81626 Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices 

proteases: cruzain, rhodesain, and 

TbCatB. J Med Chem. 2010 Jan 

14;53(1):52–60. [PubMed: 19908842] 

Patent Status: PCT Application No. 

PCT/US2009/063078 filed 03 Nov 2009, 

which published as WO 2010/059418 

on 27 May 2010 (HHS Reference No. E– 

267–2008/0–PCT–02) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Kevin W. Chang, 

Ph.D.; 301–435–5018; 

changke@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIH Chemical Genomics Center 

(NCGC) is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize appropriate lead 

compounds described in the patent 

application. Please contact Dr. Craig J. 

Thomas (craigt@nhgri.nih.gov) or Claire 

Driscoll (cdriscol@mail.nih.gov), 

Director of the NHGRI Technology 

Transfer Office, for more information. 

A Novel, Inhibitory Platelet Surface 

Protein (TREM Like Transcript, TLT–1): 

New Target for the Treatment of 

Cancer, Infectious Diseases, Cardiac 

Diseases, and Platelet-Associated 

Disorders 

Description of Technology: Triggering 

Receptors in Myeloid Cells (TREM) 

recently were discovered to modulate 

innate and adaptive immunity. 

Specifically, TREM1 amplifies the 

response to sepsis in innate immunity 

by activating neutrophils and other 

leukocytes; and TREM2 potentiates 

dendritic cell maturation in adaptive 

immunity. 

This invention describes a novel, 

inhibitory platelet surface protein 

known as TREM like Transcript (TLT– 

1). TLT–1 is the first inhibitory receptor 

discovered to reside within the TREM 

gene locus. Structurally, TLT–1 also 

possesses inhibitory domains that 

indicate this regulatory function. TLT– 

1 is highly expressed in peripheral 

blood platelets and may modulate many 

other types of myeloid cells. 

Additionally, the invention describes 

specific, human, single chain antibodies 

(scFvs) that recognize TLT–1. 

Applications 

• This discovery implies the receptor 

has an important regulatory role in both 

innate and adaptive immunity. 

• TLT–1 is a potential therapeutic 

target for thrombosis and other plateletassociated disorders, as well as immune 

disorders, cancer, septic shock, 

infectious disease, stroke, heart disease, 

myocardial infarction, vascular 

disorders. 

• Detection of soluble TLT–1 in 

patient plasma suggests the protein is a 

marker of ongoing coagulopathies. 

• Defective platelet aggregation in 

TLT–1 null mice confirms a role for the 

protein in regulation of thrombosis 

associated with inflammation. 

Advantages 

• In vitro proof of concept data 

available—Three of the anti-TLT–1 

scFvs inhibit thrombin-induced 

aggregation of human platelets in a 

dose-dependent manner. 

• Complete human origin of these 

antibodies suggests negligible 

immunogenicity and minimizes the 

problem of adverse immune responses 

in human therapy. 

• Target validation is complete. TLT– 

1 null mice demonstrate defects in 

platelet aggregation with no gross 

bleeding defect. 

Development Status: In vitro 

experiments completed. Target 

validation with null mice completed. In 

vivo animal studies with scFv are 

currently ongoing. 

Inventors: Toshiyuki Mori et al. (NCI) 

Related Publication: Giomarelli B, 

Washington VA, Chisholm MM, Quigley 

L, McMahon JB, Mori T, McVicar DW. 

Inhibition of thrombin-induced platelet 

aggregation using human single-chain 

Fv antibodies specific for TREM-like 

transcript-1. Thromb Haemost. 2007 

Jun;97(6):955–963. [PubMed: 17549298] 

Patent Status: U.S. Patent No. 

7,553,936 issued on 30 Jun 2009 (HHS 

Reference No. E–177–2006/0–US–01) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

PhD; 301–594–6565; 

tongb@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute’s 

Molecular Targets Development 

Program is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize antibodies that react 

specifically with TLT–1. Please contact 

John D. Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Dated: December 21, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–32629 Filed 12–27–10; 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. 

Engineered Biological Pacemakers 

Description of Technology: A common 

symptom of many heart diseases is an 

abnormal heart rhythm or arrhythmia. 

