LICENSE AGREEMENT
Exhibit 4.17
This License Agreement (this “Agreement”), dated November 21, 2011 (the “Effective Date”), is made by and between CAN-XXXX Biopharma Ltd., a public company incorporated under the laws of the State of Israel (“CANFITE”), and Eye-Xxxx Ltd., a private company incorporated under the laws of the State of Israel (“EYEFITE”). CANFITE and EYEFITE are sometimes hereinafter referred to each as a “Party” and collectively as the “Parties.”
WHEREAS, said PHS Patents are among the CANFITE Patent Rights licensed to EYEFITE, and
NOW, THEREFORE, the Parties hereby agree as follows:
For the purpose of this Agreement, the following words and phrases shall have the meanings set forth below:
1.1 “Affiliate” means with respect to a party, any other business entity that directly controls, is controlled by, or is under common control with, such party. A business entity or party shall be regarded as in control of another business entity if it owns, or controls, more than fifty percent (50%) of the voting stock or other voting ownership interest of the other business entity, or if it directly or indirectly possesses the power to direct or cause the direction of the management and policies of the other business entity by any means whatsoever.
1.2 “Annual” means from January 1 to December 31 of any given calendar year.
1.3 “Approval” means, with respect to any Licensed Product in any regulatory jurisdiction, approval from the applicable Regulatory Authority sufficient for the manufacture, offer for sale, sale, distribution, importation or use of the Licensed Product in such jurisdiction in accordance with applicable Laws.
1.4 “CANFITE Know-How” means all Technology owned, licensed or otherwise Controlled by CANFITE or any of its Affiliates as of the Effective Date, that is related to the Licensed Compound or Licensed Product, or that is essential, necessary or useful for the manufacture, use, sale, offer for sale, importation, research, development, commercialization or other exploitation of the Licensed Compound or Licensed Product in the Field.
1.5 “CANFITE Patent Rights” means the PHS Patents and the patents and patent applications listed in Exhibit A attached hereto, as amended from time to time during the term of this Agreement by mutual agreement of the Parties (for example to incorporate patent rights relating to new inventions that EYEFITE may require for development or commercialization of the Licensed Product in the Field in the Territory), and (a) any foreign counterparts thereof, (b) all divisionals, continuations, continuations-in-part thereof or any other patent application claiming priority directly or indirectly to (i) any of the patents or patent applications identified in Exhibit A or (ii) any patent or patent application from which the patents or patent applications identified in Exhibit A claim direct or indirect priority, and (c) all patents issuing on any of the foregoing, and any foreign counterparts thereof, together with all registrations, reissues, re-examinations, renewals, supplemental protection certificates, or extensions of any of the foregoing, and any foreign counterparts thereof. The parties shall update Exhibit A from time to time during the term of this Agreement as may be required.
1.6 “CF101” means the adenosine A3 receptor agonist designated by CANFITE as CF101, and known generically as IB-MECA (Methyl 1-[N6-(3-iodobenzyl)-adenin-9-yl]- β-D-Ibofuronamid).
1.7 “Clinical Data” means the information with respect to the Licensed Product or the Licensed Compound made, collected or otherwise generated under or in connection with pre-clinical, clinical, or the post-Approval studies for the Licensed Compound or Licensed Product, including any data, reports and results with respect to any of the foregoing.
1.8 “Commercially Reasonable Efforts” means, with respect to Licensed Products, the carrying out of development and commercialization activities in a manner comparable to that which a company within the pharmaceutical industry that is similarly situated to EYEFITE and its Affiliates, taken collectively, would reasonably devote to a product of similar market potential based on conditions then prevailing and taking into account, without limitation, issues of safety and efficacy, product profile, the proprietary position, the then current competitive environment for such product and the timing of such product’s entry into the market, the regulatory environment and status of such product, and other relevant scientific, technical and commercial factors.
1.9 “Confidential Information” means all data or information received by a Party or its Affiliates (“Receiving Party”) that is of value to the Party or its Affiliates disclosing or providing such data or information (“Disclosing Party”) including, but not limited to, Technology; marketing plans or strategies; formulas; methods; techniques; drawings; processes; financial data; financial plans; product plans; lists of actual or potential customers, vendors and/or employees; potential packaging; advertising materials; trademarks, service marks and trade dress; price lists; pricing policies; and competitive strategies. Confidential Information also includes any compilation or organization of information which, divided into individually segregated segments, may not be deemed confidential but in its organized completed format is unique, proprietary and confidential to the Disclosing Party. Additionally, Confidential Information includes any information described in this provision which the Disclosing Party obtains from another party and which the Disclosing Party treats as proprietary or designates as confidential information, whether or not owned or developed by the Disclosing Party. Confidential Information shall be treated as such regardless of whether it is marked “confidential” or “proprietary” or communicated by the Disclosing Party or its Affiliates in oral, written, graphic, or electronic form.
1.10 “Controlled” or “Controls”, means, when used in reference to intellectual property (including, but not limited to, patents, trademarks, know-how or Technology), the legal authority or right of a person or entity to license or sublicense such intellectual property to another person or entity, or to provide or disclose such intellectual property to such other person or entity, in each case, without breaching any contractual or fiduciary obligations.
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1.11 “EMEA” means the European Agency for the Evaluation of Medicinal Products, or any successor agency thereto.
1.12 “EU” means the European Union, as its membership may be altered from time to time, and any successor thereto, and which, as of the Effective Date, consists of Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, The Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom, and that certain portion of Cyprus included in such organization.
1.13 “Europe” means the countries comprising the EU as it may be constituted from time to time, together with those additional countries included in the European Economic Area as it may be constituted from time to time.
1.14 “EYEFITE Patent Rights” means the CANFITE Patent Rights that encompass within their scope the use of the Licensed Compound or the Licensed Product in the Field and that in the absence of a license would be infringed by the development of the Licensed Product in the Field in the Territory (and that are licensed to EYEFITE within the framework of this Agreement).
1.15 “FDA” means the United States Food and Drug Administration or any successor agency thereto.
1.16 “Field” means the treatment of any ophthalmic disease, disorder and conditions in humans.
