[Federal Register Volume 67, Number 102 (Tuesday, May 28, 2002)]
[Notices]
[Pages 36902-36904]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-13196]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Opportunity for Cooperative Research and Development Agreement(s) 
(CRADAs) and/or License(s) for the Development and Commercialization of 
Nitric Oxide-Releasing Drugs and Biomaterials

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The National Cancer Institute (NCI) seeks Licensee(s) and/or 
Cooperative Research and Development Agreement (CRADA) Collaborator(s) 
for the development and commercialization of Nitric Oxide (NO)-
Releasing Drugs and Biomaterials as embodied in a variety of recent NCI 
publications, as well as, in the patents and patent applications listed 
below.

DATES: Confidential CRADA proposal summaries, preferably one page or 
less, and a signed Confidential Disclosure Agreement (CDA) (http://ttb.nci.nih.gov/forms.html) must be submitted to the NCI Technology 
Transfer Branch (TTB) on or before June 24, 2002, to take full 
advantage of this opportunity. CRADA proposal summaries submitted 
thereafter may be considered if a suitable CRADA Collaborator is not 
selected from among the timely responses. Guidelines for preparing a 
full CRADA proposal will be communicated shortly thereafter to all 
respondents with whom initial confidential discussions will have 
established sufficient mutual interest.
    Respondees interested in licensing the invention(s) should submit 
an
    ``Application for License to Public Health Service Inventions''. 
The licensing application, model licenses and other information on 
licensing NIH technologies can be found at http://ott.od.nih.gov under 
Intramural Licensing Program.

ADDRESSES: CRADA information may be obtained by contacting Dr. 
Charmaine Richman, Technology Transfer Specialist, Technology Transfer 
Branch, National Cancer Institute, 1003 West Seventh Street, Suite 500, 
Frederick, Maryland 21701; telephone: 301-846-5465; fax 301-846-6820; 
e-mail: [email protected].
    Licensing information and copies of the issued U.S. patents 
referenced below may be obtained by contacting Dr. Norbert Pontzer, 
Technology Licensing Specialist, Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; telephone: 301-496-7057 ext. 284; fax 
301-402-0220; e-mail: [email protected]. A signed Confidential 
Disclosure Agreement will be required to receive copies of patent 
applications that have not yet issued.
    Scientific inquiries may be directed to Dr. Larry Keefer, National 
Cancer Institute/Center for Cancer Research (CCR) at Frederick, 
Building 538, Room 205F, Frederick, MD 21702-1201; telephone : 301-846-
1467; e-mail: [email protected].

SUPPLEMENTARY INFORMATION: NIH scientists are developing a variety of 
novel techniques for delivering nitric oxide (NO) to specific organs 
and cell types for therapeutic benefit. Methods for targeting lung, 
liver, and other tissues have been introduced to the literature, as 
have NO-releasing proteins and insoluble polymers. The compounds and 
drug delivery strategies developed thus far have shown promising 
activities that have been demonstrated in relevant experimental animal 
models. These include inhibition of thrombosis, treatment of vasospasm, 
relief of respiratory distress, protection against toxic liver injury, 
radiosensitization of hypoxic tumors, correction of genitourinary tract 
dysfunction, antimicrobial effects, protection against ischemia-
reperfusion injury and whole-body radiation, and preservation of organ 
transplants. Inventions described in the patents are available for 
either exclusive or non-exclusive licensing in accordance with 35 
U.S.C. 207 and 37 CFR 404.
    A Cooperative Research and Development Agreement (CRADA) is the 
anticipated joint agreement to be entered into with NCI pursuant to the 
Federal Technology Transfer Act of 1986 and Executive Order 12591 of 
April 10, 1987, as amended. A CRADA is an agreement designed to enable 
certain collaborations between Government laboratories and non-
Government laboratories. It is not a grant, and it is not a contract 
for procurement of goods/services. The NCI is prohibited from 
transferring funds to a CRADA collaborator. Under a CRADA, NCI can 
contribute facilities, staff, materials, and expertise. The CRADA 
Collaborator will have an option to negotiate the terms of an exclusive 
or nonexclusive commercialization license to subject inventions arising 
under the CRADA. CRADA applicants should be aware that a license to the 
above-mentioned patent rights may be necessary in order to 
commercialize products arising from a CRADA. The expected duration of 
the CRADA(s) would be for up to five (5) years. The goals of CRADAs 
include rapid publication of research results and timely 
commercialization of products, diagnostics, and treatments that result 
from the research.

