[Federal Register Volume 61, Number 77 (Friday, April 19, 1996)]
[Notices]
[Pages 17311-17314]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-9615]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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    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

[[Page 17312]]

commercialization of results of federally funded research and 
development. Foreign patent applications are filed on selected 
inventions to extend market coverage for U.S. 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 301/496-7075; fax 301/402-0220). A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

A Gene Encoding a Human Reduced Folate Carrier (RFC) and Methods for 
the Treatment of Methotrexate-Resistant, Transport-Deficient Cancer 
Cells

Moscow, J., Cowan, K.H., He, R. (NCI)
Filed 7 Jun 95
Serial Nos. 08/484,840 and 08/483,094
Licensing Contact: Allan Kiang, 301/496-7735 ext 270

    Methotrexate (MTX), a folate agonist that inhibits the cellular 
enzyme dihydrofolate reductase, is effective for the treatment of 
several types of cancer including non-Hodgkin's lymphoma, childhood 
acute lymphoblastic leukemia, osteosarcoma, and breast cancer. A major 
drawback of MTX therapy, however, is that previously responsible tumor 
cells may become resistant to MTX after continued exposure. Increased 
expression of the reduced folate carrier (RFC) protein can restore 
sensitivity to MTX. This intention embodies methods to treat various 
forms of cancer that have become resistant to MTX by increasing 
expression of RFC protein in tumor cells via gene therapy, thereby 
restoring MTX sensitivity. Methods for determining the level of RFC 
expression, employing antibodies or specific nucleic acid probes, are 
also described. (portfolio: Cancer--Therapeutics, conventional 
chemotherapy, other)

Hepatocellular Carcinoma Oncogene

Yang, S.S. (NCI)
Filed 6 Jun 95
Serial No. 08/471,540 [DIV of 08/324,445 which is FWC of 07/575,524 
(Aban) which is CIP of 07/451,953 (Aban in favor of FWC 07/774,156, 
which issued as U.S. Patent No. 5,403,926 4 Apr 95)]
Licensing Contact: Ken Hemby, 301/496-7735 ext 265

    Hepatocellular carcinoma is a liver cancer which has high levels of 
incidence in Asian populations, e.g., China, Korea. Incidence of 
hepatocellular carcinoma is greater among chronic carriers of 
hepatitis. A transforming sequence or oncoprotein, hhcM has been 
identified which is the amplified gene expression product of hepatoma. 
Antibodies to the hhcM product or the cDNA itself can be used for 
diagnostic, therapeutic, and screening tests. They may also be used as 
research tools in studying hepatocellular carcinoma. (portfolio: 
Cancer--Diagnostics; Cancer--Research Reagents)

Antiproliferative Protein

Nuell, M.J., McClung, J.K., Danner, D.B., Stuart, D. (NIA)
Filed 5 June 95
Serial No. 08/466,762 (CON of 07/612,674)
Licensing Contact: Ken Hemby, 301/496-7056 ext 265

    Controlled division is central to proper cellular function. 
Inability to regulate cell division can lead to uncontrolled growth, 
such as cancer, or cell death, apoptosis. Cellular proteins that are 
involved in inhibiting tumor growth, the tumor suppressor genes, have 
been identified. A second class of negative regulatory genes that when 
mutated lead to cell death also exist. This invention embodies a 
member, prohibition, of this second class of genes. Prohibition may be 
useful for the treatment of unregulated cell growth, cancer. In 
addition, inactivation of the prohibition gene or its product may be 
useful for conditions characterized by insufficient cellular 
proliferation, such as osteoporosis, fragile skin, and poor wound 
healing. (portfolio: Cancer--Therapeutics)

Method for Treatment of Kaposi's Sarcoma (KS) by Antisense 
Olingonucleotides

Ensoli, B., Gallo, R.C. (NCI)
Filed 5 Jun 95
Serial No. 08/463,978 (DIV of 08/072,575)
Licensing Contact: Cindy K. Fuchs, 301/496-7735 ext 232

