Federal Register / Vol. 73, No. 168 / Thursday, August 28, 2008 / Notices 50827 

TABLE 1.—LIST OF SAFETY AND EFFECTIVENESS SUMMARIES FOR APPROVED PMAS MADE AVAILABLE FROM JANUARY 1, 

2008, THROUGH MARCH 31, 2008—Continued 

PMA No. 

Docket No. Applicant TRADE NAME Approval Date 

P070001 

FDA–2008–M–0100 (formerly 

2008M–0013) 

Synthes Spine, Inc. PRODISC–C TOTAL DISC PEPLACEMENT December 17, 2007 

P050045 

FDA–2008–M–0182 

Dako Denmark a/s DAKO TOP2A FISH PHARM DX KIT January 11, 2008 

P060033 

FDA–2008–M–0109 

Medtronic Vascular ENDEAVOR ZOTAROLIMUS-ELUTING CORONARY 

STENT ON THE OVER THE WIRE (OTW), RAPID 

EXCHANGE (RX), OR MULTI-EXHANGE II (MX2) 

STENT DELIVERY SYSTEM 

February 1, 2008 

II. Electronic Access 

Persons with access to the Internet 

may obtain the documents at http:// 

www.fda.gov/cdrh/pmapage.html. 

Dated: August 14, 2008. 

Daniel G. Schultz, 

Director, Center for Devices and Radiological 

Health. 

[FR Doc. E8–19907 Filed 8–27–08; 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. 

Identification and Characterization of 

Folliculin-Interacting Protein 2, FNIP2 

Description of Technology: The 

invention describes the identification 

and characterization of a FNIP1 

homolog, folliculin-interacting protein 2 

(FNIP2), that interacts with folliculin, 

the protein encoded by the FLCN gene, 

which is responsible for the Birt-HoggDube’ (BHD) syndrome. BHD is a 

dermatologic disorder associated with 

an increased risk for developing renal 

cancer, spontaneous pneumothorax and 

lung cysts. FNIP2 binds to the 

C-terminus of folliculin and to AMPK. 

Importantly, FNIP2 expression was 

elevated in renal tumors seen in BDH 

patients. This finding suggests that 

FNIP2 may serve as a biomarker for 

BHD. 

Applications: Research tool; 

Diagnostic applications. 

Advantages: Could facilitate the 

development of therapeutic drugs to 

treat the skin lesions and renal tumors 

that develop in BHD patients. 

Development Status: Early stage of 

development. 

Market: Dermatologic products; 

Diagnostic applications. 

Inventors: Laura S. Schmidt et al. 

(NCI). 

Relevant Publication: H Hasumi et al. 

Identification and characterization of a 

novel folliculin-interacting protein 

FNIP2. (2008) Gene, in press. 

Patent Status: HHS Reference No. E–

213–2008/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

biological materials licensing only. 

Licensing Contact: John Stansberry, 

Ph.D.; 301–435–5236; 

stansbej@mail.nih.gov. 

Collaborative Research Opportunity: 

The Urologic Oncology Branch at the 

National Cancer Institute is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize detection methods 

specific for FNIP2 to be used to screen 

FNIP2 as a biomarker for renal cancer. 

This may include development of an 

efficient FNIP2 antibody which does not 

cross react with FNIP1 for 

immunhistochemical screening of renal 

tumors for FNIP2 expression. Please 

contact John D. Hewes, Ph.D. at 301–

435–3121 or hewesj@mail.nih.gov for 

more information. 

Immunotoxins Made With Modified 

Cholix Toxin and Uses Thereof 

Description of Technology: 

Immunotoxins are chimeric molecules 

comprising an antibody targeting moiety 

and a toxin domain capable of killing a 

cell. Immunotoxins represent an 

important therapeutic tool for the 

treatment of cancer because they are 

able to specifically target cancer cells 

while ignoring healthy cells. The major 

drawback to immunotoxins is the 

development of neutralizing antibodies 

against the toxin portion of the 

immunotoxin. Many patients treated 

with Pseudomonas exotoxin A (PE) 

based immunotoxins develop 

neutralizing antibodies after the first 

administration. As a result, only one 

effective administration of a PE-based 

immunotoxin is often possible. 

