48216 Federal Register / Vol. 73, No. 160 / Monday, August 18, 2008 / Notices 

2. YW Lin et al., NUP98-HOXD13 

transgenic mice develop a highly 

penetrant, severe myelodysplastic 

syndrome that progresses to acute 

leukemia. Blood. 2005 Jul 1;106(1):287–

295. 

Patent Status: HHS Reference No. E–

071–2007/0—Research Tool. 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Jennifer Wong; 

301–435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The Leukemia Biology Section, Genetics 

Branch, National Cancer Institute is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize the 

NHD13 mouse model. Please contact 

John D. Hewes, Ph.D. at 301–435–3121 

or hewesj@mail.nih.gov for more 

information. 

Conjugates of Ligand, Linker, and 

Cytotoxic Agent and Related 

Compositions and Methods of Use 

Description of Technology: Systemic 

toxicity of drugs is one of the most 

serious problems in cancer 

chemotherapy and frequently is dose 

limiting. Specific delivery of cytotoxic 

drugs to cancer cells remains among the 

most intractable problems of cancer 

therapy. Targeted delivery of antiproliferation drugs through the cell 

surface receptors that are over expressed 

on cancer cells can reduce systemic 

toxicity and increase effectiveness of a 

treatment. 

The present invention describes 

cytotoxic compounds with an 

intracellular target that can selectively 

enter tumor cells through specific 

receptors on the cell surface. The 

invention also describes a conjugate 

comprising a cytotoxic agent, a linker 

arm and a ligand capable of delivering 

a cytotoxic agent in a cell specific 

manner. Such conjugates of a cytotoxic 

agent and a ligand (delivery moiety) 

have increased selectivity for tumor 

cells. The toxic moiety and the ligand 

are joined by a linker arm that is stable 

in circulation, but is easily cleaved in 

lysosomes upon internalization of the 

conjugate. A panel of compounds 

comprised of a variety of cytotoxic 

warheads, against various intracellular 

targets linked to an assortment of 

ligands, has been developed and tested 

in a model system. Ligand moieties of 

these conjugates are capable of specific 

delivery of cytotoxic agents to receptors 

that are frequently over expressed in 

gastric, colon, lung, breast, ovarian and 

pancreatic tumors. These compounds 

have the potential to be highly effective 

anti-tumor agents with considerably 

little negative effect. This disclosed 

technology could provide new and 

exciting methodologies to treat cancer. 

Applications: Anti-tumor agent for 

gastric, colon, lung, breast, ovarian and 

pancreatic tumors. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Nadya I. Tarasova et al. 

(NCI). 

Patent Status: U.S. Patent Application 

No. 10/505,239 filed 19 Aug 2004, 

claiming priority to 27 Feb 2002 (HHS 

Reference No. E–057–2002/2-US–02). 

Licensing Contact: Adaku 

Nwachukwu, J.D.; 301/435–5560; 

madua@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute Structural 

Biophysics Laboratory is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize Conjugates of Ligand, 

Linker, and Cytotoxic Agent and Related 

Compositions and Methods of Use. 

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

301–435–3121 or hewesj@mail.nih.gov 

for more information. 

SH2 Domain Binding Inhibitors 

Description of Technology: Signal 

transduction processes underlie the 

transfer of extracellular information to 

the interior of the cell and ultimately to 

the nucleus. A variety of signal 

transduction processes are critical for 

normal cellular homeostasis, with 

protein-tyrosine kinases (PTKs) playing 

central roles in many of these pathways. 

Examples of such PTKs include the 

PDGF receptor, the FGF receptor, the 

HGF receptor, members of the EGF 

receptor family, such as the EGF 

receptor, erb-B2, erb-B3 and erb-B4, the 

src kinase family, Fak kinase and the Jak 

kinase family. Protein-tyrosine 

phosphorylation that results from the 

action of PTKs can modulate the activity 

of certain target enzymes as well as 

facilitate the formation of specific multiprotein signaling complexes through the 

actions of homologous protein modules 

termed Src homology 2 (SH2) domains, 

which recognize specific 

phosphotyrosyl containing sequences. A 

malfunction in this system through 

tyrosine kinase overexpression and/or 

deregulation can be manifested by 

various oncogenic and 

hyperproliferative disorders, including 

cancers, inflammation, autoimmune 

disease, hyperproliferative skin 

disorders, psoriasis and allergy/asthma, 

etc. The disclosed compounds, e.g. 

peptides, preferably, macrocyclic 

peptides, are Grb2 SH2 domain 

signaling antagonists with enhanced 

binding affinity. The claims of the 

current application are directed to 

compositions of matter and methods of 

use which provide for the diagnosis, 

testing and treatment of the 

aforementioned disease states. 

