New antibody or antigen-binding portion that competes for binding to P-cadherin or binds to the same epitope of P-cadherin, useful for treating abnormal cell growth, including cancer, e.g. prostate cancer or bladder cancer

摘要

An antibody or antigen-binding portion that increases spheroid disruption in a P-cadherin-dependent spheroid disruption assay, competes for binding to P-cadherin, or binds to the same epitope of P-cadherin, is new. A new antibody or antigen-binding portion has at least one property selected from: (a) a K d(E)/K d(P) that is greater than or equal to 1.5; (b) binds to P-cadherin with a K d of 50 nM or less as measured by surface plasmon resonance; (c) a k off for P-cadherin of less than or equal to 0.01 s-1> as measured by surface plasmon resonance; (d) an IC 50 of 50 nM or less as measured by a P-cadherin dependent cell adhesion assay; (e) an IC 50 of 50 nM or less as measured by a P-cadherin dependent cell aggregation assay; (f) increases spheroid disruption in a P-cadherin-dependent spheroid disruption assay by a factor of 2 or more as compared to a control sample with no IgG; (g) competes for binding to P-cadherin with an antibody selected from 194-e06; 194-a02; 194-b09; 195-e11; 194-g09; 196-h02; 194-e01; 196-d10; 196-g03; 196-e06; 195-a09; 198-a09; 200-h06; g-194-b09; g-194-g09; g-196-g03; g-196-h02; g-194-e01; g-194-e06; 129-1c4; or g-129-1c4; (h) cross-competes for binding to P-cadherin with an antibody selected from 194-e06; 194-a02; 194-b09; 195-e11; 194-g09; 196-h02; 194-e01; 196-d10; 196-g03; 196-e06; 195-a09; 198-a09; 200-h06; g-194-b09; g-194-g09; g-196-g03; g-196-h02; g-194-e01; g-194-e06129-1c4; or g-129lc4; (i) binds to the same epitope of P-cadherin as an antibody selected from 194-e06; 194-a02; 194-b09; 195-e11; 194-g09; 196-h02; 194-e01; 196-d10; 196-g03; 196-e06; 195-a09; 198-a09; 200-h06; g-194-b09; g-194-g09; g-196-g03; g-196-h02; g-194-e01; g-194-e06; 129-1c4; or g-129-1c4; (j) binds to P-cadherin with substantially the same K d as an antibody selected from 194-e06; 194-a02; 194-b09; 195-e11; 194-909; 196-h02; 194-e01; 196-d10; 196-g03; 196-e06; 195-a09; 198-a09; 200-h06; g-194-b09; g-194-g09; g-196-g03; g-196-h02; g-194-e01; g-194-e06; 129-1c4; or g-129-1c4; or (k) binds to P-cadherin with substantially the same koff as an antibody selected from 194-e06; 194-a02; 194-b09; 195-e11; 194-g09; 196-h02; 194-e01; 196-d10; 196-g03; 196-e06; 195-a09; 198-a09; 200-h06; g-194-b09; g-194-g09; g-196-g03; g-196-h02; g-194-e01; g-194-e06; 129-1c4; and g-129-1c4. ACTIVITY : Cytostatic. No biological data given. MECHANISM OF ACTION : Gene therapy; P-cadherin antagonist.