Federal Register / Vol. 75, No. 185 / Friday, September 24, 2010 / Notices 58401 

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. 

Phantasmidine, a Nicotinic Receptor 

Agonist for the Treatment of Addiction 

and Neurological Disorders 

Description of Invention: The 

inventors have isolated and 

characterized an alkaloid, 

phantasmidine, from the skin of the 

Ecuadoran poison frog E. anthonyi. 

Phantasmidine is selective for b4- 

containing receptor subtypes, unlike 

many nicotinic receptor agonists 

currently in development, which target 

b2-containing receptor subtypes. This 

selectivity makes phantasmidine a 

unique pharmacological probe, as well 

as a promising lead compound for the 

development of selective therapeutics 

targeting b4-containing receptor 

subtypes, which appear to play any 

important role in nicotine addiction and 

other substance dependencies. 

Nicotinic acetylcholine receptors 

(nAChRs) are broadly distributed in 

both the peripheral and central nervous 

systems; activation of brain nAChRs 

results in enhanced release of various 

key neurotransmitters. Dysfunction of 

these receptors is associated with a 

variety of neurological diseases, 

including nicotine addiction. Nicotinic 

agonists, which enhance action at 

nicotinic acetylcholine receptors, have 

been shown to possess potential clinical 

utility in many of these diseases, 

although development is hindered by 

the existence of a large number of 

nAChR subtypes with highly variable 

properties. 

Alkaloids, such as epibatidine found 

in skin from the frog species E. tricolor, 

have been shown to activate nicotinic 

acetylcholine receptors. However, while 

epibatidine has been shown to be a 

powerful analgesic, it is also extremely 

toxic, so research has focused on the 

identification and development of less 

toxic analogs. 

Applications 

• Development of therapies for the 

treatment of addiction, including 

nicotine and alcohol addictions. 

• Development of therapies for 

neurological diseases such as 

Alzheimer’s disease, attention deficit 

hyperactivity disorder (ADHD), and 

schizophrenia. 

• Development of selective 

pharmacological probes for bioimaging, 

binding assays, and functional assays of 

nicotinic receptors. 

Inventors: Richard W. Fitch et al. 

(NIDDK) 

Related Publication: R Fitch et al. 

Phantasmidine: An epibatidine 

congener from the Ecuadorian poison 

frog Epipedobates anthonyi. J Nat Prod. 

2010 Mar 26;73(3):331–337. [PubMed: 

20337496] 

Patent Status: U.S. Provisional 

Application No. 61/315,674 filed 19 

March 2010 (HHS Reference No. E–125– 

2010/0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Tara Kirby, PhD; 

301–435–4426; tarak@mail.nih.gov. 

Transplant and Autoimmune Therapy 

Using T-Cells Expressing Programmed 

Death Ligand-1 (PD–L1) 

Description of Invention: Transplant 

complications (graft rejection and graftversus-host disease) and autoimmune 

diseases are primarily caused by T cell 

immune responses against normal host 

tissue or transplanted tissues. These 

disorders can lead to serious 

complications and may be chronic, 

debilitating, and fatal. Current treatment 

for these disorders is oftentimes not 

effective, and is typically associated 

with significant side effects, including 

global immune suppression, which 

increases the rate of infection and 

cancer. Hence, there is a need for new 

technologies to more specifically 

suppress the immune system for 

treatment of these diseases. 

Programmed death (PD) ligand 1 (PD– 

L1) is an immune molecule present on 

regulatory T cells (Tregs), other 

suppressor cell populations, and tumor 

cells; the function of PD–L1 is to 

suppress the function of pathogenic T 

cells that express the PD1 receptor. 

Therefore, it has been hypothesized that 

the transfer of T cells that are enriched 

for PD–L1 expression might represent 

an effective method to suppress 

autoimmunity or transplant 

complications. Adoptive T cell therapy 

using Tregs is one such approach; 

however, this approach is limited due to 

the relative rarity of Tregs and their 

tendency to possess differentiation 

plasticity towards pathogenic T cell 

subsets such as the Th17 subset. Ex vivo 

co-stimulated and expanded effector T 

cells can be generated in sufficient 

numbers for cell therapy; however, such 

cells are not enriched for PD–L1 

expression. 

