Federal Register / Vol. 74, No. 157 / Monday, August 17, 2009 / Notices 41443 

billion by 2012 according to some 

reports. 

Overall, the potential commercial 

opportunity based on the subject 

technology is immense. 

Inventors: Bernard Moss et al. 

(NIAID). 

Publications: The inventor, Dr. 

Bernard Moss, is an author of more than 

100 publications in the area covered by 

the subject patents. The following is just 

a sampling of his publications in the 

area: 

1. B Moss and PL Earl. Overview of the 

vaccinia virus expression system. Curr Protoc 

Mol Biol. 2002 Nov; Chapter 16: Unit16.15. 

2. HL Robinson, S Sharma, J Zhao, S 

Kannanganat, L Lai, L Chennareddi, T Yu, 

DC Montefiori, RR Amara, LS Wyatt, B Moss. 

Immunogenicity in macaques of the clinical 

product for a clade B DNA/MVA HIV 

vaccine: elicitation of IFN-gamma, IL–2, and 

TNF-alpha coproducing CD4 and CD8 T 

cells. AIDS Res Hum Retroviruses. 2007 

Dec;23(12):1555–1562. 

3. LS Wyatt, PL Earl, J Vogt, LA Eller, D 

Chandran, J Liu, HL Robinson, B Moss. 

Correlation of immunogenicities and in vitro 

expression levels of recombinant modified 

vaccinia virus Ankara HIV vaccines. Vaccine 

2008 Jan 24;26(4):486–493. 

4. M Hebben, J Brants, C Birck, JP Samama, 

B Wasylyk, D Spehner, K Pradeau, A Domi, 

B Moss, P Schultz, R Drillien. High level 

protein expression in mammalian cells using 

a safe viral vector: modified vaccinia virus 

Ankara. Protein Expr Purif. 2007 

Dec;56(2):269–278. 

Patent Status: The technology is 

described and claimed in the following 

four (4) patents that were issued in the 

U.S. in 2006 (HHS Reference E–552– 

1982/2): 

1. USPN 6,998,252 issued February 

14, 2006, ‘‘Recombinant Poxviruses 

Having Foreign DNA Expressed under 

the Control of Poxvirus Regulatory 

Sequences’’. 

2. USPN 7,015,024 issued March 21, 

2006, ‘‘Compositions Containing 

Recombinant Poxviruses Having Foreign 

DNA Expressed Under the Control of 

Poxvirus Regulatory Sequences’’. 

3. USPN 7,045,313 issued May 16, 

2006, ‘‘Recombinant Vaccinia Virus 

Containing Chimeric Gene Having 

Foreign DNA Flanked by Vaccinia 

Regulatory DNA’’. 

4. USPN 7,045,136 issued May 16, 

2006, ‘‘Methods of Immunization Using 

Recombinant Poxviruses Having Foreign 

DNA Expressed Under the Control of 

Poxvirus Regulatory Sequences’’. 

Licensing Status: Available for 

licensing. 

Licensing Contacts: Uri Reichman, 

Ph.D., MBA; 301–435–4616; 

ur7a@nih.gov; RC Tang, JD, LLM; 301– 

435–5031; tangrc@mail.nih.gov. 

Dated: August 10, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–19693 Filed 8–14–09; 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. 

Superior Method of Preparing 

Dendrimers for Use as Magnetic 

Resonance Imaging (MRI) Contrast 

Agents 

Description of Technology: There is a 

need to develop more efficient 

gadolinium-containing (Gd) contrast 

agents for magnetic resonance imaging 

(MRI) as the small molecules presently 

used clinically have the disadvantage of 

being rapidly cleared from circulation 

and excreted by the kidneys. 

Dendrimer-based macromolecular 

MRI contrast agents in which numerous 

chelated Gd ions are covalently attached 

to a multivalent dendritic architecture 

are a promising class of diagnostic 

agents for medical imaging applications. 

Clinical development of the dendrimerbased agents has been limited as the 

current methods for synthesizing them 

result in a complex mixture that 

produces inconsistent imaging results. 

