Federal Register / Vol. 74, No. 59 / Monday, March 30, 2009 / Notices 14139 

from a patient (R2) with broadly HIV-l 

neutralizing antibodies. Virology. 2007 

Jun 20;363(1):79–90. 

6. Z Zhu, S Chakraborti, Y He, A 

Roberts, T Sheahan, X Xiao, LE Hensley, 

P Prabakaran, B Rockx, IA Sidorov, D 

Corti, L Vogel, Y Feng, JO Kim, LF 

Wang, R Baric, A Lanzavecchia, KM 

Curtis, GJ Nabel, K Subbarao, S Jiang, 

DS Dimitrov. Potent cross-reactive 

neutralization of SARS coronavirus 

isolates by human monoclonal 

antibodies. Proc Natl Acad Sci USA. 

2007 Jul 17;104(29):12123–12128. 

7. Z Zhu, KN Bossart, KA Bishop, G 

Crameri, AS Dimitrov, JA McEachern, Y 

Feng, D Middleton, LF Wang, CC 

Broder, DS Dimitrov. Exceptionally 

potent cross-reactive neutralization of 

Nipah and Hendra viruses by a human 

monoclonal antibody. J Infect Dis. 2008 

Mar 15;197(6):846–853. 

8. MY Zhang, BK Vu, A Choudhary, 

H Lu, M Humbert, H Ong, M Alam, RM 

Ruprecht, G Quinnan, S Jiang, DC 

Montefiori, JR Mascola, CC Broder, BF 

Haynes, DS Dimitrov. Cross-reactive 

human immunodeficiency virus type 1- 

neutralizing human monoclonal 

antibody which recognizes a novel 

conformational epitope on gp41 and 

lacks reactivity against self antigens. J 

Virol. 2008 Jul;82(14):6869–6879. 

Patent Status: U.S. Provisional 

Application No. 61/104,706 filed 11 Oct 

2008 (HHS Reference No. E–322–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sally Hu, Ph.D.; 

301–435–5606; HuS@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this method. Please 

contact John D. Hewes, Ph.D. at 301– 

435–3121 or hewesj@mail.nih.gov for 

more information. 

Anti-Hepatitis C Virus Activity of the 

Protein Scytovirin (SVN) 

Description of Technology: The 

invention provides compositions and 

methods of use for potent anti-HCV 

protein scytovirin to prevent and treat 

HCV infections. Currently there is 

neither effective treatment nor vaccine 

against HCV infection and chronic HCV 

infection may lead to liver cancer and 

death. Scytovirin can be used alone or 

in combination with other anti-HCV 

drugs for HCV treatment and 

prevention. 

Applications: The treatment and 

prevention of HCV infections. 

Advantages: Potent anti-HCV activity; 

Can be applied both systematically or 

locally. 

Development Status: In vitro data 

available. 

Market: HCV therapeutics and 

preventatives. 

Inventors: Barry R. O’Keefe et al. 

(NCI). 

Publications: Data collection and 

manuscripts may be submitted in 2009. 

Patent Status: U.S. Provisional 

Application No. 61/137,511 filed 31 Jul 

2008 (HHS Reference No. E–161–2008/ 

0–US–01). 

Related Technology: HHS Reference 

No. E–017–2002/0—Scytovirins and 

Related Conjugates, Antibodies, 

Compositions, Nucleic Acids, Vectors, 

Host Cells, Methods of Production and 

Methods of Using Scytovirin. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sally Hu, Ph.D.; 

301–435–5606, HuS@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute CCR 

Molecular Targets Development 

Program is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this technology. Please 

contact John D. Hewes, Ph.D. at 301– 

435–3121 or hewesj@mail.nih.gov for 

more information. 

Dated: March 19, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–6933 Filed 3–27–09; 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. 

Treatment of Schistosomiasis Using 

Substituted Oxadiazole 2-Oxides 

Description of Technology: Available 

for licensing and commercial 

development are pharmaceutical 

compositions and methods for the 

treatment of schistosomiasis in 

mammals. The various compositions are 

based on a number of compounds 

derived from 1,2,5-oxadiazole that are 

potent inhibitors of thioredoxin 

glutathione reductase (TGR), a critical 

parasite redox protein. 

Schistosomiasis is a chronic disease 

caused by trematode flatworms of the 

genus Schistosoma, including S. 

mansoni, S. japonicum and S. 

haematobium. Adult schistosome 

parasites live in an aerobic environment 

within human hosts, and therefore must 

have effective mechanisms to maintain 

cellular redox balance. Additionally, the 

worms must be able to evade reactive 

oxygen species generated by the host’s 

immune response. In most eukaryotes 

there are two major systems to detoxify 

reactive oxygen species, one based on 

the tripeptide glutathione and the other 

based on the protein thioredoxin. 

