18564 Federal Register / Vol. 76, No. 64 / Monday, April 4, 2011 / Notices 

Jun 16; 281(24):16681–16690. [PubMed: 

16527811] 

3. Dixit VD, Yang H, Sun Y, 

Weeraratna AT, Smith RG, Taub DD. 

Ghrelin promotes thymopoiesis during 

aging. J Clin Invest. 2007 Oct; 

117(10):2778–2790. [PubMed: 

17823656] Note: Article highlighted in 

this issue of JCI. 

4. Yang H, Dixit VD, Patel K, 

Vandanmagsar B, Collins G, Sun Y, 

Smith RG, Taub DD. Reduction in 

hypophyseal growth hormone and 

prolactin expression due to deficiency 

in ghrelin receptor signaling is 

associated with Pit-1 suppression: 

relevance to the immune system. Blood 

Behav Immun. 2008 Nov; 22(8):1138– 

1145. [PubMed: 18602461] 

5. Dixit VD, Yang H, Cooper-Jenkins 

A, Giri BB, Patel K, Taub DD. Reduction 

of T cell-derived ghrelin enhances 

proinflammatory cytokine expression: 

implications for age-associated increases 

in inflammation. Blood. 2009 May 21; 

113(21):5202–5205. [PubMed: 

19324904] 

Relevant Reviews 

6. Dixit V and Taub DD. Ghrelin and 

immunity: a young player in an old 

field. Exp. Gerontol. 2005 Nov; 

40(11):900–910. [PubMed: 16233968] 

7. Taub DD. Novel connections 

between the neuroendocrine and 

immune systems: the ghrelin 

immunoregulatory network. Vitam 

Horm. 2008; 77:325–346. [PubMed: 

17983863] 

8. Taub DD. Neuroendocrine 

interactions in the immune system. Cell 

Immunol. 2008 Mar–Apr; 252(1–2):1–6. 

[PubMed: 18619587] Note: Image from 

article used on the cover of this issue. 

9. Redelman D, Welniak LA, Taub D, 

Murphy WJ. Neuroendocrine hormones 

such as growth hormone (GH) and 

prolactin (PRL) are integral members of 

the immunological cytokine network. 

Cell Immunol. 2008 Mar–Apr; 252(1– 

2):111–121. [PubMed: 18313040] 

10. Patel K and Taub DD. Role of 

neuropeptides, hormones, and growth 

factors in regulating thymopoiesis in 

middle to old age. F1000 Biol Rep. 2009 

May 28; 1. pii: 42. [PubMed: 20948643] 

11. Taub DD, Murphy WJ, Longo DL. 

Rejuvenation of the aging thymus: 

growth hormone-mediated and ghrelinmediated signaling pathways. Curr Opin 

Pharmacol. 2010 Aug; 10(4):408–424. 

[PubMed: 20595009] 

Patent Status: U.S. Patent Application 

No. 11/596,310 filed 06 Jun 2008 (HHS 

Reference No. E–016–2004/0–US–07) 

and related international applications. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sally H. Hu, PhD, 

M.B.A.; 301–435–5606; 

hus@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

Methods of Inhibiting Proinflammatory 

Cytokine Expression Using Ghrelin. 

Please contact Nikki Guyton at 301– 

435–3101 or guytonn@mail.nih.gov for 

more information. 

Dated: March 29, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–7925 Filed 4–1–11; 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. 

Diagnostic and Prognostic Serum 

Biomarkers for Cancer Patients Treated 

With Cancer Vaccines 

Description of Technology: Although 

antibodies are a critical element of the 

immune response, the role of antibody 

responses in cancer vaccines is still 

unknown. Carbohydrate antigens, which 

are directly or indirectly involved in 

most types of cancer vaccines, are a 

class of antigens that has been largely 

understudied but play a significant role 

in the immune response of cancer 

vaccines. 

This invention involves the 

identification of serum biomarkers for 

cancer that target carbohydrate antigens. 

The biomarkers are specific subpopulations of serum antibodies present 

in the serum of patients that bind to 

various glycan and/or glycoprotein 

antigens, such as the Forssman antigen. 

The biomarkers are useful for (a) 

predicting a patient’s immune responses 

to a cancer vaccine, (b) measuring the 

efficacy of a cancer vaccine, and (c) 

determining the prognosis and longterm survival of cancer patients. 

Applications: 

• Diagnostic and prognostic test to 

monitor the progression and long-term 

survival of cancer patients. 

• Predictive indicator of cancer 

patients’ immune response to a cancer 

vaccine. 

• Indicator to monitor the efficacy of 

a cancer vaccine. 

Advantages: The technology is backed 

by clinical data. 

Development Status: Preliminary 

clinical data; validation studies are 

ongoing (confirmed findings in two 

independent patient groups). 

Market: Cancer Vaccines are emerging 

as the forefront treatment regimens for 

several cancers. Provenge® was recently 

approved by the FDA for the treatment 

of prostate cancer. There are several 

other cancer vaccines in clinical trials. 

This technology can be developed 

into a pioneering test, as no such test to 

monitor prognosis and efficacy of cancer 

vaccines currently exists in the market. 

Inventors: Jeff Gildersleeve, et al. 

(NCI). 

Publications: No publications directly 

related to this technology. 

Patent Status: 

• U.S. Provisional Application No. 

