Anti-CD45 antibody drug conjugates and uses thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsAnthony Boitano, Michael Cooke, Geoffrey O. Gillard, Charlotte Fenton McDonagh, Rahul Palchaudhuri, Bradley R. Pearse
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Abstract
The invention provides anti-CD45 antibody drug conjugates (ADCs), and methods of use thereof. In one embodiment, the invention provides methods of depleting a population of CD45+ cells from a subject, by administration of an anti-CD45 ADC provided herein. In some embodiments, the ADCs include a cytotoxin containing a benzodiazepine moiety, for example. a pyrrolobenzodiazepine (PBD) or an indolinobenzodiazepine (IGN) moiety.
Claims12
A method of depleting a population of CD45+ cells in a human patient in need of a hematopoietic stem cell (HSC) transplant, the method comprising administering to the human patient an effective amount of an antibody-drug conjugate (ADC), such that a population of CD45+ cells are depleted, wherein the ADC comprises an anti-CD45 antibody or antigen binding portion thereof conjugated to a cytotoxin (Cy) via a linker (L), wherein the cytotoxin comprises an indolinobenzodiazepine (IGN) pseudodimer, and wherein the anti-CD45 antibody is an IgG isotype,
- wherein the cytotoxin-linker conjugate, prior to conjugation to the antibody or antigen binding portion thereof, and including the reactive substituent Z′, taken together as Cy-L-Z′, wherein the linker has a structure of formula:
- (VII).
A method of conditioning a human patient for receiving a hematopoietic stem cell (HSC) transplant, the method comprising administering to the human patient an antibody-drug conjugate (ADC), wherein the ADC comprises an anti-CD45 antibody or antigen binding portion thereof conjugated to a cytotoxin (Cy) via a linker (L), wherein the cytotoxin comprises an indolinobenzodiazepine (IGN) pseudodimer, and wherein the anti-CD45 antibody is an IgG isotype,
- wherein the cytotoxin-linker conjugate, prior to conjugation to the antibody or antigen binding portion thereof, and including the reactive substituent Z′, taken together as Cy-L-Z′
- wherein the linker has a structure of formula:
Dependencies are inferred from the claim text.