[Federal Register Volume 76, Number 64 (Monday, April 4, 2011)]
[Notices]
[Pages 18561-18564]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-7925]
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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.
New Molecules for HIV Therapeutics: Fab, scFv, and Related Binding
Molecules Specific for HIV-1 Rev
Description of Invention: The invention offered for licensing and
commercial development is in the field of HIV therapeutics. More
specifically, the invention relates to methods and compositions for
treating and/or inhibiting HIV infection or any other lentivirus. The
invention describes the identification, though phage display, of a
chimeric rabbit/human anti-Rev Fab (SJS-R1) that can inhibit
polymerization of the HIV Rev protein and thus inhibit its normal
function in virus replication. The Fab binds with very high affinity to
a conformational epitope in the N-terminal half of HIV-1 Rev. The
corresponding single chain antibody (scFv) was also prepared and
characterized. Methods of making and using SJS-R1 Fab and SJS-R1 scFv,
and antibodies and antibody fragments that share at least one CDR with
SJS-R1 Fab, are provided. Specific described methods include methods of
preventing or reversing polymerization of HIV Rev, methods of reducing
infectivity of replication of a lentivirus, inhibiting Rev function in
a cell infected with a lentivirus, and methods of treating a
[[Page 18562]]
disease or symptom associated with Rev expression in an animal.
Applications: HIV therapeutics.
Advantages
The invention utilizes a novel target and thus can be
effective in conjunction with other HIV drugs.
The chimeric structure of the Fab makes it possible to
produce it in rabbit in high yields while being readily applicable for
human treatment.
Development Status: The therapeutic molecules have been produced
and their strong affinity to Rev and its inhibitory effect on HIV
proliferation was demonstrated.
Inventors: Stephen J. Stahl (NIAMS) et al.
Patent Status: U.S. Provisional Application No. 61/439,307 filed
February 3, 2011 (HHS Reference No. E-064-2011/0-US-01), entitled
``Generation and Use of Fab, scFv, and Related Binding Molecules
Specific for HIV-1 Rev.''
Related Publications
1. Stahl SJ, Watts NR, Rader C, DiMattia MA, Mage RG, Palmer I,
Kaufman JD, Grimes JM, Stuart DI, Steven AC, Wingfield PT. Generation
and characterization of a chimeric rabbit/human Fab for co-
crystallization of HIV-1 Rev. J Mol Biol. 2010 Apr 2;397(3):697-708.
[PubMed: 20138059]
2. DiMattia MA, Watts NR, Stahl SJ, Rader C, Wingfield PT, Stuart
DI, Steven AC, Grimes JM. Implications of the HIV-1 Rev dimer structure
at 3.2 A resolution for binding to the Rev response element. Proc Natl
Acad Sci U S A. 2010 Mar 30;107(13):5810-5814. [PubMed: 20231488]
Licensing Status: Available for licensing and commercial
development.
Licensing Contacts
Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
John Stansberry, PhD; 301-435-5236; [email protected].
Collaborative Research Opportunity: The National Institute of
Arthritis and Musculoskeletal and Skin Diseases, Protein Expression
Laboratory is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate, or
commercialize the technology. Please contact Cecilia Pazman, PhD at
301-402-5579 for more information.
Modulation of Leucine-Rich Repeats and Calponin Homology Domain-
Containing Protein 4 (Lrch4) Activity for Therapeutic Applications
Description of Invention: NIH Inventors have recently discovered a
novel Leucine-rich repeat and calponin homology domain-containing
protein 4 (Lrch4) in a proteomic screen of the plasma membrane of
lipopolysaccharide (LPS)-exposed macrophages. Expression data by RT-PCR
revealed that all Lrch family members (1-4) are expressed in
macrophages, but only Lrch4 was recruited into lipid rafts (signaling
microdomains of the plasma membrane) by LPS. Lrch4 is the most highly
expressed Lrch family member in mouse tissues. It is a predicted
single-spanning transmembrane protein that is encoded by the Lrch4 gene
in humans. The Lrch4 ectodomain is predicted to have a series of
leucine-rich repeats, the motifs by which Toll like Receptors (TLR) are
thought to bind microbial ligands. The human form of Lrch4 is 83%
identical to murine Lrch4 and is predicted to have 680 amino acids and
a molecular weight of 73 kDa.
