Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 26707 

Dated: May 27, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–12873 Filed 6–2–09; 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. 

Diagnostic Markers for Melanoma 

Description of Technology: This 

invention relates to diagnostic and 

prognostic markers for melanoma. It 

discloses the identification of somatic 

mutations in genes of the 

microphthalmia-associated transcription 

factor (MITF) pathway in patients with 

melanoma. 

Melanoma is an aggressive and often 

fatal cancer with increasing incidence 

worldwide. Previous studies have 

linked the MITF pathway to the 

progression of melanoma. However, 

little is known about somatic mutations 

in genes of the MITF pathway that 

contribute to the development and 

progression of melanoma. To assess the 

role of the MITF pathway in melanoma, 

NIH investigators evaluated primary and 

metastatic melanoma samples for the 

presence of somatic mutations in two 

genes of the MITF pathway, MITF and 

SRY (sex determining region Y)—box 10 

(SOX10). They identified 16 previously 

unidentified somatic mutations in these 

genes. These studies suggest that MITF 

and SOX10 genes be used as diagnostic 

markers in human metastatic melanoma. 

Applications 

• Diagnosis and prognosis of patients 

with melanoma by detecting any 

mutations in the MITF or SOX10 gene. 

• Selection of therapy for melanoma 

patient; an MITF inhibitor can be 

selected for therapy if the patient has 

any of the disclosed mutations in MITF. 

Market: Cancer is the second leading 

cause of death in the U.S. There is an 

acute need for cancer biomarkers that 

can be detected from clinically relevant 

samples and used for early diagnosis, 

therapeutic follow-up and prognosis of 

malignant diseases. Melanoma is the 

most serious type of cancer of the skin. 

The percentage of people who develop 

melanoma has more than doubled in the 

past 30 years. There are 68,720 

estimated new cases and 8,650 

estimated deaths from melanoma in the 

United States in 2009, according to the 

National Cancer Institute. 

Inventors: Yardena R. Samuels et al. 

(NHGRI). 

Publication: Cronin JC WJ, Loftus SK, 

Prickett TD, Wei X, Ridd, Vemula S, 

Burrell AS, Agrawal NS, Lin JC, Banister 

CE, Buckhaults P, Rosenberg SA, 

Bastian BC, Pavan WJ, Samuels Y: 

Frequent mutations in the MITF 

pathway in melanoma. Pigment Cell and 

Melanoma Research 2009, (In Press). 

Patent Status: U.S. Provisional 

Application No. 61/214,415 filed 22 Apr 

2009 (HHS Reference No. E–053–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

Ph.D; 301–594–6565; 

tongb@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Human Genome Research 

Institute’s Cancer Genetics Branch is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

these newly identified candidate 

melanoma diagnostic and prognostic 

markers. Please contact NHGRI’s 

Technology Development Coordinator 

(TDC) Claire T. Driscoll at 

cdriscol@mail.nih.gov for more 

information. 

T Cells Attacking Cancer: T Cell 

Receptors That Recognize the 

Tyrosinase Tumor Antigen 

Description of Technology: A problem 

with current chemotherapy-based 

cancer treatments is the harsh sideeffects associated with many cancer 

drugs. Thus, there is an urgent need to 

develop new therapeutic strategies 

combining fewer side-effects and more 

specific anti-tumor activity. Adoptive 

cell transfer (ACT) is a promising new 

immunotherapeutic approach to treat 

cancer and other diseases by directing 

an individual’s innate and adaptive 

immune system to recognize specific 

disease-associated antigens. 

T cell receptors (TCRs) are proteins 

that recognize antigens in the context of 

infected or transformed cells and 

activate T cells to mediate an immune 

response and destroy abnormal cells. 

TCRs consist of two domains, one 

variable domain that recognizes the 

antigen and one constant region that 

helps the TCR anchor to the membrane 

and transmit recognition signals by 

interacting with other proteins. 