61/371,537 filed August 6, 2010 (HHS 

Reference No. E–234–2010/0–US–01). 

• U.S. Provisional Application No. 

61/443,955 filed February 17, 2011 

(HHS Reference No. E–234–2010/1–US– 

01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sabarni Chatterjee, 

M.B.A., PhD; 301–435–5587; 

chatterjeesa@mail.nih.gov. 

Collaborative Research Opportunity: 

The Center for Cancer Research, 

Chemical Biology Laboratory, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize anti-glycan serum 

antibodies as biomarkers for cancer or 


Emcdonald on DSK2BSOYB1PROD with NOTICES
Federal Register / Vol. 76, No. 64 / Monday, April 4, 2011 / Notices 18565 

HIV vaccines and/or as prognostic 

biomarkers. Please contact John Hewes, 

PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

A New Class of Antibiotics: NaturallyOccurring Chrysophaetins and Their 

Analogues 

Description of Invention: This 

invention, offered for licensing and 

commercial development, relates to a 

new class of naturally occurring 

antimicrobial compounds called 

Chrysophaetins, and to their synthetic 

analogues. Isolated from an alga species, 

the mechanism of action of these 

compounds is through the inhibition of 

bacterial cytoskeletal protein FtsZ, an 

enzyme necessary for the replication of 

bacteria. FtsZ is responsible for Z-ring 

assembly in bacteria, which leads to 

bacterial cell division. Highly conserved 

among all bacteria, FtsZ is a very 

attractive antimicrobial target. 

The chrysophaetin exhibits 

antimicrobial activity against drug 

resistant bacteria, methicillin-resistant 

Staphylococcus aureus (MRSA) and 

vancomycin-resistant Enterococcus 

faecalis (VRE), as well as other drug 

susceptible strains. The general 

structure of the natural compound is 

shown below: 

BILLING CODE 4140–01–C 

The inventors are working on a 

synthetic route for the compound and 

analogs. They have made progress and 

now have two halves of the molecule. 

These will be further dimerized to 

produce a synthetic chrysophaentin. It 

is expected that the analogues will show 

similar antimicrobial activity to the 

natural products and will utilize the 

same mechanism of action. 

The market potential for the disclosed 

compounds is huge ($24 billion in 2008) 

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). A development of new drugs 

with distinct mechanism of action and 

efficacy against resistant bacterial 

strains may therefore be commercially 

attractive. 

Advantages include: 

• Structurally distinct antimicrobial 

compounds. 

• Attack newly validated antibacterial 

targeted protein FtsZ. 

• These compounds have a unique 

mechanism of action which works by 

inhibiting FtsZ GTPase activity. 

• The chrysophaentins can be 

obtained by synthetic routes through 

dimerization of their synthetic shorter 

analogues. 

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 do not share sequence homology to 

eukaryotic cytoskeletal protein tubulin, 

these compounds may have antitumor 

properties against some cancer types or 

cell lines. 

Development Status: 

• Initial isolation and chemical 

structural characterization using NMR 

spectroscopy have been conducted. 

• Antimicrobial testing against 

MRSA, Enterococcus 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. 

• Shorter analogues of the natural 

products have shown to be readily 

synthesized and synthetic 

chrysophaentins can be obtained from 

them by chemical dimerization. 

Inventors: Carole A Bewley Clore 

(NIDDK); Peter Wipf (U. of Pittsburgh). 

Relevant Publications: 

1. A. Plaza et al. Chrysophaentins 

A–H, antibacterial bisdiarylbutene 

macrocycles that inhibit the bacterial 

cell division protein FtsZ. J Am Chem 

Soc. 2010 Jul 7;132(26):9069–77. 

[PubMed: 20536175]. 

2. DJ Haydon et al. An inhibitor of 

FtsZ with potent and selective antistaphylococcal activity. Science. 2008 

Sept 19; 321(5896):1673–1675. 

[PubMed: 18801997]. 

3. 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]. 

4. 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]. 

5. P Domadia et al. Berberine targets 

assembly of Escherichia coli cell 

division protein FtsZ. Biochemistry. 

2008 Mar 11; 47(10):3225–3234. 

[PubMed: 18275156] 

6. P Domadia et al. Inhibition of 

bacterial cell division protein FtsZ by 

cinamaldehyde. Biochem Pharmacol. 

2007 Sep 15:74(6):831–840. [PubMed: 

17662960] 

7. 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: 

• PCT Application No. PCT/US2011/ 

026220 filed February 25, 2011 (HHS 

Reference No. E–116–2010/0–PCT–02). 

• U.S. Provisional Application No. 

61/446,978 filed February 25, 2011 

(HHS Reference No. E–115–2011/0–US– 

01). 

Licensing Status: Available for 

licensing. 

Licensing Contacts: 

• Uri Reichman, PhD, MBA; 301– 

435–4616; UR7a@nih.gov. 

• John Stansberry PhD; 301–435– 

5236; js852e@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 Marguerite J. Miller at 301–451– 

3636 or millermarg@niddk.nih.gov for 

more information. 

Dated: March 29, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–7921 Filed 4–1–11; 8:45 am] 

BILLING CODE 4140–01–P 


Emcdonald on DSK2BSOYB1PROD with NOTICESEN04AP11.006</GPH>