26402 Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices 

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. 

Selenocysteine Mediated Hybrid 

Antibody Molecules 

Description of Technology: Available 

for licensing is a new class of hybrid 

molecules composed of an antibody, or 

antibody fragment, and a small 

synthetic molecule (such as a small 

molecule inhibitor, or cytotoxic 

compound). These biological and 

chemical components are covalently 

linked at an engineered selenocysteine 

near the C-terminus of the antibody, or 

antibody fragment. Through this 

covalent linkage, the chemical and the 

biological component can acquire 

properties of one another. For example, 

the synthetic molecule acquires 

antibody properties such as circulatory 

half-life, effector functions, and ability 

to interfere with protein interactions 

whereas the antibody, or antibody 

fragment, acquires properties of the 

small synthetic molecule such as 

specificity, affinity, and stability to bind 

to targets that are sterically inaccessible 

to immunoglobulins. The technology 

can also be used to equip an antibody, 

or antibody fragment, with a small 

synthetic molecule that enhances target 

destruction or imaging capabilities 

through site-selective biotinylation, 

PEGylation, addition of an imaging 

agent, or addition of a cytotoxic agent 

such as a chemotherapeutic drug or a 

chelate for radioisotope labeling. The 

hybrid antibody molecules can be 

engineered with a variety of small 

synthetic molecules, and the 

combination of immunogenic properties 

and those of the small synthetic 

molecules results in compounds with 

powerful target destruction or imaging 

capabilities. This technology could be 

applied towards the targeted delivery of 

small synthetic molecules to various 

cell surface receptors, and may have 

applicability as a prevention, diagnosis, 

or therapy for numerous disease states. 

Applications: Potent novel 

compositions that retains immunogenic 

properties and those of small synthetic 

molecules that can be produced at a 

large scale; Method to prevent, 

diagnose, and treat cancer, infectious 

diseases and autoimmune diseases. 

Market: Monoclonal antibody market 

is projected to exceed $30 billion by 

2010; Revenue from antibodies for 

therapeutics and diagnostic uses are 

expected to grow at an average annual 

growth rate of 11.5%. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Christoph Rader et al. 

(NCI). 

Patent Status: U.S. Provisional 

Application No. 60/909,665 filed 02 Apr 

2007 (HHS Reference No. E–146–2007/ 

0–US–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Jennifer Wong; 

301/435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Center for 

Cancer Research, Experimental 

Transplantation and Immunology 

Branch, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize Selenocysteine Mediated 

Hybrid Antibody Molecules. Please 

contact Dr. Christoph Rader at (301) 

451–2235 or raderc@mail.nih.gov for 

more information. 

Mutant Alleles of Hsp90 that Modulates 

the Lifespan of Yeast 

Description of Technology: Heat shock 

protein 90 (Hsp90) are a class of 

chaperone proteins that are up-regulated 

in response to elevated temperature and 

other environmental stresses. They act 

as chaperones to other cellular proteins 

and facilitate their proper folding and 

repair, and aid in the refolding of 

misfolded client proteins. 

This invention identifies Hsp90 

mutant residues that affect the 

chronological lifespan of yeast. These 

mutations in addition to a deletion in 

the sch9 allele, the yeast homolog to 

human kinase AKT, can increase yeast 

lifespan from 45 to 57 days, 

approximately 20% longer than the 

wildtype strain. These genetically 

engineered yeast strains may have the 

longest chronological lifespan reported 

to date. 

Applications: Model to study aging 

and longevity factors; Model to screen 

compounds that affect lifespan; A longlived yeast strain could be used to 

ferment alcohol in a more efficient and 

cost effective as an alternative fuel 

source; Method to extend lifespan of 

transgenic farm animals. 

Market: Anti-aging and alternative 

fuel industries are worth billions of 

dollars. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Bradley T. Scroggins (NCI) 

et al. 

Related Publication: BT Scroggins et 

al. An acetylation site in the middle 

domain of Hsp90 regulates chaperone 

function. Mol Cell. 2007 Jan 

12;25(1):151–159. 

Patent Status: U.S. Provisional 

Application No. 60/848,346 filed 09 Sep 

2006 (HHS Reference No. E–319–2006/ 

0–US–01). 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Jennifer Wong; 

301/435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute’s Urologic 

Oncology Branch is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize models to study aging 

and longevity factors. Please contact 

John D. Hewes, Ph.D. at 301–435–3121 

or hewesj@mail.nih.gov for more 

information. 

