Attachment3SOW-AP.pdf

ATTACHMENT 3 - STATEMENT OF WORK

Title: Collection and Taxonomy of Shallow Water Marine Organisms

STATEMENT OF WORK

June 24, 2008

a. Independently and not as an agent of the US Government, the contractor shall furnish all the necessary services, qualified personnel, material, equipment and facilities, not otherwise provided by the Government as needed to collect sufficient quantities of 450-500 marine macro-organisms per year which will yield 10-20 gram samples of extract after processing by a separate extraction facility. From previous studies, this would require the collection of ca 1000 grams, frozen wet weight of a given sample.

Specimens of all organisms collected shall be submitted to the Natural Products Repository at NCI-Frederick, Frederick, MD., for deposition.

Collections shall be concentrated in the Indo-Pacific and some Atlantic regions, including, but not limited to, locations such as Papua New Guinea, Australia, New Zealand, The Philippines, the Indochina Peninsular, Malaysia, Melanesia, Micronesia and Indian Ocean Islands, the Caribbean and surrounding areas, Atlantic islands and additional collection areas [less than 20% overall] may be suggested by offerors in addition to these, provided adequate scientific justification is given for the sites proposed. Portions of these collections may be performed by sub-contractors or consultants to the prime contractor.

b. Specifically, the Contractor shall:

1. Furnish qualified personnel, materials and equipment for the collection, identification, storage and shipping of frozen marine invertebrate and frozen marine plant samples to the Natural Products Repository, NCI-Frederick, Frederick, MD.

2. Collect, store and ship approximately 450-500 marine organism samples per year [on average] from the collection region, each being approximately 1-1.5 Kg from depths accessible by well-trained SCUBA divers. Conventionally, this would be from 40 meters or less, but if suitably experienced divers are part of the team, depths of up to 50-150 meters may be accessed with correct safeguards for decompression diving and/or self-contained rebreathers. If suitable apparatus is available, together with trained and qualified personnel, then depths of greater than these may be suggested by a contractor as part of a “vertical study of diversity”.

Up to 20% of the organisms may be provided in quantities from 300 to 500 grams when the collectors judge that [I.] they will provide adequate amounts of organic extract or [II.] the organism is from an unusual taxonomic group and is not abundant. Ecologically sound collection practices must be used.

3. Undertake the complete identification to species level of every sample collected, as soon as possible (normally within 6 months but in the cases of “new to Science” then the taxonomist will proceed as expeditiously as is feasible to identify to species) after collection.

4. Avoid, as far as is possible, duplicate collections of species over the full contract period from the same or close by sites [generally less than 1 kilometer away]. This restriction is not designed to stop the "stockpiling" of a particular organism from the vicinity of the original collection in order to achieve a suitable weight; nor the collection of a similar species from a distant site where the reef environment is different. In fact, the latter may be encouraged in particular cases.

5. Prepare suitable voucher specimens and high-resolution in situ digitized photographs of each species collected. If color corrected 35 mm color slides are chosen instead, then high-resolution digitized images will be provided in addition to the slides. Vouchers shall be shipped to the Smithsonian Institution's Museum of Natural History, Washington, DC for verification of identity and storage and the photographs to the NCI Project Officer. Proper relaxation and preservation procedures shall be used. The number of voucher specimens collected shall be dependent on the organism, but should reflect the diversity of the sample collected. In general, three to five specimens should be sufficient, but in instances of diverse sample collections, as many as 10 specimens might be required for taxonomic purposes.

In addition, provisions shall be made for the donation of comparable voucher and slide sets of each species collected to the relevant authority in the "Source Country".

6. Document the collection of each sample by providing the details listed on the attached example [Exhibit A] at a minimum. Copies of the data in electronic format shall be submitted at suitable intervals to the NCI Project Officer [vide section 7 below].

The "Collector Number" shall be given as a composite alphanumeric code consisting of the Collector Code plus a four digit sequential number: This Collector Code/No shall be attached to each sample and corresponding voucher, photograph, report, etc.

Date[s] of Collection

Geographic Coordinates [GPS; with locations to 1/100 minute]

Habitat: Vegetation, rocks, reefs, etc.

Photographs: High quality underwater high resolution digitized photographs are required. In the event of 35 mm slides being offered, then these will be color-corrected [preferably Ektachrome or equivalent] and then digitized and submitted as the digitized image at the highest resolution possible. Surface photographs of either type will only be acceptable in unusual circumstances. These will be submitted at regular intervals to the NCI Project Officer.

Taxonomy: Performed as rapidly as possible to species level. Samples may be submitted to the Natural Products Repository before taxonomy is completed, but in all cases, at least the Phylum designation must accompany the samples.

Toxicity: All known and/or observed toxic effects.

Collection Conditions: Details such as weather conditions, water temperature, tide, currents, turbidity etc., are useful items of information and should be noted.

