Federal Register / Vol. 75, No. 213 / Thursday, November 4, 2010 / Notices 67985 

ADDRESSES: 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: 

Peter C. Beckerman, Office of Policy, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 32, Rm. 

4238, Silver Spring, MD 20993–0002, 

301–796–4830, Fax: 301–847–3541, Email: peter.beckerman@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register of August 9, 

2010 (75 FR 47820), FDA published a 

notice of a public meeting on the 

development of a generic drug user fee 

program. In that notice, FDA posed 

several questions related to a user fee for 

human generic drugs, and sought public 

input on such a program. The Agency 

received submissions and presentations 

from the public meeting, which are now 

posted on FDA’s Web site. Some 

submissions arrived after the formal 

closing of the docket and FDA has 

decided to reopen the docket to permit 

public input on all the submissions. 

Interested persons were originally 

given until October 17, 2010, to 

comment on the development of a 

generic drug user fee program. FDA is 

now reopening the docket to permit 

comment until December 6, 2010. 

II. Request for Comments 

Following publication of the August 

9, 2010, meeting notice and request for 

comment, FDA received a request to 

allow interested persons additional time 

to comment. The requester asserted that 

the time period of 30 days was 

insufficient to respond fully to FDA’s 

specific requests for comments and to 

allow potential respondents to 

thoroughly evaluate and address 

pertinent issues. In light of this request, 

and the arrival of late submitted 

comments, FDA is reopening the 

comment period for an additional 30 

days. 

III. How To Submit Comments 

Regardless of attendance at the public 

meeting, interested persons may submit 

to the Division of Dockets Management 

(see ADDRESSES) either electronic or 

written comments regarding this 

document. It is only necessary to send 

one set of comments. It is no longer 

necessary to send two copies of mailed 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

Dated: October 29, 2010. 

David Dorsey, 

Acting Deputy Commissioner for Policy, 

Planning and Budget. 

[FR Doc. 2010–27824 Filed 11–3–10; 8:45 am] 

BILLING CODE 4160–01–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. 

System for Magnetic Resonance 

Spectroscopy of Brain Tissue for 

Pattern-Based Diagnostics 

Description of Invention: Available for 

licensing and commercial development 

is a system for preprocessing magnetic 

resonance spectroscopy (MRS) data of 

brain tissue for pattern-based 

diagnostics. The MRS preprocessing 

system includes an MRS preprocessing 

module that executes an operation that 

normalizes MRS spectrum data, 

recalibrates and scales the normalized 

MRS spectrum data, and then 

renormalizes the scaled MRS spectrum 

data. The resulting preprocessed MRS 

data is used to assist in identifying 

abnormalities in tissues shown in MRS 

scans. Raw MRS spectrum data and 

scaling the raw MRS spectrum data is 

achieved by a plurality of weighting 

constants to generate a preprocessed 

MRS spectrum data. The method may 

also include providing raw MRS 

spectrum data, recalibrating the raw 

MRS spectrum data, and scaling the 

recalibrated MRS spectrum data by 

using a plurality of weighting constants 

to generate a preprocessed MRS 

spectrum data. 

Applications 

• MRI Imaging. 

• Brain Imaging. 

• Neurology. 

Inventors: Jon G. Wilkes (FDA/NCTR), 

Dan A. Buzatu (FDA/NCTR), Pierre 

Alusta (FDA/NCTR), Bruce A. Pearce 

(FDA/NCTR), Richard Beger (FDA/ 

NCTR), Inessa Im (FDA/NCTR). 

Patent Status: U.S. Provisional 

Application No. 61/261,170 filed 13 

Nov 2009 (HHS Reference No. E–298– 

2009/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael A. 

Shmilovich, Esq.; 301–435–5019; 

shmilovm@mail.nih.gov. 

Collaborative Research Opportunity: 

The FDA National Center for 

Toxicological Research is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize FDA’s magnetic 

resonance spectroscopy technology in 

various imaging and diagnostic 

applications. Please contact Alice Y. 

Welch, PhD at 301–796–8449 or 

alice.welch@fda.hhs.gov for more 

information. 

Cancer-Linked Sequences Encoding the 

A2BP1/FOX1 Gene 

Description of Invention: 

Mesothelioma is a rare type of cancer in 

which malignant cells are found in the 

lining of the chest or abdomen. 

Symptoms are frequently misdiagnosed 

and an accurate diagnosis generally 

does not occur until advanced stages, 

and patients live on average nine to 

thirteen months after an accurate 

diagnosis. To date, there are no effective 

systemic treatments. 

