[Federal Register Volume 64, Number 49 (Monday, March 15, 1999)]
[Notices]
[Pages 12814-12815]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-6204]


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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 Joseph Hemby, 
J.D., at the Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-
3804; telephone: 301/496-7057 ext. 265; fax: 301/402-0220; e-mail: 
[email protected]. A signed Confidential Disclosure Agreement will be 
required to receive copies of the patent applications.

A Novel ATP Binding Cassette Responsible for Cytotoxin Resistance

Michael C. Dean, Susan Bates, Tito A Fojo, Rando Allikmets (NCI)
Serial No. 60/110,473 filed 30 Nov 98

    This technology describes a new human gene (ABCP) that is a member 
of a subfamily that includes several multidrug resistance (MDR) 
transporters. It is highly expressed in placenta and is amplified 10-12 
fold in the MCF ADVp3000 cells (mitoxantrone-resistant cells), but not 
in the SI-m1-0 (human colon carcinoma cells). The gene is important in 
the study of MDR and the development of drugs to block the 
transporter's function in MDR, as well as important in the role in 
placental function and fetal health. Mutations in this gene may 
predispose individuals to miscarriages or birth defects. The described 
technology may have utility as a diagnostic marker for drug resistance 
and drug screening for drugs that block the gene. The gene may also be 
a diagnostic marker for tumors of the breast and other tissues. 
Monoclonal antibodies to the ABCP gene are described in this 
technology. Also described are methods for overexpressing the ABCP gene 
in a cell. Protein and cDNA sequences of the ABCP gene are also 
disclosed.

Cloning and Characterization of Two Novel Human Factors, p52 and 
p75, That Mediate Transcriptional Activation and/or Pre-mRNA 
Splicing

Hui Ge (NICHD)
Serial No. 60/108,248 filed 13 Nov 98

    This technology involves two novel, human transcriptional co-
activators, p52 and p75 which are 52kd and 75kd polypeptides purified 
with Positive Co-factor 4 (PC4) and are involved in the regulation of 
transcription. Mediation of transcription is extremely important since 
it is involved in almost every biological function. The co-activator, 
p52, has been implicated in pre-mRNA through interaction with 
Alternative Splicing Factor (ASF)/Splicing Factor 2 (SF2). Pre-mRNA 
splicing can generate multiple mRNAs for different proteins with 
different functions from a single gene, which is considered to be 
essential for the viability of many vertebrate organisms. These factors 
control and regulate gene expression of most genes and thus may have 
diagnostic, prognostic, and therapeutic utilities in the detection and 
treatment of many cancers and other genetic disease. The technology 
further describes the isolation of the cDNAs encoding the two 
transcriptional co-activators. The two co-activators share a region of 
325 residues; however, they show distinct co-activator properties. Both 
co-activators interact directly with the VP16 activation domain and 
with components of the general transcription machinery. Sp1, a 
glutamine rich cellular activator which can bind the GC-box present in 
many cellular and viral promotors, is essential for the activation of 
the HIV-1 gene and others, requires the presence of the transcriptional 
co-activator p52. Thus, the technology may have a therapeutic utility 
in the prevention and therapy of AIDS.

Triplex Mediated Site Directed Mutagenesis

TA Winters, K Mezhevaya, I Panyutin, RD Neumann (CC)
DHHS Reference No. E-285-98/0 filed 08 Oct 98

    This technology describes triple helix forming oligonucleotides 
(TFOs) which specifically bind to a target site in a DNA molecule to 
induce double strand breaks (DSB's). These TFO's are labeled with \125\ 
I and are used to generate mutations at specific target sites. DNA 
DSB's are known to be highly mutagenic. Auger emitting radioisotopes 
such as \125\ I are known to induce DNA DSB's when they disintegrate in 
close proximity to, or within the DNA duplex. In addition, 
radionuclides such as \125\ I which emit  20 Auger 
electrons upon disintegration would be expected to produce DSB sites 
that also contain base damage proximal to the strand break ends.
    Potential applications of this technology include diagnostics or 
therapeutics where site specific mutagenic disruption or knock-out of 
target genes involved in genetic diseases such as cancer, HIV, human 
hepatitis B

[[Page 12815]]

or C, human herpes, or Parkinson's disease is desired. Other 
applications include inducing site specific reversion mutations in 
defective disease causing genes to produce a phenotypic shift back to 
wild type.
    Additionally, this technology could be used for in situ 
identification and in-vivo imaging of diagnostic gene rearrangements as 
well as monitoring/assessing the efficacy of gene therapy by 
specifically activating or deactivating transferred genes without 
affecting endogenous cellular genes.

