[Federal Register Volume 71, Number 26 (Wednesday, February 8, 2006)]
[Notices]
[Pages 6506-6508]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-1653]


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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, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency 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.

Oligodeoxyribonucleotides Comprising O\6\6-Benzylguanine and Their Use

Robert C. Moschel et al. (NCI)
U.S. Patent No. 6,060,458 issued 09 May 2000 (HHS Reference No. E-104-
1998/0-US-01).
Licensing Contact: George G. Pipia, PhD.; 301/435-5560; 
[email protected].

    Chemotherapy is a common treatment for a variety of cancers. 
Chemotherapeutic alkylating agents represent a key category of commonly 
used antineoplastic drugs. These drugs are active against chronic 
leukemias, non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma, 
lung, breast, ovarian cancer, and certain other cancers. The DNA repair 
protein, O\6\-alkylguanine-DNA alkyltransferase (AGT), is a primary 
source of tumor cell resistance to the alkylating drugs that alkylate 
the O\6\ position of guanine in DNA. AGT therefore becomes the prime 
target for modulation. Currently, AGT inactivators are used as 
adjuvants to enhance chemotherapy by the alkylating drugs.
    O\6\-Benzylguanine is the prototype AGT inactivator in phase I, II 
and III clinical trials as an adjuvant to improve chemotherapy. 
Although O\6\-benzylguanine is a promising AGT inactivator, it is not 
an ideal drug. O\6\-Benzylguanine is only sparingly soluble in water, 
and it is not effective in inactivating some mutant alkyltransferase 
proteins that could possibly be produced after repeated chemotherapy 
cycles. The present invention describes oligodeoxyribonucleotides 
containing O\6\-benzylguanine residues as another class of AGT 
inactivators, and discusses the advantages of their use in comparison 
to O\6\-benzylguanine as the free base. Oligodeoxyribonucleotides 
containing O\6\-benzylguanine residues are extremely water soluble and 
can efficiently inactivate AGT at much lower concentrations than O\6\-
benzylguanine. In addition, they are effective in inactivating several 
mutant alkyltransferase proteins that are highly resistant to 
inactivation by O\6\-benzylguanine. Furthermore, positioning O\6\-
benzylguanine near the 3'-or 5'-terminus of these 
oligodeoxyribonucleotides improves their resistance to degradation by 
cellular nuclease proteins. Therefore, oligodeoxyribonucleotides 
containing multiple O\6\-benzylguanine residues may be more effective 
chemotherapy adjuvants than O\6\-benzylguanine.

The CCHC Zinc Fingers of the Retroviral Nucleocapsid Protein Comprises 
a New Target Useful in Identification and Evaluation of Anti-HIV 
Therapeutics

Louis E. Henderson et al. (NCI)
U.S. Patent No. 6,001,555 issued 14 Dec 1999 (HHS Reference No. E-174-
1993/1-US-01).
Licensing Contact: Sally H. Hu, PhD., M.B.A.; 301/435-5606; 
[email protected].

    According to a recently released report from the WHO, an estimated 
40.3 million people worldwide are currently living with HIV infection, 
and more than three million people died of AIDS-related illnesses in 
2005. In response to increased prevalence of HIV/AIDS, the search for 
effective antiretroviral therapy is intensive. The present invention 
describes compounds that may be useful for developing new types of 
antiretroviral therapeutics for HIV infection.
    HIV-1 contains domains known as ``CCHC zinc fingers'' in the 
retroviral nucleocapsid (NC) protein. Nucleocapsid CCHC zinc fingers 
are highly conserved throughout nearly all retroviruses. They are 
sequences of 14 amino acids with four invariant residues, 
Cys(X)2Cys(X)4His(X)4Cys, which 
chelate zinc and perform essential functions in viral infectivity. HIV-
1 NC has two CCHC zinc fingers, both of which are necessary for 
infectivity. Many compounds that disrupt the CCHC zinc fingers also 
inactivate HIV-1 by preventing the initiation of reverse transcription 
and by blocking production of infectious virus from previously infected 
cells. Compounds with this activity may be useful for developing new 
types of antiretroviral drugs. In addition, compounds with this 
activity can be useful for production of chemically inactivated 
retroviral particles that lack infectivity but retain structurally and 
functionally intact envelope glycoproteins. Such inactivated particles 
may be useful both as in vitro reagents in a variety of applications 
and as immunogens for whole inactivated virus vaccines.
    The present invention concerns antiretroviral compounds that 
disrupt the CCHC zinc fingers and assays for identifying such 
compounds. The invariant nature of retroviral zinc fingers also extends 
the usefulness of these compounds to other retroviruses. Thus these 
assays are also useful for screening compounds effective against