The current technology overcomes 

these limitations through transduction 

of co-stimulated T cells with a lentiviral 

expression vector that dictates T cell 

expression of PD–L1. In this method, 

the co-stimulated T cells acquire the 

immunosuppressant characteristics of 

Treg cells. The PD–L1 gene expression 

construct co-expresses a cell surface 

molecule (i.e., CD19 or CD34) that 

allows enrichment of the gene-modified 

T cells to high purity. Also the construct 

co-expresses another gene, TMPK, 

which acts as a safety cell fate switch 

because the TMPK can specifically 

activate the cytotoxic prodrug, AZT. By 

incorporation of this TMPK/AZT cell 

fate safety switch, the current 

technology will allow for PD–L1 

therapeutic delivery, with subsequent 

elimination of the therapeutic cells in 

the event of toxicity. 

Applications: Co-stimulated T cells 

expressing the PD–L1, CD19–TMPK 

construct can be adoptively transferred 

into patients to: (1) Treat autoimmune 

diseases; (2) prevent graft-versus-host 

disease (GVHD), which remains the 

primary lethal complication after 

hematopoietic cell transplantation 

(HCT); and (3) prevent solid organ or 

HCT transplant rejection. 

Advantages 

(1) Relative to other proposed cell 

therapies such as Treg therapy, costimulated T cells expressing the gene 

construct can be manufactured in 

clinically relevant numbers, possess a 

defined mechanism of action, and can 

be specifically modulated (eliminated) 

in vivo. 

(2) The proposed immuno-gene 

therapy would prove advantageous to 

current immune suppressive therapies, 

which cause many side effects. 


srobinson on DSKHWCL6B1PROD with NOTICES
58402 Federal Register / Vol. 75, No. 185 / Friday, September 24, 2010 / Notices 

Market 

(1) Many diseases have been 

identified to represent autoimmune 

disorders, including but not limited to: 

inflammatory bowel disease (IBD; 

including Crohn’s disease); multiple 

sclerosis (MS); systemic lupus 

erythematosis (SLE); rheumatoid 

arthritis; and immune-mediated (type-1) 

diabetes mellitus. Approximately 1 in 

every 31 people in the U.S. suffers from 

an autoimmune disease; women suffer 

disproportionately from autoimmune 

diseases as they represent about 75% of 

cases. 

(2) Graft rejection can occur in the 

setting of solid organ transplantation 

(for example, pancreatic, renal, cardiac, 

and liver transplantation) and also 

occurs after hematopoietic stem cell or 

bone marrow transplantation (including 

matched sibling, unrelated donor, and 

cord blood transplantation). More than 

19,000 transplants are performed each 

year in the United States and the 

prevalence of graft rejection is 

considerable in these transplant 

recipients. In addition to graft rejection, 

graft-versus-host disease (GVHD) 

represents a significant transplant 

complication. Acute GVHD can occur in 

all types of hematopoietic stem cell or 

bone marrow transplantation (matched 

related, unrelated, or cord blood) and 

ranges in incidence from 30–80%. 

Chronic disease can also occur in 

approximately 54–70% of 

hematopoietic stem cell transplant 

recipients. 

Development Status: Early-stage 

development. 

Inventors: Daniel H. Fowler and 

Shoba Amarnath (NCI). 

Publication: Amarnath S, Costanzo 

CM, Mariotti J, Ullman JL, Telford WG, 

Kapoor V, Riley JL, Levine BL, June CH, 

Fong T, Warner NL, Fowler DH. 

Regulatory T cells and human myeloid 

dendritic cells promote tolerance via 

programmed death ligand-1. PLoS Biol. 

2010 Feb 2;8(2):e1000302. [PubMed: 

20126379]. 

Patent Status: U.S. Patent Application 

No. 61/261,081 filed 13 Nov 2009 (HHS 

Reference No. E–022–2010/0–US–01). 

Related Technologies: HHS Reference 

No. E–058–2006. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Surekha Vathyam, 

PhD; 301–435–4076; 

Surekha.Vathyam@nih.gov. 

Collaborative Research Opportunity: 

The Center for Cancer Research, 

Experimental Transplantation and 

Immunology Branch, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

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

3121 or hewesj@mail.nih.gov for more 

information. 

