[Federal Register Volume 75, Number 108 (Monday, June 7, 2010)]
[Notices]
[Pages 32184-32185]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-13606]



[[Page 32184]]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

Improving the Therapeutic Effectiveness of Foreign Proteins

    Description of Invention: Foreign proteins are recognized by the 
immune system, which typically responds by creating neutralizing 
antibodies to the foreign protein. While this is helpful in response to 
an infection or the administration of a vaccine, it is troublesome when 
foreign proteins are administered for the treatment of disease in a 
non-vaccine capacity (e.g., an immunotoxin, therapeutic antibody, 
protein replacement therapy, etc.). These neutralizing antibodies 
decrease the therapeutic effectiveness of the protein, ultimately 
resulting in the inability to administer the foreign protein to a 
patient with any benefit. Thus, if a particular disease requires 
multiple administrations, the chance of achieving a successful response 
with the foreign protein becomes unlikely.
    A particular instance where neutralizing antibodies have reduced 
therapeutic effectiveness is the use of immunotoxins for treatment of 
cancer. Immunotoxins comprise an antibody domain for targeting a 
surface antigen on a cancer cell and a toxin domain that is capable of 
killing the targeted cell. The toxin domain is typically a modified 
form of a bacterial toxin, such as Pseudomonas exotoxin A, and is 
therefore recognized as a foreign protein by the patient's immune 
system. Although immunotoxins have an initial therapeutic effect, the 
effectiveness is ultimately mitigated by neutralizing antibodies 
against the toxin domain of the immunotoxin. Thus there is a clear need 
to reduce the formation of neutralizing antibodies in patients who are 
administered a foreign protein like an immunotoxin.
    This technology addresses this need by reducing the formation of 
neutralizing antibodies through the co-administration of the 
immunosuppressive agent CP-690,550 with a therapeutic foreign protein. 
Specifically, the inventors found that co-administering CP-690,550 and 
an immunotoxin to a mouse model reduced the production of neutralizing 
antibodies to the immunotoxin. These results suggest that the use of 
CP-690,550 in combination with any foreign protein therapeutic could 
allow multiple cycles of therapy and result in improved therapeutic 
efficacy.
    Applications:
     Improved efficacy of treatments that utilize the foreign 
proteins that can be neutralized by patient immune systems.
     Administration of CP-690,550 with an immunotoxin, for the 
treatment of cancers such as mesothelioma, lung cancer, leukemia, 
lymphoma, ovarian cancer, etc.
    Advantages:
     Broad applicability to any treatment where a foreign 
protein is used as a therapeutic agent.
     Overcomes a persistent challenge to the use of protein 
biologics as therapeutics.
     Reduction of the immune response by a patient reduces the 
production of neutralizing antibodies, increasing the success rate of 
the treatment.
     Fewer neutralizing antibodies increases the duration in 
which a foreign protein can achieve a therapeutic concentration.
     Fewer neutralizing antibodies also allows multiple rounds 
of effective administration of the foreign protein.
     Longer duration for a therapeutic concentration and the 
ability to administer multiple doses increase the chances of a 
therapeutic response.
    Development Status: Preclinical stage of development; preliminary 
mouse model data.
    Inventors: David J. FitzGerald (NCI) et al.
    Patent Status: U.S. Provisional Application No. 61/304,293 (E-082-
2010/0-US-01).
    For more information, see:
    1. Pastan et al. PCT Publication WO 2009/032954 ``Deletions in 
Domain II of Pseudomonas Exotoxin A that Reduce Non-Specific 
Toxicity.''
    2. Pastan et al. U.S. Patent Publication 2009/0142341 ``Mutated 
Pseudomonas Exotoxins with Reduced Antigenicity.''
    3. Changelian et al. Science 2003 Oct 31;302(5646):875-878. 
``Prevention of organ allograft rejection by a specific Janus kinase 3 
inhibitor.'' [PubMed: 14593182].
    4. Pastan et al. U.S. Patent 7,355,012 ``Mutated Anti-CD22 
Antibodies with Increased Affinity to CD22 Expressing Leukemia Cells.''
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Molecular Biology, is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize this technology. Please contact 
John Hewes, PhD at 301-435-3131 or [email protected] for more 
information.

Parkin and PINK1-Based Therapies for Parkinson's Disease and Other 
Mitochondrial Diseases

    Description of Invention: This technology provides methods for 
treating Parkinson's disease and other diseases associated with 
mitochondrial dysfunction.
    Mutations in mitochondrial DNA (mtDNA) are responsible for a broad 
spectrum of inherited diseases, with symptoms that can range from mild 
to very severe. Accumulated mutations in mtDNA have also been linked to 
the pathogenesis of common diseases such as cancer, diabetes mellitus, 
and neurodegenerative disorders. In Parkinson's disease, for example, 
the accumulation of defective mitochondria appears to be responsible 
for the loss of midbrain neurons that produce dopamine 
neurotransmitter, which is a key feature of this disease.
    In their recent work, Dr. Richard Youle and co-investigators have 
linked the fields of mitochondrial quality control and the genetics of 
Parkinson's disease. They have discovered that the Parkin protein is 
selectively recruited to damaged mitochondria, and promotes autophagic 
degradation of these mitochondria; ablation of Parkin increases levels 
of damaged mitochondria in cells. They have also discovered that 
another protein associated with mitochondrial disease,

