[Federal Register Volume 65, Number 245 (Wednesday, December 20, 2000)]
[Notices]
[Pages 79869-79870]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-32366]


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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 contacting Vasant Gandhi, 
J.D., Ph.D., at the Office of Technology Transfer, National Institutes 
of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 
20852-3804; telephone: 301/496-7056 ext. 224; fax: 301/402-0220; e-
mail: [email protected]. A signed Confidential Disclosure Agreement 
will be required to receive copies of the patent applications.

Human Erythropoietin Receptor Transgenic Mice

Constance T. Noguchi (NIDDK)
DHHS Reference No. E-272-00/0

    The inventors have developed a transgenic mouse which expresses the 
human erythropoietin receptor. Erythropoietin is a cytokine or hormone 
required for the production of red blood cells and acts by binding on 
early, undifferentiated blood progenitor cells to stimulate red blood 
cell formation. The model is particularly useful as human infectious 
agents or gene therapy vectors that selectively target human cells 
expressing the erythropoietin receptor can be studied.
    Background scientific detail may be found in Liu, C., Liu, Z.Y., 
Shen, K. and Noguchi, C. T. (1997), ``Regulated human erythropoietin 
receptor expression in mouse brain'', J. Biol. Chem. 272:32395-32400.

Antitumor Immunity Elicited by Defensin-Tumor Antigen Fusions

Arya Biragyn, Larry W. Kwak (NCI)
DHHS Reference No. E-196-00/0 filed 15 Sep 2000

    Tumor antigens are known to be poorly immunogenic and attempts to 
elicit immune responses against the epitopes of antigens specific to 
tumor cells have been largely unsuccessful. The inventors have 
developed a cancer vaccine comprising a defensin fused to a tumor 
antigen or viral antigen to enhance the immunogenicity of the tumor 
antigen or viral antigen. The inventors have demonstrated, with animal 
data, that chimeric proteins, comprising a defensin fused to a model 
tumor antigen (lymphoma-derived single-chain Fv), when administered to 
a subject, generate a measurable humoral and anti-tumor cellular immune 
response.

Methods and Compositions of Viral Chemokine-Antigen Fusion Proteins 
as Vaccines for Tumors and AIDS

Arya Biragyn, Larry W. Kwak (NCI)
DHHS Reference No. E-194-00/0 filed 15 Sep 2000

    Tumor antigens are known to be poorly immunogenic and attempts to 
elicit immune responses against the epitopes of antigens specific to 
tumor cells have been largely unsuccessful. The inventors have 
developed a cancer vaccine comprising a tumor antigen fused with a 
human chemokine or viral antigen to enhance the immunogenicity of the 
tumor antigen or viral antigen. The inventors have demonstrated, with 
animal data, that chimeric proteins, comprising a viral chemokine fused 
to a model tumor antigen (lymphoma-derived single-chain Fv), when 
administered to a subject, generate a measurable humoral and anti-tumor 
cellular immune response.

HCDS1 Kinase Activates Breast Tumor Suppressor BRCA1 and Promotes 
DNA Damage Repair

Jay H. Chung (NHLBI)
DHHS Reference No. E-192-00/0 filed 06 Jul 2000


    BRCA1 plays an important role in the cellular response to DNA 
damage. The technology relates to the development of BRCA1 serine 988 
mutants and a method to modulate BRCA1 activity. For example, one 
mutant interferes with normal BRCA1 function and may thereby increase 
sensitivity of tumor cells to chemotherapeutic agents. Another mutant 
shows constitutive activity in the absence of cell cycle checkpoint 
enzyme hCds1 activation and may thereby increase the resistance of 
normal tissue to genotoxic agents such as ionizing radiation.

Specific Binding Agents for KSHV vIL-6 that Neutralize a Biological 
Activity

Yoshiyasu Aoki, Giovanna Tosato (NCI)
DHHS Reference No. E-180-00/0 filed 31 Jul 2000

    This invention relates to the field of herpesviruses, more 
specifically to human herpesvirus 8 (HHV-8), also known as Kaposi's 
sarcoma associated herpesvirus (KSHV), and to agents that bind the 
viral IL-6 encoded by this virus. KSHV encodes various proteins that 
have features suggesting their role in promoting cellular growth and 
transformation, including viral homologues of cyclin D, G-protein 
coupled receptor, interferon regulatory factor, macrophage inflammatory 
proteins and IL-6. All these viral proteins display structural 
similarities to their cellular counterparts. The inventors have 
developed a specific binding agent for KSHV interleukin-6 (vIL-6), 
which neutralizes vIL-6 activity.

