IP Library › Granted Patent US 9,725,505

Granted Patent B2

US 9,725,505 · App. 14/863,870 · Granted Aug 8, 2017

Methods of treatment using anti-GDF15 antibodies

Inventors: Lorena Lerner (Newton Centre, MA); Sandra Abbott (Boston, MA); Ailin Bai (Newton, MA); Ting Chen (Acton, MA); Maria I. Chiu (Newton Centre, MA); Qing Liu (Acton, MA); Laura Poling (Boston, MA); Nianjun Tao (Brighton, MA); Solly Weiler (Newton, MA); Zhigang Weng (Brookline, MA); William M. Winston, Jr. (Marlborough, MA); Jeno Gyuris (Lincoln, MA)

Assignee: AVEO Pharmaceuticals, Inc.

C07K16/22 A61K39/3955 A61K45/06 A61K2039/505 C07K2317/24 C07K2317/76 C07K2317/92 C07K2319/30

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Quick Facts

Patent No.: US 9,725,505
App. No.: 14/863,870
Granted: Aug 8, 2017
Kind: B2

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Abstract

Monoclonal antibodies that bind and inhibit the activity of human GDF15 are disclosed. The antibodies can be used to treat body weight loss, including cachexia, associated with the over-expression of human GDF15.

Claims (1079)

1. A method of treating cachexia in a mammal comprising administering an effective amount of an anti-GDF15 antibody or antigen-binding fragment thereof comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region selected from the group consisting of:

(a) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F2), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:237, SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-18 F2), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F2); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(b) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:234 and SEQ ID NO:235 (Hu01G06 IGHV1-69 F1), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:238, SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-69 F1), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(c) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L, a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(d) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:2 (03G05), a CDR H2 comprising the amino acid sequence of SEQ ID NO:8 (03G05), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:16 (03G05); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:22 (03G05), a CDR L2 comprising the amino acid sequence of SEQ ID NO:27 (03G05), and a CDR L3 comprising the amino acid sequence of SEQ ID NO 33 (03G05);

(e) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:3 (04F08), a CDR H2 comprising the amino acid sequence of SEQ ID NO:9 (04F08), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:17 (04F08); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (04F08), a CDR L2 comprising the amino acid sequence of SEQ ID NO:28 (04F08), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:34 (04F08);

(f) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:4 (06C11, Ch06C11 Chimeric, Hu06C11 IGHV2-5), a CDR H2 comprising the amino acid sequence of SEQ ID NO:9 (06C11, Ch06C11 Chimeric, Hu06C11 IGHV2-5), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:18 (06C11, Ch06C11 Chimeric, Hu06C11 IGHV2-5); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (06C11, Ch06C11 Chimeric, Sh06C11 IGKV1-16), a CDR L2 comprising the amino acid sequence of SEQ ID NO:28 (06C11, Ch06C11 Chimeric, Sh06C11 IGKV1-16), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:35 (06C11, Ch06C11 Chimeric, Sh06C11 IGKV1-16);

(g) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:1 (08G01), a CDR H2 comprising the amino acid sequence of SEQ ID NO:10 (08G01), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:15 (08G01); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:24 (08G01), a CDR L2 comprising the amino acid sequence of SEQ ID NO:29 (08G01), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (08G01);

(h) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:5 (14F11, Ch14F11 Chimeric, Sh14F11 IGHV2-5, Sh14F11 IGHV2-70), a CDR H2 comprising the amino acid sequence of SEQ ID NO:11 (14F11, Ch14F11 Chimeric, Sh14F11 IGHV2-5, Sh14F11 IGHV2-70), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:19 (14F11, Ch14F11 Chimeric, Sh14F11 IGHV2-5, Sh14F11 IGHV2-70); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (14F11, Ch14F11 Chimeric, Hu14F11 IGKV1-16), a CDR L2 comprising the amino acid sequence of SEQ ID NO:30 (14F11, Ch14F11 Chimeric, Hu14F11 IGKV1-16), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:36 (14F11, Ch14F11 Chimeric, Hu14F11 IGKV1-16);

(i) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:6 (17B11), a CDR H2 comprising the amino acid sequence of SEQ ID NO:12 (17B11), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:20 (17B11); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:25 (17B11), a CDR L2 comprising the amino acid sequence of SEQ ID NO:31 (17B11), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:37 (17B11);

(j) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q); and

(k) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F1), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:236, SEQ ID NO:240 and SEQ ID NO:242 (Hu01G06 IGHV1-18 F1), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(l) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:234, and SEQ ID NO:235 (Hu01G06 IGHV1-69 F2), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:239, SEQ ID NO:240 and SEQ ID NO:242 (Hu01G06 IGHV1-69 F2), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F2); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(m) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:234 and SEQ ID NO:235 (Hu01G06 IGHV1-69 F2), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:239, SEQ ID NO:240 and SEQ ID NO:242 (Hu01G06 IGHV1-69 F2), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F2); and

(n) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:4 (HE LM 06C11 IGHV2-70), a CDR H2 comprising the amino acid sequence of SEQ ID NO:14 (HE LM 06C11 IGHV2-70), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:18 (HE LM 06C11 IGHV2-70); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (Ch06C11 Chimeric, Sh06C11 IGKV1-16), a CDR L2 comprising the amino acid sequence of SEQ ID NO:28 (Ch06C11 Chimeric, Sh06C11 IGKV1-16), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:35 (Ch06C11 Chimeric, Sh06C11 IGKV1-16);