[[Page 6507]]

adult T cell leukemia, tropical spastic paraparesis caused by HTLV-I 
and HTLV-II, feline leukemia virus, feline immunodeficiency virus, 
equine infectious virus, and lentivirus infections in other animals, 
and potentially useful for the production of whole inactivated particle 
vaccines against the pathogens.

Use of Inhibitors of 3-Hydroxy-3- Methylglutaryl Coenzyme A Reductase 
as a Modality in Cancer Therapy

Charles Myers et al. (NCI)
U.S. Patent No. 6,040,334 issued 21 Mar 2000 (HHS Reference No. E-146-
1992/0-US-23).
Licensing Contact: George G. Pipia, PhD.; 301/435-5560; 
[email protected].

    HMG Co-A reductase inhibitors, also known as statins, are a type of 
drugs taken by millions of Americans to lower blood cholesterol levels. 
In the United States, statins available by prescription include 
atorvastatin (LipitorTM), lovastatin (MevacorTM), 
and simvastatin (ZocorTM). Recently, there has been a surge 
in interest in the potential use of statins in the treatment or 
prevention of cancer. By exploring the effects of statins on the 
process of cancer at the molecular level, scientists have found that 
they work against critical cellular functions that may help control 
tumor initiation, tumor growth, and metastasis. With years of strong 
evidence that these agents are relatively safe, statins present 
themselves as good candidates for cancer therapeutics with added 
advantages.
    This invention describes a method for treating mammalian 
adenocarcinomas and sarcomas with an effective amount of an inhibitor 
of HMG Co-A reductase or homologues of the inhibitor. Adenocarcinoma is 
known to afflict the prostate, stomach, lung, breast and colon, as well 
as other sites. Lovastatin and simvastatin, as well as their 
homologues, are examples of compounds useful in the present invention. 
Also included are compounds classified as HMG Co-A reductase 
inhibitors, as well as their homologues or analogues. Though the 
inhibitors of HMG Co-A reductase are generally known to reduce serum 
cholesterol in humans, the present invention focuses rather on the 
compounds' ability to treat selected cancers, such as adenocarcinomas 
of the prostate, stomach, lung, breast and colon and certain sarcomas 
such as Ewing's sarcoma.
    Also provided by the invention is a method of reducing prostate 
specific antigen (PSA) levels in a patient having prostatic 
adenocarcinoma by administration of an effective amount of a compound 
which is an inhibitor of HMG Co-A reductase or a homologue of such 
inhibitor, as well as a method of reducing PSA in conjunction with 
another treatment modality.

Potent Peptide for Stimulation of Cytotoxic T Lymphocyte Specific for 
the HIV-1 Envelope

Jay A. Berzofsky et al. (NCI)
U.S. Patent No. 5,976,541 issued 02 Nov 1999 (HHS Reference No. E-072-
1992/0-US-01).
Licensing Contact: Robert M. Joynes, J.D.; 301/594-6565; 
[email protected].

