[Federal Register Volume 63, Number 176 (Friday, September 11, 1998)]
[Notices]
[Pages 48738-48740]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24368]


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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 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.

LIF And Related Cytokines That Operate Through The gp130 Receptor 
Pathway As A Means To Enhancing Embryo Implantation In Mammals And 
As An Alternative To Using Estrogen

CL Stewart, T Shatzer, T Sullivan, JR Chen, L Hernandez (NCI)

DDHS Reference No. E-166-98/0 filed 06 Jul 98

Licensing Contact: Dennis Penn, 301/496-7056 ext. 211

    The present invention is directed to the use of Leukemia Inhibitory 
Factor (LIF), or certain other cytokines as a means for enhancing 
successful embryo implantation. This discovery may lead to increased 
success rates in normal embryonic development in human and non-human 
embryos following in vitro fertilization. The present invention, tested 
in LIF deficient mice, confirms that single injections of LIF lead to 
implantation and the embryo's normal development to birth. LIF may be 
useful as a replacement for estrogen in inducing embryo implantation. 
The invention indicates that LIF can substitute for estrogen in animal 
models, in regulating the receptibility of the uterus to the implanting 
embryo, and results in a significant increase in successful 
implantation. This technology has both human and veterinary 
applications.

Protection Of Neural Cells From Catecholamine-Induced Apoptosis By 
Macrophage Migration Inhibitory Factor (MIF)

G Wistow (NEI)

DDHS Reference No. E-028-98/0 filed 28 Jul 98

Licensing Contact: Stephen Finley, 301/496-7735 ext. 215

    Macrophage Migration Inhibitory Factor (MIF) was shown to have 
neuroprotective properties with important implications for conditions 
such as Parkinson's Disease (PD). MIF is widely distributed in 
mammalian tissues. However, in vivo studies show that while the levels 
of MIF expression significantly decrease with age in most tissues, 
including lens, liver and kidney, it is maintained at high levels in 
neural tissues, brain and retina. This suggests the possibility of an 
important role for MIF in aging neural tissues. It was also shown that 
MIF has catalytic enzyme activity towards the toxic 
quinonesdopaminechrome (DNC), epinephrinechrome (EC) and 
noreprinephrine (NEC) which arises by oxidation of the catecholamine 
neurotransmitters dopamine, epinephrine and norepinephrine. These 
catecholamines induce cell death by apoptosis in cultured neural cells 
and other cell types. It was shown that in cell culture, MIF can block 
this catecholamine-induced cell death. Death of catecholaminergic 
neurons is an important feature of PD in human brain. This suggests a 
physiological and/or therapeutic role for MIF in protection of neural 
and other cells from apoptosis induced by toxic quinones. Decreased 
levels of MIF in the aging brain may be a risk factor for PD and 
similar neurodegenerative disorders. MIF may also be involved in the 
synthesis of neuromelanin, which is prominent in the aging human 
substantia nigra, since the guinones DNC, EC and NEC are known 
neuromelanin precursors.
    A surprising additional property of MIF was also observed. Lens 
epithelial cell cultures differentiated into neuronlike cells, 
containing neuronal cell markers, axons, and processes, upon the 
constitutive expression of endogenous recombinant MIF. Thus, in 
addition to its neuroprotective properties, MIF has potential to 
contribute to culture methods for neural cells that may be useful in 
transplantation.

G-Protein Coupled Receptor Antagonists

N Tarasova, SJ Michejda (NCI)

Serial No. 60/076,105 filed 27 Feb 98

Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    This invention is a potentially broadly applicable method of 
disrupting the functioning of G-protein coupled receptors (GPCR). GPCRs 
are a large familly of receptors involved in the regulation of 
physiological activities. GPCRs have seven transmembrane regions, i.e. 
they cross the cell membrane seven times. The inventors have found that 
if a peptide consisting of one of the transmembrane regions of a GPCR 
with an added charged amino acid on the extracellular side, is brought 
into contact with a cell having the same GPCR, the functioning of the 
GPCR is disrupted. It is thought that the added peptide interferes with 
the correct assembly of the GPCR. Cells containing

[[Page 48739]]

the CXCR4 receptor, a co-receptor with CD4 for the entry of certain 
strains of HIV-1 into T-cells, are much less receptive to infection by 
HIV in the presence of a particular transmembrane peptide from the 
CXCR4 receptor. Therefore, this method of disrupting the functioning of 
particular GPCRs could be used to treat diseases which are mediated by 
functioning GPCRs, such as HIV.