Glutathione reductase (GR) reduces 

glutathione disulfide, whereas 

thioredoxin reductases (TrxR) are 

pivotal in the Trx-dependent system. It 

was recently discovered that specialized 

TrxR and GR enzymes are absent in 

schistosomes. Instead, they are replaced 

by the unique multifunctional enzyme 

TGR. This reliance on a single enzyme 

for both glutathione disulfide and 

thioredoxin reduction suggests that the 

parasite’s redox systems are subject to a 

bottleneck dependence on TGR, and 

that TGR represents a potentially 

important drug target. 

Schistosomiasis remains a major and 

neglected health problem in many 

tropical areas. The health burden 

resulting from schistosomiasis is 

estimated to include more than 200 

million people infected, 779 million at 

risk of infection, 280,000 deaths 

annually, and more than 20 million 

individuals experiencing high 

morbidity. Clinical manifestations of 

schistosomiasis infection include 

abdominal pain, cough, diarrhea, 


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14140 Federal Register / Vol. 74, No. 59 / Monday, March 30, 2009 / Notices 

eosinophilia, fever, fatigue, and 

hepatosplenomegaly. The primary route 

of infection occurs through contact with 

infected river and lake water, at which 

time the parasite burrows into the skin, 

matures, then migrates to other areas of 

the body. Adult schistosome parasites 

reside in the mesenteric veins of their 

human hosts, where they can survive for 

up to 30 years. The need to control 

schistosomiasis is acute and efforts have 

been ongoing for years on three main 

fronts: Prevention (via establishment 

and maintenance of sources of safe 

potable water), development of a 

vaccine, and use of drugs to treat the 

infection. 

Applications: Treatment of 

schistosomiasis. 

Advantages: The specific inhibition of 

TGR by the composition of this 

invention could satisfy the current need 

for new broad spectrum drugs to treat 

schistosomiasis, given the limitations of 

other drugs currently used or under 

development. Praziquantel, the only 

drug currently used against the 

infection, although stable, effective and 

relatively inexpensive, must be 

administered on an annual or semiannual basis. Furthermore, there are 

preliminary reports of praziquantelresistant cases. Arteminisinin has 

shown promise as a new drug for the 

treatment of schistosomiasis, but its use 

must be restricted in areas of malaria 

transmission so that its use as an 

antimalarial is not put at risk. 

Oxamniquine, a tetrahydroquinoline 

derivative, is effective only against S. 

mansoni and resistance has been 

reported, further reducing its potential 

value in schistosomiasis control. 

Development Status: To date, the 

general oxadiazole-2-oxide chemotype 

described here has shown efficacy in 

animal models. Efforts to define the 

pharmacophore and optimize this 

chemotype in terms of potency, efficacy 

and selectivity will be reported in due 

course. Currently, selected oxadiazole-2- 

oxides are being evaluated in advanced 

ADME/T assays and are being 

formulated for oral dosing experiments. 

Inventors: Craig J. Thomas (NHGRI) et 

al. 

Publications 

1. G Rai et al. Structure-mechanism 

insights and the role of nitric oxide 

donation guide the development of 

oxadiazole-2-oxides as targeted agents 

against Schistosomiasis. In preparation. 

2. G Rai, CJ Thomas, W Leister, DJ 

Maloney. Synthesis of oxadiazole-2- 

oxide analogues as potential 

antischistosomal agents. Tetrahedron 

Lett., accepted. 

3. AA Sayed, A Simeonov, CJ 

Thomas, J Inglese, CP Austin, DL 

Williams. Identification of oxadiazoles 

as new drug leads for the control of 

schistosomiasis. Nat Med. 2008 

Apr;14(4):407–412. 

4. A Simeonov, A Jadhav, AA Sayed, 

Y Wang, ME Nelson, CJ Thomas, J 

Inglese, DL Williams, CP Austin. 

Schistosoma mansoni thioredoxinglutathione reductase (TGR) inhibitors 

identified via quantitative highthroughput screen. PLoS Negl Trop Dis. 

2007;2:1–10. 

Patent Status: U.S. Provisional 

Application No. 61/088,970 filed 14 

Aug 2008, entitled ‘‘Oxadiazole-2- 

Oxides as Antischistosomal Agents’’ 

(HHS Reference No. E–162–2008/0–US– 

01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Cristina 

Thalhammer-Reyero, Ph.D., MBA; 301– 

435–4507; thalhamc@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIH Chemical Genomics Center is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

appropriate lead compounds described 

in U.S. Provisional Application No. 61/ 

088,970. Please contact Dr. Craig J. 

Thomas via e-mail 

(craigt@nhgri.nih.gov) for more 

information. 