The present technology describes the 

development of a new method of preforming the metal-ligand chelate in 

alcohol prior to conjugation to the 

dendrimer. Specifically, for example, a 

1B4M–DTPA–Gd chelate is preformed 

in methanol and purified prior to 

conjugation to a PAMAM dendrimer 

molecule. This results in a dendrimerbased MRI contrast agent with greatly 

improved homogeneity and stability, 

and possessing an unexpectedly greater 

molar relaxivity that allows the use of 

much less of the agent than previously 

required to obtain comparable images. 

The use of a DOTA–Gd chelate is 

equally possible. 

Application: An improved method for 

synthesis of dendrimer-based MRI 

contrast agents that is greatly suited for 

clinical development. 

Advantages 

• Efficient preparation of stable 

dendrimer-based contrast agents 

suitable for medical imaging. 

• Higher molar relaxivity translates 

into a lower dosage needed for imaging. 

• Ability to control dendrimer size 

conducive for development of 

compartment-specific imaging agents. 

Market: Dendrimers show particular 

promise for the development of cancer 

imaging agents. The ability to 

exquisitely control dendrimer size 

enables delivering them to specific 

compartments such as small tumors 

allowing for early cancer detection. 

Gadolinium (Gd) chelates are 

extensively used as MRI contrast agents 

and have proven to be safe. The 

combination of gadolinium chelates 

with dendrimer chemistry could greatly 

enhance the versatility of MRI imaging. 

Inventors: Kido Nwe and Martin W. 

Brechbiel (NCI). 

Publications 

1. K Nwe, H Xu, CA Regino, M Bernardo, L 

Ileva, L Riffle, KJ Wong, MW Brechbiel. 

A new approach in the preparation of 

dendrimer-based bifunctional 

diethylenetriaminepentaacetic acid MR 

contrast agent derivatives. Bioconjugate 

Chem. 2009 Jul;20(7):1412–1418. 

2. OA Gansow, MW Brechbiel, MA 

Magerstadt. Complexes of functionalized 

tetraazacyclododecane chelates with 

bismuth, lead, yttrium, actinium, or 

lanthanide metal ions. U.S. Patent 

5,428,154 issued 27 Jun 1995. 

Patent Status: U.S. Provisional 

Application No. 61/180,327 filed 21 

May 2009 (HHS Reference No. E–207– 

2009/0–US–01). 

Related Technology: OA Gansow, MW 

Brechbiel, MA Magerstadt, ‘‘Complexes 

of Functionalized 

Tetraazacyclododecane Chelates with 

Bismuth, Lead, Yttrium, Actinium, or 

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Lanthanide Metal Ions,’’ U.S. Patent 

5,428,154 issued 27 Jun 1995 (HHS 

Reference No. E–347–1996/0–US–22). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sabarni Chatterjee, 

Ph.D.; 301–435–5587; 

chatterjeesa@mail.nih.gov. 

Collaborative Research Opportunity: 

The Inorganic & Radioimmune 

Chemistry Section, ROB, CCR, NCI is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

macromolecular (dendrimer-based) MR 

contrast agents as well as multimodality analogs. Please contact John D. 

Hewes, Ph.D. at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Two Types of Dentin 

Sialophosphoprotein (DSPP) Knockout 

Mice 

Description of Technology: Two types 

of dentin sialophosphoprotein knockout 

mice are available for licensing. The 

technology relates to two separate 

knockout mouse models of the role of 

dentin sialophosphoprotein in dentin 

mineralization and development of 

teeth. The first knockout mouse is a 

knockout of the entire DSPP gene, 

which results in a phenotype similar to 

human autosomal dominant 

dentinogenesis imperfecta, in which 

teeth have widened predentin and 

irregular dentin mineralization resulting 

in sporadic unmineralized areas in 

dentin and frequent pulp exposures. 

