发明名称 |
Bi- and monospecific, asymmetric antibodies and methods of generating the same |
摘要 |
An antibody is provided. The antibody comprises an Fc region and a Fab region, wherein:
(i) the Fc region comprises two non-identical heavy chains, wherein at least one of the two non-identical heavy chains comprises an amino acid modification so as to form complementation between the two non-identical heavy chains thereby increasing the probability of forming heterodimers of the non-identical heavy chains and decreasing the probability of forming homodimers of identical heavy chains; and(ii) the Fab region comprises a first covalent link between a first heavy chain and a first light chain of the Fab region and a second covalent link between a second heavy chain and a second light chain of said Fab region, wherein a position of the first covalent link relative to the first heavy chain is different to a position of the second covalent link relative to the second heavy chain. |
申请公布号 |
US9624291(B2) |
申请公布日期 |
2017.04.18 |
申请号 |
US201214005580 |
申请日期 |
2012.03.15 |
申请人 |
Ramot at Tel-Aviv University Ltd. |
发明人 |
Benhar Itai;Vaks Lilach |
分类号 |
C07K16/00;C07K16/32;C07K16/28;A61K39/00 |
主分类号 |
C07K16/00 |
代理机构 |
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代理人 |
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主权项 |
1. A method of preparing a bispecific antibody comprising an Fc region and a Fab region,
(a) providing a first nucleic acid molecule encoding a first heavy chain having a tryptophan at position 366 on a CH3 domain so as to generate a protuberance; (b) providing a second nucleic acid molecule encoding a second heavy chain having a serine at position 366, an anlanine at position 368 and a valine at position 407 on a CH3 thereof wherein the VH domain of said second heavy chain further comprises a cysteine at position 44 and an alanine at position 222; (c) providing a third nucleic acid molecule encoding a native first light chain; (d) providing a fourth nucleic acid molecule encoding a second light chain, wherein the VL domain thereof has a cysteine at position 100 and has a cysteine deletion at the position of its native disulfide bond with said second heavy chain; (e) culturing host cells comprising said first, second, third and fourth nucleic acid molecules under conditions that permit expression of the nucleic acid molecules; and (f) recovering the antibody, wherein the numbering of said position is according to Kabat and Wu. |
地址 |
Tel-Aviv IL |