While effectively improving the lives of 

many patients, implantable pacemakers 

have significant limitations such as 

limited power sources, risk of 

infections, potential for interference 

from other devices, and absence of 

autonomic rate modulation. 

The technology consists of biological 

pacemakers engineered to generate 

normal heart rhythm. The biological 

pacemakers include cardiac cells or 

cardiac-like cells derived from 

embryonic stem cells or mesenchymal 

stem cells. The biological pacemakers 

naturally integrate into the heart. Their 

generation of rhythmic electric impulses 

involves coupling factors, such as 

cAMP-dependent PKA and Ca2+

-dependent CaMK II, which are 

regulatory proteins capable of 

modulating/enhancing interactions (i.e. 

coupling) of the sarcoplasmic reticulumbased, intracellular Ca2+ clock and the 

surface membrane voltage clock, thereby 

converting irregularly or rarely 

spontaneously active cells into 

pacemakers generating rhythmic 

excitations. 


emcdonald on DSK2BSOYB1PROD with NOTICES
Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices 81627 

Applications: This technology can be 

utilized in heart disease characterized 

by arrhythmia or situations requiring an 

implantable cardiac pacemaker. 

Advantages: In contrast to current 

implantable cardiac pacemaker 

technology, this technology is not 

externally powered, has a lower risk of 

infection, has decreased potential for 

interference from other devices, and has 

full autonomic rate modulation. 

Development Status: Early stage. 

Inventors: Victor A. Maltsev et al. 

(NIA) 

Publications: 

1. VA Maltsev and EG Lakatta. 

Synergism of coupled subsarcolemmal 

Ca2+ clocks and sarcolemmal voltage 

clocks confers robust and flexible 

pacemaker function in a novel 

pacemaker cell model. Am J Physiol 

Heart Circ Physiol. 2009 

Mar;296(3):H594–H615. [PubMed: 

19136600] 

2. VA Maltsev and EG Lakatta. 

Dynamic interactions of an intracellular 

Ca2+ clock and membrane ion channel 

clock underlie robust initiation and 

regulation of cardiac pacemaker 

function. Cardiovasc Res. 2008 Jan 

15;77(2):274–284. [PubMed: 18006441] 

Patent Status: PCT Application No. 

PCT/US2010/035823 filed 21 May 2010 

(HHS Reference No. E–134–2009/0– 

PCT–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging, 

Cellular Biophysics Section, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize this technology. Please 

contact Vio Conley at 301–496–0477 or 

conleyv@mail.nih.gov for more 

information. 

Method of Detecting and Quantifying 

Contaminants in Heparin Preparations 

Description of Technology: Heparin is 

a naturally occurring acidic 

carbohydrate produced commercially 

from extracts of animal tissues (such as 

bovine lung or porcine intestine) and is 

used in the treatment of a wide range of 

diseases in addition to their classic 

anticoagulant activity. Heparin is also 

used to coat many medical devices, 

such as catheters, syringes, stents and 

filters. Recently, certain lots of heparin 

were associated with serious side effects 

and adverse events. Recalls were issued 

in multiple countries and it became 

evident that there was an extensive 

problem with heparin manufacture. 

Traditional tests may not be able to 

determine the presence of 

contaminant(s) without lyophilizing and 

concentrating each sample and may not 

be suitable for testing finished medical 

devices. Therefore, there is a 

demonstrated need to develop other 

assay methods for detecting 

contaminating oversulfated compounds 

of any source in heparin and heparin 

derived products. 

This technology relates to methods for 

detecting and/or quantifying 

oversulfated glycosaminoglycans based 

on inhibition of nucleic acid 

polymerases and resistance to 

enzymatic degradation. It also relates to 

the use of these methods to screen and 

quantify pharmaceutical preparations 

such as heparin preparations for 

oversulfated contaminants. 

Potential Applications: Robust, 

simple and effective method for 

detecting and optionally quantifying 

oversulfated contaminants in heparin 

preparations. 

Development Status: The method has 

been developed and qualified for 

sensitivity and identity, but full 

validation and commercialization have 

not been undertaken. 

Inventor: Daniela Verthelyi et al. 

