38442 Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 

21R or anti-IL–21 monoclonal 

antibodies has been demonstrated to 

reduce TH2 immune responses 

associated with fibrosis in animal 

models. 

The causes of chronic tissue fibrosis 

are diverse and the market for a 

therapeutic that targets fibrosis is large. 

Fibrosis is associated with diverse 

causes which include: genetic diseases 

(such as cystic fibrosis); autoimmune 

diseases (such as scleroderma); chronic 

viral infections (such as hepatitis), 

parasitic infections (such as 

schistosomiasis); and occupational 

exposures to causative agents (such as 

asbestosis). Additionally, many cases of 

tissue fibrosis are idiopathic. 

Application: The treatment or 

amelioration of tissue fibrosis. 

Inventors: Thomas A. Wynn (NIAID); 

Deborah A Young; Mary Collins; and 

Michael J. Grusby. 

Relevant Publication: J Pesce et al. 

The IL–21 receptor augments Th2 

effector function and alternative 

macrophage activation. J Clin Invest 

2006 Jul;116(7):2044–2055. 

Patent Status: U.S. patent application 

no. 11/402,885 (priority date April 14, 

2005) and international patent 

applications including European patent 

application No. EP06/0750009 (HHS 

Reference No. E–250–2005). 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Surekha Vathyam, 

Ph.D.; 301–435–4076; 

vathyams@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Allergy and 

Infectious Diseases is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this invention. Please 

contact Nicole Mahoney at 301–435– 

9017 or mahoneyn@niaid.nih.gov for 

more information. 

Use of Discoidin Domain Receptor 1 

(DDR1) and Agents That Affect the 

DDR1/Collagen Pathway 

Description of Invention: Dendritic 

cells (DCs) are pivotal antigenpresenting cells for initiation of an 

immune response. Indeed, dendritic 

cells provide the basis for the 

production of an effective immune 

response to a vaccine, particularly for 

antigens wherein conventional 

vaccination is inadequate. DCs are also 

important in the production on an 

immune response to tumor antigens. 

The present invention discloses 

methods of using the receptor tyrosine 

kinase discoidin domain receptor 1 

(DDR1) to facilitate the maturation/ 

differentiation of DCs or macrophages. 

Activating agents of DDR1 may be 

useful in the induction of highly potent, 

mature DCs or highly differentiated 

macrophages from DC precursors, such 

as monocytes. Use of this method may 

enhance the antigen presenting 

capabilities of the immune system, 

leading to a more effective overall 

immune response. 

Inventor: Teizo Yoshimura (NCI). 

Relevant Publications 

1. H Kamohara et al. Discoidin 

domain receptor 1 isoform-a (DDR1a) 

promotes migration of leukocytes in 

three-dimensional collagen lattices. 

FASEB J. 2001 Dec;15(14):2724–2726. 

2. W Matsuyama et al. Interaction of 

discoidin domain receptor 1 isoform b 

(DDR1b) with collagen activates p38 

mitogen-activated protein kinase and 

promotes differentiation of 

macrophages. FASEB J. 2003 

Jul;17(10):1286–1288. 

Patent Status: U.S. Application No. 

10/507,385 filed 09 Sep 2004 (HHS 

Reference No. E–083–2002/2–US–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

Ph.D.; 301–594–6565; 

tongb@mail.nih.gov. 

Dated: July 28, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–18504 Filed 7–31–09; 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. 

A Tumorigenic MEF/3T3 Tet-Off Mouse 

Fibroblast Cell Line Stably Transfected 

With a T7–Tagged Srp20 Expression 

Construct (pJR17) 

Description of Technology: 

Alternative RNA splicing is a means by 

which the human genome can produce 

many more proteins from the genes 

available. It is emerging that aberrations 

in alternative RNA splicing contributes 

to the development of cancers. SRp20 is 

a cellular splicing factor that is involved 

in the process of alternative splicing of 

RNA. Investigators at the National 

Cancer Institute (NCI), National 

Institutes of Health (NIH) have 

discovered that SRp20 is overexpressed 

in many types of cancer and 

furthermore promotes the induction and 

maintenance of tumor cell growth. This 

was demonstrated in part by 

engineering a non-tumorigenic cell to 

become tumorigenic in mice by 

overexpressing SRp20. 

Research Material available for 

licensing is a tumorigenic MEF/3T3 tetoff mouse fibroblast cell line stably 

transfected with a T7-tagged SRp20 

expression construct (pJR17) that is 

under the transcriptional control of 

tetracycline. 

Applications: Use in pre-clinical 

development of therapeutic approaches 

to cancer that target aberrant alternative 

RNA splicing. 