Researchers at the National Cancer 

Institute, NIH, have identified a 

recurrent alteration in the DNA 

sequence for ataxin-2 binding protein 

(A2BP1/FOX1) in human mesothelioma 

and colorectal cancers that is present in 

at least twenty percent (20%) of cancer 

cell lines and primary tumor samples. 

The sequence is not present in normal 

tissue, proving that it has arisen as an 

acquired somatic mutation in cancer. 

Furthermore, additional data suggests a 

possible role for the alteration in 

neurological diseases such as autism, 


jlentini on DSKJ8SOYB1PROD with NOTICES
67986 Federal Register / Vol. 75, No. 213 / Thursday, November 4, 2010 / Notices 

inherited mental retardation, and 

seizures. 

This discovery offers a new approach 

for the diagnosis and early detection of 

cancer. 

Applications: Development of assays 

for detection, diagnosis, or prognosis of 

diseases associated with chromosomal 

disruptions of the ataxin-2 binding 

protein 1 (A2BP1 or FOX1) gene, such 

as cancer and neurological disorders. 

Development Status: Pre-clinical. 

Inventors: Frederic J. Kaye (NCI). 

Relevant Publication: Beroukhim R et 

al. The landscape of somatic copynumber alteration across human 

cancers. Nature 2010 Feb 18; 

463(7283):899–905. [PubMed: 

20164920] 

Patent Status 

• U.S. Provisional Application No. 

61/121,997 filed 12 Dec 2008 (HHS 

Reference No. E–180–2008/0–US–01). 

• International Patent Application 

No. PCT/US09/67502 filed 10 Dec 2009, 

which published as WO 2010/068757 

on 17 Jun 2010 (HHS Reference No. E– 

180–2008/0–PCT–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Patrick P. McCue, 

PhD; 301–435–5560; 

mccuepat@mail.nih.gov. 

Insertion of Foreign Genes in Rubella 

Virus and Their Stable Expression in a 

Live, Attenuated Viral Vaccine 

Description of Invention: Rubella 

virus (RUB) is the only member of the 

Rubivirus genus of the family 

Togaviridae. The RUB genomic RNA is 

a single-stranded, 9762-nt, positivesense RNA that contains two long open 

reading frames (ORFs): A 5′-proximal 

ORF which encodes nonstructural 

proteins (NSP) that function primarily 

in viral RNA replication, including the 

RdRp, and a 3′-proximal ORF which 

encodes the virion structural proteins 

(SP), the capsid protein (C), and two 

envelope glycoproteins, E1 and E2. The 

genomic RNA serves as a template for 

synthesis of a complementary minusstrand RNA which is the template for 

synthesis of both the genomic RNA and 

the subgenomic (SG) RNA, from which 

the structural proteins are translated. 

All earlier efforts at expressing foreign 

genes in rubella virus failed due to 

stability of the insert. The inventors 

have found a way to insert foreign genes 

into rubella virus such that the foreign 

genes can be expressed stably over 

many passages of the virus. More 

specifically, based on an earlier 

observation that rubella virus can 

tolerate a small deletion in the 

nonstructural genes and still replicate 

normally, the inventors’ have used this 

deletion to make room for insertion of 

a foreign gene. Thus, the inventors have 

conceptualized and reduced to practice 

a new way to use the already-approved 

rubella vaccine as a viral vector to 

express the additional protein antigens 

of a second (or multiple other) viruses. 

This is highly advantageous because it 

allows for production of a live virus 

vaccine when attenuation is not 

possible for highly virulent viruses such 

as HIV. 

Furthermore, another advantage of 

this vaccine is that virus titers in cell 

culture reach one thousand (1000) 

human doses per milliliter (ml) of 

culture supernatant. This is highly 

desirable for production of multiple 

millions of doses for the developing 

world. In the developed world, this 

vaccine could be substituted for the 

current vaccine at almost no cost and 

used to immunize against rubella plus 

the inserted antigen(s). Without 

vaccination, the average age of 

becoming seropositive for rubella is 

approximately nine (9) years old. This 

new vaccine could be given to one to 

two year olds with a booster at nine 

years old. Additionally, this vaccine is 

already approved, so the safe and 

immunogenic doses are already known. 

Applications 

• Vaccines for the prevention of 

rubella and other indications. 

• Use of rubella vector for expression 

of foreign genes. 

Advantages 

• Novel vaccine candidate 

• Rapid production time 

Development Status: Preclinical 

studies have been conducted by the 

inventors. 

Inventors: Ira Berkower and Angelo 

Spadaccini (FDA). 

