Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices 23727 

FDA received 146,274 mandatory 

reports to CDRH during 2007. Based on 

this experience, FDA estimates that 

CDRH will receive 146,274 mandatory 

reports annually from 1,665 users of the 

electronic reporting system (a group 

comprised of facilities, importers, and 

manufacturers). FDA estimates the 

maximum reporting burden for a 

mandatory report to be 1 hour, for a 

total burden of 146,274 hours (146,274 

reports x 1 hour = 146,274 hours) or a 

minimum burden of 99,466 hours with 

((146,274 reports x 80% x 0.60 hour) + 

(146,274 reports x 20% x 1 hour) = 

99,466.32 hours). FDA received 5,000 

voluntary reports to CFSAN during 

2007. Based on this experience, FDA 

estimates that CFSAN will receive 5,000 

voluntary reports annually from 5,000 

users of the electronic reporting system. 

FDA estimates the reporting burden for 

a voluntary report to be 0.6 hours, for 

a total burden of 3,000 hours (5,000 

reports x 0.6 hours = 3,000 hours). 

FDA received 214 mandatory dietary 

supplement reports to CFSAN from 

January 1, 2008, to April 15, 2008. 

Based on this experience, FDA estimates 

that CFSAN will receive 856 mandatory 

reports annually from 150 users of the 

electronic reporting system. FDA 

estimates the maximum reporting 

burden for a mandatory report to be 1 

hour, for a total burden of 856 hours 

(856 reports x 1 hour = 856 hours) or a 

minimum burden of 582 hours with 

((856 reports x 80% x 0.60 hour) + (856 

reports x 20% x 1 hour) = 582.08 hours). 

FDA received 163 voluntary reports to 

CVM during 2007. Based on this 

experience, FDA estimates that CVM 

will receive 163 voluntary reports 

annually from 163 users of the 

electronic reporting system. FDA 

estimates the reporting burden for a 

voluntary report to be 0.6 hours for a 

total burden of 98 hours (163 reports x 

0.6 hours = 97.8 hours). 

FDA received 35,765 mandatory 

reports to CVM during 2007. Based on 

this experience, FDA estimates that 

CVM will receive 35,765 mandatory 

reports annually from 808 users of the 

electronic reporting system. FDA 

estimates the maximum reporting 

burden for a mandatory report to be 1 

hour, for a total burden of 35,765 hours 

(35,765 reports x 1 hour = 35,765 hours) 

or a minimum burden of 24,320 hours 

with ((35,765 reports x 80% x 0.6 hour) 

+ (35,765 reports x 20% x 1 hour) = 

24,320.20 hours). 

FDA received 5,000 voluntary reports 

to ORA during 2007. Based on this 

experience, FDA estimates that ORA 

will receive 5,000 voluntary reports 

annually from 5,000 users of the 

electronic reporting system. FDA 

estimates the reporting burden for a 

voluntary report to be 0.6 hours, for a 

total burden of 3,000 hours (5,000 

reports x 0.6 hours = 3,000 hours). ORA 

does not receive mandatory reports. 

FDAAA, Section 1005, the Reportable 

Food Registry, established new 

electronic mandatory and voluntary 

reporting requirements for instances of 

‘‘reportable’’ food, meaning an article of 

food (other than infant formula) for 

which there is a reasonable probability 

that the use of, or exposure to, such 

article of food will cause serious adverse 

health consequences or death to humans 

or animals. FDA received 625 voluntary 

food complaints leading to adverse 

events from January 1, 2008, to June 30, 

2008, and there were 206 and 182 Class 

1 Recalls for human food in Fiscal Years 

2006 and 2007, respectively. Based on 

these experiences, FDA estimates that 

FDA could receive 200 to 1,200 

‘‘reportable’’ food reports annually from 

200 to 1,200 mandatory and voluntary 

users of the electronic reporting system. 

FDA will utilize the upper-bound 

estimate of 1,200 for these calculations. 

FDA estimates the reporting burden for 

a mandatory ‘‘reportable’’ food report to 

be 0.6 hours, for a total burden of 720 

hours (1,200 reports x 0.6 hours = 720 

hours). FDA estimates the reporting 

burden for a voluntary ‘‘reportable’’ 

food report to be 0.6 hours, for a total 

burden of 720 hours (1,200 reports x 0.6 

hours = 720 hours). 

FDAAA, Section 1002, Early Warning 

Recall, mandated FDA establish a 

system to receive voluntary pet food 

complaint reports and provide an Early 

Warning Recall system for the public. 