NIH inventors have shown that Lrch4 is expressed on the plasma
membrane of macrophages. They have determined that Lrch4 regulates pro-
inflammatory signals (NF-[kappa]B activation, cytokine induction)
emanating from all TLRs tested, and also regulates ligand-independent
signals from MyD88. Further, LPS-induced p38, JNK, and NF[kappa]B
activation are attenuated following Lrch4 knockdown, indicating that
Lrch4 regulates upstream LPS signaling events. LPS-induced expression
of the NF-[kappa]B-dependent cytokine TNF[alpha] was attenuated
following Lrch4 knockdown at the level of both transcript and protein.
Based on these and other findings, the inventors of this technology
propose that Lrch4 may be a novel component of TLR receptor complexes
and that modulation of Lrch4 activity might open up new opportunities
for developing novel therapeutics for inflammatory diseases.
Applications: Identification and development of modulators of Lrch4
activity to treat inflammatory disorders, cancer, and sepsis.
Development Status: Early-stage.
Inventors: Michael B. Fessler, et al. (NIEHS).
Related Publication: Dhungana S et al. Quantitative proteomics
analysis of macrophage rafts reveals compartmentalized activation of
the proteasome and of proteasome-mediated ERK activation in response to
lipopolysaccharide. Mol Cell Proteomics 2009 Jan; 8(1):201-213.
[PubMed: 18815123]
Patent Status: U.S. Provisional Application No. 61/433,491 filed 17
January 2011 (HHS Reference No. E-012-2011/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Suryanarayana Vepa, PhD, J.D.; 301-435-5020;
[email protected].
Collaborative Research Opportunity: The National Institute of
Environmental Health Sciences (NIEHS) Laboratory of Respiratory Biology
is seeking statements of capability or interest from parties interested
in collaborative research to further develop, evaluate, or
commercialize Lrch4. Please contact Dr. Elizabeth M. Denholm at
[email protected] for more information.
Superparamagnetic Nanocomplexes and Their Use as Contrast Agents in MRI
Description of Invention: The invention offered for licensing and
commercial development relates to the fields of cell therapy and
tracking of such therapy by magnetic resonance imaging. More
specifically the technology describes novel superparamagnetic magnetic
resonance contrast agents, methods of making the agents, and methods of
labeling cells with the contrast agents and imaging the labeled cells
using magnetic resonance.
The self assembled agents are composed of three (3) components:
Superparamagnetic iron oxide nanoparticle (e.g. F3O4), associated with
a carbohydrate coating (e.g., a polycation (e.g., Protamine Sulfate);
and a polycation (e.g., glycosaminoglycan:Heparin). Self-assembling
superparamagnetic nanocomplexes made from simple commercially available
chemicals such as Heparin sulfate (H), Protamine sulfate (P), and
Ferumoxytol nanocomplexes (HPF nanocomplexes) can effectively label
stem cells, immune cells, tumor cells, or any other therapeutically
engineered cells for cellular MRI. Biological cells can be labeled with
the nanocomplexes by contacting cells under conditions sufficient to
produce the nanocomplexes, or by contacting the cells with pre-
assembled nanocomplexes. The labeled biological cells can be
transplanted into an individual, imaged by MRI and the migration
pattern and/or cellular distribution pattern of the labeled biological
cells in the subject can then be detected. This technique will readily
facilitate the tracking of the therapeutic cells, and thus render cell-
based therapy and/or tissue repair more precise, accurate and
effective.
Applications
Clinical--
Cell-based therapy (e.g. stem cells, or immune cells
therapy, genetic engineered cells); monitoring and
[[Page 18563]]
detecting cell trafficking and distribution.
Diagnostics.
Research--
Cell-based therapy.
Tissue regeneration.
Advantages
Avoid radioactive labeling.
More efficient cell incorporation than the use of
noncomplexed paramagnetic or superparamagnetic particles.
Non toxic.
Easily prepared from three (3) commercially available FDA
approved drugs off label. No synthesis is required (self assembled).
No FDA approved MRI contrast agent containing paramagnetic
or superparamagnetic iron oxide nanoparticles.
Development Status
The labeling complex has been repeatedly prepared. May
require some further optimization for specific cell products and scale
up.
Incorporation into mammal cells has been demonstrated.