    A novel method of blocking the growth of Kaposi's Sarcoma (KS) 
lesions using antisense oligonucleotides has been developed. This 
method offers a means to significantly improve the treatment of this 
condition. KS is a proliferation disease of vascular origin frequently 
seen in patients infected with the human immunodeficiency virus type-I 
(HIV-I), the etiologic agent of acquired immunodeficiency syndrome 
(AIDS). It typically occurs as lesions in the skin and, in more 
advanced stages, the lesions appear as multiple purplish to brown 
subcutaneous plaques or nodules. Supernatants from AIDS-KS derived 
(AIDS-KS) cells have been shown to induce normal endothelial cells to 
proliferate, degrade and cross the membrane basement, following by 
migration and organization into tube-like structures. These are the 
same events that are required for the formation of new blood vessels, 
or angiogenesis. Furthermore, molecular analysis of the factors 
produced by AIDS-KS cells revealed that, in particular, mRNA encoding 
basic fibroblast growth factor (bFGF) is expressed in relatively high 
quantities and bFGF is indeed responsible for the growth and 
proliferation of AIDS-KS cells. A number of unique antisense 
oligonucleotides with high binding affinity for bFGF mRNA are provided 
which effectively inhibit the progression of AIDS-KS cells in patients. 
This invention includes a method for administering the treatment as 
well as for monitoring the progress of KS in a patient. (portfolio: 
Gene-Based Therapies--Therapeutics, oligonucleotide-base therapies, 
antisense; Infectious Diseases--Therapeutics, antivirals, AIDS)

Human-Derived Monocyte Attracting Purified Protein Product Useful in a 
Method of Treating Infection and Neoplasms in a Human Body, and the 
Cloning of a Full-Length cDNA Thereof

Yoshimura, T., Robinson, E.A., Appella, E., Leonard, E.J. (NCI)
Filed 24 May 95
Serial No. 08/449,552 (DIV of 07/686,264, CON of 07/304,234)
Licensing Contact: Jaconda Wagner, 301/496-7735 ext 284

    A novel class of human-derived peptide products offers an important 
new tool for the treatment of a variety of infections and neoplasms in 
the human body. Macrophages, which are derived from monocytes, play a 
central role in human immune response and defense against infection. 
Previously, no pure human leukocyte-derived monocyte-attracting 
substance has been isolated. These newly isolated peptide products, 
which exhibit potent monocyte chemotactic activity, may be helpful in 
enhancing immune response to a variety of infections as well as 
cancers. (portfolio: Cancer--Therapeutics)

Retrovirus Vectors Derived From Avian Sarcoma Leukosis Viruses 
Permitting Transfer of Genes Into Mammalian Cells and Therapeutic Uses 
Thereof

Barsov, E., Hughes, S.H. (NCI)
Filed 22 may 95

[[Page 17313]]

Serial No. 08/445,462
Licensing Contact: Larry Tiffany, 301/496-7056 ext 206

    For sensitive applications (like human gene therapy) it has been 
relatively difficult to develop high titer defective retroviral vector 
stocks that are routinely and reliably free of recombinant replication 
competent virus. The new invention, which is based on an avian leukosis 
virus (ALV) vector, addresses this issue. The new ALV vector has an 
envelope gene derived from a mammalian retrovirus. The new vector is 
replication competent in avian cells, so that high titer viral stocks 
can be prepared simply and rapidly. Although the new vector can 
efficiently infect mammalian cells, including human cells, the vector 
is constitutively replication defective in mammalian cells. Since these 
vectors are incapable of replicating in mammalian cells, they should be 
safe for a number of sensitive applications, including human gene 
therapy. (portfolio: Gene-Based Therapies--Therapeutics, vectors, 
viral)

