CONFIDENTIAL INFORMATION OMITTED AND FILED SEPARATELY WITH SECURITIES AND EXCHANGE COMMISSION ASTERISKS DENOTE SUCH OMISSION LICENSE AGREEMENT

 

 

This License Agreement (the “Agreement”) is made and entered into as of January 14, 2008 (the “Effective Date”), between Alfacell Corporation, a Delaware corporation with its principal place of business at 300 Atrium Drive, Somerset, New Jersey 08873 (“Alfacell”), and Par Pharmaceutical, Inc., a Delaware corporation with its principal place of business at 300 Tice Boulevard, Woodcliff Lake, New Jersey 07677 (“Par”). Alfacell and Par may be referred to herein individually as a “Party”, or together as the “Parties”.

 

 

Whereas, Alfacell has expertise developing pharmaceutical products and has developed and owns certain proprietary technology and know-how relating to the design and manufacture of the Product (as defined in Section 1.1) in the Field; and

 

Whereas, Par has expertise in developing, manufacturing and marketing certain pharmaceutical products and wishes to develop and market the Product in the Field in the Territory as further described herein, and Alfacell agrees to grant Par the rights to do so pursuant to the terms of this Agreement.

 

Now, Therefore, in consideration of the foregoing and the covenants and promises contained herein, the Parties hereby agree as follows:

 

 

 

1.1 Definitions. For the purposes of this Agreement, the following defined terms have the respective meanings set forth below:

 

“Accelerated Approval” means approval of a Product NDA pursuant to 21 C.F.R. Part 314 Subpart H (a) in which the FDA evaluation of the NDA is performed on the basis of a surrogate marker (a measurement intended to be a substitute for the clinical measurement of interest) that is considered likely to predict patient benefit and (b) that may be a provisional approval, with a required written commitment to complete clinical studies that formally demonstrate patient benefit.

 

“Affiliate” means, with respect to a Party and for so long as the relationship exists, any other entity that directly or indirectly controls, is controlled by, or is under common control with, such Party. An entity shall be regarded as in control of another entity if it owns, or directly or indirectly controls, greater than fifty percent (50%) of the voting stock or other ownership interest of such entity, or if it directly or indirectly possesses the power to direct or cause the direction of the management and policies of the other entity by any means whatsoever.

 

 

“AG Product” means a generically-labeled version of the Product (i.e., such Product does not bear the Trade Name) supplied by Alfacell and sold by Par and/or its Sub-distributors or permitted sublicensees.

 

“Agreement” has the meaning set forth in the introductory paragraph.

 

“Alfacell” has the meaning set forth in the introductory paragraph.

 

“Alfacell Indemnitee” has the meaning set forth in Section 12.2.

 

“Alfacell Information” means any Product-related information Owned or Controlled by Alfacell as of the Effective Date or Owned or Controlled by Alfacell after the Effective Date that, with respect to a Product in the Field in the Territory, (a) is directly related to use or sale of the Commercialized Product, (b) is included in an Alfacell NDA filing for the Product within the scope of this Agreement, (c) is otherwise reasonably requested by Par and provided by Alfacell in its sole discretion, or (d) is lawfully obtained by Alfacell from a Third Party without restriction on disclosure to Par, but only to the extent that such Product-related information is necessary or useful for, and is specific to use, utilization, or sale of the Product, and is disclosed to Par by Alfacell pursuant to this Agreement. Program Developments Owned or Controlled by Alfacell that are not Alfacell Patents, shall be Alfacell Information. For the avoidance of doubt, Alfacell shall have no obligation to disclose to Par any Ranpirnase or Product manufacturing Know-How Owned or Controlled by Alfacell, except in connection with Section 4.2 of this Agreement.

 

“Alfacell Patents” means any United States patents and patent applications Owned or Controlled by Alfacell as of the Effective Date or Owned or Controlled by Alfacell after the Effective Date that cover Ranpirnase or Product, the importation, use or making of Ranpirnase or Product, or any part of the foregoing or that in Par’s opinion may cover Competing Products, the importation, use or making of Competing Product, or any part thereof. Such Alfacell patents and patent applications as of the Effective Date are set forth on Schedule 1.1, which is attached hereto and made part of this Agreement. Schedule 1.1 shall be amended from time to time during the Term to reflect any such patents Owned or Controlled by Alfacell after the Effective Date. The term “Alfacell Patents” shall include continuations, divisions, provisionals or any substitute applications of the patents and patent applications set forth on Schedule 1.1, any patent issued with respect to any such patent applications, and any reissue, reexamination, renewal or extension (whether by patent law or regulation, or any other law or regulation, for example FDA related extensions) of any such patent.

 

“Alfacell Technology” means Alfacell Patents and Alfacell Information.

 

“Amphinase(s)” means all pharmaceutical agents disclosed or claimed in one or more of the following:

 

 

Patent No. US 7,229,824 B1

U.S. Patent Application No. 11/759,247 filed 7 JUN 2007

U.S. Patent Application No. 11/759,249 filed 7 JUN 2007

U.S. Patent Application No. 11/759,250 filed 7 JUN 2007

U.S. Patent Application No. 11/759,251 filed 7 JUN 2007

U.S. Patent Application No. 11/759,952 filed 8 JUN 2007

U.S. Patent Application No. 11/759,953 filed 8 JUN 2007

U.S. Patent Application No. 11/759,954 filed 8 JUN 2007

U.S. Patent Application No. 11/759,955 filed 8 JUN 2007

The term “Amphinase” also means and includes all pharmaceutical agents disclosed or claimed in any patents issuing on any of the above-referenced patent applications, and all pharmaceutical agents disclosed or claimed in any continuation, division, reexamination, or reissue thereof.

 

“cGMP” means the regulatory requirements for current good manufacturing practices promulgated by the FDA under authority of the U.S. Food, Drug and Cosmetic Act, particularly 21 C.F.R. Section 210 et seq., as the same may be amended from time to time.

 

“Change of Control” means, in respect of either Party, an event in which: (a) any other person or group of persons (as the term “person” is used for purposes of Section 13(d) or 14(d) of the Exchange Act) not then beneficially owning more than fifty percent (50%) of the voting power of the outstanding securities of such Party acquires or otherwise becomes the beneficial owner (within the meaning of Rule 13d-3 promulgated under the Exchange Act) of securities of such Party representing more than fifty percent (50%) of the voting power of the then outstanding securities of such Party with respect to the election of directors of such Party; or (b) such Party (i) consummates a merger, consolidation or similar transaction with another person where the voting securities of such Party outstanding immediately preceding such transaction (or the voting securities issued with respect to the voting securities of such Party outstanding immediately preceding such transaction) represent less than fifty percent (50%) of the voting power of such Party or surviving entity, as the case may be, immediately following such transaction, or (ii) disposes by sale, assignment, exclusive license or otherwise of all or substantially all of its intellectual property rights, except for licenses under such intellectual property rights in the ordinary course of business and any isolated sale or assignment of specific items of intellectual property.

 

 

“Clinical Supplies” means supplies of the Product, manufactured, packaged and labeled in compliance with cGMP and applicable law, in such form and dosage as is determined by Alfacell pursuant to the Development Program, and suitable for use in the conduct of pre-clinical and/or human clinical trials of the Product in the United States pursuant to the Development Program.

 

“CMC Section” means the Chemistry, Manufacturing and Controls section of an NDA submission.

 

“Code” has the meaning set forth in Section 13.3.

 

“Commercialization” means the marketing, promotion, advertising, selling and/or distribution of the Product in the Field in the Territory after Regulatory Approval has been obtained; and the term “Commercialize” has a corresponding meaning.

 

“Commercialization Committee” has the meaning set forth in Section 2.2.

 

“Commercially Reasonable Efforts” means, with respect to each Party, the continuous and diligent efforts and commitment of resources of a degree and kind in accordance with such Party’s reasonable business, legal, medical and scientific judgment that are consistent with the efforts and resources such Party uses for other products owned by it or to which it has similar rights, which are of similar market potential and at a similar stage in their life cycle, taking into account the competitiveness of the marketplace, the regulatory structure involved and other relevant factors; and the term “Commercially Reasonable” has a corresponding meaning. For a Product other than an AG Product, Par’s efforts and commitments for purposes of this definition will be determined by comparison to Par’s branded products; for an AG Product, Par’s efforts and commitments for purposes of this definition will be determined by comparison to Par’s other authorized generic products.

 

“Competing Product” means any pharmaceutical product containing (a) Ranpirnase or (b) any compound or moiety that includes Ranpirnase or is derived from, or substantially similar to, Ranpirnase or its nucleic acid sequences as a starting material, intermediate or base material and, in either case (i) for parenteral administration or (ii) in the Field; provided, however, that (x) no Amphinase shall be considered a Competing Product, and (y) on and after the date that a Third Party sells or offers for sale a generically-labeled version of the Product, the definition of the term “Competing Product” will be limited to a pharmaceutical product containing Ranpirnase and any generic equivalent thereof (as determined by the FDA).