    According to a new annual report from the WHO, an estimated 40.3 
million people worldwide are currently living with HIV infection, and 
more than three million people died of AIDS-related illnesses in 2005. 
Despite intensive efforts to improve antiretroviral treatment, a safe 
and effective HIV preventive vaccine is the best long-term hope to 
bring the HIV/AIDS epidemic under control. Though there are many 
clinical trial studies being conducted for HIV/AIDS vaccine, there is 
no such vaccine approved for use yet.
    This invention described peptide constructs that may be of clinical 
importance in HIV/AIDS vaccine development. A vaccine for the 
prevention and/or treatment of HIV infection would ideally elicit a 
response in a broad range of the population. It would also have the 
capability of inducing high titered neutralizing antibodies, cytotoxic 
T lymphocytes, and helper T cells specific for HIV-1 gp160 envelope 
protein. A vaccine based on the synthetic or recombinant peptides has 
been developed which elicits these responses while avoiding the 
potential safety risks of live or killed viruses. Unlike previously 
developed vaccines, this invention avoids those regions of gp 160 which 
may contribute to acceleration of infection or the development of 
immune deficiency. Peptides having high activity in the eliciting of a 
cytotoxic T lymphocyte response to the HIV-1 envelope glycoprotein 
gp160 are described. The activation of 12-15 residue peptides by 
proteolytic degradation to shorter peptides is shown as are general 
techniques for characterizing such activation processes. The peptide 
described is recognized by both human and murine cytotoxic T 
lymphocytes, and is immunodominant in H-2d mice such as BALB/c, B10.D2, 
DBA/2, etc. This makes it ideal for determining responses in animal 
models preclinically before use in human trials. It is also ideal for 
detecting cytotoxic T lymphocyte responses to HIV envelope in these 
strains of mice.

Multideterminant Peptides That Elicit Helper T-Lymphocyte Cytotoxic T-
Lymphocyte and Neutralizing Antibody Responses Against HIV-1

Jay A. Berzofsky et al. (NCI)
U.S. Patent No. 6,294,322 issued 25 Sep 2001 (HHS Reference No. E-152-
1991/1-US-01).
Licensing Contact: Robert M. Joynes, J.D.; 301/594-6565; 
[email protected].
    According to a new annual report from the WHO, an estimated 40.3 
million people worldwide are currently living with HIV infection, and 
more than three million people died of AIDS-related illnesses in 2005. 
Despite intensive efforts to improve antiretroviral treatment, a safe 
and effective HIV preventive vaccine is the best long-term hope to 
bring the HIV/AIDS epidemic under control. Though there are many 
clinical trial studies being conducted for HIV/AIDS vaccine, there is 
no such vaccine approved for use yet.
    This invention described peptide constructs that may be of clinical 
importance in HIV/AIDS vaccine development. A vaccine for the 
prevention and/or treatment of HIV infection would ideally elicit a 
response in a broad range of the population. It would also have the 
capability of inducing high titered neutralizing antibodies, cytotoxic 
T lymphocytes, and helper T cells specific for HIV-1 gp 160 envelope 
protein. A vaccine based on synthetic or recombinant peptides has been 
developed which elicits these responses while avoiding the potential 
safety risks of live or killed viruses. Unlike previously developed 
vaccines this invention avoids those regions of gp 160 which may 
contribute to acceleration of infection or the development of immune 
deficiency. This invention provides peptides up to 44 amino acid 
residues long that stimulate helper T-cell response to HIV in a range 
of human subjects. Six multideterminant regions have been identified in 
which overlapping peptides are recognized by mice of either three or 
all four MHC types. Four of the six regions have sequences relatively 
conserved among HIV-I isolates. These multideterminant cluster peptides 
are recognized by T cells from humans of multiple HLA types, and have 
been found in a phase I clinical trial to elicit neutralizing 
antibodies, cytotoxic T cells, and helper T cells in at least some of 
the human subjects. These peptides are currently being

[[Page 6508]]

tested in primates. Once delivery systems and a stronger mucosal 
response are induced, NCI plans to use these peptides in human clinical 
trials.

    Dated: January 30, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E6-1653 Filed 2-7-06; 8:45 am]
BILLING CODE 4140-01-P