[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

[[Page 67124]]

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