Scientists at the National Institutes of 

Health (NIH) have isolated T cells that 

recognize the human tyrosinase tumorassociated antigen (TAA) from the 

tumor infiltrating lymphocytes (TIL) of 

a melanoma cancer patient. The human 

tyrosinase antigen is a tumor antigen 

expressed in a variety of cancers, 

including skin cancer (melanoma) and 

brain cancer (glioblastoma). Utilizing 

the tyrosinase specific T cells, these 

scientists developed human/mouse 

hybrid TCRs with enhanced affinity for 

the tyrosinase TAA. The TCR sequences 

were modified by making specific 

amino acid substitutions and replacing 

certain TCR regions with mouse 

homologues. These TCRs also showed 

CD8-independency and, thus, can be 

expressed in both CD8 and CD4 T cells. 

T cells expressing these engineered 

TCRs recognize skin and brain tumor 

cells in culture. These T cells also 

exhibit enhanced cytokine induction 

and better tumor reactivity compared to 

unmodified TCRs. Previous versions of 

gene-modified T cells developed by NIH 

researchers demonstrated objective 

clinical responses in some cancer 

patients, which have validated genemodified T cell immunotherapy as a 

promising cancer treatment strategy. 

TCRs directed against the tyrosinase 

TAA could serve as valuable new 

immunotherapeutic tools for attacking 

tumors, especially in patients whose 

tumors do not express other common 

TAAs. 

Applications 

• Immunotherapeutics to treat and/or 

prevent the recurrence of a variety of 

human cancers, including melanomas 

and glioblastomas, that express 

tyrosinase by transferring T cells 

engineered with tyrosinase-specific 

TCRs into cancer patients. 


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• A drug component of a combination 

immunotherapy regimen aimed at 

targeting the specific tumor-associated 

antigens expressed by the cancer cells of 

individual patients. 

• Immunotherapeutic to treat and/or 

prevent tumors that do not express other 

common tumor-associated antigens, 

such as MART–1, gp100, and 

NY–ESO–1. 

Advantages 

• The parent tyrosinase-specific TCR 

was isolated from tumor infiltrating 

lymphocytes, so the geneticallymodified versions should have an 

elevated affinity for tyrosinase. 

• The tyrosinase-specific T cells 

recognize skin and brain cancer cells in 

culture. These T cells are predicted to 

have broad anti-cancer activity once 

developed to a clinical level. 

• CD8 independency: The tyrosinasespecific TCRs can be expressed in both 

CD8 and CD4 T cells to maximize the 

cell-mediated immune response to the 

tumor. 

• The tyrosinase-specific T cells 

should not be rejected by a patient’s 

immune system since the mouse 

tyrosinase-recognition enhancing TCR 

sequences are incorporated into a 

human TCR backbone. 

Market: Cancer continues to be a 

medical and financial burden on U.S. 

public health. According to U.S. 

estimates, cancer is the second leading 

cause of death with over 565,000 deaths 

reported in 2008 and almost 1.5 million 

new cases were reported (excluding 

some skin cancers) in 2008. In 2007, the 

NIH estimated that the overall cost of 

cancer was $219.2 billion dollars and 

$89 billion went to direct medical costs. 

Despite our increasing knowledge of 

oncology and cancer treatment methods, 

the fight against cancer will continue to 

benefit from the development of new 

therapeutics aimed at treating 

individual patients. 

Inventors: Steven A. Rosenberg et al. 

(NCI). 

Development Status: This technology 

is in the pre-clinical stage of 

development. The inventors plan to 

develop the technology into clinical 

grade reagent for a clinical trial if the 

pre-clinical data continues to show 

promising results. 

Patent Status: U.S. Provisional 

Application No. 61/147,846 filed 28 Jan 

2009 (HHS Reference No. E–043–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Samuel E. Bish, 

PhD; 301–435–5282; 

bishse@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Surgery 

Branch, Tumor Immunology Section, is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize T 

Cells Attacking Cancer: T Cell Receptors 

that Recognize the Tyrosinase Tumor 

Antigen. Please contact John D. Hewes, 

PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Genomics-Based Diagnostic Assay for 

Cancer 

Description of Technology: Molecular 

profiling with high throughput assays 

has gained utility in the management of 

select cancer patients and several gene 

expression-based assays are now 

marketed for improved prognostic 

accuracy for patients with cancer. 