Nitric Oxide Patents

    Patent Status: Compositions and uses covered in:
    1. Keefer, L.K., Wink, D.A., Dunams, T.M., and Hrabie, J.A.: 
Stabilized nitric oxide-primary amine complexes useful as 
cardiovascular agents. U.S. Patent 4,954,526, September 4, 1990.
    2. Keefer, L.K., Wink, D.A., Dunams, T.M., and Hrabie, J.A.: Anti-
hypertensive compositions of secondary amine-nitric oxide adducts and 
use thereof. U.S. Patent 5,039,705, August 13, 1991.
    3. Keefer, L.K., and Hrabie, J.A.: Complexes of nitric oxides with 
polyamines. U.S. Patent 5,155,137, October 13, 1992.
    4. Diodati, J.G., and Keefer, L.K.: Therapeutic inhibition of 
platelet aggregation by nucleophile-nitric oxide complexes and 
derivatives thereof. U.S. Patent 5,185,376, February 9, 1993.
    5. Keefer, L.K., Wink, D.A., Dunams, T.M., and Hrabie, J.A.: Anti-
hypertensive compositions of secondary amine-nitric oxide adducts and 
use thereof. U.S. Patent 5,208,233, May 4, 1993 (continuation in part 
of U.S. Patent 5,039,705).
    6. Keefer, L.K., Wink, D.A., Dunams, T.M., and Hrabie, J.A.: Anti-
hypertensive compositions and use thereof. U.S. Patent 5,212,204, May 
18, 1993.
    7. Keefer, L.K., and Hrabie, J.A.: Complexes of nitric oxide with 
polyamines. U.S. Patent 5,250,550, October 5, 1993 (continuation in 
part of U.S. Patent 5,155,137).
    8. Keefer, L. K., Dunams, T.M., and Saavedra, J.E.: Oxygen-
substituted

[[Page 36903]]

