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
Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices 81629 

• Structurally distinct antimicrobial 

compounds. 

• Attack newly validated antibacterial 

targeted protein FtsZ. 

• These compounds have a unique 

mechanism of action which inhibit FtsZ 

by inhibiting FtsZ GTPase activity. 

• Inhibit drug-susceptible and drugresistant bacteria. 

Development Status: 

• Initial isolation and chemical 

structural characterization using NMR 

spectroscopy have been conducted. 

• Antimicrobial testing against 

MRSA, Enterrococcus faecium, and VRE 

were conducted in vitro using a 

modified disk diffusion assay and 

microbroth liquid dilution assays. 

• MIC50 values were determined 

using a microbroth dilution assay. 

• Mode of action was elucidated and 

Saturation Transfer Difference (STD) 

NMR was conducted to map the binding 

epitope of one of these compounds in 

complex with recombinant FtsZ. 

• Other experiments on different 

areas to further characterize these 

compounds and their mode of action are 

currently ongoing. 

Market: The market potential for the 

disclosed compounds is huge due to the 

very limited number of new antibiotics 

developed in recent decades and the 

increased epidemic of infectious 

diseases. In fact, infectious diseases are 

the leading cause of death worldwide. 

In the United States alone, more people 

die from MRSA than from HIV (Journal 

of the American Medical Association, 

2007) and more than 90,000 people die 

each year from hospital acquired 

bacterial infections (Centers for Disease 

Control). 

According to the recent report, 

‘‘Antibiotics Resistance and Antibiotic 

Technologies: Global Markets’’ 

published in November 2009, there has 

been a revival in the antibiotics sector 

over the past few years. Although some 

companies are developing analogues of 

existing antibiotic classes and putting 

them into clinical trials, other start-up 

biotechnology companies have come up 

with molecules that adopt new 

approaches in tackling antimicrobial 

infections. The antibacterials market can 

be split into two major groups: The 

community market and the hospital 

market. The smaller hospital market is 

expanding more rapidly, driven by 

rising resistant rates, a more severely ill 

patient population and newer, 

premium-priced injectable antibiotics. 

Interestingly, several big pharmaceutical 

companies have recently made strategic 

decisions to expand their presence in 

this sector by either acquiring other 

companies or in-licensing new 

compounds. 

While the number of such new 

molecules in the approval stages is still 

low, R&D pipelines are promising, and 

several novel classes of antibiotics are in 

their early stages of development. This 

antibacterial R&D bailout that started 

about 5 years ago due to tougher 

regulatory conditions, restrictions on 

the use of antibiotics and emergence of 

resistance to newer antibiotics within 3 

years has helped create a global 

antimicrobial therapeutic market of $24 

billion in 2008 with 14 products 

recording sales of more than $1 billion. 

Inventors: Carole A. Bewley et al. 

(NIDDK). 

Related Publications: 

1. DJ Haydon et al. An inhibitor of 

FtsZ with potent and selective antistaphylococcal activity. Science. 2008 

Sept 19; 321(5896):1673–1675. 

[PubMed: 18801997]. 

2. NR Stokes et al. Novel inhibitors of 

bacterial cytokinesis identified by a cellbased antibiotic screening assay. J Biol 

Chem. 2005 Dec 2; 280(48):39709– 

39715. [PubMed: 16174771]. 

3. J Wang et al. Discovery of small 

molecule that inhibits cell division by 

blocking FtsZ, a novel therapeutic target 

of antibiotics. J Biol Chem. 2003 Nov 7; 

278(45):44424–44428. [PubMed: 

12952956]. 

4. P Domadia et al. Berberine targets 

assembly of Escherichia coli cell 

division protein FtsZ. Biochemistry. 

2008 Mar 11; 47(10):3225–3234. 

[PubMed: 18275156]. 

5. P Domadia et al. Inhibition of 

bacterial cell division protein FtsZ by 

cinamaldehyde. Biochem Pharmacol. 

2007 Sep 15:74(6):831–840. [PubMed: 

17662960]. 

