[Federal Register Volume 69, Number 33 (Thursday, February 19, 2004)]
[Notices]
[Pages 7764-7765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3526]



[[Page 7764]]

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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 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.

2-Amino-O4-Substituted Pteridines and Their Use as 
Inactivators of O6-Alkylguanine-DNA Alkyltransferase

Robert C. Moschel et al. (NCI)
DHHS Reference No. E-274-2003/0-US-01 filed 06 Jan 2004
Licensing Contact: George Pipia; 301/435-5560; [email protected]

    This invention is directed to 2-amino-O4-benzylpteridine 
derivatives targeted for use in cancer treatment in combination with 
chemotherapeutic agents such as 1,3-bis(2-chloroethyl)-1-nitrosurea 
(BCNU) or temozolomide. The derivatives of the present invention 
inactivate the O6-alkylguanine-DNA-alkyltransferase repair 
protein and thus enhance activity of such chemotherapeutic agents. 
Examples of these derivatives have advantages over the earlier 
O6-benzylguanine compounds from this research group. Some 
compounds of the current invention are more water soluble compared to 
O6-benzylguanine and they exhibit greater specificity for 
inactivating O6-alkylguanine-DNA-alkyltransferase in certain 
tumor cells, compared to normal cells.

Interference With c-maf Function in Multiple Myeloma Retards Tumor 
Adherence and Progression and Decreases Expression of Integrin [beta]7, 
C-C Chemokine Receptor 1, and Cyclin D2

Louis Staudt et al. (NCI)
DHHS Reference No. E-173-2003/0-PCT-01 filed 17 Oct 2003
Licensing Contact: Catherine Joyce; 301/435-5031; e-mail: 
[email protected]

    Multiple myeloma (MM) is an incurable malignancy of the plasma cell 
that accounts for 20% of all hematologic malignancies. It has been 
shown that there are recurrent genetic lesions associated with the 
disease. One of the recurrent lesions, occurring in approximately 5-10% 
of the cases, is a translocation involving the c-maf gene which results 
in overexpression of the c-maf gene.
    Unexpectedly, the inventors have found that overexpression of the 
c-maf gene is more frequent than the occurrence of the genetic lesion, 
with approximately 50% of MM samples showing overexpression of c-maf. 
Additionally, the inventors have shown that the interference with c-maf 
function markedly decreases expression of integrin [beta]7, C-C 
chemokine receptor1, and cyclin D2. The inventors have also 
demonstrated that decreased expression of integrin [beta]7 markedly 
decreases the ability of tumor cells to bind to bone marrow stroma and 
that the proliferation of myeloma cells was slowed significantly by the 
inhibition of c-maf expression. Therefore, c-maf appears to play a 
central role in regulating the proliferation and survival of tumor 
cells in MM.
    The above-mentioned invention is available for licensing on an 
exclusive or a non-exclusive basis.

Glioma-Selective Polypeptides, Alone or Coupled to a Therapeutic/
Diagnostic Agent, Compositions Comprising Same, and Uses Thereof

Howard A. Fine (NCI), Benjamin Purow (CC)
U.S. Provisional Application No. 60/509,737 filed 08 Oct 2003 (DHHS 
Reference No. E-244-2002/0-US-01)
Licensing Contact: Matthew Kiser; 301/435-5236; [email protected]

    Primary brain tumors are an important cause of cancer mortality in 
the U.S., representing the leading cause of cancer-related death in 
children and the fourth leading cause of cancer-related death in young 
adults. Progress in the treatment of these tumors has been slow, since 
the demonstration of more than 20 years ago that fractionated 
radiotherapy could significantly extend survival. Although improved 
neurosurgical techniques have lessened the morbidity of extensive 
resections, the impact of such procedures on the overall survival of 
patients with the most malignant gliomas remains modest, at best, given 
the diffuse infiltrative nature of the tumor. Chemotherapy recently has 
been demonstrated to have some activity for specific subtypes of 
malignant gliomas, such as oligodendrogliomas and anaplastic 
astrocytomas. The effectiveness, however, of standard chemotherapy for 
the most common and malignant of the gliomas, glioblastoma, is marginal 
at best. Clearly, novel therapeutic approaches and novel drug targets 
are needed. In view of the foregoing, it is an object of the present 
invention to provide new agents and compositions that can be used in 
the diagnosis and treatment of glioma. This and other objects and 
advantages of the present invention, as well as additional inventive 
features, will be apparent from the detailed description provided in 
the patent application.
    The present invention relates to glioma-selective polypeptides, 
which can be used alone or coupled to a therapeutic or diagnostic 
agent, in the diagnosis and therapy of glioma. Also provided by the 
present invention is a composition comprising the above-described 
polypeptide, desirably coupled to a diagnostic agent or a therapeutic 
agent, and a carrier.
    Additionally, a method of diagnosing glioma in an animal is 
provided. The method comprises administering to the animal a 
polypeptide coupled to a diagnostic agent as described above, or a 
composition comprising same and a carrier therefore, and assaying for 
the presence of the diagnostic agent in the central nervous system 
(CNS). The presence of the diagnostic agent in the CNS is indicative of 
the presence of glioma in the animal.
    A method of inhibiting the proliferation of a glioma cell in an 
animal having a glioma is also provided. The method comprises 
administering to the animal in an amount sufficient to inhibit the 
proliferation of the glioma cell in the animal a polypeptide coupled to 
a therapeutic agent as described above, or a composition comprising the 
same and a carrier, whereupon the proliferation of the glioma cell in 
the animal is inhibited.