 

“Confidential Information” means information of a Party that is disclosed to or obtained by the other Party (including information obtained by a Party as a result of access to the facilities of the other Party) either prior to or during the Term, which information is non-public, confidential or proprietary in nature, including trade secrets, financial data, product information, manufacturing methods, market research data, marketing plans, identity of customers, nature and source of raw materials, product formulation and methods of producing, testing and packaging; provided, however, that Confidential Information shall not include information that a Party can demonstrate by written evidence: (a) is in the public domain other than as a result of a breach by such Party (or any of its Sub-distributors) of its obligations of confidentiality contained herein; (b) was known by the receiving Party prior to receipt from the disclosing Party; (c) has been developed by the receiving Party independent of any Confidential Information of the disclosing Party; or (d) was subsequently, lawfully and in good faith, obtained by the receiving Party on a non-confidential basis from a Third Party that was not under an obligation to treat such information in a confidential manner and had a lawful right to make such disclosure. Without limiting the foregoing, the terms of this Agreement shall constitute “Confidential Information” of both Parties hereunder.

 

 

“Contract Year” means (a) if the Initial Commercial Sale occurs during the first 45 days of a calendar quarter, a twelve (12) month period starting on the first day of the calendar quarter in which the Initial Commercial Sale (or an anniversary thereof, as the case may be) occurs or (b) if the Initial Commercial Sale occurs other than during the first 45 days of a calendar quarter, a twelve (12) month period starting on the first day of the calendar quarter immediately following the calendar quarter in which the Initial Commercial Sale (or an anniversary thereof, as the case may be) occurs; provided, however, that if a Contract Year is triggered pursuant to the foregoing clause (b), then, for purposes of computing Net Sales during the initial Contract Year, the Parties will include the Net Sales during the forty-five (45) days immediately prior to thereto.

 

“CPR” has the meaning set forth in Section 14.5.

 

“Damages” has the meaning set forth in Section 9.3(e).

 

“Detail” means, with respect to the Product, a face-to-face contact between a sales representative and a physician or other medical professional licensed in the Territory to prescribe drugs, during which a First Position Detail or Secondary Position Detail is made to such person, in each case as measured by each Party’s internal recording of such activity; provided, that such meeting is consistent with and in accordance with the requirements of applicable laws and this Agreement.

 

“Development Committee” has the meaning set forth Section 2.1(a).

 

“Development Costs” means all direct and indirect costs and expenses incurred by Alfacell in connection with the Development Program, which may include (a) costs associated with designing, planning and conducting Phase III Clinical Trials and/or the Phase IIB studies for the Product and all subsequent clinical testing and trials, including all third-party costs and expenses of any and all Phase IIIB and Phase IV studies with respect to the Product that are required by the FDA, and including all costs associated with meeting with the ODAC and/or completion of any studies as a result of such meetings, (b) costs in connection with seeking, obtaining and maintaining Regulatory Approval, including all FDA filing fees, (c) payments made to Third Parties in connection with the Development Program, (d) materials and supplies, and (e) license or acquisition fees and other costs and expenses associated with Alfacell’s obtaining from a Third Party any trademarks, tradenames, logos, trade dress or similar intellectual property rights licensed or acquired by Alfacell after the Effective Date for use in connection with Commercialization of the Product in the Field in the Territory.

 

 

“Development Program” means Alfacell’s activities associated with Alfacell’s development of the Product in the Field for sale in the Territory by Par pursuant to this Agreement, including (a) research and development of a recombinant version of Ranpirnase; (b) manufacture and formulation of the Product for preclinical and clinical studies; (c) planning, implementation, evaluation and administration of human clinical trials of the Product in the Field in the Territory; (d) manufacturing process development and scale-up for the manufacture of the Product; (e) preparation and submission of applications for Regulatory Approval in the Field in the Territory; and (f) post-market surveillance of approved Product Indications.

 

“Direct Cost” means the actual costs and expenses paid by Alfacell to Third Party manufacturers for Product in finished form, filled, labeled and packaged for commercial sale, such costs and expenses not to exceed $*** per 1 mg vial except with the prior written consent of Par, which consent shall not be unreasonably withheld; provided, however, that if the Parties determine to launch a Product where Ranpirnase has been obtained from a recombinant source, then the Direct Cost shall be amended as the Parties mutually agree.

 

“Effective Date” means the date set forth in the introductory paragraph.

 

“Ex-U.S. Shipping Costs” means, if Alfacell’s manufacturing facility or that of its Third Party Manufacturer (as defined in the Supply Agreement) as designated by Alfacell pursuant to Section 5.1 of the Supply Agreement is located outside of the continental United States, all charges and fees for freight, shipping, customs, duties, and insurance incurred by Par for shipment of Product from such facility.

 

“Fair Market Value” means, when determined on an annual basis, the total annual cost per sales representative including salary, commission, benefits, car allowance and legitimate reimbursable travel and/or home office expenses, divided by the number of annual Details delivered by the sales representative, multiplied by the percentage of Product presentation time per Detail (based on the Product presentation position in the Detail, e.g., 60% for First Position Details, 40% for Secondary Position Details). The Fair Market Value may also be determined on a calendar quarter basis, as applicable.

 

“FDA” means The Food and Drug Administration of the United States Department of Health and Human Services, or any successor agency(ies) thereof performing similar functions.

 

“Field” means all uses for cancer in humans.

 

“First Position Detail” means a Detail in which no more than three (3) products are presented, in which key attributes of the Product are verbally presented consistent with the terms of this Agreement and applicable laws, and where the Product receives *** percent (***%) or more of the total call time and is given primary emphasis (i.e., an emphasis that is more important than the emphasis given to any other product presented).

 

“Force Majeure Event” has the meaning set forth in Section 14.7.

 

 

“Future Indication” means an Indication of the Product for the treatment of *** any other specific disease or condition in the Field to which the Parties mutually agree in writing.

 

“Full Approval” means, in respect of the Product for the Primary UMM Indication, Secondary UMM Indication or any Future Indication, Regulatory Approval upon which the FDA has granted full approval (i.e., any FDA approval that is not Accelerated Approval) to market the Product for such Indication in the United States.

 

“GAAP” means generally accepted accounting principles in the United States, as in effect from time to time.

 

“Governmental Authority” means any court, tribunal, arbitrator, agency, legislative body, commission, official or other instrumentality of (a) any government of any country, (b) a federal, state, province, county, city or other political subdivision thereof or (c) any supranational body. The term “Governmental Authority” includes the FDA.

 

“Indemnitor” has the meaning set forth in Section 12.3.

 

“Indication” means any approved human therapeutic use(s) for the Product in the Field.

 

“Initial Commercial Sale” means the first sale of the Product by Par or a Sub-distributor to a Third Party in the Field in the Territory following Regulatory Approval for the Primary UMM Indication, the Secondary UMM Indication or a Future Indication (whichever Indication is approved for the first Product sale in the Territory).

 

“Insolvent Party” has the meaning set forth in Section 13.3.

 

“Knowledge” of Alfacell means the actual knowledge of Kuslima Shogen, Lawrence A. Kenyon, Andrew P. Aromando and/or Diane Scudiery, in each case after due and reasonable inquiry.

 

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

 

“Material Commercialization Decision” has the meaning set forth in Section 2.2(d).

 

“Material Development Decision” has the meaning set forth in Section 2.1(b)(iii).

 

“Modified Targeted Ranpirnase” means Targeted Ranpirnase other than for UMM or any Future Indication.

 

“Net Margin” means Net Sales minus Ex-U.S. Shipping Costs (if applicable).

 

“Net Sales” means, ***.

 

“NDA” means the New Drug Application and all amendments and supplements thereto for the Product submitted by Alfacell to the FDA, including all documents, data and other information included in an accepted NDA submission for Regulatory Approval to market and sell the Product in the Field in the Territory.

 

 

“ODAC” has the meaning set forth in Section 3.1.

 

“Owned or Controlled by” means, with respect to any patent or other intellectual property right, the possession of the ability, whether directly or indirectly, and whether by ownership, license or otherwise, to grant a license, sublicense or other right to or under such Patent or right as provided for herein without violating the terms of any agreement or other arrangement with any Third Party (and in the case of United States Patent Nos. 6,649,392 and 6,649,393, subject to the interests of the U.S. Government therein).

 

“Par” has the meaning set forth in the introductory paragraph.

 

“Par Indemnitee” has the meaning set forth in Section 12.1.

 

“Par Promoted Products” means all FDA-approved branded products that Par is promoting or co-promoting in the Territory for their approved indications.

 

“Party” and “Parties” have the meaning set forth in the introductory paragraph.

 

“Phase III Clinical Trials” means that portion of the Development Program that provides for human clinical studies in the Field that (a) are conducted in a number of patients that is intended to be sufficient to obtain a definitive evaluation of the therapeutic efficacy and safety of a Product in patients for a given Indication as required by 21 C.F.R. §312.21(c), and (b) are needed to evaluate the overall risk-benefit relationship of the Product and to provide adequate basis for obtaining requisite Regulatory Approvals.

 

“Primary UMM Indication” means the Indication of the Product for the treatment of patients with UMM whose disease is either unresectable or who are otherwise not candidates for surgery, wherein (a) the labeling for such Indication recites “ONCONASE® (ranpirnase) in combination with doxorubicin is indicated for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery” or a substantially equivalent or broader label for such Indication, (b) neither the indication nor clinical pharmacology section of the label is limited to use only in patients who have first used and/or failed Altima, and (c) such Indication is supported by data from a pivotal study that demonstrates a statistically significant survival benefit of at least two months.

 

“Product” means any pharmaceutical product containing Ranpirnase for parenteral administration that has been developed by Alfacell or is developed by Alfacell pursuant to this Agreement, including as the Product may be modified to obtain Regulatory Approval thereof, including the AG Product.

 

“Product Infringement” has the meaning set forth in 9.3(c).

