[Federal Register Volume 77, Number 30 (Tuesday, February 14, 2012)]
[Notices]
[Pages 8264-8266]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-3412]
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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.
Encapsulated N-Acetylmannosamine or N-Acetylneuraminic Acid as a
Therapeutic Agent for Increasing Sialylation in Certain Muscular
Atrophies, Kidney Disorders, Cancers or Poor Immune Function
Description of Technology: N-acetylmannosamine is a precursor for
the synthesis of sugar molecules known as sialic acids, which play an
important role in specific biological processes such as cellular
adhesion, cellular communication and signal transduction. Lack of
sialic acids also plays a crucial role in disease processes such as
inflammation, immune responses, as well as certain muscular atrophies
(including hereditary inclusion body myopathy (HIBM) and distal
myopathy with rimmed vacuoles (DMRV or Nonaka myopathy)), certain
kidney disorders with proteinuria and hematuria (including minimal
change nephrosis and focal segmental glomerulosclerosis), and certain
cancers (including bladder cancer and myeloid leukemia).
This technology relates to methods of administering liposome-
encapsulated N-acetylmannosamine, N-acetylneuraminic acid, or their
derivatives to treat human disorders of hyposialylation (by increasing
sialic acid production in patients who are deficient in that sugar
molecule). Liposome-encapsulated delivery of these monosaccharides
enhances successful systemic delivery, including to the central nervous
system (crossing the blood-brain barrier), and liposome encapsulation
protects against gastrointestinal tract degradation.
Potential Commercial Applications:
Treatment of rare diseases such as HIBM and Nonaka
myopathy (or DMRV).
Treatment of kidney conditions involving sialic acid
deficiencies, resulting in proteinuria and hematuria.
Treatment of other diseases involving sialic acid
deficiencies.
Use as immune stimulant since adequate sialic acid is
important for robust immune function.
Competitive Advantages:
N-acetylmannosamine is the only uncharged sugar in the
sialic acid biosynthesis pathway (thus making it easier to deliver than
charged sugars) and is located after the rate-limiting step.
N-acetyl mannosamine and N-acetylneuraminic acid have been
shown to rescue hyposialylation in mouse models of HIBM.
Encapsulated N-acetylmannosamine or N-acetylneuraminic
acid crosses the blood-brain barrier and prevents gastrointestinal
tract degradation more efficiently than unencapsulated drug.
Development Stage:
Pre-clinical
In vitro data available
In vivo data available (animal)
Inventors: Marjan Huizing et al. (NHGRI).
Publications:
1. Galeano B, et al. Mutation in the key enzyme of sialic acid
biosynthesis causes severe glomerular proteinuria and is rescued by N-
acetylmannosamine. J Clin Invest. 2007 Jun;117(6):1585-1594. [PMID
17549255]
2. Nemunaitis G, et al. Hereditary inclusion body myopathy: single
patient response to intravenous dosing of GNE gene lipoplex. Hum Gene
Ther. 2011 Nov;22(11):1331-1341. [PMID 21517694]
3. Kakani S, et al. The Gne M712T mouse as a model for human
glomerulopathy. Am J Pathol., in press (Dec 2011) (available online in
Feb 2012)
Intellectual Property: HHS Reference No. E-270-2011/0 -- U.S.
Application No. 61/531,934 filed 07 Sep 2011.
Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426;
[email protected].
[[Page 8265]]
Chimeric Antigen Receptors to CD22 for Treating Hematological Cancers
Description of Technology: Chimeric antigen receptors (CARs) are
hybrid proteins consisting of an antibody binding fragment fused to
protein signaling domains that cause some T-cells to become cytotoxic.
Once activated, these cytotoxic T-cells can selectively eliminate the
cells which they recognize. Thus, by engineering a T-cell to express a
CAR that is specific for a certain cell surface protein, it is possible
to selectively target cells for destruction. This is a promising new
therapeutic approach known as adoptive cell therapy.
CD22 is a cell surface protein that is expressed on a large number
of B-cell lineage hematological cancers. Several promising therapies
are being developed which target CD22, including therapeutic antibodies
and immunotoxins. This technology concerns the use of a high affinity
antibody binding fragment to CD22 as the targeting moiety of a CAR,
adding adoptive cell therapy as a new prospective treatment for certain
leukemias and lymphomas.