FDA received 270 voluntary pet food 

reports from January 1, 2008, to June 30, 

2008. FDA received 10,740 and 99 pet 

food complaints in FY 2007 and 2006, 

respectively. Based on these 

experiences, FDA estimates that FDA 

could receive 540 voluntary pet food 

reports annually from 540 users of the 

electronic reporting system. FDA 

estimates the reporting burden for a 

voluntary ‘‘Early Warning Recall’’ report 

to be 0.6 hours, for a total burden of 324 

hours (540 reports x 0.6 hours = 324 

hours). 

Dated: May 13, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–11687 Filed 5–19–09; 8:45 am] 

BILLING CODE 4160–01–S 

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. 

A549 Cells: A Well-Characterized Lung 

Carcinoma Cell Line Utilized for a 

Variety of Scientific Studies, Including 

Adenovirus Production and Testing 

Description of Technology: Scientists 

at the National Institutes of Health have 

developed a cell line designated A549 

that was derived from explanted 

cultures of human lung cancer tissue. 

The A549 cell line has been tested 

under the guidance of the United States 

Food and Drug Administration (FDA) 

so, under current Good Manufacturing 

Practices (GMP), these cells may be 

suitable for use in manufacturing 

constructs for use in clinical trials. The 

A549 cell line has also been found to be 

suitable for adenovirus production, 

most notably replicating adenovirus 

constructs that do not require 

complementation by the viral oncogene, 

early region 1A (E1A), which is 

responsible for viral gene transcription. 

This cell line is further utilized as a 

negative control in assays to measure 

the replication of adenoviruses that lack 

E1A and as a target cell line to detect 

replication competent adenoviruses 

(RCA). A549 cells have been well 

characterized through their use in a 

wide variety of molecular studies, such 

as anti-tumor drug permeability and 

23728 Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices 

efficacy analysis, infection assays, 

respiratory immunotoxicity tests, cell 

senescence studies, and cytokine 

expression profiling. These cells can 

also be utilized to study a variety of 

molecular characteristics for human 

tumors in culture. 

Application: 

• Cell bank tested under cGMPcompliance regulations and used to 

produce adenoviruses for use in clinical 

trials. 

• Research tool to analyze the efficacy 

of potential anti-cancer agents to devise 

better cancer treatments for 

malignancies, such as non-small cell 

lung cancer (NSCLC). 

• Research tool to study the 

infectivity of viruses that cause asthma 

in order to develop better asthma 

treatments. 

• Standard research tool to analyze a 

variety of molecular biology procedures, 

for example, cell senescence, cytokine 

induction, protein expression, 

apoptosis, and receptor-ligand 

interactions. 

Advantages: 

• A549 cells are a well-characterized 

standard among the human lung 

carcinoma/alveolar cell lines used in 

molecular biology. 

• The A549 cells stored at the NIH 

were tested under the guidance of the 

FDA’s cGMP regulations. 

• The A549 cells stored at the NIH 

may be suitable for producing 

adenoviruses that can be used in 

clinical trials and analyzing adenoviralbased therapies and vaccine strategies. 

Inventors: Wade P. Parks, Donald J. 

Giard, and Stuart Aaronson (all formerly 

NCI). 

Publication: DJ Giard et al. In vitro 

cultivation of human tumors: 

Establishment of cell lines derived from 

a series of solid tumors. J Natl Cancer 

Inst. 1973 Nov; 51(5):1417–1423. 

Patent Status: HHS Reference No. E– 

129–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Samuel E. Bish, 

PhD; 301–435–5282; 

bishse@mail.nih.gov. 

Mobilizing the Body to Fight Cancer: T 

Cell Receptors Specific for the Tumor 

Antigen Survivin 

Description of Technology: A major 

drawback of current chemotherapybased cancer treatments is the harsh 

side-effects associated with many cancer 

drugs. Thus, there is an urgent need to 

develop new therapeutic strategies 

combining fewer side-effects and more 

specific anti-tumor activity. 

Immunotherapy is a promising new 

cancer therapeutic approach that directs 

an individual’s innate and adaptive 

immune system to fight against specific 

diseases, including cancer. 

T cell receptors (TCRs) are proteins 

that recognize antigens in the context of 

infected or transformed cells and 

activate T cells to mediate an immune 

response and destroy abnormal cells. 

TCRs consist of two domains, one 

variable domain that recognizes the 

antigen and one constant region that 

helps the TCR anchor to the membrane 

and transmit recognition signals by 

interacting with other proteins. 

