESEARCH LICENSE AND OPTION AGREEMENT This Research License and Option Agreement (this " Agreement" ) is made effective as of June 11, 2008 (the " Effective Date" ), by and between Archemix Corp, a Delaware corporation with offices at 300 Third Street, Cambridge, MA 02142 (" Archemix" ), and Ribomic, Inc., a corporation organized under the laws of Japan with offices at Shirokanedai Usui Building, 3-16-13 Shirokanedai, Minato-ku, Tokyo 108-0071 Japan (" Ribomic" ). Archemix and Ribomic are each sometimes hereinafter referred to individually as a " Party" and collectively as the " Parties." WHEREAS, Archemix is the owner of or otherwise controls, certain patents related to (a) the identification and optimization of aptamers using its proprietary SELEX Process and SELEX Technology (each as defined herein) and (b) the use of such aptamers for controlling, curing, treating, preventing or delaying the onset or progression of human diseases and conditions; WHEREAS, Ribomic desires to obtain from Archemix a non-exclusive license under such patents to conduct Research Activities (as defined below) with respect to certain Active Targets (as defined below) and an Option (as defined below) to obtain an exclusive license to develop and commercialize Aptamers against such Active Targets; and WHEREAS, Archemix desires to grant such license and Option to Ribomic 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: 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 " Active Aptamer" means any Aptamer that binds to an Active Target and any Aptamer(s) Derived therefrom that binds to such Active Target. 1.2 " Active Target" means the Targets listed on the Active Target List. 1.3 " Active Target List" means the list of up to six (6) Active Targets set forth on Schedule 1 attached hereto, as amended from time to time by the Parties pursuant to Section 2.2.1(a). 1.4 " 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.


1.5 " 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. 1.6 " Aptamer" means (a) any naturally or non-naturally occurring oligonucleotide identified through the SELEX Process that binds with high specificity and affinity to an Active Target, and (b) any oligonucleotide derived from an oligonucleotide of clause (a) that has such high specificity and affinity to such Active Target, but excluding Spiegelmers. 1.7 " Archemix-Gilead License Agreement" means the License Agreement between Gilead Sciences, Inc. and Archemix dated October 21, 2001, as amended. 1.8 " 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. 1.9 " Challenge" means any challenge to the validity or enforceability of any Licensed Patent Right in the absence of a breach of this Agreement 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 [***] 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. 1.10 " Commercially Reasonable Efforts" means, with respect to the research activities of Ribomic under this Agreement, the efforts and resources customarily used by similarly sized biotechnology companies in the performance of such research 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. 1.11 " 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 (" Representatives" ) 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 Representatives, 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 Representatives 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 Representatives; or (d) it is independently developed by or for the Receiving Party or its Representatives without reference to or use of any Confidential Information of the Disclosing 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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Party or its Representatives 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 shall constitute Confidential Information of the Disclosing Party. 1.12 " 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 without the payment of additional consideration to, and without violating the terms of any agreement or arrangement with, any Third Party and without violating any Applicable Laws. 1.13 " Derived" means identified, developed, created, synthesized, designed, resulting or generated from, conjugated to or complexed with (whether directly or indirectly, or in whole or in part). 1.14 " 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. 1.15 " Diagnostic Product" means, collectively, In Vitro Diagnostic Agents, In Vivo Diagnostic Agents and any aptamer product used for Diagnosis. 1.16 " Existing License Agreements" means, collectively, (a) the Non-Exclusive IgG Antibody Purification License Agreement dated as of October 31, 2006, by and between Ribomic and Archemix, (b) the Exclusive License Agreement by and between Ribomic and Archemix dated as of December 10, 2007 and (c) any License Agreement executed by the Parties upon the exercise of any Option pursuant to this Agreement. 1.17 " Failed Target" means any Active Target that is removed from the Active Target List by Ribomic pursuant to Section 2.2.1(a), or is otherwise deemed to be a Failed Target pursuant to Section 2.4.4 and/or 8.3.1(c). 