Advantages: Transcriptional control 

of expression using Tet-off system; 

Availability of stably transfected cell 

line saves time and effort for other 

investigators. 

Market: Research Tool. 

Development Status: Ready to use. 

Inventors: Zhi-Ming Zheng and Rong 

Jia (NCI). 

Publications: Manuscript in 

preparation. 

Patent Status: HHS Reference No. E– 

229–2009/0—Research Material. Patent 

protection is not being sought for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sabarni Chatterjee, 

Ph.D.; 301–435–5587; 

chatterjeesa@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Center for 

Cancer Research, HIV and AIDS 

Malignancy Branch, is seeking 

statements of capability or interest from 


sroberts on DSKD5P82C1PROD with NOTICES
Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 38443 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize A Tumorigenic MEF/3T3 

Tet-Off Mouse Fibroblast Cell Line 

Stably Transfected with a T7–Tagged 

Srp20 Expression Construct (pJR17). 

Please contact John D. Hewes, Ph.D. at 

301–435–3121 or hewesj@mail.nih.gov 

for more information. 

Truncated Methanocarba Adenosine 

Derivatives as A3 Adenosine Receptor 

Antagonists 

Description of Technology: Novel A3

adenosine antagonists available for 

licensing. A3 receptors are particularly 

highly expressed in inflammatory cells, 

making it a potentially desirable target 

for inflammatory diseases. This 

technology relates to highly specific 

antagonists and partial agonists of A3

adenosine receptors, which are 

negatively coupled to adenylate cyclase 

and have been broadly implicated in 

inflammation, cardiovascular disease, 

and cancer. Further, A3 adenosine 

receptors have been implicated in 

allergies, asthma, and chronic 

obstructive pulmonary disease. 

Advantages: There are four known 

subtypes of adenosine receptors (A1,

A2A, A2B, and A3). All are positively or 

negatively linked to cAMP, but have 

different distributions and different 

therapeutic potentials. In particular, the 

use of A1 and A2 selective ligands has 

been limited by the ubiquity of 

expression of the receptors throughout 

the body and the resultant side effects. 

On the other hand, high levels of A3

receptor expression are limited to the 

CNS, testes, and the immune system. 

Thus, A3 receptors represent a 

potentially highly specific target for 

treating related diseases. 

Inventor: Kenneth A. Jacobson 

(NIDDK). 

Related Publication: A Melman, B 

Wang, BV Joshi, ZG Gao, S de Castro, CL 

Heller, SK Kim, LS Jeong, KA Jacobson. 

Selective A3 adenosine receptor 

antagonists derived from nucleosides 

containing a bicyclo[3.1.0]hexane ring 

system. Bioorg Med Chem. 2008 Sep 

15;16(18):8546–8556. 

Patent Status: U.S. Provisional 

Application No. 61/085,588 filed 01 

Aug 2008 (HHS Reference No. E–285– 

2008/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Steve Standley, 

Ph.D.; 301–435–4074; 

sstand@mail.nih.gov 

Collaborative Research Opportunity: 

The NIDDK, Laboratory of Bioorganic 

Chemistry is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize A3 adenosine receptor 

antagonists. Please contact Kenneth A. 

Jacobson, Ph.D. at 

kajacobs@helix.nih.gov or the NIDDK 

Office of Technology Transfer and 

Development at 301–451–3636 for more 

information. 

Novel Proteins From the Sand Fly 

Lutzomyia longipalpis Are Potent 

Inhibitors of Complement Activity 

Description of Technology: This 

invention relates to the discovery that 

five proteins from the salivary glands of 

Lutzomyia longipalpis, LJM04, LJM11, 

LJM19, LJM26, and LJL143, have anticomplement activity. These proteins 

demonstrate potent inhibition of both 

the classical and alternative pathways 

for complement activation. All proteins, 

excluding LJM19, were shown to bind 

and inhibit the C3b molecule, thus 

inactivating an integral component of 

the complement pathway. 

The complement system is a very 

important line of defense against 

pathogens, and is involved in many 

pathologies and syndromes affecting 

human health. It is therefore envisioned 

that these five novel proteins may be 

used to treat conditions where the 

complement system is involved 

including lupus erythematosus, juvenile 

arthritis, and complications associated 

with cardiac surgery and hemodialysis. 

Applications: 

• Potent inhibition of complement 

activity. 

• Treatment of diseases involving the 

complement system. 

Development Status: Early Stage. 

Inventors: Jesus G. Valenzuela et al. 

(NIAID). 