A New ‘‘Destination’’ for Protein 

Expression: A Lentiviral Gateway®

Destination Vector for High-Level 

Protein Expression (pDEST–673) 

Description of Invention: A laboratory 

at the Science Applications 

International Corporation in Frederick, 

MD (SAIC–Frederick) has developed a 

lentiviral vector, pDEST–673, for high 

protein expression yields in cells. The 

pDEST–673 vector combines three 

features that make it optimal for protein 

expression in lentiviruses: the pFUGW 

backbone, a Gateway® vector 

conversion cassette, and a neomycin 

antibiotic resistance marker. The 

pFUGW portion contains a highly 

potent polypurine tract (PPT) that 

allows for the production of higher viral 

titers within transfected cells and a 

woodchuck regulatory element (WRE) to 

enhance protein expression. The 

addition of the Gateway® conversion 

cassette converts the vector into a 

Destination vector and the neomycin 

resistance marker allows for researchers 

to select for stable transfectants using 

antibiotic selection (a feature not 

possessed by many lentiviral vectors). 

This lentiviral Destination vector should 

be useful for researchers desiring to 

utilize neomycin resistance to select for 

proteins expressed in cells stably 

transfected with lentiviruses. 

Applications 

• Research tool for high quantity 

production of a protein(s) of interest for 

studying the role of the protein(s) in a 

variety of biological processes, 

including pathologies such as cancers, 

infectious diseases, autoimmune 

diseases, and many other disorders. 

• Research tool for selecting stable 

lentiviral transfectants following the 

insertion of the vector into tumor cells. 

• Potential tool for enhancing 

production of proteins that are normally 

difficult to express in other types of 

bacterial, insect, or mammalian 

expression systems. 

Advantages 

• The pFUGW backbone provides the 

pDEST–673 vector with optimal protein 

expression properties: The polypurine 

tract (PPT) region in the vector allows 

for efficient viral transcription leading 

to increased lentiviral production in 

cells. The woodchuck regulatory 

element acts as a posttranscriptional 

enhancer to promote the conversion of 

more mRNA transcripts into protein to 

yield high-levels of the protein of 

interest. These elements are not found 

in most commercially available 

lentiviral vectors. 

• The incorporation of the neomycin 

resistance marker facilitates selection of 

the transfectants of interest: Many 

laboratories rely on neomycin selection 

as a key selectable marker in their 

protein expression experiments. Few 

commercially available lentiviral 

vectors contain a neomycin resistance 

marker. 

Inventors: Dominic Esposito (SAIC). 

Selected Publications 

1. A Ventura, et al. Cre-lox-regulated 

conditional RNA interference from 

transgenes. Proc. Natl. Acad. Sci. USA. 

2004 Jul 13;101(28):10380–10385. 

[PubMed: 15240889]. 

2. C Lois, et al. Germline transmission 

and tissue-specific expression of 

transgenes delivered by lentiviral 

vectors. Science 2002 Feb 

1;295(5556):868–872. [PubMed: 

11786607]. 

Patent Status: HHS Reference No. E– 

119–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Samuel E. Bish, 

PhD; 301–435–5282; 

bishse@mail.nih.gov. 

A Hand Held Portable Device Based on 

Light Emitting Diodes (LEDs) as a Light 

Source for Use in the Detection of 

Counterfeit Pharmaceutical Drugs and 

Packaging 

Purpose: The FDA is seeking a device 

company to commercialize its patent 

pending hand held portable device for 

the detection of counterfeited 

pharmaceuticals. The device will be 

based on the technology described 

below. The invention was further 

described and claimed in provisional 

patent application 61/165,395 filed 

March 31, 2009. The FDA scientists 

have built highly reliable prototypes of 

two different models of the device and 

demonstrated the validity of the device 

for multiple applications. 

Description of Technology: A hand 

held portable device was designed and 

developed for use in the detection of 

counterfeit pharmaceutical products 

and packaging. The light source of the 

device emits different wavelengths of 

light onto a sample. The device 

incorporates the use of single 

wavelength light emitting diodes (LEDs) 

which generate intense single 

wavelengths of light. Two models of the 

device have been developed and 


srobinson on DSKHWCL6B1PROD with NOTICES
Federal Register / Vol. 75, No. 185 / Friday, September 24, 2010 / Notices 58403 

manufactured. The first model 

incorporates only LEDs at specific 

wavelengths and the second model 

incorporates a camera and display along 

with the LEDs at specific wavelengths. 