A Method of Reversing Resistance to Cisplatin Utilizing a Dominant-
Negative Construct

Maria Bonovich, Eddie Reed, Charles Vinson (NCI)
Serial No. 60/103,330 filed 07 Oct 98

    This technology describes an acidic amphipathic domain (A-Zip) 
transcription factor, A-FOS, a dominant negative, that has high binding 
affinity with a basic leucine zipper (B-ZIP) transcription factor, AP-
1, to selectively prevent binding of AP-1 to the Excision Repair Cross-
Complementing-1 (ERCC1) DNA repair gene at the cis element of cisplatin 
resistant cells. Binding is selectively inhibited at the cis-element of 
the ERCC1 promotor region which is important or ERCC1 expression in 
cisplatin resistant cells and thus ERCC1 transcription is 
preferentially inhibited in the cisplatin resistant cells. Increased 
mRNA expression of ERCC1 is associated with resistance in cancer cells, 
particularly ovarian cancer cells, to chemotherapeutic drugs such as 
cisplatin. ERCC1 is involved in DNA repair of damage caused by adducts 
which are formed by cisplatin. The AP-1 transcription complex, 
consisting of Jun and Fos, is thought to upregulate ERCC1 in cancer 
cells, such as ovarian cancer cells. In particular, the application 
describes an adenoviral replication defective infection system which 
delivers A-Zip's to a cell, resulting in heterodimerization with AP-1, 
thus competing with the ERCC1 gene for binding of AP-1 and selectively 
inhibiting the expression of ERCC1 in cisplatin resistant cells and not 
parental cells. Thus, this invention has utility as a therapeutic 
method in the treatment of cancer.

Identification of the Factor in Bone Responsible for Prostate 
Cancer Cell Metastasis

K Jacob, H Kleinman, D Benayahu (NIDCR)
Serial No. 60/102,918 filed 02 Oct 98

    This technology describes a bone matrix protein which may be a 
member of the bone matrix protein family of osteonectin/SPARC/BM40, a 
chemoattractant. Also described is the role protein plays in making 
breast, and particularly prostate cancer cells highly invasive, 
migratory, and metastatic to bone. Osteonectin is a 32,000 dalton bone-
specific protein that binds selectively to both hydroxyapatite and 
collagen. The level of the receptor for osteonectin may be a marker of 
metastatic potential for both breast and prostate cancer, lending 
itself as an assay for determining the diagnosis and prognosis of 
prostate and breast cancer. Levels of osteonectin in serum may also 
have utility as a marker of prostate cancer.

PB39, A Novel Isolated Complete cDNA Whose Function Is Dysregulated 
in Prostate Cancer

Rodrigo Chaugui, Lance A. Liotta, Kristina A. Cole (NCI) Serial No. 60/
094, 137 filed 14 Jul 98

    This technology describes the identification and cloning of two 
cDNAs derived from a human prostate cancer. In addition, the technology 
describes the cDNA for the murine homolog as well as the murine genomic 
sequence has been determined. The human gene is located on chromosome 
11 and the gene product appears to exist in two forms, PB-39A (adult) 
and PB-39B (fetal). The products of the gene, which correspond to these 
cDNAs, are over-expressed in prostate cancer and PB-39 is over-
expressed in prostate intraepithelial neoplasia (PIN). PIN is an early 
precursor of cancer; therefore, the PB-39B gene product may serve as an 
early marker for prostate cancer. The over-expression of PB-39A or PB-
39B in prostate cancer when compared to normal tissue indicates that 
either may be used in the diagnosis of prostate cancer. Early results 
indicated that PB-39B may be a more reliable indicator (3/4 samples 
were positive for PB-39B while 5/11 samples were positive for PB-39A).

Screening Assays for Compounds That Cause Apoptosis and Related 
Compounds

CC Harris, XW Wang (NCI)
Serial No. 08/675,631 filed 01 Jul 96
    This technology describes peptides which may be useful as 
therapeutics due to their ability to cause apoptosis and assays which 
can be used to screen compounds for their ability to cause apoptosis. 
Preferably, the peptides are derived from the carboxy (COOH) terminus 
of the amino acid sequence of the known protein p53. More preferably, 
the peptides correspond to amino acids 367-387, 319-393, 350-380, 355-
375, and 360-370 of the COOH terminus of p53. In particular, a single 
peptide derived from amino acid residues 360-370 of p53 is described. 
Diseases and conditions which have been linked to defects in apoptosis 
include cancer, heart attack, Parkinson's, Alzheimer's and stroke.

    Dated: March 5, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-6204 Filed 3-12-99; 8:45 am]
BILLING CODE 4140-01-M