1.17 “First Commercial Sale” means, with respect to any Licensed Product on a country-by-country basis, the first sale for use by the general public of such Licensed Product in such country after Approval of such Licensed Product has been granted, or marketing and sale of such Licensed Product is otherwise permitted, by the applicable Regulatory Authority of such country.
1.18 “FTE” means full-time equivalent.
1.19 “Governmental Authority” means any supranational, national, federal, state or local judicial, legislative, executive or regulatory authority or any arbitrator or arbitration tribunal.
1.20 “IND” means an investigational new drug application filed with a Regulatory Authority such as the FDA for authorization to commence clinical studies or post-Approval studies and its equivalent in other countries or regulatory jurisdictions.
1.21 “Koseisho” means the Japanese Ministry of Health and Welfare, or any successor agency thereto.
1.22 “Laws” means all laws, statutes, rules, regulations, ordinances and other pronouncements having the effect of law of any federal, national, multinational, state, provincial, county, city or other political subdivision, domestic or foreign.
1.23 “Licensed Compound” means CF101.
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1.24 “Licensed Product” means any pharmaceutical product in all forms, presentations, formulations and dosage forms containing a Licensed Compound, either alone or in combination with one or more other active ingredients, to be used solely for the Field.
1.25 “NDA” means a New Drug Application filed with a Regulatory Authority such as the FDA seeking approval to market a Licensed Product in the Territory.
1.26 “NDA Filing” means an NDA for a Licensed Product that has been accepted for filing by a Regulatory Authority such as the FDA.
1.27 “Net Sales” means the definition set out in Paragraph 2.10 of the PHS Agreement.
1.28 “Phase III Trial” means the Phase III Trial of CF101 in the dry eye syndrome indication as set forth in the Development Plan attached hereto as Exhibit B.
1.29 “PHS Agreement” means that that certain Patent License Agreement dated December 3, 2002 entered into between CANFITE and the PHS, a copy of which is attached hereto as Appendix A.
1.30 “PHS” means singly or collectively the National Institutes of Health, the Centers for Disease Control and Prevention, or the FDA.
1.31 “PHS Patents” means the patents exclusively licensed to CANFITE under the PHS Agreement and detailed in Exhibit C attached hereto.
1.32 “Regulatory Authority” means any national or supranational governmental authority, including, without limitation, the FDA, EMEA or Koseisho, that has responsibility in countries in the Territory over the development and/or commercialization of the Licensed Compound and Licensed Product.
1.33 “Regulatory Documentation” means all applications, registrations, licenses, authorizations and approvals (including all Approvals), all correspondence submitted to or received from Regulatory Authorities (including minutes and official contact reports relating to any communications with any Regulatory Authority) and all supporting documents and all preclinical and clinical studies and tests, relating to the Licensed Compound or the Licensed Product and all data contained in any of the foregoing, including all NDAs, regulatory drug lists, advertising and promotion documents, manufacturing data, Clinical Data, adverse event files and complaint files.
1.34 “Technology” means know-how, trade secrets, chemical and biological materials, formulations, information, documents, studies, results, data and regulatory approvals, filings and correspondence (including drug master files), including biological, chemical, pharmacological, toxicological, pre-clinical, clinical and assay data, manufacturing processes and data, specifications, sourcing information, assays, and quality control and testing procedures, whether or not patented or patentable, in each case, to the extent related to the Licensed Compound or Licensed Product.
1.35 “Territory” means all countries of the world.
1.36 “Third Party” means any person or entity other than EYEFITE or CANFITE or any of their Affiliates.
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1.37 “Trademark” means any word, name, symbol, color, designation or device or any combination thereof, including any trademark, trade dress, brand xxxx, service xxxx, trade name, brand name, logo or business symbol, whether or not registered.
Section 2. License and Assignment Grants by CANFITE.
(a) Right to Sublicense. The licenses granted in Section 2.1 include the right to grant sublicenses (through multiple tiers) to Third Parties (each such Third Party sublicensee, a “Sublicensee”), provided that: (1) each such sublicense shall be subordinate to this Agreement, (2) no such sublicense shall impair EYEFITE (directly or with and through its Sublicensees) to perform its obligations hereunder, (3) no such sublicense shall limit or impair CANFITE’s rights hereunder, (4) no such sublicense shall limit or impair PHS’s rights under the PHS Agreement, (5) EYEFITE shall remain responsible for its, its Affiliates and its Sublicensees conformity to the terms and conditions set forth herein, including without limitation, the obligation to use Commercially Reasonable Efforts to develop and commercialize the Licensed Compound and Licensed Product, the obligation to make payments as and when due hereunder, and the obligation to keep records and make reports hereunder, (6) the sublicense will require the approval of CANFITE, which will not be unreasonably withheld, and (7) as far as such sublicense includes also the PHS Patents, also the approval of PHS, as stipulated in the PHS Agreement. EYEFITE shall provide CANFITE with a true, accurate and complete copy of each sublicense agreement with its Sublicensees promptly after execution. Each sublicense granted to a Sublicensee by EYEFITE to any rights licensed to it hereunder shall terminate immediately upon the termination of the license from CANFITE to EYEFITE with respect to such rights as of the effective date of such termination by CANFITE pursuant to Section 11.2(b), provided however, that if a Sublicensee is not in material default of its obligations to EYEFITE under its sublicense agreement, and within sixty (60) days of such termination the Sublicensee agrees in writing to be bound directly to CANFITE under a license agreement substantially similar to this Agreement with respect to the rights sublicensed hereunder, substituting such Sublicensee for EYEFITE, then such sublicense shall not so terminate.
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Section 3. Regulatory Matters in the Territory.
(a) EYEFITE shall promptly inform CANFITE of any action, correspondence or reports to or from governmental authorities (other than Regulatory Authorities) that would reasonably be expected to materially affect the current or anticipated development or commercialization of the Licensed Product or Licensed Compound, and shall furnish CANFITE with copies of any relevant documents relating thereto.
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LICENSE AGREEMENT
Section 4. Performance of Duties.
For a period of three (3) years following the Effective Date, CANFITE shall be responsible for and shall perform any necessary stability testing of the Inventory of samples of batches of supplied Licensed Compound and/or said Licensed Product.
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LICENSE AGREEMENT
Section 5. Development and Commercialization.
