29766 Federal Register / Vol. 75, No. 102 / Thursday, May 27, 2010 / Notices 

potent against virions produced from 

PBMC, perhaps due to differences in 

glycosylation. Importantly, the 

bifunctional protein is composed of 

almost entirely human sequences. It 

potentially can be linked to other 

functional moieties to achieve desired 

properties (longer plasma half-life, 

selective killing of HIV-infected cells, 

imaging of viral reservoirs, etc.). 

The chimeric protein of this invention 

has considerable potential for 

prevention of HIV–1 infection, both as 

a topical microbicide and as a systemic 

agent to protect during and after acute 

exposure (e.g. vertical transmission, 

post exposure prophylaxis). It also has 

potential utility for treatment of chronic 

infection, including gene therapy 

strategies involving hematopoietic stem 

cells and/or viral vectors. Such proteins, 

nucleic acid molecules encoding them, 

and their production and use in 

preventing or treating viral infections 

are claimed in the patents issued for this 

invention. 

Applications: 

• Prophylactic and/or therapeutic 

treatment for HIV infection. 

• Topical microbicide treatment to 

protect against HIV infection. 

• Imaging of HIV infected cells in 

tissues. 

Advantages: 

• High neutralization efficiency due 

to unique bifunctional binding 

characteristics. 

• Potentially minimally immunogenic 

or toxic (human sequences and possibly 

low treatment doses). 

• Broad neutralizing activity. 

• Mechanism of action less 

susceptible to resistance. 

Development Status: 

• Reproducible production and scaleup of chimeric protein has been 

demonstrated. 

• Potent and broad neutralization of 

genetically diverse HIV–1 clinical 

isolates was demonstrated. 

Market: The race to develop effective 

antiviral strategies against HIV infection 

is ongoing. The problems exhibited by 

conventional drugs such (i.e. toxicity 

and resistance) have triggered the 

pursuit of alternative approaches to 

HIV/AIDS prevention and treatment. 

One of the new approaches is the 

development of neutralizing antibodies 

against the HIV envelope proteins. This 

approach has not yet yielded any 

commercially viable treatment. It is 

believed that the approach presented in 

the subject invention will circumvent 

many of the shortcomings of the existing 

drugs and other pursued approaches. If 

this approach is successful the 

commercial rewards will be huge 

because of the global magnitude of HIV 

epidemics. 

Inventor: Edward A. Berger (NIAID). 

Related Publications: 

1. Lagenaur LA, Villarroel VA, 

Bundoc V, Dey B, Berger EA. sCD4–17b 

bifunctional protein: Extremely broad 

and potent neutralization of HIV–1 

pseudotyped viruses from genetically 

diverse primary isolates. Retrovirology 

2010 Feb 16; 7:11. [PubMed: 20158904] 

2. Dey B, Del Castillo CS, Berger EA. 

Neutralization of human 

immunodeficiency virus type 1 by 

sCD4–17b, a single-chain chimeric 

protein, based on sequential interaction 

of gp120 with CD4 and coreceptor. J 

Virol. 2003 March; 77(5):2859–2865. 

[PubMed: 12584309] 

Patent Status: 

HHS Reference No. E–039–1999/0— 

• U.S. Patent No. 7,115,262, issued 03 

Oct 2006. 

• U.S. Application No. 11/535,957, 

filed 27 Sep 2006, published 18 Oct 

2007 as 20070243208. 

• Australian Patent No. 765218, 

issued 30 Jul 2003. 

• European Patent No. 1161445 

issued 03 Sep 2008 for France, 

Germany, Great Britain, Italy. 

• Applications pending in Canada, 

Japan. 

Licensing Status: Available for 

licensing. 

Licensing Contacts: Uri Reichman, 

PhD, MBA; 301–435–4616; 

ur7a@nih.gov; or Susan Ano, PhD, 301– 

435–5515; anos@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID, Office of Technology 

Development, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize ‘‘A Novel Chimeric 

Protein for Prevention and Treatment of 

HIV Infection.’’ Please contact 

Marguerite J. Miller at 301–435–8619 for 

more information. 

Dated: May 20, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–12794 Filed 5–26–10; 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. 

