Model Letter of Collaboration between the Developmental Therapeutics Program Division of Cancer Treatment/Diagnosis National Cancer Institute, United States of America (DTP/NCI) and a Source Country Government (SCG)/Source Country Organization(s) (SCO)

(TTB Version 02/2002)

LETTER OF COLLECTION

The Developmental Therapeutics Program ("DTP"), Division of Cancer Treatment and Diagnosis ("DCTD"), National Cancer Institute ("NCI") is currently investigating plants, microbes, and marine macro-organisms as potential sources of novel anticancer and AIDS-antiviral drugs. The DTP is the drug discovery program of the NCI which is an Institute of the National Institutes of Health ("NIH"), an arm of the Department of Health and Human Services of the United States Government. While investigating the potential of natural products in drug discovery and development, NCI wishes to promote the conservation of biological diversity, and recognizes the need to compensate [Source Country, SC] organizations and peoples in the event of commercialization of a drug developed from an organism collected within their borders.

As part of the drug discovery program, DTP has contracts with various organizations for the collection of plants, microbes and marine macro-organisms worldwide. DTP has an interest in investigating plants, microbes and marine macro-organisms from [Source Country], and wishes to collaborate with the [Source Country Government ("SCG") or Source Country Organization(s) ("SGO")] as appropriate in this investigation. The collection of plants, microbes, and marine macro-organisms will be within the framework of the collection contract between the NCI and the NCI Contractor ("Contractor") which will collaborate with the appropriate agency in the [SCG or SCO]. The NCI will make sincere efforts to transfer knowledge, expertise, and technology related to drug discovery and development to the [appropriate Source Country Institution ("SCI")] in [Source Country] as the agent appointed by the [SCG or SCO], subject to the provision of mutually acceptable guarantees for the protection of intellectual property associated with any patented technology. The [SCG or SCO], in turn, desires to collaborate closely with the DTP/NCI in pursuit of the investigation of its plants, microbes and marine macro-organisms, subject to the conditions and stipulations of this agreement.

A. The role of DTP, DCTD, NCI in the collaboration will include the following:

1) DTP/NCI will screen the extracts of all plants, microbes and marine macro-organisms provided from [Source Country] for anticancer and AIDS-antiviral activity, and will provide the test results to [SCI] on a quarterly basis. Such results will be channeled via Contractor.

2) The test results will be kept confidential by all parties, with any publication delayed until DTP/NCI has an opportunity to file a patent application in the United States of America on any active agents isolated. Such application will be made according to the terms stated in Article 6.

3) Any extracts exhibiting significant activity will be further studied by bioassay-guided fractionation in order to isolate the pure compounds(s) responsible for the observed activity. Since the relevant bioassays are only available at DTP/NCI, such fractionation will be carried out in DTP/NCI laboratories. A suitably qualified scientist designated by [SCI] may participate in this process subject to the terms stated in Section A / Article 4. In addition, in the course of the contract period, DTP/NCI will assist the [SCO], in conjunction with [SCI], thereby assisting the [SC], to develop the capacity to undertake drug discovery and development, including capabilities for the screening and isolation of active compounds from plants, microbes and marine organisms.

4) Subject to the provision that suitable laboratory space and other necessary resources are available, DTP/NCI agrees to invite a senior technician or scientist designated by [SCI] to work in the laboratories of DTP/NCI or, if the parties agree, in laboratories using technology which would be useful in furthering work under this agreement. The duration of such a visit would not exceed one year except by prior agreement between [SCI] and DTP/NCI. The designated Guest Researcher will be subject to provisions usually governing Guest Researchers at NIH, except when carrying out research on materials provided through collections in [Source Country]. Salary and other conditions of exchange will be negotiated in good faith.

5) In the event of the isolation of a promising agent from a plant, microbe or marine macro-organism collected in [Source Country], further development of the agent will be undertaken by DTP/NCI in collaboration with [SCI]. Once an active agent is approved by the DTP/NCI for preclinical development, [SCI] and the DTP/NCI will discuss participation by SCI scientists in the development of the specific agent.

The DTP/NCI will make a sincere effort to transfer any knowledge, expertise, and technology developed during such collaboration in the discovery and development process to [SCI], subject to the provision of mutually acceptable guarantees for the protection of intellectual property associated with any patented technology.

6) DTP/NCI will, as appropriate, seek patent protection on all inventions developed under this agreement by DTP/NCI employees alone or by DTP/NCI and [SCG or SCO or SCI] employees jointly, and will seek appropriate protection abroad, including in [Source Country], if appropriate.

7) All licenses granted on any patents arising from this collaboration shall contain a clause referring to this agreement and shall indicate that the licensee has been apprized of this agreement.