Brother of the Regulator of Imprinted Sites (BORIS)

Victor Lobanenkov et al. (NIAID)
U.S. Provisional Application No. 60/358,889 filed 22 Feb 2002 (DHHS 
Reference No. E-227-2001/0-US-01);

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PCT Application No. PCT/US03/05186 filed 21 Feb 2003 (DHHS Reference 
No. E-227-2001/0-PCT-02)
    Licensing Contact: Matthew Kiser; 301/435-5236; [email protected]

    The subject application discloses an isolated or purified nucleic 
acid molecule consisting essentially of a nucleotide sequence encoding 
a human or a non-human BORIS, or a fragment of either of the foregoing; 
an isolated or purified nucleic acid molecule consisting essentially of 
a nucleotide sequence that is complementary to a nucleotide sequence 
encoding a human or a non-human BORIS, or a fragment of either of the 
following; a vector comprising such an isolated or purified polypeptide 
molecule consisting essentially of an amino acid sequence encoding a 
human or a non-human BORIS, or a fragment or either of the foregoing; a 
cell line that produces a monoclonal antibody that is specific for an 
aforementioned isolated or purified polypeptide molecule; and the 
monoclonal antibody produced by the cell line; methods of diagnosing a 
cancer or a predisposition to a cancer in a male or female mammal; a 
method of prognosticating a cancer in a mammal; a method of assessing 
the effectiveness of treatment of a cancer in a mammal; a method of 
treating a mammal prophylactically or therapeutically for a cancer; and 
a composition comprising a carrier and an inhibitor of BORIS.

Use of IL-13 Inhibitors To Prevent Tumor Recurrence

Jay Berzofsky et al. (NCI).
PCT Application No. PCT/US01/51339 filed 22 Oct 2001 (DHHS Reference 
No. E-037-2001/1-PCT-02).
Licensing Contact: Catherine Joyce; 301/435-5031; e-mail: 
[email protected]

    This invention relates to the discovery of a role for IL-13 in the 
down-regulation of tumor immunosurveillance. Using a mouse model in 
which tumors show a growth-regression-recurrence pattern, the 
mechanisms for down-regulation of cytotoxic T lymphocyte-mediated tumor 
immunosurveillance was investigated. It was discovered that interleukin 
4 receptor (IL-4R) knockout mice, and downstream signal transducer and 
activator of transcription 6 (STAT6) knockout mice, but not IL-4 
knockout mice, resisted tumor recurrence. Thus, IL-13, the only other 
cytokine that uses the IL-4R-STAT6 pathway, was discovered to have a 
role in the down-regulation of tumor immunosurveillance. The use of an 
IL-13 inhibitor confirmed these results.
    Additionally, loss of natural killer T cells (NKT cells) in CD1 
knockout mice resulted in decreased IL-13 production and resistance to 
recurrence. Therefore, NKT cells and IL-13, possibly produced by NKT 
cells and signaling through the IL-4R-STAT6 pathway, are necessary for 
down-regulation of tumor immunosurveillance. Thus, the inventors have 
discovered a method of inhibiting tumor growth which comprises the 
administration of an IL-13 inhibitor. This invention is described in 
PCT application, PCT Publication No. WO 02/055100.
    This technology is available for licensing on a non-exclusive 
basis.

Interleukin-2 Stimulated T-Lymphocyte Cell Death for the Treatment of 
Autoimmune Diseases, Allergic Disorders and Graft Rejection

Michael J. Lenardo (NIAID).
U.S. Patent 6,083,503 issued 07 Jul 2000 (DHHS Reference No. E-137-
1991/0-US-03); U.S. Patent 5,989,546 issued 23 Nov 1999 (DHHS Reference 
No. E-137-1991/0-US-04).
Licensing Contact: Matthew Kiser; 301/435-5236; [email protected]

    T-cell apoptosis induced by administration of IL-2 and antigen 
offers an important new treatment for allergic disorders, which are due 
to the effects of antigen-activated T-cells. Antigen-activated T-cells 
cause the release of harmful lymphokines and the production of 
immunoglobulin E by B cells. Presently available methods for treating 
allergies have limitations because they are nonspecific in their action 
and have side effects and limited efficacy. IL-2 and antigen stimulates 
the programmed death of only antigen-specific T-cells while leaving the 
rest of the patient's T-cells and other immune cells intact. This 
invention is also useful in treating HIV. Both fields of use, allergies 
and HIV, are available for licensing.

Interleukin-4 Stimulated T-Lymphocyte Cell Death for the Treatment of 
Autoimmune Diseases, Allergic Disorders and Graft Rejection

Michael J. Lenardo, Stefen A. Boehme, Jeffrey Critchfield (NIAID).
U.S. Patent 5,935,575 issued 10 Aug 1999 (DHHS Reference No. E-151-
1992/0-US-11).
Licensing Contact: Matthew Kiser; 301/435-5236; [email protected]

    The discovery that interleukin-4 (IL-4) predisposes T lymphocytes 
to programmed cell death (apoptosis) allows for a novel method of 
therapeutic intervention in diseases caused by the action of IL-4-
responsive T cells. Specifically, the therapy induces the death of a 
subpopulation of T lymphocytes that are capable of causing disease. 
Current therapies may cause general death or suppression of immune 
responses involving T-cells, severely comprising a patient's immune 
system. This treatment affects only the subset of T cells that react 
with a specified antigen, thereby leaving a patients immune system 
uncompromised. This invention is useful in treating allergies and HIV 
complications. Both fields are available for licensing.

    Dated: February 9, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-3526 Filed 2-18-04; 8:45 am]
BILLING CODE 4140-01-P