[Federal Register Volume 77, Number 40 (Wednesday, February 29, 2012)]
[Notices]
[Pages 12316-12317]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-4736]



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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.

Intrathecal (IT) Administration of Rituximab to Treat Multiple 
Sclerosis (MS)

    Description of Technology: Multiple sclerosis (MS) is a chronic, 
neurological, autoimmune, demyelinating disease. The pathology of MS is 
characterized by an abnormal immune response directed against the 
central nervous system. In particular, T-lymphocytes are activated 
against the myelin sheath of the neurons of the central nervous system 
causing demyelination. Secondary-progressive multiple sclerosis (SP-MS) 
is the chronic phase of MS. The majority of people who have relapsing-
remitting MS eventually develop SP-MS. There are currently no effective 
treatments for SP-MS patients who do not have evidence for focal brain 
inflammation measured by contrast enhancing lesions (CEL) on brain MRI. 
NIH investigators have proposed that intrathecal administration of 
Rituximab, a monoclonal antibody (Ab) that depletes B cells and 
effectively decreases CEL in relapsing-remitting MS (RR-MS) but does 
not affect progression of disability in progressive MS, may deplete B 
cells from the intrathecal compartment leading to inhibition of T cell 
activation within intrathecal compartment, and thereby provide a novel 
therapeutic approach to treat SP-MS. A Clinical trial is in progress to 
evaluate this novel approach.
    Potential Commercial Applications: Improved therapeutics to treat 
or prevent Secondary-progressive multiple sclerosis (SP-MS).
    Competitive Advantages: This technology would provide the first 
effective therapy for Secondary-progressive multiple sclerosis patients 
lacking contrast enhancing lesions.

Development Stage

    <bullet> Clinical.
    <bullet> In vivo data available (animal).
    Inventor: Bibiana Bielekova (NINDS).
    Publication: Double Blind Combination of Rituximab by Intravenous 
and Intrathecal Injection Versus Placebo in Patients With Low-
Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe). 
ClinicalTrials.gov Identifier: NCT01212094 (http://clinicaltrials.gov/ct2/show/NCT01212094).
    Intellectual Property: HHS Reference No. E-249-2011/0--U.S. 
Provisional Application No. 61/539,870 filed 27 Sep 2011.
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-
5020; <a href="/cdn-cgi/l/email-protection#c4b2a1b4a5b784a9a5ada8eaaaadaceaa3abb2"><span class="__cf_email__" data-cfemail="ef998a9f8e9caf828e8683c1818687c1888099">[email protected]</span></a>.

miR126 for the Mobilization of Hematopoietic Stem/Progenitor Cells 
(HSPCs) into Peripheral Blood

    Description of Technology: The NIH inventors have discovered that a 
micro RNA, miR126, mobilizes hematopoietic stem/progenitor cells 
(HSPCs) from the bone marrow into blood. These mobilized HSPCs can be 
easily collected from blood and used for reconstitution of ablated or 
functionally-impaired bone marrow. miR126 may also facilitate 
mobilization of bone-resident cancer cells into the circulation where 
they could be more easily targeted by cancer therapeutics. This 
discovery could replace bone marrow transplantation as we do it today. 
Rather than using the current non-selective agent G-CSF (which 
preferentially mobilizes mature myeloid cells rather than stem/
progenitor cells), miR126 could be used for selective mobilization of 
the HSPCs needed for hematopoietic cell transplantation. Additionally, 
miR126 could be used to mobilize malignant cells from the bone marrow 
and render them more easy targets for therapy. It was previously shown 
that the bone marrow cavity promotes the survival of many cells 
including tumor cells, and that such cells may easily die when removed 
from the bone marrow niche and moved to the blood. Therefore, this 
discovery could also change treatment of many cancers that arise within 
the bone marrow or metastasize to the bone. Since the mechanism by 
which miR126 promotes HSPCs/tumor cell mobilization is attributable to 
the inhibition of VCAM-1 expression, miR126 could be used to treat 
inflammatory states where the expression of VCAM1 provides an anchor 
for inflammatory cells at sites of inflammation.