6. S Urgaonkar et al. Synthesis of 

antimicrobial natural products targeting 

FtsZ: (+/-)-dichamanetin and (+/-)-2′′′- 

hydroxy-5′′-benzylisouvarinol-B. Org 

Lett. 2005 Dec 8;7(25):5609–5612. 

[PubMed: 16321003]. 

Patent Status: U.S. Provisional 

Application No. 61/308,911 filed 27 Feb 

2010 (HHS Reference No. E–116–2010/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contacts: 

• Uri Reichman, Ph.D., MBA; 301– 

435–4616; UR7a@nih.gov. 

• John Stansberry, Ph.D.; 301–435– 

5236; stansbej@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Diabetes and 

Digestive and Kidney Diseases, 

Laboratory of Bioorganic Chemistry is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize the 

chrysophaentin antibiotics. Please 

contact Cindy K. Fuchs at 301–451– 

3636 or cfuchs@mail.nih.gov for more 

information. 

GATA–3 Reporter Plasmids for 

Revealing Underlying Mechanisms in 

Breast Cancer 

Description of Technology: Scientists 

at the National Institutes of Health (NIH) 

have developed GATA–3 gene reporter 

plasmids that express a green 

fluorescent protein (GFP) or luciferase 

reporter protein under the control of a 

GATA–3 promoter. Cells expressing this 

plasmid will glow fluorescent green or 

emit light energy, respectively, if 

GATA–3 gene expression is activated in 

the cells. The reporter construct allows 

cells where GATA–3 gene expression is 

activated to be isolated and collected for 

further analysis or be monitored in the 

host environment. 

GATA–3 is a transcription factor that 

is highly expressed in several types of 

cells and is a critical transcription factor 

for the development of particular 

lineages of hematopoietic cells and 

normal mammary luminal epithelium. 

GATA–3 plays a regulatory role in 

determining the fate of cells in the 

hematopoietic systems and the 

mammary gland. Disruption of GATA– 

3 expression leads to defects in the 

development of sub-types of lymphoid 

cells and luminal mammary epithelial 

cells. GATA–3 expression is highly 

associated with luminal sub-types of 

breast cancer, whereas expression of 

GATA–3 is low or undetectable in basal 

subtypes of breast cancer which often 

have a poor prognosis. Low or limited 

GATA–3 expression is correlated with 

larger tumors, increased likelihood of 

tumor-positive lymph nodes, and 

predicts an overall poorer clinical 

outcome compared to patients with 

higher mammary GATA–3 expression. 

Researchers believe that a better 

understanding of GATA–3 function and 

its dysregulation during the onset and 

progression of breast cancer will lead to 

new strategies in diagnosing and 

treating the disease. 

Applications: 

• Research tool to help identify 

factors that modify GATA–3 expression 

that may serve as potential therapeutic 

targets for developing drugs to treat 

breast cancer or hematologic 

malignancies. 

• Research tool that could be utilized 

as an important component of a breast 

cancer diagnostic kit or platform to 

better understand the most effective 

treatment options for individual breast 

cancer patients. 

• Molecular tool to better understand 

the mechanisms that contribute to 

hematopoietic and mammary cell/gland 


emcdonald on DSK2BSOYB1PROD with NOTICES
81630 Federal Register / Vol. 75, No. 248 / Tuesday, December 28, 2010 / Notices 

development and differentiation in 

order to identify the critical stages 

where dysfunction can lead to the onset 

of breast cancer. 

• Molecular biology laboratory tool 

for sorting breast cancer positive and 

negative cells so that further 

comparative experiments can be 

performed to understand the cellular 

properties of the two sets of cells. 

Advantages: 

• Useful for in vitro and in vivo 

assays: Using the GFP or luciferase 

expression of these reporter plasmids, 

researchers can identify cells expressing 

various levels of GATA–3 and isolate 

these different subsets in vitro. These 

reporter constructs can also be 

transfected into cells to measure 

GATA–3 expression levels in vivo in 

real time from hematopoietic and breast 

cancer models. 

