[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]


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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.

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:

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     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