15326 Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 

tumor progression in an oral-specific 

chemical carcinogenesis model. Cancer 

Prevention Res. 2009 Jan;2(1):27–36. 

[PubMed: 19139015] 

3. Raimondi AR, Molinolo A, Gutkind 

JS. Rapamycin prevents early onset of 

tumorigenesis in an oral-specific K-ras 

and p53 two-hit carcinogenesis model. 

Cancer Res. 2009 May 15;69(10):4159– 

4166. [PubMed: 19435901] 

Patent Status: U.S. Patent Application 

No. 13/059,335 filed August 20, 2009 

(HHS Reference No. E–302–2008/0–US– 

05) and related international filings 

Related Technology: International 

Application No. PCT/IL2010/000694 

filed August 25, 2010 (HHS Reference 

No. E–282–2009/0–PCT–02), entitled 

‘‘Prevention and Treatment of Oral and 

Lips Diseases Using Sirolimus and 

Derivatives Sustained Release Delivery 

Systems for Local Application to the 

Oral Cavity and Lips’’ 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@mail.nih.gov 

Collaborative Research Opportunity: 

The National Institute of Dental and 

Craniofacial Research, Oral and 

Pharyngeal Cancer Branch, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

contact David W. Bradley, PhD at 

bradleyda@nidcr.nih.gov for more 

information. 

Three-Dimensional Co-Culture Assay 

System for Angiogenesis and Metastasis 

Description of Technology: This 

technology features an assay for the 

detection and measurement of 

angiogenesis (formation of new blood 

vessels) and metastasis (spread of 

cancer). The inventors have developed a 

three-dimensional co-culture system 

that closely mimics the in vivo 

environment in which angiogenesis and 

metastatic tumors develop. The coculture system consists of cancerous 

cells (tumor spheroid or biopsy), 

endothelial cells, and a combination of 

other mammalian cells (mast cells, 

adipocytes, fibroblasts, macrophages, 

etc.). The cancerous cells can be 

obtained from cell lines or biopsied 

tumors from various cancers, such as 

melanoma, ovarian cancer, 

hepatocellular cancer, or colon cancer. 

Cells in the three-dimensional coculture system express a fluorescent 

protein having a different emission 

spectrum. Consequently, the co-culture 

systems can be used to identify, 

monitor, and measure changes in 

morphology, migration, proliferation 

and apoptosis of cells involved in 

angiogenesis and/or metastasis. The cocultures are developed in 96-well plates 

to allow rapid and efficient screening 

for whether a drug impacts multiple cell 

types, modulates angiogenesis and/or 

has a therapeutic impact on metastasis. 

This technology not only represents an 

important tool for angiogenesis and 

cancer research, but also may be 

developed into a diagnostic test that 

allows the development of personalized 

therapies for cancer and other 

angiogenesis-mediated disease. 

Applications: 

• Personalized therapies for cancer 

and other angiogenesis-mediated 

diseases 

• Screening for cytotoxic compounds, 

modulators of angiogenesis, and antimetastatic compounds 

• Basic research applications, such as 

fluorescence-activated cell sorting 

(FACS), time-lapse cinematography, and 

confocal microscopy 

Advantages: 

• Closely mimics tumor 

microenvironment 

• Efficient screening method for basic 

research, drug discovery and for clinical 

use 

Development Status: Experimental 

data available; inventors have also 

developed a high-throughput screening 

assay based on this technology 

Inventors: Changge Fang, Enrique 

Zudaire, Frank Cuttitta (NCI) 

Patent Status: 

• U.S. Provisional Application No. 

60/976,732 filed 01 Oct 2007 (HHS 

Reference No. E–281–2007/0–US–01) 

• U.S. Application No. 12/802,666 

filed 10 Jun 2010 (HHS Reference No. 

E–281–2007/1–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301.435.4426; kirbyt@mail.nih.gov. 

Collaborative Research Opportunity: 

We are very interested in setting up 

collaborations with pharmaceutical, 

biomedical, or academic investigators to 

use our technology in the form of a 

CRADA or joint grant submission (e.g. 

