[Federal Register Volume 69, Number 36 (Tuesday, February 24, 2004)]
[Notices]
[Pages 8471-8472]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3906]


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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 an agency 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.

SAP/SH2D1A Knockout Mice: A Model for X-linked Lymphoproliferative 
Disease

Pamela L. Schwartzberg (NHGRI),
DHHS Reference No. E-343-2003/0--Research Tool,
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    NIH announces the availability for licensing of SAP/SH2D1A knockout 
mice, which can be used as a model for X-linked lymphoproliferative 
disease (XLP), and exploited to design therapeutics or gene-therapy for 
XLP. These knockout mice can be used as well to study other T cell-
mediated diseases, such as asthma and hypersensitivity, involving Th2 
cells. This model is also useful for researchers interested in T-cell 
signaling and cytokine production by T-helper cells.
    SAP (SLAM-associated protein) is a small lymphocyte-specific 
signaling molecule that is defective or absent in patients with XLP. 
SAP has unusually high affinity for SLAM (also called CD150) and has 
been suggested to function by blocking binding of SHP-2 or other SH2-
containing signaling proteins to SLAM receptors. SAP has also been 
shown to be required for

[[Page 8472]]

recruitment and activation of the Src-family kinase FynT after SLAM 
ligation, where the SAP SH2 domain binds to the SH3 domain of FynT and 
directly couples FynT to SLAM.
    Mutations in the SH2D1 A gene on the Xq24-26 chromosome are known 
to be responsible for many cases of X-linked Lymphoproliferative 
syndrome.

Immunoglobulins With Potent and Broad Antiviral (HIV) Activity Based on 
scFv Joined by Flexible Linker to Fc

Drs. Dimiter Dimitrov (NCI) and Mei-Yun Zhang (SAIC),
U.S. Provisional Patent Application filed 29 Sep 2003 (DHHS Reference 
No. E-316-2003/0-US-01),
Licensing Contact: Sally Hu; (301) 435-5606; [email protected].

    This invention describes methods of inhibiting viral infection 
(e.g., HIV-1 infection). The method comprises administering a fusion 
protein comprising a small size, single chain Fv (scFv) antibody 
binding domain joined to an Fc region by a long flexible linker. In 
particular, scFv m6 or m9, the single chain variable fragments that 
were previously identified from a phage display library for binding to 
gp14089.6, gp120JRFL, gp140IIIB, and 
their complex with two-domain soluble CD4 is joined to Fc by a long 
flexible linker to provide a new agent for the inhibition of HIV 
infection or immunotherapy of HIV-infected individuals. The Fc region 
provides stability, long half-life, and biological effector functions. 
The scFv-Fc fragment provides antigen recognition and neutralizing 
activity. The small size of the scFv-Fc fusion molecule provides easy 
access to conserved viral epitopes exposed before or during viral 
entry. In addition, these fusion molecules exhibit neutralization 
activity that is higher than that of whole IgGs. Thus, this invention 
may offer a novel approach to treat and prevent HIV-1 infection and/or 
AIDS.

Potent Combinations of mRNA Transport Elements

Barbara K. Felber et al. (NCI),
U.S. Provisional Application No. 60/471,988 filed 19 May 2003 (DHHS 
Reference No. E-223-2003/0-US-01);
U.S. Provisional Application No. 60/472,223, filed 20 May 2003 (DHHS 
Reference No. E-258-2003/0-US-01),
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    This technology relates to improving levels of gene expression 
using a combination of a constitutive RNA transport element (CTE) with 
a mutant form of another RNA transport element (RTE). The combination 
of these elements results in a synergistic effect on stability, and 
therefore expression levels, of mRNA transcripts. Using HIV-1 gag as 
reporter mRNA, one mutated RTE in combination with a CTE was found to 
improve expression of unstable mRNA by about 500-fold. Similarly this 
combination of elements lead to synergistically elevated levels of HIV-
1 env expression. The function of CTEs and RTEs is conserved in 
mammalian cells, so this technology is a simple and useful way of 
obtaining high levels of expression of otherwise poorly expressed genes 
and can be used in a number of applications such as but not limited to 
improvements of gene therapy vectors, expression vectors for mammalian 
cells.

Safer Attenuated Virus Vaccines With Missing or Diminished Latency of 
Infection

Jeffrey Cohen (NIAID), Edward Cox (FDA), Lesley Pesnicak (NIAID),
U.S. Provisional Application No. 60/423,603 filed 05 Nov 2002 (DHHS 
Reference No. E-250-2002/0-US-01); PCT Application No. PCT/US03/35167 
filed 05 Nov 2003 (DHHS Reference No. E-250-2002/0-PCT-02),
Licensing Contact: Susan Ano; (301) 435-5515; [email protected].

    This technology describes viruses that have weakened ability to 
establish and/or maintain latency and their use as live vaccines. The 
viruses have one or more genetic mutations that allow for continued 
replication but that inhibit latency. The vaccine materials and methods 
for their construction are exemplified with the virus that causes 
chickenpox and whose latent infection results in shingles, a condition 
that affects up to an estimated 1 million people per year in the United 
States alone. Specific examples of gene deletion are described. 
Furthermore, replacement of these deleted genes with other desirable 
viral antigen encoding sequence(s) and/or cytokine genes in order to 
enhance a desired immunological response is also described. Aspects of 
this technology are relevant to other live virus vaccines, thus 
increasing the safety of such vaccines.

Novel Receptor for Pathogenic Fungi

Victor Jimenez (EM), Victor Ginsburg (NIDDK), Howard Krivan (NIDDK),
U.S. Patent Application No. 07/472,128 filed 30 Jan 1990, which issued 
as U.S. Patent 5,242,800 on 07 Sep 1993 (DHHS Reference No. E-145-1989/
0-US-01),
Licensing Contact: Michael Ambrose; (301) 594-6565; 
[email protected].

    A specific receptor for pathogenic fungi has been isolated and 
substantially purified for the first time, and a method of using the 
receptor to prevent adhesion of pathogenic fungi to host cells has been 
developed. A kit for detecting the presence of certain fungi was also 
described. These products make possible the detection and removal of 
two important pathogenic fungi, Candida albicans and Cryptococcus 
neoformans, and may be useful in preventing yeast diseases.

    Dated: February 17, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-3906 Filed 2-23-04; 8:45 am]
BILLING CODE 4140-01-P