Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices 18581 

commercialize in vitro assembly of 

protein microarrays. Please contact John 

D. Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Methods and Compositions for HighThroughput Detection of Protein/ 

Protein Interactions Ex Vivo 

Description of Technology: This 

invention relates to methods and 

compositions for the high-throughput 

detection of protein-protein interactions 

using a lambda phage display system. 

One of the central challenges in systems 

biology is defining the interactome, or 

set of all protein-protein interactions 

within a living cell, as a basis for 

understanding biological processes for 

early diagnosis of disease and for drug 

development. The invention provides a 

novel proteomic toolbox for highthroughput medical research based in 

combining phage lambda protein 

display and recent advances in 

manipulation of the phage’s genome. 

The method uses the bacteriophage 

lambda vector to express proteins on its 

surface, and is based on the use of 

mutant phage vectors such that only 

interacting phages will be able to 

reproduce and co-infect an otherwise 

non-permissive host and produce 

plaques. 

Application: The invention allows for 

the characterization of bacteriophage 

display libraries that could be easily 

adapted to be used in large-scale 

functional protein chip assays. 

Inventors: Sankar Adhya and Amos 

Oppenheim (NCI). 

Patent Status: U.S. Patent Application 

No. 11/719,925 filed 22 May 2007 (HHS 

Reference No. E–264–2004/0–US–03). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James, 

PhD; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Therapeutic Methods Based on In Vivo 

Modulation of the Production of 

Interferon Gamma 

Description of Technology: The 

technology offered for licensing is in the 

field of Therapeutics. More specifically, 

the technology relates to biological 

ligands and their use as modulators of 

the production of Interferon gamma as 

a means to treat a broad spectrum of 

diseases. The invention describes and 

claims antibodies and other ligands that 

can stimulate Natural Killer (NK) 

immune cells to produce Interferon 

gamma which contributes to the combat 

against foreign pathogens. Conversely, 

the invention also describes and claims 

methods that can inhibit such Interferon 

gamma production for treatment of 

diseases where excess of Interferon is 

not desirable. The invention also 

describes methods and assays to 

identify both inducing and inhibiting 

ligands. 

The license agreement may include 

biological materials, such as monoclonal 

antibodies that were made and 

identified by the inventors as Interferon 

gamma stimulators. 

Interferon-gamma is a potent antiviral 

and antimicrobial substance produced 

by natural killer (NK) white blood cells. 

NK cells are activated during infections 

by viruses and by other intracellular 

pathogens, such as parasites and 

bacteria. Soluble substances, such as 

interleukins, produced by infected cells 

activate NK cells to secrete interferongamma. Injection of interleukins into 

patients to stimulate NK cells to secrete 

interferon-gamma has not been a 

successful therapeutic approach because 

of the toxicity involved. The invention 

is based on the discovery by the 

inventors that activation of the KIR2DL4 

receptor expressed by all NK cells 

stimulates them to produce interferongamma. The invention claims 

monoclonal antibodies and derivatives 

thereof, as well as natural and synthetic 

ligands of KIR2DL4 that can be utilized 

to stimulate interferon-gamma 

production by NK cells without any 

other stimulus. The possibility of 

inducing interferon-gamma production 

by NK cells without the toxic side 

effects of interleukins could be an 

effective therapy for various types of 

infections and of cancers. Also claimed 

in the invention are methods of treating 

various cancers and viral infections, 

methods of treating autoimmune 

disease, and methods of administration 

of the antibody or derivatives thereof. 

Certain diseases benefit from reduction 

in the amount of Interferon gamma. The 

instant invention claims such ligands 

that are capable of inhibiting KIR2DL4 

from producing interferon gamma. It 

also describes methods of identifying 

such ligands. 

Applications: 

• Therapeutics of infectious diseases, 

cancer and autoimmune diseases 

• The mAbs can be used as research 

reagents 

Advantages: Absence of toxicity as 

compared with current methods such as 

IL–2 treatment. 

Development Status: The inventors 

generated monoclonal antibodies that 

have demonstrated stimulation of 

Interferon gamma production. Proof of 

concept has been demonstrated. 

Market: The technology lends itself to 

treatment of viral and microbial-caused 

infectious disease and possibly as 

therapy for certain cancers and 

autoimmune disease. Collectively, these 

medical areas represent a huge market 

of multi billion dollars and thus 

significant commercial opportunities. 

Inventors: Eric O. Long and Sumati 

Rajagopalan (NIAID). 

Relevant Publications: 

1. S Rajagopalan, J Fu, EO Long. 

Cutting edge: induction of IFN-gamma 

production but not cytotoxicity by the 

killer cell Ig-like receptor KIR2DL4 

(CD158d) in resting NK cells. J 

Immunol. 2001 Aug 15;167(4):1877– 

1881. 

2. A Kikuchi-Maki, TL Catina, KS 

Campbell. Cutting edge: KIR2DL4 

transduces signals into human NK cells 

through association with the fc receptor 

gamma protein. J Immunol. 2005 Apr 

1;174(7):3859–3863. 

3. S Rajagopalan, YT Bryceson, SP 

Kuppusamy, DE Geraghty, A van der 

Meer, I Joosten, EO Long. Activation of 

NK cells by an endocytosed receptor for 

soluble HLA–G. PLoS Biol 2006 

Jan;4(1):e9. 

Patent Status: U.S. Patent 7,435,801 

issued 14 Oct 2008 (HHS Reference No. 

E–255–2000/0–US–03); U.S. Patent 

Application No. 12/249,703 filed 10 Oct 

2008 (HHS Reference No. E–255–2000/ 

0–US–04); both entitled ‘‘Antibodies 

and Other Ligands Directed Against 

KIR2DL4 Receptor for Production of 

Interferon-Gamma’’. 