Potential Commercial Applications

    <bullet> Method of mobilizing hematopoietic stem/progenitor cells 
(HSPCs) from the bone marrow to the blood.
    <bullet> Use in hematopoietic cell transplantation and treatment of 
hematopoietic deficiency, hematological failure, and cancer treatments.
    <bullet> To mobilize cancer cells from the bone marrow and thus 
serve as adjuvant cancer therapy.
    <bullet> As an anti-inflammatory agent to reduce inflammatory cell 
infiltrates at sites of inflammation.
    Competitive Advantages: Mobilization of HSPCs yielding high-level, 
selective and rapid mobilization of HSPCs to the peripheral blood.

Development Stage

    <bullet> Pre-clinical.
    <bullet> In vivo data available (animal).
    Inventors: Giovanna Tosato and Ombretta Salvucci (NCI).
    Publication: Salvucci O, et al. MicroRNA126 contributes to G-CSF-
induced hematopoietic progenitor cell mobilization by reducing VCAM-1 
expression. Haematologica. 2012 Jan 22; Epub ahead of print. [PMID 
22271895].
    Intellectual Property: HHS Reference No. E-197-2011/0--U.S. 
Provisional Application No. 61/542,468 filed 02 Oct 2011.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
<a href="/cdn-cgi/l/email-protection#b9d1d8cacdd0d7decef9d4d8d0d597d7d0d197ded6"><span class="__cf_email__" data-cfemail="1a727b696e73747d6d5a777b737634747372347d75">[email protected]</span></a>v.
    Collaborative Research Opportunity: The National Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
miR126 and Mobilization of Hematopoietic Stem/Progenitor Cells. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
<a href="/cdn-cgi/l/email-protection#660e031103150c260b070f0a48080f0e48010910"><span class="__cf_email__" data-cfemail="d8b0bdafbdabb298b5b9b1b4f6b6b1b0f6bfb7ae">[email protected]</span></a>.

Use of Frizzled (Fzd) as a Biomarker for Cancer Patient Selection and 
Therapeutic Intervention

    Description of Technology: Personalized medicine is becoming more 
important in the diagnosis and treatment of diseases, particularly 
cancer. One signaling pathway which

[[Page 12317]]

has been demonstrated to be involved in cancer is the Wnt/beta catenin 
signaling pathway. The NIH scientists associated with this technology 
have identified a potential new biomarker for cancer based on their 
investigation of the role of the secreted frizzled related proteins, 
sFRP's, which are known to play a role in Wnt/beta catenin signaling. 
In particular, the scientists have determined that different Frizzled 
receptors (Fzd) have different and opposite roles in Wnt/beta catenin 
signaling with the expression of certain Fzd receptors, e.g. Fzd5, 
being associated with an increase in Wnt/beta catenin signaling and the 
expression of other Fzd receptors, e.g., Fzd2, being associated with a 
decrease in Wnt/beta catenin signaling.

Potential Commercial Applications

    <bullet> As a diagnostic to identify patients for whom frizzled 
antagonists may be useful therapeutic agents.
    <bullet> As an aid for determining the appropriate level of 
frizzled antagonist to be given to a patient.
    <bullet> As an aid in drug discovery for the evaluation of Wnt/
frizzled antagonists.

Competitive Advantages

    <bullet> Ability to stratify clinical trials by identifying 
patients whose tumor has the appropriate molecular signature.
    <bullet> Ability to provide an appropriate dosing regimen based on 
the specificity of the drug for a particular Fzd.
    <bullet> Tool for further characterizing cancer drugs which target 
the Wnt/beta catenin pathway providing for more well characterized and 
specific drugs.

Development Stage

    <bullet> Early-stage.
    <bullet> In vitro data available.
    Inventors: Jeffrey S. Rubin, Charles P. Xavier, and Maria Melikova 
(all of NCI).

