[Federal Register Volume 65, Number 146 (Friday, July 28, 2000)]
[Notices]
[Pages 46474-46475]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-19150]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 Susan S. 
Rucker, J.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. 245; fax: 301/402-0220; e-
mail: [email protected]. A signed Confidential Disclosure Agreement 
will be required to receive copies of the patent applications.

Establishment of Cellular Manipulations Which Enhance Oligo-
Mediated Gene Targeting

MM Seidman and A Majumdar (both of NIA)
Serial No. 60/191,996 filed 24 Mar 2000

    This application relates to gene targeting, illustrated by the use 
of triplex-forming oligonucleotides (TFO's). In particular, the 
application describes and claims methods for improving the efficiency 
of the modification of gene sequence (including mutation and/or 
recombination) through the use of cells which have been cultured so as 
to synchronize their cell cycles. According to the method described and 
claimed in the application gene targeting reagents, as demonstrated by, 
but not limited to, triple helix forming oligonucleotides, are 
introduced into cultured, synchronized cells. Gene targeting 
applications are useful in research applications for the generation of 
transgenic animals and plants, including animals used as model systems, 
such as knockout mice, and animals or plants used for production of the 
product of the transgene of interest. In addition, efficient methods of 
gene targeting may also be useful in improving or carrying out gene 
therapy applications.

AAV5 Vector for Transducing Brain Cells and Lung Cells

JA Chiorini (NHLBI/NIDCR), RM Kotin (NHLBI)
Serial No. 09/533,427 filed 22 Mar 2000

    The invention described and claimed in this patent application is 
related to the delivery of heterologous nucleic acids or genes to 
particular target cells. In particular, the application relates to 
methods of delivering a heterologous nucleic acid or gene of interest 
to particular target cells using an Adeno-

[[Page 46475]]

Associated Virus of serotype 5 (AAV5). The particular target cells 
identified include the alveolar cells of the lung and cerebellar and 
ependymal cells of the brain. The methods described herein may be 
useful in carrying out gene therapy related to diseases of the brain or 
central nervous system and the respiratory tract.
    This work has been published, in part, at Davidson BL, et al. PNAS, 
USA 97(7):3428-32 (March 28, 2000) and Zabner J, et al. J Virol. 
74(8):3852-8 (April 2000).
    In addition to this patent application, PHS owns additional 
intellectual property related to this technology. The patent 
application has been published as WO 99/61601 on December 2, 1999 and 
the research corresponding thereto has been published at Chiorini JA, 
et al. J. Virol. 73(5): 4293-98 (May 1999) and Chiorini JA, et al. J. 
Virol. 73(2): 1309-19 (Feb. 1999).

AAV4 Vector and Uses Thereof

JA Chiorini (NHLBI/NIDCR), RM Kotin, B Safer (both of NHLBI)
Serial No. 09/532,594 filed 22 Mar 2000

    The invention described and claimed in this patent application 
relates to the delivery of heterologous nucleic acids or genes to 
particular target cells. In particular, the application relates to 
methods of delivering a heterologous nucleic acid or gene of interest 
to particular target cells using Adeno-Associated Virus of serotype 4 
(AAV4). The particular target cells identified are the ependymal cells 
of the brain. The methods described herein may be useful in carrying 
out gene therapy for diseases of the brain or central nervous system.
    This work has been published in part at Davidson, BL, et al. 
``Recombinant adeno-associated virus type 2, 4, and 5 vectors: 
transduction of variant cell types and regions in the mammalian central 
nervous system'' PNAS USA 97(7):3428-32 (March 28, 2000).
    In addition, PHS owns additional intellectual property related to 
this technology describing an AAV4-based vector system. The material 
contained in the patent application has been published as WO 98/11244 
(March 19, 1998) and the research corresponding thereto has been 
published in J. Virology 71(9): 6823-33 (Sept 1997).

A Novel Pro-Apoptotic Protein, ARTS

S Larisch-Bloch, SJ Kim, RJ Lechleider, AB Roberts and Y Yi (all of 
NCI)
Serial No. 60/178,866 filed 29 Jan 2000

    This application relates to the field of apoptosis, in particular 
the application relates to a novel gene product which is associated 
with induction of apoptosis by Transforming Growth Factor Beta (TGF-
). Apoptosis is a critical event in developmental processes 
and homeostasis; its dysregulation is often central to pathogenic 
mechanisms. Apoptotic aberrations contribute to the development of the 
transformed phenotype; both metastatic potential and tumor 
aggressiveness are associated with increased resistance to apoptosis. 
Certain chemotherapeutic agents act by increasing the sensitivity of 
cells to apoptosis and patients with mutations in genes regulating 
apoptosis are known to have a poor prognosis.
    The application describes the cloning of a gene which encodes a 
splice variant of the known gene designated H5/PNUTL2/CDCrel-2a/2b and 
the isolation and characterization of its protein product. The newly 
identified protein, designated ARTS (Apoptosis Related Protein in the 
TGF- Signaling Pathway), is a member of the septin family of 
proteins. It is localized to mitochondria and translocates to the 
nucleus where ARTS induces apoptosis in response to TGF-. ARTS 
is the first septin shown to be essential for mediating TGF- 
dependent apoptosis. Antisense ARTS nucleic acids are also 
contemplated. Because of its role in regulating the sensitivity of 
cells to TGF- induced apoptosis ARTS derived products may 
provide a means for treating conditions where increased TGF- 
induced apoptosis is desired (e.g., cancer) and where decreased TGF-
 induced apoptosis is desired (e.g., neurodegenerative 
diseases).
    This work has been published in part at Larisch-Bloch S et al. 
``Selective loss of the transforming growth factor-beta apoptotic 
signaling pathway in mutant NRP-154 rat prostatic epithelial cells'' 
Cell Growth Differ 11(1):1-10 (Jan 2000).

Replication Deficient Retroviral Vector System and Methods of Using

WJ Ramsey (NHGRI)

Serial No. 60/101,425 filed 22 Sep 1998; PCT/US99/21393
    The technology described and claimed in this application relates to 
the field of gene therapy. More particularly, the technology described 
and claimed in the application relates to a method for producing 
replication deficient, but infectious, retroviral vectors. This method 
of producing replication deficient retroviral vectors for gene therapy 
yields virus in high titer and is readily adaptable to large scale 
production. In the methods described herein a producer cell is 
transformed with an integrating proviral sequence which includes a pair 
of retroviral LTRs, a retroviral packaging signal and the gene of 
interest. A second viral vector, containing trans complementing 
functions, such as the gag, pol, and env genes, is then used to infect/
transform the cells containing the integrated proviral sequence 
enabling the generation of a replication deficient vector. This second 
viral vector may be chimeric, e.g., have an adenoviral backbone and 
retroviral trans complementing functions. Producer cells, which now 
contain the trans complementing vector and the integrated proviral 
vector are then cultured to obtain the replication deficient viral 
vector from the medium.
    The PCT application has been published as WO 00/17736 (March 30, 
2000). Related technology describing chimeric vectors for gene therapy 
is also available for licensing. It is described in USSN 09/058,686 
filed 10 Apr 1998 (published as WO 98/46778 (Oct. 22, 1998).

    Dated: July 19, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-19150 Filed 7-27-00; 8:45 am]
BILLING CODE 4140-01-P