Human antibody molecules for IL-13
Specific binding members, in particular human anti-IL-13 antibody molecules and especially those which neutralise IL-13 activity. Methods for using anti-IL-13 antibody molecules in diagnosis or treatment of IL-13 related disorders, including asthma, atopic dermatitis, allergic rhinitis, fibrosis, inflammatory bowel disease and Hodgkin's lymphoma.
1. An isolated specific binding member for human IL-13, comprising an antibody antigen-binding domain site which is composed of a human antibody VH domain and a human antibody VL domain and which comprises a set of CDRs, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the VH domain comprises HCDR1, HCDR2 and HCDR3 and the VL domain comprises LCDR1, LCDR2 and LCDR3, wherein HCDR1 is of amino acid sequence which has the formula
HX 1 HX 2 G HX 3 S
(SEQ ID NO: 176)
wherein
HX 1 is selected from the group consisting of N, Q, D, L, G and E,
HX 2 is selected from the group consisting of Y and T,
HX 3 is selected from the group consisting of V, I, F and L,
HCDR2 is of amino acid sequence which has the formula
(SEQ ID NO: 177)
W I HX 4 HX 5 HX 6 HX 7 G HX 8 T HX 9 Y HX 10 HX 11 HX 12 F
HX 13 HX 14
wherein
HX 4 is selected from the group consisting of S, D, N, A, R, G and E,
HX 5 is selected from the group consisting of A, D, G, T, P, N and Y,
HX 6 is selected from the group consisting of N, D, L, A, P, T, S, I and R,
HX 7 is selected from the group consisting of N, S, T, D, G, K and I,
HX 8 is selected from the group consisting of D, T, E, Q, L, Y, N, V, A, M and G,
HX 9 is selected from the group consisting of N, I, L, Q, S, M, H, D and K,
HX 10 is selected from the group consisting of G and R,
HX 11 is selected from the group consisting of Q and R,
HX 12 is selected from the group consisting of E, K and G,
HX 13 is selected from the group consisting of Q and R,
HX 14 is selected from the group consisting of G and K,
HCDR3 is of amino acid sequence which has the formula
(SEQ ID NO: 178)
D HX 15 HX 16 HX 17 HX 18 W A R W HX 19 F HX 20 L
wherein
HX 15 is selected from the group consisting of S, R and D,
HX 16 is selected from the group consisting of S, N, D, T and P,
HX 17 is selected from the group consisting of S and R,
HX 18 is selected from the group consisting of S, N, A, I, R, P and K,
HX 19 is selected from the group consisting of F and Y,
HX 20 is selected from the group consisting of D and Y,
LCDR1 is of amino acid sequence which has the formula
G G LX 1 LX 2 LX 3 G LX 4 LX 5 L V H
(SEQ ID NO: 179)
wherein
LX 1 is selected from the group consisting of N, D and S,
LX 2 is selected from the group consisting of N, I, L, M, C, V, K, Y, F, R, T, S, A, H and G,
LX 3 is selected from the group consisting of I and V,
LX 4 is selected from the group consisting of S and G,
LX 5 is selected from the group consisting of K and R,
LCDR2 is of amino acid sequence which has the formula
D D G D R P LX 6
(SEQ ID NO: 180)
wherein
LX 6 is selected from the group consisting of S and T,
LCDR3 is of amino acid sequence which has the formula
Q V W D T G S LX 7 P V LX 8
(SEQ ID NO: 181)
wherein
LX 7 is selected from the group consisting of D and N,
LX 8 is selected from the group consisting of V and I.
2. An isolated specific binding member according to claim 1 , wherein
HX 1 is selected from the group consisting of D and N,
HX 2 is Y,
HX 3 is L,
HX 4 is selected from the group consisting of S and G,
HX 5 is selected from the group consisting of T and A,
HX 6 is N,
HX 7 is selected from the group consisting of N and I,
HX 8 is D,
HX 9 is selected from the group consisting of N, D and K,
HX 10 is G,
HX 12 is selected from the group consisting of E and G,
HX 13 is Q,
HX 19 is F,
LX 1 is selected from the group consisting of N and S,
LX 2 is selected from the group consisting of N, Y, T, S, and I,
LX 6 is S,
LX 7 is D.
