Antibodies binding to CD30 and CD3
The invention relates to multispecific antibodies binding to CD3 and CD30. The invention further provides pharmaceutical compositions comprising antibodies of the invention, nucleic acids encoding the antibodies, host cells that produce the antibodies, methods of producing the antibodies and uses of the antibodies, in particular for cancer therapy.
1. A bispecific antibody comprising a CD30 binding region comprising a first heavy chain comprising the amino acid sequence of SEQ ID NO: 17 and a first light chain comprising the amino acid sequence of SEQ ID NO: 18, and a CD3 binding region comprising a second heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a second light chain comprising the amino acid sequence of SEQ ID NO: 20.
2. A nucleic acid construct, or a combination of nucleic acid constructs, encoding the bispecific antibody according to claim 1 .
3. An expression vector, or a combination of expression vectors, comprising the nucleic acid construct(s) according to claim 2 .
4. A delivery vehicle comprising the expression vector, or combination of expression vectors, according to claim 3 .
5. A recombinant host cell capable of producing the bispecific antibody according to claim 1 .
6. A method for producing a bispecific antibody comprising
(i) culturing the recombinant host cell according to claim 5 under conditions wherein the antibody is produced, and
(ii) isolating the produced bispecific antibody from the culture.
7. A pharmaceutical composition comprising the bispecific antibody according to claim 1 and a pharmaceutically-acceptable carrier.
8. A method of treating cancer comprising administering to a subject in need thereof an effective amount of the bispecific antibody according to claim 1 .
9. The method according to claim 8 , wherein the cancer is Hodgkin's lymphoma or Non-Hodgkin's lymphoma (NHL).
10. The method according to claim 9 , wherein the Non-Hodgkin's lymphoma is T cell Non-Hodgkin's lymphoma (T-NHL).
11. The method according to claim 9 , wherein the Hodgkin's lymphoma is classical Hodgkin's lymphoma (cHL).
12. The method according to claim 8 , wherein the bispecific antibody is administered intravenously and/or subcutaneously.
13. The method according to claim 12 , wherein the bispecific antibody is administered subcutaneously.
14. A method for producing a bispecific antibody comprising
a) providing a first antibody comprising a CD30 binding region and a second antibody comprising a CD3 binding region, wherein both the CD30 binding region and CD3 binding region comprise the amino acid sequences described in claim 1 ,
wherein the first and second antibodies comprise an Fc region, and
wherein the amino acid sequences of the first and second CH3 regions of the first and second antibodies are different and are such that the heterodimeric interaction between the first and second CH3 regions is stronger than each of the homodimeric interactions of the first and second CH3 regions;
b) incubating the first antibody together with the second antibody under reducing conditions sufficient to allow the cysteines in the hinge regions to undergo disulfide-bond isomerization; and
c) obtaining the bispecific antibody comprising the first immunoglobulin heavy chain and the first immunoglobulin light chain of the first antibody and the second immunoglobulin heavy chain and the second immunoglobulin light chain of the second antibody.
15. A kit-of-parts comprising the bispecific antibody according to claim 1 , and instructions for use.
16. A diagnostic composition comprising the bispecific antibody according to claim 1 .