Antibodies that bind IL-4 and/or IL-13 and their uses
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-039/00
C07K-016/24
C07K-016/46
A61K-047/48
출원번호
US-0794295
(2013-03-11)
등록번호
US-9738728
(2017-08-22)
우선권정보
EP-07291259 (2007-10-15)
발명자
/ 주소
Rao, Ercole
Mikol, Vincent
Li, Danxi
Kruip, Jochen
Davison, Matthew
출원인 / 주소
Sanofi
대리인 / 주소
Morrison & Foerster LLP
인용정보
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0인용 특허 :
73
초록▼
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 dise
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.
대표청구항▼
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 antibod
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); andwherein:(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 linked to a constant heavy chain domain (CH1); andwherein:(a) the outer (N-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 inner (C-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 outer (N-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), and the inner (C-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); or(b) the outer (N-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 inner (C-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 outer (N-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), and the inner (C-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). 15. The method of claim 14, wherein the outer (N-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 inner (C-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 outer (N-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), and the inner (C-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). 16. The method of claim 14, wherein the outer (N-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 inner (C-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 outer (N-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), and the inner (C-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). 17. The method of claim 14, 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: 3, 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: 1, 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: 4, 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: 2. 18. The method of claim 14, 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: 3, 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: 1, 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: 5, 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: 2. 19. The method of claim 14, wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 4, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2. 20. The method of claim 14, wherein the outer (N-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 3, the inner (C-terminal) variable light chain domain comprises the amino acid sequence of SEQ ID NO: 1, the outer (N-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 5, and the inner (C-terminal) variable heavy chain domain comprises the amino acid sequence of SEQ ID NO: 2. 21. The method of any one of claims 14-20, 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. 22. The method of claim 21, wherein the linker comprises the amino acid sequence of SEQ ID NO:6. 23. The method of claim 14, wherein the second pair of polypeptides further comprises CH2 and CH3 domains. 24. The method of claim 14, wherein the method is for treating asthma. 25. The method of claim 14, wherein the method is for treating idiopathic pulmonary fibrosis. 26. The method of claim 14, wherein the mammal is a human.
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