28256 Federal Register / Vol. 74, No. 113 / Monday, June 15, 2009 / Notices 

Application No. Drug Applicant 

NDA 18–154 LONITEN (minoxidil) Tablets, 2.5 mg and 10 

mg 

Pharmacia & Upjohn Co., c/o Pfizer, Inc. 

NDA 18–285 VISKEN (pindolol) Tablets, 5 mg and 10 mg Novartis Pharmaceuticals Corp. 

NDA 18–445 DOLOBID (diflunisal) Tablets, 250 mg and 

500 mg 

Merck & Co., Inc., Sunneytown Pike, P.O. 

Box 4, BLA–20, West Point, PA 19486 

NDA 19–661 CYTOVENE IV (ganciclovir sodium) Injection, 

EQ 500 mg base/vial 

Roche Laboratories, Inc., 340 Kingsland St., 

Nutley, NJ 07110–1199 

NDA 20–027 CARDIZEM (diltiazem HCl) Injection, 5 mg/ 

mL and 25 mg/vial 

Biovail Pharmaecuticals, Inc. 

NDA 20–137 DEMADEX (torsemide) Injection, 20 mg/2 mL 

(10 mg/mL) and 50 mg/5 mL (10 mg/mL) 

Roche Laboratories, Inc. 

NDA 20–154 VIDEX (didanosine) Chewable Tablets, 25 

mg, 50 mg, 100 mg, 150 mg, and 200 mg 

Bristol-Myers Squibb Co., P.O. Box 5100, 

Wallingford, CT 06492–7660 

NDA 20–225 IMDUR (isosorbide mononitrate) ExtendedRelease Tablets, 30 mg, 60 mg, and 120 

mg 

Schering Corp., 2000 Galloping Hill Rd., Kenilworth, NJ 07033 

NDA 21–238 KYTRIL (granisetron HCl) Oral Solution, EQ 

2 mg base/10 mL 

Roche Laboratories, Inc. 

NDA 21–301 LEVOXYL (levothyroxine sodium) Tablet, 0.3 

mg 

King Pharmaceuticals, Inc., 501 Fifth St., 

Bristol, TN 37620 

FDA has reviewed its records and, 

under § 314.161, has determined that 

the drug products listed in this 

document were not withdrawn from 

sale for reasons of safety or 

effectiveness. Accordingly, the agency 

will continue to list the drug products 

listed in this document in the 

‘‘Discontinued Drug Product List’’ 

section of the Orange Book. The 

‘‘Discontinued Drug Product List’’ 

identifies, among other items, drug 

products that have been discontinued 

from marketing for reasons other than 

safety or effectiveness. 

Approved ANDAs that refer to the 

NDAs listed in this document are 

unaffected by the discontinued 

marketing of the products subject to 

those NDAs. Additional ANDAs that 

refer to these products may also be 

approved by the agency if they comply 

with relevant legal and regulatory 

requirements. If FDA determines that 

labeling for these drug products should 

be revised to meet current standards, the 

agency will advise ANDA applicants to 

submit such labeling. 

Dated: June 5, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–14000 Filed 6–12–09; 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. 

Improved Antibodies Against ErbB4/ 

Her4 

Description of Technology: ErbB4/ 

Her4 is a receptor tyrosine kinase that 

regulates cell proliferation, cell 

differentiation and cell survival. ErbB4 

has been implicated in the pathology of 

numerous cancers (e.g., breast cancer, 

non-small cell lung carcinoma, 

adenocarcinoma), as well as psychiatric 

disorders (e.g., schizophrenia). As a 

result, ErbB4 is an excellent target for 

developing therapies against these 

diseases. Unfortunately, the study of 

ErbB4 has been slowed by the lack of 

highly specific and functional 

antibodies against the receptor. 

In order to overcome the deficiencies 

with current ErbB4 antibodies, NIH 

inventors have generated three rabbit 

monoclonal antibodies with improved 

properties and versatility. Specifically, 

the mAb-6, mAb-7 and mAb-10 

hybridomas produce antibodies with a 

high degree of specificity and affinity 

for ErbB4. These antibodies recognize 

specific epitopes on the intracellular 

domains of ErbB4 without crossreaction against other proteins, and can 

be used successfully in the 

immunostaining of fixed tissue. Each 

antibody recognizes both human and 

mouse ErbB4, whereas only mAb-7 and 

mAb-10 recognize rat ErbB4. 