(FDA) 

Publication: C Tami, M Puig, JC 

Reepmeyer, H Ye, DA D’Avignon, 

L Buhse, D Verthelyi. Inhibition of Taq 

polymerase as a method for screening 

heparin for oversulfated contaminants. 

Biomaterials 2008 Dec;29(36):4808– 

4814. [PubMed: 18801571] 

Patent Status: PCT Application No. 

PCT/US2009/056263 filed 08 Sep 2009, 

which published as WO 2010/030608 

on 18 Mar 2010 (HHS Reference No. 

E–227–2008/0–PCT–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The FDA, Division of Therapeutic 

Proteins, Laboratory of Immunology, is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize this 

high throughput screening test for 

oversulfated glycosamineglycan 

contaminants in heparin. Please contact 

Daniela Verthelyi at 

daniela.verthelyi@fda.hhs.gov or Alice 

Welch at alice.welch@fda.hhs.gov for 

more information. 

Method for the Diagnosis and Prognosis 

of Age-Related Cardiovascular 

Disorders 

Description of Technology: NIH 

investigators have discovered a method 

for the diagnosis and prognosis of 

cardiovascular aging. Current 

methodologies include the measurement 

of patient lipid profiles or expression of 

up to two proteins. In contrast, this 

technology utilizes the expression levels 

of a panel of proteins not previously 

known to be related to cardiovascular 

aging and may prove to be a more 

accurate diagnostic or prognostic of 

cardiovascular aging than currently 

available tests or it may improve the 

accuracy of currently available tests 

when used in concert. 

The technology relates to methods for 

determining susceptibility to having an 

extremely common age-associated 

vascular disorder. It also describes the 

subsequent use of these proteins as 

markers for disease. While the 

underlying cellular and molecular 

mechanisms of age-related vascular 

disease remain largely undefined, the 

expression levels of the genes described 

in this technology have been 

empirically determined to differ 

between healthy and age-inflamed 

arterial tissue. Further, this technology 

includes a companion mass 

spectroscopic-based methodology for 

reproducible quantification of specific 

expression levels of interest. 

Application: Diagnosis of age-related 

vascular disorder. 

Development Status: Early stage. 

Inventors: Mingyi Wang et al. (NIA). 

Patent Status: PCT Application No. 

PCT/US2010/024816 filed 19 Feb 2010, 

which published as WO 2010/096713 

on 26 Aug 2010 (HHS Reference No. E– 

219–2008/0–PCT–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

MHPM; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging, 

Cardiovascular Biology Unit—Vascular 

Group, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize idea of how to assess and 

retard accelerated arterial aging and its 

attendant risks for atherosclerosis and 

hypertension. Please contact Vio Conley 

at 301–496–0477 or 

conleyv@mail.nih.gov for more 

information. 


emcdonald on DSK2BSOYB1PROD with NOTICES
81628 Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices 

Identification of Subjects Likely To 

Benefit From Copper Treatment 

Description of Technology: Menkes 

disease is an infantile onset X-linked 

recessive neurodegenerative disorder 

caused by deficiency or dysfunction of 

a copper-transporting ATPase, ATP7A. 

The clinical and pathologic features of 

this condition reflect decreased 

activities of enzymes that require copper 

as a cofactor, including dopamine-bhydrolase, cytochrome c oxidase and 

lysyl oxidase. Recent studies indicate 

that ATP7A normally responds to 

N-methyl-D-aspartate receptor 

activation in the brain, and an impaired 

response probably contributes to the 

neuropathology of Menkes disease. 

Affected infants appear healthy at birth 

and develop normally for 6 to 8 weeks. 

Subsequently, hypotonia, seizures and 

failure to thrive occur and death by 3 

years of age is typical. Occipital horn 

syndrome (OHS) is also caused by 

mutations in the copper transporting 

ATPase ATP7A, although its symptoms 

are milder than Menkes syndrome, 

including occipital horns and lax skin 

and joints. 

Treatment with daily copper 

injections may improve the outcome in 

Menkes disease if commenced within 

days after birth; however, newborn 

screening for this disorder is not 

available and early detection is difficult 

because clinical abnormalities in 

affected newborns are absent or subtle. 