NIH inventors have created a novel 

immunotoxin, where the toxin portion 

is a truncated Cholera exotoxin (cholix 

toxin). Although cholix toxin retains 

strong functional and structural 

similarity to PE, neutralizing antibodies 

to PE do not affect the truncated cholix 

toxin. As a result, cholix toxin-based 

immunotoxins are of potential utility 

after a patient has developed 

neutralizing antibodies to PE. The 

ability to deliver two rounds of 

immunotoxins to a patient will increase 

the successful treatment of various 

diseases, including cancer. 

Application: 


jlentini on PROD1PC65 with NOTICES
50828 Federal Register / Vol. 73, No. 168 / Thursday, August 28, 2008 / Notices 

• Used as an alternative toxin moiety 

in immunotoxins. 

• Immunotoxins can be used for the 

treatment of various cancers, depending 

on the targeting antibody. 

• Can be used in tandem 

immunotoxin therapy with 

immunotoxins having distinct toxin 

moiety, such as PE-based 

immunotoxins. 

Advantages: 

• Cholix toxin-based immunotoxins 

are not affected by neutralizing 

antibodies to by PE-based 

immunotoxins, permitting multiple 

rounds of immunotoxin therapy. 

• Ability to target specific cells by 

choosing specific targeting antibodies. 

Inventors: David J. FitzGerald and 

Robert J. Sarnovsky (NCI). 

Patent Status: U.S. Provisional 

Application No. 61/058,872 filed 04 Jun 

2008 (HHS Reference No. E–194–2008/ 

0–US–01). 

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, CCR, 

Laboratory of Molecular Biology is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

immunotoxins composed of cholera 

exotoxin. Please contact John D. Hewes, 

Ph.D. at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Large Semi-Synthetic Human Antibody 

Domain Fragment Library 

Description of Technology: Human 

monoclonal antibodies are important for 

the development of inhibitors, vaccines, 

diagnostic and research tools. 

Previously a large non-immune human 

antibody library (15 billion (15 × 109) 

clones) was constructed from the lymph 

nodes, spleen and peripheral blood 

lymphocytes of 50 donors. One 

antibody, isolated from this library, 

includes a stop codon in the light chain 

but was still expressed and included a 

functional heavy chain. The VH domain 

exhibits high levels of expression and 

high solubility even in the absence of a 

light chain variable domain. This VH 

domain was used as a framework to 

construct a large human VH domain 

library (25 billion clones) by grafting 

naturally occurring complementarity 

determining regions (CDRs) from other 

human antibody libraries and randomly 

mutating one of the CDRs. This library 

has been used internally for selecting 

anti-HIV antibodies, viruses of 

biodefense interest and cancer-related 

antigens and is available for licensing as 

a biological material. Several highaffinity binders have already been 

identified. 

The antibodies generated from this 

library are small (e.g., about more than 

14 kDa), highly stable and can be 

expressed at high levels as monomers. 

The library permits the isolation of 

antibodies with favorable properties: 

affinity, stability, solubility, high levels 

of expression (at low cost), low rejection 

rates and low toxicity. 

Applications: Antibody discovery; 

Therapeutics; Diagnostics; Research 

Materials. 

Inventors: Dimiter S. Dimitrov and 

Weizao Chen (NCI). 

Relevant Publications: 

1. W Chen, Z Zhu, Y Feng, X Xiao, DS 

Dimitrov. Construction of a large phagedisplayed human antibody domain 

library with a scaffold based on a newly 

identified highly soluble, stable heavy 

chain variable domain. J Mol Biol 

(2008), in press. 

2. P Jirholt et al. Exploiting sequence 

space: Shuffling in vivo formed 

complementarity determining regions 

into a master framework. Gene. 1998 Jul 

30;215(2):471–476. 

3. Y Reiter et al. An antibody singledomain phage display library of a native 

heavy chain variable region: Isolation of 

functional single-domain VH molecules 

with a unique interface. J Mol Biol. 1999 

Jul 16;290(3):685–698. 

4. E So ̈derlind et al. Recombining 

germline-derived CDR sequences for 

creating diverse single framework 

antibody libraries. Nat Biotechnol. 2000 

Aug 18;18(8):852–856. 