1.18 " Field" means the control, prevention, treatment, cure or delay of onset or progression of any Indication in animals and humans, but excluding, without limitation, Diagnostic Products, In Vivo Imaging Applications and all non-therapeutic uses. 1.19 " FDA" means the United States Food and Drug Administration and any successor agency or authority thereto. 1.20 " Indication" means any indication, disease, disorder or condition in the Field, which can be treated, controlled, prevented, cured or the onset or progression of which can be delayed. 1.21 " In Vitro Diagnostic Agent" means any product that uses the SELEX Process or one or more 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 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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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 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 uses described in this Section 1.21(c) conducted in the conduct of Research Activities with respect to Active Targets under this Agreement. 1.22 " In Vivo Diagnostic Agent" means any product containing one or more Aptamers that is used 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. 1.23 " Joint Patent Rights" means Patent Rights that contain one or more claims that cover Joint Technology. 1.24 " Joint Technology" means any Technology (including, without limitation, any new and useful process, method of manufacture or composition of matter) that is jointly conceived or first reduced to practice (actively or constructively) by employees of or consultants to Ribomic and employees of or consultants to Archemix at any meeting of the RC. 1.25 " Knowledge" means, with respect to Archemix, the actual knowledge of the chief executive officer, any vice president or the chief legal officer of Archemix. 1.26 " License Agreement" means the license agreement substantially in the form of Exhibit B attached hereto to be executed by the Parties upon the exercise of any Option pursuant to Section 2.4.2. 1.27 " Licensed Patent Rights" means all Patent Rights Controlled by Archemix or any of its Affiliates and listed on Exhibit A to the extent that they are (a) issued patents as of the Effective Date or (b) pending patent applications as of the Effective Date that will expire on or before September 23, 2014 as well as any patent issuing on said pending patent applications and, in any case, are necessary for Ribomic to practice the licenses granted to it hereunder. It is understood that any pending patent applications listed on Exhibit A that will expire after September 23, 2014 as well as any patent issuing thereon shall become part of the Licensed Patent Rights only by mutual agreement of the Parties. 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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1.28 " Patent Rights" means all rights and interests in and to issued patents and pending patent applications including, without limitation, 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. 1.29 " Permitted Archemix Activities" means (a) with respect to any Active Target, any screening activities conducted by Archemix with respect to such Active Target for itself and/or for any Third Party for the purpose of identifying aptamers that bind to a Target other than an Active Target; and (b) any grant by Archemix to any Third Party of rights to discover, develop and/or commercialize aptamers that bind to Targets (including Active Targets) outside of the Field. 1.30 " Permitted Ribomic Activities" means, on a country-by-country and Valid Claim-by-Valid Claim basis, any activity conducted by Ribomic or any of its Affiliates (a) involving the discovery, research, development and commercialization of therapeutic aptamers in a country for use in the Field against any Target other than the Active Targets at any time on and after the expiration of the last to expire applicable Valid Claim of the Licensed Patent Rights in such country or (b) pursuant to the terms of the Existing License Agreements, for so long as the Existing License Agreements continue in full force and effect. 1.31 " Person" means an individual, sole proprietorship, partnership, limited partnership, limited liability partnership, corporation, limited liability company, business trust, 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. 1.32 " Radio Therapeutics" means any product for human therapeutic use that contains one or more Aptamers that targets specifically any diseased tissue, cells or disease-specific molecules or any tissue or cells which are affected by a disease or located in the close neighborhood of a disease process and is linked to or incorporates (a) radionucleotides or (b) any structure or elements which develop therapeutic effects similar to the effect of linking or incorporating radionucleotides after submission of any kind of radiation. 1.33 " Research Activities" means the generation by Ribomic of Aptamers against Active Targets, and/or the use by Ribomic of the SELEX Process and the SELEX Technology against Active Targets, in either case, at the Ribomic Facility. 