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US 4,981,953 AGranted
Immunotoxins, process for their preparation and pharmaceutical compositions in which they are present
AssigneeSanofi
InventorsLuigi Barbieri, Pierre Casellas, Fiorenzo Stirpe
Life of this patent
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Abstract
The present invention relates to the immunotoxines which are obtained by the covalent coupling of, on the one hand, trichosanthin or trichokirin, as such or appropriately modified with, on the other hand, an antibody or antibody fragment, used in its natural form or correctly modified, which is capable of selectively recognizing an antigen carried by the target cells to be destroyed.
Claims12
An immunotoxin formed by the coupling of an antibody with trichokirin, having the following statistical formula:
- P'--W--A'
- in which P' represents the radical of a protein P which is an antibody or antibody fragment, A' represents the radical of a protein A which is trichokirin, and W represents a divalent covalent structure containing at least one thioether group or one disulfide group in which one of the sulfur atoms is selected from the sulfurs of the cysteines of P or A or is bonded to the groups belonging to P and/or A by spacing structures carrying a functional group bonded to the said groups belonging to P and A.
A process for the preparation of an immunotoxin having the following statistical formula:
- P'--W--A'
- in which P' represents the radical of a protein which is an antibody or antibody fragment, A' represents the radical of a protein A which is trichokirin, and W represents a divalent covalent structure containing at least one thioether group or one disulfide group in which one of the sulfur atoms is selected from the sulfurs of the cysteines of P or A or is bonded to the groups belonging to P and/or A by spacing structures carrying a functional group bonded to the said groups belonging to P and/or A, wherein a protein P.sub.1, which is modified trichokirin or an antibody or antibody fragment, carrying at least one free thiol group attached to the said protein P.sub.1 directly or via a spacing structure, is reacted, in aqueous solution and at room temperature, with a protein P.sub.2 which is different from .sub.1, which is modified trichokirin or an antibody or antibody fragment, carrying a group capable of coupling with the free thiol of the protein P.sub.1 to form a thioether or disulfide bond.
Dependencies are inferred from the claim text.