Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 15323 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) electronic or written 

comments and written petitions. It is 

only necessary to send one set of 

comments. It is no longer necessary to 

send three copies of mailed comments. 

However, if you submit a written 

petition, you must submit three copies 

of the petition. Identify comments with 

the docket number found in brackets in 

the heading of this document. 

Comments and petitions that have not 

been made publicly available on 

http://www.regulations.gov may be 

viewed in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: February 14, 2011. 

Jane A. Axelrad, 

Associate Director for Policy, Center for Drug 

Evaluation and Research. 

[FR Doc. 2011–6514 Filed 3–18–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–E–0241] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; ATRYN 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

the regulatory review period for ATRYN 

and is publishing this notice of that 

determination as required by law. FDA 

has made the determination because of 

the submission of an application to the 

Director of Patents and Trademarks, 

Department of Commerce, for the 

extension of a patent which claims that 

human biological product. 

ADDRESSES: Submit electronic 

comments to http:// 

www.regulations.gov. Submit written 

petitions along with three copies and 

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: 

Beverly Friedman, Office of Regulatory 

Policy, Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 51, 

rm. 6222, Silver Spring, MD 20993– 

0002. 301–796–3602. 

SUPPLEMENTARY INFORMATION: The Drug 

Price Competition and Patent Term 

Restoration Act of 1984 (Pub. L. 98–417) 

and the Generic Animal Drug and Patent 

Term Restoration Act (Pub. L. 100–670) 

generally provide that a patent may be 

extended for a period of up to 5 years 

so long as the patented item (human 

drug product, animal drug product, 

medical device, food additive, or color 

additive) was subject to regulatory 

review by FDA before the item was 

marketed. Under these acts, a product’s 

regulatory review period forms the basis 

for determining the amount of extension 

an applicant may receive. 

A regulatory review period consists of 

two periods of time: A testing phase and 

an approval phase. For human 

biological products, the testing phase 

begins when the exemption to permit 

the clinical investigations of the 

biological becomes effective and runs 

until the approval phase begins. The 

approval phase starts with the initial 

submission of an application to market 

the human biological product and 

continues until FDA grants permission 

to market the biological product. 

Although only a portion of a regulatory 

review period may count toward the 

actual amount of extension that the 

Director of Patents and Trademarks may 

award (for example, half the testing 

phase must be subtracted as well as any 

time that may have occurred before the 

patent was issued), FDA’s determination 

of the length of a regulatory review 

period for a human biological product 

will include all of the testing phase and 

approval phase as specified in 35 U.S.C. 

156(g)(1)(B). 

FDA recently approved for marketing 

the human biologic product ATRYN 

(antithrombin (recombinant)). ATRYN is 

indicated for the prevention of perioperative and peri-partum 

thromboembolic events in hereditary 

antithrombin deficient patients. 

Subsequent to this approval, the Patent 

and Trademark Office received a patent 

term restoration application for ATRYN 

(U.S. Patent No. 6,441,145) from GTC 

Biotherapeutics, Inc., and the Patent and 

Trademark Office requested FDA’s 

assistance in determining this patent’s 

eligibility for patent term restoration. In 

a letter dated February 17, 2010, FDA 

advised the Patent and Trademark 

Office that this human biological 

product had undergone a regulatory 

review period and that the approval of 

ATRYN represented the first permitted 

commercial marketing or use of the 

recombinant product. Thereafter, the 

Patent and Trademark Office requested 

that FDA determine the product’s 

regulatory review period. 

FDA has determined that the 

applicable regulatory review period for 

ATRYN is 4,468 days. Of this time, 

4,285 days occurred during the testing 

phase of the regulatory review period, 

while 183 days occurred during the 

approval phase. These periods of time 

were derived from the following dates: 

1. The date an exemption under 

section 505(i) of the Federal Food, Drug, 

and Cosmetic Act (21 U.S.C. 355(i)) 

became effective: November 15, 1996. 

The applicant claims November 14, 

1996, as the date the investigational new 

drug application (IND) became effective. 

However, FDA records indicate that the 

IND effective date was November 15, 

1996, which was 30 days after FDA 

receipt of the IND. 

2. The date the application was 

initially submitted with respect to the 

human biological product under section 

351 of the Public Health Service Act (42 

U.S.C. 262): August 8, 2008. The 

applicant claims January 31, 2008, as 

the date the biologics license 

application (BLA) for ATRYN (BLA 

125284) was initially submitted. 

However, FDA records indicate that 

BLA 125284 was submitted on August 

8, 2008. 

3. The date the application was 

approved: February 6, 2009. FDA has 

verified the applicant’s claim that BLA 

125284 was approved on February 6, 

2009. 

This determination of the regulatory 

review period establishes the maximum 

potential length of a patent extension. 

However, the U.S. Patent and 

Trademark Office applies several 

statutory limitations in its calculations 

of the actual period for patent extension. 

In its application for patent extension, 

this applicant seeks 1,243 days of patent 

term extension. 

Anyone with knowledge that any of 

the dates as published are incorrect may 

submit to the Division of Dockets 

Management (see ADDRESSES) either 

electronic or written comments and ask 

for a redetermination by May 20, 2011. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

September 19, 2011. To meet its burden, 

the petition must contain sufficient facts 

to merit an FDA investigation. (See H. 

Rept. 857, part 1, 98th Cong., 2d sess., 

pp. 41–42, 1984.) Petitions should be in 

the format specified in 21 CFR 10.30. 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) electronic or written 

comments and written petitions. It is 

only necessary to send one set of 

comments. It is no longer necessary to 

send three copies of mailed comments. 