5. LJ Holt et al. Domain antibodies: 

Proteins for therapy. Trends Biotechnol. 

2003 Nov;21(11):484–490. 

6. L Riechmann and S Muyldermans. 

Single domain antibodies: Comparison 

of camel VH and camelised human VH 

domains. J Immunol Methods. 1999 Dec 

10;231(1–2)25–38. 

Patent Status: HHS Reference No. E–

037–2008/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Michael A. 

Shmilovich, Esq.; 301/435–5019; 

shmilovm@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Nanobiology Program is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize Large Semi-Synthetic 

Human Antibody Domain Library. 

Please contact John D. Hewes, PhD at 

301–435–3121 or hewesj@mail.nih.gov 

for more information. 

Methods of Preventing Tissue Ischemia 

Description of Technology: Nitric 

oxide (NO) plays an important role as a 

major intrinsic vasodilator, and 

increases blood flow to tissues and 

organs. Disruption of this process leads 

to peripheral vascular disease, ischemic 

heart disease, stroke, diabetes, and 

many more significant diseases. 

Researchers at the NIH have 

discovered that the matrix protein 

thrombospondin-1 blocks the beneficial 

effects of NO, and prevents it from 

dilating blood vessels and increasing 

blood flow to organs and tissues. 

Additionally, the inventors discovered 

that this regulation requires interaction 

with thrombospondin-1’s cell receptor 

CD47. Murine studies revealed that, in 

the presence of NO, genetically altered 

mice, lacking either thrombospondin-1 

or CD47, showed dramatically improved 

blood flow and tissue oxygenation. The 

inventors have also shown in both mice 

and pigs that by targeting 

thrombospondin-1 and/or CD47, blood 

flow can be dramatically increased to 

ischemic tissues. The same therapeutics 

also were found to protect tissues from 

ischemia/reperfusion injury. 

Available for licensing and 

commercial development are: 

• Compositions and methods of 

treating tissue ischemia and/or tissue 

damage due to ischemia, increasing 

blood vessel diameter, blood flow and 

tissue perfusion in the presence of 

vascular disease including peripheral 

vascular disease, atherosclerotic 

vascular disease and stroke. 

• Compositions and methods for 

decreasing blood flow as in the case of 

cancer through mimicking the effects of 

thrombospondin-1 and CD47 on blood 

vessel diameter and blood flow. 

Applications: 

• Potential therapeutics for precise 

regulation of blood flow to tissues and 

organs. 

• Efficient methods to increase tissue 

survival under conditions of trauma and 

surgery. 

• Efficient methods for the treatment 

of elderly subjects using agents that 

affect thrombospondin-1 and CD47 and 

thereby affect tissue perfusion. 

• Methods for treatment of ischemia/ 

reperfusion injury as associated with 

transplant surgery. 

Market: 

• People with ischemic disease are at 

increased risk of heart attack 

(myocardial infarction), stroke and 

peripheral vascular disease (PVD). 

Ischemic heart disease attributes to 


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Federal Register / Vol. 73, No. 168 / Thursday, August 28, 2008 / Notices 50829 

more deaths, with 24 percent in the 

U.S., than any other cause. 

• Cerebral ischemia is the third 

leading cause of death after heart 

diseases and cancer. 

• Decreased blood flow underlies a 

significant number of chronic diseases 

that account for the majority of 

morbidity and mortality for elderly 

adults in this country. 

• Cancer patients and traumatic 

injury victims requiring reconstructive 

surgery. 

• Burn patients requiring skin 

transplants. 

• Organ transplant patients. 

Development Status: Early-stage of 

development (in vivo data available in 

mice and pigs). 

Inventors: Jeff S. Isenberg et al. (NCI). 

Patent Status: PCT Application No. 

PCT/US2007/080647 filed 5 Oct 2007, 

which published as WO 2008/060785 

on 22 May 2008 (HHS Reference No. 

E–227–2006/5–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Charlene A. 

Sydnor, PhD; 301–435–4689; 

sydnorc@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute Center for 

Cancer Research, Laboratory of 

Pathology is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize therapeutics targeting 

CD47 or thrombospondin-1. Please 

contact John D. Hewes, PhD at 301–435–

3121 or hewesj@mail.nih.gov for more 

information. 