Inhibitors of Ubiquitin E1 

Description of Technology: The 

present invention discloses novel 

pyrazolidinyl compounds that inhibit 

undesired cell proliferation. The 

compounds inhibit ubiquitin E1 and can 

be useful for regulating protein 

ubiquitination. Specifically, the novel 

pyrazolidinyl compounds can stabilize 

p53 and induce apoptosis in 

mammalian cells through selective 

inhibition of ubiquitin E1. 

Ubiquitin-mediated proteolysis is an 

important pathway of non-lysosomal 

protein degradation that controls the 

timed destruction of a number of 

cellular regulatory proteins including 

p53. The ubiquitin pathway leads to the 


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Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices 26403 

covalent attachment of poly-ubiquitin 

chains to target substrates which are 

then degraded by a multi-catalytic 

proteosome complex. 

The compounds can be useful in the 

treatment of solid and disseminated 

cancers or other undesired cell 

proliferation disease or retroviral 

infections such as HIV. 

Applications and Modality: Treatment 

of disorders related to ubiquitin E1, 

such as HIV and viral infections; 

Compounds are the first general 

inhibitors of Ubiquitin E1 with broader 

biological effects than existing 

proteosome inhibitors; The compounds 

can serve as a probe to understand the 

ubiquitin system. 

Market: Bortezomib (marketed as 

VelcadeTM by Millennium 

Pharmaceuticals) is the first therapeutic 

proteasome inhibitor approved by the 

FDA. Severe side effects such as 

peripheral neuropathy occur in 30% of 

patients treated with Bortezomib. New 

drugs targeting proteins in 

ubiquitination pathway are needed that 

will have broader efficacy and reduced 

side effects. 

Development Status: The technology 

is in the pre-clinical stage of 

development. 

Inventors: Allan M. Weissman et al. 

(NCI). 

Related Publications: 

1. A manuscript related to this 

technology will be available as soon as 

it is accepted for publication. 

2. Y Yang et al. Small molecule 

inhibitors of HDM2 ubiquitin ligase 

activity stabilize and activate p53 in 

cells. Cancer Cell. 2005 Jun;7(6):547–

559. 

Patent Status: U.S. Provisional 

Application No. 60/738,242 filed 19 

Nov 2005, entitled ‘‘Inhibitors of 

Ubiquitin E1’’ (HHS Reference No. E–

070–2005/0–US–01); International 

Patent Application No. PCT/US2006/ 

0045032 filed 20 Nov 2006, entitled 

‘‘Inhibitors of Ubiquitin E1’’ (HHS 

Reference No. E–070–2005/0–PCT–02) 

Licensing Status: Available for 

exclusive and non-exclusive licensing. 

Licensing Contact: Thomas P. Clouse; 

301/435–4076; clousetp@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Laboratory of Protein Dynamics and 

Signaling is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize inhibitors of ubiquitin 

E1. Please contact John D. Hewes, Ph.D. 

at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Biomarkers for Tissue Status 

Description of Technology: Tissue 

regeneration and tumorigenesis are 

complex, adaptive processes controlled 

by cues from the tissue 

microenvironment. There are complex 

processes both characterized by cell 

proliferation, migration, and 

angiogenesis suggesting that wounds 

and cancer share a number of 

phenotypic similarities including 

cellular behavior, signaling molecules, 

and gene expression. 

Utilizing the kidneys as a model to 

compare renal regeneration and repair 

(RRR) from ischemically-injured tissues 

and renal cellular carcinoma (RCC), the 

inventors have identified biomarkers 

which are differentially expressed. The 

invention relates to methods of quickly 

and accurately diagnosing RCC and 

monitoring renal tissue health as well as 

RCC treatment. 

Applications: Method to accurately 

diagnose RCC; RCC biomarker inhibitors 

such siRNA; Method to treat RCC; 

Method to determine and monitor renal 

tissue health status; Method for 

improving renal ischemia recovery 

without promoting RCC; Biomarkers for 

immunotherapy, drug targeting and 

drug screening, for targeting tumors and 

not normal regenerating tissue; 

Biomarkers for immunotherapy, drug 

targeting and drug screening, for 

targeting ischemic tissue and not 

tumors. 

Market: Kidney cancer is one of the 

top ten most prevalent cancers in the 

U.S. and it accounts for 12,200 deaths 

annually; Approximately 35,000 new 

cases of kidney cancer are diagnosed 

annually; 50% survival rate after five 

years of diagnosis; Renal cancer 

accounts for 3% of all adult male 

malignancies. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Joseph Riss (NCI) et al. 