Relaxation Procedure/Preservative: Only necessary in the case of voucher specimens.

7. Provide the above collection data in computerized form (see below) to the Project Officer at intervals decided in conjunction with the

PO.

Data input shall be according to NCI specifications as a minimum

[see Exhibit A]. Other fields may be added as the Contractor desires. Any Windows/"Xbase" product that is compatible with the dBase "dbf" file format may be used with the permission of the Project Officer. Thus MS Access may be utilized but information is transferred as a “.dbf file” The use of a Macintosh will be considered if the program used is convertible by the Contractor to a Windows-based environment. Currently, the only known program that is totally "cross-platform compatible" is Claris Filemaker Pro.

An example of the data fields in the computerized database is shown in Exhibit B.

Data shall be transferred to the Project Officer [for inputting into the

NCI computer system] by the Contractor either electronically or on magnetic computer medium. The Contractor shall provide suitable micro-computers capable of running or converting to the "dbf" file format, and all submissions shall be in Windows XP SP2 or greater readable format. Alternatively, with the prior approval of the Project Officer, the Contractor may maintain the data in an ORACLE-based database and transfer it electronically; or may directly enter the data to a specific NCI computer via an appropriate tele-communications link at the Contractor's expense.

An internet-accessible entry system will be provided by NCI;

however, if due to geographic location of the contractor, such data submission would be overly expensive, then the contractor may submit data by mail on suitable media or as email attachments.

8. Label all samples and specimens clearly with the collector's sample number, taxonomic details [as detailed as possible], and note any known or observable toxicity. Waterproof labels and ink must be used. The label media used must also be capable of withstanding freezing to -76 oC as the samples will be shipped on solid CO2.

9. Obtain all necessary permits including visas, collection, shipping and export permits from the relevant foreign governments and agencies. Since NCI is part of a US Government Agency, permits must be obtained from the Central Government Agency[ies] or their designated permitting authority for collections. Simple permission from the authorities in the collection area will not suffice.

All collections will be undertaken under the conditions of the NCI's

"Letter of Collection" [LOC, a current copy of which is attached Exhibit B]. Conditions outlined in the LOC apply whether or not the Source Country has signed the LOC, is negotiating with NCI on the LOC or has not yet been approached with respect to the LOC. If requested, NCI is willing to enter into formal agreements based on the LOC with relevant source country organizations or government agencies.

10. Copies of a “Port Exception” import permit, issued by the Fish and

Wildlife Service [Department of the Interior] to the Natural Products Branch, NCI will be provided to the Contractor to expedite clearance by Customs and Fish and Wildlife Service Inspection officials at the U. S. Port of Entry (POE). Dulles International

Airport in Virginia is the nearest POE to Frederick.

11. Take all necessary precautions against health hazards and injuries.

The US Government bears no responsibility for any illness or injuries which might occur during the contract period.

12. Do not provide identical or taxonomically closely-related samples or sets of samples for anti-cancer screening, nor make these samples available to any other people or organizations for this purpose without the prior consent, in writing, from the Project Officer. This does not preclude the Contractor from using or testing similar samples for other biomedical, agricultural or chemical purposes provided that such collections are done at the Contractor's expense. Specific instructions governing collections for other entities are given below.

Collections For Entities Other Than NCI

The Contractor may remain in an area to collect for other entities after having completed the NCI collection, for an additional period not to exceed the time spent on the NCI collection. Approval, in writing, must be obtained from the Contracting Officer prior to undertaking such a collection.

The main purpose and focus of the collection trip should be to make collections for NCI. No trips should be planned strictly to accommodate collection opportunities for other entities.

The Contractor shall keep careful travel records which will indicate when the effort supporting NCI collections ceased. All labor, material and per diem costs and any additional travel expenses associated with collections for other entities shall be borne by said entities. In addition, the cost of return travel from the collection area to the Contractor's home facility shall be borne by said entities.

Separate permits must be obtained to collect for other entities.

Both Central Government and Local organizations collaborating with the Contractor in making the collections must be informed, and must fully comprehend that the collections are for the other entity, and are definitely not a continuation of the NCI collection. NCI is making special efforts to ensure that good relationships are formed [and continue] with authorities and scientists in the "Source Countries", and these efforts, together with the fact that NCI is an agency of the US Federal Government, facilitate the granting of collection and export permits in many countries. NCI will not jeopardize these relationships by being associated with collections by Contractors on behalf of pharmaceutical companies or any other entity.

The Contractor (and its subcontractors/consultants) are obligated to ensure that other entities for whom they collect abide by the same principles of collaboration and long term compensation as proposed by NCI. These principles are given in the attached Letter of Collection [following the Statement of Work].

