Antibody-coupled cyclic peptide tyrosine tyrosine compounds as modulators of neuropeptide Y receptors

A pharmaceutical composition comprising:

• a. a conjugate;
• b. an additional compound selected from the group consisting of a dipeptidyl peptidase-4 (DPP-4) inhibitor, a GLP-1 receptor agonist, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, a bile acid sequestrant, and a dopamine receptor agonist;
• and
• c. a pharmaceutically acceptable carrier;
• wherein the conjugate comprises a monoclonal antibody or an antigen binding fragment thereof coupled to a cyclic PYY peptide, and wherein the conjugate has a sequence selected from the group consisting of SEQ ID NOs:
• 102-127 or a pharmaceutically acceptable salt thereof,
• wherein mAb represents the monoclonal antibody or the antigen binding fragment thereof and comprises a heavy chain complementarity determining region 1 (HCDR1), a HCDR2, a HCDR3, a light chain complementarity determining region 1 (LCDR1), a LCDR2, and a LCDR3 having the polypeptide sequences of SEQ ID NO:141, 142, 143, 144, 145, and 146, respectively, and ]2 represents that 1 or 2 of the cyclic PYY peptide are covalently conjugated to the mAb.

A pharmaceutical composition comprising:

• a) a conjugate;
• b) an additional compound selected from the group consisting of a dipeptidyl peptidase-4 (DPP-4) inhibitor, a GLP-1 receptor agonist, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, a bile acid sequestrant, and a dopamine receptor agonist;
• and
• c) a pharmaceutically acceptable carrier;
• wherein the conjugate comprises a monoclonal antibody or an antigen binding fragment thereof coupled to a cyclic PYY peptide, wherein:
• the monoclonal antibody or the antigen binding fragment thereof comprises a heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, having the polypeptide sequences of SEQ ID NO:
• 141, 142, 143, 144, 145, and 146, respectively;
• the cyclic PYY peptide comprises a polypeptide sequence selected from the group consisting of SEQ ID NOs:
• 1, 73-100, and 147-156, or a pharmaceutically acceptable salt thereof;
• and
• the monoclonal antibody or antigen binding fragment thereof is conjugated to the cyclic PYY peptide at residue 7, 9, 11, 22 or 23 of the cyclic PYY peptide, directly or via a linker.