Antibodies that bind IL-4 and/or IL-13 and their uses

Patent metadata

Field	Value
Publication number	US-9738728-B2
Application number	US-201313794295-A
Country	US
Kind code	B2
Filing date	Mar 11, 2013
Priority date	Oct 15, 2007
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

First claim

The invention claimed is:

1. A method of treating asthma or idiopathic pulmonary fibrosis in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4,
wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chain polypeptides and two heavy chain polypeptides;
wherein each of the light chain polypeptides comprises an outer (N-terminal) variable light chain domain linked to an inner (C-terminal) variable light chain domain which is linked to a constant light chain domain (CL), and each of the heavy chain polypeptides comprises an outer (N-terminal) variable heavy chain domain linked to an inner (C-terminal) variable heavy chain domain which is linked to a constant heavy chain domain (CH1); and
wherein:
(a) the outer (N-terminal) variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (CDR1; SEQ ID NO: 8), LASNLES (CDR2; SEQ ID NO: 9), and QQNAEDSRT (CDR3; SEQ ID NO: 10), the inner (C-terminal) variable light chain domain comprises the amino acid sequences HASQNIDVWLS (CDR1; SEQ ID NO: 14), KASNLHTG (CDR2; SEQ ID NO: 15), and QQAHSYPFT (CDR3; SEQ ID NO: 16), the outer (N-terminal) variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (CDR1; SEQ ID NO: 11), DGRID (CDR2; SEQ ID NO: 12), and DGYFPYAMDF (CDR3; SEQ ID NO: 13), and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (CDR1; SEQ ID NO: 17), IDPSDGETR (CDR2; SEQ ID NO: 18), and LKEYGNYDSFYFDV (CDR3; SEQ ID NO: 19); or
(b) the outer (N-terminal) variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (CDR1; SEQ ID NO: 8), LASNLES (CDR2; SEQ ID NO: 9), and QQNAEDSRT (CDR3; SEQ ID NO: 10), the inner (C-terminal) variable light chain domain comprises the amino acid sequences HASQNIDVWLS (CDR1; SEQ ID NO: 14), KASNLHTG (CDR2; SEQ ID NO: 15), and QQAHSYPFT (CDR3; SEQ ID NO: 16), the outer (N-terminal) variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (CDR1; SEQ ID NO: 11), DGRID (CDR2; SEQ ID NO: 12), and DGYFPYAMDF (CDR3; SEQ ID NO: 13), and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (CDR1; SEQ ID NO: 20), IDASDGETR (CDR2; SEQ ID NO: 21), and LKEYGNYDSFYFDV (CDR3; SEQ ID NO: 22).

2. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (CDR1; SEQ ID NO: 8), LASNLES (CDR2; SEQ ID NO: 9), and QQNAEDSRT (CDR3; SEQ ID NO: 10), the inner (C-terminal) variable light chain domain comprises the amino acid sequences HASQNIDVWLS (CDR1; SEQ ID NO: 14), KASNLHTG (CDR2; SEQ ID NO: 15), and QQAHSYPFT (CDR3; SEQ ID NO: 16), the outer (N-terminal) variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (CDR1; SEQ ID NO: 11), DGRID (CDR2; SEQ ID NO: 12), and DGYFPYAMDF (CDR3; SEQ ID NO: 13), and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (CDR1; SEQ ID NO: 17), IDPSDGETR (CDR2; SEQ ID NO: 18), and LKEYGNYDSFYFDV (CDR3; SEQ ID NO: 19).

3. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequences RASESVDSYGQSYMH (CDR1; SEQ ID NO: 8), LASNLES (CDR2; SEQ ID NO: 9), and QQNAEDSRT (CDR3; SEQ ID NO: 10), the inner (C-terminal) variable light chain domain comprises the amino acid sequences HASQNIDVWLS (CDR1; SEQ ID NO: 14), KASNLHTG (CDR2; SEQ ID NO: 15), and QQAHSYPFT (CDR3; SEQ ID NO: 16), the outer (N-terminal) variable heavy chain domain comprises the amino acid sequences GFSLTDSSIN (CDR1; SEQ ID NO: 11), DGRID (CDR2; SEQ ID NO: 12), and DGYFPYAMDF (CDR3; SEQ ID NO: 13), and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequences GYSFTSYWIH (CDR1; SEQ ID NO: 20), IDASDGETR (CDR2; SEQ ID NO: 21), and LKEYGNYDSFYFDV (CDR3; SEQ ID NO: 22).

4. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 4.

5. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises an amino acid sequence that has 95% identity to the amino acid sequence of SEQ ID NO: 5.

6. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 4.

7. The method of claim 1 , wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1, the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 5.

8. The method of any one of claim 1 , or 4 - 7 , wherein the outer variable light chain and the inner variable light chain are linked by a peptide linker and the outer variable heavy chain and the inner variable heavy chain are linked by a peptide linker.

9. The method of claim 8 , wherein the linker comprises the amino acid sequence of SEQ ID NO:6.

10. The method of claim 1 , wherein the heavy chain polypeptides further comprises CH2 and CH3 domains.

11. The method of claim 1 , wherein the method is for treating asthma.

12. The method of claim 1 , wherein the method is for treating idiopathic pulmonary fibrosis.

13. The method of claim 1 , wherein the mammal is a human.

14. A method of treating asthma or idiopathic pulmonary fibrosis in a mammal comprising the step of administering to the mammal a therapeutically effective amount of a bispecific antibody or bispecific antibody fragment thereof that specifically binds to IL-13 and IL-4,
wherein the bispecific antibody or bispecific antibody fragment thereof comprises two light chain polypeptides and two heavy chain polypeptides;
wherein each of the light chain polypeptides comprises an outer (N-terminal) variable light chain domain linked to an inner (C-terminal) variable light chain domain which is linked to a constant light chain domain (CL), and each of the heavy chain polypeptides comprises an outer (N-terminal) variable heavy chain domain linked to an inner (C-terminal) variable heavy chain domain which is l

Assignees

• Sanofi Sa

Inventors

• Rao Ercole
• Mikol Vincent
• Li Danxi
• Kruip Jochen
• Davison Matthew

Classifications

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K16/468 Primary

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• C07K16/247

  IL-4 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title