DOD). These studies could include 

expanding the complexity of a 3D coculture by increasing the partner cell 

number—paralleling the current model 

of in vivo angiogenesis. Our existing coculture assay incorporates both 

immortalized tumor and endothelial 

cells. However, other anatomically 

distinct cells could be added (e.g. 

pericytes, inflammatory cells [mast cell 

or macrophages], or fibroblasts) to more 

accurately mimic the in vivo setting. In 

addition, a more thorough analysis of 

our prior xenograft biopsy studies for 

assessing drug sensitivity could be done 

using a variety of human tumor cell 

lines that include lung, colon, breast, 

prostate, and ovarian cancer. Finally, 

this collaboration would segue into 

clinical studies taking biopsy material 

from cancer patients (following 

approved IRB protocols) to evaluate 

anti-angiogenic drug sensitivities to 

determine the most appropriate FDA 

reviewed/certified anti-cancer drugs. 

The National Cancer Institute, 

Radiation Oncology Branch, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology as noted 

above. Please contact John Hewes, PhD 

at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Dated: March 15, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–6570 Filed 3–18–11; 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. 

Synthetic Peptide Inhibitors of the Wnt 

Pathway 

Description of Technology: Available 

for licensing are peptide inhibitors of 

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Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 15327 

the Wnt signaling pathway, a pathway 

that is activated in many cancer types. 

To date, there are few small molecules 

that target canonical Wnt/b-catenin 

signaling and those that have been 

discovered have low potency and do not 

directly target b-catenin, the pathway’s 

key signal mediator. The investigators 

have developed peptide inhibitors that 

selectively target a conserved region in 

b-catenin essential for promoting cell 

growth but not cell adhesion and 

differentiation. Furthermore, these 

peptides have been synthetically 

modified to enhance cell penetration 

and structure stability thereby 

increasing their potency and efficacy. 

Interestingly, these peptides inhibit the 

canonical Wnt signaling pathway but 

not non-canonical Wnt signaling. As a 

result, these inhibitors potentially 

provide effective chemotherapies for 

tumors, such as colon and cervical, 

which depend upon canonical Wnt 

signaling. Moreover, as these inhibitors 

do not disrupt non-canonical Wnt 

signaling, which plays a role in kidney, 

lung, and vascular development, and 

they are likely to have minimal negative 

side effects. Additionally, these 

peptides can serve as an effective tool 

for researches to elucidate the roles of 

Wnt canonical and non-canonical 

signaling in development and many 

pathological conditions. 

Applications: 

• Cancer therapeutics 

• Research tool to study Wnt 

signaling pathways 

Advantages: 

• Selective inhibitors that target cell 

growth but not differentiation 

• Synthetic molecules with increased 

stability and cell penetration that can be 

manufactured in large quantities under 

GMP conditions 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Market: Peptide drug market is 

growing at a compound annual rate of 

7.5% with an estimated value in excess 

of $13 billion in 2010 

Inventors: Nadya Tarasova, Alan 

Perantoni, Shunsuke Tanigawa (NCI) 

Related Publication: S Tanigawa et al. 

Wnt4 induces nephronic tubules in 

metanephric mesenchyme by a noncanonical mechanism. Dev Biol. 2011 

Jan 20. E-pub ahead of print, 

doi:10.1016/j.physletb.2003.10.071. 

[PubMed: 21256838] 

Patent Status: U.S. Provisional 

Application No. 61/422,857 filed 14 Dec 

2010 (HHS Reference No. E–021–2011/ 

0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jennifer Wong; 

301–435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The Center for Cancer Research, Cancer 

and Inflammation Program and Cancer 

and Developmental Biology Laboratory, 

are seeking statements of capability or 

interest from parties interested in 

collaborative research to further develop 

and commercialize Wnt pathway 

inhibitors. Please contact John Hewes, 

PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Therapeutic Approach for Autoimmune 

Diseases, Inflammatory Diseases and 

Cancers by Blocking CIKS–TRAF6 

Interactions 

Description of Technology: CIKS (also 

known as Act1 or TRAF3IP2) is an 

intracellular adaptor protein involved in 

the signaling pathway of IL–17 

cytokines. Interaction between CIKS and 

tumor necrosis factor receptorassociated factor (TRAF 6) is important 

for IL–17 signaling and collectively, IL– 

17, CIKS, and TRAF6 are involved in 

inflammatory responses associated with 

autoimmune diseases, inflammatory 

diseases, and cancers. Inhibition of 

CIKS activity has been shown to prevent 

and alleviate pathological symptoms in 

an animal model of rheumatoid arthritis 

and multiple sclerosis, and it is 

hypothesized that disruption of the 

interaction between CIKS and TRAF6 is 

a therapeutic strategy for the selective 

prevention of certain IL–17-mediated 

diseases. 