Intellectual Property

    <bullet> HHS Reference No. E-196-2011/0--U.S. Provisional 
Application No. 61/497,513 filed 15 Jun 2011.
    <bullet> HHS Reference No. E-196-2011/1--U.S. Provisional 
Application No. 61/499,684 filed 21 Jun 2011.
    Related Technologies: NIH also has other intellectual property (IP) 
related to sFRP which may be useful in conjunction with the use of the 
biomarker described above. The IP includes patents belonging to:
    <bullet> HHS Reference No. E-160-1997/2--U.S. Patents 6,479,255 and 
7,183,377.
    <bullet> HHS Reference No. E-014-2000/0--U.S. Patents 6,600,018, 
7,223,853, and 7,947,651.
    <bullet> HHS Reference No. E-060-2000/1--U.S. Patent 7,488,710; 
Foreign patent protection is also available (PCT/US02/00869, published 
as WO 02/055547).
    Licensing Contact: Susan S. Rucker; 301-435-4478; 
<a href="/cdn-cgi/l/email-protection#621017010907101117220f030b0e4c0c0b0a4c050d14"><span class="__cf_email__" data-cfemail="dfadaabcb4baadacaa9fb2beb6b3f1b1b6b7f1b8b0a9">[email protected]</span></a>.
    Collaborative Research Opportunity: The National Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
Regulation of Wnt and Frizzled signaling by secreted Frizzled-related 
proteins. For collaboration opportunities, please contact John Hewes, 
Ph.D. at <a href="/cdn-cgi/l/email-protection#86eee3f1e3f5ecc6ebe7efeaa8e8efeea8e1e9f0"><span class="__cf_email__" data-cfemail="365e534153455c765b575f5a18585f5e18515940">[email protected]</span></a>.

A Highly Potent Human sRAGE Protein for Treating Vascular Disease, 
Injury, or Inflammation

    Description of Technology: The receptor for advanced glycation end 
products (RAGE) is a cell surface protein that triggers signaling 
pathways leading to inflammation. RAGE-stimulated inflammation can 
contribute to adverse vascular conditions, such as atherosclerosis and 
restenosis. The soluble version of RAGE (sRAGE) binds the same target 
molecules (advanced glycation end products), but cannot activate 
inflammatory signaling pathways. For this reason, sRAGE is thought to 
act as a decoy for RAGE. sRAGE reduces inflammation and pathogenic 
consequences associated with RAGE signaling. The administration of 
sRAGE has been used to treat atherosclerosis and arterial restenosis in 
animal models. The inventors established a way to produce human sRAGE 
with more than 1000-fold greater potency than current methods. 
Production of full length human sRAGE in cultured mammalian cells 
enables addition of mammalian post-translational modifications that 
dramatically enhance potency. This invention covers methods of 
production, the resulting modified sRAGE molecules, and methods of 
using this highly potent sRAGE for treating adverse vascular 
conditions.

Potential Commercial Applications

    <bullet> Atherosclerosis therapeutics.
    <bullet> Prevention of vascular inflammation.
    <bullet> Treating vascular injuries due to angioplasty or traumatic 
injury.
    <bullet> Treating vascular complications of diabetes mellitus.
    <bullet> Alzheimer's disease treatment based on amyloid-beta 
protein binding.

Competitive Advantages

    <bullet> Greater than 1000-fold increased potency over sRAGE 
produced in insect cells.
    <bullet> Readily scalable production as a recombinant protein 
secreted from CHO cells.
    <bullet> Simple affinity purification method.

Development Stage

    <bullet> Early-stage.
    <bullet> Pre-clinical.
    <bullet> In vitro data available.
    <bullet> In vivo data available (animal).
    Inventors: Li Lin, Sungha Park, Wen Wei, Rui-ping Xiao, and Mark 
Talan (NIA).
    Publication: Lin L, et al. RAGE signaling in inflammation and 
arterial aging. Front Biosci. 2009 Jan 1;14:1403-1413. [PMID 19273137].
    Intellectual Property: HHS Reference No. E-165-2011/0--U.S. 
Provisional Application No. 61/582,574 filed 03 Jan 2012.
    Related Technology: HHS Reference No. E-016-2009/0--U.S. Patent 
Application No. 12/652,395 filed 05 Jan 2010.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
<a href="/cdn-cgi/l/email-protection#eb9f84858c89ab868a8287c5858283c58c849d"><span class="__cf_email__" data-cfemail="5c2833323b3e1c313d353072323534723b332a">[email protected]</span></a>.
    Collaborative Research Opportunity: The National Institute on 
Aging, Laboratory of Cardiovascular Science, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize sRAGE. For 
collaboration opportunities, please contact Vio Conley, M.S. at 
<a href="/cdn-cgi/l/email-protection#395a5657555c404f795458505517575051175e564f"><span class="__cf_email__" data-cfemail="0a696564666f737c4a676b636624646362246d657c">[email protected]</span></a>.

    Dated: February 23, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-4736 Filed 2-28-12; 8:45 am]
BILLING CODE 4140-01-P


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