Human antibodies that bind human MAdCAM

Patent metadata

Field	Value
Publication number	US-9328169-B2
Application number	US-3148505-A
Country	US
Kind code	B2
Filing date	Jan 7, 2005
Priority date	Jan 9, 2004
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

The present invention relates to antibodies, including human antibodies, and antigen-binding portions thereof that specifically bind to MAdCAM, preferably human MAdCAM, and inhibit MAdCAM. The antibodies comprise the CDRs or variable domains derived from an antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909) or from an antibody comprising the amino acid sequences of SEQ ID NOs.: 34 and 36. The invention also relates to nucleic acid molecules encoding such antibodies and antigen-binding portions thereof, methods of making and using the antibodies and portions, and compositions comprising these antibodies and portions.

First claim

What is claimed is:

1. A human monoclonal antibody that specifically binds to MAdCAM, wherein the antibody comprises the amino acid sequences in SEQ ID NO: 34 and SEQ ID NO: 36 without the signal sequences; and wherein the antibody possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less; and
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM.

2. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds to MAdCAM, wherein said antibody comprises the heavy chain CDR1, CDR2 and CDR3 amino acid sequences of the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909) and the light chain CDR1, CDR2 and CDR3 amino acid sequences of the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909); and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less;
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM; and
(d) inhibits the recruitment of lymphocytes to gastrointestinal lymphoid tissue.

3. The monoclonal antibody or antigen-binding portion according to claim 2 , wherein the heavy chain, the light chain or both comprise the amino acid sequence from the beginning of the CDR1 through the end of the CDR3 of the heavy chain, the light chain or both, respectively, of the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909).

4. The monoclonal antibody according to claim 2 that is an immunoglobulin G (IgG).

5. The antigen-binding portion according to claim 2 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

6. The monoclonal antibody or antigen-binding portion according to claim 2 , wherein said antibody comprises one or more of the FR1, FR2, FR3 and FR4 amino acid sequences of the human monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909).

7. An antigen-binding portion of a monoclonal antibody, wherein the monoclonal antibody specifically binds to MAdCAM, and wherein the antibody is the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909); and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less;
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM; and
(d) inhibits the recruitment of lymphocytes to gastrointestinal lymphoid tissue.

8. An antigen-binding portion of a monoclonal antibody, wherein the monoclonal antibody specifically binds to MAdCAM, and wherein the heavy chain amino acid sequence of the monoclonal antibody is SEQ ID NO: 34 without the signal sequence, and the light chain amino acid sequence of the monoclonal antibody is SEQ ID NO: 36 without the signal sequence; and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less; and
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM.

9. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds to MAdCAM, wherein said antibody comprises the heavy chain CDR1, CDR2 and CDR3 amino acid sequences of SEQ ID NO: 34 and the light chain CDR1, CDR2 and CDR3 amino acid sequences of SEQ ID NO: 36; and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less; and
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM.

10. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds to MAdCAM, wherein said antibody comprises the light and heavy chain variable domain amino acid sequences of the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909); and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less;
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM; and
(d) inhibits the recruitment of lymphocytes to gastrointestinal lymphoid tissue.

11. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds to MAdCAM, wherein said antibody comprises the light chain variable domain amino acid sequence in SEQ ID NO: 36 and the heavy chain variable domain amino acid sequence in SEQ ID NO: 34; and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less;
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM; and
(d) inhibits the recruitment of lymphocytes to gastrointestinal lymphoid tissue.

12. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds to MAdCAM, wherein said antibody comprises the light and heavy chain amino acid sequences of the monoclonal antibody produced by the hybridoma cell line 7.16.6 (ECACC Accession No. 03090909); and wherein the antibody or portion possesses at least one of the following properties:
(a) has a selectivity for MAdCAM over VCAM or fibronectin of at least 100 fold;
(b) binds to human MAdCAM with a K d of 3×10 −10 M or less; and
(c) inhibits the binding of α 4 β 7 expressing cells to human MAdCAM.

13. The monoclonal antibody according to claim 9 that is an immunoglobulin G (IgG).

14. The monoclonal antibody according to claim 10 that is an immunoglobulin G (IgG).

15. The monoclonal antibody according to claim 11 that is an immunoglobulin G (IgG).

16. The antigen-binding portion according to claim 7 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

17. The antigen-binding portion according to claim 8 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

18. The antigen-binding portion according to claim 9 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

19. The antigen-binding portion according to claim 10 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

20. The antigen-binding portion according to claim 11 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

21. The antigen-binding portion according to claim 12 which is an Fab fragment, an F(ab′) 2 fragment, an F v fragment or a single chain antibody.

22. A pharmaceutical composition comprising an effective amount of the monoclonal antibody according to claim 1 and a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising an effective amount of the monoclonal antibody or antigen-bi

Assignees

• Pullen Nicholas
• Molloy Elizabeth
• Kellermann Sirid-Aimée
• Green Larry L
• Haak-Frendscho Mary
• Pfizer
• Amgen Fremont Inc

Inventors

• Pullen Nicholas
• Molloy Elizabeth
• Kellermann Sirid-Aimée
• Green Larry L
• Haak-Frendscho Mary

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title