30914 Federal Register / Vol. 61, No. 118 / Tuesday, June 18, 1996 / Notices

both regular and overnight mail

deliveries. Contacting PGO employees

during this time frame may also be

hindered due to the possible telephone

disruptions.

To the extent authorized, please

consider the use of voice mail, e-mail,

and facsimile transmissions to the

maximum extent practicable. Please do

not fax lengthy documents, or grant

applications.

This announcement will be available

on one of two Internet sites on the

publication date: CDC’s home page at

http://www.cdc.gov, or at the

Government Printing Office home page

(including free access to the Federal

Register) at http://www.access.gpo.gov.

Dated: June 11, 1996.

Joseph R. Carter,

Acting Associate Director for Management

and Operations, Centers for Disease Control

and Prevention (CDC).

[FR Doc. 96–15375 Filed 6–17–96; 8:45 am]

BILLING CODE 4163–18–P

National Institutes of Health

Licensing Opportunity and/or

Opportunity for a Cooperative

Research and Development Agreement

(CRADA) for the Scientific and

Commercial Development of Novel

Heparin-Binding Peptides

AGENCY: National Institutes of Health,

Public Health Services, DHHS.

ACTION: Notice.

SUMMARY: The National Institutes of

Health is seeking licensees and/or

CRADA partners for the further

development, evaluation, and

commercialization of novel heparinbinding peptides. The inventions

claimed in the patent applications

referenced below are available for either

exclusive or non-exclusive licensing (in

accordance with 35 U.S.C. 207 and 37

CFR Part 404) and/or further

development under a CRADA for

clinical and research applications

described below in Supplementary

Information.

Heparin- and Sulfatide-Binding

Peptides From the Type I Repeats of

Human Thrombospondin and

Conjugates Thereof

DD Roberts, PJ Browning, J Bryant, JK

Inman, HC Krutzsch, N Guo (NCI)

Serial No. 08/487,568, filed 07 Jun 95,

which is a CIP of

Serial No. 08/215,085, filed 21 Mar 94,

which is a CIP of

Serial No. 07/801,812, which issued as

U.S. Patent No. 5,357,041 on 18 Oct 94.

To expedite the research,

development, and commercialization of

these compounds, the National

Institutes of Health is seeking a CRADA

with a pharmaceutical or biotechnology

company in accordance with the

regulations governing the transfer of

Government-developed agents. Any

proposal to use or develop these

compounds will be considered.

ADDRESSES: CRADA proposals and

questions about this opportunity should

be addressed to: Dr. Gary D. Colby,

Office of Technology Development,

National Cancer Institute, Executive

Plaza South, Suite 450, 6120 Executive

Boulevard MSC 7182, Bethesda, MD

20892–7182; telephone: 301/496–0477;

fax: 301/402–2117.

Licensing proposals and questions

about this opportunity should be

addressed to: Ms. Carol Lavrich,

Technology Licensing Specialist, Office

of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; telephone: 301/

496–7735, ext. 287; fax: 301/402–0220.

Information about the patent

applications and pertinent information

not yet publicly described can be

obtained under a Confidential

Disclosure Agreement. Respondees

interested in licensing the invention(s)

will be required to submit an

Application for License to Public Health

Service Inventions. Respondees

interested in submitting a CRADA

proposal should be aware that it may be

necessary to secure a license to the

above patent rights in order to

commercialize products arising from a

CRADA.

DATES: There is no deadline by which

license applications must be received.

CRADA proposals must be received on

or before September 16, 1996.

SUPPLEMENTARY INFORMATION: These

inventions identify a family of related

peptides, peptide analogs, and

peptidomimetics useful for blocking or

modifying the biological activities of

heparin, sulfatides, fibronectin,

fibroblast growth factor and

transforming growth factor-β (TGFβ)

Among the activities exhibited by

compounds within this family of agents

are:

• Inhibition of tumor cell growth,

including inhibition of breast tumor

growth in a mouse xenograft model;

• Inhibition of Kaposi’s Sarcoma (SK)

cell proliferation and migration in

vitro and KS-like lesion formation in

vivo;

• Inhibition of endothelial and breast

carcinoma cell proliferation,

adhesion, and motility in vitro;

• Inhibition of angiogenesis in vivo;

• Specific, high affinity binding to

heparin and related sulfated

glycoconjugates, including preventing

interaction with adhesion molecules,

growth factors, cells, and heparindependent enzymes; and

• Activation of latent TGFβ.

