[Federal Register Volume 72, Number 243 (Wednesday, December 19, 2007)]
[Notices]
[Pages 71930-71931]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-24529]


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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.

Aquaporin 2 Polyclonal Antibodies

    Description of Technology: Aquaporins, also known as water 
channels, form pores in cell membranes and selectively transport water 
in and out of the cell. Aquaporins are involved in regulation of water 
balance and blood pressure, and thirteen different isoforms have been 
found in mammals. Aquaporin 2 (AQP2) is located in the collecting duct 
of the kidney, and is regulated by the peptide hormone vasopressin. 
AQP2 expression is increased in conditions where there is water 
retention, such as pregnancy and congestive heart failure, and 
mutations of AQP2 are associated with nephrogenic diabetes insipidus. 
Also, lithium treatment, often administered for bipolar disorder, can 
cause acquired diabetes insipidus by decreasing AQP2 expression.
    The inventors have developed rabbit polyclonal antibodies directed 
against a peptide sequence in the C-terminal region of AQP2 
(LKGLEPDTDWEEREVRRRQ). The sequence is upstream of phosphorylation 
sites in this region, and consequently the antibodies recognize both 
unphosphorylated and phosphorylated AQP2. The sequence is identical in 
human, rat, mouse, cow, and sheep.
    Applications: Western blotting, immunohistochemistry, and 
immunoprecipitation.
    Inventor: Mark A. Knepper (NHLBI).
    Related Publication: SR DiGiovanni, S Nielsen, EI Christensen, MA 
Knepper. Regulation of collecting duct water channel expression by 
vasopressin in Brattleboro rat. Proc Natl Acad Sci U S A. 1994 Sep 
13;91(19):8984-8988.
    Patent Status: HHS Reference No. E-045-2008/0--Research Tool. 
Patent prosecution is not being pursued for this technology.
    Licensing Status: This technology is available as a research tool 
under a Biological Materials License.
    Licensing Contact: Tara L. Kirby, PhD; 301/435-4426; 
[email protected].

Treatment for Chronic Inflammatory Disease and Cancer by Inhibition of 
MMP-1

    Description of Technology: The breakdown of connective tissue is a 
feature of many pathological diseases, including tumors as well as 
inflammatory diseases such as atherosclerosis, rheumatoid arthritis, 
and periodontitis. Proteases involved in connective tissue turnover, 
such as matrix metalloproteinases (MMPs) and the plasminogen activation 
system, have been shown to play a pivotal role in inflammatory disease 
and in tumor cell invasion, growth and metastasis. Matrix 
metalloproteinase-1 (MMP-1), a collagenase, is expressed in areas of 
rapid remodeling of the extracellular matrix in both normal and 
pathological conditions.
    The inventors have determined that the serine protease plasmin 
stimulates MMP-1 production in monocytes through binding to the annexin 
A2 heterotetramer. The inventors have also determined that inactive 
plasmin is an inhibitor of plasmin induction of MMP-1. The invention 
discloses new methods of suppressing inflammation and tumors through 
inhibition of plasmin activity, for example by using agents, including 
inactive plasmin, to inhibit plasmin-stimulated MMP-1 production.
    Applications: Therapeutics for inflammatory disease and tumor 
suppression.
    Market: In the United States, approximately two percent of the 
population have atherosclerosis, more than five percent have an 
autoimmune inflammatory disease, and approximately fifty percent of all 
adults over thirty have periodontitis.
    Development Status: Early stage.
    Inventors: Yahong Zhang and Larry M. Wahl (NIDCR).

[[Page 71931]]

    Related Publication: Y Zhang, ZH Zhou, TH Bugge, LM Wahl. 
Urokinase-type plasminogen activator stimulation of monocyte matrix 
metalloproteinase-1 production is mediated by plasmin-dependent 
signaling through annexin A2 and inhibited by inactive plasmin. J 
Immunol. 2007 Sep 1;179(5):3297-3304.
    Patent Status: U.S. Provisional Application No. 60/980,009 filed 15 
Oct 2007 (HHS Reference No. E-168-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Tara Kirby, PhD; 301/435-4426; 
[email protected].

Establishment of Two Cell Lines That Stably Express Luciferase for In 
Vivo Tracking

    Description of Technology: Available for licensing are two renal 
carcinoma cell lines, 786-O(luc) and 786-O/VHL/(luc) which both stably 
express luciferase. 786-O(luc) lacks von Hippel-Landau (VHL) protein 
expression and it has constitutively high expression of hypoxia-
inducible transcription factor-2alpha (HIF-2alpha). The second stably 
expresses VHL, a tumor suppressor, and has minimal HIF-2alpha 
expression. These cell lines can be tracked in vivo and can be used to 
study VHL-dependent and HIF-2alpha-dependent events such as 
tumorigenesis. VHL mutations lead to the clinical manifestations of von 
Hippel-Lindau disease, a rare autosomal dominant syndrome characterized 
by abnormal growth of blood vessels in multiple organs, including the 
brain and kidneys.
    Applications: Model to study VHL pathology.
    Advantages: Cell lines that stably express luciferase for in vivo 
tracking.
    Benefits: Easy, ready to use positive and negative VHL and HIF-
2alpha cells that stably express luciferase for in vivo tests.
    Market: Incidence of VHL syndrome is 1 in 38,951; HCC is the third 
leading cause of cancer death worldwide; HCC is the fifth most common 
cancer in the world; Post-operative five year survival rate of HCC 
patients is 30-40%.
    Inventor: Leonard M. Neckers, Marston Linehan (NCI).
    Patent Status: HHS Reference No. E-005-2007/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
(Urologic Oncology Branch) is seeking statements of capability or 
interest from parties interested in collaborative research to develop 
further uses for these two cell lines that stably express luciferase 
for in vivo tracking. Please contact John D. Hewes, PhD at 301-435-3121 
or [email protected] for more information.

HIV gp41-Membrane Proximal Region Arrayed on Hepatitis B Surface 
Antigen Particles for HIV Diagnostic and Vaccine Applications

    Description of Invention: This technology describes vectors 
encoding the membrane proximal region (MPR) and select variants from 
HIV-1 gp41 linked to the hepatitis B surface antigen (HBsAg) and the 
resulting expressed particles for use in HIV diagnostic and vaccine 
applications. HIV-1 gp41 membrane proximal region contains two epitopes 
recognized by broadly neutralizing human monoclonal antibodies 2F5 and 
4E10. However, immunization with gp41 MPR or the 2F5 or 4E10 epitopes 
have failed to raise neutralizing antibodies. In the subject 
technology, the particles were shown to bind antibodies from broadly 
neutralizing human sera and to the two known broadly neutralizing 
antibodies 2F5 and 4E10 with high relative affinities, demonstrating 
that the relevant epitopes are accessible for antibody binding and the 
potential utility of the particles in diagnostic applications. 
Additionally, these particles could be used to screen phage-display 
libraries for novel broadly cross-reactive neutralizing antibodies, of 
which only five are currently known. These particles could also be used 
for selection of MPR specific B cells. Lastly, these particles have 
been shown to be immunogenic and raise antibodies that recognize HIV-1 
Env gp160 expressed on the cell surface. These immunogens can elicit 
neutralizing antibodies specific for HIV gp41 MPR, the MPR of gp41 is 
highly conserved across various HIV clades and therefore is likely to 
generate broadly neutralizing antibodies when administered in a proper 
presentation in a lipid context as is the case in HBsAg particles. 
Multiple copies of the MPR of HIV-1 gp41 arrayed on the particles could 
significantly increase the immunogenic potential compared to monomeric 
molecules. An increase of this nature has been observed with HBsAg and 
HPV virus-like particles in hepatitis B and cervical cancer vaccines, 
respectively, suggesting that particulate array may improve the 
presentation of selected epitopes to the immune system.
    Applications: HIV vaccines; HIV diagnostics.
    Advantages: These immunogens can elicit neutralizing antibodies 
specific for HIV gp41 MPR, which is highly conserved across various HIV 
clades and therefore is likely to generate broadly neutralizing 
antibodies when administered in a proper presentation in a lipid 
context as is the case in HBsAg particles. Multiple copies of the MPR 
of HIV-1 gp41 arrayed on the particles could significantly increase the 
immunogenic potential compared to monomeric molecules.
    Inventors: Richard T. Wyatt (NIAID), Sanjay K. Phogat (NIAID), Ira 
Berkower (FDA).
    Patent Status: U.S. Provisional Application No. 60/653,930 filed 18 
Feb 2005 (HHS Reference No. E-123-2005/0-US-01); PCT Application No. 
PCT/US2006/005613 filed 17 Feb 2006, which published as WO 2006/112929 
on 30 Nov 2006 (HHS Reference No. E-123-2005/1-PCT-01); U.S. Patent 
Application No. 11/816,069 filed 10 Aug 2007 (HHS Reference No. E-123-
2005/1-US-02).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, Ph.D.; 301/435-5515; 
[email protected].
    Collaborative Research Opportunity: The NIAID Vaccine Research 
Center Structural Virology Section is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize HIV-1 MPR regions coupled 
with the hepatitis B surface antigen particles. Please contact Richard 
Wyatt, Ph.D. at [email protected] for more information.

    Dated: December 11, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-24529 Filed 12-18-07; 8:45 am]
BILLING CODE 4140-01-P