AR097401A1 - ANTIBODIES THAT JOIN THE PROLACTIN RECEIVER (ANTI-PRLR) AND USES OF THE SAME - Google Patents

Abstract

In accordance with certain embodiments, the antibodies herein bind to human PRLR with high affinity. In certain embodiments, antibodies that bind to PRLR and block prolactin-mediated cell signaling are included. In other embodiments, antibodies that bind PRLR are included, but do not block prolactin-mediated cell signaling. The antibodies can be fully human antibodies. It includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide or other moiety that is detrimental to cell growth or proliferation. Antibodies are useful for the treatment of different cancers, as well as other disorders related to PRLR. It also includes antibody and drug conjugates comprising an antibody or antigen binding fragment thereof that specifically binds to a class I cytokine receptor, wherein the antibody or antigen binding fragment thereof is conjugated to a cytotoxic agent Claim 1: An isolated antibody or antigen-binding fragment thereof that binds to the prolactin receptor (PRLR), wherein the antibody or antigen-binding fragment thereof exhibits one or more properties selected from the group consisting of: (i ) binds to the monomeric human PRLR at 37 ° C with a KD of less than about 4.0 nM, measured by surface plasmon resonance; (ii) binds to the monomeric human PRLR at 37 ° C with a t½ of more than about 5 minutes, measured by surface plasmon resonance; (iii) binds to the dimeric human PRLR at 37 ° C with a KD of less than about 250 pM, measured by surface plasmon resonance; (iv) binds to the dimeric human PRLR at 37 ° C with a t½ of more than about 55 minutes, measured by surface plasmon resonance; and (v) blocks prolactin-mediated signaling in cells expressing human PRLR with an IC₅₀ of less than about 1.3 nM.