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US 2022/0177589 A1Published application
Btla antibodies
AssigneesOxford University Innovation Limited, MiroBio Limited
InventorsSimon John Davis, Richard John Cornall, Christopher Douglas Paluch
Life of this patent
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Abstract
This invention relates generally to antibodies or antigen binding fragments that bind to human B and T lymphocyte attenuator (BTLA) and uses thereof. More specifically, the invention relates to agonistic antibodies that bind human BTLA and modulate its activity, and their use in treating inflammatory, autoimmune and proliferative diseases and disorders.
Claims22
1-95. (canceled)
A method of modulating an immune response in a subject, comprising administering to the subject an antibody or an antigen-binding fragment thereof that specifically binds B and T Lymphocyte Attenuator (BTLA),
- wherein the antibody or antigen-binding fragment thereof:
- (i) comprises a heavy chain and a light chain;
- (ii) agonizes BTLA expressed on the surface of an immune cell;
- and
- (iii) binds a residue of BTLA selected from the group consisting of:
- D52, P53, E55, E57, E83, Q86, E103, L106 and E92.
3 more elements
The method of 105, wherein CDRL2 has no amino acid modifications as compared to SEQ ID NO:
- 143.
The method of 105, wherein CDRH2 has an amino acid modification at position 5, position 7, or both, numbered according to SEQ ID NO:
- 387.
The method of 107, wherein CDRL2 has no amino acid modifications as compared to SEQ ID NO:
- 143.
The method of 105, wherein the light chain variable region comprises the amino acid sequence as set forth in SEQ ID NO:
- 378.
An antibody or an antigen-binding fragment thereof that specifically binds BTLA, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising three CDRs:
- CDRH1, CDRH2 and CDRH3, wherein (1) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 31, SEQ ID NO:
- 32, and SEQ ID NO:
- 33, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 34, SEQ ID NO:
- 35, and SEQ ID NO:
- 36, respectively, with from 0 to 3 amino acid modifications;
- (2) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 37, SEQ ID NO:
- 38, and SEQ ID NO:
- 39, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 40, SEQ ID NO:
- 41, and SEQ ID NO:
- 42, respectively, with from 0 to 3 amino acid modifications;
- (3) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 43, SEQ ID NO:
- 44, and SEQ ID NO:
- 45, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 6, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, respectively, with from 0 to 3 amino acid modifications;
- (4) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 43, SEQ ID NO:
- 56, and SEQ ID NO:
- 57, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 58, SEQ ID NO:
- 59, and SEQ ID NO:
- 60, respectively, with from 0 to 3 amino acid modifications;
- (5) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 61, SEQ ID NO:
- 62, and SEQ ID NO:
- 63, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 64, SEQ ID NO:
- 65, and SEQ ID NO:
- 66, respectively, with from 0 to 3 amino acid modifications;
- (6) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 31, SEQ ID NO:
- 32, and SEQ ID NO:
- 69, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 34, SEQ ID NO:
- 35, and SEQ ID NO:
- 72, respectively, with from 0 to 3 amino acid modifications;
- (7) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 73, SEQ ID NO:
- 74, and SEQ ID NO:
- 75, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 76, SEQ ID NO:
- 47, and SEQ ID NO:
- 78, respectively, with from 0 to 3 amino acid modifications;
- (8) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 79, SEQ ID NO:
- 80, and SEQ ID NO:
- 81, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 82, SEQ ID NO:
- 83, and SEQ ID NO:
- 84, respectively, with from 0 to 3 amino acid modifications;
- (9) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 85, SEQ ID NO:
- 86, and SEQ ID NO:
- 87, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 88, SEQ ID NO:
- 89, and SEQ ID NO:
- 90, respectively, with from 0 to 3 amino acid modifications;
- (10) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 61, SEQ ID NO:
- 92, and SEQ ID NO:
- 93, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 94, SEQ ID NO:
- 95, and SEQ ID NO:
- 96, respectively, with from 0 to 3 amino acid modifications;
- (11) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 97, SEQ ID NO:
- 98, and SEQ ID NO:
- 99, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 100, SEQ ID NO:
- 101, and SEQ ID NO:
- 102, respectively, with from 0 to 3 amino acid modifications;
- (12) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 103, SEQ ID NO:
- 104, and SEQ ID NO:
- 105, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 64, SEQ ID NO:
- 107, and SEQ ID NO:
- 108, respectively, with from 0 to 3 amino acid modifications;
- (13) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 109, SEQ ID NO:
- 110, and SEQ ID NO:
- 111, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 88, SEQ ID NO:
- 89, and SEQ ID NO:
- 114, respectively, with from 0 to 3 amino acid modifications;
- (14) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 85, SEQ ID NO:
- 110, and SEQ ID NO:
- 117, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 88, SEQ ID NO:
- 89, and SEQ ID NO:
- 114, respectively, with from 0 to 3 amino acid modifications;
- (15) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 121, SEQ ID NO:
- 122, and SEQ ID NO:
- 123, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 124, SEQ ID NO:
- 125, and SEQ ID NO:
- 126, respectively, with from 0 to 3 amino acid modifications;
- (16) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 127, SEQ ID NO:
- 128, and SEQ ID NO:
- 129, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 34, SEQ ID NO:
- 35, and SEQ ID NO:
- 36, respectively, with from 0 to 3 amino acid modifications;
- (17) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 133, SEQ ID NO:
- 134, and SEQ ID NO:
- 135, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 136, SEQ ID NO:
- 137, and SEQ ID NO:
- 138, respectively, with from 0 to 3 amino acid modifications;
- (18) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 139, SEQ ID NO:
- 140, and SEQ ID NO:
- 141, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 142, SEQ ID NO:
- 143, and SEQ ID NO:
- 144, respectively, with from 0 to 3 amino acid modifications;
- (19) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 145, SEQ ID NO:
- 146, and SEQ ID NO:
- 147, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 148, SEQ ID NO:
- 149, and SEQ ID NO:
- 150, respectively, with from 0 to 3 amino acid modifications;
- (20) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 31, SEQ ID NO:
- 32, and SEQ ID NO:
- 33, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 148, SEQ ID NO:
- 149, and SEQ ID NO:
- 150, respectively, with from 0 to 3 amino acid modifications;
- (21) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 31, SEQ ID NO:
- 32, and SEQ ID NO:
- 159, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 136, SEQ ID NO:
- 137, and SEQ ID NO:
- 162, respectively, with from 0 to 3 amino acid modifications;
- (22) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 169, SEQ ID NO:
- 170, and SEQ ID NO:
- 171, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 172, SEQ ID NO:
- 173, and SEQ ID NO:
- 174, respectively, with from 0 to 3 amino acid modifications;
- (23) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 61, SEQ ID NO:
- 62, and SEQ ID NO:
- 63, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 64, SEQ ID NO:
- 65, and SEQ ID NO:
- 180, respectively, with from 0 to 3 amino acid modifications;
- (24) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 31, SEQ ID NO:
- 182, and SEQ ID NO:
- 183, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 136, SEQ ID NO:
- 137, and SEQ ID NO:
- 186, respectively, with from 0 to 3 amino acid modifications;
- (25) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 187, SEQ ID NO:
- 188, and SEQ ID NO:
- 189, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 190, SEQ ID NO:
- 191, and SEQ ID NO:
- 192, respectively, with from 0 to 3 amino acid modifications;
- (26) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 193, SEQ ID NO:
- 194, and SEQ ID NO:
- 195, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 196, SEQ ID NO:
- 197, and SEQ ID NO:
- 12, respectively, with from 0 to 3 amino acid modifications;
- (27) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 199, SEQ ID NO:
- 200, and SEQ ID NO:
- 201, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 202, SEQ ID NO:
- 203, and SEQ ID NO:
- 6, respectively, with from 0 to 3 amino acid modifications;
- (28) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 211, SEQ ID NO:
- 212, and SEQ ID NO:
- 213, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 214, SEQ ID NO:
- 35, and SEQ ID NO:
- 216, respectively, with from 0 to 3 amino acid modification;
- (29) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 127, SEQ ID NO:
- 386, and SEQ ID NO:
- 129, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 34, SEQ ID NO:
- 35, and SEQ ID NO:
- 36, respectively, with from 0 to 3 amino acid modification;
- ;
- or (30) CDRH1, CDRH2, CDRH3 have an amino acid sequence as set forth in SEQ ID NO:
- 127, SEQ ID NO:
- 388, and SEQ ID NO:
- 129, respectively, with from 0 to 3 amino acid modification, and CDRL1, CDRL2, and CDRL3 have an amino acid sequence as set forth in SEQ ID NO:
- 34, SEQ ID NO:
- 35, and SEQ ID NO:
- 36, respectively, with from 0 to 3 amino acid modification.
208 more elements
Dependencies are inferred from the claim text.