UOK 257, the First BHD Tumor Cell 

Line, and UOK257–2 Wild Type FLCNRestored Renal Cell Line as In Vitro 

and In Vivo Models of Energy/Nutrient 

Sensing Through the AMPK and mTOR 

Signaling Pathways 

Description of Invention: Scientists at 

the National Institutes of Health (NIH) 

have developed a novel renal cell 

carcinoma (RCC) cell line designated 

UOK257, which was derived from the 

surgical kidney tissue of a patient with 

hereditary Birt-Hogg-Dube’ (BHD) 

syndrome and companion cell line 

UOK257–2 in which FLCN expression 

has been restored by lentivirus 

infection. These cell lines harbors a 

germline mutation of FLCN gene (alias 

BHD) and displays loss of 

heterozygosity, can grow as xenograft in 

nude mice. Patients affected with BHD 

develop skin papules 

(fibrofolliculomas), lung cysts, 

spontaneous pneumothorax and an 

increased risk for bilateral multifocal 

renal tumors. Loss of both copies of the 

FLCN gene has been documented in 

BHD renal tumors; however, the 

molecular mechanisms by which 

inactivation of the encoded protein, 

folliculin, leads to the BHD phenotype 

are currently unknown. They have 

developed an important research tool 

for in vitro folliculin functional studies. 

The companion cell line will be 

extremely useful for comparative 

biochemical analyses of cell culture 

systems in which the FLCN gene is 

either expressed or inactivated, 

including identification of renal tumor 

biomarkers, alteration of biochemical 

pathways resulting from loss of FLCN 


wwoods2 on DSK1DXX6B1PROD with NOTICES
Federal Register / Vol. 75, No. 102 / Thursday, May 27, 2010 / Notices 29767 

function, tumorigenicity of FLCN null 

versus FLCN restored cells, preclinical 

therapeutic drug testing in xenograft 

animal models produced from injection 

of these cell lines, etc. UOK 257 and 

UOK257–2 are thus useful cell models 

for studying the underlying molecular 

derangements associated with mTOR 

pathways and other biogenesis 

pathways in human kidney cancer and 

for evaluating novel therapeutic 

approaches for this disease. UOK257 is 

also one of the 40-member renal cancer 

cell lines in the Tumor Cell Line 

Repository of the Urologic Oncology 

Branch (UOB), National Cancer Institute 

(NCI). 

Applications 

• In vitro and in vivo cell model for 

BHD cancer syndrome. Research tool for 

investigating the underlying molecular 

mechanisms contributing to advanced 

BHD, including the identification of 

new BHD tumor antigens for 

immunotherapy. 

• Research tool for studying genes 

transcription status of genes involved in 

BHD to reveal the genetic processes 

occurring in BHD tissues that may 

contribute to advanced disease. 

• Positive control cell line for FLCN 

gene expression and function studies, 

including cytogenetics, gene mutation 

research, and examination abnormalities 

of interaction with other proteins that 

may contribute to BHD. 

• Research tools for testing the 

activity of potential anti-cancer drugs 

against BHD, a disease which has no 

effective treatment options; tool for 

searching tumor markers for diagnosis, 

prognosis and drug resistance. 

• Therapeutic drug testing for 

targeting BHD renal tumors, possible 

starting material for developing a cancer 

vaccine against BHD. 

Advantages 

• Cell line is derived from a BHD 

patient: These cell lines are anticipated 

to retain many features of primary BHD 

samples and novel BHD antigens 

identified from this cell line are likely 

to correlate with antigens expressed on 

human BHD type of RCC tumors. 

Studies performed using these cell lines 

may have a direct correlation to the 

initiation, progression, treatment, and 

prevention of BHD type of RCC in 

humans. 

• Molecular and genetic features are 

well characterized: This cell line is part 

of NCI Urologic Oncology Branch’s 

Tumor Cell Line Repository. The 

inventor has elucidated many physical 

characteristics of the cell lines, 

including chromosomal attributes and 

valuable studies on functions of BHD 

gene, their data suggest that FLCN, 

mutated in the BHD syndrome, and its 

novel interacting partner, folliculininteracting protein (FNIP1), may be 

involved in energy and/or nutrient 

sensing through the AMPK and mTOR 

signaling pathways. 

Inventor: W. Marston Linehan (NCI). 

Related Publications 

1. Yang Y, Padilla-Nash HM, Vira MA, 

Abu-Asab MS, Val D, Worrell R, Tsokos 

M, Merino MJ, Pavlovich CP, Ried T, 

Linehan WM, Vocke CD. The UOK 257 

cell line: a novel model for studies of 

the human Birt-Hogg-Dube ́ gene 

pathway. Cancer Genet Cytogenet. 2008 

Jan 15;180(2):100–109. [PubMed: 

18206534.] 

2. Baba M, Hong SB, Sharma N, 

Warren MB, Nickerson ML, Iwamatsu A, 

Esposito D, Gillette WK, Hopkins RF 

3rd, Hartley JL, Furihata M, Oishi S, 

Zhen W, Burke TR Jr, Linehan WM, 

Schmidt LS, Zbar B. Folliculin encoded 

by the BHD gene interacts with a 

binding protein, FNIP1, and AMPK, and 

is involved in AMPK and mTOR 

signaling. Proc Natl Acad Sci USA. 2006 

Oct 17;103(42):15552–15557. [PubMed: 

17028174.] 

