Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 11 to 14 amino acid residues in defined sequence
Patent
1989-05-17
1992-06-16
Nucker, Christine
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
11 to 14 amino acid residues in defined sequence
424 852, 424 854, 424 855, 424 856, 424 857, 424 8591, 514 2, 514 3, 514 4, 514 8, 514 14, 514 21, 514 23, 514 34, 530303, 530328, 530351, 530394, 530399, 530402, 530404, 530405, 530408, 530409, 5303919, 536 11, 536 64, A61K 3726, A61K 3743, A61K 3766, A61K 3944, C07K 708, C07K 730, C07K 740, C07K 1706
Patent
active
051223686
ABSTRACT:
The invention relates to anthracycline conjugates comprising at least one anthracycline molecule linked to a molecule that is reactive with a cell population to be eliminated such as antibody, bombesin, EGF and transferrin. Each anthracycline molecule, having a keto group at the C-13 position, is conjugated to the antibody via a linker arm and is bound to that linker arm via an acid-sensitive acylhydrazone bond at the 13-keto position of the anthracycline. The linker additionally contains a disulfide or thioether linkage as part of the antibody or ligand attachment to the immunoconjugate. The novel anthracycline acylhydrazone derivatives are useful in the preparation of the conjugates of this invention. The acid-sensitive hydrazone bond of the conjugates of this invention allows the release of free anthracycline from the conjugates in the acidic external or internal environment of the target cell. The conjugates and methods of the invention are therefore useful in antibody- or ligand-mediated drug delivery systems for the preferential killing of a selected cell population in the treatment of diseases such as cancers and other tumors, non-cytocidal viral or other pathogenic infections, and autoimmune disorders.
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Braslawsky Gary R.
Greenfield Robert S.
Kaneko Takushi
Kiener Peter A,
Olech Lee J.
Barnett Deborah
Bristol--Myers Squibb Company
Kim Kay K.
Nucker Christine
Yang Mollie M.
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