Relevant Publication: RR Cavalcante, 

MH Pereira, NF Gontijo. Anticomplement activity in the saliva of 

phlebotomine sand flies and other 

haematophagous insects. Parasitology 

2003 Jul;127(Pt 1):87–93. 

Patent Status: U.S. Provisional 

Application No. 61/142,098 filed 31 Dec 

2008 (HHS Reference No. E–205–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James, 

PhD; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Potent Anti-Coagulant Activity of a 

Novel Protein From the Sand Fly 

Lutzomyia longipalpis 

Description of Technology: The 

salivary gland lysates of Lutzomyia 

longipalpis, the New World sand fly and 

main vector for visceral leishmaniasis, 

contain an anti-coagulant protein that 

helps the fly complete its blood meal. 

This invention relates to the 

identification of LJL143, a salivary gland 

protein of L. longipalpis, as a specific 

inhibitor of coagulation factor Xa. 

LJLl43 is secreted in the saliva of L. 

longipalpis and exerts its effects by 

tightly binding the catalytic site of factor 

Xa. By directly binding the catalytic 

site, it is believed that the potent anticoagulant activity of LJL143 will be 

accompanied by reduced side effects 

compared to anti-coagulant drugs that 

rely on activating serine proteases. 

LJL143 has a novel sequence with no 

reported homology in the gene bank, 

and is the first anti-coagulant factor 

identified in sand flies. 

LJLl43 may be used for inhibiting 

factor Xa activity in vivo or as a 

prototype for designing specific 

inhibitors of factor Xa. Because of its 

high specificity, LJLl43 may be used as 

an anti-coagulant in a number of procoagulant diseased states including 

deep venous thrombosis, coronary 

artery disease, non-hemorrhagic stroke, 

and unstable angina with potentially 

reduced side effects. 

Applications: 

• Safe and effective anti-coagulant for 

therapeutic use. 

• Treatment of several conditions 

such as deep venous thrombosis, 

coronary artery disease, nonhemorrhagic stroke, and unstable 

angina. 

Advantages: May be safer than other 

important blood thinning drugs such as 

Warfarin. 

Development Status: Early Stage. 

Market: Predicted $7.4 billion anticoagulant market by 2016. 

Inventors: Jesus G. Valenzuela et al. 

(NIAID). 

Publication: JG Valenzuela, M 

Garfield, ED Rowton, VM Pham. 

Identification of the most abundant 

secreted proteins from the salivary 

glands of the sand fly Lutzomyia 

longipalpis, vector of Leishmania 

chagasi. J Exp Biol. 2004 Oct;207(Pt 

21):3717–3729. 

Patent Status: U.S. Provisional 

Application No. 61/142,107 filed 31 Dec 

2008 (HHS Reference No. E–204–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey A. James, 

PhD; 301–435–5474; 

jeffreyja@mail.nih.gov. 

Novel Dopamine Receptor Ligands as 

Therapeutics for Central Nervous 

System Disorders 

Description of Technology: The 

dopamine D3 receptor subtype is a 

member of the dopamine D2 subclass of 

receptors. These receptors have been 


sroberts on DSKD5P82C1PROD with NOTICES
38444 Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 

implicated in a number of CNS 

disorders, including psychostimulant 

abuse, psychosis and Parkinson’s 

disease. Compounds that bind with high 

affinity and selectivity to D3 receptors 

can not only provide important tools 

with which to study the structure and 

function of this receptor subtype, but 

may also have therapeutic potential in 

the treatment of numerous psychiatric 

and neurologic disorders. 

The 4-phenylpiperazine derivatives 

are an important class of dopamine D3 

selective ligands. However, due to their 

highly lipophilic nature, these 

compounds suffer from solubility 

problems in aqueous media and reduced 

bioavailability. To address this problem, 

a process was designed to introduce 

functionality into the carbon chain 

linker of these compounds. Compared to 

currently available dopamine D3 

receptor ligands, the resulting 

compounds show improved 

pharmacological properties and D3 

selectivities but due to their more 

hydrophilic nature, these derivatives are 

predicted to have improved water 

solubility and bioavailability. 

Applications: 

• Therapeutics for a variety of 

psychiatric and neurologic disorders 

• Research tools to study D3 receptor 

structure and function 

Advantages: 

• Improved pharmacological 

properties and selectivity over existing 

dopamine D3 receptor ligands 

• Hydrophilic nature likely to lead to 

improved water solubility and 

bioavailability 

Development Status: Pre-clinical 

discovery. 

Further R&D Needed: 

• Evaluate selected compounds in 

animal models of drug abuse, psychosis, 

obesity and Parkinson’s disease. 

• Design and synthesize novel, 

functionalized analogs using both 

classical and computational drug design 

to improve D3 receptor affinity and 

selectivity. 