Inhibition of HFG/SF Cleavage/Activation by Suramin and Other 
Related Small Molecules

C Webb, ME Jeffers, G Czerwinski, CJ Michejda,

GF Vande Woude (NCI)

Serial No. 60/075,994 filed 26 Feb 98

Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284

    HGF/SF, which is the ligand for the tyrosine kinase receptor 
encoded by the c-Met proto-oncogene, is involved in tumor 
establishment, progression and metastasis. HGF/SF is synthesized as a 
90 kDa single chain precursor polypeptide (pro-HGF/SF) which is devoid 
of biological activity. The critical step in HGF/SF activition is 
proteolytic cleavage generating an  heterodimer in which an 
 chain of 60 kDa and a  chain of 32-36 kDa are bound 
to one another by a disulfide bridge. The cleavage/activation of pro-
HGF/SF represents the initial stage of HGF/SF-met activation and 
provides a possible point for interference by potential inhibitors.
    This invention is based on the discovery that suramin and related 
polysulfonated compounds inhibit cleavage of pro-HGF/SF. The invention 
provides an efficient assay for identifying inhiitors of HGF/SF 
activation. The invention also describes suramin-like compounds that 
can be used to inhibit HGF/SF activation, thereby inhibiting tumor 
growth and metastasis. These compounds are less toxic than comparable 
molecules.

Vaccines For Blocking Transmission of Plasmodium vivax

DC Kaslow, T Tsuboi, M. Torii (NIAID)

Serial No. 60/067,596 filed 05 Dec 97

Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    This invention relates to novel methods and compositions for 
blocking transmission of Plasmodium vivax which cause malaria. In 
particular, Pvs25 and Pvs28 polypeptides, variants and fusion proteins 
thereof, are disclosed which, when administered to a susceptible 
organism, induce an immune response against a 25 kD and 28 kD protein, 
respectively, on the surface of Plasmodium vivax zygotes and ookinetes. 
This immune response in the susceptible organism can block transmission 
of malaria.

Stromal Cell Derived Factor-1 (SDF-1) And Method of Use For 
Diagnostic And Prognostic Indicator Or AIDS Pathogenesis

C. Winkler, S O' Brien (NCI)

Serial No. 60.063,832 filed 30 Oct 97

Licensing Contact: Carol Salata, 301/496-7735 ext. 232

    Stromal cell derived factor-1 (SDF-1) is the principal ligand for 
CXCR4 (a 7-transmembrane G/coupled receptor) which, with CD4, provides 
an entry port for T-tropic HIV-1, a variety that frequently develops in 
AIDS patients just prior to T-lymphocyte depletion. This invention is 
based on the discovery of a correlation between the presence of a 
mutation at one nucleotide position of the 3'untranslated region of the 
SDF1 gene and delayed progression to AIDS and death due to HIV 
infection. Based on this discovery, it is the object of the present 
invention to provide diagnostic and therapeutic approaches to treating 
HIV infection by diagnosing the mutation and down regulating the CXCR4 
receptor with native or synthetic SDF-1.

Recominant Adenoviral Targeting Vector

SE Spence, JR Keller, JS Smith (NCI)

Serial No. 60/061,587 filed 10 Oct 97

Licensing Contact: Elaine Gese, 301/496-7056 ext. 282

    The current invention embodies recombinant adenoviral vectors for 
use in targeted gene transfer. The method by which these vectors are 
generated involves no molecular modifications to the adenovirus genome, 
and allows for the production of vectors targeted specifically to 
virtually any cell line of choice. Specifically, the vectors are 
generated by directly linking biotin to the capsid of advenovirus 
particles. The particles are then treated with streptavidin and 
subsequently incubated with a biotinylated targeting moiety which is 
capable of recognizing a specific marker which is expressed on the 
surface of selected cells.
    The resulting adenoviral vectors would appear to be of value for 
use in gene transfer, and can be targeted to virtually any cell type of 
interest via incubation with a specific targeting moiety.
    To date, the inventors have demonstrated that these vectors can be 
specifically directed to target and infect hematopoietic cell lines 
which display the c-kit receptor, and are capable of achieving high 
levels of expression in these cell lines. Also, these vectors can be 
specifically directed to cell surface markers such as CD34, CD 44 and 
others through antibodies directly attached to the biotynilated 
adenoviral vectors. Such gene transfer may represent a potential means 
by which various diseases, including immunodeficiency diseases, blood 
cell disorders, AIDS, and various cancers, could be treated. Therefore, 
the current invention appears to represent a novel gene therapy 
approach upon which the development of specific therapies against a 
broad range of diseases may be based.

Recombinant Proteins of a Pakistani Strain of Hepatitis E and Their 
Use in Diagnostic Methods and Vaccines

SA Tsarev, SU Emerson, RH Purcell (NIAID)

Serial No. 08/809,523 filed 28 Jun 97; PCT filed

Licensing Contact: Carol Salata, 301/496-7735, ext. 232

    A strain of hepatitis E virus from Pakistan (SAR-55) implicated in 
an epidemic of enterically transmitted non-A, non-B hepatitis, now 
called hepatitis E, is disclosed. The invention relates to the 
expression of the whole structural region of SAR-55, designated open 
reading frame 2 (ORF-2), in a eukaryotic expression system. The 
expressed protein is capable of forming HEV virus-like particles which 
can serve as an antigen in diagnostic immunoassays and as an immunogen 
or vaccine to protect against infection by hepatitis E.

