Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 14591 

APCs also enhances the interaction of 

HAVCR1 with HAV. 

Aspects of the technology are further 

described in Tami et al., 2007. J. Virol., 

in press. 

Applications: Therapies that target the 

interaction of HAVCR1 with the ligand 

on APCs, such as small molecules or 

monoclonal antibodies, can control 

immune responses, the development of 

asthma, allergies and other atopic 

diseases, hepatitis A, kidney 

regeneration, and cancer. 

Development Status: The technology 

is in early stages of development. 

Inventors: Gerardo Kaplan (CBER/ 

FDA), et al. 

Patent Status: U.S. Provisional 

Application No. 60/865,631 filed 13 

Nov 2006 (HHS Reference No. E–035–

2005/0–US–01). 

Licensing Status: Available for nonexclusive or exclusive licensing. 

Licensing Contact: Cristina 

Thalhammer-Reyero, PhD, M.B.A.; 301/ 

435–4507; thalhamc@mail.nih.gov. 

Collaborative Research Opportunity: 

The Food and Drug Administration, 

Center of Biologics Research and 

Evaluation, Laboratory of Hepatitis and 

Related Emerging Agents, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize the hepatitis A virus 

cellular receptor as a potent activator of 

antigen presenting cells. Please contact 

Beatrice Droke, 301/872–7008 or 

beatrice.droke@fda.hhs.gov, for more 

information. 

Cyanovirins and Related Conjugates, 

Compositions, Nucleic Acids, Vectors, 

Host Cells, Methods of Production and 

Methods of Use for Microbicide 

Development 

Description of Technology: The 

development of an effective anti-HIV 

topical microbicide, especially a femalecontrolled, vaginal microbicide, has 

been deemed an urgent global priority 

by numerous international agencies, 

including the World Health 

Organization, the U.S. Department of 

Health and Human Services, the 

National Institute of Allergy and 

Infectious Diseases, and others. The 

present invention provides antiviral 

proteins (collectively referred to as 

cyanovirins), conjugates thereof, DNA 

sequences encoding such agents, host 

cells containing such DNA sequences, 

antibodies directed to such agents, 

compositions comprising such agents, 

and methods of obtaining and using 

such agents for the production of 

microbicides. 

Cyanovirin-N (CV-N) potently and 

irreversibly inactivates diverse primary 

strains of HIV-1, including M-tropic 

forms involved in sexual transmission 

of HIV, as well as T-tropic and dualtropic forms; CV-N also blocks cell-tocell transmission of HIV infection. CVN is directly virucidal, interacting in an 

unusual manner with the viral 

envelope, apparently binding with 

extremely high affinity to poorly 

immunogenic epitopes on gp120. 

Further, cyanovirin-N (CV-N) and 

homologous proteins and peptides 

potently inhibit diverse isolates of 

influenza viruses A and B, the two 

major types of influenza virus that infect 

humans. 

The described technology includes 

glycosylation-resistant mutants of CV-N, 

which code sequences to enable ultra 

large-scale recombinant production of 

functional cyanovirins in non-bacterial 

(yeast or insect) host cells or in 

transgenic animals or plants. Therefore, 

these glycosylation-resistant mutants 

may allow industry to produce CV-Ns 

on a large scale and make CV-Ns cheap 

enough for developing countries to 

benefit from this invention. 

CV-N was benign in vivo when tested 

in the rabbit vaginal toxicity/irritancy 

model, and was not cytotoxic in vitro 

against human immune cells and 

lactobacilli (unpublished). CV-N is 

readily soluble in aqueous media, is 

remarkably resistant to physicochemical 

degradation and is amenable to very 

large-scale production by a variety of 

genetic engineering approaches. 

Applications: Development of 

microbicides against HIV and influenza. 

Development Status: Preclinical data 

is available at this time. 

Inventors: Michael Boyd (NCI), Robert 

Shoemaker (NCI), Barry O’Keefe (NCI), 

Toshiyuki Mori (NCI), Angela 

Gronenborn (NIDDK). 

Related Publications: 

1. B Giomarelli, R Provvedi, F Meacci, 

T Maggi, D Medaglini, G Pozzi, T Mori, 

JB McMahon, R Gardella, MR Boyd. The 

microbicide cyanovirin-N expressed on 

the surface of commensal bacterium 

Streptococcus gordonii captures HIV-1. 

AIDS. 2002 Jul 5;16(10):1351–1356. 

