[Federal Register Volume 73, Number 168 (Thursday, August 28, 2008)]
[Notices]
[Pages 50827-50829]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-19914]
-----------------------------------------------------------------------
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.
Identification and Characterization of Folliculin-Interacting Protein
2, FNIP2
Description of Technology: The invention describes the
identification and characterization of a FNIP1 homolog, folliculin-
interacting protein 2 (FNIP2), that interacts with folliculin, the
protein encoded by the FLCN gene, which is responsible for the Birt-
Hogg-Dube' (BHD) syndrome. BHD is a dermatologic disorder associated
with an increased risk for developing renal cancer, spontaneous
pneumothorax and lung cysts. FNIP2 binds to the C-terminus of
folliculin and to AMPK. Importantly, FNIP2 expression was elevated in
renal tumors seen in BDH patients. This finding suggests that FNIP2 may
serve as a biomarker for BHD.
Applications: Research tool; Diagnostic applications.
Advantages: Could facilitate the development of therapeutic drugs
to treat the skin lesions and renal tumors that develop in BHD
patients.
Development Status: Early stage of development.
Market: Dermatologic products; Diagnostic applications.
Inventors: Laura S. Schmidt et al. (NCI).
Relevant Publication: H Hasumi et al. Identification and
characterization of a novel folliculin-interacting protein FNIP2.
(2008) Gene, in press.
Patent Status: HHS Reference No. E-213-2008/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for biological materials licensing
only.
Licensing Contact: John Stansberry, Ph.D.; 301-435-5236;
[email protected].
Collaborative Research Opportunity: The Urologic Oncology Branch at
the National Cancer Institute is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize detection methods specific for
FNIP2 to be used to screen FNIP2 as a biomarker for renal cancer. This
may include development of an efficient FNIP2 antibody which does not
cross react with FNIP1 for immunhistochemical screening of renal tumors
for FNIP2 expression. Please contact John D. Hewes, Ph.D. at 301-435-
3121 or [email protected] for more information.
Immunotoxins Made With Modified Cholix Toxin and Uses Thereof
Description of Technology: Immunotoxins are chimeric molecules
comprising an antibody targeting moiety and a toxin domain capable of
killing a cell. Immunotoxins represent an important therapeutic tool
for the treatment of cancer because they are able to specifically
target cancer cells while ignoring healthy cells. The major drawback to
immunotoxins is the development of neutralizing antibodies against the
toxin portion of the immunotoxin. Many patients treated with
Pseudomonas exotoxin A (PE) based immunotoxins develop neutralizing
antibodies after the first administration. As a result, only one
effective administration of a PE-based immunotoxin is often possible.
NIH inventors have created a novel immunotoxin, where the toxin
portion is a truncated Cholera exotoxin (cholix toxin). Although cholix
toxin retains strong functional and structural similarity to PE,
neutralizing antibodies to PE do not affect the truncated cholix toxin.
As a result, cholix toxin-based immunotoxins are of potential utility
after a patient has developed neutralizing antibodies to PE. The
ability to deliver two rounds of immunotoxins to a patient will
increase the successful treatment of various diseases, including
cancer.
Application:
[[Page 50828]]
Used as an alternative toxin moiety in immunotoxins.
Immunotoxins can be used for the treatment of various
cancers, depending on the targeting antibody.
Can be used in tandem immunotoxin therapy with
immunotoxins having distinct toxin moiety, such as PE-based
immunotoxins.
Advantages:
Cholix toxin-based immunotoxins are not affected by
neutralizing antibodies to by PE-based immunotoxins, permitting
multiple rounds of immunotoxin therapy.
Ability to target specific cells by choosing specific
targeting antibodies.
Inventors: David J. FitzGerald and Robert J. Sarnovsky (NCI).
Patent Status: U.S. Provisional Application No. 61/058,872 filed 04
Jun 2008 (HHS Reference No. E-194-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
CCR, Laboratory of Molecular Biology is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize immunotoxins
composed of cholera exotoxin. Please contact John D. Hewes, Ph.D. at
301-435-3121 or [email protected] for more information.