Section 6. EYEFITE Obligations.
(b) Royalties on Net Sales - EYEFITE agrees to pay PHS earned royalties on Net Sales by or on behalf of EYEFITE and its Sublicensees or Affiliates in those territories in which PHS Patents exist, calculated on an annual basis in each calendar year and graded as follows:
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(i) Royalties of five and one half percent (5.5%) on an amount of annual Net Sales of Licensed Products in the Territory of up to and including twenty-five million U.S. dollars ($25,000,000);
(ii) Royalties of four and one half percent (4.5%) on an amount of annual Net Sales of Licensed Products in the Territory between twenty five million U.S. dollars ($25,000,000) and one hundred million US Dollars ($100,000,000);
(iii) Royalties of four percent (4.0%) on an amount of annual Net Sales of Licensed Products in the Territory of greater than and including one hundred million U.S. dollars ($100,000,000).
In case sales are made in any calendar year by both CANFITE and EYEFITE, EYEFITE will pay its pro-rated share of the aggregate sales of both Parties out of the payment Schedule listed under (i) – (iii) of this Sub-Section (b).
(c) Milestone Payments – EYEFITE agrees to pay PHS milestone payments as follows:
(i) Twenty Five Thousand ($25,000) Dollars payable within sixty (60) days after the initiation of the first Phase I clinical trials (or its equivalent) per indication of the Licensed Product in the Field.
(ii) Seventy Five Thousand ($75,000) Dollars payable within sixty (60) days after the initiation of the first Phase II clinical trials (or its equivalent) per indication of the Licensed Product in the Field.
(iii) One Hundred Thousand ($100,000) Dollars payable within sixty (60) days after the initiation of the first Phase III clinical trials (or its equivalent) per indication of the Licensed Product in the Field.
(iv) Five Hundred Thousand ($500,000) Dollars payable within ninety (90) days after each FDA (or its equivalent) approval in each major market area (U.S.A., Europe, or Japan) per indication of the Licensed Product in the Field.
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LICENSE AGREEMENT
(g) The license of the CANFITE Patent Rights other than the PHS Patents will be free of any royalties and milestone payments.
(f) Other terms of the PHS Agreement. EYEFITE shall be bound by and subject to all other terms and conditions set out in the PHS Agreement which relate to the payment of any annual payments, royalties, milestone payments or sublicensing payments as set out herein.
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LICENSE AGREEMENT
(g) Payment to PHS. Attached as Exhibit E are payment options for paying royalties to PHS. EyeFite, in coordination with CanFite, will make payments as stipulated herein using one of these payment options.
Section 7. Patent Prosecution, Infringement and Extensions.
7.1 Ownership of Inventions; Royalty-Free Licenses.
(a) Inventorship of information, know-how, data, discoveries, developments, designs, inventions, methods, processes, techniques, materials, formulae, trade secrets, trademarks, copyrights, patents and patent applications and other proprietary information conceived and/or reduced to practice in connection with, or as a result of, EYEFITE’s activities hereunder (the “Inventions”) shall be determined in accordance with the patent laws of the country in which such invention occurred.
(b) All Inventions relating to the Licensed Compound or the Licensed Product (whether invented solely by CANFITE or by EYEFITE or jointly by CANFITE and EYEFITE) shall belong to CANFITE (each a “CANFITE Invention”). CANFITE hereby grants to EYEFITE a royalty-free, exclusive license to use and exploit CANFITE Inventions in connection with the Licensed Product in the Field in accordance with this Agreement.
7.2 Prosecution and Maintenance of CANFITE Patent Rights.
(a) CANFITE shall be solely responsible for the preparation, prosecution (including any interferences, oppositions, reissue proceedings and reexaminations) and maintenance of the CANFITE Patent Rights. CANFITE shall use Commercially Reasonable Efforts to obtain appropriate patent protection for the EYEFITE Patent Rights.
(b) Without limiting the foregoing, CANFITE shall not knowingly permit any of the CANFITE Patent Rights which may include EYEFITE Patent Rights to be abandoned in any country without EYEFITE first being given an opportunity to assume full responsibility and costs for the continued prosecution and maintenance of same.
(c) CANFITE shall be responsible for the preparation, prosecution (including any interferences, oppositions, reissue proceedings and reexaminations) and maintenance of all EYEFITE Patent Rights, and all preparation, filing, prosecution, and maintenance decisions with respect to the EYEFITE Patent Rights shall be made by CANFITE with the goal and intention of obtaining appropriate patent protection for the Licensed Compound and Licensed Product for the Field in the Territory. CANFITE shall reasonably consult with EYEFITE with respect to the preparation, filing, prosecution and maintenance of the EYEFITE Patent Rights. CANFITE shall keep EYEFITE advised of the status of such activities and shall also inform EYEFITE in a timely manner of any material communications CANFITE receives from the relevant patent office with respect to such activities, including providing EYEFITE with copies of any papers relating to the filing, prosecution or maintenance of the EYEFITE Patent Rights. EYEFITE shall forward to CANFITE copies of any papers relating to the filing, prosecution or maintenance of the CANFITE Patent Rights promptly upon receipt. As of the Effective Date, EYEFITE shall be responsible for all its costs incurred for such preparation, filing, prosecution and maintenance of the EYEFITE Patent Rights and shall reimburse CANFITE for any such costs relating thereto.
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LICENSE AGREEMENT
7.3 Enforcement and Defense of CANFITE Patent Rights.
7.4 Patent Extensions; Orange Book Listings; Patent Certifications.
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(b) Data Exclusivity. With respect to any data exclusivity periods, such as those periods listed in the FDA’s Orange Book (including any available pediatric exclusivities) or other exclusivity periods under national implementations of Article 10.1(a)(iii) of Directive 2001/EC/83 (and all equivalents in any country), CANFITE shall have the sole right to seek and maintain all such data exclusivity periods available for the Licensed Compound or Licensed Product.
Section 8. Confidential Information and Publicity.