This technology describes a genomics 

based diagnostic assay for the diagnosis 

and prognosis of cancer patients. Using 

a mouse model of breast cancer, the 

inventors identified a gene expression 

signature that can predict the outcome 

for human breast cancer patients with as 

few as six genes. The gene signature 

includes a total of 79 cancer survival 

factor-associated genes and was 

validated using available genomic test 

sets that were based on previously 

conducted human clinical trials. More 

recently, the six-gene-model was 

validated for cancers other than breast 

using multiple, independent, publiclyavailable human lung cancer datasets. In 

addition to predicting the outcome of 

cancer patients, this technology could 

also be used to stratify patients for 

further therapy and treat patients by 

administering therapeutic agents that 

alter the activity of one of the 

aforementioned cancer survival factorassociated genes. 

Applications 

• Methods for cancer diagnosis and 

prognosis by evaluating expression 

levels of certain cancer survival factorassociated molecules in patients. 

• Treatment of cancer by 

administering therapeutic agents that 

alter biological activity of cancer 

survival factor-associated molecule. 

Advantages: Prognostic outcome of 

breast and lung cancer patients can be 

identified in as few as six genes. 

Development Status: Pre-clinical stage 

of development. 

Inventors: Steven K. Libutti and Mei 

He (NCI). 

Patent Status: U.S. Provisional 

Application No. 61/152,597 filed 13 Feb 

2009 (HHS Reference No. E–023–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney A. 

Hastings; 301–451–7337; 

hastingsw@mail.nih.gov. 

New Weapons To Attack Cancer: T Cell 

Receptors Designed To Recognize 

Tumors With Enhanced Affinity 

Description of Technology: Given the 

unpleasant side-effects associated with 

many cancer drugs, there is an urgent 

need to develop new therapeutic 

strategies combining fewer side-effects 

and more specific anti-tumor activity. 

Adoptive immunotherapy is a 

promising new approach to cancer 

treatment that engineers an individual’s 

innate and adaptive immune system to 

fight against specific diseases, including 

cancer. 

T cell receptors (TCRs) are proteins 

that recognize antigens in the context of 

infected or transformed cells and 

activate T cells to mediate an immune 

response and destroy abnormal cells. 

TCRs consist of two domains, one 

variable domain that recognizes the 

antigen and one constant region that 

helps the TCR anchor to the membrane 

and transmit recognition signals by 

interacting with other proteins. 

Scientists at the National Institutes of 

Health (NIH) have developed T cells 

with an enhanced ability to recognize 

the tumor associated antigens (TAAs) 

NY–ESO–1 and MART–1. These T cells 

were engineered to increase their ability 

to recognize these TAAs by making 

small genetic modifications to the TCRs 

that recognize these TAAs. NY–ESO–1 

is a cancer-testis antigen found in 

normal testis and various tumors. 

MART–1 is a melanoma antigen found 

on normal melanocytes and 

overexpressed in malignant melanomas. 

Previous versions of gene-modified T 

cells developed by these researchers to 

attack tumors demonstrated objective 

clinical responses in some cancer 

patients, which validated gene-modified 

T cell adoptive immunotherapy as a 

promising cancer treatment strategy. 

These latest versions of the NY–ESO–1 

and MART–1 specific TCRs, designated 

1G4 NY–ESO–1 and DMF5 MART–1, 

were rationally engineered to enhance 

anti-tumor activity. These TCRs cause T 

cells to exhibit enhanced cytokine 

production and increased lysis of tumor 

cells when stimulated with NY–ESO–1 

or MART–1. Infusing these T cells into 

patients via adoptive immunotherapy 

could prove to be powerful new tools 

for attacking tumors. 

Applications 

• Immunotherapeutics to treat and/or 

prevent the recurrence of a variety of 


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Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 26709 

human cancers that overexpress the 

NY–ESO–1 or MART–1 TAA, including 

melanoma, lung, breast, ovarian, 

prostate, thyroid, and bladder cancer, by 

adoptively transferring gene-modified T 

cells into patients. 

• A drug component of a combination 

immunotherapy regimen aimed at 

targeting the specific tumor-associated 

antigens expressed by cancer cells 

within individual patients. 