NIAID investigators have discovered a 

short sequence within CIKS that is 

responsible for CIKS interaction with 

TRAF6. The disclosed sequence can be 

used to develop blocking peptides for 

the treatment of IL–17-mediated 

autoimmune diseases, inflammatory 

diseases, and cancers. 

Applications: Therapeutics for IL–17- 

mediated diseases, such as 

inflammatory diseases, autoimmune 

diseases, and cancer. 

Advantages: Selective inhibition of 

CIKS–TRAF6 interactions. 

Development Status: Basic research. 

Inventors: Ulrich Siebenlist, Soeren U. 

Soender, Sun Saret (NIAID). 

Publications: 

1. Pisitkun P, et al. (2010) [PubMed: 

20662069] 

2. Claudio E, et al. (2009) [PubMed: 

19155511] 

Patent Status: U.S. Provisional 

Application No. 61/418,782 filed 01 Dec 

2010 (HHS Reference No. E–268–2010/ 

0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Tara L. Kirby, PhD; 

301–435–4426; tarak@mail.nih.gov. 

Tiopronin Specifically Kills and Resensitizes Multi-Drug Resistant Cells to 

Chemotherapy 

Description of Technology: One of the 

major hindrances to successful cancer 

chemotherapy is the development of 

multi-drug resistance (MDR) in cancer 

cells. MDR is frequently caused by the 

increased expression or activity of ABC 

transporter proteins in response to the 

toxic agents used in chemotherapy. The 

increased expression or activity of the 

ABC transporter proteins causes the 

toxic agents to be removed from cells 

before they can kill the cell. As a result, 

research has generally been directed to 

overcoming MDR by inhibiting the 

activity of ABC transporters, thus 

causing the chemotherapeutic agents to 

remain in the cell long enough to exert 

their effects. However, compounds that 

inhibit ABC transporter activity often 

elicit strong and undesirable side-effects 

due to the inhibition of ABC transporter 

function in normal cells, thereby 

restricting their usefulness as 

therapeutics. 

Investigators at the NIH have now 

discovered that the amino acid analog 

Tiopronin has the ability to kill multidrug resistant cancer cells while leaving 

normal cells relatively unharmed. This 

suggests that Tiopronin can be 

developed as a therapeutic for multidrug resistant cancers. Furthermore, 

Tiopronin re-sensitizes multi-drug 

resistant cells to chemotherapeutic 

agents over time. This may allow 

cyclical administration of 

chemotherapeutics without the 

development of permanent resistance to 

the agents, increasing the effectiveness 

of chemotherapy as a cancer treatment. 

Importantly, Tiopronin is not an 

inhibitor of ABC transporter function 

because it kills multi-drug resistant cells 

without affecting the activity of ABC 

transporters. As a result, the undesirable 

side-effects that have prevented the use 

of inhibitors of ABC transporters as 

therapeutics should not affect the 

therapeutic application of Tiopronin. 

Applications: 

• Treatment of cancers associated 

with MDR, either alone or in 

combination with other therapeutics 

• Resensitization of multi-drug 

resistant cells to chemotherapeutic 

agents, allowing cyclical administration 

of chemotherapy 

Advantages: 

• Tiopronin capitalizes on one of the 

most common drawbacks to cancer 

therapies (MDR) by using it as an 

advantage for treating cancer 

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15328 Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 

• Tiopronin does not inhibit the 

activity of ABC transporters, thereby 

reducing the chance of undesired sideeffects during treatment 

• The effects of Tiopronin correlates 

with the level of ABC transporter 

expression, allowing healthy cells to 

better survive treatments 

• Tiopronin can also improve the 

effectiveness of chemotherapy by resensitizing resistant cells that were 

previously considered impervious to 

treatment 

• Tiopronin has already been 

approved for use in humans for the 

treatment of cytinuria, facilitating the 

pathway for use in humans as a 

treatment for cancer 

Development Status: Preclinical stage 

of development, in vitro data 

Inventors: Andrew S. Goldsborough et 

al. (NCI) 

US Patent Status: US Provisional 

Application 61/407,948 (E–227–2010/0– 

US–01) 

Licensing Status: The technology is 

available for exclusive licensing. 

Licensing Contact: David Lambertson, 

PhD; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, 

Multidrug Resistance Section, 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– 

3121 or hewesj@mail.nih.gov for more 

information. 

