[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