Applications: 

• Basic research tool for the study of 

ErbB4; 


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Federal Register / Vol. 74, No. 113 / Monday, June 15, 2009 / Notices 28257 

• Reagent for diagnostic applications 

such as Western Blotting, ELISA, 

immunofluorescence and 

immunohistochemistry in fixed tissue 

samples; 

• Reagent for biochemical techniques 

such as immunoprecipitation. 

Advantages: 

• Potential to be the gold standard for 

ErbB4 antibodies due to its specificity 

and affinity; 

• Greater affinity for ErbB4 than 

currently available antibodies, giving 

them superior properties in diagnostic 

and biochemical applications; 

• Unlike currently available 

polyclonal antibodies to ErbB4, the 

monoclonal antibodies do not crossreact with other proteins; 

• Unlike currently available 

antibodies, these antibodies are capable 

of immunostaining fixed tissue samples; 

• The epitopes on ErbB4 that are 

recognized by each monoclonal 

antibody have been mapped. 

Relevant Publications: 

1. G Carpenter. ErbB-4: mechanism of 

action and biology. Exp Cell Res. 2003 

Mar 10;284(1):66–77. 

2. S Britsch. The neruregulin-1/ErbB 

signaling system in development and 

disease. Adv Anat Embryol Cell Biol. 

2007;190:1–65. 

Inventors: Andres Buonanno and 

Detlef Vullhorst (NICHD) 

Patent Status: HHS Reference No. E– 

171–2009/0—Research Material. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: The technology is 

available under a biological materials 

license. 

Licensing Contact: David A. 

Lambertson, PhD; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The Eunice Kennedy Shriever National 

Institute of Child Health and Human 

Development, Section on Molecular 

Neurobiology, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further evaluate or commercialize 

specific rabbit monoclonal antibodies 

generated against the ErbB4 receptor 

(also known as HER4). Please contact 

Joseph Conrad III, PhD at 301–435–3107 

or jmconrad@mail.nih.gov for more 

information. 

Mouse Model of Individual 

Unresponsive to Interferon 

Description of Technology: NIAID has 

developed a mouse model that produces 

very high levels of Interferon-alphareceptor 2 (IFNAR2), both in liver cells 

and free-floating in serum. 

Chronic co-infection of HIV and 

hepatitis C virus (HCV) is associated 

with increased overall morbidity and 

mortality compared to those infected 

with just one virus. Recent data further 

suggests that co-infection is also 

associated with a more rapid 

progression of liver disease, higher HCV 

RNA viral levels, decreased cure rate of 

HCV, and increased toxicities of antiHCV therapy. Finally, clinical trials 

have shown that many patients infected 

with both viruses do not respond to 

Interferon-based therapy. Research 

strongly suggests that non-responding 

patients have an increased level of a 

free-floating form of IFNAR2, which 

could block Interferon activity. 

Resistance to Interferon therapy also 

occurs in other diseases, such as 

autoimmune diseases (e.g., lupus, 

scleroderma, psoriasis, vasculitis) and 

certain forms of cancer (e.g., Kaposi’s 

sarcoma, follicular lymphoma). The 

various means by which resistance 

arises is currently being researched. 

Applications: Study of mechanisms of 

resistance to Interferon therapy in 

selected diseases, such as HCV/HIV coinfection and certain cancers; study of 

Interferon-alpha in auto-immune 

diseases such as lupus, scleroderma, 

psoriasis, and vasculitis; drug design 

and screening. 

Advantages: 

• A model to screen, develop, and 

test drugs for HCV among HCV/HIV coinfected patients not responding to 

Interferon; 

• A model for basic research, to study 

the biology and role of IFNAR2 and its 

function, along with the role of the 

Interferon receptor in the development 

of disease resulting from activation of 

the immune system. 

Development Status: Proof-ofprinciple studies showing that the mice 

represent HCV/HIV co-infected 

individuals not responding to Interferon 

treatment. 

Market: HIV/HCV co-infection is 

documented in one-third of all HIVinfected persons in the United States, an 

estimated 250,000 people. Moreover, 

certain cancers (e.g., Kaposi’s sarcoma, 

follicular lymphoma) normally treated 

with Interferon-alpha either show initial 

resistance or develop resistance during 

therapy, but the mechanism of 

resistance is highly complex; this mouse 

model will be useful in learning the 

paths through which resistance 

develops, and perhaps in designing 

strategies to overcome resistance. 

