[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]


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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, Public Health Service, DHHS.

ACTION: Notice.

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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