Dendrimer Conjugates Targeting 

Adenosine Receptors, P2Y Receptors 

and Other Receptors of the GPCR 

Superfamily, for Use in the Treatment 

of Various Disorders, Including 

Neurodegenerative Diseases, Stroke, 

Epilepsy, Pain and Thrombosis 

Description of Technology: Available 

for licensing and commercial 

development are conjugate 

compositions useful in the treatment of 

a variety of diseases, comprising a 

dendrimer and a ligand. The ligand is a 

functionalized congener of an agonist or 

antagonist of a receptor of the G-protein 

coupled receptor (GPCR) superfamily. 

More specifically, the invention focuses 

on several agonists and antagonists of 

A1, A2A, A2B, and A3 adenosine 

receptors and P2Y receptors, all 

members of the GPCR superfamily. For 

example, an agonist of the A1 adenosine 

receptor is useful for treating a number 

of diseases including 

neurodegeneration, stroke, epilepsy, and 

pain. Antithrombotic treatment is 

another example of the use of this 

dendrimer technology. Dendrimers are 

polymers made from branched 

monomers through the iterative organic 

synthesis by adding one layer at each 

step to provide a symmetrical structure. 

Certain drugs, such as taxol, cisplatin, 

methotrexate, and ibuprofen, have been 

covalently linked to dendrimers in a 

reversible fashion. However, dendrimer 

conjugates in this application are 

biologically active without cleavage of 

the drug or cellular uptake. The 

conjugate of the invention can include 

any suitable dendrimer, particularly a 

poly(amidoamine) (PAMAM) 

dendrimer. The invention further 

provides pharmaceutical compositions 

and methods of treating various diseases 

and diagnostic methods employing such 

conjugates. 

Applications 

• Treatment of a number of diseases 

involving receptors of the GPCR 

superfamily. 

• Determination of a potential 

treatment of a patient with an agonist or 

antagonist or receptors of the GPCR 

superfamily. 

Advantages: The dendrimer 

conjugates described in this invention 

have one or more advantages over 

corresponding monomeric drugs, 

including altered pharmacokinetics, 

decreased toxicity, increased solubility, 

enhanced potency or selectivity due to 

the multivalency. 

Development Status: The 

development is still in the early stages. 

Inventors: Kenneth A. Jacobson et al. 

(NIDDK). 

Relevant Publications: The published 

patent applications are listed below. In 

addition, the technology is further 

described in the following publications: 

1. Y Kim, B Hechler, A Klutz, C 

Gachet, KA Jacobson. Toward 

multivalent signaling across G proteincoupled receptors from 

poly(amidoamine) dendrimers. 

Bioconjug Chem. 2008 Feb;19(2):406– 

411. 

2. Y Kim, AM Klutz, KA Jacobson. 

Systematic investigation of 

polyamidoamine dendrimers surfacemodified with poly(ethylene glycol) for 

drug delivery applications: Synthesis, 

characterization, and evaluation of 

cytotoxicity. Bioconjug Chem. 2008 

Aug;19(8):1660–1672. 

3. Y Kim, AM Klutz, B Hechler, ZG 

Gao, C Gachet, KA Jacobson. 

Application of the functionalized 

congener approach to dendrimer-based 

signaling agents acting through A2A

adenosine receptors. Purinergic Signal. 

2009 Mar;5(1):39–50. 

4. AA Ivanov and KA Jacobson. 

Molecular modeling of a PAMAM– 

CGS21680 dendrimer bound to an A2A

adenosine receptor homodimer. Bioorg 

Med Chem Lett. 2008 Aug 

1;18(15):4312–4315. 


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Federal Register / Vol. 74, No. 59 / Monday, March 30, 2009 / Notices 14141 

5. AM Klutz, ZG Gao, J Lloyd, A 

Shainberg, KA Jacobson. Enhanced A3

adenosine receptor selectivity of 

multivalent nucleoside-dendrimer 

conjugates. J Nanobiotechnol. 2008 Oct 

23;6:12. 

Patent Status 

• U.S. Provisional Application No. 

60/947,121 filed 20 Jun 2007 (HHS 

Reference No. E–219–2007/0–US–01). 

• U.S. Provisional Application No. 

61/045,498 filed 16 Apr 2008 (HHS 

Reference No. E–219–2007/1–US–01). 

• International Application No. PCT/ 

US08/067683 filed 20 Jun 2008, which 

published as WO2009/006046 on 08 Jan 

2009 (HHS Reference No. E–219–2007/ 

2–PCT–01). 

• U.S. Patent Application No.12/ 

143,451 filed 20 Jun 2008, which 

published as U.S. 20090012035 on 08 

Jan 2009 (HHS Reference No. E–219– 

2007/2–US–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Cristina 

Thalhammer-Reyero, PhD, MBA; 301– 

435–4507; thalhamc@mail.nih.gov. 