Chimeric Gag Pseudovirions

GJ Tobin, MA Gonda (NCI)

Serial No. 08/857,385 filed 15 May 97

Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264

    The human immunodeficiency virus (HIV) is the causative agent of 
acquired immunodeficiency syndrome (AIDS). The HIV virion basically 
consists of a viral core and envelope. The core consists predominantly 
of gag- and pol- encoded proteins and the viral RNA. Expression of 
recombinant Gag precursor proteins can lead to assembly and budding of 
virus-like particles (pseudovirions). The production of Gag-based 
pseudovirions in mammalian and insect cell systems using recombinant 
virus vectors provides a novel technology for engineering recombinant 
protein-based particulate vaccines for HIV and other viruses. The 
incorporation of additional viral or cellular, peptides and 
polypeptides may be advantageous in vaccine

[[Page 48740]]

preparations, since they may contain antigenic epitopes that may play a 
role in inducing protection from infection or disease.
    The subject invention provides chimeric nucleic acids comprising a 
retroviral gag sequence, a target nucleic acid sequence derived from a 
nucleic acid encoding a fusion partner, and a frame shift site. 
Expression of the chimeric gene cassette results in packaging the 
fusion partner into the Gag pseudovirion. Suitable fusion partners can 
be derived from any protein of interest which has a biological activity 
or which elicits a cellular or humoral immune response.

Method For Measuring Mechanical Properties of the Collagen Network 
in Cartilage

PJ Basser, A Maroudas (NICHD)

Serial No. 60/038,005 filed 14 Feb 97; PCT/US98/02727 filed 17 Mar 98

Licensing Contact: John Fahner-Vihtelic, 301/496-7735 ext. 270

    The present application describes a methodology for assessing the 
mechanical integrity of extracellular matrices such as cartilage. 
Specifically, the invention teaches how to characterize the mechanical 
integrity of the collagen network as well as the swelling properties of 
the proteoglycans trapped within it. This is done by performing an 
osmotic stress titration experiment on a tissue specimen, and 
interpreting the results using a simple mathematical model. This 
invention provides the necessary experimental and theoretical tools to 
understand functional consequences of: (1) endogenous changes in 
cartilage structure that occur normally due to growth or aging; (2) 
exogenous changes in cartilage structure due to the addition of 
biochemical agents or caused by genetic manipulations; and (3) inherent 
differences between cartilage specimens that are obtained from 
different joints within the same subject or from different subjects. 
These methods can also be applied to characterize the mechanical 
integrity of tissue cultured or ``tissue engineered'' cartilage.

Vectors for Delivering Viral and Oncogenic Inhibitors

SM Rybak, A Cara, GL Gusella, DL Newton (NCI)

Serial No. 60/022,052 filed 22 Jul 96; PCT/US97/12637 filed 17 Jul 97

Licensing Contact: Carol Salata, 301/496-7735, ext. 232

    The invention concerns cell transduction vectors which are capable 
of inhibiting viral replication in cells transduced with these vectors, 
and which also are capable of inhibiting the growth of cancer cells. 
Specifically, these expressions vectors produce protective genes which 
interfere with viral replication. These genes are tightly regulated by 
HIV-1 Tat and Rev proteins, which if produced after infection can 
induce expression of the protective genes. The vectors contain either a 
single gene (delta-gag), or a combination of two different genes 
(delta-gag and RNAse) which interfere with HIV-1 replication at 
different stages of the HIV-1 life cycle. Following transduction of 
target cells, the mRNA for the protective genes is incorporated into 
the newly budding virion along with the viral genomic mRNA. Following 
infection of neighboring cells, the mRNA for the protective gene can be 
reverse transcribed and integrated into these cells, thereby increasing 
the proportion of cells containing the protective gene.
    In providing protection against viral replication, the vectors 
embodied in this invention could be used in gene therapy against HIV 
and against other viral diseases. In addition, the vectors could be 
used for introducing specific genes into neoplastic cells and thereby 
be effective in treating cancer and other diseases.

Anti-Viral Pharmaceutical Compositions Containing 1,2-Dithiane 
Compounds and Methods of Using Thereof

WG Rice, R Schultz, D Baker, LE Henderson (NCI)

Serial No. 60/021,665 filed 05 July 96; PCT/US97/10870 filed 03 Jul 97

Licensing Contact: J. Peter Kim, 301/496-7056 ext. 264

    Certain highly conserved structures, known as retroviral-type CCHC 
zinc fingers, are found in the nucleocapsid proteins of all 
retroviruses, including HIV-1 and HIV-2. It is known that these zinc 
finger structures perform essential functions in viral infection and 
replication.
    The subject invention provides for pharmaceutical compositions 
comprising dithiane dioxide compounds which are useful as antiviral 
agents and are particularly effective at inhibiting the replication of 
retroviruses and for treating retroviral pathologies. The 1,2-dithiane 
compounds target the zinc fingers of the nucleocapsid protein. These 
compositions represent potential agents for prevention and treatment of 
HIV and of other retroviral diseases. The subject invention also 
embodies methods for the administration of these compositions, a kit 
containing these compositions, and methods for the inactivation of 
contaminating retrovirus in samples of potentially infected body 
fluids.

    Dated: September 3, 1998.
Jack Spiegel,
Diretor, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 98-24368 Filed 9-10-98; 8:45 am]
BILLING CODE 4140-01-M