 

 

 

“Product Studies” means clinical studies, pre-clinical studies, safety studies, epidemiological studies, modeling and pharmacoeconomic studies, in each case including any ancillary or incidental development, investigation or research pertaining thereto, that are designed (a) to support Regulatory Approval for the Product in the Field in the Territory, or (b) to support publications, promotional and educational activities, future labeling changes or new Indications for Ranpirnase. Unless otherwise expressly provided herein or agreed to by the Parties, all “Product Studies” shall be owned by Alfacell.

 

“Program Developments” means all inventions, discoveries, patents, patent applications, know-how, copyrights and works of authorship and other intellectual property that are related to Ranpirnase in the Field and are made, developed, created, conceived or reduced to practice during the Term of this Agreement by Alfacell in connection with its work in the Development Program, regardless of whether the invention, discovery, patent application, know-how, or work is patentable.

 

“Ranpirnase” means the active pharmaceutical ingredient described in Exhibit A, which may be obtained from natural sources or a recombinant source. For the sake of clarity, sequence variants, and fusion proteins and conjugates that incorporate Ranpirnase, are expressly excluded, but various formulations of the active pharmaceutical ingredient described in Exhibit A are included.

 

“Regulatory Approval” means all approvals (including, where applicable, pricing and reimbursement approval and schedule classifications), product and/or establishment licenses, registrations or authorizations of any Governmental Authority, necessary for the commercialization, use, storage, import, export, transport, offer for sale, or sale of a pharmaceutical product for human use in a regulatory jurisdiction within the Territory, including, if and as applicable, the issuance by the FDA of an action letter indicating approval of the NDA; provided, however, that Regulatory Approval for the Product in any Future Indication can occur following issuance by the FDA of an action letter indicating Accelerated Approval of the NDA.

 

“Representatives” has the meaning set forth in Section 8.1.

 

“Royalty” has the meaning set forth in Section 6.3(a).

 

“SEC” has the meaning set forth in Section 14.13.

 

“Secondary Position Detail” shall mean a Detail in which no more than three products are presented, in which key attributes of the Product are verbally presented consistent with the terms of this Agreement and applicable laws, and where the Product is given significant emphasis (i.e., an emphasis that is more important than the emphasis given to any other product presented (other than the product that is presented as the First Position Detail)).

 

“Secondary UMM Indication” means an Indication of the Product for the treatment of UMM, other than the Primary UMM Indication.

 

“Solvent Party” has the meaning set forth in Section 13.3.

 

 

“Sub-distributor” has the meaning set forth in Section 4.3.

 

“Supply Agreement” has the meaning set forth in Section 2.4.

 

“Targeted Ranpirnase” means any Competing Product that is designed to act, and does act, or is reasonably understood to act, only in a specific manner on only a particular cell, tissue or organ system, for an indication in the Field.

 

“Territory” means the United States of America, including its territories, possessions, protectorates and the Commonwealth of Puerto Rico and any United States military base or installation located outside of the United States of America.

 

“Term” has the meaning set forth in Section 13.1.

 

“Third Party” means any person or entity other than Alfacell or Par or an Affiliate of Alfacell or Par.

 

“Third Party Product Event” has the meaning set forth in Section 7.4.

 

“Trademark” means the trademark under which the Product may be sold in the Field in the Territory, including as set forth in Exhibit B, as may be amended by the Parties from time to time.

 

“Trade Name” means each trade name (i.e., Trademark) established for the Product under this Agreement.

 

“Transfer Price” means ***.

 

“UMM” means unresectable malignant mesothelioma or mesothelioma presented in a patient who otherwise is not a candidate for surgery.

 

“Valid Claim” means (a) an unexpired claim of an issued patent within the Alfacell Patents that has not been held to be unpatentable, invalid or unenforceable by a United States court, the United States Patent and Trademark Office, or other authority in the United States, from which decision no appeal is taken or can be taken; and (b) a claim of a pending application within the Alfacell Patents.

 

1.2 Certain Rules of Construction.

 

(a) As used in this Agreement, unless the context otherwise requires: Section, Schedule, Article and Exhibit references are intended to refer to this Agreement; words describing the singular number shall include the plural and vice versa; words denoting any gender shall include all genders; words denoting natural persons shall include corporations, partnerships and other entities, and vice versa; the words “hereof”, “herein” and “hereunder”, and words of similar import, shall refer to this Agreement as a whole, and not to any particular provision of this Agreement; the term “include” and derivations thereof are not intended to apply any limitation to the item(s) specified; and terms such as licensor, licensee and license will be interpreted broadly to refer also to sub-licensing arrangements and/or the Parties thereto.

 

 

(b) This Agreement is between financially sophisticated and knowledgeable entities and is entered into by the Parties in reliance upon the economic and legal bargains contained herein, the language used in this Agreement has been negotiated by the Parties hereto and shall be interpreted and construed in a fair and impartial manner without regard to such factors as the Party who prepared, or caused the preparation of, this Agreement or the relative bargaining power of the Parties.

 

 

2.1 Development Committee.

 

(a) Establishment. The Parties hereby establish a committee consisting of such even number as shall be agreed by the Parties, fifty percent (50%) of whom shall be Par designees and fifty percent (50%) of whom shall be Alfacell designees (the “Development Committee”). Each of the Development Committee members shall have appropriate expertise to perform the functions assigned to the Development Committee pursuant to this Agreement. The initial Development Committee shall consist of a total of six (6) members who shall be designated by each Party within ten (10) business days after the Effective Date. Each Party shall have the right at any time and from time to time to designate a replacement, on a permanent or temporary basis, for any or all of its previously-designated members of the Development Committee. At the beginning of each calendar year during the Term, each Party shall appoint one of its designees to serve as a Co-Chair of the Development Committee. The initial Co-Chairs shall be designated by each Party within ten (10) business days after the Effective Date.

 

(b) Meetings and Procedures.

 

(i) The Development Committee shall meet at least once per calendar quarter, and more frequently at the reasonable request of either Party or as required to discuss and make efforts to resolve disputes, disagreements or deadlocks of the Development Committee, on such dates, and at such places and times, as the Parties shall agree; provided, however, that the Parties shall use their Commercially Reasonable Efforts to cause the first meeting of the Development Committee to occur within thirty (30) days after the Effective Date. The two Co-Chairs shall cooperate to send a notice and agenda for each meeting of the Development Committee to all members of the Development Committee reasonably in advance of the meeting. The location of regularly-scheduled Development Committee meetings shall alternate between the offices of the Parties, unless otherwise agreed. The members of the Development Committee also may convene or be polled or consulted from time to time by means of telephone conference, video conference, electronic mail or correspondence and the like, as deemed necessary or appropriate by the Co-Chairs. The Party hosting any Development Committee meeting shall appoint one person (who need not be a member of the Development Committee) to attend the meeting and record the minutes of the meeting in writing. Such minutes shall be circulated to the members of the Development Committee promptly following the meeting for review and comment.

 

 

 

(ii) Alfacell agrees to keep the Development Committee reasonably informed in respect of its conduct of the Development Program pursuant to its authority and responsibility set forth in Section 3.1, and in particular Alfacell shall provide the Development Committee with information related to the overall progress of the Development Program. Upon the request of Par’s members, Alfacell shall provide copies and updates of its development plans to the Development Committee. Par’s members shall provide advice, suggestions and constructive feedback on the Development Program. Additionally, Alfacell shall promptly notify the Development Committee if, during the Term, it discovers any new, reproducible uses for Ranpirnase in the Field which have been confirmed by Alfacell and/or are the subject of an invention disclosure or draft patent application, and relevant information related thereto (as such information provided by Alfacell shall be deemed Alfacell Information hereunder).

 

(iii) The Development Committee has no decision-making authority except as expressly set forth herein. Subject to Section 3.7, the final protocol design for any Phase III Clinical Trials for any Future Indication, including any material modification thereof (the “Material Development Decision”), shall be determined by a vote of the Development Committee. All decisions of the Development Committee shall be made by unanimous vote or unanimous written consent of both Parties, with each Party having, collectively among its respective designees, one vote in all decisions. The members of the Development Committee shall use Commercially Reasonable Efforts to decide all matters assigned to the Development Committee under this Agreement or otherwise referred to it by mutual agreement of the Parties; provided, however, that if the members of the Development Committee are unable to make a decision by unanimous vote or unanimous written consent within ten (10) days after commencing discussions regarding such decision, or if Development Program timing constraints make submission of any matter to the Development Committee impracticable, then Alfacell shall have the final decision-making authority with respect to such decision, except (A) in respect of the Material Development Decision, and/or (B) in respect of the Development Committee’s recommendation that Alfacell should not pursue a recombinant source of Ranpirnase, wherein any final decision not to pursue a recombinant source of Ranpirnase shall require the written approval of both Parties.