2. CC Tsai, P Emau, Y Jiang, MB Agy, 

RJ Shattock, A Schmidt, WR Morton, KR 

Gustafson, MR Boyd. Cyanovirin-N 

inhibits AIDS virus infections in vaginal 

transmission models. AIDS Res Hum 

Retroviruses. 2004 Jan;20(1):11–18. 

Patent Status: 

1. Patent Cooperation Treaty Serial 

No. PCT/US00/06247 filed 10 Mar 2000; 

National Stage Filing in United States, 

Japan, Australia, Europe, Germany, 

France, China, United Kingdom, and 

Belgium (HHS Reference No. E–074–

1999/2). 

2. Patent Cooperation Treaty Serial 

No. PCT/US99/18975 filed 19 Aug 1999; 

National Stage Filing in United States, 

Japan, Australia, Europe, Germany, 

France, China, United Kingdom, and 

Belgium (HHS Reference No. E–117–

1995/3). 

Licensing Status: Available for 

licensing and commercial development. 

Licensing Contact: Sally Hu, PhD; 

301/435–5606; HuS@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Molecular Targets Development 

Program is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize microbicides for HIV and 

influenza. Please contact John D. Hewes 

at (301) 435–3121 or hewesj@mail. 

nih.gov for more information. 

Dated: March 16, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–5670 Filed 3–27–07; 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. 


sroberts on PROD1PC70 with NOTICES
14592 Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 

Enhanced Function of Gene Modified TCells: Identification of T-Cell Receptors 

(TCR) with Altered Amino Acid 

Sequence 

Description of Technology: A major 

limitation of the current chemotherapybased therapeutics is the cytotoxic sideeffects associated with them. Thus there 

is a dire need to develop new 

therapeutic strategies with fewer sideeffects. Immunotherapy has taken a lead 

among the new cancer therapeutic 

approaches. Adoptive immunotherapy 

is one of the most promising new 

therapeutic approaches that enhance the 

innate immunity of an individual to 

fight against a certain disease. 

T cell receptors (TCR) are the proteins 

responsible for the T cell’s ability to 

recognize infected or transformed cells. 

TCR consists of two domains, one 

variable domain that recognizes the 

antigen and one constant region that 

helps the TCR anchor to the membrane 

and transmit the recognition signal by 

interacting with other proteins. 

This invention is directed to 

substitutions in gene sequences that 

code for T cell receptors, specifically the 

inventors found that one to two amino 

acid substitutions in the TCRs that 

recognize 1G4 XY-ESO-1 and MART-1 

resulted in a marked increase of these 

modified TCRs to recognize tumor cell 

targets. These mutated sequences are 

currently being evaluated as candidates 

for clinical development. The inventors 

also consider the invention as providing 

a ‘‘general paradigm’’ that will allow the 

generation of TCR directed against a 

variety of antigens that can enhance the 

function of gene modified T cells. 

Applications: 

1. Improved ability of modified TCRs 

to recognize tumor cell targets. 

2. High affinity TR can be generated 

that recognizes a variety of antigens that 

can be potentially used for the diagnosis 

and treatment of patients with a variety 

of conditions that include cancer, 

infectious diseases and autoimmunity. 

3. Mutant high affinity TR can also be 

used to transduce T cells in order to 

generate cells reactive with tumor 

antigens as well as viral antigens. 

Development Status: Pre-clinical work 

has been completed and clinical work is 

undergoing. 

Inventors: Paul F. Robbins (NCI), 

Steven A. Rosenberg (NCI), Richard A. 

Morgan (NCI), et al. 

Relevant Publication: A manuscript 

relating to this invention is under 

preparation and will be available once 

accepted. 

Patent Status: U.S. Provisional 

Application No. 60/847,447 filed 26 Sep 

2006 (HHS Reference No. E–304–2006/ 

0–US–01). 

Licensing Status: This technology is 

available for licensing under an 

exclusive or non-exclusive patent 

license. 

Licensing Contact: Michelle Booden, 

PhD; 301/451–7337; 

boodenm@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIH Surgery Branch is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize adoptive 

immunotherapy. Please contact John D. 

Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Novel Benzindole Based Compounds 

for HIV Therapy 

Description of Technology: The HIV/ 

AIDS epidemic continues despite efforts 

from scientists, drug companies, and 

non-profit organizations. Although the 

existing therapy, is effective in the 

treatment of many infected individuals 

in developed nations, the infected 

individual is not cured and therapy 

must be life-long. There are problems 

with drug toxicity, the development of 

resistant viral strains, and with the cost 

of therapy. New anti-viral agents are 

needed for a more effective, and a more 

cost-effective, treatment of HIV. 

