32184 Federal Register / Vol. 75, No. 108 / Monday, June 7, 2010 / Notices 

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 coadministration 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; 

lambertsond@mail.nih.gov. 

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 

hewesj@mail.nih.gov 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, 

WReier-Aviles on DSKGBLS3C1PROD with NOTICES

Federal Register / Vol. 75, No. 108 / Monday, June 7, 2010 / Notices 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; tarak@mail.nih.gov. 

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 lubetm@mail.nih.gov 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 IL15 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 IL15R 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 (sIL15R 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; 

chatterjeesa@mail.nih.gov. 

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 hewesj@mail.nih.gov 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 

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 

WReier-Aviles on DSKGBLS3C1PROD with NOTICES