derivatives of nucleophile-nitric oxide adducts as nitric oxide donor 
prodrugs. U.S. Patent 5,366,997, November 22, 1994.
    9. Christodoulou, D.D., Wink, D.A., and Keefer, L.K.: Mixed ligand 
metal complexes of nitric oxide nucleophile adducts useful as 
cardiovascular agents. U.S. Patent 5,389,675, February 14, 1995.
    10. Keefer, L.K., and Hrabie, J.A.: Polymer-bound nitric oxide/
nucleophile adduct compositions, pharmaceutical compositions 
incorporating same and methods of treating biological disorders using 
same. U.S. Patent 5,405,919, April 11, 1995.
    11. Keefer, L.K., Hrabie, J.A., and Saavedra, J.E.: Polymer-bound 
nitric oxide/nucleophile adduct compositions, pharmaceutical 
compositions incorporating same and methods of treating biological 
disorders using same. U.S. Patent 5,525,357, June 11, 1996 
(continuation in part of U.S. Patent 5,405,919).
    12. Malinski, T., Wink, D.A., Younathan, J., Murray, R.W., 
Sullivan, M., Meyer, T.J., and Christodoulou, D.D. Nitric oxide sensor. 
U.S. Patent 5,603,820, February 18, 1997.
    13. Saavedra, J.E., Keefer, L.K., Roller, P. P., and Akamatsu, M.: 
Bipolymer-bound nitric oxide-releasing compositions, pharmaceutical 
compositions incorporating same and methods of treating biological 
disorders using same. U.S. Patent 5,632,981, May 27, 1997 (continuation 
in part of U.S. Patent 5,525,357).
    14. Mitchell, J.B., Russo, A., Krishna, M.C., Wink, D.A., and 
Liebmann, J.E. Use of nitric oxide releasing compounds as hypoxic cell 
radiation sensitizers. U.S. Patent 5,650,442, July 22, 1997.
    15. Keefer, L.K., and Hrabie, J.A.: Implants, prostheses, and 
stents comprising polymer-bound nitric oxide-nucleophile adducts 
capable of releasing nitric oxide. U.S. Patent 5,676,963, October 14, 
1997.
    16. Hrabie, J.A., and Keefer, L.K.: Method of generating nitric 
oxide gas using nitric oxide complexes. U.S. Patent 5,683,668, November 
4, 1997.
    17. Smith, D.J., Chakravarthy, D., and Keefer, L.K.: 
Polysaccharide-bound nitric oxide-nucleophile adducts. U.S. Patent 
5,691,423, November 25, 1997 (continuation in part of U.S. Patent 
5,405,919).
    18. Korthuis, R.J., Kong, L., and Keefer, L.K.: Use of nitric 
oxide-releasing agents for reducing metastasis risk. U.S. Patent 
5,700,830, December 23, 1997.
    19. Saavedra, J.E., Keefer, L.K., and Billiar, T.R.: Selective 
prevention of organ injury in sepsis and shock using selective release 
of nitric oxide in vulnerable organs. U.S. Patent 5,714,511, February 
3, 1998.
    20. Keefer, L.K., and Hrabie, J.A.: Polymer-bound nitric oxide/
nucleophile adduct compositions, pharmaceutical compositions 
incorporating same and methods of treating biological disorders using 
same. U.S. Patent 5,718,892, February 17, 1998 (divisional application 
of U.S. Patent 5,405,919).
    21. Keefer, L.K., Saavedra, J.E., and Hrabie, J.A.: N-Substituted 
piperazine NONOates. U.S. Patent 5,721,365, February 24, 1998.
    22. Keefer, L.K., Wink, D.A., Dunams, T.M., and Hrabie, J.A.: Anti-
hypertensive compositions of secondary amine-nitric oxide adducts and 
use thereof. U.S. Patent 5,731,305, March 24, 1998.
    23. Wink, D.A., Mitchell, J.B., Russo, A., Krishna, M.C., Hanbauer, 
I., Grisham, M.B., and Granger, D.N. Nitric oxide releasing compounds 
as protective agents in ischemia reperfusion injury. U.S. Patent 
5,789,447, August 4, 1998.
    24. Mitchell, J.B., Russo, A., Krishna, M.C., Wink, D.A., and 
Liebmann, J.E. Use of nitric oxide-releasing compounds as hypoxic cell 
radiation sensitizers. U.S. Patent 5,814,667, September 19, 1998 
(divisional application of U.S. Patent 5,650,442).
    25. Green, S.J., and Keefer, L.K.: Encapsulated and non-
encapsulated nitric oxide generators used as antimicrobial agents. U.S. 
Patent 5,814,666, September 29, 1998.
    26. Saavedra, J.E., and Keefer, L.K.: Selective prevention of organ 
injury in sepsis and shock using selective release of nitric oxide in 
vulnerable organs. U.S. Patent 5,814,656, September 29, 1998 
(divisional application of U.S. Patent 5,714,511).
    27. Keefer, L.K., Saavedra, J.E., Doherty, P.C., Hanamoto, M.S., 
and Place, V.A.: Use of nitric oxide-releasing agents to treat 
impotency. U.S. Patent 5,910,316, June 8, 1999 (continuation in part of 
U.S. Patent 5,525,357).
    28. Keefer, L.K., and Hrabie, J.A.: Polymer-bound nitric oxide/
nucleophile adduct compositions, pharmaceutical compositions 
incorporating same and methods of treating biological disorders using 
same. U.S. Patent 6,110,453, August 29, 2000 (divisional application of 
U.S. Patent 5,718,892).
    29. Saavedra, J.E., Keefer, L.K., Roller, P.P., and Akamatsu, M.: 
Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical 
compositions incorporating same and methods of treating biological 
disorders using same. U.S. Patent 6,200,558, March 13, 2001 
(continuation in part of U.S. Patent 5,525,357).
    30. Hrabie, J.A., and Keefer, L K.: Nitric oxide-releasing amidine- 
and enamine-derived diazeniumdiolates, compositions and uses thereof 
and methods of making same. U.S. Patent 6,232,336, May 15, 2001.
    31. Keefer, L.K., Saavedra, J.E., Doherty, P.C., Hanamoto, M.S., 
Place, V. A.: Use of nitric oxide-releasing agents to treat impotency. 
U.S. Patent 6,290,981, September 18, 2001.
    32. Saavedra, J.E., Srinivasan, A., and Keefer, L.K.: O2-Aryl 
substituted diazeniumdiolates. U.S. Patent Application 60/026,816, 
filed September 27, 1996.
    33. Saavedra, J.E., Keefer, L.K., and Bogdan, C.: O2-Glycosylated 
1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-[(2-
carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolates. U.S. Patent 
Application 60/051,696, filed July 3, 1997.
    34. Saavedra, J.E., et al.: Nitric oxide-releasing 1-[(2 
carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2,-diolates and composition 
comprising same. U.S. Patent Application 09/666,668, filed September 
20, 2000.

