[Federal Register Volume 63, Number 201 (Monday, October 19, 1998)]
[Notices]
[Pages 55878-55880]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-27959]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, DHHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: 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 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 will be required to receive
copies of the patent applications.
Agents That Bind To and Inhibit Cytochrome P450 2A6
HV Gelboin, FJ Gonzalez (NCI)
Serial No. 60/093,936 filed 23 Jul 98
Licensing Contact: Dennis Penn, 301/496-7056 ext. 211
The cytochrome P450 family of enzymes is primarily responsible for
the metabolism of xenobiotics such as drugs, carcinogens and
environmental chemicals, as well as several classes of endobiotics such
as steroids and prostiglandins. Members of the cytochrome P450 family
are present in varying levels and their expression and activities are
controlled by variables such as chemical environment, sex,
developmental stage, nutrition and age.
There are multiple forms of these P450 and each of the individual
forms exhibit degrees of specificity towards individual chemicals of
the above classes. Genetic polymorphisms of cytochrome P450 2A6 result
in phenotypically distinct deficient subpopulations that differ in
their ability to perform biotransformations of a particular drug and
other chemical compounds.
This invention describes monoclonal antibody Mab 151-45-4, which is
highly specific for human cytochrome P450 2A6 and does not cross react
with 12 other human P450s. The inhibitory and immunoblotting monoclonal
antibody that are described in this invention report is unique and is
the only known inhibitory monoclonal antibody to human P450 2A6. Its
inhibitory activity P450 2A6 is greater than 90%. This monoclonal
antibody may be used as a diagnostic probe identifying the distribution
of 2A6 in populations and thus identifying enzyme deficient individuals
that are sensitive to 2A6 metabolized drugs. This Mab will also
identify those drugs that are currently used and in the process of drug
development which are substrates for 2A6. Metabolism of partner drugs
by P450 2A6 may be the basis for drug-drug toxicity.
Agents That Bind To and Inhibit Human Cytochrome P450 1A2
HV Gelboin, FJ Gonzalez, TJ Yang (NCI)
Serial No. 60/093,913 filed 23 Jun 98
Licensing Contact: Dennis Penn, 301/466-7056 ext. 211
The cytochrome P450 family of enzymes is primarily responsible for
the metabolism of xenobiotics such as drugs, food pyrolysate,
carcinogens and environmental chemicals, as well as several classes of
endobiotics such as steroids and prostaglandins. Members of the
cytochrome P450 family are present in varying levels in human tissue.
There are multiple forms of these P450 and each of the individual
forms exhibit metabolic activity, often overlapping, towards individual
chemicals of the above classes. Genetic polymorphisms of cytochrome
P450 result in phenotypically distinct subpopulations that differ in
their ability to perform biotransformations of a particular drug and
other chemical compounds.
This invention describes monoclonal antibodies Mab 26-7-5, Mab 951-
5-1 and Mab 1812-2-4, which are highly specific for human cytochrome
P450 1A2 and do not cross react with 11 other human P450s. These Mabs
exhibit strong immunoblotting activity and enzyme inhibitory activity
greater than 85%. The inhibitory and immunoblotting monoclonal antibody
that are described in this invention report is unique and is the only
known inhibitory monoclonal antibody to
[[Page 55879]]
human P450 1A2. Thus these Mabs may be used to identify drugs,
carcinogens and other xenobiotics metabolized by P450 1A2 in human
liver. The inhibitory properties can determine the quantitative
metabolic contribution of P450 1A2 in human liver relative to that of
other P450s that may also metabolize 1A2 substrates. These Mabs can
identify drugs currently in use and in the process of drug development
which are substrates for 1A2. The Mab can also identify partner drugs
metabolized by 1A2 that may be a basis of drug-drug toxicity. The Mabs
are also diagnostic probes identifying the distribution of 1A2 in
populations and thus identifying enzyme deficient individuals that are
sensitive to 1A2 metabolized drugs.
AAV5 Vector and Uses Thereof
JA Chiorini (NHLBI)
Serial No. 60/087,029 filed 28 May 98
Licensing Contact: Susan S. Rucker, 301/496-7056 ext. 245
The invention described and claimed in this patent application
provides for novel vectors and viral particles which comprise adeno-
associated virus serotype 5 (AAV5). AAV5 is a single-stranded DNA virus
of either plus or minus polarity which, like other AAV serotypes (AAV4,
AAV2) requires a helper virus for replication. AAV type 2 has the
interesting and potentially useful ability to integrate into human
chromosome 19 q 13.3-q ter. This activity is dependent on the non-
structural, Rep, proteins of AAV2. The Rep proteins of AAV types 2 and
5 are dissimilar and are not able to substitute in DNA replication of
the heterologous serotype. Based on preliminary fluorescent in situ
hybridization (FISH) results, the integration of AAV type 5 occurs
specifically, but at a different genetic locus to that of AAV type 2.