Large Semi-Synthetic Human Antibody Domain Fragment Library
Description of Technology: Human monoclonal antibodies are
important for the development of inhibitors, vaccines, diagnostic and
research tools. Previously a large non-immune human antibody library
(15 billion (15 x 10\9\) clones) was constructed from the lymph nodes,
spleen and peripheral blood lymphocytes of 50 donors. One antibody,
isolated from this library, includes a stop codon in the light chain
but was still expressed and included a functional heavy chain. The VH
domain exhibits high levels of expression and high solubility even in
the absence of a light chain variable domain. This VH domain was used
as a framework to construct a large human VH domain library (25 billion
clones) by grafting naturally occurring complementarity determining
regions (CDRs) from other human antibody libraries and randomly
mutating one of the CDRs. This library has been used internally for
selecting anti-HIV antibodies, viruses of biodefense interest and
cancer-related antigens and is available for licensing as a biological
material. Several high-affinity binders have already been identified.
The antibodies generated from this library are small (e.g., about
more than 14 kDa), highly stable and can be expressed at high levels as
monomers. The library permits the isolation of antibodies with
favorable properties: affinity, stability, solubility, high levels of
expression (at low cost), low rejection rates and low toxicity.
Applications: Antibody discovery; Therapeutics; Diagnostics;
Research Materials.
Inventors: Dimiter S. Dimitrov and Weizao Chen (NCI).
Relevant Publications:
1. W Chen, Z Zhu, Y Feng, X Xiao, DS Dimitrov. Construction of a
large phage-displayed human antibody domain library with a scaffold
based on a newly identified highly soluble, stable heavy chain variable
domain. J Mol Biol (2008), in press.
2. P Jirholt et al. Exploiting sequence space: Shuffling in vivo
formed complementarity determining regions into a master framework.
Gene. 1998 Jul 30;215(2):471-476.
3. Y Reiter et al. An antibody single-domain phage display library
of a native heavy chain variable region: Isolation of functional
single-domain VH molecules with a unique interface. J Mol Biol. 1999
Jul 16;290(3):685-698.
4. E Soderlind et al. Recombining germline-derived CDR sequences
for creating diverse single framework antibody libraries. Nat
Biotechnol. 2000 Aug 18;18(8):852-856.
5. LJ Holt et al. Domain antibodies: Proteins for therapy. Trends
Biotechnol. 2003 Nov;21(11):484-490.
6. L Riechmann and S Muyldermans. Single domain antibodies:
Comparison of camel VH and camelised human VH domains. J Immunol
Methods. 1999 Dec 10;231(1-2)25-38.
Patent Status: HHS Reference No. E-037-2008/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Michael A. Shmilovich, Esq.; 301/435-5019;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute's
Nanobiology Program is seeking statements of capability or interest
from parties interested in collaborative research to further develop,
evaluate, or commercialize Large Semi-Synthetic Human Antibody Domain
Library. Please contact John D. Hewes, PhD at 301-435-3121 or
[email protected] for more information.
Methods of Preventing Tissue Ischemia
Description of Technology: Nitric oxide (NO) plays an important
role as a major intrinsic vasodilator, and increases blood flow to
tissues and organs. Disruption of this process leads to peripheral
vascular disease, ischemic heart disease, stroke, diabetes, and many
more significant diseases.
Researchers at the NIH have discovered that the matrix protein
thrombospondin-1 blocks the beneficial effects of NO, and prevents it
from dilating blood vessels and increasing blood flow to organs and
tissues. Additionally, the inventors discovered that this regulation
requires interaction with thrombospondin-1's cell receptor CD47. Murine
studies revealed that, in the presence of NO, genetically altered mice,
lacking either thrombospondin-1 or CD47, showed dramatically improved
blood flow and tissue oxygenation. The inventors have also shown in
both mice and pigs that by targeting thrombospondin-1 and/or CD47,
blood flow can be dramatically increased to ischemic tissues. The same
therapeutics also were found to protect tissues from ischemia/
reperfusion injury.