(i) is publicly disclosed by the Disclosing Party, either before or after it is disclosed to the Receiving Party hereunder;
(ii) was known to the Receiving Party or any of its Affiliates, without any obligation to keep it confidential or any restriction on its use, prior to disclosure by the Disclosing Party;
(iii) is subsequently disclosed to the Receiving Party or any of its Affiliates by a Third Party lawfully in possession thereof and without any obligation to keep it confidential or any restriction on its use;
(iv) is published by a Third Party or otherwise becomes publicly available or enters the public domain, either before or after it is disclosed to the Receiving Party;
(v) has been independently developed by employees or contractors of the Receiving Party or any of its Affiliates without the aid, application or use of Confidential Information of the Disclosing Party; or
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LICENSE AGREEMENT
(vi) Information provided or will be provided by CANFITE to third parties under a confidentiality disclosure agreement (“CDA”), which is relevant for the use of the License Product outside of the Field.
(a) A mutually agreed upon press release detailing the transaction set out herein pre approved by both Parties;
(b) CANFITE shall be permitted to disclose the terms hereof to PHS; and
(c) The Parties shall each be permitted to disclose the terms of this Agreement and the PHS Agreement (i) in communication with investors, consultants, advisors or others on a need-to-know basis, in each case under appropriate confidentiality provisions substantially equivalent to those of this Agreement; (ii) as necessary to comply with applicable governmental Laws and regulations (including, without limitation, the rules and regulations of the Securities and Exchange Commission or any national securities exchange) and with judicial process; or (iii) to other parties under a written confidentiality agreement.
Section 9. Adverse Experience.
9.1 As stated in Sections 9.2 and 9.3, EYEFITE shall keep (and EYEFITE shall cause its sublicensees to keep under terms and conditions equal to those set forth in this Section 9) CANFITE, during the term of this Agreement, promptly and fully informed of all pharmaceutical, toxicological and clinical findings relating to adverse experience of the Licensed Product or Licensed Compound. CANFITE shall be permitted to share with PHS all data and information provided under this Article 9 by EYEFITE.
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9.2 EYEFITE undertakes to notify CANFITE promptly with written confirmation by immediate telecopy of any information concerning any serious adverse event as defined by C.I.O.M.S. or any Regulatory Authority, as applicable, reasonably associated with clinical studies or attributed to the use or application of the Licensed Product or Licensed Compound. In any event the above notification shall be made within two (2) working days after Licensee first learns or is advised of relevant information with respect to such serious adverse event.
9.3 EYEFITE shall also forward regularly (and usually every six (6) months unless the Parties agree on another period) to CANFITE any information on all other adverse effects or any difficulty associated with the clinical use, studies, investigations, tests and prescription of the Licensed Product or Licensed Compound.
9.4 EYEFITE shall provide upon request the information on estimated patient days of exposure.
9.5 EYEFITE shall inform CANFITE, without delay, of any governmental action, correspondence or reports to or from governmental authorities that may affect the situation of the Licensed Product or Licensed Compound and furnish CANFITE with copies of any relevant documents relating thereto.
Section 10. Warranties; Limitations of Liability; Indemnification; Covenants.
(a) Such Party is a corporation duly organized and validly existing under the Laws of the state in which it is incorporated, and it has full right and authority to enter into this Agreement and to accept the rights and licenses granted as herein described.
(b) This Agreement has been duly authorized by all requisite corporate action, and when executed and delivered will become a valid and binding contract of such Party enforceable against it in accordance with its terms, subject to applicable bankruptcy, insolvency, reorganization, moratorium and other Laws affecting creditors’ rights generally from time to time if effect, and to general principles of equity.
(c) The execution, delivery and performance of this Agreement does not conflict with any other agreement, contract, instrument or understanding, oral or written, to which such Party is bound, nor will it violate any law applicable to such Party.
(d) All necessary consents, approvals and authorizations of all regulatory and governmental authorities and other persons or entities required to be obtained by such Party in connection with the execution and delivery of this Agreement and the performance of its obligations hereunder have been obtained.
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(a) CANFITE, through in-licensing or ownership, controls the patents and patent applications that are included within the CANFITE Patent Rights as of the Effective Date and CANFITE Controls the CANFITE Know-How, in both cases, for use with the Licensed Compound within the Field;
(b) To the best of its knowledge and belief, all of the issued patents within the CANFITE Patent Rights are in good standing;
(c) To the best of its knowledge and belief, CANFITE is not aware of any notice from any Third Party asserting any ownership rights to any CANFITE Know-How for use with the Licensed Compound within the Field;
(d) To the best of its knowledge and belief, CANFITE is not aware of any pending or threatened action, suit, proceeding or claim by a Third Party asserting that CANFITE is infringing or has misappropriated or otherwise is violating any patent, trade secret or other proprietary right of any Third Party as would reasonably be expected to result in CANFITE being unable to grant the rights and licenses to EYEFITE under this Agreement;
(e) CANFITE has not granted any right or license or other encumbrance of any kind in the FIELD to any Third Party relating to the CANFITE Patent Rights and CANFITE Know-How that conflicts with any of the rights granted to EYEFITE hereunder;
(f) There are no claims, actions, or proceedings pending or, to CANFITE’s knowledge, threatened; nor are there any formal inquiries or notices that may lead to the institution of such legal proceedings, against CANFITE or its Affiliates or PHS or its Affiliates, which if adversely decided, would, individually or in the aggregate, have a material adverse effect on, or prevent CANFITE’s ability to grant the licenses and assignments to EYEFITE contemplated hereunder; and
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LICENSE AGREEMENT
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LICENSE AGREEMENT
(a) CANFITE shall not take any action, or omit to take any action, that would (i) encumber any of its right, title and interest in and to the Licensed Compounds or the Licensed Products in any way that would have a material adverse effect on the rights and licenses granted to EYEFITE hereunder, or (ii) cause CANFITE to be in breach under the PHS Agreement.
(b) EYEFITE agrees to be bound by the following obligations towards PHS (all capitalized terms in this Sub-Section 10.8 (b) shall have the meaning ascribed to them in the PHS Agreement):
(i) PHS reserves on behalf of the Government an irrevocable, nonexclusive, nontransferable, royalty-free license for the practice of all inventions licensed under the Licensed Patent Rights throughout the world by or on behalf of the Government and on behalf of any foreign government or international organization pursuant to any existing or future treaty or agreement to which the Government is a signatory.