8) Should the agent eventually be licensed to a pharmaceutical company for production and marketing, DTP/NCI, will require the successful licensee to negotiate and enter into agreement(s) with the [SCG] agency(ies) or [SCO] as appropriate. This agreement(s) will address the concern on the part of the [SCG or SCO] that pertinent agencies, institutions and/or persons receive royalties and other forms of compensation, as appropriate.

9) Such terms shall apply equally to instances where an invention is directed to a direct isolate from a natural product material, a product structurally based upon an isolate from the natural product material, a synthetic material for which the natural product material provided a key development lead, or a method of synthesis or use of any aforementioned isolate, product or material; though the percentage of royalties negotiated as payment might vary depending upon the relationship of the marketed drug to the originally isolated product. It is understood that the eventual development of a drug to the stage of marketing is a long term process which may require 10-15 years.

10) In obtaining licensees, the DTP/NCI will require the license applicant to seek as its first source of supply the natural products from [Source Country]. If no appropriate licensee is found that will use natural products available from [Source Country], or if the [SCG] or [SCO] as appropriate, or its suppliers cannot provide adequate amounts of raw materials at a mutually agreeable fair price, the licensee will be required to pay the [SCG] or [SCO] as appropriate, an amount of money (to be negotiated) to be used for expenses associated with cultivation of medicinal plant, microbe or marine macro-organism species that are endangered by deforestation, or for other appropriate conservation measures. These terms will also apply in the event that the licensee begins to market a synthetic material for which a material from [Source Country] provided a key development lead.

11) Section 10 shall not apply to organisms which are freely available from different countries (i.e., common weeds, agricultural crops, ornamental plants, fouling organisms) unless information indicating a particular use of the organism (e.g., medicinal, pesticidal) was provided by local residents to guide the collection of such an organism from [Source Country], or unless other justification acceptable to both the [SCG or SCO] and the DTP/NCI is provided. In the case where an organism is freely available from different countries, but a phenotype producing an active agent is found only in [Source Country], Article 10 shall apply.

12) DTP/NCI will test any pure compounds submitted by the [SCG or SCO] and [SCI] scientists for anti-tumor and anti HIV/AIDS activity, provided such compounds have not been tested previously in the DTP/NCI screens. If significant anti-tumor or anti HIV/AIDS activity is detected, further development of the compound and investigation of patent rights will, as appropriate, be undertaken by DTP/NCI in consultation with [SCI] and the [SCG or SCO].

Should an agent derived from the compound eventually be licensed to a pharmaceutical company for production and marketing, DTP/NCI will require the successful licensee to negotiate and enter into agreement(s) with the appropriate [SCG agency(ies) or SCO]. This agreement will address the concern on the part of the [SCG or SCO] that pertinent agencies, institutions and/or persons receive royalties and other forms of compensation, as appropriate.

13) DTP/NCI may send selected samples to other organizations for investigation of their anti-cancer, anti-HIV or other therapeutic potential. Such samples will be restricted to those collected by NCI contractors unless specifically authorized by the [SCG or SCO]. Any organization receiving samples must agree to compensate the [SCG or SCO] and individuals, as appropriate, in the same fashion as described in Articles 8-10 above, notwithstanding anything to the contrary in Section 11.

B. The role of the Source Country Government ("SCG") or Source Country Organization(s) ("SCO") in the collaboration will include the following:

1) The appropriate agency in [SCG or SCO] will collaborate with Contractor in the collection of plants, microbes and marine macro-organisms, and will work with Contractor to arrange the necessary permits to ensure the timely collection and export of materials to DTP/NCI.

2) Should the appropriate agency in [SCG or SCO] have any knowledge of the medicinal use of any plants, microbes and marine macro-organisms by the local population or traditional healers, this information will be used to guide the collection of plants, microbes or marine macro-organisms on a priority basis where possible. Details of the methods of administration (e.g., hot infusion, etc.) used by the traditional healers will be provided where applicable to enable suitable extracts to be made. All such information will be kept confidential by DTP/NCI until both parties agree to publication.

The permission of the traditional healer or community will be sought before publication of their information, and proper acknowledgment will be made of their contribution.

3) The appropriate agency in [SCG or SCO] and Contractor will collaborate in the provision of further quantities of active raw material if required for development studies.

4) In the event of large amounts of raw material being required for production, the appropriate agency of the [SCG or SCO] and Contractor will investigate the mass propagation of the material in [Source Country]. Consideration should also be given to sustainable harvest of the material while conserving the biological diversity of the region, and involvement of the local population in the planning and implementation stages.

5) [SCG or SCG] and SCI scientists and their collaborators may screen additional samples of the same raw materials for other biological activities and develop them for such purposes independently of this agreement.

This agreement shall be valid as of the date of the final authorized signature below for an initial period of five (5) years, after which it can be renewed by mutual agreement. It may be amended at any time subject to the written agreement of both parties. Copies of such amendments will be kept on file at both of the addresses indicated below.