AAV5 offers several advantages which make it attractive for use in
gene therapy: 1. increased production (10-50 fold greater than AAV2);
2. distinct integration locus when compared to AAV2; 3. Rep protein and
ITR regions do not complement other AAV serotypes; 4. appears to
utilize different cell surface attachment molecules than those of AAV
type 2.
Variant Peptide Ligands That Selectively Induce Apoptosis
MJ Lenardo, RN Germain, B Combadiere, C Reis e Sousa (NIAID)
Serial No. 60/072,952 filed 29 Jan 98
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
This invention relates to selective modulation of specific T cell
responses. Variant peptide ligands for the T cell receptor have been
identified and characterized. These variant peptide ligands act as
partial agonists. Specifically, the ligands induce apoptosis in T cells
without the concomitant production and release of non-death inducing
cytokines. These variant peptide ligands can be used to treat or
prevent T cell associated disorders such as autoimmune diseases,
allergic disorders, graft rejection and graft versus host disease by
selectively eliminating specific T cell populations.
Method For Synthesizing 9-(2,3-Dideoxy-2-fluoro--D-threo-
pentofuranosyl)adenine (-Fdda)
VE Marquez, MA Siddiqui, JS Driscoll (NCI)
Serial No. 60/067,765 filed 10 Dec 97
Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264
AIDS (acquired immunodeficiency syndrome), first reported in the
United States in 1981, has become a worldwide epidemic, crossing all
geographic and demographic boundaries. More than 475,000 cases of AIDS
have been reported in the United States since 1981 and more than
295,000 deaths have resulted in the U.S. from AIDS. Over 1.5 million
Americans are thought to be infected with HIV (human immunodeficiency
virus),the causative agent of AIDS. One clinically useful anti-HIV
nucleoside is 9-(2,3-Dideoxy-2-fluoro--D-threo-
pentofuranosyl)adenine (-Fdda.)
The subject invention relates to methods and compounds for a highly
effective synthesis of clinically useful anti-HIV active nucleosides
such as 9- (2,3-Dideoxy-2-fluoro--D-threo-pentofuranosyl)
adenine (-FddA), and analogues and prodrugs thereof.
Single-Shot Spiral Scanning Magnetic Resonance Imaging Using
Trapezoidal Gradients
JH Duyn (CC)
Serial No. 60/067,670 filed 05 Dec 97
Licensing Contact: John Fahner-Vihtelic, 301/496-7735 ext. 270
The present application describes a magnetic resonance imaging
(MRI) apparatus which employs trapezoidal gradients. This apparatus
allows for fast MRI scanning with excellent signal to noise ratio that
is relatively insensitive to motion. Single-shot spiral scanning places
high demands on gradient hardware which creates a need for carefully
designed gradient waveforms. Use of the trapezoidal wave forms embodied
in this invention overcome problems such as large heat load to the
pulse-width modulators. The present technology applies to cardiac
imaging as well as functional neuroimaging using fMRI based on blood
oxygenation (BOLD) dependent contrast.
Methods of Using CR3 and CR4 Ligands for Inhibiting IL-12 To Treat
Autoimmune Disease
B Kelsall, W Strober, I Fuss, T Marth (NIAID)
Serial No. 60/066,238 filed 20 Nov 97
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
This invention provides a novel approach to downregulating the
production of IL-12. Specifically, Marth and Kelsall have shown that
IL-12 production can be modulated via the complement receptors CR3 and
CR4. By binding a ligand, such as an antibody, to the complement
receptors, an IL-12 induced inflammatory response can be modulated.
This method can be used to treat various autoimmune diseases.
Real-Time Monitoring of Electrocardiogram During Magnetic Resonance
Scanning
A Berson (NHLBI)
Serial No. 08/965,869 filed 07 Nov 97
Licensing Contact: John Fahner-Vihtelic, 301/496-7735 ext. 270
The present application describes an apparatus and method for
monitoring an electrocardiogram (ECG) during magnetic resonance (MR)
scanning. This device consists of a unique electrode system that allows
the ECG to be obtained by a series of potential measurements between
certain of the placed electrodes. Monitoring the ECG in patients
undergoing MR scanning can be extremely important if the subject of the
MR scan is a cardiac patient or is being stressed at the time of the
scan. Interference of ECG by the magnetic field associated with MR
scanning, gradient fields, RF sampling fields, and magnetohydrodynamics
incidental to blood flow, can be overcome with this invention.