Publications: 

1. Journal of Urology, May 2007, Vol. 

177 No. 5, in press. 

2. J Riss et al. Cancers as wounds that 

do not heal: differences and similarities 

between renal regeneration/repair and 

renal cell carcinoma. Cancer Res. 2006 

July 15;66(14):7216–7224. 

Patent Status: U.S. Provisional 

Application No. 60/649,208 filed 01 Feb 

2005 (HHS Reference No. E–064–2005/ 

0–US–01); PCT Application No. PCT/ 

US2006/003611 filed 01 Feb 2006 (HHS 

Reference No. E–064–2005/0–PCT–02). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Jennifer Wong; 

301/435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Center for 

Cancer Research, Laboratory of Cancer 

Biology and Genetics, Wound Healing 

and Oncogenesis (NCI/CCR/LCBG), is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

topics of invention or related to cancer 

biology, metastasis, wound healing, 

bioinformatics, pharmacogenomics and 

therapeutic. Please contact John D. 

Hewes, Ph.D. at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

New Maleiimide Anti-Phosphatase 

Inhibitors 

Description of Technology: The 

present invention describes novel 

phenyl maleiimide phosphatase 

inhibitors that appear to target the 

Cdc25 family of phosphatases. The new 

compounds are inhibitors of several 

human tumor cell lines. The 

compounds have potent activity against 

human liver cancer cells in vitro and in 

vivo against an orthotopic liver cancer 

in rats. In tumor cells, these new 

inhibitors appear to target the 

phosphorylation status of several cell 

cycle proteins that are important for cell 

survival and thus could represent a 

novel class of chemotherapeutic agents 

targeting cancer cells. 

Applications and Modality: 

Compound targets Cdc25 family of 

phosphatases and inhibit growth of 

several human tumor cell lines; Potent 

activity in vitro against human liver 

cancer cells and in vivo against 

orthotopic liver cancer in rats; Targets 

phosphorylation of cell cycle proteins 

important for cell survival. 

Market: 600,000 deaths from cancer 

related diseases were estimated in 2006; 

In 2006, cancer drug sales were 

estimated to be $25 billion. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Christopher Michejda (NCI) 

et al. 

Relevant Publication: S Kar, M Wang, 

W Yao, CJ Michejda, BI Carr. PM–20, A 

novel inhibitor of Cdc25A, induces 

extracellular signal-regulated kinase 1/2 

phosphorylation and inhibits 

hepatocellular carcinoma growth in 

vitro and in vivo. Mol Cancer Ther. 

2006 Jun;5(6):1511–1519. 

Patent Status: PCT Patent Application 

No. PCT/US2005/05742 filed 22 Feb 

2005, which published as WO 2005/ 

081972 on 09 Sep 2005 (HHS Reference 

No. E–110–2004/0–PCT–02); U.S. Patent 

Application No. 11/508,605 filed 22 


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26404 Federal Register / Vol. 72, No. 89 / Wednesday, May 9, 2007 / Notices 

Aug 2006 (HHS Ref. No. E–110–2004/0–

US–06). 

Licensing Status: Available for 

exclusive and non-exclusive licensing. 

Licensing Contact: Adaku 

Nwachukwu, J.D.; 301/435–5560; 

madua@mail.nih.gov. 

Leu574 of HIF–1alpha as a Molecular 

Basis for Therapeutic Application 

Description of Technology: The 

hypoxia-inducible factor 1 (HIF–1) is a 

transcription factor that plays a pivotal 

role in cellular adaptation to oxygen 

availability. HIF–1alpha protein is a 

subunit of HIF–1. Although the gene for 

HIF–1alpha is constitutively expressed, 

it is an extremely short-lived protein 

under normoxic conditions and is 

targeted for destruction via the 

proteosome pathway by an E3 ubiquitin 

ligase involving the VHL protein. 

The invention relates to the discovery 

that mutations or deletions of Leu574 

result in a more stable and more active 

form of HIF–1alpha. Therefore, the 

invention relates to methods and 

compositions for modulating oxygen 

homeostasis for therapeutic application. 

In one aspect, the inventors contemplate 

the use of a more stable form of HIF–

1alpha protein for therapeutic 

angiogenesis purposes such as may be 

useful in ischemic vascular disease. In 

another aspect, the inventors 

contemplate the use of this particular 

site in a screen for targeted drugs that 

modulates HIF–1alpha activity. The 

inventors also suggest that Leu574 could 

be used for developing drugs targeted to 

HIF hydroxylase binding, thereby 

altering HIF–1alpha stability. 