(ii) Prior to the First Commercial Sale, EYEFITE agrees to provide PHS reasonable quantities of Licensed Products or materials made through the Licensed Processes for PHS research use.
(iii) In the event that Licensed Patent Rights are Subject Inventions made under a Cooperative Research and Development Agreement (CRADA), EYEFITE grants to the Government, pursuant to 15 U.S.C. 3710a(b)(1)(A), a nonexclusive, nontransferable, irrevocable, paid-up license to practice Licensed Patent Rights or have Licensed Patent Rights practiced throughout the world by or on behalf of the Government. In the exercise of such license, the Government shall not publicly disclose trade secrets or commercial or financial information that is privileged or confidential within the meaning of 5 U.S.C. 552(b)(4) or which would be considered as such if it had been obtained from a non-Federal party. Prior to the First Commercial Sale, EYEFITE agrees to provide PHS reasonable quantities of Licensed Products or materials made through the Licensed Processes for PHS research use.
(iv) EYEFITE agrees that products used or sold in the United States embodying Licensed Products or produced through use of Licensed Processes shall be manufactured substantially in the United States, unless a written waiver is obtained in advance from PHS.
(v) EYEFITE acknowledges that PHS may enter into future Cooperative Research and Development Agreements (CRADAs) under the Federal Technology Transfer Act of 1986 that relate to the subject matter of this Agreement. EYEFITE agrees not to unreasonably deny requests for a Research License from such future collaborators with PHS when acquiring such rights is necessary in order to make a Cooperative Research and Development Agreement (CRADA) project feasible. EYEFITE may request an opportunity to join as a party to the proposed Cooperative Research and Development Agreement (CRADA).
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LICENSE AGREEMENT
(vi) (a) In addition to the reserved license of Paragraph 5.01 of the PHS Agreement, PHS reserves the right to grant nonexclusive Research Licenses directly or to require EYEFITE to grant nonexclusive Research Licenses on reasonable terms. The purpose of this Research License is to encourage basic research, whether conducted at an academic or corporate facility. In order to safeguard the Licensed Patent Rights, however, PHS shall consult with EYEFITE before granting to commercial entities a Research License or providing to them research samples of materials made through the Licensed Processes.
(vii) (b) In exceptional circumstances, and in the event that Licensed Patent Rights are Subject Inventions made under a Cooperative Research and Development Agreement (CRADA), the Government, pursuant to 15 U.S.C. 3710a(b)(1)(B), retains the right to require the EYEFITE to grant to a responsible applicant a nonexclusive, partially exclusive, or exclusive sublicense to use Licensed Patent Rights in EYEFITE’s field of use on terms that are reasonable under the circumstances; or if EYEFITE fails to grant such a license, the Government retains the right to grant the license itself. The exercise of such rights by the Government shall only be in exceptional circumstances and only if the Government determines (i) the action is necessary to meet health or safety needs that are not reasonably satisfied by EYEFITE; (ii) the action is necessary to meet requirements for public use specified by Federal regulations, and such requirements are not reasonably satisfied by the EYEFITE; or (iii) the EYEFITE has failed to comply with an agreement containing provisions described in 15 U.S.C. 3710a(c)(4)(B). The determination made by the Government under this Article is subject to administrative appeal and judicial review under 35 U.S.C. 203(2).
(viii) EYEFITE agrees to keep accurate and correct records of Licensed Products made, used, sold, or imported and Licensed Processes practiced under this Agreement appropriate to determine the amount of royalties due PHS. Such records shall be retained for at least five (5) years following a given reporting period and shall be available during normal business hours for inspection at the expense of PHS by an accountant or other designated auditor selected by PHS for the sole purpose of verifying reports and payments hereunder. The accountant or auditor shall only disclose to PHS information relating to the accuracy of reports and payments made under this Agreement. If an inspection shows an underreporting or underpayment in excess of five percent (5%) for any twelve (12) month period, then EYEFITE shall reimburse PHS for the cost of the inspection at the time EYEFITE pays the unreported royalties, including any late charges as required by Paragraph 9.08 of the PHS Agreement. All payments required under this Paragraph shall be due within thirty (30) days of the date PHS provides EYEFITE notice of the payment due.
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(ix) EYEFITE shall use its reasonable best efforts to bring the Licensed Products and Licensed Processes to Practical Application.
(x) Upon the First Commercial Sale, until the expiration of this Agreement, EYEFITE shall use its reasonable best efforts to make Licensed Products and Licensed Processes reasonably accessible to the United States public.
(xi) EYEFITE shall indemnify and hold PHS, its employees, students, fellows, agents, and consultants harmless from and against all liability, demands, damages, expenses, and losses, including but not limited to death, personal injury, illness, or property damage in connection with or arising out of: a) the use by or on behalf of EYEFITE, its sublicensees, directors, employees, or third parties of any Licensed Patent Rights; or b) the design, manufacture, distribution, or use of any Licensed Products, Licensed Processes or materials by EYEFITE, or other products or processes developed in connection with or arising out of the Licensed Patent Rights. EYEFITE agrees to maintain a liability insurance program consistent with sound business practice.
(xii) PHS reserves the right according to 35 U.S.C. . 209(f)(4) to terminate or modify the terms of the PHS Agreement if it is determined that such action is necessary to meet requirements for public use specified by federal regulations issued after the date of the license and such requirements are not reasonably satisfied by EYEFITE.
(xiii) Within thirty (30) days of receipt of written notice of PHS’s unilateral decision to modify or terminate the PHS Agreement, EYEFITE may, consistent with the provisions of 37 CFR 404.11, appeal the decision by written submission to the designated PHS official. The decision of the designated PHS official shall be the final agency decision. EYEFITE may thereafter exercise any and all administrative or judicial remedies that may be available.
(xiv) Within ninety (90) days of expiration or termination of the PHS Agreement under Article 13 of the PHS Agreement, a final report shall be submitted by EYEFITE. Any royalty payments, including those incurred but not yet paid (such as the full minimum annual royalty), and those related to patent expense, due to PHS shall become immediately due and payable upon termination or expiration. If terminated under Article 13 of the PHS Agreement, sublicensees may elect to convert their sublicenses to direct licenses with PHS pursuant to Paragraph 4.03 of the PHS Agreement. Unless otherwise specifically provided for under this Agreement, upon termination or expiration of this Agreement, EYEFITE shall return all Licensed Products or other materials included within the Licensed Patent Rights to PHS or provide PHS with certification of the destruction thereof.
