[Federal Register Volume 74, Number 87 (Thursday, May 7, 2009)]
[Notices]
[Pages 21372-21374]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-10549]


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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, HHS.

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.

Novel Inhibitors of Bone Morphogenetic Proteins

    Description of Technology: Bone Morphogenetic Proteins (BMPs) are 
signaling molecules that are central in a variety of biological 
processes, but were first recognized for their role in inducing bone 
and cartilage development. Abnormal BMP signaling has been implicated 
in the pathogenesis of a class of joint disorders known as 
spondyloarthropathies which includes

[[Page 21373]]

ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and 
arthritis associated with inflammatory bowel disease. Therefore, 
inhibitors and modulators of BMP signaling may be useful in managing 
these disorders. Moreover, the BMPs and their antagonists have now been 
implicated in myriad cell and tissue differentiation and fate 
specification processes, extending their utility far beyond orthopedic 
and rheumatologic applications. Scientists at the Food and Drug 
Administration, National Institutes of Health and Katholieke 
Universiteit Leuven have discovered a novel inhibitor of BMPs called 
Secreted Modular Calcium Binding protein (SMOC) which is unrelated to 
known BMP inhibitors.
    This technology relates to a method for treating disorders 
including joint disorders by administering a SMOC polypeptide to induce 
intracellular mitogen activated protein (MAP) kinase activity to effect 
a reduction of BMP signaling activity in the cells of a patient. It 
also encompasses methods to manipulate differentiation processes 
regulated by BMPs. One prominent example is the specification of 
neural, as opposed to epithelial, cell fate.

Applications

     Treatment of joint diseases.
     Manipulation of tissue fate specification in vitro, alone 
or in combination with other materials, in production of therapeutic 
cells and tissues.

Advantages

     Ability to interrupt BMP signaling by a novel mechanism;
     Predictable synergy with other BMP antagonists;
     No indication of being immunosuppressive;
     In some instances SMOC is associated with extracellular 
matrix molecules, allowing for spatially restricted BMP antagonism not 
possible with diffusible factors such as noggin.
    Development Status: Early stage.
    Market: Modulation of BMP signaling by secreted inhibitors is 
involved in formation of the body axis, limbs and joints, all organs, 
and nervous tissue, to name a few. The applications of SMOC in 
conjunction with other growth factors in vitro in various developmental 
programs to produce therapeutic cells and/or tissues are therefore 
numerous. In addition, BMPs are involved in many disorders in man, and 
modulating their activities may provide a therapeutic benefit for a 
number of diseases and disorders such as arthritis and 
spondyloarthropathies.
    Inventors: Malcolm C. Moos et al. (CBER/FDA), Frank P. Luyten 
(NIDCR).
    Publications: None related to this invention.
    Patent Status: U.S. Provisional Application No. 61/086,679 filed 06 
Aug 2008 (HHS Reference No. E-338-2005/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].

Salcut-NH2: A Novel Target for Development of Anti-Tumorigenic, Anti-
Angiogenic Therapeutics and Diagnostics

    Description of Technology: Salcut-NH2, a novel amidated peptide 
derived from the Apelin proprotein, is shown to induce the 
proliferation of cells. Uncontrolled cell proliferation is the salient 
feature of cancer. Thus, therapeutics that stop this aberrant cell 
division are very desirable. Salcut-NH2 can be the basis for developing 
novel inhibitors of cancer growth such as modified peptide antagonists 
like salcut-glycine (salcut-Gly). Alternately, salcut-NH2 could be the 
target of antibody therapies that block its activity. In some 
instances, such as wound healing, inducing cell proliferation would be 
advantageous. It also has been demonstrated that salcut-NH2 induces 
angiogenesis so it may also have application as a topically 
administered therapeutic for speeding the healing of skin wounds. 
Finally, increasing levels of salcut-NH2 in body fluids may be 
reflective of disease progression. A diagnostic kit for salcut-NH2 
could potentially be developed for the prognosis of a variety of 
diseases associated with aberrant cell proliferation or angiogenesis.

Applications

     Development of therapeutics that inhibit cancer growth or 
diseases related to aberrant angiogenesis.
     Topical therapeutic to hasten wound healing.
     Diagnostic for the prognosis of cancer or diseases related 
to aberrant growth of blood vessels.