Collaborative Research Opportunity: 

The Laboratory of Bioorganic Chemistry 

of the National Institute of Diabetes & 

Digestive & Kidney Diseases is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize dendrimer conjugates of 

suitably functionalized small molecule 

ligands of adenosine receptors and P2Y 

nucleotide receptors. Please contact Dr. 

Kenneth A. Jacobson at 301–496–9024, 

or e-mail kajacobs@helix.nih.gov, for 

more information. 

Dated: March 19, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–6935 Filed 3–27–09; 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. 

M2e Peptide Vaccine Against Influenza 

Virus 

Description of Technology: The 

invention offered here is a vaccine 

candidate that can potentially confer 

protection against many types of 

influenza. Current vaccines against 

influenza virus are comprised of 

inactivated virus or purified influenza 

virus proteins and are targeted primarily 

to induce neutralizing antibodies 

against the viral hemagglutinin (HA) 

protein. The virus can mutate or shift 

antigenic types of HA rapidly rendering 

the vaccines ineffective and thus the 

vaccine has to be evaluated yearly to 

predict next year’s circulating strains for 

vaccine preparation. Unlike HA, the 

small M2 protein is highly conserved 

among different strains of influenza 

virus and thus vaccines based on the M2 

protein have the potential to be effective 

against different strains of influenza. 

The current invention relates to peptide 

vaccines composed of the extracellular 

domain of the M2 protein (M2e) 

conjugated to a carrier protein. In 

animals studies a mutant diphtheria 

toxin-M2e—conjugate induced high 

antibody levels to both vaccine 

components in mice. 

Applications: 

• Preventative and therapeutic for 

influenza virus. 

• Vaccine against seasonal and 

pandemic influenza virus strains. 

Advantages: Novel vaccine candidate 

with potential heterosubtypic 

protection. 

Development Status: In vitro and in 

vivo data can be provided upon request. 

Market: Influenza virus vaccines. 

Inventors: Mark A. Miller (FIC), 

Rachel Schneerson (NICHD), Joanna 

Kubler-Kielb (NICHD), John B. Robbins 

(NICHD), Zuzanna Biesova (NICHD), 

and Jerry Keith (NICHD). 

Patent Status: U.S. Provisional 

Application No. 61/089,384 filed 15 

Aug 2008 (HHS Reference No. E–304– 

2008/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Kevin W. Chang, 

Ph.D.; 301–435–5018; 

changke@mail.nih.gov. 

Therapeutic HIV Vaccine and 

Associated Protocols 

Description of Technology: This 

technology describes a therapeutic HIV 

DNA vaccine to be administered to 

individuals who have previously 

experienced or are undergoing 

antiretroviral therapy (ART). The 

therapeutic DNA vaccine can also be 

administered in combination with a 

vector encoding an IL–15 and/or IL–15 

receptor alpha (IL–15Ra) polypeptide. In 

primate studies, the technology was 

found to be particularly effective when 

the vaccine composition was 

administered by electroporation and 

expressed six (6) HIV antigens 

(including two (2) gag polypeptides and 

two (2) envelope polypeptides) and IL– 

15 and IL–15Ra. The antigens are 

typically modified with a destabilizing 

sequence, a secretory polypeptide and/ 

or a degradation signal. Successive 

administration up to as many as nine 

resulted in continual boost of the 

immune response against the encoded 

antigen. A potent immunotherapeutic 

vaccine as described here could be an 

important technology for the fight 

against HIV/AIDS. 

Applications: Therapeutic HIV DNA 

vaccines. 

Development Status: Primate data 

available. 

Inventor: Barbara Felber et al. (NCI). 

Patent Status: 

PCT Application No. PCT/US2008/ 

51004 filed 14 Jan 2008, which 

published as WO 2008/089144 on 24 Jul 

2008 (HHS Reference No. E–103–2007/ 

0–PCT–02); claiming priority to 12 Jan 

2007. 

PCT Application No. PCT/US2007/ 

000774 filed 12 Jan 2007, which 

published as WO 2007/084342 on 26 Jul 

2007 (HHS Reference No. E–254–2005/ 

2–PCT–01); claiming priority to 13 Jan 

2006. National Stage filed in AU, BR, 

CA, CN, EP, IL, IN, JP, MX, NZ, and US. 

PCT Application No. PCT/US2001/ 

45624 filed 01 Nov 2001, which 

published as WO 2002/36806 on 10 May 

2002 (HHS Reference No. E–308–2000/ 

0–PCT–02); claiming priority to 01 Nov 

2000. National Stage filed in AU, CA, 

EP, JP, and US. 

U.S. Patent Application No. 11/ 

571,879 filed 09 Jan 2007 (HHS 

Reference No. E–249–2004/1–US–02). 

Licensing Status: Available for 

licensing. 


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