[[Page 79870]]

Utilization of Non-Viral Sequences for Minus-Strand DNA Transfer 
and Gene Reconstitution

Wei-Shau Hu, Vinay K. Pathak (NCI)
DHHS Reference No. E-134-00/0 filed 19 May 2000

    This technology relates to novel retroviral vectors for the 
introduction of heterologous nucleic acid into a host cell. Integration 
of these vectors into the nucleic acid of a host cell results in 
reconstitution and duplication of the heterologous nucleic acid in the 
cellular genome. The invention describes a method to efficiently 
reconstitute genes during virus replication. Vectors have been 
developed that enable gene reconstitution, by including two halves of a 
gene, each half having a small region of homology. The 3' half of the 
gene is inserted into the 5' terminal repeat, before the ``R'' region, 
and the 5' half of the gene is inserted into the 3' terminal repeat, 
between the ``U3'' region and the ``R'' region. Upon transfer into a 
cell and viral integration into the genome, two complete copies of the 
gene are reconstituted (gene duplication), one in the 5' long terminal 
repeat (LTR) and one in the 3' LTR. The virus can be used to transfer 
two copies of genes, such as toxic genes, into a desired cell 
population, or can be used to detect the presence of competent 
retroviruses (as a detection system). This technique can be utilized 
for delivery of toxic genes for cancer gene therapy or for high-
sensitivity detection of replication-competent retroviruses during 
propagation of viral stocks.

Gadd45a-Null Mice (45C Clone) and Cells Derived from Them

MC Hollander, MS Sheikh, D Bulavin, LA Henmueller (NCI)
DHHS Reference No. E-129-00/0

    This technology relates to the creation of a mouse cell line that 
harbor homozygous deletions of the Gadd45 gene. Gadd45 was the first 
gene discovered to be controlled by another gene, p53, the most highly 
mutated gene in human cancer. Cells lacking Gadd45 are less able to 
deal with DNA damage and are prone to alternations in genomic 
integrity. Both of these attributes are critical for the prevention of 
cancer. Gadd45 null mice have a high frequency of parturition failure.
    The mice can be used to investigate the effect that the 
aforementioned attributes have a cell growth and integrity and 
carcinogenesis. As the Gadd45a-null nice show defects in cell cycle 
control and DNA repair, they will be useful in toxicology and drug 
screening. For pharmaceutical studies using chemical libraries, these 
mice and their derived cells may be useful in identifying inhibitors of 
specific molecular pathways. Also, the mice will be a useful model for 
studying delivery failure and cervical dilation.

Usage of Two Yeast Strains in the Identification of Specific 
Inhibitors of Polo Kinases

Kyung S. Lee, Sukgil Song (NCI)
DHHS reference No. E-100-00/0 filed 23 May 2000

    This technology relates to the usage of two yeast strains in the 
identification of specific inhibitors of polo kinases. Polo kinases are 
characterized by the presence of a distinct region of homology in the 
non-catalytic C-terminal domain termed the ``polo-box''. The polo 
subfamily of protein kinases appears to play a critical role in cell 
proliferation and cell division. The polo-box domain of mammalian polo 
kinase, Plk, and the budding yeast functional homolog, Cdc5, are 
essential for their subcellular localization and functions. The two 
yeast mutants can be used to screen for inhibitors of polo-box 
function.

A Transgenic Mouse Model for Tetracycline Regulated Gene Expression 
in the Mouse Epidermis

Adam B. Glick (NCI)
DHHS Reference No. E-226-99/0

    This technology related to the creation of several transgenic mouse 
lines that will produce conditional overexpression of foreign genes in 
the mouse epidermis. Foreign genes are frequently expressed in mice to 
create models of human disease by using a promoter or regulatory region 
that is tissue specific. In previous models expression of the target 
gene is always on. In these new models expression is conditional such 
that timing and level of expression can be completely controlled by the 
investigator. The inventor has taken advantage of the bigenic 
tetracycline regulatory system first described by Grossen and Bujard to 
create the present transgenic mouse lines. The system utilizes two 
transgenic lines that are then bred together to create a double 
transgenic mouse. One transgenic line expresses the tetracycline 
regulated transcriptional transactivator tTA or rTA linked to keratin 5 
(K5) promoter. These transgenic lines have been designated K5/tTA and 
K5/rTA. The K5 promoter is expressed in the epidermis hair follicles 
and several other squamous epithelia such as tongue trachea and 
forestomach. The second transgenic line carries the target gene linked 
to the tetO binding sites for the tTA or rTA proteins. In double 
transgenic mice, the tTA binds to the tetO sequence and causes high 
levels of expression of the target gene. However, the ability of the 
tTA to bind to DNA is prevented by the antibiotic tetracycline. If 
animals are maintained on tetracycline in the drinking water or fed, 
the expression of the target gene is suppressed; upon removal of the 
antibiotic, gene expression is induced. In contrast tetracyclines are 
required to induce expression of the target by the rTA. The ability of 
this bigenic system to suppress expression of the target gene is 
crucial for a functional analysis of genes which produce an embryonic 
or neonatal lethal phenotype when expressed at high levels during 
gestation. In addition, different levels of gene expression can be 
achieved through titration of the tetracycline dose. Studies in the 
inventor's laboratory has confirmed that the K5/tTA and rTA can 
transactivate expression of target genes in the epidermis at high 
levels, uniformly throughout the tissue, and that transactivation is 
tightly controlled by tetracycline analogues. The mouse epidermis is a 
useful system for modeling for human fibrotic and blistering skin 
diseases, dissecting the critical factors in would healing and 
multistage carcinogenesis in lining epithelia. This conditional 
expression system should greatly enhance the ability to assess function 
of specific target genes in these processes, and to create useful in 
vivo models for the development of novel therapeutics.

    Dated: December 12, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-32366 Filed 12-19-00; 8:45 am]
BILLING CODE 4140-01-P