However, if you submit a written 

petition, you must submit three copies 

of the petition. Identify comments with 

mstockstill on DSKH9S0YB1PROD with NOTICES

15324 Federal Register / Vol. 76, No. 54 / Monday, March 21, 2011 / Notices 

the docket number found in brackets in 

the heading of this document. 

Comments and petitions that have not 

been made publicly available on 

http://www.regulations.gov may be 

viewed in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: February 14, 2011. 

Jane A. Axelrad, 

Associate Director for Policy, Center for Drug 

Evaluation and Research. 

[FR Doc. 2011–6509 Filed 3–18–11; 8:45 am] 

BILLING CODE 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 268 Cell Line for Hereditary 

Leiomyomatosis and Renal Cell 

Carcinoma 

Description of Technology: Hereditary 

Leiomyomatosis and Renal Cell 

Carcinoma (HLRCC) is an extremely 

aggressive cancer syndrome with no 

effective treatment regimen and 

currently no cure. The progress of 

identifying HLRCC treatments and cures 

has likely been hindered due to the lack 

of an HLRCC model for studying the 

cancer syndrome and for screening 

therapeutic drug candidates. 

This technology describes the UOK 

268 cell line, a spontaneously 

immortalized renal tumor cell line that 

may be of great interest to industry for 

studying HLRCC, drug screening, and 

searching for tumor markers related to 

diagnosis, prognosis, and drug 

resistance. This cell line is only the 

second spontaneously immortalized 

cancer cell line of its kind in the world 

and is unique in that it is a primary 

tumor cell model (the other cell line, 

UOK 262, is from a metastasis cell 

model). The UOK 268 cell line is an 

established, clonal, immortalized renal 

cancer cell line derived from the longterm culture of aggressive tumor tissues 

of HLRCC in a specially designed 

culture medium under strict culture 

conditions. The UOK 268 exhibits an 

array of HLRCC kidney cancer 

characteristics that can promote protein 

and fatty acid biosynthesis and 

modulate HIF activities in a manner 

conducive to cancer cell proliferation. 

Benefits: 

• This is only one of two 

immortalized HLRCC cell lines, and is 

unique in that it is from a primary 

tumor cell model. 

• Developing a diagnostic to search 

for tumor targets and screen for HLRCC 

and related cancers drug candidates will 

have significant benefits, including 

early detection and treatment. 

Applications: 

• In vitro and in vivo cell model for 

understanding the biology of HLRCC 

and related cancers, including growth, 

motility, invasion, and metabolite 

production. 

• High throughput screening to test 

for drug candidates that could be used 

to treat particular cancers, such as 

HLRCC. 

• Diagnostic tool for the diagnosis, 

prognosis, and drug resistance of tumor 

markers. 

Advantages: 

• Cell line is derived from a HLRCC 

patient: This cell line is anticipated to 

retain many features of primary HLRCC 

samples and novel HLRCC antigens 

identified from this cell line are likely 

to correlate with antigens expressed on 

human HLRCC tumors. Studies 

performed using this cell lines may have 

a direct correlation to the initiation, 

progression, treatment, and prevention 

of HLRCC in humans. 

• Molecular and genetic features are 

well characterized: The inventors have 

elucidated many physical 

characteristics of the cell lines and their 

data reveals previously unrecognized 

coordination between mammalian 

glucose and iron metabolisms through 

AMPK signaling, and a novel 

mechanism for modulating HIF 

activities in renal cancers. 

Inventors: W. Marston Linehan and 

Youfeng Yang (NCI) 

Publications: 

1. Youfeng Yang et al. Distinct Mitotranscriptome Profiling in Fumarate 

Hydratase-deficient Novel Primary 

Tumor Cell Line UOK268 Leads to 

Better Understanding of Early Human 

HLRCC-associated Cancer with Multiple 

Dysregulated Molecular Events and 

Metabolic Shunts. Under submission. 

2. Wing-Hang Tong et al. 

Hypoactivation of AMPK pathway and 

remodeling of iron metabolism in 

hereditary leiomyomatosis and renal 

cell carcinoma tumorigenesis. Under 

resubmission. 

Patent Status: HHS Reference No. E– 

254–2010/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@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 UOK268 as human 

HLRCC primary cell line model to 

comparing previously established 

UOK262, which was from metastasis 

lympho node. UOK 268 is a unique cell 

model for studying the underlying 

molecular derangements associated with 

impaired oxidative phosphorylation in 

cancer and for evaluating novel 

therapeutic approaches for this HLRCCassociated kidney cancer. Please contact 

John Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Agonistic Human Monoclonal 

Antibodies Against DR4 

Description of Technology: The tumor 

necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL) and its 

functional receptors, DR4 and DR5, have 

been recognized as promising targets for 

cancer treatment. Therapeutics targeting 

TRAIL and its receptors are not only 

effective in killing many types of tumors 

but they also synergize with traditional 

therapies, and show efficacy against 

tumors that are otherwise resistant to 

conventional treatments. 

The researchers at the NIH have 

developed two human monoclonal 

antibodies (mAbs) that bind to death 

receptor 4 (‘‘DR4’’). One of the mAbs is 

agonistic and inhibits the growth of 

ST486 cells with IC50 of about 10nM. 

The two mAbs were selected from a 

human phage-displayed Fab library by 

panning against a recombinant DR4 

mstockstill on DSKH9S0YB1PROD with NOTICES