Anti-αvβ6 antibodies and uses thereof

• US 7,943,742 B2
• Filed: 07/10/2006
• Issued: 05/17/2011
• Est. Priority Date: 07/08/2005
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Saldanha, Jose W., Violette, Shelia M., Koopman, Louise A., Simon, Kenneth J., van Vlijmen, Herman W. T., Weinreb, Paul H., Lugovskoy, Alexey A.
• Primary Examiner(s): Blanchard; David J.
• Application Number:
  US11/483,190
• Publication Number:
  US 20080286269A1
• Time in Patent Office: 1,772 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2839 : against the integrin superfamily
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 : Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: G01N 2333/70546 : Integrin superfamily, e.g. VLAs, leuCAM, GPIIb/GPIIIa, LPAM
• CPC Class Codes: G01N 2800/085 : Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
• CPC Class Codes: G01N 2800/12 : Pulmonary diseases
• CPC Class Codes: G01N 2800/20 : Dermatological disorders
• CPC Class Codes: G01N 2800/347 : Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
• CPC Class Codes: G01N 33/57407 : Specifically defined cancers
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere
• CPC Class Codes: Y10S 424/80 : Antibody or fragment thereof whose amino acid sequence is disclosed in whole or in part
• CPC Class Codes: Y10S 424/801 : involving antibody or fragment thereof produced by recombinant dna technology

Abstract

The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize α_vβ₆ integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-α_vβ₆ antibodies of the invention. The invention also relates to the identification of differential expression of the integrin α_vβ₆ on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin α_vβ₆.

Claims

1. A humanized antibody that specifically binds to α

_vβ

₆ comprising a heavy chain variable domain sequence of SEQ ID NO;

1 and a light chain variable domain of SEQ ID NO;

2.

13. A composition comprising the antibody of any one of claims 1, 2, 3, 7, 4, 5, 8, 9, 10, 11, and 12, and a pharmaceutically acceptable carrier.

2. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a heavy chain variable domain selected from the group consisting of SEQ ID NO;

144, SEQ ID NO;

145, or SEQ ID NO;

146 and a light chain variable domain sequence selected from the group consisting of SEQ ID NO;

139, SEQ ID NO;

140, SEQ ID NO;

141, SEQ ID N;

142 and SEQ ID NO;

143.

7. The humanized antibody of claim 2, wherein said antibody comprises a heavy chain variable domain (HV1) sequence of SEQ ID NO:

144 and a light chain variable domain sequence of SEQ ID NO;

139.

3. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a heavy chain variable domain sequence of SEQ ID NO;

146 and a light chain variable domain sequence of SEQ ID NO;

141 or SEQ ID NO;

143.

4. A humanized antibody that specifically binds α

_vβ

₆, wherein said antibody comprises a heavy chain variable domain (HV2) sequence of SEQ ID NO;

145 and a light chain variable domain of SEQ ID NO;

140.

5. A humanized antibody that specifically binds to α

_vβ

₆ and comprises a heavy chain variable domain sequence of SEQ ID NO;

146 (HV3) and a light chain variable domain of SEQ ID NO;

143 (LV5).

6. A humanized antibody that specifically binds to α

_vβ

₆ comprising a heavy chain variable domain sequence of SEQ ID NO;

3 and a light chain variable domain of SEQ ID NO;

4.

14. A composition comprising the antibody of claim 6 and a pharmaceutically acceptable carrier.

8. A humanized antibody that specifically binds to α

_vβ

₆ comprising a variant of a heavy chain variable domain sequence of SEQ ID NO;

1 and/or a variant of a light chain variable domain of SEQ ID NO;

2, wherein said variant of SEQ ID NO;

1 comprises one or both of Q3M and N73S and said variant of SEQ ID NO;

2 comprises one or more of the variations selected from the group consisting of L48W, I59V, A61V and Y88F as compared to SEQ ID NO;

2.

9. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a heavy chain variable domain sequence selected from the group consisting of SEQ ID NO;

78, SEQ ID NO;

79, and SEQ ID NO;

80 and the light chain variable domain sequence selected from the group consisting of SEQ ID NO;

75, SEQ ID NO;

76, and SEQ ID NO;

77.

10. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO;

75 and a heavy chain variable domain sequence of SEQ ID NO;

78.

11. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO;

76 and a heavy chain variable domain sequence of SEQ ID NO;

79.

12. A humanized antibody that specifically binds α

_vβ

₆ wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO;

77 and a heavy chain variable domain sequence of SEQ ID NO;

80.