[[Page 32185]]

the mitochondrial PTEN-induced kinase-1 (PINK1), accumulates on the 
surface on damaged mitochondria, and that the presence of full-length 
PINK1 is necessary and sufficient for Parkin recruitment to the 
mitochondria. Thus, both Parkin and PINK1 play specific and important 
roles in mitochondrial quality control and disposal.
    This technology describes methods of treating Parkinson's disease 
or other mitochondrial diseases such as KSS (Kearns Sayre syndrome), 
MERRF (Myoclonus epilepsy ragged-red fibers), MELAS (mitochondrial 
encephalomyopathy, lactic acidosis and stroke-like episodes), NARP 
(Neuropathy ataxia, retinitis pigmentosa), and LHON (Leber hereditary 
optic neuropathy) by increasing PINK1 or Parkin expression or activity, 
as well as methods of reducing the number of defective mitochondria in 
a cell by increasing PINK1 or Parkin expression or activity.
    Applications:
     Development of therapies for Parkinson's disease and other 
diseases associated with mitochondrial dysfunction.
     Development of individualized treatment regimens for 
mitochondrial diseases through ex vivo or in vitro testing of candidate 
drugs.
    Inventors: Richard J. Youle et al. (NINDS).
    Related Publications:
    1. A Abeliovich. Parkinson's disease: Mitochondrial damage control. 
News and Views, Nature 2010 Feb 11:463:744-745. [PubMed: 20148026].
    2. D Narendra et al. PINK1 is selectively stabilized on impaired 
mitochondria to activate Parkin. PLoS Biol. 2010 Jan 26;8(1):e1000298. 
[PubMed: 20126261].
    3. D Narendra et al. Parkin-induced mitophagy in the pathogenesis 
of Parkinson disease. Autophagy. 2009 Jul;5(5):706-708. [PubMed: 
19377297].
    4. D Narendra et al. Parkin is recruited selectively to impaired 
mitochondria and promotes their autophagy. J Cell Biol. 2008 Dec 
1;183(5):795-803. [PubMed: 19029340].
    Patent Status: U.S. Provisional Application No. 61/256,601 filed 30 
Oct 2009 (HHS Reference No. E-225-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Tara Kirby, PhD; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Neurological Disorders and Stroke is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize methods of treating 
mitochondrial diseases by increasing PINK1 or Parkin expression or 
activity. Please contact Dr. Martha Lubet at 301-435-3120 or 
[email protected] for more information.

A Highly Sensitive ELISA for Detection of Serum Levels of Soluble IL-15 
Receptor Alpha

    Description of Invention: The invention is an ELISA based assay 
that can be used in the clinical setting to detect the presence of 
soluble human IL-15 receptor (IL-15R) in the serum or plasma.
    Interleukin-15 (IL-15), a cytokine has potential as an 
immunotherapeutic agent for cancer treatment because it is a critical 
factor for the proliferation and activation of natural killer (NK) and 
CD8+ T-cells.
    In addition to studies directed toward augmenting IL-15 action to 
increase patient immune responses to their tumor, IL-15R alpha play a 
pathogenic role in leukemia and autoimmune disorders. IL-15 and IL-15R 
alpha are coexpressed in association with a number of autoimmune 
disorders including rheumatoid arthritis, psoriasis, inflammatory bowel 
disease, multiple sclerosis, chronic liver disease, and refractory 
celiac syndrome including that disease associated with the development 
of enteropathy associated CD8 T-cell lymphoma. An assay for the 
released serum form of IL-15R alpha is required to evaluate these IL-
15R alpha inducing agents.
    Applications:
     The assay has the potential of being a commercial assay 
for clinical use to detect soluble human IL-15R alpha (sIL-15R alpha) 
in serum or plasma.
     The assay will help in predicting the efficacy of IL-15-
based therapies since high levels of IL-15R are thought to be necessary 
to optimize the therapeutic effects of IL-15.
     The assay can be used to identify patients who can be good 
candidates for IL-15 therapy.
     The assay may also help clinicians identify patients 
susceptible to diseases associated with disorders of IL-15R expression.
    Advantages:
     The assay is in the industry accepted ELISA format.
     This non-radioactive ELISA assay has a sensitivity of 1pg/
ml that is significantly more sensitive than the current industry 
detection level of 20 pg/ml.
    Development Status: Developed at the proof-of concept level and 
laboratory setting. Clinical validation of the assay is currently being 
planned.
    Market: The assay can be used in the clinical setting to detect 
very low levels of IL-15R alpha in the serum or plasma of patients.
    IL-15R alpha disorders have been demonstrated in leukemia and 
autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, 
celiac disease, and psoriasis as well as those with disorders 
associated with the retrovirus, HTLV-I. Additionally, select lymphomas 
express IL-15R alpha.
    Inventors: Thomas A. Waldmann and Jing Chen (NCI).
    Related Publication: Waldmann TA. The biology of interleukin-2 and 
interleukin-15: Implications for cancer therapy and vaccine design. Nat 
Rev Immunol. 2006 Aug;6(8):595-601. [PubMed: 16868550].
    Patent Status:
     U.S. Provisional Application No. 61/241,265 filed 10 Sep 
2009 (HHS Reference No. E-079-2009/0-US-01).
     U.S. Provisional Application No. 61/242,595 filed 10 Sep 
2009 (HHS Reference No. E-079-2009/1-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Sabarni Chatterjee, PhD; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Metabolism Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize this technology. Please contact John Hewes, 
PhD at 301-435-3131 or [email protected] for more information.

    Dated: June 1, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-13606 Filed 6-4-10; 8:45 am]
BILLING CODE 4140-01-P