Market: The total U.S. market for imaging reagents was $2.8 billion
in 2003 and is expected to grow to $4.5 billion by 2010 at an average
annual growth rate of 6.9%. Sales of MRI reagents for cardiovascular
applications were $770 million in 2003 and are expected to rise at an
average annual growth rate of 7.0%. Reagents used in oncology and
gastrointestinal tract are rising at average annual growth rates of
7.0% and 5.1%, respectively. The subject technology maybe readily
applied in both diagnostics and therapeutic fields. A commercial
development of the subject technology may therefore be attractive for
commercial organizations.
Inventors: Joseph A. Frank et al. (CC).
Patent Status: U.S. Provisional Application No. 61/439,106 filed
February 3, 2011 (HHS Reference No. E-285-2010/0-US-01), entitled
``Superparamagnetic Nanocomplexes, Articles, and Methods of Use
Thereof''.
Relevant Publications
1. Frank JA, Anderson SA, Kalsih H, Lewis BK, Yocum GT, Arbab AS.
Methods for magnetically labeling stem and other cells for detection by
in vivo magnetic resonance imaging. Cytotherapy. 2004; 6(6):621-625.
[PubMed: 15773025]
2. Arbab AS, Liu W, Frank JA. Cellular magnetic resonance imaging:
current status and future prospects. Expert Rev Med Devices. 2006
Jul;3(4):427-439. [PubMed: 16866640]
Licensing Status: Available for licensing and commercial
development.
Licensing Contacts
Uri Reichman, PhD, MBA; 301-435-4616; [email protected].
John Stansberry, PhD; 301-435-5236; [email protected].
Collaborative Research Opportunity: The Clinical Center, Frank
Laboratory, Radiology and Imaging Sciences, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize this
technology. Please contact Joseph A. Frank MS MD at 301-402-4314 or
[email protected] for more information.
Methods of Treating Age-Related Macular Degeneration
Description of Invention: Available for licensing is a novel method
of treating age related macular degeneration (AMD). AMD is the leading
cause of irreversible blindness in elderly populations worldwide.
Inflammation, among other factors, has been suggested to play an
important role in AMD pathogenesis. Recent studies have demonstrated a
link between the complement system, inflammation, and AMD pathogenesis.
Notably, researchers at NEI have shown that certain members of the C5a
pathway are increased in AMD patients, and in vitro experiments
demonstrated that those same pathway members cause a decrease in
retinal pigment epithelium (RPE) viability, a hallmark of AMD. Blocking
the C5a pathway presents a promising approach to prevent and treat AMD.
Application: Prevention and/or treatment of Age-related Macular
Degeneration.
Development Status: In vivo mouse studies are in progress to test
the effectiveness of the treatment.
Market: Age-related macular degeneration is a leading cause of
severe, irreversible vision impairment in developed countries (http://geteyesmart.org/eyesmart/diseases/amd.cfm). It is estimated that 1.8
million Americans 40 years and older are affected by AMD and an
additional 7.3 million with large drusen (yellow or white deposits
under the retina) are at substantial risk of developing AMD. The number
of people with AMD is estimated to reach 2.95 million in 2020. AMD is
the leading cause of permanent impairment of reading and fine or close-
up vision among people aged 65 years and older (http://www.cdc.gov/visionhealth/basic_information/eye_disorders.htm).
Inventors: Robert B. Nussenblatt et al. (NEI).
Patent Status: U.S. Provisional Application No. 61/429,580 filed 04
Jan 2011 (HHS Reference No. E-099-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Jaime M. Greene, M.S.; 301-435-5559;
[email protected].
Methods for Inhibiting Proinflammatory Cytokine Expression Using
Ghrelin
Description of Invention: Ghrelin, an endogenous ligand for growth
hormone secretagogue receptors (GHS-R), is primarily produced by the
stomach but also by many other organs systems in the body (including
the immune system) serves as a potent circulating orexigen controlling
energy expenditure, adiposity and GH secretion. We have discovered that
ghrelin exerts anti-inflammatory effects via inhibiting the secretion
of both acute and chronic cytokines including IL-1, IL-6, TNF-alpha,
IFN-gamma, IL-12 p40, Il-17, various chemokines and CSFs in vitro in
human and murine cells as well as in vivo in murine models of sepsis,
inflammation and aging. We also found that ghrelin directly controls
human growth hormone and insulin growth factor expression by human
immune cells.
Applications: This invention is useful for treatment of various
inflammatory disorders including inflammatory bowel disease, Crohn's
disease, rheumatoid arthritis, multiple sclerosis, atherosclerosis,
endotoxemia and graft-versus-host disease.
