[Federal Register Volume 63, Number 233 (Friday, December 4, 1998)]
[Notices]
[Pages 67122-67124]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-32318]
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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.
A Display Technique for Identifying LINE-1 Insertion Site
Polymorphisms
G Swergold, F Sheen (FDA)
DHHS Reference No. E-285-97/1 filed 29 Sept 98 (claiming priority of
U.S. Provisional 60/060,353 filed 29 Sept 97)
Licensing Contact: Charles Maynard, 301/496-7735 ext. 243
The invention is a novel method to detect frequent insertion site
polymorphisms in the human genome. Much of the repetitive DNA of
mammalian genomes consists of long interspersed sequences or elements
(LINES). Typical mammalian genomes contain over 20,000 copies of one of
these LINES called LINE-1. These sequences actually create new copies
of themselves in new places in the genome, and contribute to the
variation in DNA between individuals. The present invention is a
powerful new method for the detection of LINE-1 insertion sites. This
method allows the analysis of the DNA from an individual, yielding DNA
fingerprint information as well as information useful for the
understanding of genetic variation in a population.
Mice With A Fluorescent Marker For Interleukin-2 Gene Activation
H Gu, M Naramura, R Hu (NIAID)
DHHS Reference No. E-279-98/0
Licensing Contact: Jaconda Wagner, 301/496-7735 ext. 284
A complex scheme of events unfolds during an immune response and
involves a variety of cell types and soluble factors. New tools are
constantly needed to assess this scheme of events and help tease apart
the roles of accessory, helper and effector cells. A mutant mouse
strain has been developed, and it was generated by
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replacing the interleukin-2 (IL-2) gene with a cDNA encoding the green
fluorescent protein (GFP) from A. victoria. This unique modification
should allow researchers to better monitor the early stages of T cell
activation because IL-2 is one of a few cytokines that naive resting T
cells can produce during primary T cell antigen receptor (TCR)
stimulation. An additional benefit of using IL-2 is that IL-2
production, unlike cytokines such as interferon-gamma and interleukin-
four, is restricted to activated T cells. This would therefore increase
the specificity of this model, and it should decrease the extensive
manipulation of cells that is currently necessary and minimize invasive
protocols. This invention could be used as a screening assay for
substances of immune modulators by manufacturers of a variety of
products. It could provide a valuable research tool for the discovery
genes and their products that induce the production of IL-2.
Additionally, various T cell clones derived from these mice can be used
as the sensitive tool to screen even trace amounts of pathogens, such
as bacteria, in food.
Inhibitors Of Formation Of Transmissible Spongiform Encephalopathy-
Associated Prion Protein By Porphyrins And Phthalocyanines
W Caughey, L Raymond, M Horiuchi, B Caughey (NIAID) Serial No. 60/
096,148, filed 11 Aug 98
Licensing Contact: George Keller, 301/496-7735 ext. 246
The current invention provides for certain tetrapyrroles that
specifically inhibit the conversion of protease-sensitive prion protein
(PrP-sen) to the abnormal protease-resistant form (PrP-res) without
apparent cytotoxic effects. These compounds represent a new class of
inhibitors of PrP-res formation that are a source of therapeutic agents
for transmissible spongiform encephalopathies or prion diseases. For
more information, see Caughey, W. et al. (1998) Inhibition of Protease-
Resistant Prion Formation by Porphyrins and Phthalocyanines, Proc.
Natl. Acad. Sci. USA 95, 12117-12122.
Use Of Constitutive Transport Elements To Control The Host Range Of
Retroviral Vectors
AL Ferris, SH Hughes (NCI) Serial No. 60/094,535 filed 29 Jul 98
Licensing Contact: Richard Rodriguez, 301/496-7056 ext. 287
The major host range determinant for retroviruses and for
retroviral vectors is the envelope glycoprotein. However there is a
second element, the constitutive transport element, or CTE, that also
plays an important role in determining host range. In order to
replicate, retroviruses must transport both spliced and unspliced RNAs
from the nucleus to the cytoplasm. For simple retroviruses, transport
of the unspliced RNA requires an interaction between the CTE--which is
small element in the viral RNA--and host factors. The CTE of avian
sarcome/leukosis viruses (ASLV) does not function in mammalian cells.