Advantages 

• NY–ESO–1 and MART–1 are 

overexpressed on a variety of cancers. 

Thus, this gene-modified TCR 

immunotherapy has wide applicability 

to treat a host of cancer types while 

reducing the side-effects of treatment. 

• These latest engineered TCRs have 

improved affinity for their 

corresponding TAA compared to 

previously developed TCRs with 

modified sequences. 

Development Status: These 

technologies are in clinical 

development. A clinical protocol (08–C– 

0121) is being conducted with the 

enhanced 1G4 NY–ESO–1 TCR. 

Market: Cancer continues to be a 

medical and financial burden on U.S. 

public health. According to U.S. 

estimates, cancer is the second leading 

cause of death with over 565,000 deaths 

reported in 2008 and almost 1.5 million 

new cases were reported (excluding 

some skin cancers) in 2008. In 2007, the 

NIH estimated that the overall cost of 

cancer was $219.2 billion dollars and 

$89 billion went to direct medical costs. 

Despite our increasing knowledge of 

oncology and cancer treatment methods, 

the fight against cancer will continue to 

benefit from the development of new 

therapeutics aimed at treating 

individual patients. 

Inventors: Paul F. Robbins et al. (NCI). 

Publications 

1. PF Robbins et al. Single and dual 

amino acid substitutions in TCR CDRs 

can enhance antigen-specific T cell 

functions. J Immunol. 2008 May 

1;180(9):6116–6131. 

2. Y Zhao et al. High-affinity TCRs 

generated by phage display provide 

CD4+ T cells with the ability to 

recognize and kill tumor cell lines. J 

Immunol. 2007 Nov 1;179(9):5845– 

5854. 

Patent Status 

• U.S. Provisional Patent Application 

No. 60/974,872 filed 25 Sep 2007 (HHS 

Reference No. E–312–2007/0–US–01). 

• PCT Patent Application No. PCT/ 

US2008/77333 filed 23 Sep 2008 (HHS 

Reference No. E–312–2007/1–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Samuel E. Bish, 

PhD; 301–435–5282; 

bishse@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Center for 

Cancer Research, Surgery Branch, is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

TCRs that enhance the function of genemodified T cells. Please contact John D. 

Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Steroid Derivatives as Inhibitors of 

Human Tyrosyl-DNA 

Phosphodiesterase (Tdp1) 

Description of Technology: TyrosylDNA phosphodiesterase (Tdp1) is an 

enzyme that repairs topoisomerase I 

(Top1)-mediated DNA damage induced 

by chemotherapeutic agents and 

ubiquitous DNA lesions that interfere 

with transcription. The current 

technology are steroid derivatives that 

human inhibit Tdp1. 

Currently, there are various types of 

Top1 inhibitors used in chemotherapy, 

e.g., camptothecin. However, Tdp1 

inhibitors are expected to be effective in 

combination therapy with Top1 

inhibitors for the treatment of cancers. 

Combining Tdp1 inhibitors with Top1 

inhibitors would allow Tdp1 to 

potentiate the antiproliferative activity 

of Top1 inhibitors. In addition to Tdp1’s 

effect on Top1, Tdp1 inhibitors can also 

exhibit antitumor activity 

independently, as tumors are shown to 

have excess free radicals, and Tdp1 

repairs DNA damage by oxygen radicals. 

Applications: It is anticipated that 

Tdp1 inhibitors in association with 

Top1 inhibitors can have selective 

activity toward tumor tissues. Tdp1 

inhibitors may exhibit antitumor 

activity by themselves because tumors 

have excess free radicals. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Yves Pommier et al. (NCI) 

Relevant Publication: A manuscript 

directly related to the above technology 

will be available as soon as it is 

accepted for publication. 

Patent Status: PCT Application No. 

PCT/US2008/004541 filed 5 Apr 2008, 

claiming priority to 5 Apr 2007 (HHS 

Reference No. E–130–2007/2–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty Tong, Ph.D.; 

301–594–6565; tongb@mail.nih.gov. 