 

(c) Purposes and Powers. The principal purpose of the Development Committee shall be to provide a forum for open communication between the Parties with respect to development and manufacturing of the Product in general, and for Par to act in an advisory and consultative capacity with respect to the Development Program. The Development Committee shall make recommendations regarding the overall strategy for the Development Program, and shall provide advice, guidance, direction and other recommendations with respect to the Development Program. Subject to the express rights of the Parties as set forth herein, the functions of the Development Committee shall include:

 

(i) Acting as liaison between the Parties to ensure open and regular communication channels, and more particularly to ensure that the Parties are informed of, and have a forum to discuss, the ongoing progress of the Development Program;

 

 

(ii) Reviewing and recommending (or declining to recommend) proposed amendments to the Development Program;

 

(iii) Reviewing, consulting on and providing input in respect of activities related to the manufacturing of the Product and the selection of manufacturer(s) of the Product (provided that Alfacell shall not be required to renegotiate any previously negotiated terms and conditions with any such Product manufacturer(s), and further provided that such consultation and input shall not unreasonably delay Alfacell’s negotiation and completion of its Product contract manufacturing arrangements, wherein the reasonableness of any delay shall be determined by Alfacell in good faith after consultation with Par);

 

(iv) Reviewing and recommending (or declining to recommend), in consultation with the Commercialization Committee, activities (A) related to the publication and/or dissemination of the clinical data and reports related to Product Studies, including publications, posters, abstracts and presentations, and (B) with respect to other matters that intersect or overlap with Commercialization activities; and

 

(v) Performing such other activities and discharging such other responsibilities as may be assigned to the Development Committee by the Parties pursuant to this Agreement or as may be mutually agreed upon by the Parties from time to time.

 

2.2 Commercialization Committee.

 

(a) The Parties hereby establish a committee, separate from the Development Committee, which shall provide a forum for open communication between the Parties regarding Product Commercialization activities in the Field, and which shall be responsible for such matters related to Commercialization of the Products in the Field in the Territory as may be described below. The Commercialization Committee shall consist of such even number as shall be agreed by the Parties, fifty percent (50%) of whom shall be Par designees and fifty percent (50%) of whom shall be Alfacell designees (the “Commercialization Committee”). Each Party shall have the right at any time and from time to time to designate a replacement, on a permanent or temporary basis, for any or all of its previously-designated members of the Commercialization Committee. At the beginning of each calendar year during the Term, each Party shall appoint one of its designees to serve as a Co-Chair of the Commercialization Committee. The initial Commercialization Committee shall consist of six (6) members (including the Co-Chairs of such Committee), who shall be designated by each Party within ten (10) business days after the Effective Date. For the sake of clarity, an individual may serve on both the Development Committee and the Commercialization Committee. The Commercialization Committee shall meet at least once per calendar quarter, and more frequently as mutually agreed by the Parties, on such dates, and at such places and times, as the Parties shall agree.

 

 

(b) Par agrees to keep the Commercialization Committee reasonably informed in respect of its Commercialization of Products in the Field in the Territory pursuant to its authority and responsibility set forth in Section 5.1, and in particular Par shall (a) provide the Commercialization Committee at its regularly scheduled meetings with copies of Par’s annual Product marketing plans, information regarding Par’s Commercialization strategy, and updates regarding the foregoing and the progress of Par’s Commercialization activities, (b) promptly advise the Commercialization Committee of any unforeseen material problems or delays encountered since the date of its last report in connection with the Commercialization activities, and (c) provide Alfacell as soon as reasonably practicable with such other material information as Alfacell’s Commercialization Committee members may reasonably request in writing from time to time with respect to the status of the Commercialization activities and progress. Alfacell’s members shall provide advice, suggestions and constructive feedback on such Commercialization strategy, plans and activities (especially in view of Alfacell’s retained rights regarding Product commercialization outside of the Field and outside of the Territory, and Alfacell’s desire to achieve (to the extent appropriate) global harmonization of Product commercialization (including branding) worldwide). Par will reasonably and in good faith consider any comments and recommendations that the Commercialization Committee may have with respect to the Commercialization of the Product.

 

(c) The Commercialization Committee shall (i) review and recommend (or decline to recommend), in consultation with the Development Committee, (A) activities related to the publication and/or dissemination of the clinical data and reports related to Product Studies, including publications, posters, abstracts and presentations and (B) matters that intersect or overlap with Product development and/or manufacturing activities, (ii) support Par’s strategy and plans regarding Commercialization (to the extent that such strategy and plans have been provided to the Commercialization Committee), and (iii) perform such other activities and discharge such other responsibilities as may be assigned to the Commercialization Committee by the Parties pursuant to this Agreement or as may be mutually agreed upon by the Parties from time to time. Par will reasonably and in good faith consider any comments and recommendations that the Commercialization Committee may have with respect to the Commercialization of the Product.

 

(d) The Commercialization Committee has no decision-making authority except as expressly set forth herein. All Commercialization issues related to the initial medical claims for the core launch materials for the Product that will be submitted to the FDA for pre-clearance review (the “Material Commercialization Decision”) shall be determined by a vote of the Commercialization Committee. If the Commercialization Committee is unable to agree on the Material Commercialization Decision, such dispute or disagreement shall be referred to the CEO of Alfacell and the CEO of Par for resolution, and the CEOs shall resolve the matter (without resort to Section 14.5). All decisions of the Commercialization Committee shall be made by unanimous vote or unanimous written consent of both Parties, with each Party having, collectively among its respective designees, one vote in all decisions. The members of the Commercialization Committee shall use Commercially Reasonable Efforts to decide all matters assigned to the Commercialization Committee under this Agreement or otherwise referred to it by mutual agreement of the Parties; provided, however, that if the members of the Commercialization Committee are unable to make a decision by unanimous vote or unanimous written consent within ten (10) days after commencing discussions regarding such decision, then, except in respect of any Material Commercialization Decision, Par shall have the final decision-making authority with respect to such decision (subject to any limitations on such authority expressly set forth herein); provided, however, that if Commercialization timing constraints make submission of the matter to the Commercialization Committee impracticable, then Par shall have the discretion to make such determination.

 

 

2.3 Expenses. Each Party shall be responsible for all travel and related costs and expenses for its members and approved invitees to attend meetings of, and otherwise participate on, the Development Committee and/or Commercialization Committee.

 

2.4 Ancillary Agreements. All designees of each Party serving on the Development Committee and/or the Commercialization Committee shall as a condition to such service execute a nondisclosure agreement in form and substance reasonably satisfactory to the Parties. Additionally (i) as of the Effective Date, the Parties shall enter into a Supply Agreement which is attached hereto as Exhibit C (the “Supply Agreement”), and (ii) within sixty (60) days of the date that the first NDA is submitted to the FDA by Alfacell, the Parties shall enter into a Quality Agreement on mutually agreeable and customary terms, and (iii) within sixty (60) days after Alfacell’s election to co-promote Product pursuant to Section 5.3 or 5.4, the Parties shall enter into a definitive, written Co-Promotion Agreement on mutually agreeable terms in accordance with Section 5.4.

 

 

 

3.1 Alfacell Responsibility and Control. Subject to Sections 2.1(b)(iii) and 3.7, Alfacell shall have final decision-making authority and primary responsibility for the Development Program and all non-Commercialization strategies, plans and activities regarding the Product. Alfacell shall use its Commercially Reasonable Efforts to conduct the Development Program, to obtain Regulatory Approval for the Product, and to manufacture the Product, all in accordance with this Agreement. More specifically, Alfacell shall use its Commercially Reasonable Efforts to (a) develop the Product for the Primary UMM Indication and, subject to Section 3.7, at least one Future Indication, (b) prepare and submit all required application(s) for Regulatory Approval in the Field in the Territory in respect of the Product for such Indications, including the applicable NDA(s), and (c) if necessary, and subject to Section 6.2(a)(ii), work in consultation with the Development Committee to prepare for any meeting before, and comply with any action plans negotiated by Alfacell and the FDA in response to requests of, the Oncologic Drugs Advisory Committee to the FDA (the “ODAC”). Subject to Section 3.7, Alfacell has the sole right to develop the Product for Future Indications. Subject to the terms and conditions contained in this Agreement, Alfacell shall have sole responsibility and control over development and manufacture of the Product for use in the Field for the Territory and, subject to Section 3.3(b), all regulatory matters related thereto, including control over and responsibility for executing all aspects of the Development Program, including planning, strategy, administrative management, and fiscal control; provided, however, that, subject to Section 6.2(a)(ii), Alfacell shall include Par (through the Development Committee) in such efforts in an advisory and consultative capacity. As of the Effective Date, the Parties anticipate that the Development Program shall be conducted at and coordinated from the facilities of Alfacell. Alfacell shall comply, and shall require all of its Third Party agents and contractors, if any, to comply, with all applicable laws in the conduct of the Development Program.

 

3.2 Development Program. Subject to the provisions of this Agreement, Alfacell shall determine the development plan(s) and the Development Program, and the execution thereof shall be within Alfacell’s decision-making authority and control (subject to Section 2.1(b)(iii)). Notwithstanding the foregoing or any other provision of this Agreement, Par acknowledges and agrees that (a) the Development Program is experimental in nature; and (b) Alfacell does not guarantee that the Development Program will be successful or that Regulatory Approval will be obtained for the Product in the Field in the Territory. During the Term, subject to the other provisions of this Agreement, Alfacell may revise the development plan(s) and/or the Development Program at any time and from time to time, provided that (y) Alfacell provides the Development Committee with a reasonable opportunity to review and comment on any proposed revision to the development plan(s) and/or the Development Program, and (z) Alfacell shall consider in good faith any such comments prior to the adoption and implementation of such revisions.