The different LED wavelengths of light 

interact with the sample by either being 

absorbed, reflected or by generating an 

apparent color change in the sample. 

The absorption, reflection or apparent 

color change by the sample may be 

observed using different colored goggles 

(yellow, orange, red). The fluorescence 

profiles of suspect pills can be 

compared with the authentic article to 

determine legitimacy. The device can be 

used for field examination of suspect 

counterfeit pharmaceutical products, 

packaging and diverted pharmaceutical 

products. Due to its size, and the 

simplicity in design and use, the hand 

held portable LED light source can be 

used by health safety officials (e.g. FDA 

investigators), by law enforcement 

authorities, or by the pharmaceutical 

companies themselves, to rapidly screen 

samples for suspect counterfeit products 

improving the safety of that the U.S. 

drug distribution chain. 

Applications 

• Testing for authenticity of 

pharmaceutical products. 

• Combating the ever growing 

problem of counterfeiting in 

pharmaceutical products to protect 

public safety. 

• Traditional law enforcement 

activities. 

Advantages: Current methods of 

detecting counterfeit pharmaceuticals 

include vibrational spectroscopy, x-ray 

diffraction, gas chromatography, liquid 

chromatography, and mass 

spectrometry. These methods although 

often effective, require expensive and 

bulky instrumentation, and are 

generally performed in a laboratory by 

highly trained operators. The LED 

devices based on the subject technology 

thus offer the following advantages: 

• Small size, light and portable. 

• Tests can be performed at desired 

location outside of lab setting. 

• Simple to use and does not require 

special technical skills. 

• Low cost and simple to 

manufacture. 

• Reliable and provides reproducible 

results. 

• Image capture and storage 

capabilities. 

Development Status: Fully developed 

and ready for manufacturing. 

Market: The volume of counterfeit 

pharmaceuticals entering the United 

States and other countries continues to 

increase. Counterfeit pharmaceuticals 

are illegally imported and are 

commonly available over the Internet. It 

is often difficult to determine the 

authenticity of a pharmaceutical, since 

the genuine and counterfeit products 

often have nearly identical appearance 

and markings (shape, color, size, 

packing, labeling etc.), even when 

viewed by professionals. Detection of 

counterfeit pharmaceuticals is of 

extreme importance since the efficacy of 

a counterfeit product is often lower than 

the actual product. In addition, the 

counterfeit product may contain toxic 

components, and result in side effects 

which are not associated with the 

authentic product. Such counterfeit 

products also result in monetary loss to 

pharmaceutical companies and retailers. 

It is for these reasons, i.e. health safety 

and economic loss, that the commercial 

potential of devices that detect such 

counterfeit products is large. Due to the 

advantages offered by the subject 

invention as outlined above, it is 

predicted that both models of subject 

device will enjoy commercial success. 

The ease of use allows for examination 

of products anywhere an investigator or 

inspector can travel and gives a 

preliminary result that would allow 

action to be taken. The device has the 

potential to be expanded to uses related 

to product tampering, counterterrorism 

and other traditional law enforcement 

applications. 

Inventors: Nicola Ranieri (FDA) et al. 

Patent Status 

• U.S. Provisional Application No. 

61/165,395 filed 31 Mar 2009, entitled 

‘‘Device and Method for Detection of 

Counterfeit Pharmaceuticals’’ (HHS 

Reference No. E–206–2008/0–US–01). 

• PCT Application No. PCT/US2010/ 

029502 filed 31 Mar 2010 (HHS 

Reference No. E–206–2008/0–PCT–03). 

Licensing Status: Available for 

licensing. 

Licensing Contacts 

• Uri Reichman, PhD, MBA; 301– 

435–4616; UR7a@nih.gov. 

• Michael Shmilovich, Esq.; 301– 

435–5019; shmilovm@mail.nih.gov. 

Methods for Treatment and Diagnosis 

of Psychiatric Disorders 

Description of Invention: Current 

drugs used to treat schizophrenia block 

dopamine receptors. These drugs can 

effectively suppress the ‘‘positive’’ 

symptoms of schizophrenia but have 

little impact on the debilitating or 

‘‘negative’’ symptoms of the disease 

which include social withdrawal, 

emotional unresponsiveness, difficulty 

with attention and memory, and apathy. 