Collaborative Research Opportunity: 

The Center for Cancer Research, 

National Cancer Institute, Laboratory of 

Molecular Pharmacology, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize inhibitors of TyrosylDNA phosphodiesterase (Tdp1). Please 

contact John D. Hewes, Ph.D. at 301– 

435–3121 or hewesj@mail.nih.gov for 

more information. 

Method for Spectroscopic Quantitation 

of HER2 in Biological Samples 

Description of Technology: An 

important clinical objective in certain 

cancer patients is the quantitation of 

HER2. The level of HER2 expression in 

some tumors correlates with disease 

stage and severity. For example, HER2 

positive breast cancer is a more 

aggressive disease with a greater 

likelihood of recurrence, a poorer 

prognosis, and a decreased chance of 

survival compared with HER2-negative 

breast cancer. 

This invention discloses a mass 

spectrometry method for quantitatively 

measuring HER2 in a variety of 

biological samples such as tissue, 

serum, or plasma. This invention is 

unlike traditional assays that use 

antibodies for detection of a HER2 and 

is superior to the current 

immunohistochemistry methods to stage 

tumor development. Consequently, a 

mass spectrometry-based clinical assay 

could be used to allow physicians to 

more effectively determine patient 

treatment. Furthermore, since this 

technology can also be used to assay 

formalin-fixed prostate tissue (FFPE) 

tissues, it could be a useful biomarker 

for pathology labs. 

Applications 

• Diagnostic assay for cancer that 

measures HER2 levels in clinical 

samples, such as tissues and biological 

fluids. 

• Prognostic assay to determine the 

stage of cancer and the appropriate 

cancer treatment. 

• Research tool that could be used to 

correlate HER2 expression with the 

expression of other proteins. 

Market 

• This novel in vitro diagnostic test 

for cancer has use in oncology and 

pathology laboratories of hospitals and 

commercial clinical laboratories. 

• In the United States, almost 1.5 

million new cancer cases are expected 

to be diagnosed in 2009. 

Development Status: Pre-clinical stage 

of development. 


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26710 Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 

Inventors: Thomas P. Conrads (NCI) et 

al. 

Relevant Publications 

1. BL Hood, MM Darfler, TG Guiel, B 

Furusato, DA Lucas, BR Ringeisen, IA 

Sesterhenn, TP Conrads, TD Veenstra, 

DB Krizman. Proteomic analysis of 

formalin-fixed prostate tissue. Mol Cell 

Proteomics 2005 Nov;4(11):1741–1753. 

2. DA Prieto, BL Hood, MM Darfler, 

TG Guiel, DA Lucas, TP Conrads, TD 

Veenstra, DB Krizman. Liquid tissueTM: 

proteomic profiling of formalin fixed 

tissues. Biotechniques 2005 Jun;38:S32– 

S35. 

3. DS Kirkpatrick, SA Gerber, SP Gygi. 

The absolute quantification strategy: A 

general procedure for the quantification 

of proteins and post-translational 

modifications. Methods 2005 

Mar;35(3):265–273. 

4. AM Hawkridge et al. Quantitative 

mass spectral evidence for the absence 

of circulating brain natriuretic peptide 

(BNP–32) in severe human heart failure. 

Proc Natl Acad Sci USA 2005 Nov 

29;102(48):17442–17447. 

5. L Anderson and CL Hunter. 

Quantitative mass spectrometric MRM 

assays for major plasma proteins. Mol 

Cell Proteomics 2006 Apr;5(4):573–588. 

Patent Status: PCT Application No. 

PCT/US2007/003478 filed 4 Sep 2008 

(HHS Reference No. E–204–2006/0– 

PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@mail.nih.gov. 

Tools To Identify Candidates for 

Effective Cancer Therapy: Antibodies to 

Human Asparagine Synthetase 

Description of Technology: Scientists 

at the National Institutes of Health (NIH) 

have developed peptide-specific 

polyclonal antibodies against human 

asparagine synthetase (ASNS), the 

enzyme that forms asparagine from 

aspartate using ATP. ASNS serves as a 

key biomarker for acute lymphoblastic 

leukemia (ALL) and other malignancies 

because these cancer cells express little 

or no ASNS compared to normal cells. 