Applications: For treatment of cancer, 

inflammation, autoimmune diseases, 

hyperproliferative skin disorders, 

psoriasis and asthma. 

Development Status: The technology 

is currently in an early pre-clinical stage 

of development. 

Inventors: Terrence R. Burke, Jr., et al. 

(NCI). 

Patent Status: 

• U.S. Patent No. 6,977,241 issued 20 

Dec 2005 (HHS Reference No. E–262–

2000/0–US–03). 

• U.S. Patent Application No. 10/ 

517,717 filed 17 Mar 2005, allowed 

(HHS Reference No. E–262–2000/1-US–

03). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Adaku 

Nwachukwu, J.D.; 301–435–5560; 

madua@mail.nih.gov. 

Dated: August 7, 2008. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E8–18982 Filed 8–19–08; 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/ 


sroberts on PROD1PC70 with NOTICES
Federal Register / Vol. 73, No. 160 / Monday, August 18, 2008 / Notices 48217 

496–7057; fax: 301/402–0220. A signed 

Confidential Disclosure Agreement will 

be required to receive copies of the 

patent applications. 

Broadly Neutralizing Anti-HIV 

Monoclonal Antibody That Targets a 

New Epitope on gp41 

Description of Technology: Blocking 

entry of HIV into cells and vaccine 

development against HIV are the prime 

targets of HIV therapy and prevention, 

respectively. Current invention 

describes a monoclonal Fab anti-HIV 

antibody isolated through panning 

against the chimeric construct NCCGgp41 by Antibodies-by-Design 

(Morphosys). One of the antibodies has 

broadly neutralization ability against 

several HIV subtypes in an envelopepseudotyped-virus neutralization assay. 

This antibody was also shown to have 

synergistic effect with a gp41-derived 

peptide discovered in this laboratory in 

inhibiting HIV–1 fusion. 

Applications: Research tool or 

screening for HIV vaccine. 

Advantages: Can be potentially used 

as a therapeutic agent to block HIV–1 

entry into cells. 

Development Status: In vitro data 

available. 

Market: For the development of drugs 

against HIV. 

Inventors: G. Marius Clore et al. 

(NIDDK). 

Publications: 

1. E Gustchina et al. A monoclonal 

Fab derived from a human nonimmune 

phage library reveals a new epitope on 

gp41 and neutralizes diverse human 

immunodeficiency virus type 1 strains. 

J Virol. 2007 Dec;81(23):12946–12953. 

2. E Gustchina et al. Sequestering the 

pre-hairpin intermediate of gp41 by 

peptide N36Mut(e,g) potentiates the 

human immunodeficiency virus type 1 

neutralizing activity of monoclonal 

antibodies against the N-terminal helical 

repeat of gp41. J. Virol. in press (2008). 

Patent Status: HHS Reference No. E–

229–2008/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: This invention is 

available for non-exclusive licensing as 

a research tool. 

Licensing Contact: Sally Hu, Ph.D.; 

301–435–5606; HuS@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIH, Laboratory of Chemical 

Physics is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this monoclonal Fab. 

Please contact Dr. G.M. Clore at 301–496 

0782 and/or e-mail at 

mariusc@mail.nih.gov for more 

information. 

Polyamine Compounds That Bind Tar 

RNA of HIV and Methods of Treating 

Viral Disorders 

Description of Technology: Current 

HIV treatment involves applying 

cocktail of drugs targeting either virus 

entry or one of three viral enzymes. 

Because patients eventually develop 

resistance to the cocktail, a new class of 

drugs is urgently needed. Current 

invention describes a new class of 

polyamine compounds that specifically 

bind to HIV RNA at micromolar range 

to prevent binding of viral RNA to viral 

proteins and therefore blocking viral 

replication. This differs with the 

mechanisms of current HIV drugs in the 

market and therefore offers new strategy 

in HIV treatment and prevention. 

Furthermore, this class of compound 

may aid future development of drugs 

targeting RNA. 

Applications: Treatment and 

prevention of HIV infection. 

Advantages: Novel strategy for HIV 

treatment and prevention; Specific 

binding to HIV RNA and strong activity. 

Development Status: In vitro data 

available. 

Market: HIV therapeutics and 

preventatives. 

Inventors: Daniel Appella et al. 

(NIDDK). 

Publications: Manuscripts in 

preparation. 

