Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: March 24, 2008 (Volume 73, Number 57)             
                  Page 15531-15533

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.

HIV Monoclonal Antibodies

    Description of Technology: This technology describes several 
hybridomas that produce monoclonal antibodies (mAbs) useful in HIV 
research applications. The mAbs are specific for either gp41 or gp120. 
In particular, the hybridomas producing mAbs designated D19, D56, M12, 
T8 and T24 (all anti-gp120), and T32 and T33 (gp41 specific) were found 
to be of particular utility. Additional hybridomas expressing mAbs 
disclosed in the publications may also be available.
    Applications: HIV research.
    Development Status: Murine hybridomas available; T32 mAb available.

[[Page 15532]]

    Inventors: Bernard Moss, Patricia Earl, Christopher Broder, and 
Robert Doms (NIAID).

Publications:

    1. PL Earl, CC Broder, RW Doms, B Moss. Epitope map of human 
immunodeficiency virus type 1 gp41 derived from 47 monoclonal 
antibodies produced by immunization with oligomeric envelope protein. J 
Virol. 1997 Apr;71(4):2674-2684.
    2. U.S. Patents 6,039,957 and 6,171,596 (gp140 mAbs).
    3. PL Earl, CC Broder, D Long, SA Lee, J Peterson, S Chakrabarti, 
RW Doms, B Moss. J Virol. 1994 May;68(5):3015-3026 (gp140 mAbs).

Patent Status:

    HHS Reference No. E-109-2008/0 (anti-gp41mAbs)--Research Tool. 
Patent protection is not being pursued for this technology.
    HHS Reference No. E-200-1993/1 (anti-gp140 mAbs).
    Licensing Status: Available for biological materials licensing 
only; the IP that includes descriptions of the anti-gp120 and gp41 mAbs 
is available for exclusive or non-exclusive licensing.
    Licensing Contact: Susan Ano, PhD; 301-435-5515; anos@mail.nih.gov.
    Collaborative Research Opportunity: The NIAID/DIR/LVD is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
HIV Monoclonal Antibodies. Please contact either Michael Pizali or Dana 
Hsu at 301-496-2644 for more information.

Epoxy-guaiane Cancer Inhibitors: New Class of Natural Products Isolated 
from the African Plant Phyllanthus englerii

    Description of Technology: The present invention involves the 
observation of renal selective inhibitory activity by the extracts of 
the African plant Phyllanthus englerii. Bioassay-guided fractionation 
of the purified extracts revealed a series of novel chemical entities 
which are named Englerin A-F. The englerins and their derivatives are 
useful in the treatment of a number of cancers, particularly renal 
cancer. The englerins exhibit selective and potent renal cell 
inhibitory activity in vitro.
    These compounds are recoverable in reasonable yield from natural 
product extracts and are considered to be reasonably tractable for 
synthetic chemistry schemes. Sufficient supply of several analogs had 
been extracted from repository samples for identification and initial 
biological characterization. Subsequent five-dose testing in the NCI60 
screening panel indicated and confirmed impressive renal-selective 
activity.
    Applications: The new chemical entities can be potential cancer 
therapeutics, especially for renal cancer.

Advantages:

    There is reasonable yield and recovery of the compounds from the 
natural product extracts.
    The synthetic chemistry schemes for synthesis of these compounds 
are considered to be reasonably tractable.
    Development Status: Proof of concept in vitro studies have been 
completed and further in vitro and in vivo animal model studies are 
ongoing.
    Inventors: John A. Beutler et al. (NCI).
    Relevant Publication: S. Sutthivaiyakit et al. A novel 29-nor-3,4-
seco-friedelane triterpene and a new guaiane sesquiterpene from the 
roots of Phyllanthus oxyphyllus. Tetrahedron 2003 Dec 8;59(50):9991-
9995.
    Patent Status: U.S. Provisional Application No. 61/018,938 filed 04 
Jan 2008 (HHS Ref. No. E-064-2008/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
vathyams@mail.nih.gov.
    Collaborative Research Opportunity: The National Cancer Institute 
Molecular Targets Development Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize epoxy-guaiane 
cancer inhibitors. Please contact John D. Hewes, Ph.D. at 301-435-3121 
or hewesj@mail.nih.gov for more information.

