NINDS High Throughput Drug Screening Service Facility for Neurodegeneration at Southern Research Institute

New NINDS HTS Service Facility

Recent advances in the study of neurodegenerative disease have provided molecular and cellular models for studying the underlying disease mechanisms. These models may also serve as targets for drug discovery. One effective strategy used in the pharmaceutical industry to identify new drugs is high throughput drug screening (HTS), the robotic application of thousands of different small molecules to miniaturized versions of disease models. Used in academic research, HTS has the potential to yield both mechanistic insights and new drug leads with unparalleled efficiency.

To encourage the use of HTS for neurodegeneration research and drug discovery, NINDS awarded a contract to Southern Research Institute in Birmingham, Alabama in September 2002. Southern Research will provide two kinds of expertise to the research community: first, adapting assays for high throughput applications and second, testing assays against a large, diverse collection of compounds.

Researchers participating in the program will be provided with the complete results of the screening including the identity of compounds active in their neurodegeneration assays. These compounds will be useful as research tools and drug leads. In the process, assay automation and screening at Southern Research will evaluate assays as possible HTS targets to encourage their use in further drug development outside the contract.

Services Provided

1. Assay development: Assays for testing at the facility will be selected by NINDS and may be cell-or protein-based models of neurodegenerative disease. Southern Research will modify assays for automated screening. The goal of this contract is to develop and screen assays at the rate of approximately three per year. To efficiently transfer the assays to Southern Research for development, collaborating investigators will be accommodated at Southern Research for the period required to train staff in successful and reproducible use and interpretation of the assay.

2. Compound Library: Southern Research will assemble a large, diverse collection of approximately 100,000 compounds suitable for HTS. All of these compounds will be in the public domain.

3. Screening: Southern Research will subject the assays to HTS and analyze the results to identify individual compounds that are active in each assay. Active compounds will be tested over a limited concentration range.

4. Data Analysis: Southern Research will perform structure-function analysis of compounds active in individual assays. This will identify common chemical moieties that have activity within a given assay. In addition, NINDS intends to analyze the assembled data from all assays to identify commonalities. Any data relevant to a specific assay will be shared with the collaborating investigator.

Reports Provided to Investigators

Southern Research will produce HTS reports that include the following information: 1) the nature of the modifications and tests performed on the assay, 2) the compounds screened with the assay, 3) the identities of active compounds and their effective concentrations, and 4) SAR analysis of active compounds. NINDS will provide these reports to the investigator who submitted the assay for screening.

In addition, Southern Research will assist investigators in obtaining active compounds for their use in research. For example, they may identify a source for purchase or synthesis of particular compounds.

Assay Selection

Assay proposals will be solicited by NINDS through notices published in the NIH Guide for Grants and Contracts. NINDS will convene a steering committee to consider applications for assays to be screened under the contract. NINDS will make the final decision as to which assays will be screened. Although the goal of this contract is to encourage the use of high throughput drug screening in the academic research community, applications from non-profit institutions and small businesses will also be considered.

Materials Transfer Agreements

Assays will be transferred to Southern Research under a Materials Transfer Agreement (MTA - see sample MTA below). In general, Southern Research will have no intellectual property position in assays that require only routine or minor modification for HTS. In some cases, however, extensive modification of an assay requiring significant intellectual input from Southern Research might be necessary for HTS implementation of the assay. In cases where such an assay is selected for screening under the contract, a MTA will be negotiated directly between the contractor and the collaborating investigator before work is begun on the assay. This agreement may allow for joint ownership of any intellectual property that results from the modification of the assay for use in HTS. The use of the joint intellectual property and/or the sharing of any income derived from such jointly owned intellectual property would be negotiated in good faith by the parties depending upon their relative contribution. As appropriate, Southern Research and the collaborating investigator will mutually agree on further development, patenting, and commercialization activities for any jointly owned intellectual property of interest. Such agreements are outside the contract under which the initial HTS work is being done.

SAMPLE TECHNOLOGY/MATERIALS TRANSFER AGREEMENT

THIS TECHNOLOGY/MATERIALS TRANSFER AGREEMENT ("AGREEMENT") is made and entered into on - date --, by and between PROVIDER'S NAME AND ADDRESS HERE (hereinafter referred to as "PROVIDER") and Southern Research, 2000 Ninth Avenue South, Birmingham, Alabama, 35205, a not-for-profit corporation organized under the laws of the State of Alabama (hereinafter referred to as "RECIPIENT").

In consideration of the premises and in consideration of the mutual promises and covenants herein contained, both PROVIDER and RECIPIENT agree as follows:

"PROVIDER TECHNOLOGY/MATERIAL" shall mean _________________.

PROVIDER TECHNOLOGY/MATERIAL is the proprietary property of PROVIDER.

Using PROVIDER TECHNOLOGY/MATERIAL, RECIPIENT desires to conduct research under NIH Contract No. ________ (the "Contract").

