Methods for treating autoimmune diseases

A method of conditioning a human patient having an autoimmune disease for receiving a hematopoietic stem cell (HSC) transplant, the method comprising administering to the human patient having the autoimmune disease an antibody-drug conjugate (ADC) comprising an anti-CD45 antibody, or antigen binding portion thereof, conjugated to a cytotoxin via a linker.

A method of treating a patient having scleroderma or multiple sclerosis, said method comprising administering an anti-CD45 antibody drug conjugate (ADC) to the patient having scGVHD, such that the scGVHD is treated, wherein the anti-CD45 ADC comprises an anti-CD45 antibody, or fragment thereof, conjugated to a cytotoxin via a linker.

The method of any one of the preceding claims, wherein the anti-CD45 ADC is administered to the patient as a single dose or as a fractionated dose.

The method of any one of the preceding claims, wherein the patient does not require treatment for the autoimmune disease following transplantation.

The method of any one of the preceding claims, wherein the anti-CD45 antibody is a chimeric antibody or a humanized antibody.

The method of any one of the preceding claims, wherein the anti-CD45 antibody is a human antibody.

The method of any one of the preceding claims, wherein the anti-CD45 antibody is intact.

The method of any one of the preceding claims, wherein the anti-CD45 antibody or antigen-binding portion thereof is selected from the group consisting of a monoclonal antibody or antigen-binding portion thereof, a polyclonal antibody or antigen-binding portion thereof, a bispecific antibody or antigen-binding portion thereof, a dual-variable immunoglobulin domain, a single-chain Fv molecule (scFv), a diabody, a triabody, a nanobody, an antibody-like protein scaffold, a Fv fragment, a Fab fragment, a F(ab′)2 molecule, and a tandem di-scFv.

The method of any one of the preceding claims, wherein the anti-CD45 antibody has an isotype selected from the group consisting of IgG, IgA, IgM, IgD, and IgE.

The method of any one of the preceding claims, wherein the anti-CD45 antibody, or antigen binding 85 portion thereof, comprises an Fc domain, and wherein the anti-CD45 antibody, or antigen binding portion thereof, is conjugated to the cytotoxin by way of a cysteine residue in the Fc domain.

The method of any one of the preceding claims, wherein the cytotoxin is selected from the group consisting of an pseudomonas exotoxin A, deBouganin, diphtheria toxin, saporin, maytansine, a maytansinoid, an auristatin, an anthracycline, a calicheamicin, irinotecan, SN-38, a duocarmycin, a pyrrolobenzodiazepine, a pyrrolobenzodiazepine dimer, an indolinobenzodiazepine, and an indolinobenzodiazepine dimer.

The method of any one of the preceding claims, wherein the anti-CD45 ADC has a formula of

• wherein Ab represents the anti-CD45 antibody.

The method of any one of the preceding claims, wherein the anti-CD45 ADC has a formula of

• wherein Ab represents the anti-CD45 antibody.

A method of depleting a population of CD45+ cells in a human patient having an autoimmune disease, the method comprising administering to the patient having the autoimmune disease an effective amount of an engineered toxin body targeting CD45.