As a consequence ASLV, and vectors derived from ASLV, will not
replicate in mammalian cells even if the host/virus system is modified
so that the entry of the ASLV into mammalian cells is efficient. This
invention demonstrates how this barrier to viral replication is
overcome by introducing sequences from an amphotropic murine leukemia
virus (MLV) into a modified ASLV vector. The resulting vector can
replicate in mammalian cells if the host cell/vector system is designed
to provide compatibility between the envelope of the virus and the
receptor on the host cell. The resulting ASLV vector should be useful
for experimental applications both in cultured cells and in animal
models. In addition to being able to extend the host range of
retroviruses by modifying their CTEs, it is also possible to restrict
their host range. A modified MLV virus that replicates only in avian
cells, not in mammalian cells has been developed. This virus can be
used to develop a new generation of safer MLV-based vectors. Therefore,
this invention provides the advantages of being able to restrict or
extend the ability of retroviral vectors to replicate in defined hosts
by manipulating their CTEs. This will be useful in the development of a
new generation of retroviral vectors that are both safer and more
useful than those currently available.
Cloned Genomes Of Infectious Hepatitis C Virus And Uses Thereof
M Yanagi, J Bukh, S Emerson, R Purcell (NIAID) Serial No. 09/014,416,
filed 27 Jan 98
Licensing Contact: George Keller, 301/496-7735 ext. 246
The current invention provides nucleic acid sequences comprising
the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and
1b. It covers the use of these sequences, and polypeptides encoded by
all or part of sequences, in the development of vaccines and diagnostic
assays for HCV and the development of screening assays for the
identification of antiviral agents for HCV. Additional information can
be found in Yanagi et al., (1997) Proc. Natl. Acad. Sci., USA 94, 8738-
8743 and Yanagi et al., (1998) Virology 244, 151-172.
Chemokine Variants And Methods Of Use
T Oravecz, MA Norcross (FDA) Serial No. 60/067,033 filed 01 Dec 97
Licensing Contact: Carol Salata, 301/496-7735 ext. 216
This invention relates to a nucleotide and amino acid sequence of
truncated RANTES (3-68) which is different from the wild type RANTES in
two amino acid positions. CD26 is a leukocyte activation marker that
possesses dipeptidyl peptidase IV (DPPIV) activity but whose natural
substrates and immunological functions had not been previously defined.
Several chemokines, including RANTES (regulated on activation, normal T
expressed and secreted) are provided, which are substrates for human
CD26. RANTES (3-68) retains the ability to stimulate CCR5 receptors and
to inhibit the cytopathic effects of HIV-1. The invention provides
methods for identifying compounds that affect DDPIV-mediated chemokine
cleavage, methods for inhibiting HIV infection and treating individuals
having or at risk of having HIV infection, methods for diagnosis and/or
prognosis of individuals having a chemokine-associated disorder and
methods for accelerating wound healing and angiogenesis, all based on
the discovery of DPPIV-mediated cleavage of chemokines.
Infectious Papillomavirus Pseudoviral Particles
DR Lowy, JT Schiller, RB Roden (NCI)
DHHS Reference No. E-032-96/1; PCT/US97/12115 filed 14 Jul 97, with
priority to 17 Jul 96
Licensing Contact: Robert Benson, 301/496-7056 ext. 267
This invention describes pseudoviral particles of papillomavirus
capsids encapsidating DNA useful for gene therapy and as vaccines. The
pseudoviral particles are made by co-expressing the papillomavirus L1,
L2 and E2 genes in a cell line along with a vector comprising the
useful DNA and DNA containing E2 protein binding sites (E2BS). It is
the discovery of the inventors that the presence of the E2BS containing
DNA results in the encapsidation of the DNA. The encapsidated DNA can
be a gene to replace a defective gene, or can encode an antigen, for
gene therapy or immunization respectively. Since
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papillomaviruses selectively multiply in epithelial cells, the capsids
may be particularly useful for mucosal vaccines, and for delivering
genes to epithelial tissues. The existence of many non-crossreacting
serotypes of human papillomaviruses can be taken advantage of to
eliminate the problem of immune rejection of a pseudoviral particle.