Inventors: Vishwa D. Dixit and Dennis D. Taub (NIA).
Relevant Publications
1. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK,
Palaniappan R, Lillard JW Jr, Taub DD. Ghrelin inhibits leptin- and
activation-induced proinflammatory cytokine expression by human
monocytes and T cells. J Clin Invest. 2004 Jul; 114(1):57-66. [PubMed:
15232612] Note: Article highlighted in this issue of JCI. This was also
the subject of a Science SAGE KE News Focus article--M Leslie.
Opposites Detract. Sci Aging Knowl Environ. 2004 Jul 14; 28:nf65 [doi:
10.1126/sageke.2004.28.nf65].
2. Dixit VD, Weeraratna AT, Yang H, Bertak D, Cooper-Jenkins A,
Riggins GJ, Eberhart CG, Taub DD. Ghrelin and the growth hormone
secretagogue receptor constitute a novel autocrine pathway in
astrocytoma motility. J Biol Chem. 2006
[[Page 18564]]
Jun 16; 281(24):16681-16690. [PubMed: 16527811]
3. Dixit VD, Yang H, Sun Y, Weeraratna AT, Smith RG, Taub DD.
Ghrelin promotes thymopoiesis during aging. J Clin Invest. 2007 Oct;
117(10):2778-2790. [PubMed: 17823656] Note: Article highlighted in this
issue of JCI.
4. Yang H, Dixit VD, Patel K, Vandanmagsar B, Collins G, Sun Y,
Smith RG, Taub DD. Reduction in hypophyseal growth hormone and
prolactin expression due to deficiency in ghrelin receptor signaling is
associated with Pit-1 suppression: relevance to the immune system.
Blood Behav Immun. 2008 Nov; 22(8):1138-1145. [PubMed: 18602461]
5. Dixit VD, Yang H, Cooper-Jenkins A, Giri BB, Patel K, Taub DD.
Reduction of T cell-derived ghrelin enhances proinflammatory cytokine
expression: implications for age-associated increases in inflammation.
Blood. 2009 May 21; 113(21):5202-5205. [PubMed: 19324904]
Relevant Reviews
6. Dixit V and Taub DD. Ghrelin and immunity: a young player in an
old field. Exp. Gerontol. 2005 Nov; 40(11):900-910. [PubMed: 16233968]
7. Taub DD. Novel connections between the neuroendocrine and immune
systems: the ghrelin immunoregulatory network. Vitam Horm. 2008;
77:325-346. [PubMed: 17983863]
8. Taub DD. Neuroendocrine interactions in the immune system. Cell
Immunol. 2008 Mar-Apr; 252(1-2):1-6. [PubMed: 18619587] Note: Image
from article used on the cover of this issue.
9. Redelman D, Welniak LA, Taub D, Murphy WJ. Neuroendocrine
hormones such as growth hormone (GH) and prolactin (PRL) are integral
members of the immunological cytokine network. Cell Immunol. 2008 Mar-
Apr; 252(1-2):111-121. [PubMed: 18313040]
10. Patel K and Taub DD. Role of neuropeptides, hormones, and
growth factors in regulating thymopoiesis in middle to old age. F1000
Biol Rep. 2009 May 28; 1. pii: 42. [PubMed: 20948643]
11. Taub DD, Murphy WJ, Longo DL. Rejuvenation of the aging thymus:
growth hormone-mediated and ghrelin-mediated signaling pathways. Curr
Opin Pharmacol. 2010 Aug; 10(4):408-424. [PubMed: 20595009]
Patent Status: U.S. Patent Application No. 11/596,310 filed 06 Jun
2008 (HHS Reference No. E-016-2004/0-US-07) and related international
applications.
Licensing Status: Available for licensing.
Licensing Contact: Sally H. Hu, PhD, M.B.A.; 301-435-5606;
[email protected].
Collaborative Research Opportunity: The National Institute on Aging
is seeking statements of capability or interest from parties interested
in collaborative research to further develop, evaluate, or
commercialize Methods of Inhibiting Proinflammatory Cytokine Expression
Using Ghrelin. Please contact Nikki Guyton at 301-435-3101 or
[email protected] for more information.
Dated: March 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-7925 Filed 4-1-11; 8:45 am]
BILLING CODE 4140-01-P