Title:
COMPOSITIONS AND METHODS RELATING TO A MUTANT CLOSTRIDIUM DIFFICILE TOXIN
Document Type and Number:
WIPO Patent Application WO/2014/060898
Kind Code:
A3
Abstract:
In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. The mutant toxin may include a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to methods and compositions for use in culturing Clostridium difficile and in producing C. difficile toxins.
Inventors:
JANSEN KATHRIN UTE (US)
ANDERSON ANNALIESA SYBIL (US)
DONALD ROBERT G K (US)
FLINT MICHAEL JAMES (US)
KALYAN NARENDER KUMAR (US)
LOTVIN JASON ARNOLD (US)
SIDHU MANINDER K (US)
MORAN JUSTIN KEITH (US)
RUPPEN MARK EDWARD (US)
SUN WEIQIANG (US)
ANDERSON ANNALIESA SYBIL (US)
DONALD ROBERT G K (US)
FLINT MICHAEL JAMES (US)
KALYAN NARENDER KUMAR (US)
LOTVIN JASON ARNOLD (US)
SIDHU MANINDER K (US)
MORAN JUSTIN KEITH (US)
RUPPEN MARK EDWARD (US)
SUN WEIQIANG (US)
Application Number:
PCT/IB2013/059183
Publication Date:
June 12, 2014
Filing Date:
October 07, 2013
Export Citation:
Assignee:
PFIZER (US)
International Classes:
C12N1/20; C07K14/33
Domestic Patent References:
| WO2012143902A1 | 2012-10-26 |
Other References:
A. FANG ET AL: "Production of Clostridium difficile toxin in a medium totally free of both animal and dairy proteins or digests", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 106, no. 32, 11 August 2009 (2009-08-11), pages 13225 - 13229, XP055095937, ISSN: 0027-8424, DOI: 10.1073/pnas.0906425106
R. G. K. DONALD ET AL: "A novel approach to generate a recombinant toxoid vaccine against Clostridium difficile", MICROBIOLOGY, vol. 159, no. Pt_7, 29 April 2013 (2013-04-29), pages 1254 - 1266, XP055095934, ISSN: 1350-0872, DOI: 10.1099/mic.0.066712-0
MICHAELS J D ET AL: "Polyvinyl alcohol and polyethylene glycol as protectants against fluid-mechanical injury of freely-suspended animal cells (CRL 8018)", JOURNAL OF BIOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 19, no. 2-3, 1 July 1991 (1991-07-01), pages 241 - 257, XP023944215, ISSN: 0168-1656, [retrieved on 19910701], DOI: 10.1016/0168-1656(91)90062-Z
HEAP J T ET AL: "A modular system for Clostridium shuttle plasmids", JOURNAL OF MICROBIOLOGICAL METHODS, ELSEVIER, AMSTERDAM, NL, vol. 78, no. 1, 1 July 2009 (2009-07-01), pages 79 - 85, XP026148475, ISSN: 0167-7012, [retrieved on 20090513], DOI: 10.1016/J.MIMET.2009.05.004
J SCOTT MONCRIEF ET AL: "Isolates by PCR difficile Clostridium A-Negative, Toxin B-Positive Genetic Characterization of Toxin", 1 January 2000 (2000-01-01), pages 3072, XP055095950, Retrieved from the Internet
HEAP J T ET AL: "The ClosTron: Mutagenesis in Clostridium refined and streamlined", JOURNAL OF MICROBIOLOGICAL METHODS, ELSEVIER, AMSTERDAM, NL, vol. 80, no. 1, 1 January 2010 (2010-01-01), pages 49 - 55, XP026807597, ISSN: 0167-7012, [retrieved on 20091103]
DATABASE Geneseq [online] 26 April 2012 (2012-04-26), "Clostridium difficile strain 630 trdA protein SEQ:6.", XP002718658, retrieved from EBI accession no. GSP:AZU07697 Database accession no. AZU07697
DATABASE Geneseq [online] 21 February 2008 (2008-02-21), "Clostridium difficile toxin B protein.", XP002718659, retrieved from EBI accession no. GSP:AOG16927 Database accession no. AOG16927
R. G. K. DONALD ET AL: "A novel approach to generate a recombinant toxoid vaccine against Clostridium difficile", MICROBIOLOGY, vol. 159, no. Pt_7, 29 April 2013 (2013-04-29), pages 1254 - 1266, XP055095934, ISSN: 1350-0872, DOI: 10.1099/mic.0.066712-0
MICHAELS J D ET AL: "Polyvinyl alcohol and polyethylene glycol as protectants against fluid-mechanical injury of freely-suspended animal cells (CRL 8018)", JOURNAL OF BIOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 19, no. 2-3, 1 July 1991 (1991-07-01), pages 241 - 257, XP023944215, ISSN: 0168-1656, [retrieved on 19910701], DOI: 10.1016/0168-1656(91)90062-Z
HEAP J T ET AL: "A modular system for Clostridium shuttle plasmids", JOURNAL OF MICROBIOLOGICAL METHODS, ELSEVIER, AMSTERDAM, NL, vol. 78, no. 1, 1 July 2009 (2009-07-01), pages 79 - 85, XP026148475, ISSN: 0167-7012, [retrieved on 20090513], DOI: 10.1016/J.MIMET.2009.05.004
J SCOTT MONCRIEF ET AL: "Isolates by PCR difficile Clostridium A-Negative, Toxin B-Positive Genetic Characterization of Toxin", 1 January 2000 (2000-01-01), pages 3072, XP055095950, Retrieved from the Internet
HEAP J T ET AL: "The ClosTron: Mutagenesis in Clostridium refined and streamlined", JOURNAL OF MICROBIOLOGICAL METHODS, ELSEVIER, AMSTERDAM, NL, vol. 80, no. 1, 1 January 2010 (2010-01-01), pages 49 - 55, XP026807597, ISSN: 0167-7012, [retrieved on 20091103]
DATABASE Geneseq [online] 26 April 2012 (2012-04-26), "Clostridium difficile strain 630 trdA protein SEQ:6.", XP002718658, retrieved from EBI accession no. GSP:AZU07697 Database accession no. AZU07697
DATABASE Geneseq [online] 21 February 2008 (2008-02-21), "Clostridium difficile toxin B protein.", XP002718659, retrieved from EBI accession no. GSP:AOG16927 Database accession no. AOG16927
Attorney, Agent or Firm:
KLEIMAN, Gabriel L. (235 East 42nd StreetNew York, New York, US)
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