Samples collected for NCI may not be duplicated for any other entity performing anti-cancer screening. NCI expects that the contractor will make the best collections possible for NCI, and will not allow these collections to be influenced by the dictates of other entities.

The results obtained in the screening of samples collected for NCI must be considered strictly confidential, and must not be used for guiding the nature of samples collected for other entities without the prior written approval of the Project Officer.

13. Recollect up to 20 marine samples per year, in quantities of 10-50

Kg, depending on the size and availability, as directed by the Project Officer. Exact equivalencies will be negotiated at the time of the Project Officer's request to allow for abundance of the organism, but a typical equivalency will be: a 10 Kg re-collection is equivalent to 5 samples and a 50 Kg re-collection is equivalent to 15 samples.

14. The Contractor shall undertake the complete identification to species level of every organism collected as soon as possible after collection. It is permissible to provide updated information at any time throughout the contract; thus sample identifications can be submitted with the best available information at a given time.

Updated records should be identified by a suitable electronic flag.

c. Specifically, the Contractor shall follow these collection instructions:

1. Collections shall include species from as wide a variety of phyla and classes as possible, and should not concentrate on too many species from one class to the exclusion of those from other classes.

Collections shall be predominately marine invertebrates with up to approximately 10% of the collection being marine plants.

Vertebrates are specifically excluded from the collection.

Where screening results indicate families or genera of high interest, priorities may change, and future efforts may be concentrated on the collection of such genera. Such priorities will be decided by the Project Officer.

2. Certain genera and classes shall be given low priority since prior screening has shown their extracts to be either totally inactive or highly toxic. These include:

Gonyaulax, Protogonyaulax [Dinopytha]

Gorgonians, soft corals [Octocorallia]

Laurencia [Rhodophyta]

Despite being assigned a low priority in the program, a limited number of examples [5-10 per family] shall be collected, since these will provide useful data for comparison with earlier test results.

3. Good in situ underwater high-resolution digitized photographs (or color-corrected 35 mm slides that are then digitized) are important for identification purposes. In the cases where surface photographs are necessary, suitable color wedges shall be used, together with an indication of scale. Photographs under the latter conditions should be taken as soon as possible after removal of the sample from its site.

4. Samples intended for extraction by the Government shall be stored and shipped in a continuously frozen condition. Strong, self-sealing or heat-sealed plastic bags, resistant to fracture at low temperatures [to -70 oC] shall be used for storage, and waterproof labeling media shall be enclosed with the sample. The Contractor shall be responsible for the delivery of the continuously frozen samples to the Natural Products Repository in Frederick, MD., in good condition. Because of the time involved, it is expected that air-freight will be the method of shipment to the USA, with Dulles Airport in Virginia being the closest international airport to the repository.

5. Voucher specimens shall be properly relaxed and stored in an appropriate preservation medium in a wide-necked inert good quality plastic container [Nalgene or equivalent]. These should be stored under suitable conditions (in solvent systems such as aqueous formalin or ethanol and in air-conditioned repositories) at the Contractor's base site and shipped to the designated repository at the Smithsonian Institution, currently in the Department of Invertebrate Zoology at the National History Museum, Washington, DC at suitable intervals (usually when shipments are of sufficient number to warrant shipping of vouchers. Once or twice a year is the norm.). Shipment of drained samples in self-sealing plastic bags has been found to be satisfactory in the past. In addition, suitable voucher samples shall be provided to the collaborating institution[s] in the "Source Country".

In cases where the facilities in the collection region are considered inadequate or "museum" staff insufficiently trained to house the NCI donated samples in a proper manner, small payments [not to exceed $5,000 per year in toto] may be made by the Contractor to improve facilities and/or provide training of local staff. Such payments will require prior Contracting Officer approval and appropriate justification.

6. When shipping samples and specimens in large containers, shipping lists giving details of the number of samples in the container, together with their collector numbers and identity, shall be included with each container. Copies of the air bill and of a shipping list containing at a minimum, the collector numbers and phylum designations, shall be faxed to the Project Officer at a number to be given, or sent as an attachment to an email in a format to be decided between the Project Officer and the Contractor, so that it will arrive at the Natural Products Branch at least three (3) working days prior to the arrival date in the US of the shipment.

The necessary completed FWS form 3-177 and a copy of the then current FWS import permit will accompany each shipment. It is strongly recommended that consideration be given to the use of an accompanying courier or provision for constant supervision of frozen shipments be made, as it is the sole responsibility of the contractor to deliver the materials in a still-frozen, never thawed condition to the NCI in Frederick, MD.