VEGF-B as a Therapeutic Agent for Neurodegenerative Disease

    Description of Technology: This technology identifies vascular 
endothelial growth factor-B (VEGF-B) as a potent inhibitor of apoptosis 
in neuronal and other types of cells, and highlights its ability to 
rescue these cells from apoptosis in the brain and retina. Members of 
the VEGF family of proteins are noted for their angiogenic and blood 
vessel permeabilizing abilities. Some members of this family, such as 
VEGF-A, may promote neurogenesis; however, the neuroprotective effects 
are accompanied by inherent angiogenic and vessel permeabilizing 
activities, which make VEGF-A treatment unsuitable for clinical use as 
neuroprotective agents. The inventor has recently discovered that 
unlike the other VEGF family members, the neuroprotective effects of 
VEGF-B are not associated with undesired angiogenesis or increased 
blood vessel permeability, but rather through inhibiting apoptosis via 
suppressing the expression of the apoptotic/cell death related genes 
(1). This discovery, that the use of VEGF-B can protect endangered 
neurons from death and avoid the undesirable effects associated with 
other VEGF family members, makes it a promising candidate for the 
treatment of neurodegenerative and other diseases that involve neuronal 
impairment and/or excessive apoptosis, such as muscular dystrophy, 
stroke, brain injury, myocardial infarction, ischemic renal damage, 
etc.
    In-vivo trials have already demonstrated the efficacy of VEGF-B as 
a therapeutic agent. VEGF-B has shown efficacy in mouse models 
suffering from optic nerve crush injury (ONC). ONC induces the 
apoptotic death of retinal ganglion cells (RGCs) in the retina. 
However, intravitreal administration of a single dose of the VEGF-B 
protein significantly restored the number of RGCs by 1.7 fold, 
demonstrating the potential use of the protein in treating degenerative 
ocular diseases, such as glaucoma. Similar results were obtained when 
exogenous administration of VEGF-B to the brain cortex was shown to 
significantly reduce ischemia-induced stroke volume and to protect 
neurons from apoptosis in the brain. Further, intracerebroventricular 
injection of VEGF-B in mutant knockout mice lacking the gene for VEGF-B 
(VEGFB-KO) has caused a complete reversal of neuronal impairment and 
restored neurogenesis back to normal levels.
    Applications: VEGF-B as a powerful therapeutic agent for use in a 
wide range of therapeutic intervention regimes where neuronal repair 
and inhibition of apoptosis are required.
    Inventors: Xuri Li (NEI).

Relevant Publications

    1. Yang Li, Fan Zhang, Nobuo Nagai, Zhongshu Tang, Shuihua Zhang, 
Pierre Scotney, Johan Lennartsson, Chaoyong Zhu, Yi Qu, Changge Fang, 
Jianyuan Hua, Osamu Matsuo, Guo-Hua Fong, Hao Ding, Yihai Cao, Kevin G. 
Becker, Andrew Nash, Carl-Henrik Heldin, and Xuri Li. VEGF-B inhibits 
apoptosis via VEGFR-1-mediated suppression of the expression of BH3-
only protein genes in mice and rats. J Clin Invest. 2008 Mar 
3;118(3):913-923. Published online 2008 Feb 7, doi 10.1172/JCI33673.
    2. Yunjuan Sun, Kunlin Jin, Jocelyn T. Childs, Lin Xie, Xiao Ou 
Mao, David A. Greenberg. Vascular endothelial growth factor-B (VEGFB) 
stimulates

[[Page 15533]]

neurogenesis: Evidence from knockout mice and growth factor 
administration. Dev Biol. 2006 Jan 15;289(2):329-335.
    Patent Status: U.S. Provisional Application No. 60/972,780 filed 15 
Sep 2007 (HHS Reference No. E-154-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jasbir (Jesse) S. Kindra, J.D., M.S.; 301-435-
5170; kindraj@mail.nih.gov.
    Collaborative Research Opportunity: The National Eye Institute, 
NIH, Office of Scientific Director, Unit of Retinal Vascular 
Neurobiology, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize VEGF-B as a therapeutic agent in treating 
various types of degenerative (neural, vascular, muscular, etc.) 
diseases, and to study the molecular and cellular mechanisms involved. 
Please contact John D. Hewes, PhD at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

Rapid Clostridium botulinum Diagnostic for Food Safety and Biodefense 
Applications