The invention describes compounds 

based on a benzindole moiety, which 

alkylates DNA. The compounds 

comprise a benzindole moiety, a 

bifunctional linker, and a fatty acid 

residue or dendrimer residue 

comprising at least one fatty acid. 

Several benzindole derivatives are 

synthesized. The compounds bind to 

the minor groove of DNA and can be 

useful in the inhibition of gene 

expression. The advantage of the 

compounds is that they remain inactive 

until conformational change induced by 

DNA binding makes them active. The 

fatty acid moiety immobilizes them on 

the cytoplasmic side of the plasma 

membrane. These anchored compounds 

are specifically designed to inhibit 

retroviral DNA before it translocates to 

the host nucleus and integrates with the 

host genome. 

Applications and Modality: 

1. Novel benzindole-based 

compounds for HIV therapy. 

2. Compounds are specifically 

designed to inhibit retroviral DNA 

before it can integrate with the host 

genome. 

3. Additionally, compounds might 

have potential anti-cancer activities. 

Market: 

1. More than 45 million people are 

living with HIV/AIDS worldwide. 

2. More than 3 million estimated 

deaths due to HIV/AIDS occurred 

worldwide in 2003. 

3. HIV/AIDS epidemic has caused 

more than 30 million deaths. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Inventors: Christopher J. Michejda 

(NCI), Stephen H. Hughes (NCI), et al. 

Relevant Publication: A manuscript 

directly related to the above technology 

will be available as soon as it is 

accepted for publication. 

Patent Status: U.S. Provisional 

Application No. 60/850,437 filed 10 Oct 

2006 (HHS Reference No. E–126–2006/ 

0–US–01). 

Licensing Availability: Available for 

exclusive and non-exclusive licensing. 

Licensing Contact: Adaku 

Nwachukwu, J.D.; 301/435–5560; 

madua@mail.nih.gov 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Structural Biophysics Laboratory is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

novel benzindole based compounds for 

HIV therapy. Please contact John D. 

Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Cloning and Characterization of an 

Avian Adeno-Associated Virus and 

Uses Thereof 

Description of Technology: Currently, 

adeno-associated virus (AAV) represents 

the gene therapy vehicle of choice 

because it has many advantages over 

current strategies for therapeutic gene 

insertion. AAV is less pathogenic than 

other virus types; stably integrates into 

dividing and non-dividing cells; 

integrates at a consistent site in the host 

genome; and shows good specificity 

towards various cell types for targeted 

gene delivery. 

To date, 11 AAV isolates have been 

isolated and characterized. New 

serotypes derived from non-human 

animal species have added to the 

specificity and repertoire of current 

AAV gene therapy techniques by 

avoiding the immunologic 

complications associated with human 

isolates. 

This invention describes vectors 

derived from an avian AAV. These 

vectors have innate properties related to 

their origin that may confer them with 

a unique cellular specificity in targeted 

human gene therapy and a unique 

immunologic profile that would avoid 

neutralization by pre-existing 

antibodies. Therefore, vectors derived 


sroberts on PROD1PC70 with NOTICES
Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 14593 

from this avian AAV are likely to find 

novel applications for gene therapy in 

humans. Furthermore because of their 

species of origin, this vector would also 

be useful in the engineering of avian 

cells. 

Inventors: Ioannis Bossis and John A. 

Chiorini (NIDCR). 

Publication: I Bossis, JA Chiorini. 

Cloning of an avian adeno-associated 

virus (AAAV) and generation of 

recombinant AAAV particles. J Virol. 

2003 Jun;77(12):6799–6810. 

Patent Status: U.S. Patent Application 

No. 10/557,662 filed 21 Dec 2006 (HHS 

Reference No. E–105–2003/0–US–03). 

Licensing Status: Available for nonexclusive or exclusive licensing. 

Licensing Contact: Jesse S. Kindra, 

J.D.; 301/435–5559; 

kindraj@mail.nih.gov 

Collaborative Research Opportunity: 

The National Institute of Dental and 

Craniofacial Research, Laboratory of Dr. 

John Chiorini, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize gene therapy methods 

using AAV vectors. Please contact David 

W. Bradley, PhD at 

bradleyda@nidcr.nih.gov for more 

information. 

Serotonin-Deficient Knock-Out Mouse 

Description of Technology: Serotonin 

is an important modulator of many 

developmental, behavioral, and 

physiological processes, and it has been 

implicated in depression, anxiety, 

schizophrenia, obsessive compulsive 

disorders, and substance abuse. 