Exhibit A NCI Marine Collection Program Minimal Field Data Record

Collector Number Date Collected by Depth Latitude Longitude Type of Shore Distance to Shore Type of Bottom Photographs Taxonomy Relaxation Procedure/Preservative Toxicity Site Name/Identifier Contractor’s Record Number (if different)

Minimal Data Record Collector Number Site name Date Depth Wet Weight Habitat Substrate Hazard Code Abundance External Color Internal Color Mucus Odor Morphology Epibiont Cover Symbionts Cyanobacteria Zooanthellae Associations/Interactions Phylum, Class, Order, Family, Species Literature authority Taxonomist Local name Bioactivity Preservation Method General Notes Composite Sample of

Exhibit B LETTER OF COLLECTION

Agreement Between

[Source Country Organization, SCO] and the

Developmental Therapeutics Program Division of Cancer Treatment and Diagnosis National Cancer Institute

The Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis (“DCTD”), National Cancer Institute (NCI) is currently investigating plants, micro-organisms, and marine macro-organisms as potential sources of novel anticancer 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 (DHHS) of the United States Government. While investigating the potential of natural products in drug discovery and development, NCI wishes to promote the conservation and sustainable utility 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 country’s borders.

As part of the drug discovery program, DTP has contracts with various organizations for the collection of plants, micro-organisms and marine macro-organisms worldwide. DTP has an interest in investigating plants, micro-organisms and marine macro-organisms from [Source Country], and wishes to collaborate with the [Source Country Government (SCG) or Source Country Organization(s) (SCO)] as appropriate in this investigation. The collection of plants, micro-organisms 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 Organization (SCO] 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, micro-organisms 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, micro-organisms and marine macro-organisms provided from [Source Country] for anticancer activity, and will provide the test results to [SCO] on an annual basis. Such results will be channeled via Contractor.

2) The parties will keep the test results and subsequently-developed data confidential until approved for publication by the parties.

Before either party submits a paper or abstract containing test results for publication, the other party shall have 60 days to review and, as necessary file a sole or joint patent application in accordance with 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 [SCO] may participate in this process subject to the terms stated in Article 4. In addition, in the course of the contract period, DTP/NCI will assist the [SCO], thereby assisting the [Source Country], to develop the capacity to undertake drug discovery and development, including capabilities for the screening and isolation of active compounds from plants, micro-organisms 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 [SCO] 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 visits would not exceed one year except by prior agreement between [SCO] and DTP/NCI. The designated visiting scientist(s) will be subject to provisions usually governing Guest Researchers at NIH. Salary and other conditions of exchange will be negotiated in good faith. Costs and other conditions of visits will also be negotiated in good faith prior to the arrival of the visiting scientist(s).

5) In the event of the isolation of a promising agent from a plant, micro-organism or marine macro-organism collected in [Source Country], further development of the agent will be undertaken by DTP/NCI in collaboration with [SCO]. Once an active agent is approved by the DTP/NCI for preclinical development, [SCO] and the DTP/NCI will discuss participation by SCO 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 [SCO], subject to the provision of mutually acceptable guarantees for the protection of intellectual property associated with any patented technology.

6) DTP/NCI/NIH 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] employees jointly, and will seek appropriate protection abroad, including in [Source Country], if appropriate. All resulting patent applications and patents shall be assigned to the U.S. Department of Health and Human Services and managed by NIH. Under current NIH policy, all inventors of such assigned patents may receive royalties in accordance with said NIH policy for any royalty-bearing license(s) for these patent(s).

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

8) Should an agent derived from an organism collected under the terms of this agreement eventually be licensed to a pharmaceutical company for production and marketing, DTP/NCI will request that NIH/OTT require the successful licensee to negotiate and enter into agreement(s) with the appropriate [SCG] agency(ies) or [SCO] within twelve (12) months from the execution of said license. 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) The terms of Article 8 shall apply equally to inventions 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/NIH 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 to the [SCG] or [SCO] as appropriate, compensation (to be negotiated) to be used for expenses associated with cultivation of medicinal organisms that are endangered 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) Article 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 independently submitted by the [SCG or SCO] scientists for antitumor activity, provided such compounds have not been tested previously in the DTP/NCI screens. If significant antitumor activity is detected, further development of the compound may, as appropriate, be undertaken by DTP/NCI in consultation with the [SCG or SCO].

Should an NCI/NIH patent on an agent derived from the submitted compound(s) eventually be licensed to a pharmaceutical company for production and marketing, DTP/NCI will request that NIH/OTT require the successful licensee to negotiate and enter into agreement(s) with the appropriate [SCG agency(ies) or SCO] within twelve (12) months from the execution of said license. 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 Article 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, micro-organisms 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, micro-organisms and marine macro-organisms by the local population or traditional healers, this information will be used to guide the collection of plants, micro-organisms 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 SCO 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.

For the National Cancer Institute: For [SCI] or [SCO]:

John E. Niederhuber, M.D. Name (typed):

Director, National Cancer Institute Title:

Date Date mailing and contact address: mailing and contact address:

National Cancer Institute at Frederick Frederick, Maryland 21701-8512 U.S.A.