3. An isolated specific binding member according to claim 1 , wherein
HX 1 is selected from the group consisting of N and D,
HX 2 is Y,
HX 3 is L,
HX 4 is selected from the group consisting of S and C,
HX 5 is selected from the group consisting of A and T,
HX 6 is N,
HX 7 is N,
HX 8 is selected from the group consisting of D and G,
HX 9 is selected from the group consisting of I, S, N and D,
HX 11 is Q,
HX 12 is E and K,
HX 14 is G,
HX 15 is S,
HX 16 is selected from the group consisting of S and N,
HX 17 is S,
HX 18 is selected from the group consisting of S and N,
HX 19 is F,
HX 20 is D,
LX 1 is selected from the group consisting of N and D,
LX 3 is I,
LX 8 is V.
4. An isolated specific binding member according to claim 1 , wherein
HX 7 is selected from the group consisting of N, S, T, D, G and K,
HX 8 is selected from the group consisting of D, T, E, Q, L, Y, N, V, A, M,
HX 9 is selected from the group consisting of N, I, L, Q, S, M and H,
HX 10 is G,
HX 11 is Q,
HX 12 is F,
HX 13 is Q,
HX 14 is G,
HX 15 is S,
HX 16 is selected from the group consisting of N and S,
HX 17 is S,
HX 18 is selected from the group consisting of N and S,
HX 19 is F,
HX 20 is D,
LX 1 is N,
LX 2 is selected from the group consisting of N and I,
LX 3 is I,
LX 4 is S,
LX 5 is K,
LX 6 is S,
LX 7 is D,
LX 8 is V.
5. An isolated specific binding member according to claim 4 , wherein
HX 1 is selected from the group consisting of N, Q and D,
HX 3 is selected from the group consisting of L, V and I,
HX 4 is selected from the group consisting of S, N, A and R,
HX 5 is selected from the group consisting of A, D, T, G, N and Y,
HX 6 is selected from the group consisting of N, A, P, S, D and I,
HX 7 is selected from the group consisting of N, T, D and G,
HX 8 is selected from the group consisting of D, Q, Y and N,
HX 9 is selected from the group consisting of N, Q, S and I.
6. A specific binding member according to claim 1 that neutralizes human IL-13.
7. A specific binding member according to claim 6 that neutralizes human IL-13, with a potency equal to or better than the potency of a IL-13 antigen-binding site formed by the BAK502G9 VH domain (SEQ ID NO: 15) and the BAK502G9 VL domain (SEQ ID NO: 16), the potency of the specific binding member and the potency of the antigen-binding site being as determined under the same conditions.
8. A specific binding member according to claim 1 that comprises an scFv antibody molecule.
9. A specific binding member according to claim 1 that comprises an antibody constant region.
10. A specific binding member according to claim 9 that comprises a whole antibody.
11. A specific binding member according to claim 10 wherein the whole antibody comprises IgG4.
12. An isolated specific binding member according to claim 1 which binds a human IL-13 variant in which arginine at position 130 is replaced by glutamine.
13. An isolated specific binding member according to claim 1 which binds non-human primate IL-13.
14. An isolated specific binding member according to claim 13 wherein the non-human primate IL-13 is rhesus or cynomolgus.
15. An isolated antibody comprising a VL domain and a VH domain, wherein the VH domain is the BAK502G9 VH domain (SEQ ID NO: 15).
16. An isolated antibody comprising a VL domain and a VH domain wherein the VL domain is the BAK502G9 VL domain (SEQ ID NO: 16).
17. A composition comprising the isolated antibody of claim 15 or 16 , and at least one additional component.
18. A composition according to claim 17 comprising a pharmaceutically acceptable excipient, vehicle or carrier.