1.34 " Ribomic Facility" means (a) Ribomic' s facility located at Shirokanedai Usui Building, 3-16-13 Shirokanedai, Minato-ku, Tokyo 108-0071 Japan and (b) Ribomic' s facility located at 4-6-1, Crest Hall, Shirokanedai, Minato-ku, Tokyo; provided, that the location of either Ribomic Facility may be changed or added by Ribomic by providing not less than [***] days' prior written notice to Archemix. 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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1.35 " Ribomic SELEX Patent Rights" means any Patent Rights that contain one or more claims that cover Ribomic SELEX Technology. For purposes of clarity, the Ribomic SELEX Patent Rights, as of the Effective Date, include without limitation the Patent Rights listed on Exhibit C attached hereto. 1.36 " Ribomic SELEX Technology" means any Technology that is Controlled by Ribomic as of the Effective Date or during the Term relating to or constituting aptamer compositions or that is useful for the identification, generation, modification, optimization, stabilization or use of aptamers. 1.37 " Ribomic Target Specific Patent Rights" means any Patent Rights Controlled by Ribomic that contain one or more claims that cover Ribomic Target Specific Technology. 1.38 " Ribomic Target Specific Technology" means any Technology that is Controlled by Ribomic during the Term that is necessary or useful for the research, development, manufacture, use, sale, importation or exportation of any Failed Target. 1.39 " SELEX Portfolio" means those Patent Rights licensed by Gilead to Archemix pursuant to the Archemix-Gilead License Agreement. 1.40 " SELEX Process" means any process 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, those that are covered by the claims in (a) the SELEX Portfolio, including, without limitation, U.S. Patent Nos. [***] or [***], (b) any other Patent Rights Controlled by Archemix or (c) any continuation, divisional, continuation-in-part, substitution, renewal, reissue, re-examination or extension, or any foreign equivalent, of any of the foregoing Patent Rights. 1.41 " SELEX Technology" means (a) oligonucleotides that bind to an Active Target by means other than Watson-Crick base-pairing that consist of or incorporate structural elements that are generally applicable to such oligonucleotides independent of Active Targets (e.g., a novel nucleoside, bond or linkage or combination(s) thereof, for example, deoxypurine and 2' O-methyl substituted prymidine compositions) as used in such oligonucleotides, and (b) any process for modifying, optimizing and/or stabilizing oligonucleotides that bind to a Target by means other than Watson-Crick base-pairing that is generally applicable to such oligonucleotides independent of Active Targets wherein such modification, optimization or stabilization includes, without limitation, minimization, truncation, conjugation, pegylation, complexation, substitution, deletion and/or incorporation of modified nucleotides; provided, however, that SELEX Technology does not include Active Aptamers. 1.42 " Spiegelmer" means an oligonucleotide consisting of at least [***] percent ([***]%) [***], including any structural variations and modifications, derivatives, homologs, analogs and/or mimetics to the [***] components (other than [***]), identified through the use of the SELEX Process. 1.43 " Target" means a protein, cytokine, enzyme, receptor, transducer, transcription factor, antigen or any other non-nucleic acid molecule. 1.44 " Technology" means, collectively, inventions, discoveries, improvements, trade 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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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). 1.45 " Territory" means all countries and jurisdictions of the world. 1.46 " Third Party" means any person or entity other than Ribomic, Archemix and their respective Affiliates. 1.47 " ULEHI" means University License Equity Holdings, Inc., formerly known as UTC. 1.48 " 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. 1.49 " UTC" means University Technology Corporation, the successor in interest to the University Research Corporation. 1.50 " Valid Claim" means any claim of a pending patent application or an issued, unexpired patent covered under the Licensed Patent Rights which, but for the license granted by Archemix hereunder, would be infringed by the Research Activities (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, or (d) is not lost through an interference proceeding. Additional Definitions . In addition, each of the following definitions shall have the respective meanings set forth in the section of this Agreement indicated below: Definition Section AAA 9.2.1Active Target Replacement Notice 2.2.1(a)Agreement RecitalsArchemix RecitalsArchemix Indemnitees 7.1Archemix SELEX License 2.1.2(a)Archemix Target License 2.1.2(a)Bankruptcy Action 8.2.4Chosen Courts 9.2.2Claims 7.1Disclosing Party 1.11Discussioon 2.4.4Dispute 9.2.1 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.