Identification of EGFR as a Receptor for 

AAV6 Transduction 

Description of Technology: AAV 

vectors offer unique advantages in gene 

therapy applications. Studies have 

shown that these replication deficient 

parvovirus vectors can deliver DNA to 

specific tissues and confer long-term 

transgene expression in a variety of 

systems. Although many studies have 

looked at the tissue-specific expression 

elicited by each of the AAV serotypes, 

a true understanding of how AAV 

transduces these tissues is still unclear. 

Of the large AAV family, only a few 

receptors or co-receptors have been 

identified. The ability to better target 

transduction to specific tissues on the 

basis of the receptors that each serotype 

uses for entry is essential for selecting 

a serotype given the receptor expression 

in specific tissue, or to exploit altered 

receptor expression under disease 

conditions. 

AAV6 has been reported to effectively 

transduce muscle, lung, brain, and 

multiple types of tumors, including 

gliomas and lung adenocarcinomas. By 

using a bioinformatics based screen 

approach, the NIH investigators 

discovered that the epidermal growth 

factor receptor (EGFR) is a co-receptor 

for AAV6 infection in mammalian cells, 

and is necessary for efficient vector 

internalization. 

Applications and Market: Improved 

gene therapy applications. 

Development Status: Pre-clinical stage 

of development. 

Inventors: John A. Chiorini, Melodie 

L. Weller, Michael Schmidt (NIDCR) 

Publication: Weller ML, 

Amornphimoltham P, Schmidt M, 

Wilson PA, Gutkind JS, Chiorini JA. 

Epidermal growth factor receptor is a 

co-receptor for adeno-associated virus 

serotype 6. Nat Med. 2010 

Jun;16(6):662–664. [PubMed: 20473307] 

Patent Status: U.S. Utility Patent 

Application No. 12/879,142 filed 10 Sep 

2010 (HHS Reference No. E–194–2010/ 

0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

PhD; 301–594–6565; 

tongb@mail.nih.gov. 

Therapeutic Approach to 

Neurodegenerative Disorders Using a 

TFP5-Peptide 

Description of Technology: This 

invention discloses methods for treating 

neurodegenerative diseases by 

administering cyclin dependent kinase 

5 (Cdk5) inhibitory peptides derived 

from P35, the activator of Cdk5. 

Abnormally hyperactive Cdk5 has been 

shown to be associated with a variety of 

neurodegenerative disorders. Disclosed 

in this invention are isolated peptide 

fragments, pharmaceutical compositions 

and methods for use of such for treating 

subjects with a neurodegenerative 

disease, such as Alzheimer’s disease 

(AD), Amyotrophic Lateral Sclerosis 

(ALS) and Parkinson’s disease (PD). An 

inhibitory fragment, TFP5, disclosed in 

this invention, has been shown to 

ameliorate symptoms of AD in disease 

animal models without any evidence of 

toxicity. In particular, TFP5 treatment of 

rat cortical neurons reduced 

hyperactivation of Cdk5 upon neuronal 

stress and insults. Following 

intraperitoneal (ip) injection, TFP5 was 

capable of crossing the BBB and 

localizing within the brain where it was 

found to rescue memory deficits and 

pathology in a double transgenic mouse 

(APP/PS1) AD model. 

Applications: Therapeutic 

developments (AD, PD, ALS) 

Advantages: The products are small 

peptides that pass the blood brain 

barrier. 

Market: Development for AD, PD, and 

ALS. 

Development Status: Pre-clinical; 

some animal data 

Inventors: Harish C. Pant (NINDS) 

Patent Status: U.S. Provisional 

Application No. 61/387,839 filed 29 Sep 

2010 (HHS Reference No. E–144–2010/ 

0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Steven H. 

Standley, PhD; 301–435–4074; 

sstand@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Neurological 

Disorders and Stroke, Neuronal 

Cytoskeletal Protein Regulation Section, 

is seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

topic of invention or related laboratory 

interests. Please contact Heather Gunas, 

J.D., M.P.H., at 301–451–3944 or 

gunash@mail.nih.gov for more 

information. 

Dated: March 15, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–6569 Filed 3–18–11; 8:45 am] 

BILLING CODE 4140–01–P 

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., 

as amended. The contract proposals and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable materials, 

and personal information concerning 

individuals associated with the contract 

proposals, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute on 

Drug Abuse Special Emphasis Panel; GISTE, 

the Geospatial Information Systems Tool 

(5558). 

Date: April 18, 2011. 

Time: 1:30 p.m. to 3 p.m. 

Agenda: To review and evaluate contract 

proposals. 

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