Nemorubicin metabolite and analog reagents, antibody-drug conjugates and methods
AssigneeGenentech, Inc.
InventorsRobert L. Cohen, Edward HyungSuk Ha, Mark E. Reynolds
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Abstract
The present invention relates to antibody-drug conjugate compounds of Formula I: Ab-(L-D)p I where one or more nemorubicin metabolite or analog drug moieties (D) are covalently attached by a linker (L) to an antibody (Ab) which binds to one or more tumor-associated antigens or cell-surface receptors. These compounds may be useful in methods of diagnosis or treatment of cancer, and other diseases and disorders.
Claims9
A drug-linker reagent comprising the structure:
- wherein X4 is a linker comprising a thiol reactive functional group selected from maleimide, iodoacetamide, bromoacetamide, vinyl pyridine, disulfide, pyridyl disulfide, isocyanate, and isothiocyanate.
An antibody-drug conjugate compound comprising an antibody covalently attached by a linker to one or more nemorubicin metabolite or analog drug moieties, the compound having Formula I:
- Ab-(L-D)p I
- or a pharmaceutically acceptable salt thereof, wherein:
- Ab is the antibody;
- L is the linker;
- and
- D is the nemorubicin metabolite or analog drug moiety having the structure:
- wherein L is attached at Z4;
- Ab is attached to L by a disulfide bond;
- and
- p is 1, 2, 3, 4, 5, 6, 7, or 8.
Dependencies are inferred from the claim text.