DSPP protein in odontoblasts is 

normally proteolytically cleaved into 

two products, dentin sialoprotein (DSP) 

and dentin phosphoprotein (DPP). To 

distinguish the role of the proteolytic 

fragments, the second knockout mouse 

(DPPcKO) consists of a transgene 

expressing the DSP fragment in a DSPP 

null background. The DPPcKO mouse 

demonstrates a partial rescue of the 

DSPP knockout effect and indicates DSP 

and PPP have distinct roles in dentin 

development. 

Applications 

• Tool for studying dentin 

development. 

• Tool for developing treatments for 

autosomal dominant dentinogenesis 

imperfecta. 

Inventors: Ashok Kulkarni and 

Shigeki Suzuki (NIDCR) 

Related Publications 

1. Sreenath T, Thyagarajan T, Hall B, 

Longenecker G, D’Souza R, Hong S, 

Wright JT, MacDougall M, Sauk J, 

Kulkarni AB. Dentin 

sialophosphoprotein knockout mouse 

teeth display widened predentin zone 

and develop defective dentin 

mineralization similar to human 

dentinogenesis imperfecta type III. J Biol 

Chem. 2003 Jul 4;278(27):24874–24880. 

2. Suzuki S, Sreenath T, Haruyama N, 

Honeycutt C, Terse A, Cho A, Kohler T, 

Muller R, Goldberg M, Kulkarni A. 

Dentin sialoprotein and dentin 

phosphoprotein have distinct roles in 

dentin mineralization. Submitted, 2009. 

Patent Status: HHS Reference No. E– 

201–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: This technology is 

available as a research tool under a 

Biological Materials License. 

Licensing Contact: Steve Standley, 

PhD; 301–435–4074; sstand@od.nih.gov. 

Novel Diagnostic and Therapeutic 

Biomarkers for Squamous Cell 

Carcinomas 

Description of Technology: Head and 

neck squamous cell carcinoma (HNSCC) 

includes tumors of the nasal cavities, 

paranasal sinuses, oral cavity, 

nasopharynx, oropharynx, 

hypopharynx, and larynx. HNSCC is an 

aggressive cancer with poor prognosis 

after metastasis. In patients where 

HNSCC is identified early, prognosis is 

better and patient survival increases. 

However, at present, very few if any 

biomarkers are available to diagnosis 

HNSCC. The overall 5-year survival rate 

for patients is only 50% and has not 

improved in over 30 years. New 

treatments and diagnostics for early 

detection are needed to improve patient 

survival and quality of life for this these 

types of cancers. 

Scientists at the National Institutes of 

Health (NIH) have discovered that the 

TGF-b signaling pathway crosstalks 

with the PI3K/Akt signaling pathway to 

suppress squamous cell carcinomas 

(SCCs). When the TGF-b pathway is 

inactivated and the PI3K pathway 

becomes hyperactive, HNSCC 

development is accelerated. Combined 

mutations in the transforming growth 

factor-b receptor type 1 (TGFbR1) gene 

and the phosphate and tensin homolog 

(PTEN) gene directly correlate with an 

individual having HNSCC or being 

increasingly susceptible to HNSCC. 

When tumor-associated mutations in 

both biomarkers were induced in animal 

subjects, spontaneous SCCs were 

developed in every test subject. Given 

this high correlation, this technology 

could be utilized to improve diagnosis 

of HNSCC at its early stages when the 

malignancy is most treatable. This 

technology also includes therapeutic 

combinations of TGF-b and PI3K/Akt 

modulators as treatments for HNSCC 

and methods of treating patients 

diagnosed with HNSCC. 

Applications 

• Biomarkers to diagnose patients 

with HNSCC or predict patients who 

have a high susceptibility for 

developing HNSCC. 

• Diagnostic tool to identify patients 

predicted to respond to specific HNSCC 

therapies as part of a personalized 

treatment strategy. 

• Therapeutic drug combinations of 

TGF-b pathway modulators and PI3K/ 

Akt inhibitors to treat various head and 

neck cancers, including nasal, oral, 

pharyngeal, laryngeal, and cranial 

tumors. 