Potential Commercial Applications:
Treatment of diseases associated with increased or
preferential expression of CD22
Specific diseases include hematological cancers such as
chronic lymphocytic leukemia, hairy cell leukemia and pediatric acute
lymphoblastic leukemia
Competitive Advantages:
Targeted therapy decreases non-specific killing of healthy,
essential cells, resulting in fewer non-specific side-effects and
healthier patients
Hematological cancers are susceptible to cytotoxic T-cells for
treating because they are present in the bloodstream
Expression of CD22 only on mature cells allows the avoidance
of stem cell elimination during treatment
High affinity of the antibody binding fragment for CD22
increases the likelihood of successful targeting
Development Stage:
Pre-clinical
In vitro data available
In vivo data available (animal)
Inventors: Rimas J. Orentas et al. (NCI).
Intellectual Property: HHS Reference No. E-265-2011/0-US-01--US
provisional application 61/549,516.
Related Technology: HHS Reference No. E-129-2001/0-US-03--US Patent
7,355,012.
Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632;
[email protected].
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
Chimeric Antigen Receptor for CD22, High Affinity. A gene vector to
target T cells to B cell leukemia and lymphoma. For collaboration
opportunities, please contact John Hewes, Ph.D. at [email protected].
Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin
Domains Lacking Both T-Cell and B-Cell Epitopes
Description of Technology: Immunotoxins can kill cancer cells while
allowing healthy, essential cells to survive. As a result, patients
receiving an immunotoxin are less likely to experience the deleterious
side-effects associated with non-discriminate therapies such as
chemotherapy or radiation therapy. Unfortunately, the continued
administration of immunotoxins often leads to a reduced patient
response due to the formation of neutralizing antibodies against
immunogenic B-cell and T-cell epitopes contained within PE. To improve
the therapeutic effectiveness of PE-containing immunotoxins through
multiple rounds of drug administration, NIH inventors have sought to
remove the B-cell and T-cell epitopes within PE. Previous work
demonstrated that the removal of the major B-cell epitopes from PE
reduced the immunogenicity of PE. This technology involves the
identification of major T-cell epitopes on PE, and the removal of the
primary T-cell epitope by mutation or deletion. By combining the T-cell
epitope mutations with modifications that remove B-cell epitopes, it is
possible to create PE-based immunotoxins that have even greater
resistance to the formation of neutralizing antibodies. Immunotoxins
containing these new PE-variants are expected to have improved
therapeutic efficacy.
Potential Commercial Applications:
Essential component of immunotoxins
Treatment of any disease associated with increased or
preferential expression a specific cell surface receptor
Specific diseases include hematological cancers, lung cancer,
ovarian cancer, breast cancer, and head and neck cancers
Competitive Advantages:
PE variants now include the removal of both B-cell and T-
cell epitopes, further reducing the formation of neutralizing
antibodies against immunotoxins which contain the PE variants.
Less immunogenic immunotoxins result in improved
therapeutic efficacy by permitting multiple rounds of administration.
Targeted therapy decreases non-specific killing of
healthy, essential cells, resulting in fewer non-specific side-effects
and healthier patients.
Development Stage: Pre-clinical.
Inventors: Ira H. Pastan et al. (NCI).
Patent Status:
HHS Reference No. E-174-2011/0-US-01 -- U.S. Provisional
Application 61/495,085.
Related Technologies:
HHS Reference No. E-269-2009/0-PCT-02 -- PCT Patent
Publication WO 2011/032022
HHS Reference No. E-292-2007/0-US-06 -- US Patent Publication
US 20100215656 A1
HHS Reference No. E-262-2005/0-US-06 -- US Patent Publication
US 20090142341 A1
HHS Reference No. E-139-1999/0-US-07 -- US Patent 7,081,518
Multiple additional patent families
Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632;
[email protected].
