US 12,473,369 B2
Fusion protein of anti-eta antibody and tgf-beta trap and pharmaceutical composition and application thereof in method of treatment
Cheng Zhang, Hangzhou (CN); Chenjiang Yao, Hangzhou (CN); Hua Zhang, Hangzhou (CN); Xiaofeng Wang, Hangzhou (CN); and Shuqian Jing, Hangzhou (CN)
Assigned to GMAX BIOPHARM LLC, Hangzhou (CN)
Appl. No. 17/627,089
Filed by GMAX BIOPHARM LLC, Hangzhou (CN)
PCT Filed Jul. 14, 2020, PCT No. PCT/CN2020/101857
§ 371(c)(1), (2) Date Jan. 13, 2022,
PCT Pub. No. WO2021/008519, PCT Pub. Date Jan. 21, 2021.
Claims priority of application No. 201910645466.X (CN), filed on Jul. 17, 2019.
Prior Publication US 2022/0265771 A1, Aug. 25, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 38/17 (2006.01); A61K 39/395 (2006.01); A61K 47/68 (2017.01); A61P 9/00 (2006.01); A61P 9/12 (2006.01); A61P 11/00 (2006.01); C07K 14/71 (2006.01); C12N 15/63 (2006.01); A61K 39/00 (2006.01); C07K 14/495 (2006.01); C07K 14/72 (2006.01)
CPC C07K 16/2869 (2013.01) [A61K 38/179 (2013.01); A61K 39/3955 (2013.01); A61K 47/6811 (2017.08); A61K 47/6835 (2017.08); A61P 9/00 (2018.01); A61P 9/12 (2018.01); A61P 11/00 (2018.01); C07K 14/71 (2013.01); C12N 15/63 (2013.01); A61K 2039/505 (2013.01); C07K 14/495 (2013.01); C07K 14/72 (2013.01); C07K 2317/565 (2013.01); C07K 2319/00 (2013.01); C07K 2319/30 (2013.01); C07K 2319/32 (2013.01)] 19 Claims
 
1. A fusion protein of an anti-endothelin A receptor (anti-ETA) antibody and a transforming growth factor β (TGF-β) Trap or a fragment thereof, structurally characterized in that the fusion protein comprises an anti-ETA antibody and a TGF-β Trap or a fragment thereof, wherein the TGF-β Trap or fragment thereof comprises the amino acid sequence of SEQ ID NO: 207, and the anti-ETA antibody comprises:
(a) light chain CDR1 amino acid sequence: SEQ ID NO: 8;
light chain CDR2 amino acid sequence: SEQ ID NO: 32;
light chain CDR3 amino acid sequence: SEQ ID NO: 50 or SEQ ID NO: 205;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 70;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 92; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 116;
(b) light chain CDR1 amino acid sequence: SEQ ID NO: 10;
light chain CDR2 amino acid sequence: SEQ ID NO: 34;
light chain CDR3 amino acid sequence: SEQ ID NO: 52;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 72;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 94; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 118;
(c) light chain CDR1 amino acid sequence: SEQ ID NO: 12;
light chain CDR2 amino acid sequence: SEQ ID NO: 36;
light chain CDR3 amino acid sequence: SEQ ID NO: 54;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 74;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 96; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 120;
(d) light chain CDR1 amino acid sequence: SEQ ID NO: 14;
light chain CDR2 amino acid sequence: SEQ ID NO: 38;
light chain CDR3 amino acid sequence: SEQ ID NO: 56;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 76;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 98; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 122;
(e) light chain CDR1 amino acid sequence: SEQ ID NO: 16;
light chain CDR2 amino acid sequence: SEQ ID NO: 40;
light chain CDR3 amino acid sequence: SEQ ID NO: 58;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 78;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 100; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 124;
(f) light chain CDR1 amino acid sequence: SEQ ID NO: 18;
light chain CDR2 amino acid sequence: SEQ ID NO: 42;
light chain CDR3 amino acid sequence: SEQ ID NO: 60;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 80;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 102; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 126;
(g) light chain CDR1 amino acid sequence: SEQ ID NO: 20;
light chain CDR2 amino acid sequence: SEQ ID NO: 44;
light chain CDR3 amino acid sequence: SEQ ID NO: 62;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 82;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 104; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 128;
(h) light chain CDR1 amino acid sequence: SEQ ID NO: 22;
light chain CDR2 amino acid sequence: SEQ ID NO: 44;
light chain CDR3 amino acid sequence: SEQ ID NO: 62;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 82;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 106; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 128;
(i) light chain CDR1 amino acid sequence: SEQ ID NO: 24;
light chain CDR2 amino acid sequence: SEQ ID NO: 44;
light chain CDR3 amino acid sequence: SEQ ID NO: 62;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 84;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 108; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 130;
(j) light chain CDR1 amino acid sequence: SEQ ID NO: 26;
light chain CDR2 amino acid sequence: SEQ ID NO: 46;
light chain CDR3 amino acid sequence: SEQ ID NO: 64;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 86;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 110; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 132;
(k) light chain CDR1 amino acid sequence: SEQ ID NO: 28;
light chain CDR2 amino acid sequence: SEQ ID NO: 46;
light chain CDR3 amino acid sequence: SEQ ID NO: 66;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 88;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 112; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 134; or
(l) light chain CDR1 amino acid sequence: SEQ ID NO: 30;
light chain CDR2 amino acid sequence: SEQ ID NO: 48;
light chain CDR3 amino acid sequence: SEQ ID NO: 68;
heavy chain CDR1 amino acid sequence: SEQ ID NO: 90;
heavy chain CDR2 amino acid sequence: SEQ ID NO: 114; and
heavy chain CDR3 amino acid sequence: SEQ ID NO: 136.