A Swine Hepatitis E Virus and Uses Thereof
Serial No. 60/053,069 filed 18 Jul 97; PCT/US98/14665 X-J Meng, RH
Purcell, SU Emerson (NIAID)
Licensing Contact: Carol Salata, 301/496-7735 ext. 232
This invention is directed to a novel swine hepatitis E virus
(swine HEV) and its partial sequence. This swine HEV is unique from
other previously-described HEV strains but is both genetically and
serologically related to human HEV. The putative capsid protein of HEV
strains, when expressed as a recombinant protein in insect cells, is
highly useful in the evaluation of infection of swine
[[Page 55880]]
as well as of humans with HEV. The recombinant HEV capsid protein may
also be useful in the vaccination of humans and animals against
infection with HEV strains.
Oligonucleotides Which Specifically Bind Retroviral Nucleocapsid
Proteins
A Rein, J Casas-Finet, R Fisher, M Fivash, LE Henderson (NCI)
PCT/US97/08936 filed 19 May 97 (claiming priority of USSN 60/017,128
filed 20 May 96)
Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264
The human immunodeficiency virus (HIV) is the causative agent of
acquired immunodeficiency syndrome (AIDS). A retroviral protein
species, the gag polyprotein, is involved in the assembly of retrovirus
particles and capable of specific interactions with nucleic acids.
After the virion is released from the cell, the polyprotein is cleaved
by the virus-encoded protease. One of the cleaved products, the
nucleocapsid (NC) protein, then binds to genomic RNA, forming the
ribonucleoprotein core of the mature particle. The interaction between
gag and genomic RNA is known to involve the NC domain of the
polyprotein.
The present invention relates to retroviral proteins, such as NC
and the gag precursor, and their ability to bind to specific nucleic
acid sequences with high affinity. Accordingly, the invention provides
for oligonucleotides which bind to nucleocapsids proteins with high
affinity, molecular decoys for retroviral nucleocapsid proteins which
inhibit viral replication, targeted molecules comprising high affinity
oligonucleotides, assays for selecting molecules which inhibit the
specific interaction between retroviral proteins and high affinity
oligonucleotides, and related kits.
Compositions for the Prevention or Retardation Of Cataracts
JS Zigler Jr., P Russell, S Tumminia, C Qin, CM Krishna (NEI)
PCT/US97/01105 filed 24 Jan 97 (claiming priority of USSN 60/010,637
filed 26 Jan 96)
Licensing Contact: David Sadowski, 301/496-7735, ext. 288
Oxidative stress is becoming recognized as a major problem, and
free radicals and activated oxygen species are recognized as agents of
tissue damage associated with a number of conditions. Aging-related
cataract is a disease of multifactorial origin involving many of the
same processes which characterize the process of aging in other
tissues. It appears that once cataractogenesis has begun, the process
of cataract development may proceed via one or more common pathways or
processes. The subject invention focuses on intervening at the level of
these common pathways in hopes of stopping or slowing the progression
of the disease process. The present invention provides methods and
compositions for the prevention and treatment of cataract formation
which comprise a nitroxide free radical compound or its hydroxylamine
and a thiol reducing agent.
Methods for Enhancing Oral Tolerance and Treating Autoimmune
Disease Using Inhibitors Of IL-12
W Strober, Brian Kelsall, T Marth (NIAID)
PCT/US96/16007 filed 11 Oct 96 designating AU, US, CA, JP (no rights in
EPO); published as WO 98/16248 on 23 Apr 98
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
Oral tolerance is the immunologic mechanism by which the mucosal
immune system maintains unresponsiveness to the myriad of antigens in
the mucosal environment which might otherwise induce untoward immune
responses. Recent studies have shown that it is mediated by several
distinct, yet interacting mechanisms including the generation of
suppressive T cells producing antigen nonspecific cytokines and the
induction of clonal deletion and/or anergy. This invention provides two
methods: 1) for enhancing oral tolerance to an antigen and 2) for
treating an autoimmune disease. By orally administering an antigen
associated with an autoimmune disease, allergic disease or graft versus
host (GvH) disease along with an inhibitor of IL-12, oral tolerance can
be enhanced. The diseases can also be treated using virtually the same
method.
Method for Protecting Bone Marrow Against Chemotherapeutic Drugs
Using Transforming Growth Factor Beta 1
JR Keller, FW Ruscetti, R Wiltrout (NCI)
U.S. Patent 5,278,145 issued 11 Jan 94
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
This invention provides a method for protecting hematopoietic stem
cells from the myelotoxicity of chemotherapeutic drugs or radiation
therapy. Chemotherapeutic agents destroy the body's ability to make
granulocytes thereby exposing patients to potentially lethal
microorganisms. Previous attempts to alleviate this problem focused on
the use of growth factors to accelerate recovery from myelotoxicity.
This invention details a method for administering TGF-1 in
conjunction with the administration of chemotherapeutic drugs in order
to reduce the number of stem cells killed thereby reducing
myelotoxicity which is an improvement to the previous method.
Dated: October 13, 1998.
Jack Spiegel, Ph.D.
Director, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 98-27959 Filed 10-16-98; 8:45 am]
BILLING CODE 4140-01-M