Patent Status: HHS Reference No. E– 

131–2010/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Betty B. Tong, 

Ph.D.; 301–594–6565; 

tongb@mail.nih.gov. 

Collaborative Research Opportunity: 

The Center for Cancer Research, 

Urologic Oncology Branch, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize kidney cancer tumor cell 

lines as described in above abstract 

through MTA, CRADAs, CTAs, BML, 

etc.: 

• For laboratory interests in the basis 

of metazoan tumor cell survival, 

including growth factor-regulated 

nutrient uptake; glucose or glutamine 

metabolism and epigenetic gene control; 

tumor cell bioenergetics and cell growth 

through AMPK and mTOR signaling 

pathways. 

• In vitro and in vivo cell model for 

BHD cancer syndrome. It is a valuable 

research tool for a laboratory interested 

in identification of new BHD tumor 

antigens for immunotherapy. 

• These paired cell lines for FLCN 

gene expression and function studies, 

including gene therapy, cytogenetics, 

gene mutation research, and 

examination of abnormalities of 

interaction with other proteins that may 

contribute to BHD. 

• The excellent in vivo model for 

preclinical xenograft imaging, including 

stable transfection. Cells could be 

labeled with reagents for PET, 

Luciferase, Fluorescence, for transgenic 

mice, optical molecular imaging, etc., 

and provides a useful platform for 

preclinical drug evaluations. 

Please contact John Hewes, Ph.D. at 

301–435–3131 or hewesj@mail.nih.gov 

for more information. 

Highly Sensitive microRNA 31 in situ 

Hybridization Assay To Detect 

Endometrial Cancer 

Description of Invention: Investigators 

at the National Cancer Institute have 

developed a sensitive, specific and 

robust human microRNA in situ 

hybridization (ISH) assay that can 

detect, quantify, and identify cancer 

biomarkers. Currently available 

microRNA (miRNA) markers can be 

detected by microarray, Northern Blot, 

real time RT–PCR, and sequencing 

analysis. However, these assays cannot 

specify tissue and cell types that contain 

miRNAs without laser microdissection 

(LMD). LMD has severe limitations as it 

requires expensive equipment and its 

miRNA yields are too low to be detected 

by the aforementioned techniques. 

Available for licensing is an 

optimized an ISH assay to detect 

miRNAs. ISH represents an efficient and 

specific assay to detect miRNA of 

interest due to direct interaction with 

specific tissue and cell types. This ISH 

assay utilized fresh cell lines and it can 

be adapted to frozen cells and tissue 

samples. Utilizing the assay, the 

investigators have found that miRNA– 

31 is decreased in cancerous 

endometrial cells in comparison to 

controls. This ISH assay provides for a 

less expensive, more efficient and 

highly sensitive assay to detect and 

quantify microRNAs. 

Applications 

• Method to detect and quantify 

miRNAs. 

• Method and kits to diagnose 

endometrial cancer. 

Advantages: Cost effective, highly 

sensitive assay to detect miRNAs. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Market 

• U.S. microRNA revenues were $20 

million in 2008 will increase to more 

than an estimated $98 million in 2015. 

• Global cancer market is worth more 

than eight percent of total global 

pharmaceutical sales. 


wwoods2 on DSK1DXX6B1PROD with NOTICES
29768 Federal Register / Vol. 75, No. 102 / Thursday, May 27, 2010 / Notices 

• Cancer industry is predicted to 

expand to $85.3 billion by 2010. 

Inventors: Hui Han and John E. 

Niederhuber (NCI). 

Patent Status: U.S. Provisional 

Application No. 61/253,617 filed 21 Oct 

2009 (HHS Reference No. E–303–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jennifer Wong; 

301–435–4633; wongje@mail.nih.gov. 

Dated: May 20, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–12790 Filed 5–26–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–1997–D–0008] (formerly 

Docket No. 1997D–0318) 

Guidance for Industry: Revised 

Preventive Measures to Reduce the 

Possible Risk of Transmission of 

Creutzfeldt-Jakob Disease (CJD) and 

Variant Creutzfeldt-Jakob Disease 

(vCJD) by Blood and Blood Products; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a document entitled 

