[Federal Register Volume 74, Number 147 (Monday, August 3, 2009)]
[Notices]
[Pages 38442-38444]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-18496]


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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.

A Tumorigenic MEF/3T3 Tet-Off Mouse Fibroblast Cell Line Stably 
Transfected With a T7-Tagged Srp20 Expression Construct (pJR17)

    Description of Technology: Alternative RNA splicing is a means by 
which the human genome can produce many more proteins from the genes 
available. It is emerging that aberrations in alternative RNA splicing 
contributes to the development of cancers. SRp20 is a cellular splicing 
factor that is involved in the process of alternative splicing of RNA. 
Investigators at the National Cancer Institute (NCI), National 
Institutes of Health (NIH) have discovered that SRp20 is overexpressed 
in many types of cancer and furthermore promotes the induction and 
maintenance of tumor cell growth. This was demonstrated in part by 
engineering a non-tumorigenic cell to become tumorigenic in mice by 
overexpressing SRp20.
    Research Material available for licensing is a tumorigenic MEF/3T3 
tet-off mouse fibroblast cell line stably transfected with a T7-tagged 
SRp20 expression construct (pJR17) that is under the transcriptional 
control of tetracycline.
    Applications: Use in pre-clinical development of therapeutic 
approaches to cancer that target aberrant alternative RNA splicing.
    Advantages: Transcriptional control of expression using Tet-off 
system; Availability of stably transfected cell line saves time and 
effort for other investigators.
    Market: Research Tool.
    Development Status: Ready to use.
    Inventors: Zhi-Ming Zheng and Rong Jia (NCI).
    Publications: Manuscript in preparation.
    Patent Status: HHS Reference No. E-229-2009/0--Research Material. 
Patent protection is not being sought for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, HIV and AIDS Malignancy Branch, is seeking 
statements of capability or interest from

[[Page 38443]]

parties interested in collaborative research to further develop, 
evaluate, or commercialize A Tumorigenic MEF/3T3 Tet-Off Mouse 
Fibroblast Cell Line Stably Transfected with a T7-Tagged Srp20 
Expression Construct (pJR17). Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

Truncated Methanocarba Adenosine Derivatives as A3 Adenosine 
Receptor Antagonists

    Description of Technology: Novel A3 adenosine 
antagonists available for licensing. A3 receptors are 
particularly highly expressed in inflammatory cells, making it a 
potentially desirable target for inflammatory diseases. This technology 
relates to highly specific antagonists and partial agonists of 
A3 adenosine receptors, which are negatively coupled to 
adenylate cyclase and have been broadly implicated in inflammation, 
cardiovascular disease, and cancer. Further, A3 adenosine 
receptors have been implicated in allergies, asthma, and chronic 
obstructive pulmonary disease.
    Advantages: There are four known subtypes of adenosine receptors 
(A1, A2A, A2B, and A3). All 
are positively or negatively linked to cAMP, but have different 
distributions and different therapeutic potentials. In particular, the 
use of A1 and A2 selective ligands has been 
limited by the ubiquity of expression of the receptors throughout the 
body and the resultant side effects. On the other hand, high levels of 
A3 receptor expression are limited to the CNS, testes, and 
the immune system. Thus, A3 receptors represent a 
potentially highly specific target for treating related diseases.
    Inventor: Kenneth A. Jacobson (NIDDK).
    Related Publication: A Melman, B Wang, BV Joshi, ZG Gao, S de 
Castro, CL Heller, SK Kim, LS Jeong, KA Jacobson. Selective 
A3 adenosine receptor antagonists derived from nucleosides 
containing a bicyclo[3.1.0]hexane ring system. Bioorg Med Chem. 2008 
Sep 15;16(18):8546-8556.
    Patent Status: U.S. Provisional Application No. 61/085,588 filed 01 
Aug 2008 (HHS Reference No. E-285-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Steve Standley, Ph.D.; 301-435-4074; 
[email protected]
    Collaborative Research Opportunity: The NIDDK, Laboratory of 
Bioorganic Chemistry is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize A3 adenosine receptor 
antagonists. Please contact Kenneth A. Jacobson, Ph.D. at 
[email protected] or the NIDDK Office of Technology Transfer and 
Development at 301-451-3636 for more information.