Advantages

     Naturally derived peptide and thus negligible 
immunogenicity.
     Amidation makes salcut-NH2 resistant to proteases and 
increases its availability.
     Small peptides are readily excreted facilitating 
measurement of salcut-NH2 for diagnostic purposes.
    Development Status: Early stage; pre-clinical data available.
    Markets:
     Cancer is the second most common cause of death in the 
U.S., exceeded only by heart disease. In the U.S., cancer accounts for 
1 of every 4 deaths and more than 2.4 million new cancer cases were 
expected to be diagnosed in 2008.
     Age-related macular degeneration (AMD) is a degenerative 
disease of the retina that eventually leads to a loss of vision. The 
wet form of AMD is the most common and is characterized by the abnormal 
growth of retina blood vessels and results in a rapid loss of central 
vision. It is estimated that AMD affects 1.75 million people in the 
United States.
    Inventors: Frank Cuttitta et al. (NCI).
    Publications: None related to this invention.
    Patent Status: U.S. Provisional Application No. 61/156,351 filed 27 
Feb 2009 (HHS Reference No. E-179-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Angiogenesis Core Facility is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize (1) Identification of new 
biological functions for Salcut-NH2 or (2) Development of compounds 
that suppress or augment Salcut-NH2 bioactivity. Please contact John D. 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

Novel Oligonucleotides for Treatment of Human Cancer

    Description of Technology: Human endogenous retroviruses (HERVs) 
are remnants of retroviruses that invaded and integrated into the human 
genome 6-15 million years ago. One significant type of HERV is ERV-9; 
approximately 5% of the total human genome comprises sequences from 
this retrovirus family. The human genome contains approximately 50 
copies of ERV-9 along with 3000-4000 copies of solitary elements of 
ERV-9 regulatory regions, called long terminal repeats (LTRs). The 
solitary LTRs contain promoter and enhancer elements that drive 
expression of genes located proximally to the LTR. Therefore, insertion 
of an ERV-9 LTR proximal to an oncogene could initiate carcinogenesis.
    This invention relates to the use of antisense and sense 
oligonucleotides (oligos) targeting the RNAs of ERV-9

[[Page 21374]]

LTR as a treatment for various cancers, including human breast, liver, 
prostate, and myeloid cancers and fibrosarcomas. The inventors have 
shown that the ERV-9 LTR sense and antisense oligos can inhibit cancer 
cell proliferation in vitro more efficiently than the antisense oligos 
of Bcl-2 (G3139) and telomerase (GRN163), both of which are currently 
in cancer clinical trials. The oligos have minimal effects on the 
proliferation of primary normal human cells in vitro. These oligos have 
potential as a new therapeutic agent to suppress tumor cell growth, 
either when used alone or in conjunction with other antisense oligos or 
with chemotherapeutic agents such as VePesid. Furthermore, sense and 
antisense RNA transcripts of ERV-9 LTR were detected in many human 
normal and tumor cells in this invention. The sense and antisense RNA 
may form double stranded RNA and act as siRNA to regulate gene 
expression.

Applications

     Therapeutic oligos of the invention can be used to treat 
variety of cancers including, but not limited to, breast, liver, 
myeloid and prostate cancers and fibrosarcomas.
     The oligos can be used either singly or as adjuvant 
therapy with chemotherapeutic agents.
     ERV-9 LTR related cancers can be diagnosed by comparative 
analysis of the levels of ERV-9 LTR RNAs in tumors versus those of 
healthy tissues.

Advantages

     Greater inhibition of cell proliferation by oligos of the 
invention compared to the Bcl-2, telomerase and MDM2-specific antisense 
oligos which are currently in development as cancer therapies.
     The therapeutic effect of the oligos is specific for 
cancer cells as the oligos do not significantly alter proliferation of 
normal human cells.
    Development Status: In vivo testing of therapeutic sense and 
antisense oligos in mouse xenograft models has been successfully 
conducted.
    Market: Cancer is the second leading cause of death in the United 
States. More than 1 million Americans are diagnosed with cancer each 
year.
    Inventors: Lai Xu (FDA/CDER), Abdel Elkahloun (NHGRI), Fabio 
Candotti (NHGRI), Amy Rosenberg. (FDA/CDER)
    Publications: None related to invention have been published.
    Patent Status: U.S. Provisional Application No. 61/191,911 filed 11 
Sep 2008 (HHS Reference No. E-092-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].

    Dated: April 30, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-10549 Filed 5-6-09; 8:45 am]
BILLING CODE 4140-01-P