Human B Lymphotropic Virus (HBLV) Isolation and Products

Salahuddin, S.Z., Ablashi, D.V., Josephs, S.F., Saxinger, W.C.,
Wong-Staal, F., Gallo, R.C. (NCI)
Filed 22 Feb 95 (priority to 4 Aug 86)
Serial No. 08/392,674
Licensing Contact: George Keller, 301/496-7735 ext 246

    This invention concerns the isolation of a new human virus, 
originally called Human B Lymphotropic Virus (HBLV), now known as Human 
Herpes Virus Type 6 (HHV-6). HHV-6 causes the common childhood disease 
roseola. It has been linked to other diseases in persons in an immune 
deficient state, including those who are HIV infected. Recently it has 
been linked to multiple sclerosis. The claims cover the virus itself, 
nucleic acid sequences from the virus and proteins they encode, cell 
cultures infected with the virus, and detection of the virus by DNA 
hybridization and immunoassay means. The application was foreign filed, 
PCT/US87/01815, and has been granted in Europe. (portfolio: Infectious 
Diseases--Diagnostics, viral; Infectious Diseases--Vaccines, viral; 
Infectious Diseases--Reagents)

Bistriazenes As Chemotherapeutic Agents

Michejda, C., Blumenstein, J. (NCI)
Filed 12 Sep 94
Serial No. 08/302,480 [CON of 07/786,001, which is CIP of 07/527,915 
(both Aban); also related to 08/082,902 filed 28 Jun 93, which is a FWC 
of 07/527,915]
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    The bistriazenes are novel alkylating agents which are structurally 
similar to polyamines, e.g., spermine, which interact with DNA. Most 
currently employed chemotherapeutic alkylating agents interact with 
DNA, after which a crosslinking reaction may occur. The bistriazene 
compounds appear to interact with the DNA, while maintaining structural 
integrity, only to subsequently decompose on the surface of DNA forming 
a highly reactive species capable of multi-strand breaks and 
interstrand crosslinks. This reactivity can be modulated depending on 
chemical modifications to the bistriazene molecule. These drugs are 
highly cytotoxic, but their chemical reactivity can be modulated in a 
highly predictable way. Thus, the bistriazene compounds of this 
invention represent an entirely novel class of chemotherapeutic 
alkylating agents, which hold promise for greater specificity and lower 
toxicity compared to other alkylating agents. (portfolio: Cancer--
Therapeutics, vaccines)

Substituted O\6\-Benzylguanines and 6(4)-Benzyloxypyrimidines

Moschel, R.C., Pegg, A.E., Dolan, M.E., Chae,M-Y. (NCI)
Filed 1 Aug 94
Serial No. 08/283,953
Licensing Contact: Joseph Contrera, 301/496-7056, ext 244

    Inactivation of the human DNA repair protein, O\6\-alkylguanine-DNA 
alkyltransferase leads to a dramatic enhancement in the cytotoxic 
response of human tumor cells and tumor xenografts to chlorethylating 
antitumor drugs. This invention embodies a series of compounds that 
effectively inactivate the alkyltransferase protein. In addition, the 
claims of this invention provide methods to enhance the 
chemotherapeutic treatment of tumor cells by treatment with 
substitutedO\6\-benzylguanines and 6(4)-benzyloxypyrimidine 
derivatives. Invention is co-owned with The University of Illinois at 
Chicago and Pennsylvania State University. (portfolio: Cancer--
Therapeutics, conventional chemotherapy, alkylating agents; Cancer--
Therapeutics, conventional chemotherapy, other)

O\6\-Substituted Guanine Compositions, and Methods for Depleting 
O\6\-Alkylguanine-DNA Alkyltransferase

Moschel, R.C. (NCI), Dolan, M.E. (Univ. Chicago), Pegg, A.E. (Penn 
State)
Filed 7 June 94
Serial No. 08/255,190 (CIP of 07/875,438, CIP of 07/805,634, DIV of 07/
492,468)
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    NCI researchers have developed a number of unique derivatives of 
the purine base, guanine base, guanine, which are particularly useful 
for increasing the anticancer effects of a wide variety of 
chemotherapeutic agents. Chemotherapeutic alkylating agents (e.g., 
chlorethylating nitrosoureas) have some clinical utility against a 
number of neoplasms but in general have only limited effectiveness in 
killing tumor cells. This resistance of tumors to the effects of 
alkylating agents is due in part to the activity of the DNA repair 
protein, 0\6\-alkylguanine-DNA alkyltransferase (AGT), which repairs 
alkylation damage to the O\6\ position of DNA guanine residues. A 
number of O\6\-benzylguanine derivatives have been shown to be 
effective in depleting AGT. This invention provides additional O\6\-
benzylguanine compositions which have been shown effective in reducing 
AGT levels in tumor cell cultures and in enhancing the effectiveness of 
alkylating agents in tumor-bearing mice. These compounds can be 
administered with any chemotherapeutic agents with a mechanism of 
action that involves modification of the O\6\ position of DNA quanine 
residues. (portfolio: Cancer--Therapeutics, conventional chemotherapy, 
alkylating agents; Cancer--Therapeutics, conventional chemotherapy, 
other)

ERBB2 Promoter Binding Protein in Neoplastic Disease

Raziuddin and Sarkar, F. (NCI)
Filed 19 Apr 94
Serial No. 08/229,515
Licensing Contact: Susan Rucker, 301/496-7735 ext 245

    Isolation of a novel ERBB2 promoter binding protein offers to 
improve the diagnosis and, specifically, the detection and monitoring 
of neoplastic diseases. This invention has particular application for 
the early detection of breast cancer. The HER-2/neu (ERBB2/c-erbB-2), 
or ERBB2, gene sequence appears to be one of the primary genes 
responsible for the transition of normal epithelial cells toward 
carcinoma and the subsequent development of invasive and metastatic 
cancer. For women, early detection of breast cancer is crucial for 
survival; however, by the time the gene product of ERBB2 is measurable 
by current methods, the prognosis of patients is not good. This 
invention improves on earlier methods for

[[Page 17314]]

detecting and treating breast cancer by providing a purified and 
isolated DNA binding protein that specifically binds to the promoter 
region of the c-ERBB2 (HER-2/neu) gene sequence (hence the term HER-2 
promoter binding protein, HPBF). Antibodies specific for this DNA 
binding protein, called HPBF, can be used to assay for the presence of 
HPBF in a biological sample and, thus, detect the presence of cancer. 
The purified HPBF also can be used to test the ability of substances to 
inhibit the activity of HPBF and thus potentially halt or reverse 
growth of the cancer. This invention includes antisense nucleotides 
that effectively prevent HPBF from binding to the promoter. (portfolio: 
Cancer--Therapeutics, biological response modifiers, growth factors)

Acridone-Derived Bisintercalators as Chemotherapeutic Agents

Michejda, C.J., Cholody, W.M. Hernandez, L. (NCI)
Filed 14 Mar 94
Serial No. 08/213,315
Licensing Contact: Joseph Contrera, 301/496-7056 ext 244

    This invention describes a noval class of acridone-derived 
intercalating agents that offer to improve the treatment of certain 
cancers. Presently available anti-tumor agents often have great 
toxicity for normal cells as well as tumor cells. Therefore, there is a 
great need for new chemotherapeutic agents that selectively kill tumor 
cells while sparing healthy cells. A number of acridine-based compounds 
have recently been discovered that exhibit high anti-tumor activity. 
This newly developed class of acridone-derived agents, which bind 
strongly to nucleic acids, have potent cytotoxic activity which is 
selective for solid tumor cells, especially for colon and prostatic 
tumors. Because some of these compounds exhibit enhanced fluorescence 
when bound to DNA, they also may be used in assays for the detection of 
DNA. (portfolio: Cancer--Therapeutics)

    Dated: April 11, 1996.
Barbara M. McGarey,
Office of Technology Transfer.
[FR Doc. 96-9615 Filed 4-18-96; 8:45 am]
BILLING CODE 4140-01-M