Cysteine engineered antibody drug conjugates
AssigneePfizer Inc.
InventorsMadan Katragadda, Russell Dushin, Lawrence Nathan Tumey
Life of this patent
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Abstract
The invention relates to polypeptides, antibodies, and antigen-binding fragments thereof, that comprise an engineered cysteine for site-specific conjugation.
Claims22
An antibody drug conjugate of formula Ab-(L-D), wherein:
- (a) Ab is an antibody or an antigen binding fragment thereof comprising an antibody heavy chain constant domain containing an engineered cysteine residue at position 334, according to the numbering of the Eu index of Kabat;
- and
- (b) L-D is a linker-drug moiety that is attached to the Ab via the engineered cysteine residue, wherein L is a linker and D is a CPI dimer.
An antibody drug conjugate of formula Ab-(L-D), wherein:
- (a) Ab is an antibody comprising an antibody heavy chain constant domain containing an engineered cysteine residue at a position corresponding to residue 104 of SEQ ID NO:
- 25, when the heavy chain constant domain is aligned with SEQ ID NO:
- 25;
- and
- (b) L-D is a linker-drug moiety, wherein L is a linker and D is a CPI dimer;
- and wherein the L-D moiety is attached to the Ab via the engineered cysteine residue.
An antibody drug conjugate of formula Ab-(L-D), wherein:
- (a) Ab is an antibody or an antigen binding fragment thereof comprising an antibody heavy chain constant domain containing an engineered cysteine residue at position 334, according to the numbering of the Eu index of Kabat;
- and
- (b) L-D is a linker-drug moiety that is attached to the Ab via the engineered cysteine site, wherein L is MalPeg6-vc-PABC-DMAE, and wherein D is a CPI dimer selected from the group consisting of:
A pharmaceutical composition comprising the antibody drug conjugate of any preceding claim and a pharmaceutically acceptable carrier.
A method of treating cancer, an autoimmune disease, an inflammatory disease, or an infectious disease, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody drug conjugate of any preceding claim.
Dependencies are inferred from the claim text.