Antibodies against IL-25
View Patent ↗The present invention relates to IL-25 antibody VH domains and target binding members (e.g., antibodies) that comprise such antibody VH domains and bind IL-25. The invention also relates to compositions comprising target binding members {e.g., antibodies) that bind IL-25, methods of producing such target binding members, and uses of such target binding members for the treatment or prevention of diseases and conditions (e.g., asthma, inflammatory bowel disease).
1. An antibody that binds interleukin 25 (IL-25), comprising a VL domain which comprises a VL CDR1, a VL CDR2 and a VL CDR3, and a VH domain which comprises SEQ ID NO: 1:
Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala
Ser Gly Tyr Ser Phe Xa1 Xa2 Tyr Thr Met Asn Trp
Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Xa3
Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ser Tyr
Asn Gln Asn Phe Lys Gly Arg Val Thr Leu Thr Xa4
Asp Thr Ser Ala Ser Thr Ala Tyr Leu Glu Leu Asn
Ser Leu Arg Ser Glu Asp Thr Gly Val Tyr Tyr Cys
Ala Arg Glu Xa5 Tyr Asp Gly Tyr Leu Tyr Phe Ala
Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
Ser Ser
wherein:
Xa1 is Ser or Thr;
Xa2 is Gly, Asp, Ala, Ser, Val, Asn, Lys, Tyr or Met;
Xa3 is Met or Ile;
Xa4 is Val or Arg; and
Xa5 is Asp or Asn.
2. The antibody of claim 1 wherein Xa2 is Gly.
3. The antibody of claim 2 wherein Xa2 is Gly and Xa5 is Asp.
4. The antibody of claim 1 wherein Xa1 is Ser.
5. The antibody of claim 1 wherein Xa1 is Thr.
6. The antibody of claim 1 wherein Xa3 is Met.
7. The antibody of claim 1 wherein Xa3 is Ile.
8. The antibody of claim 1 wherein Xa4 is Val.
9. The antibody of claim 1 wherein Xa4 is Arg.
10. The antibody of claim 1 wherein the residues Xa1-Xa5 are in the following combinations:
Kabat Res:
30
31
48
71
96
Position in SEQ ID NO: 1:
30
31
48
72
100
Seq List Res:
Xa1
Xa2
Xa3
Xa4
Xa5
SEQ ID NO: 2
Ser
Gly
Met
Val
Asp
SEQ ID NO: 3
Thr
Gly
Met
Arg
Asp
SEQ ID NO: 4
Ser
Gly
Met
Arg
Asp
SEQ ID NO: 5
Thr
Gly
Met
Val
Asp
SEQ ID NO: 6
Ser
Asp
Met
Val
Asp
SEQ ID NO: 7
Thr
Asp
Met
Arg
Asp
SEQ ID NO: 8
Thr
Asp
Met
Val
Asp
SEQ ID NO: 9
Ser
Gly
Ile
Val
Asp
SEQ ID NO: 10
Thr
Gly
Ile
Arg
Asp
SEQ ID NO: 11
Thr
Gly
Ile
Val
Asp
SEQ ID NO: 12
Ser
Asp
Ile
Val
Asp
SEQ ID NO: 13
Thr
Asp
Ile
Arg
Asp
SEQ ID NO: 14
Thr
Asp
Ile
Val
Asp
11. The antibody of claim 1 which comprises a VL domain whose Kabat CDRs 1-3 are as set out as residues 24-34 (SEQ ID NO:29); 50-56 (SEQ ID NO:30) and 89-97 (SEQ ID NO:31) respectively of SEQ ID NO: 15.
12. The antibody of claim 11 wherein the VL domain further includes residues 35-38 of SEQ ID NO: 15 adjacent to CDR1 (SEQ ID NO:29).
13. The antibody of claim 11 wherein the VL domain comprises SEQ ID NO: 15.
14. The antibody of claim 11 wherein the VL domain is humanised.
15. The antibody of claim 14 wherein the VL domain comprises amino acids 21-127 of SEQ ID NO:25.
16. The antibody of claim 1 which is a Fab, F(ab′) 2 , scFv, or Fv antibody fragment.
17. The antibody of claim 1 which comprises an antibody constant region.
18. The antibody of claim 17 wherein the constant region is a human IgG1 or IgG4 constant region.
19. The antibody of claim 17 which comprises a whole antibody.
20. An isolated nucleic acid which comprises a nucleotide sequence encoding the antibody of claim 1 .
21. An expression vector comprising the nucleic acid of claim 20 operably linked to a promoter.
22. A host cell carrying the expression vector of claim 21 .
23. A method of producing an antibody, the method comprising culturing host cells according to claim 22 under conditions for production of said antibody.
24. A method according to claim 23 further comprising isolating said antibody.
25. A method according to claim 24 further comprising formulating the antibody into a composition including at least one additional component.
26. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
27. The composition of claim 26 in the form of a lyophilized powder.
28. A method for the treatment or prevention of asthma, said method comprising administering to a subject in need of treatment an effective amount of the antibody of claim 1 .
29. A method for the treatment or prevention of ulcerative colitis, said method comprising administering to a subject in need of treatment an effective amount of the antibody of claim 1 .
30. A method of producing an antibody that binds interleukin 25 (IL-25) which comprises:
(a) providing a VH domain which comprises SEQ ID NO: 1:
Glu Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala
Ser Gly Tyr Ser Phe Xa1 Xa2 Tyr Thr Met Asn Trp
Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Xa3
Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ser Tyr
Asn Gln Asn Phe Lys Gly Arg Val Thr Leu Thr Xa4
Asp Thr Ser Ala Ser Thr Ala Tyr Leu Glu Leu Asn
Ser Leu Arg Ser Glu Asp Thr Gly Val Tyr Tyr Cys
Ala Arg Glu Xa5 Tyr Asp Gly Tyr Leu Tyr Phe Ala
Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
Ser Ser
wherein:
Xa1 is Ser or Thr;
Xa2 is Gly, Asp, Ala, Ser, Val, Asn, Lys, Tyr or Met;
Xa3 is Met or Ile;
Xa4 is Val or Arg; and
Xa5 is Asp or Asn;
(b) combining said VH domain with a plurality of antibody VL domains, wherein each VL domain comprises a VL CDR1, a VL CDR2 and a VL CDR3, to provide antibody molecules;
(c) screening said antibody molecules for binding to IL-25; and
(d) selecting an antibody molecule which binds IL-25.
31. An antibody that binds interleukin 25 (IL-25), comprising a VL domain which comprises a VL CDR1, a VL CDR2 and a VL CDR3, and a VH domain which comprises SEQ ID NO: 2.
32. An antibody that binds interleukin 25 (IL-25), comprising a VL domain which comprises a VL CDR1, a VL CDR2 and a VL CDR3, and a VH domain which comprises SEQ ID NO: 3.