Multivalent Antibodies
The present invention provides a recombinant antibody or a heavy/light chain component thereof comprising: a heavy chain comprising a C H1 constant region fragment located between a first and second variable domain, and a third variable domain linked directly or indirectly to the first or second variable domain, with the proviso that the heavy chain only contains one C H1 and only contains three variable domains, and a light chain comprising at least a C L domain located between a first and second variable domain, and a third variable domain linked directly or indirectly to the first or second variable domain, with the proviso that the light chain only contains one C L domain and only contains three variable domains, and wherein said heavy and light chains are aligned to provide a first binding site formed by the first variable domains in the light and heavy chain, a second binding site formed by the second variable domains in the light and heavy chain, and a third binding site formed by the third variable domains in the light and heavy chain.
1 . A recombinant antibody or a heavy/light chain component thereof comprising:
a heavy chain comprising a C H1 constant region fragment located between a first and second variable domain, and a third variable domain linked directly or indirectly to the first or second variable domain,
with the proviso that the heavy chain only contains one C H1 and only contains three variable domains, and
a light chain comprising at least a C L domain located between a first and second variable domain, and a third variable domain linked directly or indirectly to the first or second variable domain,
with the proviso that the light chain only contains one C L domain and only contains three variable domains, and
wherein said heavy and light chains are aligned to provide a first binding site formed by the first variable domains in the light and heavy chain, a second binding site formed by the second variable domains in the light and heavy chain, and a third binding site formed by the third variable domains in the light and heavy chain.
2 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 wherein C H1 is fused to the first variable domain in the heavy chain.
3 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 wherein C L is fused to the first variable domain in the light chain.
4 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein C H1 is also linked directly or indirectly to the second variable domain in the heavy chain.
5 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein C L is also linked directly or indirectly to the second variable domain in the light chain.
6 . A recombinant antibody or a heavy/light chain component thereof according to claim 4 wherein the indirect link is a peptide linker.
7 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein the third variable domain is linked indirectly.
8 . A recombinant antibody or a heavy/light chain component thereof according to claim 7 wherein the indirect link is a peptide linker.
9 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein the third variable domain in the heavy and/or light chain is linked to the first variable domain therein.
10 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein the third variable domain in the heavy and/or light chain is linked to the second variable domain therein.
11 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 wherein each variable domain in the heavy chain is a VH domain and each variable domain in the light chain is a VL domain.
12 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 wherein each binding site is formed by a variable domain VH/VL pair which is a cognate pair.
13 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 wherein each binding site is formed by a variable domain VH/VL pair which are a complementary VH/VL pair which bind antigen co-operatively.
14 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein the variable domains of at least one binding site are linked by a disulfide bond.
15 . A recombinant antibody or heavy/light chain component thereof according to claim 1 wherein the second variable domains forming the second binding site are stabilized by a disulfide bond.
16 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein third variable domains forming the third binding site are stabilized by a disulfide bond.
17 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 , wherein the C H1 of the heavy chain is linked to the C L of the light chain by a disulfide bond.
18 . A recombinant protein according to claim 17 , where in C H1 does not comprise a hinge region.
19 . A recombinant antibody or a heavy/light chain component thereof according to claim 1 which is monospecific, bispecific or trispecific.
20 . A recombinant antibody or a heavy/light chain component thereof according to claim 5 wherein the indirect link is a peptide linker.