Ketamine Metabolites for the Treatment of Depression and Pain
Description of Technology: The market continues to have a need for
therapeutics for treating pain and depression that have efficacy in a
high percentage of patients but have reduced anaesthetic properties and
reduced abuse liability. Ketamine, a drug currently used in human
anesthesia and veterinary medicine, has been shown in clinical studies
to be effective in the treatment of several conditions, including the
of treatment-resistant bipolar depression, major depressive disorder,
neuropathic pain, and chronic pain, including complex regional pain
syndrome (CRPS). However the routine use of the drug is hindered by
unwanted central nervous system (CNS) effects and a patient response
rate of ~70%. New data suggests that ketamine metabolites can be used
with similar results but with an increase in patient response rates and
a decrease in undesirable side effects.
Potential Commercial Applications: Treatment of pain and
depression.
Competitive Advantages:
Increased number of patients able to respond to the
treatment because it
[[Page 8266]]
bypasses the human metabolic machinery needed to convert the drug into
its active metabolite(s).
Decreased CNS side effects.
Development Stage: In vivo data available (animal).
Inventors: Irving W. Wainer, Ph.D. (NIA), Carlos A. Zarate, M.D.
(NIMH), Ruin Moaddel, Ph.D. (NIA), Michel Bernier (NIA), Michael E.
Goldberg, M.D., Marc C. Toriman, Ph.D.
Publications:
1. Moaddel R, et al. A parallel chiral-achiral liquid chromatographic
method for the determination of the stereoisomers of ketamine and
ketamine metabolites in the plasma and urine of patients with complex
regional pain syndrome. Talanta. 2010 Oct. 15;82(5):1892-1904. [PMID
20875593]
2. Zarate CA Jr., et al. Relationship of Ketamine's Plasma Metabolites
with Response and Diagnosis, and Side Effects in Major Depression.
Manuscript in preparation.
3. Ibrahim L, et al. Course of Improvement in Depressive Symptoms to a
Single Intravenous Infusion of Ketamine vs. Add-on Riluzole: Results
from a Four-Week, Double-Blind, Placebo-Controlled Study.
Neuropsychopharmacology, in press.
4. Zhao X, et al. Population Pharmacokinetic Modeling of Ketamine and
Three Major Metabolites in Patients with Treatment-Resistant Bipolar
Depression. Br. J. Clin. Phamaco., in press.
Intellectual Property: HHS Reference No. E-092-2011/0--U.S.
Provisional Application No. 61/547,336 filed 14 Oct. 2011.
Related Technologies: HHS Reference No. E-174-2006/0--
U.S. Patent Application No. 11/688,603 filed 20 Mar. 2007
Related international applications
Licensing Contact: Jaime M. Greene, M.S.; 301-435-5559;
[email protected].
Collaborative Research Opportunity: The National Institute on
Aging, Laboratory of Clinical Investigation, Bioanalytical Chemistry
and Drug Discovery Section, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate or commercialize this technology. For collaboration
opportunities, please contact Nicole Guyton, Ph.D. at
[email protected].
Improved DNA-Protein Vaccination Protocols
Description of Technology: Nucleic acid based vaccines are
attractive alternatives to conventional vaccines for a number of
reasons. One of the issues with nucleic acid based vaccines is the poor
immunogenicity in humans. The subject technology is a method for
eliciting improved immune responses with DNA based vaccines. The method
involves co-administration of a nucleic acid vaccine with a protein
vaccine for the same antigen of interest that is encoded by the DNA
vaccine in a prime-boost protocol. This methodology increased the
immune responses in a SIV macaque model to examine DNA based vaccines
of HIV and vaccine protocols. The methodology can potentially be
applied to other disease indications to elicit greater immune
responses.
Potential Commercial Applications: Improve immunogenicity of
nucleic acid based vaccines.
Competitive Advantages: The methodology increases the immune
response of DNA based vaccines.
Development Stage:
Early-stage
Pre-clinical
In vitro data available
In vivo data available (animal)
Intellectual Property: HHS Reference No. E-239-2009/0--
International PCT Application No. PCT/US2011/026325 filed 25 Feb. 2011.
Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018;
[email protected].
Dated: February 8, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-3412 Filed 2-13-12; 8:45 am]
BILLING CODE 4140-01-P