FR Doc E6-1653


[Federal Register: February 8, 2006 (Volume 71, Number 26)]
[Notices]
[Page 6506-6508]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08fe06-115]

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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; 
pipiag@mail.nih.gov.


    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; 
hus@mail.nih.gov.


    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; 
pipiag@mail.nih.gov.


    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 (Lipitor^TM), lovastatin (Mevacor^TM),
and simvastatin (Zocor^TM). 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; 
joynesr@mail.nih.gov.


    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; 
joynesr@mail.nih.gov.

    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