Total Synthesis of Northebaine, 

Normorphine, Noroxymorphone 

Enantiomers and Derivatives via N-Nor 

Intermediates 

Description of Technology: A new 

synthetic process has been found in 

which nordihydrocodeinone, an early 

intermediate in the total synthesis of 

codeine and related compounds, is 

easily formed into a number of N-nor 

compounds. These N-nor compounds 

can be used as precursors in the 

formation of narcotics, narcotic 

antagonists, or narcotic agonistantagonists. 

The manufacture of drugs of this type, 

such as northebaine or normorphine, 

can now be done without the use of 

thebaine as starting material. The 

syntheses have fewer steps than 

previous methods, and also have high 

yields. In addition, very significant 

simplification of existing thebaine based 

processes for the manufacture of opiates 

can be expected. 

Applications: Potential new 

methodology for the synthesis of 

intermediates for drugs including 

naloxone, naltrexone, percodan and 

nalbuphine. 

Market: 

• More than a quarter of Americans 

suffer daily pain, a condition that costs 

the U.S. about $60 billion a year in lost 

productivity. 

• Americans spent about $2.6 billion 

in over-the-counter pain medications 

and another nearly $14 billion on 

outpatient analgesics in 2004. 

• Worldwide, nearly 300 million 

people are believed to suffer from 

chronic pain. 

Inventors: Kenner C. Rice et al. 

(NIDDK) 

Patent Status: 

HHS Reference No. E–012–1986/1—

• Australian Patent 642447 issued 15 

Feb 1994. 

• Japanese Patent 2694156 issued 12 

Sept 1997. 

• Canadian Patent 2067200 issued 30 

Jun 1998. 

• European Patent 0496830 issued 31 

Mar 1999 in Austria, Switzerland, 

Germany, Denmark, Greece, 

Luxembourg, Spain, Belgium, The 

Netherlands, Sweden, France, Italy and 

United Kingdom. 

HHS Reference No. E–012–1986/2—

• United States Patent 5,668,285 

issued 16 Sept 1997. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Charlene A. 

Sydnor, PhD; 301–435–4689; 

sydnorc@mail.nih.gov. 

Dated: August 18, 2008. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E8–19914 Filed 8–27–08; 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. 

Botulinum Toxoid 

Description of Technology: 

Vaccination is the only approach that 

can be used to prevent botulism. A 

pentavalent botulinum toxoid 

comprised of formalin-detoxified 

botulinum neurotoxin (BoNT) BoNT/A, 

B, C, D and E hemagglutinin (Hmg) 

complexes has been used to immunize 

laboratory and military personnel since 

1961, but this has never been licensed 

by the United States Food and Drug 

Administration (FDA). Vaccination 

immediately after toxin exposure has no 

protective benefit because the immune 

response is relatively slow compared to 

the rate of intoxication. The only 

treatment that is available upon 

intoxication is antibody therapy, which 

entails the injection of equine-derived 

botulinum antitoxin (BAT) or humanderived botulinum immunoglobulin 

(BIG) to remove toxin from the blood. 

Antibody therapy does not alleviate 

symptoms of botulism, but can limit the 

amount of toxin that enters nerve 

terminals and thus may lessen the 

severity and shorten the duration of 

paralysis. 

Since a vaccine can be used to either 

protect a human population or produce 

a BAT or BIG product, it is important to 

have reliable methods to evaluate the 

antigenic integrity of botulinum 

vaccines. An in vitro assay that can 

serve in this capacity would be useful 

for evaluating the consistency of the 

antigen throughout the manufacturing 

process, as well as generating data that 

may reduce in vivo testing. 

Available for licensing are a variety of 

new toxoids useful as botulinum 

vaccine antigens, for BAT or BIG 

production, or for development of tests 

to evaluate antigenicity of botulinum 

vaccines. The toxoids of the invention 

are derived from the Serotype A and B 

150 kDa neurotoxin proteins. The 

resulting toxoids are antigenically 

identical to the native toxin as measured 

by inhibition ELISA in spite of showing 


jlentini on PROD1PC65 with NOTICES