[Federal Register Volume 72, Number 97 (Monday, May 21, 2007)]
[Notices]
[Pages 28511-28512]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-9656]


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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.

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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 Method With Increased Yield for Production of Polysaccharide-Protein 
Conjugate Vaccines Using Hydrazide Chemistry

    Description of Technology: Current methods for synthesis and 
manufacturing of polysaccharide-protein conjugate vaccines employ 
conjugation reactions with low efficiency (about twenty percent). This 
means that up to eighty percent of the added activated polysaccharide 
(PS) is lost. In addition, inclusion of a chromatographic process for 
purification of the conjugates from unconjugated PS is required.
    The present invention utilizes the characteristic chemical property 
of hydrazide groups on one reactant to react with aldehyde groups or 
cyanate esters on the other reactant with an improved conjugate yield 
of at least sixty percent. With this conjugation efficiency the 
leftover unconjugated protein and polysaccharide would not need to be 
removed and thus the purification process of the conjugate product can 
be limited to diafiltration to remove the by-products of small 
molecules. The new conjugation reaction can be carried out within one 
or two days with reactant concentrations between 1 and 25 mg/mL at PS/
protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 
degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions 
varying from PS to PS.
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee and Carl E. Frasch (CBER/FDA).
    Patent Status: U.S. Patent Application No. 10/566,899 filed 01 Feb 
2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/0-
US-10); U.S. Patent Application No. 10/566,898 filed 01 Feb 2006, 
claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/1-US-
02); International rights available.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

A Method of Immunizing Humans Against Salmonella Typhi Using a Vi-rEPA 
Conjugate Vaccine

    Description of Technology: This invention is a method of 
immunization against typhoid fever using a conjugate vaccine comprising 
the capsular polysaccharide of Salmonella typhi, Vi, conjugated through 
an adipic dihydrazide linker to nontoxic recombinant exoprotein A 
(rEPA) from Pseudomonas aeruginosa. The three licensed vaccines against 
typhoid fever, attenuated S. typhi Ty21a, killed whole cell vaccines 
and Vi polysaccharide, have limited efficacy, in particular for 
children under 5 years of age, which make an improved vaccine 
desirable.
    It is generally recognized that an effective vaccine against 
Salmonella typhi is one that increases serum anti-Vi IgG eight-fold six 
weeks after immunization. The conjugate vaccine of the invention 
increases anti-Vi IgG, 48-fold, 252-fold and 400-fold in adults, in 5-
14 years-old and 2-4 years-old children, respectively. Thus this is a 
highly effective vaccine suitable for children and should find utility 
in endemic regions and as a traveler's vaccine. The route of 
administration can also be combined with routine immunization. In 2-5 
years old, the protection against typhoid fever is 90% for 4 years. In 
school age children and in adults the protection could mount to 
completer protection according to the immunogenicity data.
    Application: Immunization against Salmonella typhi for long term 
prevention of typhoid fever in all ages.
    Developmental Status: Conjugates have been synthesized and clinical 
studies have been performed. The synthesis of the conjugates is 
described by Kossaczka et al. in Infect Immun. 1997 June;65(7):2088-
2093. Phase III clinical studies are described by Mai et al. in N Engl 
J Med. 2003 October 2; 349(14):1390-1391. Dosage studies are described 
by Canh et al. in Infect Immun. 2004 Nov;72(11):6586-6588.
    A safety and immunogenicity study in infants are underway. The aim 
is to administer the conjugate vaccine with routine infant 
immunization. Preliminary results show the vaccine is safe in 2 months 
old infants.
    Inventors: Zuzana Kossaczka, Shousun C. Szu, and John B. Robbins 
(NICHD).
    Patent Status: U.S. Patent 6,797,275 issued 28 Sep 2004 (HHS 
Reference No. E-020-1999/0-US-02); U.S. Patent Application No. 10/
866,343 filed 10 Jun 2004 (HHS Reference No. E-020-1999/0-US-03); U.S. 
Patent Application No. 11/726,304 filed 20 Mar 2007 (HHS Reference No. 
E-020-1999/0-US-04).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Laboratory of Developmental and Molecular 
Immunity, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize A Method of Immunizing Humans Against Salmonella Typhi 
Using a Vi-rEPA Conjugate Vaccine. Please contact John D. Hewes, Ph.D., 
at 301-435-3121 or [email protected] for more information.

[[Page 28512]]

Vaccine Against Escherichia Coli 0157 Infection, Composed of Detoxified 
LPS Conjugated to Proteins

    Description of Technology: This invention is a conjugate vaccine to 
prevent infection by E. coli 0157:H7, particularly in young children 
under 5 years of age. E. coli 0157:H7 is an emerging human pathogen 
which causes a spectrum of illnesses with high morbidity and mortality, 
ranging from diarrhea to hemorrhagic colitis and hemolytic-uremic 
syndrome (HUS). Infection with E. coli 0157:H7 occurs as a result of 
consumption of water, vegetables, fruits or meat contaminated by feces 
from infected animals, such as cattle. The most recent large outbreak 
in the U.S. was from contaminated bag spinach. The conjugate is 
composed of the O-specific polysaccharide isolated from E. coli 0157, 
or other Shiga-toxin producing bacteria, conjugated to carrier 
proteins, such as non-toxic P. aeruginosa exotoxin A or Shiga toxin 1. 
A Phase I clinical trial, involving adult humans, showed the vaccine is 
safe and highly immunogenic. Adults, after one injection containing 25 
[mu]g of antigen, responded with high titers of bactericidal 
antibodies. Similarly in a phase II study, fifty 2-to-5- years old 
children in U.S. were injected with the conjugate vaccines. There were 
only mild local adverse reactions. More than 90% of the children 
responded with greater than 10 fold rise of E. coli O157 antibodies of 
bactericidal ability. Thus the conjugates of the invention are 
promising vaccines, especially for children and the elderly, who are 
most likely to suffer serious consequences from infection.
    Application: Prevention of E. coli O157 infection.
    Development Status: Clinical studies have been performed and are 
described in Konadu et al., J Infect Dis. 1998 Feb; 177(2):383-387 and 
Ahmed et al., J Infect Dis. 2006 Feb; 193(2):515-526.
    Inventors: Shousun C. Szu, Edward Konadu, and John B. Robbins 
(NICHD).
    Patent Status: U.S. Patent 6,858,211 issued 22 Feb 2005 (HHS 
Reference No. E-158-1998/0-US-06); U.S. Patent Application No. 10/
987,428 filed 12 Nov 2004 (HHS Reference No. E-158-1998/0-US-07); U.S. 
Patent Application No. 11/015,436 filed 16 Dec 2004 (HHS Reference No. 
E-158-1998/0-US-08).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Laboratory of Developmental and Molecular 
Immunity, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize Vaccine for E. coli O157 for Children and Adults. Please 
contact John D. Hewes, Ph.D., at 301-435-3121 or [email protected] 
for more information.

    Dated: May 11, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E7-9656 Filed 5-18-07; 8:45 am]
BILLING CODE 4140-01-P