(xv) Any sublicenses granted by EYEFITE shall provide for the termination of the sublicense, or the conversion to a license directly between such sublicensees and PHS, at the option of the sublicensee, upon termination of the PHS Agreement under Article 13 of the PHS Agreement. Such conversion is subject to PHS approval and contingent upon acceptance by the sublicensee of the remaining provisions of the PHS Agreement.
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(xvi) The non-compliance by EYEFITE of any of the aforesaid obligation in this Sub-section 10.8(b) shall be deemed a breach of this Agreement entitling CANFITE the right to terminate the license granted hereunder, provided that EYEFITE shall have a thirty (30) day period from receipt of a written letter from CANFITE of the occurrence of such breach during which to cure such breach and comply with such obligation..
Section 11. Term and Termination.
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(a) At EYEFITE’s discretion, effective upon three (3) months prior written notice, EYEFITE may terminate this Agreement for any reason.
(b) In addition, EYEFITE may terminate this Agreement in the event of material breach by CANFITE, provided that such breach has not been cured within thirty (30) days after written notice thereof is given by EYEFITE to CANFITE. If CANFITE disputes in good faith the existence or materiality of such breach and provides notice to EYEFITE of such dispute within such thirty (30) day period, EYEFITE shall not have the right to terminate this Agreement in accordance with this Section 11.3(b) unless and until it has been determined in accordance with Section 12.7 that this Agreement was materially breached by CANFITE and CANFITE fails to cure such breach within thirty (30) days following such determination. It is understood and acknowledged that during the pendency of such a dispute, all of the terms and conditions of this Agreement shall remain in effect and the Parties shall continue to perform all of their respective obligations hereunder. The Parties further agree that any payments that are made by one Party to the other Party pursuant to this Agreement pending resolution of the dispute shall be promptly refunded if an arbitrator or court determines pursuant to Section 12.7 that such payments are to be refunded by one Party to the other Party.
(a) All rights and licenses granted to EYEFITE in Section 2 shall terminate, all rights of EYEFITE under the CANFITE Patent Rights and CANFITE Know-How shall revert to CANFITE, and EYEFITE shall cease all use of the CANFITE Patent Rights, CANFITE Know-How and Trademarks and Corporate Names of CANFITE and its Affiliates.
(b) EYEFITE shall assign to CANFITE EYEFITE’s right, title and interest in all regulatory filings (including, without limitation, all NDAs) and Approvals and other documents relating to or necessary to further develop and commercialize Licensed Compounds and Licensed Products, as they exist as of the date of such termination, and EYEFITE shall provide to CANFITE one (1) copy of the foregoing documents and filings and all documents and filings contained in or referenced in any such filings, together with the raw and summarized data for any preclinical and clinical studies of the Licensed Compounds and such Licensed Product (and where reasonably available, electronic copies thereof) at CANFITE’s cost. In addition, upon request by CANFITE, EYEFITE shall grant to CANFITE the right to access and reference any other documents (including but not limited to regulatory filings) that are available to EYEFITE and reasonably necessary for CANFITE to further develop, manufacture and commercialize the Licensed Compounds and Licensed Product.
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(c) All amounts due or payable to CANFITE, PHS or other third parties that were accrued, or that arise out of acts or events occurring, prior to the effective date of termination or expiration shall remain due and payable; but (except as otherwise expressly provided herein) no additional amounts shall be payable based on events occurring after the effective date of termination or expiration.
(d) Should EYEFITE have any inventory of the Licensed Compound suitable for use, EYEFITE shall offer to sell such Licensed Compound to CANFITE at EYEFITE’s out-of-pocket cost (but CANFITE shall be under no obligation to purchase same unless it agrees to do so in writing at such time).
(e) EYEFITE shall assign (or, if applicable, cause its Affiliate to assign) to CANFITE all of EYEFITE’s (and such Affiliates’) right, title and interest in and to any registered or unregistered trademark, trademark application, trade name or internet domain name that is specific to a Licensed Product (it being understood that the foregoing shall not include any trademarks or trade names that contain EYEFITE’s name).
(f) EYEFITE shall grant to CANFITE a license, which license shall be exclusive, with the right to grant sublicenses, under all patent rights owned or Controlled by EYEFITE as of the Termination Date to make, use, import, sell and offer for sale and otherwise develop and commercialize the Licensed Product and Licensed Compound in the Field. In consideration of the license granted by EYEFITE to CANFITE in accordance with this Section 11.4(f), CANFITE shall pay EYEFITE a royalty on a product-by-product basis at a rate equal to one percent (1%) of Net Sales (with the roles of CANFITE and EYEFITE reversed for purposes of the definition of Net Sales. The maximum cumulative royalty payments under this Section 11.4(f) shall not exceed one hundred percent (100%) of the payments due and actually paid by EYEFITE to PHS under this Agreement prior to the time EYEFITE grants CANFITE a license in accordance with this Section 11.4(f).
(g) Neither Party shall be relieved of any obligation that accrued prior to the effective date of such termination or expiration.
(h) CANFITE shall have the right to retain all amounts previously paid to CANFITE by EYEFITE, subject to any applicable determination of an arbitrator or court pursuant to Section 12.7.
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LICENSE AGREEMENT
Section 12. General Provisions.
