Fusion protein comprising apelin and an anti-APLNR antibody

A protein comprising (i) an immunoglobulin (Ig) molecule or antigen-binding fragment thereof and (ii) an apelin peptide, wherein the Ig molecule comprises a heavy chain variable region (HCVR), and a light chain variable region (LCVR), wherein:

• (a) the HCVR and LCVR together comprise six complementarity determining regions HCDR1-HCDR2-HCDR3-LCDR1-LCDR2-LCDR3 contained with an HCVR/LCVR amino acid sequence pair selected from the group consisting of SEQ ID NOs:
• 2/10, 18/26, 34/42, 50/58, 66/74, 82/90, 98/106, 114/122, 130/138, 146/154, 162/170, 178/186, 194/202, 210/218, 287/295, 303/311, 319/327, 335/343, 351/359 and 367/375;
• and
• (b) the apelin peptide:
• (i) comprises an amino acid sequence selected from the group consisting of:
• SEQ ID NO:
• 227, SEQ ID NO:
• 228, SEQ ID NO:
• 229, SEQ ID NO:
• 230, SEQ ID NO:
• 262, SEQ ID NO:
• 269, SEQ ID NO:
• 270, SEQ ID NO:
• 271, SEQ ID NO:
• 272, SEQ ID NO:
• 273, SEQ ID NO:
• 283, SEQ ID NO:
• 284, and SEQ ID NO:
• 285;
• or
• (ii) is selected from the group consisting of amino acid residues 6-77, 40-77, 42-77, 43-77, 47-77, 59-77, 61-77, 63-77, 64-77, 65-77, 66-77, 67-77, 73-77, 1-25, 6-25, 42-64, 61-64, 61-74, 61-75, 61-76, 65-76, 65-75, 42-58, 42-57, 42-56, 42-55, 42-54, 42-53, and pyroglutamylated apelin65-77 of the preproapelin polypeptide of SEQ ID NO:
• 227;
• or
• (iii) is selected from the group consisting of:
• apelin40-77 (apelin-38), apelin42-77 (apelin-36), apelin43-77 (apelin-35), apelin47-77 (apelin-31), apelin59-77 (apelin-19), apelin61-77 (apelin-17), apelin63-77 (apelin-15), apelin64-77 (apelin-14), apelin65-77 (apelin-13), apelin66-77 (apelin-12, or A12), apelin67-77 (apelin-11), apelin68-77 (apelin-10), apelin73-77 (apelin-5), apelin61-76 (apelin-K16P), apelin61-75 (apelin-K15M), apelin61-74 (apelin-K14P), and [Pyr1]Apelin-13.