• Evaluate compounds for binding in 

D3 and D2 receptor expressing cell lines 

and in in vitro functional assays. 

• Correlate in vitro binding affinities 

with in vivo function in rats and 

monkeys and evaluate compounds in 

knockout mice models. 

• Pursue PET and SPECT imaging 

agents by radiolabel of D3 ligands and 

evaluation in rats and non-human 

primates. 

Inventors: Amy H. Newman (NIDA), 

Peter Grundt (NIDA), Jianjing Cao 

(NIDA), et al. 

Patent Status: PCT Application No. 

Pct/US2007/71412 filed 15 Jun 2007, 

which published as WO 2008/153573 

on 18 Dec 2008 (HHS Reference No. E– 

128–2006/0–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Charlene Sydnor, 

PhD; 301–435–4689; 

sydnorc@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute on Drug Abuse’s 

Medications Discovery Research Branch 

is seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 4- 

phenylpiperazine derivatives as 

dopamine D3 selective ligands. Please 

contact Vio Conley, MS at 301–435– 

2031 or conleyv@mail.nih.gov for 

additional information. 

High-Yield Methods of Producing 

Biliverdin 

Description of the Technology: This 

invention describes methods of making 

high yields of biliverdin, the 

pharmaceutical compositions of 

biliverdin made using that process, and 

methods of using the compositions 

therapeutically. 

In reaction to a wide range of cellular 

stresses, hemoglobin is naturally 

metabolized to biliverdin, which is then 

quickly metabolized to bilirubin, a bile 

pigment, through a highly conserved set 

of enzymes. Both bilirubin and 

biliverdin are normally processed for 

rapid excretion, and excessive serum 

levels of bilirubin have known toxic 

effects (most notably jaundice). 

Surprisingly, research in the past 

decade has shown that decreasing 

serum levels correlate inversely with the 

prognosis of various disorders, such as 

ischemia/reperfusion injuries, 

atherosclerosis, organ transplantation, 

and several autoimmune diseases. 

Indeed, in animal-model studies, 

inducing a mild case of jaundice 

actually improved outcome. 

Unfortunately, bilirubin is relatively 

insoluble, and so is not a practical 

pharmaceutical itself. 

Biliverdin has lower direct toxicity 

and substantially greater solubility than 

bilirubin, and also appears to have some 

direct therapeutic effects similar to 

bilirubin. Accordingly, biliverdin has 

been widely studied lately. Generating 

high yields of pure biliverdin is 

difficult, however, because any system 

with the enzymes to break down 

hemoglobin also has enzymes 

converting biliverdin to bilirubin. The 

inventors have created a system of 

generating microorganisms (yeast) 

lacking the enzymes that break 

biliverdin down to bilirubin. 

Applications: Production of biliverdin 

for immunomodulatory and 

cytoprotective therapy (or adjuvant) in 

any condition involving an overactive 

immune response. 

Advantages: 

• High yield of biliverdin with low 

contamination of bilirubin. 

• Produces only active isomers of 

biliverdin. 

• Unlike prior methods, new method 

uses starting material that is 

inexpensive and plentiful. 

Development Status: Successful 

generation of Candida albicans with 

biliverdin-generating system. 

Inventors: Michael L. Pendrak and 

David D. Roberts (NCI). 

Patent Status: HHS Reference No. E– 

040–2004/0—Issued U.S. Patent 

7,504,243; Pending U.S. Application 12/ 

364,054 (divisional, filed 02 Feb 2009). 

Relevant Publication: ML Pendrak et 

al. Heme oxygenase in Candida albicans 

is regulated by hemoglobin and is 

necessary for metabolism of exogenous 

heme and hemoglobin to alphabiliverdin. J Biol Chem. 20 Jan 

2004;279(5):3426–3433. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Bruce Goldstein, 

JD, MS; (301) 435–5470; 

goldsteb@mail.nih.gov. 

Collaborative Research Opportunity: 

The Laboratory of Pathology in the 

Center for Cancer Research of the 

National Cancer Institute is seeking 

parties interested in collaborative 

research directed toward clinical 

applications of biliverdin. For more 

information about the research, please 

contact either Dr. Michael Pendrak 

(NCI/CCR Laboratory of Pathology) at 

(301) 496–6264, or Dr. April Franks 

(NCI Technology Transfer Center) at 

(301) 496–0477. 

Dated: July 28, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–18496 Filed 7–31–09; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–N–0338] 

Medical Device User Fee Rates for 

Fiscal Year 2010 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 


sroberts on DSKD5P82C1PROD with NOTICES