Party Contributions to CRADAs

    The role of the National Cancer Institute in this CRADA will 
include, but not be limited to:

    1. Providing intellectual, scientific, and technical expertise and 
experience to the research project.
    2. Providing the Collaborator with samples of the subject compounds 
for pharmacological evaluation.
    3. Planning research studies and interpreting research results.
    4. Providing support services at NCI/CCR.
    5. Publishing research results.

    The role of the CRADA Collaborator may include, but not be limited 
to:

    1. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project.
    2. Planning research studies and interpreting research results.
    3. Providing support for ongoing CRADA-related research in the 
development of the particular application of nitric oxide-releasing 
drugs/biomaterials outlined in the Agreement:
    a.Financial support to facilitate scientific goals;
    b.Technical or financial support for further design of 
applications.
    4. Publishing research results.

    Selection criteria for choosing the CRADA Collaborator may include, 
but are not limited to:


[[Page 36904]]


    1. The ability to collaborate with NCI on further research and 
development of this technology. This ability can be demonstrated 
through experience and expertise in this or related areas of technology 
indicating the ability to contribute intellectually to ongoing research 
and development.
    2. The demonstration of adequate resources to perform the research, 
development and commercialization of this technology (e.g., facilities, 
personnel and expertise) and accomplish objectives according to an 
appropriate timetable to be outlined in the CRADA Collaborator's 
proposal.
    3. The willingness to commit best effort and demonstrated resources 
to the research, development and commercialization of this technology.
    4. The demonstration of expertise in the commercial development, 
production, marketing and sales of products related to this area of 
technology.
    5. The level of financial support the CRADA Collaborator will 
provide for CRADA-related Government activities.
    6. The willingness to cooperate with the NCI in the timely 
publication of research results.
    7. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.
    8. The willingness to accept the legal provisions and language of 
the CRADA with only minor modifications, if any. These provisions 
govern the equitable distribution of patent rights to CRADA inventions. 
Generally, the rights of ownership are retained by the organization 
that is the employer of the inventor, with (1) the grant of license for 
research and other Government purposes to the Government when the CRADA 
Collaborator's employee is the sole inventor, or (2) the grant of an 
option to elect an exclusive or nonexclusive license to the CRADA 
Collaborator when the Government employee is the sole inventor.

    Dated: May 17, 2002.
Kathleen Sybert,
Chief, Technology Transfer Branch, National Cancer Institute, National 
Institutes of Health.
    Dated: May 13, 2002.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 02-13196 Filed 5-24-02; 8:45 am]
BILLING CODE 4140-01-P