 

3.3 Clinical and Regulatory Approval.

 

(a) Conduct by Alfacell. The Parties acknowledge that Alfacell has initiated Phase III Clinical Trials in the Territory in respect of the Product for the Primary UMM Indication. Alfacell shall use Commercially Reasonable Efforts to (i) conduct required clinical trials of the Product for the Primary UMM Indication in the Territory and, subject to Section 3.7, for the Future Indications in the Territory agreed to be pursued by the Parties, and undertake steps to obtain Regulatory Approval in accordance with this Agreement and in a manner consistent with the Development Program; and (ii) through the Development Committee, include Par in such efforts in an advisory and consultative capacity. Alfacell acknowledges that certain Product-related activities undertaken by Alfacell outside of the Territory may trigger material reporting obligations to the FDA and may materially affect the Commercialization of the Product by Par in the Territory, and with respect to such activities that Alfacell determines in good faith are likely to trigger such materially reporting obligations and/or are likely to materially affect such Commercialization by Par, Alfacell shall disclose such Product-related activities outside of the Territory to Par and permit Par to promptly review them and provide comments and suggestions that would enable both Parties to achieve their objectives under this Agreement. If the Parties are unable to reach mutual agreement regarding a fair and reasonable approach that would avoid or minimize any material reporting obligations and material effects on Commercialization of the Product by Par, such dispute or disagreement regarding such fair and reasonable approach shall be referred to the CEO of Alfacell and the CEO of Par for resolution, and the CEOs shall resolve the matter (without resort to Section 14.5); provided, however, that this dispute resolution provision shall not empower Par’s CEO with any decision-making authority regarding Alfacell’s Product-related activities outside the Territory, including the right to veto any such activities.

 

(b) Regulatory Submissions.

 

(i) The Parties acknowledge that no Product has been reviewed or approved for sale or use as a human therapeutic product by any Governmental Authority. Subject to Section 3.1, Alfacell shall prepare any required application(s) for Regulatory Approval in the Field in the Territory. Unless otherwise agreed by the Parties, Alfacell shall own, in its entirety, all clinical data and reports related to Product Studies including clinical trials for the Product; provided, however, that, during the Term, Par shall have the right to (i) obtain copies of, and to use, Alfacell Information that is included in Alfacell’s NDA for the Product for an Indication, as Par reasonably determines is necessary or desirable to further the Commercialization of the Product in the Field in the Territory, and (ii) request copies of, and to use, Alfacell Information that is not included in Alfacell’s NDA for the Product for an Indication, with Alfacell’s consent (such consent not to be unreasonably withheld) as Par reasonably determines is necessary or desirable to further the Commercialization of the Product in the Field in the Territory. At all times both prior to and following Regulatory Approval of the Product in the Field in the Territory, Alfacell shall (A) inform Par of all substantive communications from the FDA concerning the NDA and any other material communications from the FDA concerning the Product in the Field within forty-eight (48) hours of receipt thereof, such substantiality and materiality to be solely based on Alfacell’s reasonable evaluation, and (B) provide copies of proposed material FDA communications and submissions concerning the Product to the Development Committee and Par prior to their submission to the FDA, subject to the extent practicable, as described below. Except to the extent that Alfacell must respond to the FDA or make a submission to the FDA before receipt of the Development Committee’s and/or Par’s comments, Alfacell will not respond substantively in writing to any FDA communication or otherwise make any written submissions to the FDA concerning, in either case, the Product in the Field without first giving Par a reasonable opportunity to review and comment thereon. Such opportunity shall not exceed ten (10) days, unless otherwise required by the FDA, in which case Alfacell shall use Commercially Reasonable Efforts to provide Par with an opportunity to review and comment to the extent practicable, but Par agrees that Alfacell shall be entitled to respond in any manner as Alfacell determines in its reasonable discretion is appropriate given the timing of the FDA regulatory review process. Alfacell shall review and consider in good faith any comments received from Par related to such FDA communications or submissions related to the Product in the Field, and any comments or suggestions timely received from Par that are otherwise related to Regulatory Approvals for the Product in the Field in the Territory. For the sake of clarity, the Parties recognize that the FDA regulatory review process may involve both non-Commercialization (i.e., development and/or manufacturing) and Commercialization aspects of the Product in the Field in the Territory (for example, proposed labeling of the Product for a given Indication). If any such intersection or overlap of Alfacell’s final decision-making authority regarding development and manufacturing and Par’s final decision-making authority regarding Commercialization results in a dispute or disagreement, such dispute or disagreement shall be referred to the CEO of Alfacell and the CEO of Par for resolution, and the CEOs shall resolve the matter (without resort to Section 14.5).

 

(ii) The Parties shall cooperate in good faith with respect to obtaining, and Alfacell shall use Commercially Reasonable Efforts to enable representatives of Par to attend, if and as requested by Par and as permitted by the FDA, formal meetings with the FDA relating to Regulatory Approval of the Product in the Field in the Territory. The Parties shall cooperate in good faith with respect to the conduct of any inspections by the FDA or equivalent foreign regulatory authority of a Party’s site and facilities related to the Product. To the extent either Party receives any material written or oral communication from the FDA or equivalent foreign regulatory authority relating to the Regulatory Approval process with respect to the Product in the Field in the Territory, the Party receiving such communication shall promptly notify the other Party and provide a copy of such written communication and/or a written summary of such oral communication as soon as reasonably practicable.

 

 

(iii) If “ONCONASE^®” is not approved by the FDA as the Product Trade Name, Alfacell shall not submit any other Trade Name(s) for the Product for approval by the FDA unless such other Trade Name(s) has (have) been mutually agreed by the Parties. Subject to the license rights granted herein, Alfacell shall own all right, title, and interest to ONCONASE and all such Trade Names and intellectual property rights related thereto (including trademark and copyright), and Par shall (A) assign any right, title, and interest it has in any Trade Names (including intellectual property rights related thereto (including trademark and copyright)) to Alfacell, free and clear of all liens, claims, and encumbrances, and (B) take any and all actions reasonably requested by Alfacell in furtherance of the foregoing. *** related to the choosing of any new Trade Name for the Product in the Field in the Territory, including any market research studies conducted by Par pertaining to ONCONASE or any new proposed Trade Name(s) for the Product.

 

3.4 Development Program Funding. Except as otherwise expressly provided herein or as otherwise expressly agreed by the Parties in writing, Alfacell shall be solely responsible for payment of all Development Costs.

 

3.5 Development Program Reporting. Alfacell shall (a) provide Par at regularly scheduled meetings of the Development Committee with summary updates regarding the progress of the Development Program and Regulatory Approval process, (b) promptly advise Par of any unforeseen material problems or delays encountered since the date of its last report in connection with the Development Program, and (c) provide Par as soon as reasonably practicable with such other material information as Par may reasonably request in writing from time to time with respect to the status of the Development Program.

 

3.6 Post-Regulatory Approval. Alfacell shall, at its sole cost and expense and under its control and responsibility, (a) maintain Regulatory Approval(s) of the Product in the Field in the Territory at all times during the Term following receipt of the same, subject to Par’s cooperation with such efforts as may be required to maintain such Regulatory Approval(s) and (b) conduct any post-Regulatory Approval development programs for the Product that are required by or negotiated with the FDA as a condition to obtaining or maintaining Regulatory Approval of the Product. If mutually determined by the Parties to be beneficial to the development and/or Commercialization of Product in the Field in the Territory, the Parties shall collaborate and cooperate in conducting any post-Regulatory Approval development programs for the Product in the Field in the Territory that are not required by or negotiated with the FDA, ***. Such post-Regulatory Approval development programs shall be conducted in accordance with a written agreement and budget which are accepted in writing by both Parties.

 

3.7 Future Indications Programs. Notwithstanding the scope of Alfacell’s decision-making authority set forth herein (including in Section 3.1), (a) without the prior consent of the Development Committee, Alfacell will not initiate a Phase III Clinical Trial on the Product for any Future Indication in the Territory unless the Development Committee has agreed to the design of such trial, and (b) even with such prior consent by the Development Committee, without the prior written consent of Par, (i) in any consecutive twenty-four (24) month period Alfacell shall not initiate first Phase III Clinical Trials on, and Par shall have no financial obligations in Section 6.2(b) (Future Indication Milestones) for, more than two (2) ongoing Future Indications in the Territory (where the initiation of a first Phase III Clinical Trial in a Future Indication in the Territory shall be deemed to occur on the date of administration of the first dose of the Product to the first patient in such first Phase III Clinical Trial), and (ii) Alfacell shall not initiate, in the aggregate, first Phase III Clinical Trials on more than three (3) Future Indications in the Territory. As of the Effective Date, the Indications recited in clauses (a)-(c) of the definition of “Future Indications” have been mutually agreed by the Parties to be Indications eligible for study by Alfacell pursuant to this Section 3.7. Upon the determination of the design of the Phase III Clinical Trials for any Future Indication in the Territory by the Development Committee, Alfacell shall use Commercially Reasonable Efforts to develop the Product for such Future Indication in the Territory. In the event that the Development Committee is unable to agree as to the design of such trial described in clause (a) above, such dispute or disagreement shall be referred to the CEO of Alfacell and the CEO of Par for resolution, and the CEOs shall use their best efforts to resolve the matter in good faith within thirty (30) days after such referral, subject to Section 14.5.

 

3.8 Recombinant Source. Unless otherwise agreed by the Parties, during the Term, Alfacell shall use its Commercially Reasonable Efforts to pursue a recombinant source of Ranpirnase. As of the Effective Date, the Parties agree that obtaining such recombinant source would be advantageous and would further the objectives of both Parties under this Agreement. Notwithstanding the foregoing or any other provision of this Agreement, (i) Par acknowledges and agrees that Alfacell does not guarantee that such pursuit will be successful or that Regulatory Approval in the Field in the Territory will be obtained for any Product containing recombinant Ranpirnase and (ii) Alfacell shall not use in the manufacturer of the Product Ranpirnase that has been obtained from a recombinant source without Par’s prior written consent.

