Granted Patent B2

US 12,466,891 · App. 17/611,344 · Granted Nov 11, 2025

Inventors: Yoshiki Sumitomo (Tokyo, JP); Masayuki Kai (Tokyo, JP)

Assignee: KYOWA KIRIN CO., LTD.

C07K16/2878A61P35/00C07K16/303C07K16/46C12N15/63G01N33/574A61K2039/505

Abstract

Claims (36)

1 . A bispecific antibody, which comprises an IgG portion comprising a first antigen binding domain, and also comprises a second antigen binding domain, in which the C terminus of a heavy chain of the IgG portion binds to the second antigen binding domain either directly or via a linker,

wherein the first antigen binding domain binds to human CD40 and comprises a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 16 to 18, respectively, and a VL comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 11 to 13, respectively, and

wherein the second antigen binding domain binds to human glypican 3 (GPC3) and comprises a VL comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 11 to 13, respectively, and any one VH selected from the group consisting of the following (1a) to (1g);

(1a) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 42 to 44, respectively;

(1b) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 47 to 49, respectively;

(1c) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 52 to 54, respectively;

(1d) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 57 to 59, respectively;

(1e) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 62 to 64, respectively;

(1f) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 67 to 69, respectively; and

(1g) a VH comprising CDRs 1 to 3 comprising the amino acid sequences of SEQ ID NOs: 72 to 74, respectively.

2 . The bispecific antibody according to claim 1 , which divalently binds to each of human CD40 and human GPC3.

3 . The bispecific antibody according to claim 1 , wherein the C terminus of the heavy chain of the IgG portion directly binds to the second antigen binding domain.

4 . The bispecific antibody according to claim 1 , wherein the second antigen binding domain is Fab.

5 . The bispecific antibody according to claim 1 , which has CD40 agonistic activity.

6 . The bispecific antibody according to claim 1 , which exhibits CD40 agonistic activity only in the presence of a GPC3-expressing cell.

7 . The bispecific antibody according to claim 1 , wherein the antigen binding domain that binds to human CD40 comprises a VH comprising the amino acid sequence of SEQ ID NO: 15, and a VL comprising the amino acid sequence of SEQ ID NO: 10.

8 . The bispecific antibody according to claim 1 , wherein the antigen binding domain that binds to human GPC3 comprises a VL comprising the amino acid sequence of SEQ ID NO: 10, and any one VH selected from the group consisting of the following (2a) to (2g):

(2a) a VH comprising the amino acid sequence of SEQ ID NO: 41;

(2b) a VH comprising the amino acid sequence of SEQ ID NO: 46;

(2c) a VH comprising the amino acid sequence of SEQ ID NO: 51;

(2d) a VH comprising the amino acid sequence of SEQ ID NO: 56;

(2e) a VH comprising the amino acid sequence of SEQ ID NO: 61;

(2f) a VH comprising the amino acid sequence of SEQ ID NO: 66; and

(2g) a VH comprising the amino acid sequence of SEQ ID NO: 71.

9 . The bispecific antibody according to claim 1 , wherein the heavy chain constant region of the IgG portion comprises the amino acid sequence of SEQ ID NO: 77.

10 . The bispecific antibody according to claim 1 , which consists of two heavy chains comprising the amino acid sequence of any one selected from SEQ ID NOS: 96, 98, 100, 102 104, 106, and 108, and four light chains, wherein each light chain comprises a VL comprising the amino acid sequence of SEQ ID NO: 10.

11 . A bispecific antibody fragment of the bispecific antibody according to claim 1 .

12 . A DNA encoding the bispecific antibody according to claim 1 or a bispecific antibody fragment of the bispecific antibody.

13 . A recombinant vector, comprising the DNA according to claim 12 .

14 . A transformant strain obtained by introducing the recombinant vector according to claim 13 into a host cell.

15 . A method for producing the bispecific antibody according to claim 1 or a bispecific antibody fragment of the bispecific antibody, characterized by culturing a transformant strain obtained by introducing a recombinant vector comprising a DNA encoding the bispecific antibody or the bispecific antibody fragment into a host cell in a culture medium to produce and accumulate the bispecific antibody or the bispecific antibody fragment in a culture, and collecting the bispecific antibody or the bispecific antibody fragment from the culture.

16 . A method of treating a subject having disease associated with human CD40 and/or human GPC3, comprising administering an effective amount of the bispecific antibody according to claim 1 or a bispecific antibody fragment of the bispecific antibody to the subject.

17 . The method according to claim 16 , wherein the disease associated with at least one of human CD40 and/or human GPC3 is a cancer.

18 . A derivative of a bispecific antibody, in which a radioisotope, a low-molecular weight drug, a high-molecular weight drug, a protein, or an antibody drug is bound chemically or through genetic engineering to the bispecific antibody according to claim 1 or a bispecific antibody fragment of the bispecific antibody.

19 . A method of diagnosing a subject as having a disease associated with human CD40 and/or human GPC3, comprising administering the bispecific antibody according to claim 1 or a bispecific antibody fragment of the bispecific antibody to the subject and detecting or measuring a cell expressing human CD40 and/or human GPC3.

20 . The method according to claim 19 , wherein the disease associated with human CD40 and/or human GPC3 is a cancer.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (23)