In consideration for access to said PROVIDER TECHNOLOGY/MATERIAL, the parties agree to the following terms and conditions until said PROVIDER TECHNOLOGY/MATERIAL is made available to the public by PROVIDER or an authorized third party:

1. PROVIDER will make available PROVIDER TECHNOLOGY/MATERIAL to RECIPIENT with sufficient information to use the PROVIDER TECHNOLOGY/MATERIAL as allowed herein.

2. PROVIDER TECHNOLOGY/MATERIAL will be used for research purposes only unless for commercialization as described in Paragraph 8 below. IT IS UNDERSTOOD AND AGREED THAT ANY PROVIDER MATERIAL WILL NOT BE FOR USE IN HUMANS.

3. PROVIDER TECHNOLOGY/MATERIAL will not be distributed to others by RECIPIENT without the written permission of PROVIDER.

4. All information generated by RECIPIENT from the use of PROVIDER TECHNOLOGY/MATERIAL shall be owned jointly by PROVIDER and RECIPIENT. RECIPIENT and PROVIDER may utilize this information for any purposes they deem necessary, however, the parties agree to provide a copy of any manuscript to be presented at symposia, international, national, or regional professional meetings or to be published in journals, theses, or dissertations, or otherwise published through any means that incorporates information relating to PROVIDER TECHNOLOGY/MATERIAL or improvements made by RECIPIENT to the other party at least 60 days prior to submitting it for publication. The reviewing party shall have 60 days from date of receipt of the manuscript to review and comment on such a manuscript. RECIPIENT agrees that any proprietary information supplied to it during the course of research performed by RECIPIENT under the Contract will not be included in any published material without prior written approval from PROVIDER. Further, the publication or disclosure shall be modified or delayed upon reasonable request by a party as necessary to preserve U.S. or foreign patent or other intellectual property rights. RECIPIENT will acknowledge PROVIDER as the source of the PROVIDER TECHNOLOGY/MATERIAL in any publication of results relating to the PROVIDER TECHNOLOGY/MATERIAL.

5. No advertising or publicity matter having any reference to either RECIPIENT or PROVIDER, expressed or implied, shall be made use of by either party or anyone on behalf of either party, unless and until such matter shall have first been mutually agreed upon in writing.

6. PROVIDER shall retain its rights to all pre-existing PROVIDER TECHNOLOGY/MATERIAL inventions and shall obtain patent coverage as appropriate.

7. Recipient shall promptly notify Provider of any inventions made under the Contract using PROVIDER TECHNOLOGY/MATERIAL.

8. 1. Inventorship for patentable inventions shall be determined in accordance with U.S. patent laws. PROVIDER and RECIPIENT represent that each of its employees has entered into an employment agreement that provides for assignment to PROVIDER or RECIPIENT, respectively, of all inventions made by such employee during the course of his employment with PROVIDER or RECIPIENT.

   2. PROVIDER and RECIPIENT agree that:

      1. if only routine high throughput screening (HTS) assay implementation of an already working assay is required, RECIPIENT would have no intellectual property position; and

      2. if only minor modifications are required to move an assay to the HTS platform, it would be viewed as work required under the Contract and RECIPIENT would have no intellectual property position; and

      3. if extensive assay modifications require significant new intellectual input on RECIPIENT's part, it might result in some shared (joint) intellectual property of some sort, but such would occur only with the prior approval of the Project Officer. The use of the joint intellectual property and/or the sharing of any income derived from such jointly owned intellectual property will be negotiated in good faith by the parties hereto depending upon their relative contribution to the creation of the jointly owned intellectual property covered. As appropriate, PROVIDER and RECIPIENT will mutually agree on further development, patenting, and commercialization activities for any jointly owned intellectual property of interest. SUCH AGREEMENTS ARE OUTSIDE THE CONTRACT WITH NIH/NINDS UNDER WHICH THE INITIAL HTS WORK IS BEING DONE

9. It is understood that no right to a license is given or implied by this AGREEMENT.

10. PROVIDER shall not be responsible or liable in contract or in tort for special, indirect, incidental or consequential damages arising from any aspect of its performance of this AGREEMENT such as, but not limited to, damage to or loss of property or equipment, loss of product, profits or revenues, damage or loss from operation or nonoperation of plant, or claims of customers of RECIPIENT.

11. PROVIDER DOES NOT REPRESENT, WARRANT OR GUARANTEE THAT PROVIDER TECHNOLOGY/MATERIAL OR PRODUCT(S) PRODUCED THEREFROM ARE MERCHANTABLE OR SATISFACTORY FOR ANY PARTICULAR PURPOSE, AND THERE ARE NO WARRANTIES, EXPRESS OR IMPLIED, TO SUCH EFFECT. Acceptance, reliance on, or use of PROVIDER TECHNOLOGY/MATERIAL shall be at the sole risk of RECIPIENT. RECIPIENT hereby agrees to release, waive and forever discharge any demands, claims, suits or actions against PROVIDER arising out of or in connection with RECIPIENT 's acceptance, reliance on, or use of such results or product(s).

--PROVIDER'S NAME-- By: Name: Title:

Southern Research Institute By: Name: Title: