[Federal Register Volume 62, Number 94 (Thursday, May 15, 1997)]
[Notices]
[Pages 26809-26811]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-12783]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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    The inventions listed below are owned by agencies of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for U.S. companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804 (telephone 301/496-7057; fax 301/402-0220). A 
signed Confidential Disclosure Agreement (CDA) will be required to 
receive copies of the patent applications.

Agents That Bind To and Inhibit Human Cytochrome P450  2D6

HV Gelboin, FJ Gonzalez, KW Krausz (NCI)
OTT Ref. No. E-46-97/0 filed 22 Jan. 97
Licensing Contact: Leopold J. Luberecki, Jr., 301/496-7735 ext 223

    This invention concerns monoclonal antibodies (MAbs) and other 
binding agents specific for the 2D6 subgroup of cytochrome P450 
enzymes. The cytochrome P450s are the metabolic interface between 
xenobiotics and their metabolism in human and other species as well as 
for the metabolism of endobiotics. A large array of drugs, mutagens, 
carcinogens, pesticides, environmental chemicals, fatty acids, bile 
acids, and steroids are metabolized by individual forms of cytochrome 
P450. The invention involves the construction, isolation, and 
production of MAbs that specifically bind to human cytochrome P450 and 
2D6 and that specifically inhibit the enzyme activity of human 
cytochrome P450 and lack specific binding to other human cytochrome 
P450s. These MAbs can be used to assess adverse reactions in patients 
to compounds and to identify populations that would exhibit different 
sensitivities to the therapeutic or toxic effects of compounds. 
Cytochrome P450 2D6, also known as debrisoquine hydroxylase, is the 
best characterized polymorphic P450 in the human population. Genetic 
differences in cytochrome P450 2D6 may be associated with increased 
risk of developing environmental and occupational based diseases. In 
addition, several drugs for treating cardiovascular and psychiatric 
disorders are known substrates of cytochrome P450 2D6, and these 
compounds could be more readily prescribed to normal metabolizers as 
assessed using the MAbs described in the invention. The list of 
compounds includes -blockers and antiarrhythmics, psychoactive 
drugs including tricyclic antidepressants, and a variety of other 
commonly used drugs including codeine and dextromethorphan. A 
provisional patent application for this invention has been filed with 
the U.S. Patent and Trademark Office (PTO).
    An adjunct technology to this invention that is available for 
licensing involves two inhibitory monoclonal antibodies to human P450 
3A4 and human P450 2E1 that have been developed and filed as a separate 
patent application (U.S. Serial No. 08/599,808) with the PTO. The P450 
3A4 has likely the largest number of known drug substrates than any 
other P450. The P450 2E1 also metabolizes some drugs and has high 
activity towards smaller molecules which are found in the environment 
and which may be toxic. (portfolios: Internal Medicine--Research 
Materials; Cancer--Research Materials, MAb based; Internal Medicine--
Diagnostics; Cancer--Diagnostics, in vitro, MAb based)

Vanilloid Agonists for Desensitization of C-Fiber Sensory Afferent 
Neurons

PM Blumberg, T Biro, P Acs, G Acs (NCI)
Serial No. 60/030,999 filed 15 Nov 96
Licensing Contact: Leopold J. Luberecki, Jr., 301/496-7735 ext 223

    Capsaicin has been proven to have therapeutic utility in the 
treatment of arthritis, pruritis, bladder hyperreflexia, allergic 
responses including rhinitis, and pain, including pain associated with 
cancer, peripheral neuropathies, and postherpetic neuralgia. For a 
number of these indications, applications have been found in veterinary 
as well as human medicine. Recent advances have identified capsaicin 
analogs with ultrapotency and with a more favorable spectrum of action, 
as well as subclasses of capsaicin receptors with different effects on 
desensitization. This invention describes a method of administering to 
a capsaicin-sensitive animal a therapeutically effective combination of 
capsaicin agonists and capsaicin-like antagonists which are more 
effective than the agonist alone at desensitizing a vanilloid 
responsive cell, and thereby improve the therapeutic index of the 
capsaicin agonist and overall treatment. Also described are 
pharmaceutical compounds which are effective in this method. 
(portfolios: Central Nervous System--Therapeutics, neurological, 
narcotics and analgesics; Internal Medicine--Therapeutics, other)

Sustained-Release Derivatives of Hydroxylated Analogs of Substituted 1-
[2[bis(aryl)methoxy]-ethyl]-Piperazines and-Homopiperazines and Their 
Use As Noncompetitive Antagonists of Dopamine Reuptake Inhibitors

RB Rothman (NIDA), KC Rice (NIDDK), DB Lewis (NIDDK), D Matecka 
(NIDDK), JR Glowa (NIDDK)
Serial No. 60/030,248 filed 31 Oct 96
Licensing Contact: Leopold J. Luberecki, Jr., 301/496-7735 ext 223

    Cocaine abuse and addiction is a major public health problem in the 
United States and several other

[[Page 26810]]

countries. The biomedical and psychosocial cost of cocaine abuse and 
addiction is considerable, and to date, there is no effective treatment 
for addiction. In an effort to develop an efficacious treatment for 
cocaine addiction, this invention describes sustained-release 
derivatives of hydroxylated analogs of substituted 1-
[2bis(arly)methoxy]ethyl]-piperazines and-homopiperazines. These 
compounds bind to the dopamine transporter but do not inhibit dopamine 
reuptake, thereby providing a sustained increase in the level of 
extracellular dopamine and providing the drug abuser with some relief 
from drug craving due to dopamine deficiency, yet they simultaneously 
inhibit cocaine from further elevating the level of extracellular 
dopamine and increasing the probability of additional toxic side 
effects. These derivatives have been shown to produce moderate to long-
acting attenuation of cocaine-induced activation of mesolimbic dopamine 
neurons in rhesus monkeys, resulting in decreased cocaine self-
administration without concurrent effects on food response. The present 
invention provides these sustained-release derivatives, pharmaceutical 
compositions comprising the same, and a method of using such sustained 
release derivatives as a treatment for cocaine addiction. (portfolio: 
Central Nervous System--Therapeutics, psychotherapeutics, drug 
dependence)

Isolation and Use of Tissue Growth-Inducing FRZB Protein

FP Luyten (NIDR), M Moos Jr. (FDA), B Hoang (FDA), S Wang (FDA)
Serial No. 08/729,452 filed 11 Oct 96
Licensing Contact: Jaconda Wagner, 301/496-7735 ext 284

    A secretable protein, named FRZB because of its homology to the 
Drosophila gene frizzled, has been isolated from cartilage. This 
protein appears to be involved in the formation of cartilage, bone, 
neural and muscle tissue. A pharmaceutical composition of this protein 
may be used as regenerative agent to treat degenerative disorders, 
(i.e., Huntingdon's, Alzheimer's, or spinal cord injuries), 
myodegenerative disorders (i.e., muscular dystrophy, myasthenia gravis, 
or myotonic myopathies) and osteodegenerative disorders (i.e., 
osteoporosis or osteoarthritis). In addition, FRZB directly interacts 
with the Wnt family of signaling molecules and inhibits their 
biological function in vivo. This provides the opportunity to 
selectively block Wnt driven diseases including neoplasias. 
(portfolios: Central Nervous System--Therapeutics, neurological, 
antiparkinsonian; Central Nervous System--Therapeutics, neurological, 
Alzheimer's; Central Nervous System--Therapeutics, neurologial, other; 
Internal Medicine--Therapeutics)

Novel Human Cancer Antigen of Tyrosinase-Related Proteins 1 and 2 and 
Genes Encoding Same

RF Wang, SA Rosenberg (NCI)
Serial No. 08/599,602 filed 06 Feb 96 and Serial No. 08/725,736 filed 
04 Oct 96 (CIP)
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    Tumor infiltrating lymphocytes (TIL) from a melanoma patient 
showing regression were found to recognize epitopes from a protein 
designated gp75, now known as tyrosinase related protein 1 (TRP-1). The 
inventors found that the antigen recognized by the TIL was encoded by 
that gene but that was not the normal gene product. The TIL recognized 
a nine-amino acid peptide (ORF3P) which is the product of an 
alternative reading frame (ORF3). ORF3P cannot be lengthened or 
shortened without loss of antigenicity. The TRP-1 ORF3P antigen is only 
found in melanoma cells, melanocytes and normal retina. This technology 
was described in U.S. patent application 08/599,602 filed February 6, 
1996.
    The present invention is a CIP of 08/599,602 and was filed October 
4, 1996. This CIP application contains a novel tumor antigen (TRP-2) 
which was recognized by CTL clones derived from TIL. However, TRP-2 was 
recognized by CTL clones which are capable of recognizing the ORF3P. A 
new antigenic peptide (TRP197-205) was identified from the TRP-2 
product. The subject matter of both the parent and CIP applications 
were combined in a subsequent PCT application filed February 6, 1997.
    The use of the methods described in the present invention could 
provide a form of cancer immunotherapy for melanoma. (portfolios: 
Cancer--Therapeutics, vaccines; Cancer--Diagnostics, in vitro, MAb 
based)

PFS25-28 Fusion as a Malaria Transmission Blocking Vaccine

DC Kaslow, MM Gozar (NIAID)
Serial No. 60/027,390 filed 30 Sept 96
Licensing Contact: Gloria Richmond, 301/496-7056 ext 268

    Malaria is estimated to cause two to four million deaths per year, 
and 200 to 400 million people are infected annually with the deadliest 
of the protozoans that cause the disease, Plasmodium falciparum. The 
life cycle of the malarial parasite is very complex, involving stages 
that reside in both humans and mosquitoes. Vaccines that are able to 
inhibit the transmission of the disease at a variety of stages in the 
complex life cycle of the malarial parasite might provide an 
opportunity to effectively control and possible eradicate this disease. 
This invention relates to the generation of transmission-blocking 
antibodies to two sexual stage surface antigens, Pfs 25 and Pfs 28. Two 
issued patents cover the use of these antigens separately as 
transmission-blocking vaccines. The claims of the current invention 
relate to the production of fusion proteins between these two surface 
antigens that have increased potency as immunogens and ease of 
manufacture. (portfolios: Infectious Diseases--Vaccines, parasite)

Prostate Specific Antigen Oliog-Epitope Peptide

J Schlom, K Tsang, S Zaremba (NCI)
Serial No. 08/618,936 filed 20 Mar 96
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    Prostate Specific Antigen (PSA) is expressed in a majority of 
prostate cancers, and represents a potential target for immunotherapy. 
Previous studies have shown that two specific PSA peptides, PS1 and 
PS3, are capable of eliciting cytotoxic T-cell responses. The current 
invention embodies an oligopeptide, PSA-OP, which is comprised of the 
sequence for peptides PS1 and PS3. PS1 and PS3 are antigenic epitopes 
of PSA and are joined by a peptide linker sequence to form PSA-OP. PSA-
OP has been shown, in vitro, to be effective in eliciting a cytotoxic 
T-cell response. This novel peptide, therefore, may be used in the 
development of vaccines for use in the prevention and treatment of 
prostate cancer. (portfolio: Cancer--Therapeutics)

Immortal Human Prostate Epithelial Cell Cultures and Their Applications 
in the Research and Therapy of Prostate Cancer

SL Topalian, WM Linehan, RK Bright, CD Vocke (NCI)
OTT Reference No. E-053-96/0 (USSN 60/011,042 filed 02 Feb 96) and OTT 
Reference No. E-017-97/0 (CIP of E-053-96/0)
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    The invention describes the further characterization of single cell 
clones derived from the prostate tumor cell lines disclosed in the 
earlier application (E-053-96/0). The isolation and characterization of 
long-term human prostatic epithelial cell cultures from

[[Page 26811]]

primary adenocarcinomas of the prostate is significant in that efforts 
to establish long-term cultures of cells of this type have been 
exceptionally difficult.
    The present invention describes the characterization of single cell 
clones derived from the prostate tumor cell lines disclosed in the 
earlier application. These new clones exhibit traits which may indicate 
their usefulness as an in vitro model of human prostate cancer. The 
single cell clones are paired normal and tumor cell clones where the 
latter exhibit allelic loss of heterozygosity (LOH) indicating the 
presence of unique genetic deletions. This loss may suggest that these 
cells express unique proteins or antigens which might be of tremendous 
value in prostate cancer research. The subject matter of both the 
parent and CIP applications were combined in a subsequent PCT 
application filed January 30, 1997.
    Possible uses of these cells include testing various anti-cancer 
agents and subtraction studies for identification of gene deletions. 
These lines could establish a new basis for possible cancer vaccines 
and also be used to develop monoclonal antibodies against specific 
prostate cancer antigens. (portfolios: Cancer--Therapeutics, vaccines; 
Cancer--Therapeutics, immunomodulators and immunostimulants)

Macrophage Migration Inhibitory Factor (MIF)

Graeme J. Wistow (NEI)
Serial No. 08/202,486 filed 28 Feb 94 (allowed); DIV of U.S. Patent 
5,328,990 issued 12 Jul 94
Licensing Contact: Jaconda Wagner, 301/496-7735 ext 284

    The protein known as macrophage migration inhibitory factor (MIF) 
was one of the first cytokines to be discovered. Thirty-years ago it 
was described as a T-cell-derived factor that inhibited the random 
migration of macrophages in vitro. Today, MIF is known to be a mediator 
of the function of macrophages in host defense and its expression 
correlates with delayed hypersensitivity and cellular immunity. It 
plays an important role in the inflammatory response and is associated 
with cell differentiation. As with other lymphokines, MIF could have 
therapeutic values in stimulating the immune system and other cells. 
Hardly abundant from other sources, the high concentration of the 
protein that has been found in the eye lens could be a useful source 
for research. The present invention provides the DNA that encodes MIF. 
A related invention provides a method for isolating MIF from the ocular 
lens. (portfolio: Ophthalmology--Therapeutics; Internal Medicine--
Therapeutics, anti-inflammatory)

    Dated: April 28, 1997.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 97-12783 Filed 5-14-97; 8:45 am]
BILLING CODE 4140-01-W