• Possible identification of new 

targets for breast cancer therapy: The 

reporter plasmids could be utilized to 

identify factors that serve to activate 

GATA–3 in normal mammary cells or 

inhibit GATA–3 expression in breast 

cancer cells. Such factors could serve as 

targets for novel breast cancer therapies. 

Inventors: Hosein Kouros-Mehr 

(formerly NCI) and Jeffrey E. Green 

(NCI) 

Selected Publications: 

1. H. Kouros-Mehr, et al. GATA–3 and 

the regulation of the mammary luminal 

cell fate. Curr Opin Cell Biol. 2008 

Apr;20(2):164–170. [PubMed: 18358709] 

2. H. Kouros-Mehr, et al. GATA–3 

links tumor differentiation and 

dissemination in the luminal breast 

cancer model. Cancer Cell 2008 

Feb;13(2):141–152. [PubMed: 18242514] 

3. H. Kouros-Mehr, et al. GATA–3 

maintains the differentiation of the 

luminal cell fate in the mammary gland. 

Cell 2006 Dec 1;127(5):1041–1055. 

[PubMed: 17129787] 

Patent Status: HHS Reference No. E– 

128–2009/0—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, 

Ph.D.; 301–435–5282; 

bishse@mail.nih.gov. 

Dated: December 21, 2010. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2010–32671 Filed 12–27–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Institute of Biomedical 

Imaging and Bioengineering; Notice of 

Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: National Institute of 

Biomedical Imaging and Bioengineering 

Special Emphasis Panel. 

Date: March 16–18, 2011. 

Time: 6 p.m. to 3 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: Sheraton Fisherman’s Wharf Hotel, 

2500 Mason Street, San Francisco, CA 94133. 

Contact Person: Ruth Grossman, DDS, 

Scientific Review Officer, National Institute 

of Biomedical Imaging and Bioengineering, 

National Institutes of Health, 6707 

Democracy Boulevard, Room 960, Bethesda, 

MD 20892, 301–496–8775, 

grossmanrs@mail.nih.gov. 

Dated: December 16, 2010. 

Jennifer Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2010–32645 Filed 12–27–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Notice of 

Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Center for Scientific 

Review Special Emphasis Panel; Member 

Conflict: Cardiac Development. 

Date: January 4, 2011. 

Time: 3 p.m. to 4 p.m. 

Agenda: To review and evaluate grant 

applications. 

Place: National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892. 

(Telephone Conference Call). 

Contact Person: Joseph Thomas Peterson, 

PhD, Scientific Review Officer, Center for 

Scientific Review, National Institutes of 

Health, 6701 Rockledge Drive, Room 4118, 

MSC 7814, Bethesda, MD 20892. 301–443– 

8130. 

This notice is being published less than 15 

days prior to the meeting due to the timing 

limitations imposed by the review and 

funding cycle. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.306, Comparative Medicine; 

93.333, Clinical Research, 93.306, 93.333, 

93.337, 93.393–93.396, 93.837–93.844, 

93.846–93.878, 93.892, 93.893, National 

Institutes of Health, HHS) 

Dated: December 21, 2010. 

Jennifer S. Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2010–32639 Filed 12–27–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Amended 

Notice of Meeting 

Notice is hereby given of a change in 

the meeting of the Center for Scientific 

Review Special Emphasis Panel, January 

6, 2011, 1 p.m. to January 6, 2011, 3:30 

p.m., National Institutes of Health, 6701 

Rockledge Drive, Bethesda, MD 20892 

which was published in the Federal 

Register on December 16, 2010, 75 FR 

78719–78720. 

The meeting has been changed to an 

Internet Assisted Meeting (IAM). The 

meeting will be two days January 6, 

2011, 9 a.m. to January 7, 2011, 5 p.m. 

The meeting is closed to the public. 

Dated: December 21, 2010. 

Jennifer S. Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2010–32638 Filed 12–27–10; 8:45 am] 

BILLING CODE 4140–01–P 


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