18580 Federal Register / Vol. 74, No. 77 / Thursday, April 23, 2009 / Notices 

h. A statement as to whether or not 

information that could identify the 

donor(s) would be retained prior to the 

derivation or the use of the human 

embryonic stem cells (relevant guidance 

from the DHHS Office for Human 

Research Protections (OHRP) should be 

followed, as applicable; see OHRP’s 

Guidance for Investigators and 

Institutional Review Boards Regarding 

Research Involving Human Embryonic 

Stem Cells, Germ Cells, and Stem CellDerived Test Articles and Guidance on 

Research Involving Coded Private 

Information or Biological Specimens, or 

successor guidances); and 

i. A statement that the results of 

research using the human embryonic 

stem cells may have commercial 

potential, and a statement that the 

donor(s) would not receive financial or 

any other benefits from any such 

commercial development. 

C. Prior to the use of NIH funds: 

Funding recipients must ensure that: (1) 

The human embryonic stem cells were 

derived consistent with sections II.A 

and B of these Guidelines; and (2) the 

grantee institution maintains 

appropriate documentation 

demonstrating such consistency in 

accordance with 45 CFR 74.53, which 

also details rights of access by NIH. The 

responsible grantee institutional official 

must provide assurances with respect to 

(1) and (2) when endorsing applications 

and progress reports submitted to NIH 

for projects that utilize these cells. 

III. Research Using Human Embryonic 

Stem Cells and/or Human Induced 

Pluripotent Stem Cells That, Although 

the Cells May Come From Allowable 

Sources, Is Nevertheless Ineligible for 

NIH Funding 

This section governs research using 

human embryonic stem cells and 

human induced pluripotent stem cells, 

i.e., human cells that are capable of 

dividing without differentiating for a 

prolonged period in culture, and are 

known to develop into cells and tissues 

of the three primary germ layers. There 

are some uses of these cells that, 

although they may come from allowable 

sources, are nevertheless ineligible for 

NIH funding, as follows: 

A. Research in which human 

embryonic stem cells (even if derived 

according to these Guidelines) or human 

induced pluripotent stem cells are 

introduced into non-human primate 

blastocysts. 

B. Research involving the breeding of 

animals where the introduction of 

human embryonic stem cells (even if 

derived according to these Guidelines) 

or human induced pluripotent stem 

cells may have contributed to the germ 

line. 

IV. Other Non-Allowable Research 

A. NIH funding of the derivation of 

stem cells from human embryos is 

prohibited by the annual appropriations 

ban on funding of human embryo 

research (Consolidated Appropriations 

Act, 2009, Pub. L. 110–161, 3/11/09), 

otherwise known as the Dickey-Wicker 

Amendment. 

B. NIH funding for research using 

human embryonic stem cells derived 

from other sources, including somatic 

cell nuclear transfer, parthenogenesis, 

and/or IVF embryos created for research 

purposes, is not allowed under these 

Guidelines. 

Dated: April 17, 2009. 

Raynard S. Kington, 

Acting Director, NIH. 

[FR Doc. E9–9313 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 

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. 

On-Demand In Vitro Assembly of 

Protein Microarrays 

Description of Technology: Protein 

microarrays are becoming an 

indispensable biomedical tool to 

facilitate rapid high-throughput 

detection of protein-protein, proteindrug and protein-DNA interactions for 

large groups of proteins. The novel 

Protein Microarray of this invention is 

essentially a DNA microarray that 

becomes a protein microarray on 

demand and provides an efficient 

systematic approach to the study of 

protein interactions and drug target 

identification and validation, thereby 

speeding up the discovery process. The 

technology allows a large number of 

proteins to be synthesized and 

immobilized at their individual site of 

expression on an ordered array without 

the need for protein purification. As a 

result, proteins are ready for subsequent 

use in binding studies and other 

analysis. 

The Protein Microarray is based on 

high affinity and high specificity of the 

protein-nucleic acid interaction of the 

Tus protein and the Ter site of E. coli. 

The DNA templates are arrayed on the 

microarray to perform dual function: (1) 

Synthesizing the protein in situ (cellfree protein synthesis) in the array and 

(2) at the same time capturing the 

protein it synthesizes by DNA-protein 

interaction. This method utilizes an 

expression vector containing a DNA 

sequence which serves a dual purpose: 

(a) Encoding proteins of interest fused to 

the Tus protein for in vitro synthesis of 

the protein and (b) encoding the Ter 

sequence, which captures the fusion 

protein through the high affinity 

interaction with the Tus protein. 

Applications: 

• Simultaneous analysis of 

interactions of many proteins with other 

proteins, antibodies, nucleic acids, 

lipids, drugs, etc, in a single 

experiment. 

• Efficient discovery of novel drugs 

and drug targets. 

Development Status: The technology 

is in early stages of development. 

Inventors: Deb K. Chatterjee, 

Kalavathy Sitaraman, James L. Hartley, 

David J. Munroe, Cassio Baptista (NCI). 

Patent Status: 

U.S. Patent Application No. 11/ 

252,735 filed 19 Oct 2005 (HHS 

Reference No. E–244–2005/0–US–01). 

U.S. Patent Application No. 12/ 

105,636 filed 18 Apr 2008 (HHS 

Reference No. E–244–2005/1–US–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James, 

Ph.D.; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute Protein 

Expression Laboratory is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 


sroberts on PROD1PC70 with NOTICES
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 


sroberts on PROD1PC70 with NOTICES