Moreover, the usual biochemical 

markers (low serum copper and 

ceruloplasmin) are unreliable predictors 

in the neonatal period, since levels in 

healthy newborns are low and overlap 

with those in infants with Menkes 

disease. Although molecular diagnosis 

is available, its use is complicated by 

the diversity of mutation types and the 

large size of ATP7A (about 140kb). 

Thus, there is a need for improved 

methods for early detection of infants 

with Menkes disease or OHS in order to 

improve outcomes. 

This technology relates to methods of 

identifying individuals who may benefit 

from treatment with copper, particularly 

those having Menkes disease or 

Occipital Horn Syndrome. 

Inventor: Stephen G. Kaler (NICHD). 

Publication: SG Kaler, CS Holmes, DS 

Goldstein, JR Tang, SC Godwin, 

A Donsante, CJ Liew, S Sato, N 

Patronas. Neonatal diagnosis and 

treatment of Menkes disease. N Engl J 

Med. 2008 Feb 7;358(6):605–614. 

[PubMed: 18256395] 

Patent Status: PCT Application No. 

PCT/US2008/078966 filed 06 Oct 2008, 

which published as WO 2010/042102 

on 15 Apr 2010 (HHS Reference No. 

E–186–2008/0–PCT–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The National Institute of Child Health 

and Human Development, Division of 

Intramural Research, Molecular 

Medicine Program, Unit on Pediatric 

Genetics, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize population-based 

newborn screening for Menkes disease 

and related disorders of copper 

transport in order to identify subjects 

likely to benefit from copper injections 

and other treatments. Please contact 

Alan Hubbs, PhD at 301–594–4263 or 

hubbsa@mail.nih.gov for more 

information. 

Dated: December 21, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–32669 Filed 12–27–10; 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. 

A New Class of Antibiotics: Natural 

Inhibitors of Bacterial Cytoskeletal 

Protein FtsZ to Fight Drug-susceptible 

and Multi-drug Resistant Bacteria 

Description of Technology: The risk of 

infectious diseases epidemic has been 

alarming in recent decades. This is not 

only because of the increase incident of 

so-called ‘‘super bugs,’’ but also because 

of the scarce number of potential 

antibiotics in the pipeline. Currently, 

the need for new antibiotics is greater 

than ever! The present invention by the 

National Institute of Diabetes and 

Digestive and Kidney Disease (NIDDK), 

part of the National Institute of Health 

(NIH), address this urgent need. The 

invention is a new class of 

chrysophaentin antibiotics that inhibit 

the growth of broad-spectrum, drugsusceptible, and drug-resistant bacteria. 

Derived from the yellow algae 

Chrysophaeum taylori, the inventor has 

extracted 8 small molecules of natural 

products and tested for antimicrobial 

activity against drug resistant bacteria, 

methicillin-resistant Staphylococcus 

aureus (MRSA) and vancomycinresistant Enterococcus faecalis (VRE), as 

well as other drug susceptible strains. 

Structurally, the molecules represent a 

new class of antibiotic that also likely 

work through a distinct mechanism of 

action from that of current antibiotics, 

which is key for the further 

development of antibiotics that inhibit 

drug-resistant strains. 

The bacterial cytoskeletal protein FtsZ 

is a GTPase and has structural homology 

to the eukaryotic cytoskeletal protein 

tubulin, but lacks significant sequence 

similarity. FtsZ is essential for bacterial 

cell division. It is responsible for Z-ring 

assembly in bacteria, which leads to 

bacterial cell division. Experiments 

show that the disclosed compounds are 

competitive inhibitors of GTP binding to 

FtsZ, and must bind in the GTP-binding 

site of FtsZ. Inhibition of FtsZ stops 

bacterial cell division and is a validated 

target for new antimicrobials. FtsZ is 

highly conserved among all bacteria, 

making it a very attractive antimicrobial 

target. 

Applications: 

• Therapeutic potential for curing 

bacterial infections in vivo, including 

for clinical and veterinary applications. 

• Antiseptics in hospital settings. 

• Since FtsZ is structurally similar, 

but does not share sequence homology 

to eukaryotic cytoskeletal protein 

tubulin, these compounds may have 

antitumor properties against some 

cancer types or cell lines. 

Advantages: 


emcdonald on DSK2BSOYB1PROD with NOTICES