The compounds within this family of

agents are based upon functional

sequences from the three type I repeats

of human endothelial cell

thrombospondin. The inventions

identify particular peptides, analogs,

and peptidomimetics that have

particularly advantageous properties

such as increased physiological

stability, enhanced activity, lack of

electrostatic charge, and increased

solubility. The inventions also describe

unique approaches to constructing

water-soluble conjugates which exhibit

a number of interesting and useful

biological activities.

It is expected that the high potency of

these agents will lower the effective

dose needed, and, subsequently, will

reduce the immunological response

against the peptides and the risks of

toxicity. Among the diseases for which

these agents may prove to be

particularly useful therapeutic agents

are:

• Kaposi’s sarcoma

• Breast carcinoma

• Melanoma

• Other epithelial cancers

• Other diseases involving abnormal

vascular proliferation

The inventors of these agents seek

collaborators for their ongoing research

and development efforts. Two research

projects for which collaborators are

particularly sought involve investigation

of means of controlling angiogenesis

and investigation of means for

modulating the activity of TGFβ,

particularly to control fibrosis, using the

agents described above.

Thrombospondin has been identified

as an anti-angiogenic factor in human

epithelial tissue. Certain agents

described above have shown particular

utility for inhibition of pathological

angiogenesis in vivo. These agents have

been engineered to decrease both

proteolytic degradation and the rapidity

of their clearance from the bloodstream

and to increase their biological activity.

These agents have been shown to

influence tumor cell adhesion and

growth in vitro and in vivo. Other

peptides have been shown to inhibit

tumorigenesis and metastasis in vivo.

Further development of agents, and

their application in therapeutic

capacities, is planned.

The antiproliferative activities of

certain agents upon epithelial and breast
Federal Register / Vol. 61, No. 118 / Tuesday, June 18, 1996 / Notices 30915

carcinoma cells has demonstrated to be

independent of latent TGFβ activation.

Other agents, however, have been

shown to activate latent TGFβ. TGFβactivating agents also exhibit anti-tumor

activity in vivo. Further development of

TGFβ-modulating agents, particularly

those useful for control of fibrosis, is

planned.

Particularly sought are companies

dedicated to the development of small

therapeutic molecules, such as peptides

and their analogs. Collaborators should

have particular in-house expertise

relating to peptide research and

development. It is anticipated that

fruitful collaboration will result from

sustained and meaningful contribution

on the part of the collaborator.

The CRADA aims will include

optimizing peptide and

peptridomimetic activity in vitro and in

vivo, preclinical development of the

synthetic peptides and mimetics, and

clinical studies as warranted. The

CRADA partner will enjoy the benefit of

a right of first refusal for a license (on

a reasonable commercial terms) to

government-owned rights in any

invention arising within the scope of the

CRADA. Furthermore, the CRADA

partner will be responsible for

reimbursement of government expenses

for patenting any resulting inventions

during the term of the CRADA.

The role of the National Cancer

Institute will include the following:

1. The government will continue in

vitro and in vivo preclinical

development of the peptides and

mimetics as inhibitors of tumor growth

and metastasis and as modulators of

TGF-β activity.

2. The government will provide

available data and expertise in

structure-function relationships and

conformational analysis of the active

peptides and peptidomimetics. These

data will be evaluated jointly in order to

assess an efficient research path.

3. As appropriate, the government

will initiate collaborative clinical trials

under its extramural clinical trials

network, thus ensuring the clinical

evaluation of the compounds.

The role of the collaborator will

include the following:

1. Prepare and characterize GMP

quality nonmetabolizable analogs (as

determined by both parties) of the active

peptides and provide these to the NCI

for characterization as angiogenesis and

metastasis inhibitors or as modulators of

TGF-β activity.

2. Provide funds for preclinical

development of the peptides in vitro

and for screening activities in

appropriate animal models.