Scientists at the National Institutes of 

Health (NIH) have developed genetically 

modified T cells, which possess TCRs 

that specifically recognize human 

survivin, a tumor antigen expressed in 

many adult and pediatric cancers that is 

absent from most normal tissues. Nonhuman T cells that recognized human 

survivin peptides with high affinity in 

the context of human leukocyte antigen 

(HLA) alleles were identified. Then, 

using recombinant DNA technology, the 

survivin-specific TCRs from the nonhuman T cells were fused to human 

TCR backbones and expressed in human 

T cells. The resulting survivin-specific 

human T cells could prove to be 

powerful new immunotherapeutic tools 

for attacking survivin-expressing tumors 

after infusion into patients. 

Applications: 

• Immunotherapeutics to treat and/or 

prevent the reoccurrence of a variety of 

human cancers that overexpress human 

survivin by inserting survivin-specific 

TCR sequences into patient T cells 

• A drug component of a combination 

immunotherapy regimen aimed at 

targeting the specific tumor-associated 

antigens expressed by cancer cells 

within individual patients. 

Advantages: 

• Survivin is overexpressed in 

virtually all cancers, including lung, 

colon, breast, pancreatic, stomach, liver, 

ovarian and prostate cancer, as well as 

in melanoma and hematopoietic 

malignancies, but this antigen is not 

expressed on normal cells. Thus, 

survivin is an ideal antigen for targeted 

treatment. Anti-survivin TCR 

immunotherapy could treat a host of 

cancer types while reducing the sideeffects of treatment. 

• The survivin-specific TCR 

sequences can be derived in non-human 

species in the context of a wide variety 

of HLA molecules and, thus, TCRs 

specific for each patient’s HLA profile 

can be generated rapidly. 

• The survivin-specific T cells should 

not be rejected by a patient’s immune 

system since the survivin-specific TCR 

sequences are fused to a human TCR 

backbone. 

Development Status: This technology 

is in the pre-clinical stage of 

development. The inventors plan to 

initiate a clinical trial in the next 6–12 

months. 

Market: Cancer continues to be a 

medical and financial burden on U.S. 

public health. According to U.S. 

estimates, cancer is the second leading 

cause of death with over 565,000 deaths 

reported in 2008 and almost 1.5 million 

new cases were reported (excluding 

some skin cancers) in 2008. In 2007, the 

NIH estimated that the overall cost of 

cancer was $219.2 billion dollars and 

$89 billion went to direct medical costs. 

Despite our increasing knowledge of 

oncology and cancer treatment methods, 

the fight against cancer will continue to 

benefit from the development of new 

therapeutics aimed at treating 

individual patients. 

Inventors: Crystal L. Mackall et al. 

(NCI). 

Publications: 

1. Manuscript in preparation. 

2. CJ Cohen et al. Recognition of fresh 

human tumor by human peripheral 

blood lymphocytes transduced with a 

bicistronic retroviral vector encoding a 

murine anti-p53 TCR. J Immunol. 2005 

Nov 1;175(9):5799–5808. (Erratum in: J 

Immunol. 2006 Oct 15;177(8):5746.) 

3. RA Morgan et al. Cancer regression 

in patients after transfer of genetically 

engineered lymphocytes. Science 2006 

Oct 6;314(5796):126–129. 

Patent Status: U.S. Provisional 

Application No. 61/140,338 filed 23 Dec 

2008 (HHS Reference No. E–325–2008/ 

0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Samuel E. Bish, 

PhD; 301–435–5282; 

bishse@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute Pediatric 

Oncology Branch is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize genetically engineered 

lymphocytes with specificity for human 

survivin. Please contact John D. Hewes, 

PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Fused Azepinone Cyclin Dependent 

Kinase Inhibitors 

Description of Technology: The 

invention describes a class of cyclin 

dependent kinase (CDK) inhibitors that 

have anti-proliferative activity in human 

tumor cell lines. CDKs are important in 

Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices 23729 

the control of the cell cycle and 

alterations in CDK expression, function, 

or regulation and are associated with 

diseases characterized by cellular 

proliferation. Increasing CDK activity 

has been reported in many cancers. 

Likewise, the loss of inhibitory activity 

has been observed in a wide variety of 

primary human tumors and human 

tumor-derived cell lines, including lung, 

breast, brain, bone, skin, bladder, 

kidney, ovary, liver, colon, and pancreas 

as well as in leukemia. These 

compounds have also been found to 

potently inhibit GSK3beta activity 

which has recently been linked to a 

variety of cellular processes and several 

disparate areas of biology. In particular, 

GSK3beta activity has been strongly 

implicated in Alzheimer’s as well as 

cardiac failure. Thus, the compounds of 

this invention offer unique 

opportunities for a variety of 

indications. 

