[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