[Federal Register Volume 70, Number 250 (Friday, December 30, 2005)]
[Notices]
[Pages 77412-77413]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E5-8121]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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

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.

A Single Ribozyme To Catalyze Both Trimming and Transacting Catalysis--
Potential Therapeutic for HPV Infection and Cervical Cancer

Joseph A. DiPaolo (NCI) et al.,
U.S. Provisional Application No. 60/675,076 filed 25 April 2005 (HHS 
Reference No. E-142-2005/0-US-01),
Licensing Contact: Robert M. Joynes; 301/594-6565; 
[email protected].

    This technology relates to a potential therapeutic for treating 
human papillomavirus (HPV) infection as well as cervical cancer. It is 
acknowledged that HPV is the primary agent associated with cervical 
cancer. The life cycle of HPVs progresses with epithelial 
differentiation and may persist for decades. The E6 and E7 oncogenes 
are responsible for two viral proteins that target p53 and Rb. The 
persistence of E6 and E7 in cervical carcinomas has led to them being 
recognized as the hallmark of cervical carcinomas and makes them 
excellent targets for therapy. Previously, we reported an engineered 
hairpin ribozyme (R434) that caused down-regulation of HPV-16 E6/E7 
mRNA and inhibited growth of both HPV-16 immortalized cells and tumor 
cells. To increase efficiency of R434 we constructed a ribozyme 
expression

[[Page 77413]]

system (TRL-5) entirely based on cis-cleaving (trimming) hairpin 
ribozymes (triplex system) that release R434 from long transcripts. 
Because of the modular structure of the hairpin ribozyme, the catalytic 
domain B can independently recognize cis or trans targets allowing the 
use of the same ribozymes for both trimming and therapeutic duties. 
Thus, this improved system was designed as a three-ribozymes unit in a 
canonical triplex using an inverted cleavage from one trimming 
ribozyme.
    The Rz434bis system was designed to use a single R434 ribozyme to 
catalyze both trimming and trans-acting activities. This procedure 
resulted in a reduced-size triplex system that uses R434 catalytic 
domain to self-excise itself. RNA from Rz434bis and TRL-5 templates 
released R434 by a self-processing mechanism thus allowing for the 
individual activity of multiple trans-acting ribozymes. Both Rz434bis 
and TRL-5 systems produced an increased cleavage efficiency of HPV-16 
target site nt 410 to 445 when expressed from linear or circular 
templates. Furthermore, duplex Rz434bis and TRL-5 were more efficient 
in cleaving E6 than duplex single R434. The use of triplex 
configurations with multi-target ribozymes will ultimately result in 
better in vivo HPV-16 E6/E7 mRNA degradation. Therefore, implementation 
of the triplex systems that significantly enhance R434 in vitro 
activity is offered as an alternative to the antisense 
oligodeoxynucleotide treatment of cervical cancer.

Genomic Nucleic Acid Sequence for Cyanovirin-N and Signal Peptide 
Thereof

Dr. Angela Gronenborn (NIDDK),
U.S. Provisional Application No. 60/695,599 filed 05 Jul 2005 (HHS 
Reference No. E-133-2005/0-US-01),
Licensing Contact: Sally Hu; 301/435-5606; [email protected].

    The invention provides composition claims for an isolated or 
purified genomic nucleic acid sequence encoding a CV-N signal peptide, 
as well as an isolated or purified nucleic acid comprising a genomic 
sequence encoding a Cyanovirin-N (CV-N) polypeptide native to the 
cyanobacterium species Nostoc ellipsosporum. The signal peptide can be 
used for directing the secretion of CV-N polypeptide. Further 
development of the invention may yield novel therapies and methods in 
the prevention of HIV and other retroviruses, such as HTLV-1 and 2, 
FLV, and treatment of chronic infection in patients with resistance to 
current HIV therapies. The invention also includes vectors and cells 
comprising this sequence, methods for producing a polypeptide, and a 
method for inhibiting viral infection in a mammal by administering a 
viral-infection inhibiting amount of the nucleic acid, vector and/or 
cell of the invention. It also provides a method of inhibiting virus in 
biological samples or inanimate objects, and can also be used ex vivo 
for virucidal sterilization.

GP41 Inhibitor

G. Marius Clore et al. (NIDDK),
U.S. Provisional Application No. 60/339,751 filed 17 Dec 2001 (HHS 
Reference No. E-252-2001/0-US-01); PCT Application No. PCT/US02/40684 
filed 17 Dec 2002 (HHS Reference No. E-252-2001/0-PCT-02); U.S. Patent 
Application No. 10/499,094 filed 14 Jun 2004 (HHS Reference No. E-252-
2001/0-US-03),
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    The technology relates to a chimeric molecule, NCCG-gp41, in which 
the internal trimeric helical coiled-coil of the ectodomain of gp41 is 
fully exposed and stabilized by both fusion to a minimal ectodomain 
core of gp41 and by engineered intersubunit disulfide bonds. NCCG-gp41 
inhibits HIV envelope mediated cell fusion at nanomolar concentrations 
with an IC50 of 16 nM. It is proposed that NCCG-gp41 targets the 
exposed C-terminal region of the gp41 ectodomain in its pre-hairpin 
intermediate state, thereby preventing the formation of the fusogenic 
form of the gp41 ectodomain that comprises a highly stable trimer of 
hairpins arranged in a six-helix bundle. NCCG-gp41 has potential as (a) 
an HIV therapeutic agent that inhibits cell entry; (b) as an AIDS 
vaccine and; (c) as a component of a high throughput screening assay 
for small molecule inhibitors of HIV envelope mediated cell fusion. 
Antibodies have been raised against NCCG-gp41 that inhibit HIV envelope 
mediated cell fusion.
    This invention is further described in: J.M. Louis et al., ``Design 
and properties of NCCG-gp41, a chimeric gp41 molecule with nanomolar 
HIV fusion inhibitory activity,'' J. Biol. Chem. (2001 Aug 3) 
276(31):29485-29489; C.A. Bewley et al., ``Design of a novel peptide 
inhibitor of HIV fusion that disrupts the internal trimeric coiled-coil 
of gp41,'' J. Biol. Chem. (2002 Apr 19) 277(16):14238-14245; J.M. Louis 
et al., ``Covalent trimers of the internal N-terminal trimeric coiled-
coil of gp41 and antibodies directed against them are potent inhibitors 
of HIV envelope-mediated cell fusion,'' J. Biol. Chem. (2003 May 30) 
278(22):20278-20285; J.M. Louis et al., ``Characterization and HIV-1 
fusion inhibitory properties of monoclonal Fabs obtained from a human 
non-immune phage library selected against diverse epitopes of the 
ectodomain of HIV-1 gp41,'' J. Mol. Biol. (2005 Nov 11) 353(5):945-951.

    Dated: December 19, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E5-8121 Filed 12-29-05; 8:45 am]
BILLING CODE 4140-01-P