Available for licensing and commercial development are:
Compositions and methods of treating tissue ischemia and/
or tissue damage due to ischemia, increasing blood vessel diameter,
blood flow and tissue perfusion in the presence of vascular disease
including peripheral vascular disease, atherosclerotic vascular disease
and stroke.
Compositions and methods for decreasing blood flow as in
the case of cancer through mimicking the effects of thrombospondin-1
and CD47 on blood vessel diameter and blood flow.
Applications:
Potential therapeutics for precise regulation of blood
flow to tissues and organs.
Efficient methods to increase tissue survival under
conditions of trauma and surgery.
Efficient methods for the treatment of elderly subjects
using agents that affect thrombospondin-1 and CD47 and thereby affect
tissue perfusion.
Methods for treatment of ischemia/reperfusion injury as
associated with transplant surgery.
Market:
People with ischemic disease are at increased risk of
heart attack (myocardial infarction), stroke and peripheral vascular
disease (PVD). Ischemic heart disease attributes to
[[Page 50829]]
more deaths, with 24 percent in the U.S., than any other cause.
Cerebral ischemia is the third leading cause of death
after heart diseases and cancer.
Decreased blood flow underlies a significant number of
chronic diseases that account for the majority of morbidity and
mortality for elderly adults in this country.
Cancer patients and traumatic injury victims requiring
reconstructive surgery.
Burn patients requiring skin transplants.
Organ transplant patients.
Development Status: Early-stage of development (in vivo data
available in mice and pigs).
Inventors: Jeff S. Isenberg et al. (NCI).
Patent Status: PCT Application No. PCT/US2007/080647 filed 5 Oct
2007, which published as WO 2008/060785 on 22 May 2008 (HHS Reference
No. E-227-2006/5-PCT-01).
Licensing Status: Available for licensing.
Licensing Contact: Charlene A. Sydnor, PhD; 301-435-4689;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute
Center for Cancer Research, Laboratory of Pathology is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
therapeutics targeting CD47 or thrombospondin-1. Please contact John D.
Hewes, PhD at 301-435-3121 or [email protected] for more information.
Total Synthesis of Northebaine, Normorphine, Noroxymorphone Enantiomers
and Derivatives via N-Nor Intermediates
Description of Technology: A new synthetic process has been found
in which nordihydrocodeinone, an early intermediate in the total
synthesis of codeine and related compounds, is easily formed into a
number of N-nor compounds. These N-nor compounds can be used as
precursors in the formation of narcotics, narcotic antagonists, or
narcotic agonist-antagonists.
The manufacture of drugs of this type, such as northebaine or
normorphine, can now be done without the use of thebaine as starting
material. The syntheses have fewer steps than previous methods, and
also have high yields. In addition, very significant simplification of
existing thebaine based processes for the manufacture of opiates can be
expected.
Applications: Potential new methodology for the synthesis of
intermediates for drugs including naloxone, naltrexone, percodan and
nalbuphine.
Market:
More than a quarter of Americans suffer daily pain, a
condition that costs the U.S. about $60 billion a year in lost
productivity.
Americans spent about $2.6 billion in over-the-counter
pain medications and another nearly $14 billion on outpatient
analgesics in 2004.
Worldwide, nearly 300 million people are believed to
suffer from chronic pain.
Inventors: Kenner C. Rice et al. (NIDDK)
Patent Status:
HHS Reference No. E-012-1986/1--
Australian Patent 642447 issued 15 Feb 1994.
Japanese Patent 2694156 issued 12 Sept 1997.
Canadian Patent 2067200 issued 30 Jun 1998.
European Patent 0496830 issued 31 Mar 1999 in Austria,
Switzerland, Germany, Denmark, Greece, Luxembourg, Spain, Belgium, The
Netherlands, Sweden, France, Italy and United Kingdom.
HHS Reference No. E-012-1986/2--
United States Patent 5,668,285 issued 16 Sept 1997.
Licensing Status: Available for licensing.
Licensing Contact: Charlene A. Sydnor, PhD; 301-435-4689;
[email protected].
Dated: August 18, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E8-19914 Filed 8-27-08; 8:45 am]
BILLING CODE 4140-01-P