 

 

 

4.1 Grant to Par.

 

(a) License Generally; Appointment as Exclusive Distributor. Alfacell hereby grants to Par the following rights and licenses:

 

(i) an exclusive (even as to Alfacell, but subject to the co-exclusive rights provided for or referred to in Section 4.1(c)(iii) and 5.4), royalty-bearing license under the Alfacell Patents and under any and all applicable Regulatory Approvals in the Field to promote, market, have marketed, distribute, sell, offer for sale and otherwise Commercialize Product in the Field in the Territory and to do such other things necessary to comply with Par’s obligations under this Agreement.

 

 

(ii) as further provided in, and subject to Article IX, in order to protect the Product in the Field, an exclusive (even as to Alfacell but subject to Alfacell’s rights in Article IX) license to enforce the Alfacell Patents against any potential Third Party infringement that could reasonably be expected to adversely affect the Commercialization or value of the Product in the Territory.

 

(b) Restriction on Right to Sublicense. Notwithstanding the license grants provided in Section 4.1(a), Par (i) shall have the right to market, sell, offer for sale, and have sold AG Product only beginning (a) on the date on or, with Alfacell’s prior written consent, immediately prior to the anticipated date that a Third Party sells or offers for sale a generically-labeled version of the Product or (b) if applicable, upon (or as part of) settlement of a litigation under Section 9.3 that allows a Third Party to sell or offer for sale a generically-labeled version of the Product and (ii) shall not have a general right to sublicense, but shall have the limited right to grant sublicenses only under its rights to market, sell, offer for sale, and have sold AG Product and only in connection with settlement of a litigation under Section 9.3 that allows a Third Party to sell or offer for sale a generically-labeled version of the Product, provided, that Par has obtained the consent of Alfacell to such settlement to the extent required under Section 9.3. Par will at all times remain responsible to Alfacell for all of its obligations under this Agreement and shall be responsible for the acts or omissions of its sublicensees in exercising rights granted hereunder. Each sublicense granted by Par shall be consistent with the terms of this Agreement, and Par shall furnish Alfacell a copy of any such sublicense it grants.

 

(c) Reservation of Rights.

 

(i) Alfacell hereby retains any and all rights which are not expressly granted to Par hereunder.

 

(ii) Nothing in Section 4.1(a) limits Alfacell from exercising its co-promote rights under Section 5.4.

 

(iii) Nothing in Section 4.1(a) limits Alfacell’s ability to perform its obligations under this Agreement, the Supply Agreement, the Quality Agreement and the Co-Promotion Agreement (if Alfacell exercises its co-promote right).

 

(iv) For purposes of clarity and without limitation, Alfacell has exclusively retained (even as to Par) the right to perform (alone or with Third Parties) any and all activities related to the use, research, manufacture and development of Products within and outside the Field and the Territory, and to Commercialize the Products outside the Field in the Territory and in all fields outside the Territory.

 

 

(v) Alfacell has retained the right to enforce the Alfacell Patents as it sees fit against any potential Third Party infringement that could not reasonably be expected to adversely affect the Commercialization or value of the Product under this Agreement, including any patent rights not related to Ranpirnase, Product or Competing Product. For purposes of clarity, Par shall not have any right to enforce, and Alfacell shall exclusively have the right to enforce, each patent claim covering one or more Amphinases. Similarly, with respect to each Modified Targeted Ranpirnase that becomes subject to an Option granted to Par under Section 4.5, if Par rejects its Option under Section 4.5, or if Par does not inform Alfacell of its exercise of the Option within the required time period, or if the Parties have not executed a New License Agreement within the prescribed period under Section 4.5(b) after Par’s exercise of the Option, then thereafter Par shall not have any right to enforce, and Alfacell shall exclusively have the right to enforce, patent claims covering the particular Modified Targeted Ranpirnase that was subject to the Option. In all events, prior to the enforcement of any Alfacell Patent against any Third Party in the Territory, Par and Alfacell shall confer in good faith regarding such enforcement.

 

(d) Trademark and Trade Name License.

 

(i) Alfacell hereby grants to Par an exclusive (even as to Alfacell, subject to the co-promote right provided to Alfacell in Section 5.4), royalty-bearing (but at no additional consideration except as expressly provided herein) license in the Field in the Territory, without the right to sublicense, under the Trademark and each Trade Name that has obtained or hereafter obtains Regulatory Approval for use in connection with the Product, to promote, market, offer for sale, sell and have sold Product in the Field in the Territory; provided, however, that Alfacell retains the right to exercise the foregoing rights only as and to the extent required to permit Alfacell to exercise its co-promote right under Section 5.4 and to perform its obligations under this Agreement. To the extent required by applicable law in the Territory, Alfacell shall make applications to the applicable Governmental Authority for the registration of Par as a registered user of the Trademark and each Trade Name that has obtained or hereafter obtains Regulatory Approval for use in connection with the Product, respectively, in respect of each respective registration of the Trademark or such Trade Name(s), and Par shall cooperate with Alfacell in making such applications. For the avoidance of doubt, Alfacell retains all rights to the Trademark and each Trade Name except to the extent explicitly granted to Par hereunder, and all goodwill associated with the use of the Trademark and each Trade Name will inure exclusively to the benefit of Alfacell.

 

(ii) Par shall comply with the guidelines attached hereto (or to be attached hereto after the Effective Date by Alfacell, subject to Par's consent, not to be unreasonably withheld) as Schedule 4.1(d) in respect of the size, form, and manner of the use of the Alfacell name and logo, and the Trademark and Trade Name(s) in the Commercialization of the Product in the Field in the Territory, subject to any reasonable future revisions thereto requested by Alfacell in writing, provided that any such material revisions thereto shall not be effective unless and until consented to by Par, such consent not to be unreasonably withheld (however, if Par does not so consent, such dispute shall be resolved by the CEO of Alfacell and the CEO of Par (without resort to Section 14.5)). All packaging, inserts, labels, promotional or other materials for the Product sold or to be sold by Par and its Sub-distributors in the Territory shall display the name and Trademark of Alfacell and each such Trade Name (except in respect of the AG Product), and shall identify Alfacell as licensor and manufacturer of the Product. Any failure by Par or its Sub-distributors to comply with this Section 4.1(d) shall be a material breach of this Agreement.

 

 

(e) Challenge. If Par or any of its Affiliates or Sub-distributors directly challenges, or directly assists any Third Party in challenging, in any forum the validity, enforceability, scope or any other elements of the Alfacell Patents, then Alfacell may terminate this Agreement on thirty (30) days’ notice to Par if Par or any of its Affiliates or Sub-distributors shall not cease such challenge within such 30-day period. Without limiting the generality of the foregoing, Par specifically agrees that filing a request for reexamination, attempting to institute an interference, or filing an opposition with respect to any Alfacell Patent(s) or foreign counterparts thereof will be deemed a “challenge” under this Section 4.1(e).

 

4.2 Information Transfer.  

 

(a) Promptly after the Effective Date, Alfacell shall, at its own cost, disclose to Par in writing, or via mutually acceptable electronic media, copies or reproductions of all Alfacell Information, but only to the extent not previously disclosed to Par, that are reasonably necessary or useful for Par and its Sub-distributors to market, sell or have sold the Product in the Field in the Territory. In addition, during the Term of this Agreement, Alfacell shall promptly disclose to Par in writing, or via mutually acceptable electronic media, on an ongoing basis, copies or reproductions of all new Alfacell Information that is reasonably necessary for Par and its Sub-distributors to market, sell or have sold the Product in the Field in the Territory. Such disclosed Alfacell Information shall be automatically deemed to be within the scope of the licenses granted to Par under Section 4.1 without payment of any additional compensation.

 

(b) During the Term of this Agreement, (i) when either Party becomes aware of a potential infringement of the Alfacell Patents by a Third Party in the Field in the Territory, (ii) during the course of a Third Party infringement action brought by or against the Parties as a result of the Party’s (Parties’) activities pursuant to this Agreement, or (iii) on Par’s reasonable request, Alfacell shall promptly disclose to Par in writing, or via mutually acceptable electronic media, copies or reproductions of all new Alfacell Information described in Section 4.2(a) which has not been previously disclosed to Par and which is reasonably necessary for Par to exploit its rights under Article IX. Such disclosed Alfacell Information shall be automatically deemed to be within the scope of the licenses granted to Par under Section 4.1 without payment of any additional compensation.

 

4.3 Appointment of Sub-distributors. Par may, with the prior written consent of Alfacell in its sole discretion (such consent not to be withheld for any potential sub-distributor that is an Affiliate of Par), appoint sub-distributors (which may be Par’s Affiliates or non-Affiliates; each a “Sub-distributor”) to distribute Product for use in the Field in the Territory, subject to the following clauses (a-e) and the other terms and conditions of this Agreement:

 

(a) each agreement with a Sub-distributor shall be in writing and shall state that the Sub-distributor’s rights under such agreement are subject to all relevant terms and conditions of this Agreement, including (without limitation) provisions and restrictions relating to Field, Territory, price, payment, reporting, audit of books and records, promotional materials, trade name, and termination;

 

 

(b) if this Agreement terminates, in whole or in part, the rights of any Sub-distributors shall automatically be terminated in accordance therewith;

 

(c) Par shall promptly notify Alfacell in writing of any breaches of this Agreement that are due to any act or omission by any Sub-distributor(s), and shall report to Alfacell the full details of such breach and the actions to be taken by Par to cure such breach;

 

(d) Par shall ensure that each Sub-distributor complies with all applicable terms and conditions of this Agreement, and shall be liable to Alfacell for any failure of any Sub-distributor to do so; and

 

(e) Par shall provide Alfacell with the names and primary business addresses of all Sub-distributors and, within fifteen (15) days of the effective date of each agreement with a Sub-distributor, Par shall provide a copy of each such agreement to Alfacell.