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If to EYEFITE, to: | Eye-Xxxx Ltd |
x/x Xxxxxx & Xx. | |
00 Xxx Xxxxxx Xxxxxx, | |
Xxxxx Xxx, Xxxxxx | |
Attention: Xxxxx Xxxxxx, Adv. | |
Facsimile: (000) 00000000 | |
With a required copy to: | Xxxxxx & Co. |
00 Xxx Xxxxxx Xxxxxx, | |
Xxxxx Xxx, Xxxxxx | |
Attention: Xxxxx Xxxxxx, Adv. | |
Facsimile: (000) 00000000 | |
If to CANFITE, to: | CAN-XXXX Biopharma Ltd. |
00 Xxxxxxx Xxxxxx, | |
Xxxxxx Xxxxx, Xxxxxx | |
Attention: Xxxx. Xxxxx Xxxxxxx, CEO and Director | |
Facsimile: | |
With a required copy to: | Xxxxxx & Co. |
00 Xxx Xxxxxx Xxxxxx, | |
Xxxxx Xxx, Xxxxxx | |
Attention: Xxxxx Xxxxxx, Adv. | |
Facsimile: (000) 00000000 |
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LICENSE AGREEMENT
or to such address as each Party may hereafter designate by notice to the other Party. A notice shall be deemed to have been given on the date it is received by all required recipients for the noticed Party.
(a) In the event of a dispute between the Parties, the Parties shall first attempt in good faith to resolve such dispute by negotiation and consultation between themselves. In the event that such dispute is not resolved on an informal basis within forty-five (45) days, any Party may, by written notice to the other, have such dispute referred to each of the Parties’ respective CEOs or his or her designee (who shall be a senior executive), who shall attempt in good faith to resolve such dispute by negotiation and consultation for a thirty (30) day period following receipt of such written notice.
(b) In the event the Parties’ CEOs (or designees) are not able to resolve such dispute, either Party may at any time after such 30-day period submit such dispute to be finally settled by arbitration administered in accordance with the Commercial Arbitration Rules of the American Arbitration Association (“AAA”) in effect at the time of submission. The arbitration shall be heard and determined by three (3) arbitrators. EYEFITE and CANFITE shall each appoint one (1) arbitrator and the third arbitrator shall be selected by the two Party-appointed arbitrators, or, failing agreement within sixty (60) days following the date of receipt by the respondent of the claim, by the AAA. Such arbitration shall take place in New York, NY. The arbitration award so given shall be a final and binding determination of the dispute, shall be fully enforceable in any court of competent jurisdiction, and shall not include any damages expressly prohibited by Section 10.4.
(c) Costs of arbitration are to be divided by the Parties in the following manner: EYEFITE shall pay for the arbitrator it chooses, CANFITE shall pay for the arbitrator it chooses, and the costs of the third arbitrator shall be divided equally between the Parties. Except in a proceeding to enforce the results of the arbitration or as otherwise required by law, neither Party nor any arbitrator may disclose the existence, content or results of any arbitration hereunder without the prior written consent of both Parties.
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LICENSE AGREEMENT
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CANFITE BIOPHARMA LTD. | |||
By: | /s/ Xxxxx Xxxxxxx | /s/ Xxxxx Xxxxxxxxx | |
(Signature) | |||
Name: | Xxxxx Xxxxxxx | Xxxxx Xxxxxxxxx | |
Title: | CEO | COO | |
Date: | November 21, 2011 | ||
EYEFITE LTD. | |||
By: | /s/Xxxxx Xxxxxxx | /s/Xxxxx Xxxxxxxxx | |
(Signature) | |||
Name: | Xxxxx Xxxxxxx | Xxxxx Xxxxxxxxx | |
Title: | Director | Director | |
Date: | November 21, 2011 |
LICENSE AGREEMENT
EXHIBIT A - CANFITE PATENT RIGHTS
The CANFITE Patent Rights that are licensed to EYEFITE within the framework of this Agreement are summarized in a tabulated format below. Each Table lists all cases belonging to a single patent family (each patent family consisting of patent cases that descend from the same priority application(s)). Each table is headed by CANFITE’s respective case number and internal title (which may corresponds to the formal title).
CF19
Method for treating Xxxxxxx’x Syndrome
Application Serial | ||||||
Country | No. | Filing Date | Status | |||
Europe* | 05762145.0 | 18-Jul-2005 | Pending | |||
Japan* | 2007-523232 | 18-Jul-2005 | Issued Patent, Serial No. 4642847 | |||
US3 | 11/604,905 | 28-Nov-06 | Issued Patent, Serial No. 7,825,102 |
* All cases are national phase applications of PCT application No. IL2005/00762, which claims priority from US provisional application No. 60/591,628 filed on July 28, 2004
CF27
Treatment of dry eye
Application Serial | ||||||
Country | No. | Filing Date | Status | |||
US | 12/774,927 | 11-May-10 | Pending | |||
Australia* | 2006336834 | 1-Feb-06 | Issued Patent, Serial No. 2006336834 | |||
Brazil* | PI 0621052-0 | 1-Feb-06 | Pending | |||
Canada* | 2,622,975 | 1-Feb-06 | Pending | |||
China* | 200680047569.7 | 1-Feb-06 | Pending | |||
Europe* | 06701840.8 | 1-Feb-06 | Pending | |||
Israel* | 191271 | 1-Feb-06 | Pending | |||
India* | 1415/MUMP/2008 | 1-Feb-06 | Pending | |||
Japan* | 2008-551950 | 1-Feb-06 | Pending | |||
Rep. of Korea* | 00-0000-0000000 | 1-Feb-06 | Pending | |||
Mexico* | MX/a/2008/09506 | 1-Feb-06 | Pending |
* All cases are national phase applications of PCT application No. IL2006/000130, which claims priority from US provisional application No. 60/762,506 filed on January 27, 2006
LICENSE AGREEMENT
CF31
Process for producing CF101 (IB-MECA)
Application Serial | ||||||
Country | No. | Date | Status | |||
US* | 12/450,094 | 13-Mar-08 | Pending | |||
China* | 200880007952.9 | 13-Mar-08 | Pending | |||
India* | 1734/MUMNP/2009 | 13-Mar-08 | Pending | |||
Japan* | 2009-553282 | 13-Mar-08 | Pending | |||
Europe* | 08719985.7 | 13-Mar-08 | Pending | |||
Israel* | 200711 | 13-Mar-08 | Pending |
* All cases are national phase applications of PCT application No. IL2008/000360, which claims priority from US provisional application No. 60/906,838 filed on March 14, 2007
CF42
Composition for reduction of Intraocular Pressure
Application Serial | ||||||
Country | No. | Date | Status | |||
PCT* | PCT/IL2010/000393 | 16-May-10 | Published as WO 2010/134067 | |||
National patent | N/A | Not yet filed | To be filed by 16-Nov-2011 as national/regional applications | |||
applications in the US, | based on PCT/IL2010/000393 | |||||
Europe, Japan, China | ||||||
and other regions | ||||||
based on the PCT | ||||||
application |
* Claiming priority from the Israeli patent application No. 198787, filed on May 17, 2009
LICENSE AGREEMENT
CF44
Method for the Treatment of Uveitis
Co-owned by CANFITE and PHS. Licensed is CANFITE’s share.
