[Federal Register Volume 64, Number 108 (Monday, June 7, 1999)]
[Notices]
[Pages 30342-30343]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-14244]


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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.

Acylated Oligopeptide Derivatives Having Cell Signal Inhibiting 
Activity

Terrence R. Burke, Jr. (NCI)
Serial No. 09/236,160 filed 22 Jan 99
Licensing Contact: Richard Rodriguez; 301/496-7056, ext. 287; e-mail: 
[email protected]

    The invention is directed to pharmaceutically active compounds 
comprising an N-oxalyl peptide structure. These compounds have the 
ability to disrupt the interaction between SH2 domain (e.g., Grb2) 
containing proteins, and proteins with phosphorylated moieties, 
especially phosphorylated tyrosine moieties on protein tyrosine kinase 
(PTK) receptors. The effect of inhibiting the association of SH2 
domain-containing proteins with PTKs is to inhibit downstream signaling 
through one or more specifically targeted effector proteins. Examples 
of these SH2-containing proteins include, but are not limited to, Src, 
Lck, Fps, ras-GTPase activating protein, Fyn, Lyk, Fgr, Fes, Zap-70, 
Bcr-Abl, JAK1 and JAK2. These compounds could prove highly useful for 
the treatment of some cancers. In particular, Grb2 SH2 domains afford 
an ideal target because they provide a critical link between growth 
factor receptor PTKs and downstream signaling events involving ras-
proteins which have been directly implicated with oncogenic processes. 
Examples of this include: members of the epidermal growth factor 
receptor PTK family (ErbB-2) which are found in many breast cancers; 
the hepatocytes growth factor/scatter factor (Met) PTK which is 
overexpressed in many human tumors; and the Bcr-Abl PTK which is 
necessary for Philadelphia chromosome positive leukemia. The 
development of this technology could therefore provide for the design 
and use of powerful therapeutics for disease states where signal 
transduction becomes deregulated.

Water-Insoluble Drug Delivery System

E Tabibi, E Ezennia, BR Vishnuvajjala, S Gupta (NCI)
Serial No. 60/113,423 filed 22 Dec 98
Licensing Contact: Girish Barua; 301/496-7056, ext. 263; e-mail: 
[email protected]

    This technology describes an improved, stable drug delivery system 
for water-soluble drugs, in particular 17-allylaminogeldanamycin (17-
AAG) and a pharmaceutical composition comprising such a drug delivery 
system, as well as methods for preparing the drug delivery system. The 
water-insoluble drug is dissolved in a water miscible organic solvent 
that forms a continuous phase with water and a surface active agent. 
The application of this technology enables the more effective delivery 
of drugs such as geldanamycin and 17-AAG, with preparation of the 
system requiring less complex processing steps.

Nucleosides for Imaging and Treatment Applications

Jerry M. Collins, Raymond W. Klecker, Aspandiar G. Katki, Lawrence 
Anderson (FDA).
DHHS Reference No. E-058-97/1 filed 30 Oct 98; PCT/US98/23109
Licensing Contact: John Fahner-Vihtelic; 301/496-7735 ext. 270; e-mail: 
[email protected]

    The present application describes recently developed nucleosides 
that provide for (1) external imaging of tumor cell proliferation, (2) 
noninvasive determination of which tumors would be sensitive to drug 
therapy, and (3) potential utility as a novel antitumor treatment 
approach. No comparable procedures are available to determine, prior to 
treatment, which tumors are likely to respond to a given therapeutic 
approach. This invention also has the ability to rapidly evaluate the 
success or failure of treatment, during the course of therapy. As 
imaging agents, these nucleosides are directly targeted towards 
specific events, rather than broad measures of effect such as 
fluorodeoxyglucose. There is no currently available treatment for 
tumors with high levels of drug resistance, specifically due to 
overexpression of the key enzyme, thymidylate synthase. The utility of 
these inventions has been demonstrated in cultured human tumor cells, 
and preclinical toxicology studies have been conducted which permit 
entry into initial human testing.

Virally Mediated Gene Therapy for the Control of Chronic or 
Persistent Pain

MJ Iadarola, RM Caudle, AA Finegold, AJ Mannes (NIDCR)
DHHS Reference No. E-044-98/0 filed 23 Sep 98 Licensing Contact: Kai 
Chen; 301/496-7056 ext. 247; e-mail: [email protected]


[[Page 30343]]


    Current treatments for pain, especially chronic pain, are only 
partially effective and can eventually involve procedures that are 
invasive or associated with unacceptable side effects. In vivo gene 
transfer could be used to directly modulate pain and provide a long-
term pain control. This invention describes a method of using an 
adenovirus or an adeno-associated virus that are genetically engineered 
to deliver DNA encoded peptides or proteins to neurons involved in the 
transmission of pain. The invention provides for a novel means to treat 
chronic pain by administering a beta-endorphin-expressing recombinant 
adenovirus into the subarachnoid space. The recombinant virus infects 
the pia mater connective tissue cells and the infected cells express 
the fusion protein, wherein the fusion protein is cleaved and the 
neuroactive product is secreted into spinal cord parenchymal tissue in 
an amount effective to treat the chronic pain but not significantly 
affecting basal nociceptive responses. The invention demonstrates a 
gene transfer approach to treatment of chronic pain disorders or cancer 
pain, and may be generalized to spinal cord injury or neurodegenerative 
disorders.