‘‘Guidance for Industry: Revised 

Preventive Measures to Reduce the 

Possible Risk of Transmission of 

Creutzfeldt-Jakob Disease (CJD) and 

Variant Creutzfeldt-Jakob Disease (vCJD) 

by Blood and Blood Products’’ dated 

May 2010. The guidance announced in 

this notice provides blood collecting 

establishments and manufacturers of 

plasma derivatives with comprehensive 

FDA recommendations intended to 

minimize the possible risk of 

transmission of CJD and vCJD from 

blood and blood products. This 

guidance document amends the January 

2002 guidance document of the same 

title by: Incorporating donor deferral 

recommendations for donors who have 

received a transfusion of blood or blood 

components in France since 1980, 

providing updated scientific 

information on CJD and vCJD, revising 

labeling recommendations for Whole 

Blood and blood components intended 

for transfusion, and recognizing AABB’s 

full Donor History Questionnaire 

Version 1.3 as an acceptable mechanism 

for collection of donor history 

information. The guidance announced 

in this notice supersedes the guidance 

document entitled ‘‘Guidance for 

Industry: Revised Preventive Measures 

to Reduce the Possible Risk of 

Transmission of Creutzfeldt-Jakob 

Disease (CJD) and Variant CreutzfeldtJakob Disease (vCJD) by Blood and 

Blood Products’’ dated January 2002 

(2002 guidance), and the draft guidance 

document entitled ‘‘Draft Guidance for 

Industry: Amendment (Donor Deferral 

for Transfusion in France Since 1980) to 

‘‘Guidance for Industry: Revised 

Preventive Measures to Reduce the 

Possible Risk of Transmission of 

Creutzfeldt-Jakob Disease (CJD) and 

Variant Creutzfeldt-Jakob Disease (vCJD) 

by Blood and Blood Products’’’ dated 

August 2006 (2006 draft guidance). 

DATES: Submit electronic or written 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of the guidance to the 

Office of Communication, Outreach and 

Development (HFM–40), Center for 

Biologics Evaluation and Research 

(CBER), Food and Drug Administration, 

1401 Rockville Pike, suite 200N, 

Rockville, MD 20852–1448. Send one 

self-addressed adhesive label to assist 

the office in processing your requests. 

The guidance may also be obtained by 

mail by calling CBER at 1–800–835– 

4709 or 301–827–1800. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the guidance 

document. 

Submit electronic or written 

comments on the guidance. Submit 

electronic comments to http:// 

www.regulations.gov. Submit written 

comments to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: 

Denise Sa ́nchez, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 1401 

Rockville Pike, suite 200N, Rockville, 

MD 20852–1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a document entitled ‘‘Guidance for 

Industry: Revised Preventive Measures 

to Reduce the Possible Risk of 

Transmission of Creutzfeldt-Jakob 

Disease (CJD) and Variant CreutzfeldtJakob Disease (vCJD) by Blood and 

Blood Products’’ dated May 2010. This 

guidance amends the 2002 FDA 

guidance of the same title by 

incorporating donor deferral 

recommendations as to donors in France 

(as announced in the 2006 draft 

guidance), providing updated scientific 

information on CJD and vCJD, revising 

labeling recommendations for Whole 

Blood and blood components intended 

for transfusion, and recognizing the use 

of AABB’s full Donor History 

Questionnaire Version 1.3 as an 

acceptable mechanism that is consistent 

with FDA requirements and 

recommendations for collecting donor 

history information. 

In the Federal Register of January 16, 

2002 (67 FR 2226), FDA announced the 

availability of a guidance entitled 

‘‘Guidance for Industry: Revised 

Preventive Measures to Reduce the 

Possible Risk of Transmission of 

Creutzfeldt-Jakob Disease (CJD) and 

Variant Creutzfeldt-Jakob Disease (vCJD) 

by Blood and Blood Products’’ dated 

January 2002 (the 2002 guidance). The 

2002 guidance finalized 

recommendations to all blood collecting 

establishments and manufacturers of 

plasma derivatives for deferral of donors 

with possible exposure to the CJD and 

vCJD agents. In the Federal Register of 

August 14, 2006 (71 FR 46484), FDA 

announced the availability of a draft 

guidance entitled ‘‘Draft Guidance for 

Industry: Amendment (Donor Deferral 

for Transfusion in France Since 1980) to 

‘Guidance for Industry: Revised 

Preventive Measures to Reduce the 

Possible Risk of Transmission of 

Creutzfeldt-Jakob Disease (CJD) and 

Variant Creutzfeldt-Jakob Disease (vCJD) 

by Blood and Blood Products’’’ (the 2006 

draft guidance). The 2006 draft guidance 

was intended to amend the 2002 

guidance by adding a donor deferral 

recommendation for donors who have 

received a transfusion of blood or blood 

components in France since 1980. 

Specifically, in the 2006 draft guidance, 

we stated that we intended to 

incorporate the new donor deferral 

recommendation after receiving 

comments on the draft guidance and 

reissue the revised 2002 guidance as a 

level 2 guidance document for 

immediate implementation (71 FR 

46484, August 14, 2006). Upon further 

consideration, however, we believe it 

appropriate to issue the guidance 

announced in this notice as a level 1 

guidance document. 

The guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents FDA’s current 

thinking on this topic. It does not create 

or confer any rights for or on any person 

and does not operate to bind FDA or the 

public. An alternative approach may be 

used if such approach satisfies the 


wwoods2 on DSK1DXX6B1PROD with NOTICES