 

For the avoidance of doubt, (i) any act or omission of a Sub-distributor that would be a breach of this Agreement if performed by Par will be deemed to be a breach by Par of this Agreement, and (ii) Par’s customers (e.g., wholesalers) shall not be considered Sub-distributors for purposes of this Agreement.

 

4.4 Exclusivity.

 

(a) Alfacell agrees that, during the Term, it will not, and it will not enable or contract with any Third Party to, (i) market, sell or distribute the Product in the Field in the Territory or develop or supply the Product for sale in the Field in the Territory, except in accordance with Section 5.4 and/or for the development and supply of the Product in the Field in the Territory pursuant to this Agreement, (ii) market, sell or distribute any Competing Product in the Territory or develop or supply any Competing Product for sale in the Territory; or (iii) use the Trademark in connection with any product in the Territory other than the Product pursuant to this Agreement; provided, however, that, subject to Section 4.5, the foregoing restrictions provided in this Section 4.4(a) shall not restrict Alfacell, directly or through a Third Party, from developing, manufacturing, importing, marketing, selling or distributing Modified Targeted Ranpirnase.

 

(b) Par agrees that, and shall cause its Sub-distributors to agree that, during the Term, Par and its Sub-distributors will not, and will not enable or contract with any Third Party to manufacture, import, market, sell or distribute any Competing Product in the Territory. To the fullest extent permitted by applicable law, Par is prohibited from selling (and Par shall not permit its Sub-distributors to sell), and Par and its Sub-distributors shall not sell, Product (i) outside the Territory, (ii) to customers in the Territory that Par or its Sub-distributors know, or have reason to know, plan to resell or in the past have resold the Product for use outside the Territory, and Par shall not during the Term actively approach, or accept or fill orders from, customers outside the Territory. This prohibition includes detailing, visiting, calling, mailing, or marketing Product to such customers. If Par or its Sub-distributors knowingly sell the Product outside of the Territory, Par shall provide full details of such Product sale to Alfacell and pay Alfacell, at Alfacell’s option, in addition to any other remedies available to Alfacell, for each Product thus sold, ***. In addition, Alfacell may terminate this Agreement on sixty (60) days’ notice to Par if Par does not cease such sales, and cause its Sub-distributors to cease such sales, outside the Territory within such 60-day period. Additionally, Par agrees that, and shall cause its Sub-distributors to agree that, during the Term, Par and its Sub-distributors will not, and will not enable or contract with any Third Party to, promote, market, have marketed, distribute, offer for sale, sell or have sold the Product outside of the Field.

 

 

4.5 Right of First Negotiation.

 

(a) If, following the Effective Date, Alfacell determines that a particular Modified Targeted Ranpirnase compound demonstrates activity across one or more tumor cell types and has commercial viability (and such determination is reasonably supported by reasonable non-clinical or pre-clinical data in respect of such cell type(s)), Alfacell shall, prior to instituting any Phase III development program in respect thereof, provide Par with a one time written notice of information that Alfacell possesses or that Alfacell has a contractual right with any Third Party to obtain, subject to any corresponding contractual obligation, including copies of such data, and an estimate of the cost for developing and obtaining regulatory approval therefor, that is reasonably required by Par to determine whether or not to enter into negotiations for a license agreement with Alfacell with respect to such Modified Targeted Ranpirnase. The delivery of such notice shall automatically grant to Par an exclusive option (the “Option”) to enter into an agreement with Alfacell for an exclusive license to permit Par to market, sell and have sold such Modified Targeted Ranpirnase in respect of the applicable indications (the “New License Agreement”). Par shall determine and notify Alfacell of its determination in writing, as soon as practicable, and in any event no more than *** days after the grant of such Option by Alfacell, to (i) exercise the Option by delivery of written notice to Alfacell of its exercise of such Option, or (ii) reject the Option. The exercise, or determination not to exercise, by Par of its rights under this Section 4.5(a) in respect of any granted Option shall not affect its rights in respect of any other Modified Targeted Ranpirnase compound that was not subject to such Option. Any data or other information provided by Alfacell to Par pursuant to this Section 4.5(a) shall be deemed and treated as Confidential Information in accordance with and subject to Section 8.1. If Par fails to exercise its Option within such *** period, or if Par rejects its Option, or if the Parties do not execute a New License Agreement despite their good faith efforts during the *** described in subsection (b) below, then within ten (10) business days after such failure, rejection or absence of execution (as applicable), Par shall return to Alfacell all documentation containing Confidential Information of Alfacell that was received by Par pursuant to this Section 4.5(a).

 

(b) If Par exercises its Option, the Parties shall, during the *** from the date of exercise of the Option, negotiate exclusively a New License Agreement with one another in good faith. If, following such ***, the Parties have not executed the New License Agreement despite their good faith efforts, Alfacell may, but shall not be obligated to, offer such license for Modified Targeted Ranpirnase for the applicable indication(s) to a Third Party. If Par rejects the Option, or does not inform Alfacell of its exercise of the Option within the *** after the grant of such Option by Alfacell, (i) Alfacell may, but shall not be obligated to, negotiate and enter into a license agreement with a Third Party, and (ii) thereafter the particular Modified Targeted Ranpirnase that had been subject to such Option shall be deemed to no longer be a “Competing Product” for purposes of this Agreement.

 

 

 

 

5.1 Par Responsibility and Control. Except as otherwise expressly set forth herein, subject to the input of the Commercialization Committee, Par shall have responsibility for all Commercialization activities in the Field in the Territory, including developing strategies and tactics related to the advertising, promotion, pricing, marketing and selling the Product. Par shall have final decision-making authority and primary responsibility for all Commercialization strategies, plans and activities regarding the Product in the Field in the Territory. Par shall use its Commercially Reasonable Efforts to Commercialize the Product in the Primary UMM Indication, the Secondary UMM Indication and any Future Indications that have obtained Regulatory Approval in the Territory. Par shall include Alfacell in such efforts in an advisory and consultative capacity. Par shall comply, shall cause its Sub-distributors to comply, and shall require all of its Third Party agents and contractors, if any, to comply, with all applicable laws in Commercializing the Product in accordance with this Agreement.

 

5.2 Certain Present Intentions and General Obligations of Par. As of the Effective Date, Par intends on or before the Initial Commercial Sale to assign a dedicated product manager for Commercialization of the Product. In addition, following the Initial Commercial Sale, Par shall (if it has not theretofore) employ or engage a sales training manager (such position may be filled by an employee or a consultant experienced in oncology) and a reimbursement specialist (who shall be knowledgeable about Part B).

 

5.3 Specific Commercialization Rights and Obligations of Par.

 

(a) Following Regulatory Approval for the Product for the Primary UMM Indication, Secondary UMM Indication and any Future Indication, Par shall use Commercially Reasonable Efforts to Commercialize the Product for each such applicable Indication in accordance with this Agreement and in a manner consistent with the then-current Commercialization plan(s), and shall include Alfacell in such efforts in an advisory and consultative capacity. Subject to any conditions or limitations set forth herein, it shall be Par’s sole right and responsibility to (a) determine the commercially reasonable launch dates for the Product, (b) develop advertising and promotional materials related to the Product, (c) book sales for the Product, (d) handle all returns of the Product, (e) handle all aspects of order processing, invoicing and collection of receivables for the Product, (f) collect data regarding sales to hospitals and other end users of the Product, (g) monitor inventory levels of the Product, (h) provide first line customer support and pharmacovigilance (and after such initial support, pharmacovigilance support shall be handled in accordance with Article X), (i) warehouse the Product, and (j) determine the prices for the Product and any discounts and rebates that may be offered thereto, including decisions relating to customer allowances and credits. Par shall determine the Commercialization plan(s) and Commercialization activities, and the execution thereof shall be within Par’s decision-making authority and control. Par shall use Commercially Reasonable Efforts to achieve an Initial Commercial Sale within *** after Alfacell obtains Regulatory Approval for the Primary UMM Indication, Secondary UMM Indication and/or any Future Indication (as applicable). Par shall utilize proactive and continuous Product Commercialization efforts (which may be subject to factors that are beyond the reasonable control of Par) by Par during the first *** after Initial Commercial Sale to advance the objectives and optimize the financial returns of both Parties under this Agreement (i.e., during such ***, Par shall not cease Commercializing, or engage in di minimis Commercialization of, the Product).

 

 

(b) On no less than ninety (90) days’ written notice to Par given on or after the *** of the Initial Commercial Sale, Alfacell may elect to add up to *** sales representatives under Alfacell’s control, at Alfacell’s expense, to co-promote the Product for the approved Indication(s), subject to a mutually agreeable co-promote agreement. If Alfacell so elects, then such co-promotion by Alfacell of the Product for the approved Indication(s) (including UMM Indications) shall be deemed to be an accelerated exercise by Alfacell of its co-promote right pursuant to Section 5.4; provided, however, that Alfacell shall continue to pay for such additional sales representatives only until such time as its co-promote right could have otherwise been exercised pursuant to Section 5.4 (subject to Section 5.4(a)(z)).