Novel Proteins From the Sand Fly Lutzomyia longipalpis Are Potent 
Inhibitors of Complement Activity

    Description of Technology: This invention relates to the discovery 
that five proteins from the salivary glands of Lutzomyia longipalpis, 
LJM04, LJM11, LJM19, LJM26, and LJL143, have anti-complement activity. 
These proteins demonstrate potent inhibition of both the classical and 
alternative pathways for complement activation. All proteins, excluding 
LJM19, were shown to bind and inhibit the C3b molecule, thus 
inactivating an integral component of the complement pathway.
    The complement system is a very important line of defense against 
pathogens, and is involved in many pathologies and syndromes affecting 
human health. It is therefore envisioned that these five novel proteins 
may be used to treat conditions where the complement system is involved 
including lupus erythematosus, juvenile arthritis, and complications 
associated with cardiac surgery and hemodialysis.
    Applications:
     Potent inhibition of complement activity.
     Treatment of diseases involving the complement system.
    Development Status: Early Stage.
    Inventors: Jesus G. Valenzuela et al. (NIAID).
    Relevant Publication: RR Cavalcante, MH Pereira, NF Gontijo. Anti-
complement activity in the saliva of phlebotomine sand flies and other 
haematophagous insects. Parasitology 2003 Jul;127(Pt 1):87-93.
    Patent Status: U.S. Provisional Application No. 61/142,098 filed 31 
Dec 2008 (HHS Reference No. E-205-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey A. James, PhD; 301-435-5474; 
[email protected].

Potent Anti-Coagulant Activity of a Novel Protein From the Sand Fly 
Lutzomyia longipalpis

    Description of Technology: The salivary gland lysates of Lutzomyia 
longipalpis, the New World sand fly and main vector for visceral 
leishmaniasis, contain an anti-coagulant protein that helps the fly 
complete its blood meal. This invention relates to the identification 
of LJL143, a salivary gland protein of L. longipalpis, as a specific 
inhibitor of coagulation factor Xa. LJLl43 is secreted in the saliva of 
L. longipalpis and exerts its effects by tightly binding the catalytic 
site of factor Xa. By directly binding the catalytic site, it is 
believed that the potent anti-coagulant activity of LJL143 will be 
accompanied by reduced side effects compared to anti-coagulant drugs 
that rely on activating serine proteases. LJL143 has a novel sequence 
with no reported homology in the gene bank, and is the first anti-
coagulant factor identified in sand flies.
    LJLl43 may be used for inhibiting factor Xa activity in vivo or as 
a prototype for designing specific inhibitors of factor Xa. Because of 
its high specificity, LJLl43 may be used as an anti-coagulant in a 
number of pro-coagulant diseased states including deep venous 
thrombosis, coronary artery disease, non-hemorrhagic stroke, and 
unstable angina with potentially reduced side effects.
    Applications:
     Safe and effective anti-coagulant for therapeutic use.
     Treatment of several conditions such as deep venous 
thrombosis, coronary artery disease, non-hemorrhagic stroke, and 
unstable angina.
    Advantages: May be safer than other important blood thinning drugs 
such as Warfarin.
    Development Status: Early Stage.
    Market: Predicted $7.4 billion anti-coagulant market by 2016.
    Inventors: Jesus G. Valenzuela et al. (NIAID).
    Publication: JG Valenzuela, M Garfield, ED Rowton, VM Pham. 
Identification of the most abundant secreted proteins from the salivary 
glands of the sand fly Lutzomyia longipalpis, vector of Leishmania 
chagasi. J Exp Biol. 2004 Oct;207(Pt 21):3717-3729.
    Patent Status: U.S. Provisional Application No. 61/142,107 filed 31 
Dec 2008 (HHS Reference No. E-204-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Jeffrey A. James, PhD; 301-435-5474; 
[email protected].

Novel Dopamine Receptor Ligands as Therapeutics for Central Nervous 
System Disorders

    Description of Technology: The dopamine D3 receptor subtype is a 
member of the dopamine D2 subclass of receptors. These receptors have 
been

[[Page 38444]]

