Therapeutic human anti-IL-1R1 monoclonal antibody
View Patent ↗Antibodies that interact with interleukin-1 receptor type 1 (IL-1R1) are described. Methods of treating IL-1 mediated diseases by administering a pharmaceutically effective amount of antibodies to IL-1R1 are described. Methods of detecting the amount of IL-1R1 in a sample using antibodies to IL-1R1 are described.
1. An isolated antibody or antigen binding fragment thereof that specifically binds human interleukin-1 receptor type 1 (IL-1R1), comprising:
(a) a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 84, or the antigen binding fragment thereof, and the light chain comprises a light chain variable region comprising SEQ ID NO: 83, or the antigen binding fragment thereof, wherein the antigen binding fragment of the heavy chain variable region comprises an N-terminal or C-terminal deletion of SEQ ID NO: 84 comprising at least SEQ ID NO: 61, SEQ ID NO:64, and SEQ ID NO: 67, and the antigen binding fragment of the light chain variable region comprises an N-terminal or C-terminal deletion of SEQ ID NO: 83 comprising at least SEQ ID NO: 70, SEQ ID NO: 72, and SEQ ID NO: 74; or
(b) a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 82, or the antigen binding fragment thereof, and the light chain comprises a light chain variable region comprising SEQ ID NO: 83, or the antigen binding fragment thereof, wherein the antigen binding fragment of the heavy chain variable region comprises an N-terminal or C-terminal deletion of SEQ ID NO: 82 comprising at least SEQ ID NO: 62, SEQ ID NO:65, and SEQ ID NO: 68, and the antigen binding fragment of the light chain variable region comprises an N-terminal or C-terminal deletion of SEQ ID NO: 83 comprising at least SEQ ID NO: 70, SEQ ID NO: 72, and SEQ ID NO: 74.
2. An isolated antibody or antigen binding fragment thereof comprising:
(a) a human heavy chain comprising human heavy chain framework regions, a human heavy chain CDR1 region comprising SEQ ID NO: 61, a human heavy chain CDR2 region comprising SEQ ID NO: 64, and a human heavy chain CDR3 region comprising SEQ ID NO: 67; and a human light chain comprising human light chain framework regions, a human light chain CDR1 region comprising SEQ ID NO: 70, a human light chain CDR2 region comprising SEQ ID NO: 72, and a human light chain CDR3 region comprising SEQ ID NO: 74; or
(b) a human heavy chain comprising human heavy chain framework regions, a human heavy chain CDR1 region comprising SEQ ID NO: 62, a human heavy chain CDR2 region comprising SEQ ID NO: 65, and a human heavy chain CDR3 region comprising SEQ ID NO: 68; and a human light chain comprising human light chain framework regions, a human light chain CDR1 region comprising SEQ ID NO: 70, a human light chain CDR2 region comprising SEQ ID NO: 72, and a human light chain CDR3 region comprising SEQ ID NO: 74.
3. The antibody or antigen binding fragment of claim 2 , which is an antigen binding fragment, wherein the heavy chain and light chain of the antigen binding fragment are connected by a flexible linker to form a single-chain antibody.
4. The antibody or antigen binding fragment of claim 3 , which antigen binding fragment is a single-chain Fv antibody.
5. The antibody or antigen binding fragment of claim 2 , which is a Fab antibody fragment.
6. The antibody or antigen binding fragment of claim 2 , which is Fab′ antibody fragment.
7. The antibody or antigen binding fragment of claim 2 , which is a (Fab′) 2 antibody fragment.
8. The antibody or antigen binding fragment thereof of claim 2 , which is a fully human antibody or antigen binding fragment.
9. The antibody or antigen binding fragment thereof of claim 2 , wherein the antibody, or antigen binding fragment thereof, inhibits binding of IL-1 to human IL-1R1 receptor.
10. The antibody or antigen binding fragment thereof of claim 2 , which is an IgG2 antibody or antigen binding fragment.
11. The antibody or antigen binding fragment thereof of claim 2 , which binds specifically to the amino acid sequence of SEQ ID NO: 76.
12. The antibody or antigen binding fragment thereof of claim 2 , wherein the antibody or antigen binding fragment thereof binds specifically to a portion of the amino acid sequence of human IL-1R1, wherein the portion of the amino acid sequence to which the antibody specifically binds comprises the amino acid sequence YSV.
13. A composition comprising a pharmaceutically acceptable carrier, excipient or diluent, and the antibody or antigen binding fragment thereof of claim 2 .
14. An isolated antibody or an antigen binding fragment thereof that specifically binds human interleukin-1 receptor type 1 (IL-1R1), comprising:
(a) a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 84; or
(b) a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 82; or
(c) a heavy chain and a light chain, wherein the light chain comprises a light chain variable region comprising SEQ ID NO: 83.
15. The antibody or antigen binding fragment of claim 14 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 84.
16. The antibody or antigen binding fragment of claim 14 , wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 82.
17. The antibody or antigen binding fragment of claim 14 , wherein the antibody comprises a heavy chain and a light chain, wherein the light chain comprises a light chain variable region comprising SEQ ID NO: 83.
18. The antibody or antigen binding fragment of claim 14 , which is an antigen binding fragment, wherein the heavy chain and light chain of the antigen binding fragment are connected by a flexible linker to form a single-chain antibody.
19. The antibody or antigen binding fragment of claim 18 , which antigen binding fragment is a single-chain Fv antibody.
20. The antibody or antigen binding fragment of claim 14 , which is a Fab antibody fragment, a Fab' antibody fragment, or a (Fab′) 2 antibody fragment.
21. The antibody or antigen binding fragment thereof of claim 14 , which is a fully human antibody or antigen binding fragment.
22. The antibody or antigen binding fragment thereof of claim 14 , wherein the antibody, or antigen binding fragment thereof, inhibits binding of IL-1 to human IL-1R1.
23. The antibody or antigen binding fragment thereof of claim 14 , which is an IgG2 antibody or antigen binding fragment.
24. The antibody or antigen binding fragment thereof of claim 14 , which binds specifically to the amino acid sequence of SEQ ID NO: 76.
25. The antibody or antigen binding fragment thereof of claim 14 , wherein the antibody or antigen binding fragment thereof binds specifically to a portion of the amino acid sequence of human IL-1R1, wherein the portion of the amino acid sequence to which the antibody specifically binds comprises the amino acid sequence YSV.
26. A composition comprising a pharmaceutically acceptable carrier, excipient or diluent, and the antibody or antigen binding fragment thereof of claim 14 .