[Federal Register Volume 76, Number 64 (Monday, April 4, 2011)]
[Notices]
[Pages 18564-18565]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-7921]


-----------------------------------------------------------------------

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 
sub-populations 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 long-term 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[supreg] 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; 
[email protected].
    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

[[Page 18565]]

HIV vaccines and/or as prognostic biomarkers. Please contact John 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

A New Class of Antibiotics: Naturally-Occurring 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:
[GRAPHIC] [TIFF OMITTED] TN04AP11.006

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 
anti-staphylococcal activity. Science. 2008 Sept 19; 321(5896):1673-
1675. [PubMed: 18801997].
    3. NR Stokes et al. Novel inhibitors of bacterial cytokinesis 
identified by a cell-based 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; [email protected].
     John Stansberry PhD; 301-435-5236; [email protected].
    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 [email protected] 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