Serotonin’s pharmacology is extremely 

complex and it is mediated by seven of 

serotonin receptor subtypes and it is 

present in several tissues. Although it 

has been a subject of a number of 

studies, its role has been difficult to 

ascertain. To investigate the role of 

serotonin in these disorders, the murine 

gene was disrupted by homologous 

recombination. Results indicate that 

serotonin binding sites were absent in 

different brain regions (brain stem, 

frontal cortex, hippocampus, and 

striatum), and its concentrations were 

reduced by 60–80%. These mice 

represent a powerful tool for the 

investigation of behavioral and 

neuropsychiatric disorders, and 

development of drug treatments for 

these disorders. 

Applications: A model to study 

serotonin’s role in behavioral and 

neuropsychiatric disorders. 

Market: 

1. Serotonin inhibitors are most 

widely used treatment in 

neuropsychological disorders. Examples 

include Zoloft, Paxil, and Prozac. 

2. Depression effects approximately 

18.8 million U.S. citizens and over 121 

million people worldwide. 

3. Antidepressant market was worth 

$16.2 billion in 2005, and it has annual 

growth of 2% year on year. 

4. Anxiety disorders affect 40 million 

(18.1%) of the adult U.S. population. 

5. Global anxiety disorder market was 

$4.5 billion in 2006. 

Inventors: Dennis L. Murphy (NIMH) 

et al. 

Publications: 

1. RF Ren-Patterson, LW Cochran, A 

Holmes, S Sherrill, SJ Huang, T Tolliver, 

K-P Lesch. Loss of brain-derived 

neurotrophic factor gene allele 

exacerbates brain monoamine 

deficiencies and increases stress 

abnormalities of serotonin transporter 

knockout mice. J Neurosci Res. 2005 

Mar 15:79(6):756–771. 

2. DL Murphy, A Lerner, G Rudnick, 

K-P Lesch. Serotonin transporter: gene, 

genetic disorders, and 

pharmacogenetics. Mol Interv. 2004 

April:4(2):109–123. 

3. RF Ren-Patterson, D-K Kim, X 

Zheng, S Sherrill, S-J Huang, T Tolliver, 

DL Murphy. Serotonergic-like 

progenitor cells propagated from neural 

stem cells in vitro: survival with SERT 

protein expression following 

implantation into brains of mice lacking 

SERT. FASEB J. 2005 Sep:19(11):1537–

1539. 

4. Q Li, A Holmes, L Ma, LD Van de 

Kar, F Garcia, DL Murphy. Medical 

hypothalamic 5-hydroxytryptamine 

(5HT)1A receptors regulate 

neuroendocrine responses to stress and 

exploratory locomotor activity 

application of recombinant adenovirus 

containing 5-HT1A sequences. J 

Neurosci. 2004 Dec 1:24(48):10868–

10877. 

5. F Kilic, DL Murphy, G Rudnick. A 

human serotonin transporter mutation 

causes constitutive activation of 

transport activity. Mol Pharmacol. 2003 

Aug:64(2):440–446. 

6. DL Murphy, GR Uhl, A Holmes, R 

Ren-Patterson, FS Hall, I Sora, S DeteraWadleigh, K-P Lesch. Experimental gene 

interaction studies with SERT mutant 

mice as models for human polygenic 

and epistatic traits and disorders. Genes 

Brain Behav. 2003 Dec:2(6):350–364. 

7. N Ozaki, D Goldman, WH Kaye, K 

Plotnicov, BD Greenberg, J Lappalainen, 

G Rudnick, DL Murphy. Serotonin 

transporter missense mutation 

associated with a complex 

neuropsychiatric phenotype. Mol 

Psychiatry. 2003 Nov:8(11):933–936. 

Patent Status: HHS Reference No. 

B–019–1999/0—Research Tool. 

Licensing Status: This technology is 

available as a research tool under a 

Biological Materials License. 

Licensing Contact: Jennifer Wong; 

301/435–4633; wongje@mail.nih.gov. 

Dated: March 15, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E7–5675 Filed 3–27–07; 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. 

Microdialysis Probe for Accessing 

Tissue in-vivo 

Description of Technology: Available 

for licensing and commercial 

development is a microdialysis probe. 

This device permits in-vivo 

measurement of bioavailable substances 

(e.g., cytokines, growth factors, 

neuropeptides, inflammatory mediators, 

etc.) at picogram levels of concentration 

directly from soft tissue and organ 

systems. The probe may also serve as an 

in-situ drug delivery vehicle of micro 

doses of medication to specific 

anatomical sites by slow diffusion. It 

also permits measurement of efficacy of 

drug delivery, whether given orally, 

systemically or topically, at the local 


sroberts on PROD1PC70 with NOTICES