Licensing Status: Available for 

licensing. Monoclonal antibodies made 

by the inventors and identified as 

stimulators may be available and 

provided with the license agreement. 

Licensing Contacts: Uri Reichman, 

PhD, MBA; 301–435–4616; 

UR7a@nih.gov; Rung C. Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Dated: April 17, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–9348 Filed 4–22–09; 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 


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18582 Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices 

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. 

Identification of Subjects Likely To 

Benefit From Copper Treatment 

Description of Technology: Menkes 

disease is an infantile onset X-linked 

recessive neurodegenerative disorder 

caused by deficiency or dysfunction of 

a copper-transporting ATPase, ATP7A. 

The clinical and pathologic features of 

this condition reflect decreased 

activities of enzymes that require copper 

as a cofactor, including dopamine-bhydrolase, cytochrome c oxidase and 

lysyl oxidase. Recent studies indicate 

that ATP7A normally responds to Nmethyl-D-aspartate receptor activation 

in the brain, and an impaired response 

probably contributes to the 

neuropathology of Menkes disease. 

Affected infants appear healthy at birth 

and develop normally for 6 to 8 weeks. 

Subsequently, hypotonia, seizures and 

failure to thrive occur and death by 3 

years of age is typical. Occipital horn 

syndrome (OHS) is also caused by 

mutations in the copper transporting 

ATPase ATP7A, although its symptoms 

are milder than Menkes syndrome, 

including occipital horns and lax skin 

and joints. 

Treatment with daily copper 

injections may improve the outcome in 

Menkes disease if commenced within 

days after birth; however, newborn 

screening for this disorder is not 

available and early detection is difficult 

because clinical abnormalities in 

affected newborns are absent or subtle. 

Moreover, the usual biochemical 

markers (low serum copper and 

ceruloplasmin) are unreliable predictors 

in the neonatal period, since levels in 

healthy newborns are low and overlap 

with those in infants with Menkes 

disease. Although molecular diagnosis 

is available, its use is complicated by 

the diversity of mutation types and the 

large size of ATP7A (about 140kb). 

Thus, there is a need for improved 

methods for early detection of infants 

with Menkes disease or OHS in order to 

improve outcomes. 

This technology relates to methods of 

identifying individuals who may benefit 

from treatment with copper, particularly 

those having Menkes disease or 

Occipital Horn Syndrome. 

Inventor: Stephen G. Kaler (NICHD). 

Publication: SG Kaler, CS Holmes, DS 

Goldstein, JR Tang, SC Godwin, A 

Donsante, CJ Liew, S Sato, N Patronas. 

Neonatal diagnosis and treatment of 

Menkes disease. N Engl J Med. 2008 Feb 

7;358(6):605–614. 

Patent Status: PCT Application No. 

PCT/US2008/078966 filed 06 Oct 2008 

(HHS Reference No. E–186–2008/0– 

PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@hhs.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Child Health 

and Human Development, Division of 

Intramural Research, Molecular 

Medicine Program, Unit on Pediatric 

Genetics, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize population-based 

newborn screening for Menkes disease 

and related disorders of copper 

transport in order to identify subjects 

likely to benefit from copper injections 

and other treatments. Please contact 

Alan Hubbs, PhD at 301–594–4263 or 

hubbsa@mail.nih.gov for more 

information. 

Polyclonal Antibody Against Bloom’s 

Syndrome Protein (BLM) for Research 

and Diagnostic Use 

Description of Technology: 

Investigators at the National Institutes of 

Health have generated a polyclonal 

antibody against Bloom’s syndrome 

protein (BLM). The BLM protein is a 

DNA helicase enzyme and a key 

component of the DNA damage 

response signaling pathway. Several 

protein kinases including ATM, DNA– 

PK, and ATR can mediate the 

phosphorylation of BLM. The 

polyclonal antibody is generated by 

using a phosphorylated peptide 

belonging to the N-terminus of BLM. 

The antibody shows a rapid 

phosphorylation of BLM on threonine 

99 (T99p-BLM) following DNA damage 

by anti-cancer agents and could serve as 

a therapeutic marker of drug action on 

DNA. The antibody is also useful for 

microscopic and biochemical analysis of 

DNA damage signaling. 

Applications: 

• A therapeutic marker of drug action 

on DNA 

• A diagnostic indicator of inherent 

genomic instability 

Inventors: Yves Pommier and V. 

Ashutosh Rao (NCI) 

Patent Status: HHS Reference No. E– 

053–2006/0—Research Tool. Patent 

protection is not being sought for this 

technology. 

Licensing Status: Threonine 99 

specific polyclonal antibody against the 

BLM protein is available for licensing. 

Licensing Contact: Betty Tong, PhD; 

301–594–6565; tongb@mail.nih.gov. 

Dated: April 16, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–9345 Filed 4–22–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute on Deafness and 

Other Communication Disorders; 

Amended Notice of Meeting 

Notice is hereby given of a change in 

the meeting of the National Institute on 

Deafness and Other Communication 

Disorders Special Emphasis Panel, April 

28, 2009, 1 p.m. to April 28, 2009, 4 

p.m., National Institutes of Health, 

Bethesda, MD which was published in 

the Federal Register on April 6, 2009, 

7415501. 

The meeting will be held April 29, 

2009. The meeting is closed to the 

public. 

Dated: April 15, 2009. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. E9–9204 Filed 4–22–09; 8:45 am] 

BILLING CODE 4140–01–M 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute on Drug Abuse; 

Notice of Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meetings. 

The meetings will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 


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