Antibodies and antibody fragments that bind IgE
Provided and exemplified herein are antibodies and antibody fragments that bind an IgE constant domain.
1 . An antibody or antibody fragment that binds an IgE constant domain, wherein the antibody or antibody fragment comprises:
a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 37; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 38; a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 39; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 40; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 41; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 42.
2 . The antibody or antibody fragment of claim 1 , wherein:
(i) binding of the antibody or antibody fragment to a basophil and/or mast cell does not result in the activation of the basophil and/or mast cell,
(ii) the antibody or antibody fragment dissociates IgE from FcεRI on mast cells in 20 hours at an IC50 of IgE dissociation of less than 700 nM;
(iii) the antibody or antibody fragment dissociates IgE from FcεRI on human basophils in 20 hours at an IC 50 of IgE dissociation of less than 40 nM; and
(iv) the antibody or antibody fragment exhibits less than 8% change in main capillary isoelectric focusing (cIEF) peak percentage after heat stress at 40° C. for 14 days.
3 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises an amino acid other than aspartic acid (D) at the framework position corresponding to amino acid position 74 of SEQ ID NO: 95 (Kabat VH framework position 73).
4 . The antibody or antibody fragment of claim 1 , wherein antibody or antibody fragment further comprises a modified Fc domain comprising an amino acid modification that increases binding to the neonatal Fc receptor (FcRn) relative to wild-type IgG1 or IgG4.
5 . The antibody or antibody fragment of claim 4 , wherein the modified Fc domain comprises the amino acids Y252/T254/E256 (YTE) or L428/5434 (LS) per EU numbering.
6 . The antibody or antibody fragment of claim 1 , wherein the IgE comprises SEQ ID NO: 163.
7 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment binds IgE with an affinity (K D ) equal to or less than 5 nanomolar (nM).
8 . The antibody or antibody fragment of claim 7 , wherein the antibody or antibody fragment binds IgE with an affinity (K D ) equal to or less than 0.5 nanomolar (nM).
9 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 91; and a light chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 92.
10 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 93; and a light chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 94.
11 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 95; and a light chain variable region comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 96.
12 . The antibody or antibody fragment of claim 11 , wherein the antibody or antibody fragment comprises:
a heavy chain variable region comprising an amino sequence having 100% sequence identity to SEQ ID NO: 95; and a light chain variable region comprising an amino sequence having 100% sequence identity to SEQ ID NO: 96.
13 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 121; and a light chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 122.
14 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 123; and a light chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 124.
15 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises:
a heavy chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 125; and a light chain comprising an amino sequence having at least 85% sequence identity to SEQ ID NO: 126.
16 . The antibody or antibody fragment of claim 15 , wherein the antibody or antibody fragment comprises:
a heavy chain comprising an amino sequence having 100% sequence identity to SEQ ID NO: 125; and a light chain comprising an amino sequence having 100% sequence identity to SEQ ID NO: 126.
17 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is an antibody fragment, and wherein the antibody fragment comprises or consists of a single chain variable fragment (scFv), a Fab, Fab2, Fab3, F(ab′)2 diabody, triabody, tetrabody, BiTE, tandABs, or DART.
18 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is a full-length antibody.
19 . The antibody or antibody fragment of claim 1 , wherein a variable domain of the antibody or antibody fragment and a constant domain of the antibody or antibody fragment are directly conjugated to one another without an intervening flexible elbow.