Patent Status: U.S. Provisional 

Application No. 61/123,076 filed 04 Apr 

2008 (HHS Reference No. E–159–2008/ 

0-US–01). 

Licensing Status: This invention is 

available for exclusive or non-exclusive 

licensing. 

Licensing Contact: Sally Hu, Ph.D.; 

301–435–5606; HuS@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIDDK, Laboratory of Bioorganic 

Chemistry, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize the application of TARbinding polyamines for the treatment of 

HIV infections. Please contact Daniel 

Appella at 301–451–1052 or 

appellad@niddk.nih.gov for more 

information. 

Monoclonal Antibodies to HIV–1 Vpr 

Description of Technology: Available 

for licensing are monoclonal antibodies 

against HIV–1 viral protein R (Vpr) and 

the respective hybridoma cell lines 

expressing the same. The antibodies 

provide a means for detecting HIV–1 

Vpr. Currently, the mechanism of HIV 

pathogenesis believed to involve viral 

replication inside immune cells and 

other cells. At present, there are no 

clinical assays for detecting HIV–1 Vpr. 

Vpr circulates at detectable levels in the 

blood and is likely derived from 

degraded virions or released from 

infected cells. Vpr facilitates viral 

replication and disrupt normal cell 

function. Thus measurement of Vpr 

levels in blood, extracellular fluid, and 

tissue may be of benefit in 

understanding the pathogenesis of HIV–

1 infection and its myriad 

complications. 

The hybridoma cell lines (9F12 and 

10F2) were selected from a group of 

hybridoma cell lines. These antibodies 

can be used for detection, including 

immunoasssays (ELISA) and 

immunoaffinity-capillary 

electrophoresis. The amount of detected 

HIV–1 Vpr is compared to a 

standardized control sample for 

determining the progress of disease or 

the presence of known complications 

like neuropathy, dementia, metabolic 

syndrome, or nephropathy. 

Inventors: Jeffrey Kopp (NIDDK), 

Terence Philips (NBIB), Schubert Ulrich 

(NIAID), John Yewell (NIAID). 

Patent Status: U.S. Patent Application 

No. 11/630,880 filed 27 Jun 2005 (HHS 

Reference No. E–141–2003/0–US–03). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael 

Shmilovich, Esq.; 301–435–5019; 

shmilovm@mail.nih.gov. 

Anti-Pax 2 Antibody 

Description of Technology: Available 

for licensing and commercialization are 

anti-Pax 2 polyclonal antibodies that 

can be used for the detection of Pax-2 

protein expression in a variety of kidney 

and neuronal tissues. Pax-2 protein, a 

transcription factor active during early 

kidney development, is expressed at 

high levels in almost all renal 

proliferative diseases such as renal 

cancer, polycystic kidney disease and 

acute renal failure. 

The Pax-2 protein has also been 

linked to Wilms’ tumor, a cancerous 

kidney tumor accounting for ∼6% of 

childhood cancers, and for which ∼500 

new cases are diagnosed each year in 

the U.S. Wilms’ tumors are hard to 

diagnose in the early stage because they 

can grow quite large without causing 

any pain. While abdominal ultrasound 

may be used for detection, it is not a 

practical screening test for otherwise 

healthy children. There are no blood 

tests or other tests for screening for 

Wilms’ tumors which, if diagnosed 

sufficiently early, may be treated with 

surgery, chemotherapy, and/or radiation 

therapy. 


sroberts on PROD1PC70 with NOTICES
48218 Federal Register / Vol. 73, No. 160 / Monday, August 18, 2008 / Notices 

Potential applications of this 

technology may also include detection 

of Pax-2 protein in urine for both 

chronic and acute renal disease. 

Applications: Diagnostics for renal 

diseases; Research tools for evaluating 

disease processes of the kidney and 

other tissues through Pax-2 protein 

expression in the relevant tissues. 

Development Status: Ready for 

commercialization. 

Patent Status: HHS Reference No. B–

039–1996/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Inventor: Gregory Dressler (NICHD). 

Relevant Publications: 

1. GR Dressler. Another niche for 

Notch. Kidney Int. 2008 

Jun;73(11):1207–1209. 

2. SR Patel et al. The BRCT-domain 

containing protein PTIP links PAX2 to 

a histone H3, lysine 4 methyltransferase 

complex. Dev Cell. 2007 Oct;13(4):580–

592. 

3. GR Dressler. The cellular basis of 

kidney development. Annu Rev Cell 

Dev Biol. 2006;22:509–529. 

4. GB Silberstein et al. Expression of 

the PAX2 oncogene in human breast 

cancer and its role in progesteronedependent mammary growth. Oncogene. 