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Definition Section Effective Date RecitalsExpired Option 2.4.3Filing Party 5.4.3Gilead Indemnitee 7.3Indemnified Party 7.2Indemnifying Party 7.2Infringement 5.5.1Infringement Notice 5.5.1Non-Filing Party 5.4.3Notice Period 2.4.4Option 2.4.1Option Exercise Notice 2.4.2Option Period 2.4.2Party RecitalsParties RecitalsRC (Research Committee) 2.7Receiving Party 1.11Replacement Target Notice 2.2.2(a)Replacement Target Substitution Notice 2.2.2(b)Required Jurisdiction 5.4.2Research License 2.1.1(a)Ribomic RecitalsRibomic Patent Rights 5.2Target Bonus Term 2.2.3Term 8.1 2. GRANT OF RIGHTS 2.1 Licenses . 2.1.1 Grant of Rights to Ribomic . (a) Grant of Research License . Subject to the terms and conditions of this Agreement, Archemix hereby grants to Ribomic a non-exclusive, royalty-free, worldwide license during the Term, under the Licensed Patent Rights for the sole purpose of conducting the Research Activities (the " Research License" ). (b) Negative Covenants . Ribomic is not granted the right under this Agreement to, and hereby covenants and agrees that neither it nor its Affiliates will (i) use the SELEX Process or SELEX Technology (A) on any Target that is not identified as an Active Target on the Active Target List and (B) for any purpose other than the conduct of Research Activities at the Ribomic Facility and/or except for the conduct by Ribomic of Permitted Ribomic Activities as expressly permitted under this Agreement or (ii) research, develop, make, have made, use, have used, sell, offer for sale, have sold, import, have imported, export or have exported Diagnostic Products or Spiegelmers. Notwithstanding the foregoing, Ribomic shall not be restricted by this Section 2.1.1(b) from engaging in any (i) Permitted Ribomic Activities or (ii) activity in which Ribomic is permitted to engage pursuant to a license, sublicense or other right 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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granted to Ribomic in any agreement other than this Agreement (including, without limitation, the Existing License Agreement) with respect to the SELEX Portfolio, the SELEX Process, SELEX Technology or Aptamers, whether granted by Archemix, or any Third Party having the right to grant such license, sublicense or other right. To the extent Ribomic or its Affiliates engages in any activities in violation of the negative covenant set forth in this Section 2.1.1(b) during the Term and files any patent applications or obtains any Patent Rights related to or arising out of such activities then, without limiting any other remedy Archemix may have under this Agreement and without any further action of either Party, Ribomic shall be deemed to have granted to Archemix, effective as of the date of any such filing, an exclusive, fully-paid, perpetual, irrevocable, royalty-free license under all such Patent Rights for any and all uses. (c) Reversion of License Rights . Ribomic acknowledges and agrees that each of the URC License Agreement and the Gilead-Archemix License Agreement provides 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 cease to exercise reasonable efforts to develop the commercial applications of products and services utilizing the SELEX Process or the SELEX Technology. Ribomic further acknowledges and agrees that the URC License Agreement provides that in the event of any termination of the URC License Agreement, the license to SELEX granted to Ribomic hereunder shall remain in full force and effect in accordance with Section 3.4 of the URC License Agreement; provided, that, Ribomic is not then in breach of this Agreement and Ribomic agrees to be bound to ULEHI as the licensor under the terms and conditions of this Agreement. Archemix shall inform Ribomic of such event immediately after the Archemix rights revert to Gilead or ULEHI. (d) Gilead-Archemix License Agreement . Ribomic acknowledges and agrees that the Gilead-Archemix License Agreement provides that in the event of any termination of the Gilead-Archemix License Agreement, the license to SELEX granted to Ribomic hereunder shall remain in full force and effect in accordance with Section 2.3 of the Gilead-Archemix License Agreement; provided, that, Ribomic 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 Ribomic, Gilead, at its option, may terminate such license. Archemix shall inform Ribomic of such event promptly after the Gilead-Archemix License Agreement is terminated. 2.1.2 Grant of Rights to Archemix . (a) Grant of Licenses . Subject to the other terms and conditions of this Agreement, Ribomic hereby grants to Archemix a non-exclusive, royalty-free, paid-up, perpetual, irrevocable, worldwide license, with the right to grant sublicenses, (i) under all Ribomic Target Specific Technology and Ribomic Target Specific Patent Rights to research, develop, make, have made, use, have used, sell, offer for sale, have sold, import, have imported, export, have exported and commercialize Aptamers against Failed Targets for any and all purposes (the " Archemix Target License" ) and (ii) under Ribomic SELEX Technology, Ribomic SELEX Patent Rights and Ribomic Patent Rights (A) to research, develop, make, have made, use, have used, sell, offer for sale, have sold, import, have imported, export, have exported, and commercialize Aptamers for any and all purposes, and (B) for any and all uses of the SELEX Process and SELEX Technology (the " Archemix SELEX License" ); provided, however, that 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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license in clause (ii)(A) and (ii)(B) shall not apply to Active Aptamers or include any specific aptamer sequences that are identified through the conduct ...