Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated to proteinaceous toxin or fragment thereof
Patent
1990-12-03
2000-08-08
Eyler, Yvonne
Drug, bio-affecting and body treating compositions
Conjugate or complex of monoclonal or polyclonal antibody,...
Conjugated to proteinaceous toxin or fragment thereof
4241781, 5303917, A61K 3940, A61K 3942, A61K 3944, A61K 39395
Patent
active
060998423
ABSTRACT:
Single chain immunotoxins directed at the human transferrin receptor using PCR based methods are described. Anti-TFR(Fv)-PE40 contains DNA for the antigen binding portion (Fv) of a monoclonal antibody directed at the human transferrin receptor fused to the DNA for a 40,000 molecular weight fragment of Pseudomonas exotoxin (PE40). In another fusion protein, DT388-anti-TFR(Fv), DNA for the antigen binding portions of the anti-TFR antibody has been fused to the DNA encoding a truncated form of Diphtheria toxin. In anti-TFR(Fv)-PE40, the single chain antibody precedes the toxin whereas in DT388-anti-TFR(Fv) the single chain antibody is at the carboxyl end of toxin. The proteins encoded by these gene fusions were expressed in E.coli and purified by conventional chromatographic techniques to near homogeneity.
REFERENCES:
patent: 4892827 (1990-01-01), Pastan et al.
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Youle et al 1988 Immunotoxins. Frankel A.E. ed. 113-122.
V.K. Chaudhary, et al., A Recombinant Immunotoxin Consisting of Two Antibody Variable Domains Fused to Pseudomonas Exotoxin, Nature, vol. 339, No. 6223, Jun., 1989, pp. 394-397.
J.K. Batra, et al., Single-Chain Immunotoxins Directed at the Human Transferrin Receptor Containing Pseudomonas Exotoxin A or Diphtheria Toxin: Anti-TFR(Fv)-PE40 and DT388-Anti-TFR(Fv), Mol. Cell. Biol., vol. 11, No. 4, Apr., 1991, pp. 220-2205.
V.K. Chaudhary, et al., A Recombinant Single-Chain Immunotoxin Composed of Anti-TAC Variable Regions and A Truncated Diphtheria Toxin, Proc. Natl. Acad. Sci. USA, vol. 87, Dec., 1990, pp. 9491-9494.
J.K. Batra, et al., Anti-TAC(Fv)-PE40: A Single Chain Antibody Pseudomonas, Fusion Protein Directed at Interleukin 2 Receptor Bearing Cells, J. Biol. Chem., vol. 256, No. 25, 1990, pp. 15198-15202.
V.K. Chaudhary, et al., A Rapid Method of Cloning Functional Variable-Region Antibody Genes in Escherichia coli as Single-Chain Immunotoxins, Proc. Natl. Acad. Sci. USA, vol. 87, Feb., 1990, pp. 1066-1070.
J.K. Batra, et al., Antitumor Activity in Mice of an Immunotoxin Made with Anti-Transferrin Receptor and a Recombinant Form of Pseudomonas Exotoxin, Proc. Natl. Acad. Sci. USA, vol. 86, Nov., 1989, pp. 8545-8549.
T. Kondo, et al., Activity of Immunotoxins Constructed with Modified Pseudomonas Exotoxin a Lacking the Cell Recognition Domain, J. Biol. Chem., vol. 263, No. 10, 1988, pp. 9470-9475.
Batra Janendra
Chaudhary Vijay
FitzGerald David
Pastan Ira
Andres Janet
Eyler Yvonne
The United States of America as represented by the Department of
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