Adjuvant activities of mutants of LT-IIa and LT-IIb...

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...

Reexamination Certificate

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C424S257100, C424S234100, C424S190100, C424S282100, C424S201100, C424S203100, C424S202100, C424S192100, C424S193100, C514S002600

Reexamination Certificate

active

07455843

ABSTRACT:
The present invention describes the adjuvant activity of mutants of LT-IIa and LT-IIb enterotoxin which lack ganglioside binding activity. The adjuvant activity of the LT-IIb(T13I) mutant is comparable to that of the wild type LT-IIb. The adjuvant activity of LT-IIa(T34I) mutant is also described which exhibits a late onset adjuvant activity. These mutants are useful for enhancing immune response to antigens.

REFERENCES:
patent: 2002/0004238 (2002-01-01), Russell et al.
patent: WO- 01/27144 (2001-04-01), None
Nawar et al. Infect. Immun. 73: 1330-1342, Mar. 2005.
Connell, et al.,Molecular Genetic Analysis of Ganglioside GD1b-Binding Activity of Escherichia coli Type IIa Heat-Labile Enterotoxin by Use of Random and Site-Directed Mutagenesis, Infection and Immunity, Jan. 1992, vol. 60 No. 1, pp. 63-70.
Connell, et al.,Characterization of Hybrid Toxins Produced in Escherichi coli Assemby of A and B Polypeptides from Type I and Type II Heat-Labile Enterotoxins, Infection and Immunity, Apr. 1992, vol. 60, pp. 1653-1661.
Martin, et al.,Recombinant Antigen-Enterotoxin A2/B Chimeric Mucosal Immunogens Differentially Enhance Antibody Responses and B7-Dependent Costimulation of CD4+T Cells, Infection and Immunity, Jan. 2001, vol. 69 No. 1, pp. 252-261.
Martin, et al.,Distinct Cytokine Regulation by Cholera Toxin and Type II Heat-Labile Toxins Involves Differential Regulation of CD40 Ligand on CD4+T Cells, Infection and Immunity, Jul. 2001, vol. 69 No. 7, pp. 4486-4492.
Martin, et al.,Comparative Analysis of the Mucosal Adjuvanticity of the Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb, Infection and Immunity, Jan. 2000, vol. 68, NO. 1, pp. 281-287.
Connell, et al.,Immunostimulatory activity of LT-II a, a type II heat-labile enterotoxin of Escherichia coli, Elsevier Immunology Letters 62 (1998) pp. 117-120.
Martin, Michael,Immunomodulatory Effects of Type I and Type II Heat-Labile Enterotoxins on Mucosal and Systemic Immunity, Dissertation, (2000), Birmingham, Alabama.
Connell, et al.,Mutational analysis of the ganglioside-binding activity of the type II Escherichia coli heat-labile enterotoxin LT-IIb, Molecular Microbiology, 1995, 16(1): 21-31.
Pickett, et al.,Genetics of Type IIa Heat-Labile Enterotoxin of Escherichia coli: Operon Fusions, Nucleotide Sequence, and Hybridization Studies, Journal of Bacteriology, Nov. 1987: 5180-5187.

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