Patent Status 

• U.S. Provisional Application No. 

61/252,568 filed 16 Oct 2009 (HHS 

Reference No. E–156–2008/0–US–01). 

• International Patent Application 

No. PCT/US2010/052948 filed 15 Oct 

2010 (HHS Reference No. E–156–2008/ 

0–PCT–02). 

Relevant Publication: Spadaccini A, 

Vimik K, Ni Y, Prutzman K, Berkower 

I. Stable expression of a foreign protein 

by a replication-competent rubella viral 

vector. Vaccine. 2010 Feb 3;28(5):1181– 

1187. [PubMed: 19945412]. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 

Inhibition of Cell Motility, Angiogenesis 

and Metastasis 

Description of Invention: The present 

invention relates to potent, highly 

selective antagonists of Grb2 Src 

homology-2 (SH2) domain binding. 

Grb2, through its SH2 domain, mediates 

growth factor driven cell motility in 

vitro and angiogenesis in vivo. These 

synthetic, small molecule antagonists 

have been shown to block cell motility 

stimulated by hepatocyte growth factor 

(HGF), fibroblast growth factor (FGF), 

epidermal growth factor (EGF), and 

vascular endothelial cell growth factor 

(VEGF). They also potently inhibit HGFand VEGF-stimulated morphogenesis 

and angiogenesis, respectively, in 

several model systems. HGF stimulates 

mitogenesis, motogenesis and 

morphogenesis in a wide range of 

cellular targets during development and 

adulthood, and its signaling pathway is 

frequently over-activated in human 

cancers, including colon, gastric, breast, 

lung, thyroid and renal carcinomas, 

melanoma, several sarcomas as well as 

glioblastoma. The ability of HGF to 

initiate a program of cell dissociation 

and increased cell motility coupled with 

increased protease production promotes 

aggressive cellular invasion and is 

frequently linked to tumor metastasis. 

Metastasis, the primary cause of death 

in most forms of cancer, is a multistep 

process whereby cells from the primary 

tumor spread systemically and colonize 

distant new sites. Blocking critical steps 

in this process could potentially inhibit 

tumor metastasis and dramatically 

improve cancer survival rates. The 

small, synthetic Grb2 SH2 domain 

antagonists described in this invention 

have been shown to inhibit the induced 

and spontaneous metastasis of 

melanoma- and prostate cancer-derived 

tumor cells in mice. These results 

establish a critical role for Grb2 SH2 

domain-mediated interactions in the 

metastatic process and support the 

potential efficacy of this class of 

compound in reducing the metastatic 

spread of primary solid tumors in 

humans. 

Applications and Modality: Inhibition 

of cell motility-dependent processes, 

including angiogenesis and metastasis, 

in several types of cancer such as 

prostate, colon, gastric, breast, lung, 

thyroid and renal carcinomas, 

melanoma and various sarcomas. 

Development Status: In vivo and in 

vitro studies have been conducted on 

this technology. 

Market 

• Cancer is the second leading cause 

of death in the U.S. 


jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 75, No. 213 / Thursday, November 4, 2010 / Notices 67987 

• The worldwide incidence of new 

cancer patients is forecast to increase 

from 4.2 million cases in the major 

cancer markets in 2005 to 4.6 million in 

2010. 

• It is estimated that the worldwide 

cancer marker will be worth 85.3 billion 

in 2010. 

Inventors: Donald P. Bottaro et al. 

(NCI). 

Relevant Publications 

1. Atabey N, Gao Y, Yao Z-J, 

Breckenridge D, Soon L, Soriano JV, 

Burke TR Jr, Bottaro DP. Potent 

blockade of Hepatocyte Growth 

Factor-stimulated cell motility, 

matrix invasion and branching 

morphogenesis by antagonists of 

Grb2 Src homology 2 domain 

interactions. J Biol Chem. 2001 Apr 

27;276(17):14308–14314. [PubMed: 

11278639]. 

2. Shi Z-D, Wei C-Q, Wang X, Lee K, Liu 

H, Zhang M, Vasselli J, Bottaro DP, 

Linehan WM, Yang D, Burke TR Jr. 

Macrocyclization in the design of 

tetra-tetrapeptide mimetics that 

display potent inhibition of Grb2 

SH2 domain binding in whole cell 

systems. In: Peptide Revolution: 

Genomics, Proteomics 

Therapeutics. Chorev, M and 

Sawyer, TK, Eds. American Peptide 

Society, pp 515–517, 2003. 