Inventor: L. Eric Huang (NCI). 

Patent Status: U.S. Patent No. 

7,193,053 issued 20 Mar 2007 (HHS 

Reference No. E–281–2002/0–US–02). 

Licensing Status: This technology is 

available for licensing on an exclusive 

or a non-exclusive basis. 

Licensing Contact: Jesse S. Kindra, 

J.D.; 301/435–5559; 

kindraj@mail.nih.gov. 

Dated: April 30, 3007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer,Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–8893 Filed 5–8–07; 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. 

New Compounds and Methods for the 

Treatment of Spinal Muscular Atrophy 

and Other Diseases 

Description of Technology: Spinal 

muscular atrophy (SMA) is caused by 

mutations in the SMN1 gene that result 

in reduced expression of the survival 

motor neuron (SMN) protein and a loss 

of spinal motor neurons. An SMN2 gene 

paralog that differs from SMN by a 

single base pair has inadequate 

expression of SMN to support motor 

neuron survival. Alternative splicing 

caused by the single base substitution in 

the SMN2 gene results in a slightly 

truncated and highly unstable SMN 

protein. Drugs that allow translational 

read through of the stop codons 

introduced by the alternative splice 

event have been shown to stabilize the 

mutant protein, resulting in increased 

levels of SMN. 

A chemical library screen identified 

indoprofen, a nonsteroidal antiinflammatory drug, as an inducer of 

SMN expression in cultured cells. 

However, indoprofen cannot enter the 

brain in satisfactory amounts, has a 

relatively low level of activity and can 

cause substantial side-effects in part due 

to its cyclooxygenase inhibitory activity. 

NIH inventors designed indoprofen 

derivatives without cyclooxygenase 

activity that can enter the CNS and 

increase expression of a SMN protein 

from the SMN2 gene with increased 

potency and efficacy. The mechanism of 

action of these indoprofen analogs 

appears to be translational readthrough 

of stop codons introduced by the 

alternative SMN2 splicing event. In 

addition to treating SMA, novel drugs 

that allow read through of stop codons 

could potentially treat many other 

diseases caused by such mutations such 

as cystic fibrosis and muscular 

dystrophy. 

Available for licensing are 

compounds and methods useful for the 

treatment of spinal muscular atrophy by 

increasing SMN expression and 

increasing the expression from any 

nucleic acid that encodes a translational 

stop codon. 

Applications: Efficacious treatment 

for SMA, utilizing indoprofen analogs 

that increase SMN protein expression; 

Treatment of any genetic disease caused 

by premature termination of protein 

translation. 

Market: SMA is a rare genetic disease 

that affects approximately 1 in 6,000 

live births, and is the leading genetic 

cause of death in infants and toddlers. 

The projected market size for SMA is 

between $250 million and $750 million. 

Development Status: Clinical 

candidate selection scheduled for June 

2007. 

Inventors: Jill Heemskerk (NINDS), et 

al. 

Publication: MR Lunn, DE Root, AM 

Martino, SP Flaherty, BP Kelley, DD 

Coovert, AH Burghes, NT Man, GE 

Morris, J Zhou, EJ Androphy, CJ 

Sumner, BR Stockwell. Indoprofen 

upregulates the survival motor neuron 

protein through a cyclooxygenaseindependent mechanism. Chem. Biol. 

2004 Nov;11(11):1489–1493. 

Patent Status: U.S. Provisional 

Application No. 60/783,292 filed 17 Mar 

2006 (HHS Reference No. E–133–2006/ 

0-US–01); PCT Application No. PCT/ 

2007/006772 filed 16 Mar 2007 (HHS 

Reference No. E–133–2006/1–PCT–01) 

Licensing Availability: Available for 

exclusive and non-exclusive licensing. 

Licensing Contact: Norbert Pontzer, 

J.D., Ph.D.; 301/435–5502; 

pontzern@mail.nih.gov. 

STAMP, a Novel Cofactor and Possible 

Steroid Sparing Agent, Modulates 

Steroid-Induced Induction or 

Repression of Steroid Receptors 

Description of Technology: Steroid 

hormones such as androgens, 

glucocorticoids, and estrogens are used 

in the treatments of many diseases. 

They act to regulate many physiological 

responses by binding to steroid 


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