Anti-her2 biparatopic antibody-drug conjugates and methods of use
AssigneeZymeworks Inc.
InventorsKevin HAMBLETT, Rupert H. DAVIES, James R. RICH, Gerald J. ROWSE, Vincent K.C. FUNG, Stuart D. BARNSCHER
Life of this patent
Estimating the term…
Abstract
Anti-HER2 biparatopic antibody-drug conjugates (ADCs) in which the drug is an auristatin analogue and is conjugated to the antibody at a low average drug-to-antibody ratio (DAR), and methods of using the ADCs in the treatment of a HER2-expressing cancer. The low average DAR (<3.9) ADCs as described herein have improved tolerability and decreased toxicity as compared to a corresponding ADC having a DAR ≥3.9 when administered at the same toxin dose.
Claims57
An antibody-drug conjugate comprising an anti-HER2 biparatopic antibody conjugated to an auristatin analogue via a linker (L) at a low average drug-to-antibody ratio (DAR),
- wherein the anti-HER2 biparatopic antibody comprises a first antigen-binding polypeptide construct which binds a first HER2 epitope and a second antigen-binding polypeptide construct which binds a second HER2 epitope, wherein the first and second HER2 epitopes are on different domains of HER2,
- wherein the auristatin analogue and linker have general Formula (X)
- wherein:
- R1 is selected from:
- L is the linker, and
- represents the point of attachment of the linker to the anti-HER2 biparatopic antibody, and
- wherein the low average DAR is an average DAR of between 1.5 and 2.5.
(canceled)
(canceled)
6-8. (canceled)
10-11. (canceled)
16-17. (canceled)
26-27. (canceled)
(canceled)
31-33. (canceled)
36-37. (canceled)
(canceled)
(canceled)
(canceled)
48-49. (canceled)
The antibody-drug conjugate according to claim 491, wherein the anti-HER2 biparatopic antibody comprises an IgG Fc region that is a heterodimeric Fc region comprising a modified CH3 domain.
(canceled)
(canceled)
60-71. (canceled)
Dependencies are inferred from the claim text.