2002 Feb7;21(7):1009–1016. 

5. GR Dressler and AS Woolf. Pax2 in 

development and renal disease. Int J 

Dev Biol. 1999;43(5):463–468 (Review). 

6. GR Dressler. Pax-2, kidney 

development, and oncogenesis. Med 

Pediatr Oncol. 1996 Nov;27(5):440–444. 

7. GR Dressler and EC Douglass. Pax2 is a DNA-binding protein expressed in 

embryonic kidney and Wilms tumor. 

Proc Natl Acad Sci USA. 1992 Feb 

15;89(4):1179–1183. 

Licensing Status: Available for nonexclusive licensing as biological 

materials (internal use or commercial 

use). 

Licensing Contact: RC Tang, JD, LLM; 

301–435–5031; tangrc@mail.nih.gov. 

Dated: August 7, 2008. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E8–18983 Filed 8–19–08; 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. 

Species-Independent A3 Adenosine 

Receptor Agonists 

Description of Technology: The A3 

adenosine receptor (A3AR) subtype has 

been linked with helping protect the 

heart from ischemia, controlling 

inflammation, and regulating cell 

proliferation. Agonists of the human 

A3AR subtype have been described; 

however, they lack selectivity for the 

corresponding receptor of the mouse. 

This poses a problem for clinical 

development because animal model 

testing is important for pre-clinical 

validation of drug function. 

Consequently, a novel agonist was made 

that is selective for the mouse A3AR 

while retaining selectivity for the 

human receptor. This innovation should 

facilitate moving A3 agonists into the 

clinical phase of drug development with 

confidence. 

This invention claims speciesindependent agonists of A3AR, 

specifically (N)-methanocarba adenine 

nucleosides. In addition, it describes 

pharmaceutical compositions 

comprising such nucleosides, and 

methods of use such as administering an 

effective amount to a mammal. 

Applications: cardiac arrhythmias or 

ischemia; inflammation; stroke; 

diabetes; asthma; cancer. 

Market: Heart disease and cancer are 

the leading causes of death for both 

women and men in the United States 

despite many advances in drug 

development. Hence, there is a need for 

drugs with unique mechanism of action. 

It is noteworthy that the first synthetic 

adenosine receptor agonist has recently 

been approved for use in humans. 

Development Status: Research 

quantities of compounds have been 

synthesized and tested for receptor 

selectivity. 

Inventors: Kenneth A. Jacobson and 

Artem Melman (NIDDK). 

Publication: A Melman et al. Design 

of (N)-methanocarba adenosine 5′- 

uronamides as species-independent A3 

receptor-selective agonists. Bioorg Med 

Chem Lett. 2008 May 1;18(9):2813–

2819. 

Patent Status: U.S. Provisional 

Application No. 61/040,985 filed 31 Mar 

2008 (HHS Reference No. E–140–2008/ 

0–US–01). 

Licensing Status: Available for 

exclusive or non-exclusive licensing. 

Licensing Contact: Norbert Pontzer, 

J.D., Ph.D.; 301–435–5502; 

pontzern@mail.nih.gov. 

Fluorescent Cell Lines for Detection of 

DNA Damage 

Description of Technology: The 

Enhanced Level of Genomic instability 

1 (ELG1) protein suppresses genomic 

instability caused by DNA damage. Cell 

lines for studying human ELG1 (hELG1) 

have been established that stably 

express a fusion protein combining 

hELG1 and either Green Fluorescent 

Protein (GFP) or Cyan Fluorescent 

Protein (CFP). It has been shown that 

the fluorescent hELG1 is an excellent 

reporter for DNA damage within the 

cell, with increased hELG1 localization 

to the cell nucleus upon exposure to a 

genotoxin. Therefore, these cell lines 

may have utility as a screening tool to 

detect genotoxic agents. 

Available for licensing are the RPE 

cell line (immortalized normal retinal 

pigment epithelial cells) stably 

expressing hELG1-CFP, and the U2OS 

cell line (human osteosarcoma cells) 

stably expressing hELG1-GFP. 

Applications: High-sensitivity 

screening tool for genotoxic agents. 

Inventor: Kyungjae Myung (NHGRI). 

Relevant Publication: In preparation. 

Patent Status: DHHS Reference No. E–

108–2008/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Tara L. Kirby, 

Ph.D.; 301–435–4426; 

tarak@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Chemical Genomics 

Center is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize the assay for detection of 

genotoxic agents using RPE cell line 

having hELG1–CFP. Please contact 


sroberts on PROD1PC70 with NOTICES