The same gene or antigen encoding DNA can be incorporated in
pseudoviral particles of different serotypes for multiple dosing. The
inventors have demonstrated delivery of the neomycin resistance gene to
mammalian cells with a BPV capsid encapsidating a vector consisting of
the neomycin gene under control of a mammalian promoter and DNA
containing E2 binding sites. Claimed are the pseudoviral particles,
methods of making them, and methods of using them.
Method of Inhibiting The Activity of an Intracellular Constituent
MJ Mulligan-Kehoe (NCI)
U.S. Patent 5,702,892 issued 30 Dec 97; Serial No. 08/897,040 filed 18
Jul 97; Serial No. 09/096,889 filed 12 Jun 98
Licensing Contract: Marlene Shinn, 301/496-7056 ext. 285
Two combinatorial libraries of binding proteins have been
engineered. The libraries were designed to genetically shuffle
oligonucleotide motifs within the framework of the immunoglobulin heavy
chain gene by random mutation of either the CDRI or CDRIII
hypervariable regions. The Fd fragment of the heavy chain gene was then
reconstructed such that it contained the randomized oligonucleotides in
the hypervariable region, resulting in a collection of highly diverse
sequences. The libraries of heavy chain proteins encoded by the array
of mutated gene sequences potentially have all of the binding
characteristics of an immunoglobulin while requiring only the heavy
chain Fd protein.
The re-engineered heavy chain gene sequences were ligated into a
M13-derived bacteriophage vector that permits expression of the binding
proteins as fusion proteins with viral protein 8, which is expressed on
the phage surface.
The claims of the patent application provide methods to screen the
libraries, to identify the binding protein to a specific antigen and
the gene for that specific protein, and to re-engineer the gene for
intracellular expression in a eukaryotic cell. Inducible intracellular
inactivation of glucose-6-phosphate dehydrogenase (G6PDH) has been
demonstrated by in vivo expression of a gene construct encoding a
binding protein selected from one of the libraries and specific for
G6PDH. Removal of induction restored the enzyme activity.
The libraries of binding proteins, the screening methods, and the
methods of inhibiting intracellular components claimed in the patent
application provide powerful potential tools for cellular and molecular
biology by affording the capability of binding/inactivating any protein
of choice.
Amino Acid Sequencing Peptides and Methods for Their Use
DC Parmelee, S Sechi (NCI)
U.S. Patent 5,589,397 issued 31 Dec 96; Serial No. 08/739,819 filed 30
Oct 96
Licensing Contract: Manja Blazer, 301/496-7056 ext. 224
The present invention provides a novel internal standard for amino
acid sequencing which consist of a peptide containing at least two
different unnatural amino acid residues, such as ornithine, norvaline,
norleucine and -aminobutyric acid. The PTH-derivatives of
these have retention times distinct from those of natural amino acids.
This peptide can be sequenced simultaneously with an unknown peptide or
protein without interfering with the analysis. Simultaneous sequencing
of this standard provides information which allows for the
determination of repetitive yields, lags, N-terminal blockage and
discrimination between blank cycles caused by missed injection and
blank cycles caused by faulty delivery of chemicals during the
sequencing reactions.
Dated: November 30, 1998.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer.
[FR Doc. 98-32318 Filed 12-3-98; 8:45 am]
BILLING CODE 4140-01-M