Advantages 

• Complete Penetrance: All test 

subjects exhibiting mutations in the 

TGFbR1 and PTEN genes develop 

HNSCC. A diagnostic kit that includes 

assays for these mutations is predicted 

to have high accuracy for identifying 

HNSCC. 

• Earlier diagnosis could yield more 

effective treatments: This technology 

could provide for a more accurate and 

earlier diagnosis of SCCs to 

revolutionize the treatment of this 

malignancy. Current SCC therapies may 

become more effective treatments and 

new therapies could be developed as 

better treatment options. 

• Diagnostic for HNSCC susceptibility 

could lead to HNSCC prevention: This 

technology could identify patients 

predisposed to developing HNSCC in 

order to help prevent individuals from 

developing head and neck cancer. 

Development Status: This technology 

is in the pre-clinical stage of 

development. In vivo and in vitro mouse 

data is available. 

Market: Cancer continues to be a 

medical and financial burden on U.S. 

public health. The incidence of HNSCC 

is over 500,000 cases worldwide and 

approximately 47,000 new cases are 

diagnosed each year in the United 

States. Despite our increasing 

knowledge of cancer treatment and 

diagnosis methods, the fight against 

cancer will continue to benefit from the 

development of new technologies aimed 

at treating individuals with disease and 

diagnosing susceptible patients. 

Inventors: Ashok B. Kulkarni and 

Yansong Bian (NIDCR). 

Publications 

1. Y Bian et al. Progressive tumor formation 

in mice with conditional deletion of 

TGF-b signaling in head and neck 

epithelia is associated with activation of 

the PI3k/Akt Pathway. Manuscript in 

preparation (accepted). 

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Federal Register / Vol. 74, No. 157 / Monday, August 17, 2009 / Notices 41445 

2. Y Honjo et al. TGF-beta receptor I 

conditional knockout mice develop 

spontaneous squamous cell carcinoma. 

Cell Cycle 2007 Jun 1:6(11):1360–1366. 

Patent Status: U.S. Provisional 

Application No. 61/176,723 filed 08 

May 2009 (HHS Reference No. E–118– 

2009/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Samuel E. Bish, 

Ph.D.; 301–435–5282; 

bishse@mail.nih.gov. 

Antigen Mixtures for Serological 

Detection of HHV–8 Infection 

Description of Technology: This 

invention describes a highly specific 

and sensitive serological test for human 

herpesvirus 8 (HHV–8) infection that 

uses the Luciferase 

Immunoprecipitation System (LIPS). A 

mixture of four virus-specific antigens, 

including K8.1, v-cyclin, ORF65 and 

LANA, was shown to provide more 

robust detection of HHV–8 infection 

than traditional methods due its ability 

to detect very low viral loads. In 

addition, one of the antigens, v-cyclin, 

was identified as a new serological 

marker for HHV–8 infection, and its 

similarity to a known human oncogene, 

cyclin-D, raises the possibility of its use 

as a diagnostic tool for detecting cancer. 

This test is more sensitive and 

amenable to a high-throughput format 

than other conventional tests for HHV– 

8 infection such as Immunofluorescent 

Assays, Western Blots, ELISAs and PCR 

based approaches. It simplifies data 

collection and analysis and allows for 

more rapid clinical output. Validation 

tests on patient sera samples using this 

4-antigen mixture has shown 100% 

sensitivity and specificity compared to 

94% for ELISAs. 

The test can be incorporated into 

routine screening panels for rapid 

screening of HHV–8 infection, and may 

be potentially adapted for use as a 

diagnostic tool for detecting cancer. A 

successful embodiment of the test can 

be incorporated into routine blood 

screening panels, and may lead a 

reduced risk of transfusion-transmitted 

HHV–8 infection in patients. It may also 

be useful for detecting HHV–8 induced 

cancer in HIV infected patients. 

Applications 

• Rapid and efficient serological 

screening of HHV–8 infection. 

• Cancer diagnostics. 

Development Status: Early Stage. 

Inventors: Peter D. Burbelo (NIDCR), 

Joseph A. Kovacs (CC), Michael J. 

Iadarola (NIDCR). 

