Site specific HER2 antibody drug conjugates
The present invention provides site specific HER2 antibody drug conjugates and methods for preparing and using the same.
1. An antibody drug conjugate of the formula: Ab-(L-D),
wherein:
(a) Ab is an antibody that binds to HER2 and comprises a heavy chain comprising SEQ ID NO:18 and a light chain comprising SEQ ID NO:42; and
(b) L-D is a linker-drug moiety, wherein L is maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc) and D is 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide or a pharmaceutically acceptable salt or solvate thereof.
2. A pharmaceutical composition comprising the antibody drug conjugate of claim 1 and a pharmaceutically acceptable carrier.
3. A composition comprising a plurality of an antibody drug conjugates of claim 1 , and optionally a pharmaceutical carrier, wherein the composition has a DAR of 4.
4. An antibody drug conjugate of the formula: Ab-(L-D),
wherein:
a) Ab is an antibody that binds to HER2 and comprises a heavy chain polypeptide encoded by the nucleic acid set forth in ATCC Accession No. PTA-122673 and a light chain polypeptide encoded by the nucleic acid set forth in ATCC Accession Nos. PTA-122672; and
b) L-D is a linker-drug moiety, wherein L is maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (vc) and D is 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1 S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide or a pharmaceutically acceptable salt or solvate thereof.
5. A pharmaceutical composition comprising the antibody drug conjugate of claim 4 and a pharmaceutically acceptable carrier.
6. A composition comprising a plurality of an antibody drug conjugates of claim 4 , and optionally a pharmaceutical carrier, wherein the composition has a DAR of 4.