Applications: CDK/GSK3beta 

inhibitor therapeutics for the treatment 

of several indications including various 

cancers, neurodegenerative diseases, 

and cardiac conditions. 

Development: Pre-clinical stage of 

development. 

Inventors: Daniel W. Zaharevitz et al. 

(NCI). 

Publication: DW Zaharevitz et al. 

Discovery and initial characterization of 

the paullones, a novel class of smallmolecule inhibitors of cyclin-dependent 

kinases. Cancer Res. 1999 Jun 

1;59(11):2566–2569. 

Patent Status: HHS Reference No. E– 

025–1998/0— 

• U.S. Patent No. 6,610,684, issued 

August 26, 2003; 

• Australian Patent Nos. 780528 and 

778735, issued March 24, 2005 and 

December 16, 2004; 

• Canada Patent Application No. 

2335115, filed June 16, 1999; 

• Japanese Patent Application No. 

2000–554735, filed June 16, 1999; 

• United Kingdom Patent No. 

1086105, validated March 01, 2006 ((E– 

025–1998/0–GB–09); 

• French Patent No. 1086105, 

validated March 01, 2006 (E–025–1998/ 

0–FR–10); and 

• German Patent No. 69930120.3, 

validated March 16, 2006 (E–025–1998/ 

0–DE–11). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney A. 

Hastings; 301–451–7337; 

hastingw@mail.nih.gov. 

Dated: May 13, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–11706 Filed 5–19–09; 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. 

Antibody and Immunotoxin Treatments 

for Mesothelin-Expressing Cancers 

Description of Technology: 

Mesothelin is a cell surface protein that 

is highly expressed in aggressive 

cancers such as malignant 

mesothelioma, ovarian cancer and 

pancreatic cancer. As a result, 

mesothelin is an excellent candidate for 

tumor targeted immunotherapeutics. 

However, the antibodies against 

mesothelin that are available for clinical 

trials are of murine origin. These 

antibodies have the potential to elicit 

immune responses in patients, which 

may adversely affect the ability to 

provide patients with repeated doses. 

Thus, the clinical application of the 

antibodies may be limited. 

In order to address the issue of 

immunogenicity in patients, NIH 

inventors have generated antimesothelin antibody variable fragments 

(Fv) of human origin. These antibody 

fragments (HN1 and HN2) have the 

ability to efficiently recognize 

mesothelin on the surface of numerous 

cancer cells. As a result, these antibody 

fragments represent an attractive 

therapeutic alternative to the murine 

anti-mesothelin antibodies currently 

being tested in clinical trials. 

Application: 

• Use as an antibody therapeutic for 

mesotheliomas, pancreatic tumors and 

ovarian tumors. 

• Use in an immunotoxin therapeutic 

for mesotheliomas, pancreatic tumors 

and ovarian tumors. 

• Diagnostic for the detection of 

mesothelin positive tumors. 

• Research agent for the detection of 

mesothelin. 

Advantages: 

• Fully human antibody reduces 

potential immunogenicity, thereby 

allowing repeated dosing. 

• Antibody specificity improves the 

therapeutic efficacy of the agent. 

Development Status: Preclinical stage 

of development with some pre-clinical 

data available. 

Inventors: Mitchell Ho et al. (NCI). 

Patent Status: U.S. Provisional 

Application No. 61/162,778, filed 24 

Mar 2009 (HHS Reference E–091–2009/ 

0–US–01) 

Related Technologies/Publications: 

• U.S. Patent 6,083,502 entitled 

‘‘Mesothelium Antigen and Methods 

and Kits For Targeting It.’’ 

• PCT Application PCT/US97/0224 

entitled ‘‘Mesothelium Antigen and 

Methods and Kits For Targeting It.’’ 

• U.S. Patent 6,809,184 entitled 

‘‘Antibodies, Including Fv Molecules, 

and Immunoconjugates Having High 

Binding Affinity for Mesothelin and 

Methods for Their Use.’’ 

• PCT Application PCT/US98/25270 

entitled ‘‘Antibodies, Including Fv 

Molecules, and Immunoconjugates 

Having High Binding Affinity for 

Mesothelin and Methods for Their Use.’’ 

• U.S. Patent 7,081,518 entitled 

‘‘Anti-mesothelin antibodies having 

high binding affinity.’’ 

• PCT Application PCT/US00/14829 

entitled ‘‘Immunoconjugates Having 

High Binding Affinity Improvement of 

scFVsr Ab’s with Higher Affinity for 

Mesothelin.’’ 

Licensing Status: Available for 

licensing. 

Licensing Contact: David A. 

Lambertson, Ph.D.; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute 

Laboratory of Molecular Biology is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further