3. Collaborate in the planning and

support for clinical development

leading to FDA approval and marketing.

Selection criteria for choosing the

CRADA partner will include, but are not

limited to, the following:

1. Experience in preclinical and

clinical drug development.

2. Experience and ability to produce,

package, market, and distribute

pharmaceutical products, particularly

peptides and peptide analogs, in the

United States.

3. A willingness to cooperate with the

Public Health Service in the collection,

evaluation, publication, and

maintenance of data from clinical trials

of investigational agents.

4. Willingness to share the costs

associated with the development of the

peptides and mimetics. These costs

include acquisition of synthesis or both

of the peptides and mimetics in

amounts adequate for clinical trials and

marketing.

5. Agreement to be bound by DHHS

rules and regulations regarding the use

of human subjects in clinical

investigations, intellectual property

rights, ethical treatment of animals, and

randomized clinical trials.

6. The aggressiveness of the

development plan, including the

appropriateness of milestone and

deadlines for preclinical and clinical

development.

7. Agreement with provisions for

equitable distribution of patent rights to

any inventions developed under the

CRADA(s). Generally, the rights of

ownership are retained by the

organization which is the employer of

the inventor, with an irrevocable, nonexclusive, royalty-free license to the

Government (when a company

employee(s) is the sole inventor) or a

first option to negotiate an exclusive or

non-exclusive license to the company

on terms that are appropriate (when the

Government employee(s) is the sole or

a joint inventor).

Dated: June 7, 1996.

Barbara M. McGarey,

Deputy Director, Office of Technology

Transfer.

[FR Doc. 96–15363 Filed 6–17–96; 8:45 am]

BILLING CODE 4140–01–M

Prospective Grant of Exclusive

License: Gossypol Acetic Acid for the

Treatment of Cancer

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: This is notice in accordance

with 35 U.S.C. 209(c)(1) and 37 CFR

404.7(a)(1)(I) that the National Institutes

of Health (NIH), Department of Health

and Human Services, is contemplating

the grant of an exclusive world-wide

license to practice the inventions

embodies in U.S. Patent No. 5,385,936

and U.S. Patent Applicant No. 08/

379,872 to Cary Medical Corporation of

Great Falls, Virginia. U.S. Patent No.

5,385,936 is directed toward a method

of treating cancers using Gossypol

Acetic Acid (GAA). U.S. Patent

Application No. 08/379,872 is directed

toward the use of Gossypol for the

treatment of cancer. Patent rights in

these inventions have been assigned to

the United States of America.

The prospective exclusive license will

be royalty-bearing and will comply with

the terms and conditions of 35 U.S.C.

209 and 37 CFR 404.7. The prospective

exclusive license may be granted unless

within sixty (60) days from the date of

this published notice, NIH receives

written evidence and argument that

establishes that the grant of the license

would not be consistent with the

requirements of 35 U.S.C. 209 and 37

CFR 404.7.

Gossypol is a biphenolic compound

derived from crude cottonseed oil that

has been widely used in China as a male

contraceptive. Clinical trials have

demonstrated GAA’s efficacy against

gliomas and adrenal cancer. Clinical

trials are planned or underway for the

use of GAA in breast and prostate

cancer. GAA exhibits low toxicity

relative to other chemotherapeutic

agents and does not appear to cause

myelosuppression, significant hair loss,

cardiac failure or neurotoxicity. The

milder side effects of the use of GAA

include mild fatigue, muscle tremor, dry

mouth, dry skin, and occasional nausea.

Patients treated with GAA, therefore,

may be able to continue normal

activities.

ADDRESSES: Requests for a copy of the

issued patent, patent application,

inquiries, comments, and other

materials relating to the contemplated

license should be directed to: Allan

Kiang, Technology Licensing Specialist,

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; Telephone: (301)

496–7735 ext. 270; Fax: (301) 402–0220.

A signed Confidentiality Agreement will

be required to receive copies of the

patent application. Applications for a

license in the field of use filed in

response to this notice will be treated as

objections to the grant of the

contemplated license. Only written

comments and/or applications for a

license which are received by the NIH