Finally, autoimmune diseases known to 

be caused (in whole or in part) by 

Interferon-alpha include lupus, 

scleroderma, psoriasis, and vasculitis. 

Inventors: Shyamasundaran Kottilil 

(NIAID), Howard Young (NCI), Michael 

Polis (NIAID), Anthony Suffredini 

(NIHCC). 

Patent Status: HHS Reference No. E– 

106–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for nonexclusive Biological Materials 

Licensing. 

Licensing Contact: Bruce Goldstein, 

J.D., M.S.; 301–435–5470; 

goldsteb@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Allergy and 

Infectious Diseases, Laboratory of 

Immunoregulation, is interested in 

collaborative research directed toward 

molecular strategies for vaccine and 

antiviral development, and animal 

models of viral hepatitis C. For more 

information, please contact Rick 

Williams at 301–402–0960. 

Enhanced Immune Response Against 

Influenza Virus by Priming With a 

DNA-based Vaccine 

Description of Technology: Available 

for licensing and commercial 

development are compositions and 

methods for enhancing an immune 

response to influenza viruses by 

priming with DNA-based vaccines 

encoding influenza proteins. The 

priming compositions contain DNA 

constructs with inserted nucleic acids 

encoding influenza virus hemagglutinin 

(HA) or an epitope-bearing domain 

thereof, while the boosting 

compositions are inactivated influenza 

vaccines. The DNA constructs are based 

on proprietary expression systems that 

increase protein expression relative to 

commonly used alternatives. 

A potential influenza pandemic 

caused by H5N1 strains of avian 

influenza virus (bird flu) is a major 

global concern. The seasonal influenza 

caused by other subtypes of influenza is 

also a cause of concern. Vaccination is 

one of the most effective ways to 

minimize suffering and death from 

influenza. However, influenza 

vaccination does not reduce the risk of 

community-acquired pneumonia in 

elderly nor does it decrease the rate of 

influenza infection in children aged 6– 

23 months. Strategies to elicit protective 

immunity with greater potency and 

breadth therefore remain a priority. The 

present invention discloses the ability of 

gene-based priming with influenza 

hemagglutinin (HA) to prime for an 

increase in titer and cross-reactivity of 

the neutralizing antibody response after 

inactivated influenza virus vaccine 

boost. After priming with a DNA 

vaccine encoding HA from a H1N1 

strain, boosting with a seasonal 

influenza vaccine containing this 


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28258 Federal Register / Vol. 74, No. 113 / Monday, June 15, 2009 / Notices 

inactivated virus stimulated a 100-fold 

increase in the titer of H1 neutralizing 

antibodies. Of note, this combination 

immunization, in contrast to either 

component alone, elicited heterotypic 

neutralizing antibodies against a H5N1 

strain. Similar priming was also 

observed with a DNA vaccine encoding 

an HA from a H5N1 strain, with the 

H5N1 subvirion vaccine boost. These 

results show that gene-based priming 

prior to vaccinating with the traditional 

influenza vaccine boost induced 

humoral immunity against different 

subtypes of influenza viruses that 

increases the potency and breadth of the 

neutralizing antibody response. 

Applications: This invention provides 

a vaccine strategy for potentially 

controlling influenza epidemics, 

including avian flu should it cross over 

to humans, and seasonal flu strains. 

Development Status: Animal studies 

Inventors: Gary J. Nabel and Chih-jen 

Wei (VRC/NIAID) 

Patent Status: U.S. Provisional 

Application No. 61/100,621 filed 26 

Aug 2008, entitled ‘‘DNA Prime/ 

Inactivated Vaccine Boost Immunization 

to Influenza Virus’’ (HHS Reference No. 

E–341–2008/0–US–01). 

Related Technology: U.S. Patent No. 

7,094,598 issued 22 Aug 2006 and 

associated foreign rights (proprietary 

expression system with CMV/R 

promoter) (HHS Reference No. E–241– 

2001). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Cristina 

Thalhammer-Reyero, PhD, MBA; 301– 

435–4507; thalhamc@mail.nih.gov. 

Use of MMP–8 as a Prognostic Marker 

for Melanoma 

Description of Technology: Cutaneous 

malignant melanoma is the most 

common fatal skin cancer, and the 

incidence of this disease increases each 

year. The average survival time for 

patients diagnosed with malignant 

melanoma is less than ten months. 

Consequently, it is important to identify 

and understand genetic alterations 

leading to malignant melanoma so that 

new treatments strategies can be 

developed. 

