US 12,312,405 B2
Anti-PD-1 antibodies
David A. Blair, Sandy Hook, CT (US); Nicole K. Garaffa, Trumbull, CT (US); Pankaj Gupta, Scarsdale, NY (US); Priyanka Gupta, Newtown, CT (US); Fei Han, Acton, MA (US); Aaron Timothy Karlak, Beacon Falls, CT (US); Dongmei Liu, Oxford, CT (US); Mouhamadou Lamine Mbow, Echichens (CH); Joseph A. Mozdzierz, Mahopac, NY (US); Kerry L. M. Ralph, Bethel, CT (US); Abdulsalam Shaaban, Ridgefield, CT (US); Helen Haixia Wu, Danbury, CT (US); and Guangwei Yang, Cheshire, CT (US)
Assigned to Boehringer Ingelheim International GmbH
Filed by Boehringer Ingelheim International GmbH, Ingelheim am Rhein (DE)
Filed on May 24, 2021, as Appl. No. 17/328,050.
Claims priority of provisional application 63/039,686, filed on Jun. 16, 2020.
Claims priority of provisional application 63/029,962, filed on May 26, 2020.
Prior Publication US 2021/0380696 A1, Dec. 9, 2021
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2818 (2013.01) [C07K 16/2803 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/75 (2013.01); C07K 2317/92 (2013.01)] 86 Claims
 
1. An anti-Programmed cell death 1 (PD-1) antibody or antigen-binding fragment thereof comprising:
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 (H-CDR1); the amino acid sequence of SEQ ID NO: 44 (H-CDR2); and the amino acid sequence of SEQ ID NO: 45 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 1 (L-CDR1); the amino acid sequence of SEQ ID NO: 2 (L-CDR2); and the amino acid sequence of SEQ ID NO: 3 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 (H-CDR1); the amino acid sequence of SEQ ID NO: 46 (H-CDR2); and the amino acid sequence of SEQ ID NO: 45 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 1 (L-CDR1); the amino acid sequence of SEQ ID NO: 2 (L-CDR2); and the amino acid sequence of SEQ ID NO: 3 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 47 (H-CDR1); the amino acid sequence of SEQ ID NO: 48 (H-CDR2); and the amino acid sequence of SEQ ID NO: 49 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 (L-CDR1); the amino acid sequence of SEQ ID NO: 5 (L-CDR2); and the amino acid sequence of SEQ ID NO: 6 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 50 (H-CDR1); the amino acid sequence of SEQ ID NO: 51 (H-CDR2); and the amino acid sequence of SEQ ID NO: 52 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7 (L-CDR1); the amino acid sequence of SEQ ID NO: 8 (L-CDR2); and the amino acid sequence of SEQ ID NO: 9 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 53 (H-CDR1); the amino acid sequence of SEQ ID NO: 54 (H-CDR2); and the amino acid sequence of SEQ ID NO: 55 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 10 (L-CDR1); the amino acid sequence of SEQ ID NO: 11 (L-CDR2); and the amino acid sequence of SEQ ID NO: 12 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 56 (H-CDR1); the amino acid sequence of SEQ ID NO: 57 (H-CDR2); and the amino acid sequence of SEQ ID NO: 58 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 13 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 15 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 59 (H-CDR1); the amino acid sequence of SEQ ID NO: 60 (H-CDR2); and the amino acid sequence of SEQ ID NO: 61 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16 (L-CDR1); the amino acid sequence of SEQ ID NO: 17 (L-CDR2); and the amino acid sequence of SEQ ID NO: 18 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 62 (H-CDR1); the amino acid sequence of SEQ ID NO: 63 (H-CDR2); and the amino acid sequence of SEQ ID NO: 64 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 19 (L-CDR1); the amino acid sequence of SEQ ID NO: 20 (L-CDR2); and the amino acid sequence of SEQ ID NO: 21 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 65 (H-CDR1); the amino acid sequence of SEQ ID NO: 66 (H-CDR2); and the amino acid sequence of SEQ ID NO: 67 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22 (L-CDR1); the amino acid sequence of SEQ ID NO: 23 (L-CDR2); and the amino acid sequence of SEQ ID NO: 24 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 68 (H-CDR1); the amino acid sequence of SEQ ID NO: 69 (H-CDR2); and the amino acid sequence of SEQ ID NO: 70 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25 (L-CDR1); the amino acid sequence of SEQ ID NO: 26 (L-CDR2); and the amino acid sequence of SEQ ID NO: 27 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 71 (H-CDR1); the amino acid sequence of SEQ ID NO: 72 (H-CDR2); and the amino acid sequence of SEQ ID NO: 58 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 29 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 74 (H-CDR2); and the amino acid sequence of SEQ ID NO: 75 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 76 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 164 (L-CDR1); the amino acid sequence of SEQ ID NO: 31 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 78 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 166 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 73 (H-CDR1); the amino acid sequence of SEQ ID NO: 79 (H-CDR2); and the amino acid sequence of SEQ ID NO: 77 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 165 (L-CDR1); the amino acid sequence of SEQ ID NO: 167 (L-CDR2); and the amino acid sequence of SEQ ID NO: 32 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 80 (H-CDR1); the amino acid sequence of SEQ ID NO: 81 (H-CDR2); and the amino acid sequence of SEQ ID NO: 82 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33 (L-CDR1); the amino acid sequence of SEQ ID NO: 14 (L-CDR2); and the amino acid sequence of SEQ ID NO: 34 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 83 (H-CDR1); the amino acid sequence of SEQ ID NO: 84 (H-CDR2); and the amino acid sequence of SEQ ID NO: 85 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 16 (L-CDR1); the amino acid sequence of SEQ ID NO: 35 (L-CDR2); and the amino acid sequence of SEQ ID NO: 36 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 86 (H-CDR1); the amino acid sequence of SEQ ID NO: 87 (H-CDR2); and the amino acid sequence of SEQ ID NO: 88 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 37 (L-CDR1); the amino acid sequence of SEQ ID NO: 38 (L-CDR2); and the amino acid sequence of SEQ ID NO: 39 (L-CDR3),
or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 89 (H-CDR1); the amino acid sequence of SEQ ID NO: 90 (H-CDR2); and the amino acid sequence of SEQ ID NO: 91 (H-CDR3), and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40 (L-CDR1); the amino acid sequence of SEQ ID NO: 41 (L-CDR2); and the amino acid sequence of SEQ ID NO: 42 (L-CDR3).