implicated in a number of CNS disorders, including psychostimulant 
abuse, psychosis and Parkinson's disease. Compounds that bind with high 
affinity and selectivity to D3 receptors can not only provide important 
tools with which to study the structure and function of this receptor 
subtype, but may also have therapeutic potential in the treatment of 
numerous psychiatric and neurologic disorders.
    The 4-phenylpiperazine derivatives are an important class of 
dopamine D3 selective ligands. However, due to their highly lipophilic 
nature, these compounds suffer from solubility problems in aqueous 
media and reduced bioavailability. To address this problem, a process 
was designed to introduce functionality into the carbon chain linker of 
these compounds. Compared to currently available dopamine D3 receptor 
ligands, the resulting compounds show improved pharmacological 
properties and D3 selectivities but due to their more hydrophilic 
nature, these derivatives are predicted to have improved water 
solubility and bioavailability.
    Applications:
     Therapeutics for a variety of psychiatric and neurologic 
disorders
     Research tools to study D3 receptor structure and function
    Advantages:
     Improved pharmacological properties and selectivity over 
existing dopamine D3 receptor ligands
     Hydrophilic nature likely to lead to improved water 
solubility and bioavailability
    Development Status: Pre-clinical discovery.
    Further R&D Needed:
     Evaluate selected compounds in animal models of drug 
abuse, psychosis, obesity and Parkinson's disease.
     Design and synthesize novel, functionalized analogs using 
both classical and computational drug design to improve D3 receptor 
affinity and selectivity.
     Evaluate compounds for binding in D3 and D2 receptor 
expressing cell lines and in in vitro functional assays.
     Correlate in vitro binding affinities with in vivo 
function in rats and monkeys and evaluate compounds in knockout mice 
models.
     Pursue PET and SPECT imaging agents by radiolabel of D3 
ligands and evaluation in rats and non-human primates.
    Inventors: Amy H. Newman (NIDA), Peter Grundt (NIDA), Jianjing Cao 
(NIDA), et al.
    Patent Status: PCT Application No. Pct/US2007/71412 filed 15 Jun 
2007, which published as WO 2008/153573 on 18 Dec 2008 (HHS Reference 
No. E-128-2006/0-PCT-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Charlene Sydnor, PhD; 301-435-4689; 
[email protected].
    Collaborative Research Opportunity: The National Institute on Drug 
Abuse's Medications Discovery Research Branch is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize 4-
phenylpiperazine derivatives as dopamine D3 selective ligands. Please 
contact Vio Conley, MS at 301-435-2031 or [email protected] for 
additional information.

High-Yield Methods of Producing Biliverdin

    Description of the Technology: This invention describes methods of 
making high yields of biliverdin, the pharmaceutical compositions of 
biliverdin made using that process, and methods of using the 
compositions therapeutically.
    In reaction to a wide range of cellular stresses, hemoglobin is 
naturally metabolized to biliverdin, which is then quickly metabolized 
to bilirubin, a bile pigment, through a highly conserved set of 
enzymes. Both bilirubin and biliverdin are normally processed for rapid 
excretion, and excessive serum levels of bilirubin have known toxic 
effects (most notably jaundice). Surprisingly, research in the past 
decade has shown that decreasing serum levels correlate inversely with 
the prognosis of various disorders, such as ischemia/reperfusion 
injuries, atherosclerosis, organ transplantation, and several 
autoimmune diseases. Indeed, in animal-model studies, inducing a mild 
case of jaundice actually improved outcome. Unfortunately, bilirubin is 
relatively insoluble, and so is not a practical pharmaceutical itself.
    Biliverdin has lower direct toxicity and substantially greater 
solubility than bilirubin, and also appears to have some direct 
therapeutic effects similar to bilirubin. Accordingly, biliverdin has 
been widely studied lately. Generating high yields of pure biliverdin 
is difficult, however, because any system with the enzymes to break 
down hemoglobin also has enzymes converting biliverdin to bilirubin. 
The inventors have created a system of generating microorganisms 
(yeast) lacking the enzymes that break biliverdin down to bilirubin.
    Applications: Production of biliverdin for immunomodulatory and 
cytoprotective therapy (or adjuvant) in any condition involving an 
overactive immune response.
    Advantages:
     High yield of biliverdin with low contamination of 
bilirubin.
     Produces only active isomers of biliverdin.
     Unlike prior methods, new method uses starting material 
that is inexpensive and plentiful.
    Development Status: Successful generation of Candida albicans with 
biliverdin-generating system.
    Inventors: Michael L. Pendrak and David D. Roberts (NCI).
    Patent Status: HHS Reference No. E-040-2004/0--Issued U.S. Patent 
7,504,243; Pending U.S. Application 12/364,054 (divisional, filed 02 
Feb 2009).
    Relevant Publication: ML Pendrak et al. Heme oxygenase in Candida 
albicans is regulated by hemoglobin and is necessary for metabolism of 
exogenous heme and hemoglobin to alpha-biliverdin. J Biol Chem. 20 Jan 
2004;279(5):3426-3433.
    Licensing Status: Available for licensing.
    Licensing Contact: Bruce Goldstein, JD, MS; (301) 435-5470; 
[email protected].
    Collaborative Research Opportunity: The Laboratory of Pathology in 
the Center for Cancer Research of the National Cancer Institute is 
seeking parties interested in collaborative research directed toward 
clinical applications of biliverdin. For more information about the 
research, please contact either Dr. Michael Pendrak (NCI/CCR Laboratory 
of Pathology) at (301) 496-6264, or Dr. April Franks (NCI Technology 
Transfer Center) at (301) 496-0477.

    Dated: July 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-18496 Filed 7-31-09; 8:45 am]
BILLING CODE 4140-01-P