Alpha-fetoprotein bioconjugates for disease treatment
AssigneeAlpha Cancer Technologies Inc.
InventorsIgor Sherman, Mark Frigerio, Anthony Godwin, Jieyu Zhou
Life of this patent
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Abstract
Bioconjugates are described comprising alpha-fetoprotein (AFP) linked with a cytotoxin through a disulfide, glutathione-sensitive linker, for cancer treatment. In a preferred embodiment, the bioconjugate is an AFP variant linked with a maytansinoid cytotoxin via the glutathione-sensitive linker so that the bioconjugate comprises either specific high or low ratio of cytotoxins per AFP.
Claims21
1-101. (canceled)
A bioconjugate useful in the treatment of diseased cells, comprising
- (1) an agent that binds to alpha-fetoprotein (AFP) receptor (AFPR) on the surface of a cell;
- (2) a cytotoxin (CT) that is toxic to the cell, and
- (3) a glutathione-cleavable disulphide linker, wherein the linker
- (i) is coupled covalently between the AFPR-binding agent and the CT, and
- (ii) releases the CT intracellularly to the cell.
A bioconjugate of the formula:
- wherein AFP is an AFP receptor-binding form of alpha-fetoprotein.
A process for producing a bioconjugate whereby the cytotoxin ABZ-981 is first coupled with a glutathione-sensitive disulfide linker to produce an intermediate:
- that is then reacted with an AFPR-binding form of AFP that is recombinant [Asn233Gln] mature human AFP comprising SEQ ID No.3, and the intermediate is coupled covalently to the epsilon amino groups of lysine residues in the AFP.
Dependencies are inferred from the claim text.