FcεPE chimeric protein for targeted treatment of...

Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated to proteinaceous toxin or fragment thereof

Reexamination Certificate

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C424S144100, C424S193100, C424S197110, C530S388220, C530S391700

Reexamination Certificate

active

06919079

ABSTRACT:
The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the FcεRI receptor by a chimeric cytotoxin Fc2′-3-PE40. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE40—a truncated form of PE lacking the cell binding domain. The chimeric protein, produced inE. coli, specifically and efficiently kills mouse mast cell lines expressing the FcεRI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of FcεRI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for FcεRI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product ofPseudomonas aeruginosa. The present invention also relates to a method for the preparation of said protein. This chimeric protein is prepared by genetically fusing the Fc region of the mouse IgE molecule to PE40, a truncated form of PE lacking the cell binding domain. The present invention also provides pharmaceutical compositions, for the treatment of allergic diseases and for the treatment of hyperplasias and malignancies, comprising as an active ingredient the above mentioned chimeric protein and a conventional adjuvant product.

REFERENCES:
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patent: WO 9012592 (1990-11-01), None
patent: WO 9111456 (1991-08-01), None
patent: WO 9404689 (1994-03-01), None
Boltansky et al. Immunopharmacology, vol. 14(1) pp. 47-62, 1987.
Kondo et al. J.B.C. vol. 263(19), 9470-9475, 1988.
Nature, vol. 331, Jan. 14, 1988, pp. 180-183, Helm et al., “The mast cell binding site on human immunoglobulin E”.
The Journal of Immuonololgy, vol. 140, No. 8, Apr. 15, 1988, pp. 2585-2588, Kitani et al., “Inhibition of Allergic Reactions with Monoclonal Antibody to the High Affinity IgE Receptor”.
Nature, vol. 339, No. 6223, Jun. 1, 1989, pp. 394-397, Chaudhary V. K. et al., “A recombinant immunotoxin consisting of two antibody variable domains fused to pseudomonas exotoxin.”
The Journal of Biological Chemistry, vol. 263, No. 19, Jul. 5, 1988, pp. 9470-9475, Kondo et al., “Activity of Immunotoxins Constructed With Modified Pseudomonas Exotoxin a Lacking the Cell Recognition Domain”.

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