O2-Arylated or O2-Glycosylated 1-Substituted 
Diazen-1-ium-1,2-diolates and O2-Substituted 1-[(2-
Carboxylato) Pyrolidin-1-yl] Diazen-1-ium-1,2-diolates

JE Saavedra, LK Keefer, A Srinivasan, C Bogdan, WG Rice, X Ji, (NCI)
DHHS Reference No. E-093-96/3 filed 26 Sep 97 (U.S. Patent Application 
Serial No. 09/254,301 filed 03 Mar 99, based on Provisional U.S. Patent 
Applications No. 60/026,816 filed 27 Sep 96, No. 60/045,917 filed 07 
May 97, and No. 60/051,696 filed 03 Jul 97)
Licensing Contact: Kai Chen; 301/496-7056 ext. 247; e-mail: 
[email protected]

    Diazeniumdiolates are compounds that contain, an 
N2O2 functional group. These compounds are 
potentially useful as prodrugs because they generate nitric oxide upon 
degradation. Nitric oxide (NO) plays a role in regulation of blood 
pressure, inflammation, neurotransmission, macrophage-induced 
cytostasis, and cytotoxicity. NO is also important in the protection of 
the gastric mucosa, relaxation of smooth muscle, and control of the 
aggregation state of blood cells. Derivatives of diazeniumdiolates have 
been produced that degrade under differing environmental conditions, 
allowing for selective delivery of nitric oxide in a manner dependent 
on environment. A new series of diazeniumdiolate derivatives has been 
synthesized that are stable in neutral to acidic environments and 
generate nitric oxide in basic or nucleophilic environments. These 
derivatives are potentially suited to the delivery of nitric oxide to 
basic or nucleophilic compartments within the body. They may be useful 
for inactivating proteins to prevent detoxification of chemotherapeutic 
agents or disruption of proteins active in tumor formation, infection, 
or regulatory activities. The compounds are stable in an aqueous 
environment but can be activated by enzymatic action to release nitric 
oxide that is believed to be useful in treating fulminant liver 
failure, respiratory problems, impotence, and a variety of 
cardiovascular/hematologic disorders. The diazeniumdiolates have also 
been derivatized by their incorporation into polymers. These compounds 
may allow for site specific delivery of nitric oxide. Overall, these 
compounds appear to be applicable toward the wide variety of processes 
involving nitric oxide.

Immunologically Active Peptides From the HIV Envelope Protein 
Eliciting Both Antibody and T Cell Responses

William R. Kenealy, Stephen R. Petteway and Paul J. Durda
U.S. Patent No. 5,562,905 issued 08 Oct 96
Licensing Contact: Robert Benson; 301/496-7056 ext. 267; e-mail 
[email protected]

    This invention is a series of chemically synthesized peptides of 
about 15 amino acids in length from the gp160 envelope protein of 
various isolates of HIV-1. Antibodies raised against the peptides block 
proliferation of HIV and block HIV-induced cell fusion in cell culture. 
The peptides are potential vaccines against HIV infection and 
monoclonal antibodies raised against the peptides are potentially 
useful as therapeutics. Foreign equivalent cases to USSN 07/148,692 
(Berzofsky et al., PCT/US89/00712) are also available for licensing.
    The NIH has many other patents and pending patent applications, 
most foreign filed, claiming various peptides from the HIV envelope 
protein that are T helper epitopes, CTL epitopes and neutralizing 
antibody epitopes discovered in the laboratory of Dr. Jay Berzofsky. 
Dr. Berzofsky has designed synthetic chimeric peptides (called 
``multideterminant'' peptides) that combine a peptide containing 
several T helper epitopes which can activate many human HLA types 
(called a ``multicluster'' peptide, and claimed in USSN 08/455,685) 
with a peptide combining a CTL and neutralizing B cell epitope (called 
a ``p18'' peptide, and claimed in USSN 07/847,311 and U.S. patents 
5,820,865 and 5,562,905). These multideterminant peptides contain only 
epitopes that lead to protection without containing epitopes that are 
detrimental to protection. Two of the multicluster chimeric peptides 
are in clinical trials. Multideterminant peptides are claimed in USSN 
08/060,988 and 08/407,252.

Computational Analysis of Nucleic Acid Information Defines Binding 
Sites

Thomas D. Schneider (NCI), Peter K. Rogan
Serial No. 08/494,115 filed 23 Jun 95; U.S. Patent 5,867,402 issued 02 
Feb 99
Licensing Contact: John Fahner-Vihtelic, 301/496-7735, ext. 270; e-
mail: [email protected]

    Current approaches to determine whether a nucleotide change is a 
benign polymorphism or is associated with a genetic disease rely on 
sequence comparisons of a substantial number of individuals. This 
invention embodies a computational method that is able to predict 
whether a nucleotide change will have a deleterious effect. The claims 
of this invention relate to a computer program which has the novel 
feature in that it is designed to calculate the relative importance of 
a given nucleotide change. This program is unique in that it is capable 
of predicting the effect that a given nucleotide change would have on a 
particular sequence such as a known binding site. The method has been 
successfully applied to predicting the effects of changes at human 
splice junctions. Further information is available at ``http://
www.lecb.ncifcrf.gov/toms/walker/index.html''.

    Dated: May 26, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-14244 Filed 6-4-99; 8:45 am]
BILLING CODE 4140-01-M