There is thus a therapeutic need for 

improved antipsychotics that can 

improve both positive and negative 

symptoms. This technology describes 

novel interactions between neuregulins 

(NRGs), ErbB receptors, and dopamine 

signaling pathways that may influence 

the expression of schizophrenia. 

Researchers at the NIH demonstrated 

that NRGs reverse long term 

potentiation (LTP) when given shortly 

after LTP is established without 

affecting basal transmission. Blockade of 

ErbB receptors with antagonists 

prevented depotentiation by NRG, and 

NRG showed no effect in an ErbB–4 

knockout mouse model. Thus NRG 

regulation of LTP occurs through the 

ErbB–4 receptor. Data also showed that 

dopamine antagonists block the effects 

of NRGs on LTP. These findings could 

be useful in the development of 

antipsychotic drugs that block NRG 

actions, and in doing so, provide better 

therapies for schizophrenia. 

This technology describes methods of 

treating schizophrenia with an 

antagonist that blocks neuregulin-1 

activation of the ErbB–4 receptor 

signaling pathway, methods of 

identifying schizophrenia in affected 

patients, as well as methods of 

identifying modulators of ErbB–4 

receptor signaling. This technology may 

also be applicable for treating or 

preventing other psychiatric disorders 

such as bipolar disorder, attention 

deficit disorder (ADD), and autism. 

Applications 

• Method of diagnosis and treatment 

for schizophrenia, bipolar disease, ADD 

and autism. 

• Methods of finding modulators of 

ErbB–4 receptor signaling. 

Market 

• The U.S. schizophrenia market 

averages 10 billion dollars a year. 

• Schizophrenia affects 

approximately 1% of the population. 

Inventors: Andres Buonanno (NICHD). 

Publications 

1. Kwon OB, Longart M, Vullhorst D, 

Hoffman DA, Buonanno A. Neuregulin1 reverses long-term potentiation at CA1 

hippocampal synapses. J Neurosci. 2005 

Oct 12;25(41):9378–9383. [PubMed: 

16221846]. 

2. Kwon OB, Paredes D, Gonzalez CM, 

Neddens J, Hernandez L, Vullhorst D, 

Buonanno A. Neuregulin-1 regulates 

LTP at CA1 hippocampal synapses 

through activation of dopamine D4 

receptors. Proc Natl Acad Sci USA. 2008 

Oct 7;105(40):15587–15592. [PubMed: 

18832154]. 

3. Vullhorst D, Neddens J, Karavanova 

I, Tricoire L, Petralia RS, McBain CJ, 

Buonanno A. Selective expression of 


srobinson on DSKHWCL6B1PROD with NOTICES
58404 Federal Register / Vol. 75, No. 185 / Friday, September 24, 2010 / Notices 

ErbB4 in interneurons, but not 

pyramidal cells, of the rodent 

hippocampus. 2009 J Neurosci. Sep 

30;29(39):12255–12264. [PubMed: 

19793984]. 

4. Buonanno, A. The neuregulin 

signaling pathway and schizophrenia: 

From genes to synapses and neural 

circuits. Brain Res Bull. 2010 Aug 3; 

Epub ahead of print. [PubMed: 

20688137]. 

Patent Status 

• U.S. Provisional Application No. 

60/837,449 filed 11 Aug 2006 (HHS 

Reference No. E–304–2005/0–US–01). 

• International Application No. PCT/ 

US07/75724 filed 10 Aug 2007, which 

published as WO 2008/019394 on 14 

Feb 2008 (HHS Reference No. E–304– 

2005/0–PCT–02). 

• U.S. Patent Application No. 12/ 

377,025 filed 10 Feb 2009 (HHS 

Reference No. E–304–2005/0–US–03). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Jeffrey Clark Klein, 

PhD; 301–594–4697; 

kleinjc@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institutes 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 develop, evaluate, or 

commercialize this technology. Please 

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

3121 or hewesj@mail.nih.gov for more 

information. 

Dated: September 20, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–23977 Filed 9–23–10; 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. 

