Interferon receptor 1 antibodies and their uses

Patent metadata

Field	Value
Publication number	US-11072664-B2
Application number	US-201916503196-A
Country	US
Kind code	B2
Filing date	Jul 3, 2019
Priority date	Jun 21, 2004
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.

First claim

We claim:

1. A method for inhibiting the biological activity of a type I interferon on cells expressing interferon alpha receptor 1 (IFNAR-1) comprising contacting the cells with a monoclonal antibody, or antigen-binding portion thereof, which specifically binds to human IFNAR-1 in an amount sufficient to inhibit the biological activity of the type I interferon, wherein the antibody, or antigen-binding portion thereof, is selected from the group consisting of:
(a) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 5; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 9; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 17; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 21;
(b) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 10; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22; and
(c) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 8; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 12; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 16; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 24.

2. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells in vitro.

3. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells ex vivo.

4. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells in vivo.

5. The method of claim 1 , wherein antibody is a human antibody.

6. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 5; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 9; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 17; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 21.

7. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 10; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22.

8. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 8; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 12; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 16; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 24.

9. The method of claim 1 , wherein the antibody, or antigen-binding portion thereof, is conjugated to a therapeutic agent.

10. The method of claim 9 , wherein the therapeutic agent is a cytotoxin or a radioactive isotope.

11. A method for inhibiting the biological activity of a type I interferon on cells expressing interferon alpha receptor 1 (IFNAR-1) comprising contacting the cells with an antibody, or antigen-binding portion thereof, which specifically binds to human IFNAR-1 in an amount sufficient to inhibit the biological activity of the type I interferon, wherein the antibody, or antigen-binding portion thereof, is selected from the group consisting of:
(a) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29;
(b) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30; and
(c) an antibody, or antigen-binding portion thereof, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.

12. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells in vitro.

13. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells ex vivo.

14. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, is contacted with the cells in vivo.

15. The method of claim 11 , wherein antibody is a human antibody.

16. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29.

17. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30.

18. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.

19. The method of claim 11 , wherein the antibody, or antigen-binding portion thereof, is conjugated to a therapeutic agent.

20. The method of claim 19 , wherein the therapeutic agent is a cytotoxin or a radioactive isotope.

Assignees

• Squibb & Sons Llc

Inventors

• Cardarelli Josephine M
• Witte Alison
• Srinivasan Mohan

Classifications

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P13/12

  of the kidneys · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title