Publication: PD Burbelo, HP Leahy, S 

Groot, LR Bishop, W Miley, MJ Iadarola, 

D Whitby, JA Kovacs. Four-antigen 

mixture containing v-cyclin for 

serological screening of human 

herpesvirus 8 infection. Clin Vaccine 

Immunol. 2009 May;16(5):621–627. 

Patent Status: U.S. Patent Application 

No. 61/152,058 filed 12 Feb 2009 (HHS 

Reference No. E–063–2009/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James, 

PhD; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Oligo Microarray for Detection of All 

Known Mammalian and Avian 

Pathogenic Viruses 

Description of Technology: The 

spectrum of pathogenic viruses of 

importance in human disease, 

agriculture and biology is not only large 

and diverse, but continually evolving. 

The identification or isolation of viral 

pathogens, in correlation with the 

presence of specific disease phenotypes, 

is of paramount importance both to 

diagnosis of disease and the subsequent 

management or treatment of viral 

infection. The limitations of current 

viral detection methods, such as PCR 

and immunoassays, led to the 

development of a novel microarray 

system for specific detection of viruses. 

The technology offered here for 

licensing provides a method for highthroughput screening of known 

pathogenic viruses along with 

identification of ‘‘new’’ diseaseassociated viruses. 

The novel method is based on a viral 

microarray containing 10,000 

immobilized DNA oligonucleotide 

features, representing all known 

mammalian and avian pathogenic 

viruses (approximately 600). Software 

was also developed to analyze the viral 

microarray results. The oligonucleotide 

features in this system are 60-mer long 

and distributed across both conserved 

and non-conserved regions of known 

viral sequences. This design serves the 

dual purpose of: (1) Facilitating 

validation via redundant signals 

associated with each represented virus 

and (2) allowing for the discovery of 

new viruses, which arise due to 

recombination. In addition, positive and 

negative controls against human and 

mouse housekeeping genes are included 

along with software for analysis of virus 

microarray results. 

Further advantages of the viral 

microarray include: (a) The use of 

sample inputs as little as 10ng of either 

total DNA or RNA extracted from virus 

infected cells, representing as few as 20 

viral particles; (b) detection of viruses of 

both DNA and RNA classes; (c) a 

capacity for high-throughput screening 

of various sample types including 

serum, saliva and biopsy tissues; and (d) 

analysis of a large number of samples in 

parallel on identical arrays. 

The detection of viral DNA is unique 

to this technology, as other available 

technologies only detect viral genomic 

RNA or viral mRNA transcripts. 

Additionally, the viral chip was found 

to be highly specific and sensitive for 

detecting different viral genomic 

sequences in cell lines and multiple 

viral constructs co-infection in cultured 

cells. 

Applications 

• Detection and identification of 

viruses that cause disease. 

• Efficient discovery of new 

pathogenic viruses. 

• Diagnosis of human and animal 

disease outbreaks. 

• Identification of viral agents used in 

bioterrorism. 

Development Status 

• The pre-clinical performance of the 

viral microarray was evaluated by 

application of four virally positive 

infected cell lines (JSC–1-harboring EBV 

and KSHV, BCBL–1 harboring KSHV, 

HeLa- harboring HPV18, Cem X 174 

harboring SIV). 

• Clinical performance was tested 

and validated through analysis of total 

RNA from cold (swab), Japanese 

Encephalitis, Dengue, Ebola and West 

Nile virus samples. 

Inventors: Cassio S Baptista and David 

J Munroe (NCI). 

Patent Status: U.S. Patent Application 

No. 11/800,080 filed 02 May 2007 (HHS 

Reference No. E–206–2006/0–US–03). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James 

Ph.D.; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Collaborative Research Opportunity: 

The NCI Laboratory of Molecular 

Technology is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this oligo microarray for 

identification and detection of all 

known mammalian and avian 

pathogenic viruses. Please contact John 

D. Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Dated: August 10, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–19691 Filed 8–14–09; 8:45 am] 

BILLING CODE 4140–01–P 

mstockstill on DSKH9S0YB1PROD with NOTICES