    Description of Technology: The urgent need for a rapid diagnostic 
test capable of detecting all serotypes of C. botulinum is well known. 
Botulinum neurotoxins (BoNTs) are the most potent biological toxins 
known and are categorized as category A biodefense agents because of 
lethality and ease of production. BoNTs are also one of the most deadly 
agents associated with food poisoning. Current diagnostic methods 
include clinical observation of symptoms that could be mistaken for 
other neurological conditions and a mouse protection bioassay that 
takes as long as four days and has a number of disadvantages. The 
subject technology utilizes unique PCR primers for the detection of the 
non-toxin non-hemaglutinin (NTNH) gene of C. botulinum; this gene is 
highly conserved in all C. botulinum toxin types and subtypes. Thus, 
samples that contain botulinum can be determined regardless of serotype 
involved, providing a universal means of diagnosis. Further, the 
technology describes different PCR primers and flurogenic probes for a 
BoNT-specific assay. The type-specific assay can be used independently 
or in conjunction with the universal assay described above. The 
universal and type-specific assays were successfully used first to 
identify positively botulinum DNA samples in a test of botulinum and 
non-botulinum clostridia species then to determine the toxin type. The 
diagnostic testing described by the subject technology requires less 
significantly less time than the current gold standard diagnostic 
tests.
    Applications: Universal diagnostic test for C. botulinum; 
Diagnostic test for C. botulinum capable of detecting all seven toxin 
types; Combination diagnostic; Food safety applications; Biodefense 
applications.
    Development Status: Fully developed.
    Inventors: Daniel C. Douek et al. (VRC/NIAID).
    Patent Status: U.S. Provisional Application No. 60/884,539 filed 11 
Jan 2007 (HHS Reference No. E-046-2007/0-US-01); PCT Patent Application 
No. PCT/US2008/50872 filed 11 Jan 2008 (HHS Reference No. E-046-2007/0-
PCT-02).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, PhD; 301/435-5515; anos@mail.nih.gov.
    Collaborative Research Opportunity: The NIAID is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize ``Rapid 
Clostridium botulinum Diagnostic for Food Safety and Biodefense 
Applications.'' Please contact either Rosemary Walsh or Barry 
Buchbinder at 301-496-2644 for more information.

Prolidase Expression Construct Useful as Anti-Angiogenesis Screen

    Description of Technology: The technology describes a prolidase 
expression construct and a method of using the construct to isolate 
stable transfectants with high prolidase expression. Specifically, a 
human colorectal cancer cell line (RKO) was transfected with a plasmid 
(pcDNA3.1) expressing prolidase cDNA. Using this cell line, the 
inventors found that extracellular matrix degradation is associated 
with the prolidase-dependent activation of the hypoxia/inflammation 
pathway. The construct and transfectants can also be used to study 
other regulatory functions of prolidase.

Applications

    Prolidase as a target for anti-angiogenesis drugs: Angiogenesis, a 
prerequisite for tumor growth, requires proteolysis of the 
extracellular matrix (ECM). Prolidase participates in the degradation 
of the ECM by hydrolyzing collagen dipeptides having C-terminal proline 
or hydroxyproline. Current anti-angiogenic approaches target matrix 
metalloproteinase activity, but this can cause musculoskeletal 
complications. By modulating prolidase activity to inhibit the 
degradation of the ECM, it may be possible to provide an alternative 
anti-angiogenic approach with fewer side effects. The prolidase 
construct and transfected cell lines could be used as a screen for 
prolidase modulators, which could be developed as anti-angiogenesis 
agents.
    Prolidase as a target for anti-inflammatory drugs and wound-healing 
agents: Inherited prolidase deficiency is also associated with 
defective wound healing, extensive skin alterations, and 
immunodeficiency. Products from the prolidase activity screen may also 
have potential use in patients with prolidase deficiency, chronic 
inflammation, or problematic wound healing.
    Development Status: Pre-clinical stage.
    Inventors: Yongmin Liu (NCI), Arkadiusz Surazynski (NCI), James M. 
Phang (NCI), Sandra K. Cooper (NCI/SAIC), Steven P. Donald (NCI).
    Publication: A Surazynski, SP Donald, SK Cooper, MA Whiteside, K 
Salnikow, Y Liu, JM Phang. Extracellular matrix and HIF-1 signaling: 
The role of prolidase. Int J Cancer. 2008 Mar 15;122(6):1435-1440.
    Patent Status: HHS Reference No. E-235-2006/0--Research Material. 
Patent protection is not being sought for this technology.
    Licensing Status: This invention is available for licensing through 
a Biological Materials License.
    Licensing Contact: David A. Lambertson, PhD; 301/435-4632; 
lambertsond@mail.nih.gov.

     Dated: March 17, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-5813 Filed 3-21-08; 8:45 am]

BILLING CODE 4140-01-P