(o) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:4 (Ch06C11 Chimeric), a CDR H2 comprising the amino acid sequence of SEQ ID NO:9 (Ch06C11 Chimeric), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:18 (Ch06C11 Chimeric); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (Ch14F11 Chimeric), a CDR L2 comprising the amino acid sequence of SEQ ID NO:30 (Ch14F11 Chimeric), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:36 (Ch14F11 Chimeric);

(p) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising the amino acid sequence of SEQ ID NO:5 (Ch14F11 Chimeric), a CDR H2 comprising the amino acid sequence of SEQ ID NO:11 (Ch14F11 Chimeric), and a CDR H3 comprising the amino acid sequence of SEQ ID NO:19 (Ch14F11 Chimeric); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO:23 (Ch06C11 Chimeric), a CDR L2 comprising the amino acid sequence of SEQ ID NO:28 (Ch06C11 Chimeric), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:35 (Ch06C11 Chimeric);

(q) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Sh01G06 IGHV1-69 T30S I69L), a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-69 T30S I69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-69 T30S I69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(r) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Sh01G06 IGHV1-69 T30S K64Q I69L), a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-69 T30S K64Q I69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-69 T30S K64Q I69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(s) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F2); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:237, SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-18 F2), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F2); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(t) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(u) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-18 M69L K64Q G44S, Sh01G06 IGHV1-18 M69L K64Q); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(v) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Sh01G06 IGHV1-69 T30S I69L); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-69 T30S I69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-69 T30S I69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(w) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Sh01G06 IGHV1-69 T30S K64Q I69L); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-69 T30S K64Q I69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-69 T30S K64Q I69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(x) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F1); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:236, SEQ ID NO:240 and SEQ ID NO:242 (Hu01G06 IGHV1-18 F1), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2); and

(y) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Hu01G06 IGHV1-69 F1); a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:238, SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-69 F1), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2)

to a mammal in need thereof.

2. A method of inhibiting loss of muscle mass associated with cachexia comprising administering an effective amount of an anti-GDF15 antibody or antigen-binding fragment thereof comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region selected from the group consisting of:

(a) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F2), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:237, SEQ ID NO:241and SEQ ID NO:243 (Hu01G06 IGHV1-18 F2), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F2); and

(b) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Hu01G06 IGHV1-69 F1), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:238, SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-69 F1), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(c) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L,); and

(k) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, and SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F1), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:236, SEQ ID NO:240 and SEQ ID NO:242 (Hu01G06 IGHV1-18 F1), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2) to prevent or reduce loss of muscle mass.

3. The method of claim 2 , wherein the cachexia is associated with an underlying disease selected from the group consisting of cancer, chronic heart failure, chronic kidney disease, COPD, AIDS, multiple sclerosis, rheumatoid arthritis, sepsis, and tuberculosis.

4. The method of claim 2 , wherein the loss of muscle mass is accompanied by a loss of fat mass.

5. A method of inhibiting or reducing involuntary weight loss associated with cachexia in a mammal comprising administering an effective amount of an anti-GDF15 antibody or antigen-binding fragment thereof comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region selected from the group consisting of:

(a) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:38 and SEQ ID NO:136 (Hu01G06 IGHV1-18 F2), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:237 and SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-18 F2), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-18 F2); and

(b) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:234 and SEQ ID NO:235 (Hu01G06 IGHV1-69 F1), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:238 and SEQ ID NO:241 and SEQ ID NO:243 (Hu01G06 IGHV1-69 F1), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Hu01G06 IGHV1-69 F1); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(c) (i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:38 and SEQ ID NO:136 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:143 and SEQ ID NO:148 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L), and a CDR H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (01G06, Ch01G06 Chimeric, Hu01G06 IGHV1-18, Hu01G06 IGHV1-69, Sh01G06 IGHV1-18 M69L); and

(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F1), a CDR L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F1), and a CDR L3 comprising the amino acid sequence of SEQ ID NO:32 (Hu01G06 IGKV1-39 F1);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(r) (i) an immunoglobulin heavy chain variable region comprising a CDRH1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:234 and SEQ ID NO:235 (Sh01G06 IGHV1-69 T30S K64Ql I69L), a CDRH2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:143 and SEQ ID NO:148 (Sh01G06 IGHV1-69 T30S K64Q I69L), and a CDRH3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15 and SEQ ID NO:154 (Sh01G06 IGHV1-69 T30S K64Q I69L); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:32 (01G06, Ch01G06 Chimeric, Hu01G06 IGKV1-39, Hu01G06 IGKV1-39 S43A V48I, Hu01G06 IGKV1-39 V48I);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2);

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2); and

(ii) an immunoglobulin light chain variable region comprising a CDRL1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21 and SEQ ID NO:160 (Hu01G06 IGKV1-39 F2), a CDRL2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:26 and DAK (Hu01G06 IGKV1-39 F2); and a CDRL3 comprising the amino acid sequence of SEQ ID NO:244 (Hu01G06 IGKV1-39 F2)

to a mammal in need thereof.

6. A method of inhibiting loss of organ mass associated with cachexia comprising administering an effective amount of an anti-GDF15 antibody or antigen-binding fragment thereof comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region selected from the group consisting of: