Binding Members For IgE Molecules
This invention relates to binding members, especially antibody molecules, for IgE. The binding members are useful for, inter alia, treatment of disorders mediated by IgE including allergies and asthma.
1 - 4 . (canceled)
5 . An isolated antibody or antigen-binding fragment thereof, specific for human immunoglobulin E comprising a set of CDRs: HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 wherein the set of CDRs has 10 or fewer amino acid additions, substitutions, deletions and/or insertions from a reference set of CDRs in which:
HCDR1 has the amino acid sequence of SEQ. ID. NO: 103;
HCDR2 has the amino acid sequence of SEQ. ID. NO: 104;
HCDR3 has the amino acid sequence of SEQ. ID. NO: 105; LCDR1 has the amino acid sequence of SEQ. ID. NO: 108;
LCDR2 has the amino acid sequence of SEQ. ID. NO: 109;
LCDR3 has the amino acid sequence of SEQ. ID. NO: 110.
6 . The isolated antibody or antigen-binding fragment thereof of claim 5 wherein the amino acid substitutions comprises 6 or fewer amino acid substitutions.
7 . (canceled)
8 . The isolated antibody or antigen-binding fragment thereof of claim 5 comprising a set of CDRs:
HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 wherein the set of CDRs comprise:
HCDR1 has the amino acid sequence of SEQ. ID. NO: 103;
HCDR2 has the amino acid sequence of SEQ. ID. NO: 104; o HCDR3 has the amino acid sequence of SEQ. ID. NO: 105;
LCDR1 has the amino acid sequence of SEQ. ID. NO: 108;
LCDR2 has the amino acid sequence of SEQ. ID. NO: 109;
LCDR3 has the amino acid sequence of SEQ. ID. NO: 110.
9 . An isolated binding member or VH domain comprising the antibody 1 HCDR3 (SEQ ID NO: 5) with one or more of the following substitutions:
Kabat residue 96 replaced by S, M, or T;
Kabat residue 97 replaced L or G;
Kabat residue 98 replaced by K; o Kabat residue 99 replaced by S, W, A, T, or E;
Kabat residue 100 replaced by A or I.
10 . An isolated binding member or VL domain comprising the antibody 1 LCDR3 (SEQ ID NO 10) with one or more of the following substitutions: 5 Kabat residue 94 replaced by T, R, D, P, E, N, H, Q, or A;
Kabat residue 95 replaced T, K, S, I, G, H, M, F, R, N, K or Q;
Kabat residue 95A replaced by L, H, D, G, R, N, Q, K, or E;
Kabat residue 95B replaced by T, H, S, Y, L or N;
Kabat residue 96 replaced by G or A; 0 Kabat residue 97 replaced by P, S or G.
11 . The isolated antibody or antigen-binding fragment thereof, of claim 5 , wherein the antibody or antigen-binding fragment binds an epitope which comprises elements from a first IgE heavy chain and elements from a second IgE heavy chain.
12 . An isolated antibody or antigen-binding fragment thereof, specific for immunoglobulin E wherein said binding member binds to an epitope in immunoglobulin E comprising: residues Glu390 through to Asn394 inclusive in a first IgE heavy chain and Leu340, Arg342, Ala428 to Thr434 inclusive, Thr436, Ser437 and Glu472 in a second IgE heavy chain.
13 - 15 . (canceled)
16 . The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
17 - 19 . (canceled)
20 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof, of claim 1 and a pharmaceutically acceptable excipient.
21 - 25 . (canceled)