Use of Adenosine Agonists To Prevent 

Arterial Vascular Calcification 

Disorder 

Description of Invention: Scientists at 

the National Human Genome Research 

Institute (NHGRI) and the National 

Heart Lung and Blood Institute (NHLBI) 

at the National Institutes of Health (NIH) 

have discovered a genetic defect in the 

Ecto-5’-nucleotidase (NT5E) gene which 

results in Cluster of Differentiation 73 

(CD73) deficiency that leads to a 

decrease in adenosine, and ultimately, 

an increase in vascular calcification. 

NT5E encodes CD73, an enzyme that 

converts adenosine monophosphate 

(AMP) to adenosine in the extracellular 

region of the vascular endothelium. 

Normally, extracellular adenosine binds 

to one of the several receptors on the 

surface decreasing the production of 

cyclic AMP (cAMP) resulting in an 

inhibition of vascular calcification. 

The discovery of this genetic mutation 

leading to a decrease in adenosine 

provides a method of treating or 

preventing the disorder by using 

adenosine receptor agonists as 

therapeutic agents. Adenosine receptor 

agonists can be used to treat or prevent 

disorders associated with vascular and/ 

or joint capsule calcification, including 

for example atherosclerosis, 

Monkeberg’s medial sclerosis, CD74 

deficiency, Ehlers Danlos syndrome 

(EDS), Marfan/Loewe Dietz syndrome, 

fibromuscular dysplasia, Kawasaki 

syndrome, pseudoxanthoma elasticum, 

and premature placental calcification. 

Applications: Treatment for vascular 

calcification disorder by using 

adenosine receptor agonist agents. 

Development Status: Early-stage. 

Inventors: William A. Gahl (NHGRI), 

Thomas C. Markello (NHGRI), Shira G. 

Ziegler (NHGRI), Manfred Boehm 

(NHLBI), Cynthia Hillaire (NHLBI). 

Publication: C St. Hilaire, et al. NT5E 

Mutations are Associated with Arterial 

Calcifications. New Engl J Med., 

Submitted 2010. 

Patent Status: U.S. Provisional 

Application No. 61/319,336 filed 31 Mar 

2010 (HHS Reference No. E–094–2010/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Steve Standley, 

301–435–4074, sstand@od.nih.gov. 

Collaborative Research Opportunity: 

The NHGRI is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize adenosine receptor 

agonist compounds for therapeutic use 

including as a treatment of certain 

common as well as rare vascular 

calcification-related disorders (see 

above Description of Invention). Please 

contact NHGRI Technology 

Development Coordinator Claire T. 

Driscoll at cdriscol@mail.nih.gov for 

more information. 

Small Molecule Neuropeptide S 

Receptor (NPSR) Antagonists for the 

Treatment of Addictive Disorders, 

Mood, Anxiety and Sleep Disorders 

Description of Invention: The 

inventors, who work for the National 

Human Genome Research Institute 

(NHGRI) and the National Institute on 

Alcohol Abuse and Alcoholism 

(NIAAA) at the National Institutes of 

Health (NIH), have developed NPSR 

antagonists that hold the potential for 

being clinically useful treatments for 

alcohol and drug addiction. 

Neuropsychiatric disorders including, 

for example, mood, anxiety, eating, and 

sleep related disorders, as well as 

alcoholism and drug addiction, are 

major causes of mortality and morbidity. 

Patient relapse into drug seeking and 

use, after an interval of sobriety, is a key 

component of the addictive syndrome, 

with approximately two-thirds of 

patients relapsing within three months 

of initiating abstinence. Therefore, 

relapse prevention is a major treatment 

objective. 

Neuropeptide S (NPS), an endogenous 

ligand for the Neuropeptide S receptor 

(NPSR) has recently been shown to play 

a key role in relapse-like behavior. In 

addition, because mood, anxiety, eating, 

and sleep related behaviors are often 

closely linked with the addictive 

process, and are also affected by the 

NPS system, it is believed that the NPSR 

antagonist will also be promising as a 

useful therapeutic target in these 

clinical areas as well. 

Applications: Development of a NPSR 

antagonist for the therapies of alcohol 

and drug addiction. 

Development Status: Early-stage. 

Market: More than 700,000 Americans 

receive alcoholism treatment on any 


srobinson on DSKHWCL6B1PROD with NOTICES