Application Serial | ||||||
Country | No. | Date | Status | |||
PCT* | PCT/IL2011/000193 | 20-Feb-11 | Filed |
* Claims priority from US provisional application No. 61/310,043, filed on March 3, 2010
LICENSE AGREEMENT
EXHIBIT B - DEVELOPMENT PLAN
EYEFITE’s clinical development plan is directed to at least three ophthalmic indications of CF101:
1. | Dry Eye Syndrome (DES) - a Phase II clinical trial for CF101 in the treatment of DES was already completed. The Phase II trial data demonstrated positive results in patients with moderate to severe DES and also served as the basis for an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for a Phase III trial in the same patient population. The FDA approved the IND in September 2010 and Eye-Xxxx will conduct a Phase III clinical trial in patients with moderate to severe DES in the United States, Europe and Israel. This Phase III trial will start no later than the first anniversary from signing this Agreement. |
Eye-Xxxx anticipates that at least one additional Phase III clinical trial will be needed, and anticipates that it will be initiated by the end of second quarter 2014.
2. | Glaucoma – although the Phase II DES trial was not designed to assess the effects of treatment on intraocular pressure (IOP), it was noted that the CF101-treated group showed a statistically significant decrease in IOP from baseline. This observation indicated that CF101 may also have potential as a treatment for Glaucoma and lead to the initiation of the current Phase II clinical trial examining the safety and efficacy of CF101 administered in subjects with elevated intraocular pressure. This study is currently conducted in Israel, and maybe be expanded to additional countries at a later stage. Eye-Xxxx anticipates that the interim analysis data will be released no later the first quarter of 2013. |
3. | Uveitis - pre-clinical pharmacology studies conducted in collaboration with a research group from the U.S. National Institute of Health demonstrated that CF101 is effective in suppressing ocular inflammation in experimental murine models of Uveitis. Eye-Xxxx will continue to carry out some further pharmacological studies followed by an initiation of a Phase II trial in Uveitis, that EYEFITE anticipates to initiate no later than the third quarter of 2012. |
The Development Plan may be revised from time-to-time by EYEFITE, after obtaining the approval of CANFITE, which will not be unreasonably withheld.
LICENSE AGREEMENT
EXHIBIT C - PHS PATENTS
· | US patent No. 5,773,423 |
· | European patent No. EP0708781 and national patents based thereon |
LICENSE AGREEMENT
EXHIBIT D - ITEMS TO BE DELIVERED
1. | CF101 CIB |
2. | FDA IND documentation for Dry Eye Syndrome |
3. | Phase 3 Dry Eye Syndrome Protocol |
4. | Dry eye related manuscript “Treatment of Dry Eye Syndrome with Orally Administered CF101 - Data from a Phase 2 Clinical Trial” |
5. | Phase 2 Glaucoma Protocol |
6. | Uveitis related manuscript “Inhibition of experimental auto-immune Uveitis by the A3 adenosine receptor agonist CF101” |
7. | Uveitis Orphan Drug Application. |
LICENSE AGREEMENT
Exhibit E – ROYALTY PAYMENT OPTIONS
The XXX License Number MUST appear on payments, reports and correspondence.
Automated Clearing House (ACH) for payments through U.S. banks only
The NIH encourages our licensees to submit electronic funds transfer payments through the Automated Clearing House (ACH). Submit your ACH payment through the U.S. Treasury web site located at: xxxxx://xxx.xxx.xxx. Locate the “NIH Agency Form” through the Xxx.xxx “Agency List”.
Electronic Funds Wire Transfers
The following account information is provided for wire payments. In order to process payment via Electronic Funds Wire Transfer sender MUST supply the following information within the transmission:
Drawn on a U.S. bank account via FEDWIRE should be sent directly to the following account:
Beneficiary Account: | Federal Reserve Bank of New York or TREAS NYC | |
Bank: | Federal Reserve Bank of New York | |
ABA# | 000000000 | |
Account Number: | 00000000 | |
Bank Address: | 00 Xxxxxxx Xxxxxx, Xxx Xxxx, XX 00000 | |
Payment Details: | License Number (L-249-2001) | |
Name of Licensee |
Drawn on a foreign bank account should be sent directly to the following account. Payment must be sent in U.S. Dollars (USD) using the following instructions:
Beneficiary Account: | Federal Reserve Bank of New York/ITS or FRBNY/ITS | |
Bank: | Citibank N.A. (New York) | |
SWIFT Code: | XXXXXX00 | |
Account Number: | 00000000 | |
Bank Address: | 000 Xxxxxxxxx Xxxxxx, Xxx Xxxx, XX 00000 | |
Payment Details (Line 70): | NIH 75080031 | |
License Number (L-249-2001) | ||
Name of Licensee | ||
Detail of Charges (line 71a): | Charge Our |
LICENSE AGREEMENT
Checks
All checks should be made payable to “NIH Patent Licensing”
Checks drawn on a U.S. bank account and sent by US Postal Service should be sent directly to the following address:
National Institutes of Health (NIH)
X.X. Xxx 000000
Xx. Xxxxx, XX 00000-0000
Checks drawn on a U.S. bank account and sent by overnight or courier should be sent to the following address:
US Bank
Government Lockbox SL-MO-C2GL
0000 Xxxxxxxxxx Xxxxx
Xx. Xxxxx, XX 00000
Phone: 000-000-0000
Checks drawn on a foreign bank account should be sent directly to the following address:
National Institutes of Health (NIH)
Office of Technology Transfer
Royalties Administration Xxxx
0000 Xxxxxxxxx Xxxxxxxxx
Xxxxx 000, XXX 0000
Xxxxxxxxx, Xxxxxxxx 00000