Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1996-03-08
1998-11-17
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
514 2, 532324, 424832, A61K 3900, A61K 3902, A61K 3906
Patent
active
058372652
ABSTRACT:
The invention consists of modified Clostridium neurotoxin compounds, pharmaceutical compositions containing such compounds and methods for preparing such compounds. In particular, the compounds of the invention are purified Clostridium botulinum and Clostridium tetani neurotoxins in which the tyrosine residues have been modified to have a negative charge (e.g., by covalent attachment of a phosphate or sulphate thereto) or in which the tyrosine residues have been substituted with amino acids having a negative charge (e.g., glutamate, aspartate, or negatively charged, non-natural amino acids). Toxins having phosphorylated tyrosine residues in both the light and heavy chains of the toxins are preferred. Methods for enzymatic and chemical modification of tyrosine residues in purified Clostridium neurotoxins are provided.
REFERENCES:
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Database Medline, US National Library of Medicine (Bethesda, MD), No. 89261699, M. Woody et al., "Effects of Tetranitromethane on the Biological Activities of Botulinum Neurotixin Types A, B and E", Abstract.
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Ferrer-Montiel, et al., "Tyrosine Phosphorylation Modulates the Activity of Clostridial Neurotoxins," Journal of Biological Chemistry, vol. 271, No. 31, pp. 18322-18325, Aug. 2, 1996.
Pernollet, et al., "OH Treatment of Tetanus Toxin Reduced its Susceptibility to Limited Proteolysis with More Efficient Presentation to . . . ", Molecular Immunology, vol. 30, No. 18, pp. 1639-1646, 1993.
Chemical Abstracts, vol. 80, 1974, p. 307, col. 2, abstract No. 25783x, Bizzini et al., "Immunochemistry of Tetanus Toxin. Nitration of Tyrosyl Residues in Tetanus Toxin.", Eur. J. Biochem., 1973, vol. 39, No. 1.
Sakurai et al., "The Inactivation of Clostridium Perfringens Epsilon Toxin by Treatment with Tetranitromethane and N-Acetylimidazole," Toxicon, vol. 25, No. 3, pp. 279-284, 1987.
Woody et al. Effect of tetranitromethane on biological activities of botulinum neurotioxin types A,B, and E. Mol. Cell. Biochemistry, 85:159-169, Jan. 1989.
Ferrer-Montiel Antonio
Montal Mauricio
Borin Michael
The Regents of the University of California
Tsang Cecilia J.
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