 

5.4 Co-promote.

 

(a) Subject to Section 5.4(b) and Alfacell’s right to elect an accelerated exercise of Alfacell’s co-promote right with respect to all approved Indications pursuant to Section 5.3(b), Alfacell shall have the right to co-promote the Product on the approval of any Future Indication in the Territory (i) by providing written notice to Par at least *** in advance of Alfacell’s planned commencement of such co-promote activities and (ii) by entering into a mutually agreeable, definitive, written co-promotion agreement with Par setting forth the particulars of the Parties’ rights and obligations concerning co-promotion of the Product. The Parties shall use good faith to enter into, prior to the Initial Commercial Sale, such co-promotion agreement, which shall, among other things, include (x) an obligation of Par to pay Alfacell only the Fair Market Value per Detail for Alfacell’s sales representatives for such co-promotion, which Details provided by Alfacell’s sales representatives shall not exceed *** percent (***%) of all of the Details for the Product for the applicable Future Indication, (y) if Alfacell intends use such Alfacell sales representatives to promote or co-promote a pharmaceutical product (other than the Product) that shares an FDA-approved, labeled indication with any Par Promoted Product, Alfacell shall be entitled to promote or co-promote such pharmaceutical product if, and only if, Alfacell provides written notice of such intention to Par, and (z) if Alfacell provides such written notice indicating its intent to promote or co-promote such pharmaceutical product, or if Alfacell in fact promotes or co-promotes such pharmaceutical product, then Par shall no longer be obligated to pay to Alfacell the Fair Market Value per Detail for co-promotion by Alfacell of the Product, and such co-promotion by Alfacell of the Product shall thereafter be at Alfacell’s sole cost and expense (until such time as Alfacell no longer promotes or co-promotes such pharmaceutical product, which shall not occur prior to 60 days following the delivery by Alfacell of written notice to Par in respect thereof). Alfacell shall not be entitled to initiate any co-promotion activities for the Product unless and until the Parties enter into such co-promotion agreement.

 

 

(b) If the Product obtains Regulatory Approval for a Future Indication prior to the Regulatory Approval of the Product for the Primary UMM Indication or Secondary UMM Indication, and if the Parties do not waive the pre-condition related thereto set forth in Section 6.2(b), then, subject to Section 5.3, Alfacell’s right to co-promote the Product may not be exercised by Alfacell until the later of (i) *** following the initial commercial sale of the Product for such Future Indication and (ii) the earlier to occur of (a) Regulatory Approval of the Product for the Primary UMM Indication or Secondary UMM Indication, or (b) the *** of Regulatory Approval related to the Product for such Future Indication.

 

 

 

6.1 Upfront Payment. In consideration for the execution and delivery of this Agreement by Alfacell, Par shall pay Alfacell a fully earned, non-refundable, non-creditable license fee in the amount of US$5,000,000 by wire transfer of immediately available funds upon execution and delivery of this Agreement.

 

6.2 Milestone Payments.

 

(a) UMM Indication Milestone Payments.

 

(i) Subject to the terms and conditions of this Agreement, including Section 6.2(a)(ii):

 

(1) if Alfacell obtains Full Approval for the Product for the Primary UMM Indication on or before July 31, 2010, Par shall pay to Alfacell US$30,000,000;

 

(2) if Alfacell obtains Full Approval for the Product for the Primary UMM Indication after July 31, 2010, then in lieu of the milestone payment provided in Section 6.2(a)(i)(1), Par shall instead pay to Alfacell US$***; and

 

(3) if Alfacell has not obtained Full Approval for the Product for the Primary UMM Indication at the time that it obtains Full Approval for the Product for a Secondary UMM Indication, then, in lieu of any milestone payment provided in Section 6.2(a)(i)(1) or 6.2(a)(i)(2), Par shall pay to Alfacell US$***; provided, however, that if Alfacell subsequently obtains Full Approval for the Product for the Primary UMM Indication, then Par shall pay to Alfacell either US$*** (if such Full Approval for the Product for the Primary UMM Indication is obtained on or before July 31, 2010) or US$*** (if such Full Approval for the Product for the Primary UMM Indication is obtained after July 31, 2010), as applicable.

 

 

(ii) If a meeting with the ODAC is called for by the FDA or if Par reasonably believes that the FDA will have outstanding review issues and/or questions relevant to the CMC Section, then Par may, in its sole discretion, make a partial prepayment of the amounts provided in Section 6.2(a)(i) in an amount not to exceed US$***; provided, however, that (A) any such prepayment amount shall be used exclusively in the preparation of the CMC Section or, as applicable, preparation for the meeting with, or in compliance with any requests of, the ODAC, and (B) in consideration of such prepayment, Par and Alfacell shall be entitled to jointly control, subject to Section 14.5, the preparation for any meeting with the ODAC or preparation of the CMC Section, as applicable, the compliance with any requests of the ODAC and the allocation of funds related thereto.

 

(b) Future Indication Milestones. Provided Alfacell shall have received Full Approval for either the Primary UMM Indication or the Secondary UMM Indication, or provided that each of the Parties agrees in writing, in its sole discretion, to waive the foregoing pre-condition due to unexpected and/or unavoidable delays in receipt of such Full Approval for a UMM Indication despite Alfacell’s Commercially Reasonable Efforts to obtain such receipt, then and in addition to the milestones payments set forth in Section 6.2(a) and subject to Section 3.7, upon the achievement of certain milestones, Par shall make fully earned, non-refundable, non-creditable payments to Alfacell by wire transfer of immediately available funds as follows:

 

(i) Upon the administration of the first dose of the Product to the first patient in a first Phase III Clinical Trial for each Future Indication, Par shall pay to Alfacell US$***;

 

(ii) Upon the acceptance for filing by the FDA of Alfacell’s NDA subject to a Special Protocol Assessment (as described as of the Effective Date at http://www.fda.gov/cber/gdlns/protocol.htm#i) for each Future Indication, Par shall pay to Alfacell US$***; provided, however, that in the event a Special Protocol Assessment is not used, then, prior to filing of the applicable Alfacell NDA with the FDA, up to two (2) experts shall be retained by each Party (for a total of four (4) experts), and if such experts reasonably agree that the Phase III Clinical Trial data package is unlikely to support FDA approval for such Future Indication, then Par shall not be obligated to pay to Alfacell such amount; and

 

(iii) Upon a Regulatory Approval of each Future Indication, Par shall pay to Alfacell US$***.

 

(c) Sales Milestone Payments. In addition to the milestone payments set forth above, following the Initial Commercial Sale, on the terms and subject to the conditions contained herein, Par shall additionally be obligated as follows:

 

(i) Subject to Section 6.2(c)(ii), Par will pay to Alfacell the following one-time only milestone payments:

 

***

 

 

(ii) The milestone payments set forth in Section 6.2(c)(i) (“Sales Milestone Payments”) are subject to the following: (A) each such Sales Milestone Payment is available to Alfacell on a one-time basis, such that once achieved and paid, such Sales Milestone Payment shall not be payable again regardless of the amount of Net Sales in any future Contract Year; (B) if more than one milestone is achieved for the first time in any given Contract Year, then Par shall make each Sales Milestone Payment, and each such achieved milestone shall be forever satisfied hereunder; and (C) the aggregate of all Sales Milestone Payments under this Section 6.2(c) during the Term shall not exceed an amount equal to US$***.

 

6.3 Royalty.

 

(a) Royalty Payment. In addition to the milestone payments set forth above in Section 6.2, following the Initial Commercial Sale of the Product, in respect of any Contract Year, Par shall pay to Alfacell an amount equal to (i) *** (amounts owed to Alfacell pursuant to this Section 6.3(a), the “Royalty”).

 

(b) Royalty Step Down. Upon expiration of the last to expire Valid Claim within the Patents licensed to Par during the Term pursuant to Section 4.1, each of the royalty rates set forth in Section 6.3(a) shall be reduced as follows ***; and further provided, in the event that, after such expiration of the last to expire Valid Claim, a subsequent Valid Claim should come into existence during the Term, then the royalty rates set forth in Section 6.3(a) shall again apply without reduction pursuant to this Section 6.3(b).

 

(c) Termination of Royalty. Unless otherwise expressly provided herein, the obligation of Par to pay Royalties to Alfacell pursuant to Section 6.3(a) shall cease upon expiration or termination of this Agreement.

 

6.4 Other Payment Obligations of Par. Par shall pay to Alfacell the amounts set forth in Section 5.4 (Co-promote) and Section 7.2 (Pricing), in each case subject to the terms set forth therein.

 

6.5 Payment Procedures.

 

(a) Manner of Payment. Remittance of payments to Alfacell hereunder will be made in immediately available funds by means of wire or electronic transfer to an Alfacell account in a bank in the United States to be designated by Alfacell.

 

(b) Payments and Reports. All amounts payable to Alfacell under this Agreement shall be paid in U.S. Dollars. Milestone Payments under Section 6.2 shall be made no later than ten (10) days after the satisfaction of the milestone giving rise to the applicable payment. The Royalty shall accrue at the time of sale of the Product by Par or a Sub-distributor to a Third Party. Royalty obligations that accrue during a calendar quarter shall be paid within forty-five (45) days after the end of such calendar quarter, and other payments owing shall be made as specified herein. Each payment of Royalties due to Alfacell shall be accompanied by a report listing the number of units of Product sold, the gross invoiced sales amounts of the Product sold during such period, the calculation of Net Sales based on such sales, the applicable royalty rate, the Royalties payable, all other information necessary to determine the appropriate amount of such Royalty payments, and any additional information or reports required under this Agreement or reasonably requested by Alfacell.