As a result, these leukemia cells must 

acquire asparagine from the bloodstream 

to survive and proliferate to form 

tumors. Patients with ALL can be 

treated with L-asparaginase (L–ASP) to 

break down asparagine in the body and 

starve leukemia cells by preventing 

them from acquiring asparagine. The 

anti-ASNS antibodies could be used to 

detect ASNS levels in patient samples to 

help select patients that could benefit 

from L–ASP therapy. Studies at the NIH 

have shown that L–ASP therapy may 

prove to be a useful treatment for other 

types of cancer besides leukemia. 

Applications 

• Diagnostic tool to detect levels of 

asparagine synthetase (ASNS) in human 

samples to identify cancer patients that 

can benefit from L-asparaginase (L–ASP) 

treatment. 

• Screening tool to identify other 

cancer cell types treatable by L–ASP 

therapy, such as ovarian cancer cells, 

which show diminished ASNS levels. 

• Research tool to quantitate levels of 

ASNS in laboratory procedures, 

including various immunoassays, flow 

cytometry, and tissue sample analysis. 

Advantages: These antibodies have 

been validated in immunoassays that 

showed that ASNS expression in a 

strong predictor of L–ASP efficacy in 

NCI–60 ovarian cancer cell lines. 

Inventors: Paul K. Goldsmith et al. 

(NCI). 

Relevant Publications 

1. PL Lorenzi et al. Asparagine 

synthetase as a causal, predictive 

biomarker for L-asparaginase activity in 

ovarian cancer cells. Mol Cancer Ther. 

2006 Nov;5(11):2613–2623. 

2. KJ Bussey et al. Integrating data on 

DNA copy number with gene expression 

levels and drug sensitivities in the NCI– 

60 cell line panel. Mol Cancer Ther. 

2006 Apr;5(4):853–867. 

3. PL Lorenzi et al. Asparagine 

synthetase as a predictive biomarker for 

L-asparaginase activity in ovarian 

cancer cells. Mol Cancer Ther. 2008 

Oct;7(10):3123–3128. 

Patent Status: HHS Reference No. E– 

101–2006/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Samuel E. Bish, 

Ph.D.; 301–435–5282; 

bishse@mail.nih.gov. 

Mouse Model With Targeted Disruption 

of the Neurofibromatosis Type-1 (Nf1) 

Gene 

Description of Technology: This 

invention relates to a mouse model 

having a targeted disruption of the 

neurofibromatosis type-1 (NF1) gene. 

The neurofibromatosis (NF1) gene 

shows significant homology to 

mammalian GAP and is an important 

regulator of the Ras signal transduction 

pathway. To study the function of NF1 

in normal development and to develop 

a mouse model of NF1 disease, the 

inventors have used gene targeting in ES 

cells to generate mice carrying a null 

mutation at the mouse Nf1 locus. 

Although heterozygous mutant mice, 

aged up to 10 months, have not 

exhibited any obvious abnormalities, 

homozygous mutant embryos die in 

utero. Embryonic death is likely 

attributable to a severe malformation of 

the heart. Interestingly, mutant embryos 

also display hyperplasia of neural crestderived sympathetic ganglia. These 

results identify new roles for NF1 in 

development and indicate that some of 

the abnormal growth phenomena 

observed in NF1 patients can be 

recapitulated in neurofibromin-deficient 

mice. In addition, lethally-irradiated 

wild type mice transplanted with fetal 

liver cells taken from NF1 null embryos 

develop a form of juvenile chronic 

myelomonocytic leukemia (JMML) that 

is very similar to what is seen in 

children with NF1 disease. 

Applications 

• Research tool in studying some 

forms of human neuron diseases/ 

injuries in addition to juvenile chronic 

myelomonocytic leukemia (JMML). 

• Testing various therapeutic 

treatments for this disease. 

Inventors: Neal G. Copeland et al. 

(NCI). 

Patent Status: HHS Reference No. E– 

162–2004/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Betty Tong, Ph.D.; 

301–594–6565; tongb@mail.nih.gov. 

Dated: May 27, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–12874 Filed 6–2–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of General Medical 

Sciences; Notice of Closed Meeting 

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 meeting. 

The meeting 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., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 


PWALKER on PROD1PC71 with NOTICES