Matrix Metalloproteinases (MMPs) 

have been associated with increased 

metastasis and several small molecule 

inhibitors have been developed as 

potential anticancer agents. 

Unfortunately, these inhibitors have 

been largely unsuccessful despite the 

research suggesting otherwise and it is 

clear that additional analyses are 

warranted. The NIH inventors have 

recently performed a mutational 

analysis of the MMP gene family in 

human cutaneous metastatic melanoma 

and have identified several novel 

somatic mutations, most notably 

mutations in MMP–8. This invention 

provides methods of identifying specific 

inhibitors to MMP–8 that could be used 

to treat patients with MMP–8 mutations. 

It also provides methods for predicting 

the prognosis of patients with MMP–8 

mutations. Thus, this invention could 

not only help identify the roles of 

specific MMPs in melanoma, but also 

help further the development MMP 

inhibitors to treat melanoma patients. 

Applications: 

• Diagnostic array for the detection of 

MMP–8 mutations. 

• Method of predicting the prognosis 

of melanoma patients. 

• Method of identifying MMP–8 

activators as therapeutic agents to treat 

malignant melanoma patients. 

Development Status: The technology 

is currently in the pre-clinical stage of 

development. 

Market: 

• Approximately 160,000 new cases 

of melanoma are diagnosed worldwide 

each year. Malignant melanoma is 

increasing faster than any other cancer. 

• Melanoma is the most prevalent 

cancer among women between the ages 

of 25–29 and the second most prevalent 

cancer among woman ages 30–34. 

• Cutaneous malignant melanoma is 

the most serious form of skin cancer and 

accounts for about 75% of all skin 

cancer deaths. 

• One person dies from melanoma 

every hour. 

Inventors: Yardena R. Samuels 

(NHGRI). 

Publication: LH Palavalli et al: 

Analysis of the matrix metalloproteinase 

family reveals that MMP8 is often 

mutated in melanoma. Nat Genet 2009 

May;41(5):518–520. 

Patent Status: U.S. Provisional 

Application No. 61/198,384 filed 03 

Nov 2008 (HHS Reference No. E–273– 

2008/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Human Genome Research 

Institute’s Cancer Genetics Branch is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, and/or commercialize 

this newly identified candidate 

melanoma diagnostic and prognostic 

marker as well as to identify and 

develop possible MMP–8 activators for 

testing as possible anti-melanoma 

agents. Please contact NHGRI’s 

Technology Development Coordinator 

(TDC) Claire T. Driscoll at 

cdriscol@mail.nih.gov for more 

information. 

Methods for Preparing Immunogenic 

Conjugates 

Description of Technology: This 

technology describes improved methods 

of synthesis for conjugate vaccines, 

specifically those against anthrax. The 

inventors’ method is designed to 

synthesize immunogenic conjugates 

(i.e., a protein carrier conjugated to a 

bacterially derived synthetic peptide) 

that are prepared at a physiological pH, 

not reversible and do not require 

reduction with borohydride. The 

inventors’ method comprises reacting 

the protein carrier with a dihydrazide, 

and the peptide with a benzaldehyde, or 

the reverse, then reacting the 

derivatized peptide and the derivatized 

protein with each other to form an 

immunogenic conjugate. 

Application: Methods for making 

conjugate vaccines and reagents. 

Advantages: More efficient 

conjugation methods, higher conjugate 

yields. 

Development Status: Vaccine 

candidates have been synthesized and 

preclinical studies have been 

performed. 

Inventors: Rachel Schneerson 

(NICHD), Joanna Kubler-Kielb (NICHD), 

Fathy Majadly (NICHD), Stephen Leppla 

(NIAID), John Robbins (NICHD), Darrel 

Liu (NICHD), Joseph Shiloach (NIDDK). 

Related Publication: J Kubler-Kielb et 

al. Additional conjugation methods and 

immunogenicity of Bacillus anthracis 

poly-gamma-D-glutamic acid-protein 

conjugates. Infect Immun. 2006 

Aug;74(8):4744–4749. 

Patent Status: U.S. Patent Application 

No. 11/005,851 filed 06 Dec 2004 (HHS 

Reference No. E–040–2005/0–US–01); 

Foreign Rights Available. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Peter A. Soukas, 

J.D.; 301–435–4646; 

soukasp@mail.nih.gov. 

Dated: June 8, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–13943 Filed 6–12–09; 8:45 am] 

BILLING CODE 4140–01–P 


pwalker on PROD1PC71 with NOTICES