3. Soriano JV, Lui N, Gao Y, Yao Z-J, 

Ishibashi T, Underhill C, Burke TR 

Jr, Bottaro DP. Inhibition of 

angiogenesis by growth factor 

receptor bound protein 2-Src 

homology 2 domain bound 

antagonists. Mol Cancer Ther. 2004 

Oct;3(10):1289–1299. [PubMed: 

15486196]. 

4. Shi Z-D, Karki RG, Worthy KM, 

Bindu LK, Dharmawardana PG, 

Nicklaus MC, Bottaro DP, Fisher RJ, 

Burke TR Jr. Utilization of a 

nitrobenzoxadiazole (NBD) 

fluorophore in the design of a Grb2 

SH2 domain-binding peptide 

mimetic. Bioorg Med Chem Lett. 

2005 Mar 1;15(5):1385–1388. 

[PubMed: 15713392]. 

5. Kang S-U, Shi, Z-D, Worthy KM, 

Bindu LK, Dharmawardana PG, 

Choyke SJ, Bottaro DP, Fisher RJ, 

Burke TR Jr. Examination of 

phosphoryl-mimicking 

functionalities within a macrocyclic 

Grb2 SH2 domain-binding platform. 

J Med Chem. 2005 Jun 

16;48(12):3945–3948. [PubMed: 

15943469]. 

6. Shi Z-D, Peruzzi B, Dharmawardana 

PG, Leech T, Appella E, Worthy 

KM, Bindu LK, Fisher RJ, Bottaro 

DP, Burke TR Jr. Synthesis and use 

of C-terminally biotinylated 

peptidomimetics with high Grb2 

SH2 domain-binding affinity. In: 

Understanding Biology Using 

Peptides, Blondelle SE (Ed), 

American Peptide Society, pp 208– 

209, 2005. 

7. Dharmawardana PG, Peruzzi B, 

Giubellino A, Burke TR Jr, Bottaro 

DP. Molecular targeting of growth 

factor receptor-bound 2 (Grb-2) as 

an anti-cancer strategy. Anti-Cancer 

Drugs 2006 Jan;17(1):13–20. 

[PubMed: 16317285]. 

8. Liu F, Worthy KM, Bindu L, 

Giubellino A, Bottaro DP, Fisher RJ, 

Burke TR Jr. Utilization of achiral 

alkenyl amines for the preparation 

of high affinity Grb2 SH2 domainbinding macrocycles by ring-closing 

metathesis. Org Biomol Chem. 2007 

Jan 21;5(2):367–372. [PubMed: 

17205182]. 

9. Giubellino A, Gao Y, Lee S, Lee MJ, Vasselli JR, Medepalli S, Trepel 

JB, Burke TR Jr, Bottaro DP. 

Inhibition of tumor metastasis by a 

growth factor receptor bound 

protein Src domain-binding 

antagonist. Cancer Res. (Priority 

Report) 2007 Jul 1;67(13):6012– 

6016. [PubMed: 17616655]. 

Patent Status: U.S. Patent Application 

No. 11/525,672 filed 22 Sep 2006 (HHS 

Reference No. E–265–1999/2–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jennifer Wong; 

301–435–4633; wongje@mail.nih.gov. 

Collaborative Research Opportunity: 

The Urologic Oncology Branch of the 

National Cancer Institute is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize Grb2 SH2 domain 

antagonists as anti-cancer drugs. Please 

contact John D. Hewes, Ph.D. at 301– 

435–3121 or hewesj@mail.nih.gov for 

more information. 

Dated: October 29, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–27912 Filed 11–3–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–D–0132] 

Guidance for Industry: Cellular 

Therapy for Cardiac Disease; 

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: Cellular 

Therapy for Cardiac Disease’’ dated 

October 2010. The guidance document 

provides sponsors who are developing 

cellular therapies for the treatment of 

cardiac disease with recommendations 

on the design of preclinical and clinical 

studies and on the chemistry, 

manufacturing and controls (CMC) 

information that should be included in 

an investigational new drug application 

(IND) for cellular therapy for cardiac 

disease. The guidance announced in 

this notice finalizes the draft guidance 

entitled ‘‘Guidance for Industry: Somatic 

Cell Therapy for Cardiac Disease’’ dated 

March 2009. 

DATES: Submit either 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; or to the 

Division of Small Manufacturers, 

International, and Consumer Assistance, 

Center for Devices and Radiological 

Health, Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 66, 

rm. 4613, Silver Spring, MD 20993– 

0002. 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 comments on the 

guidance 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: 

Benjamin A. Chacko, Center for 


jlentini on DSKJ8SOYB1PROD with NOTICES