JPWO2020011964A5

JPWO2020011964A5 -

Info

Publication number: JPWO2020011964A5
Application number: JP2021500385A
Authority: JP
Publication date: 2022-07-20
Anticipated expiration: 2039-07-12

Description

抗体分子のＣＨ３ドメインは、任意選択により、ＣＨ３ドメイン配列のＣ末端のすぐ隣に追加のリジン残基（Ｋ）を含み得る。
The CH3 domain of the antibody molecule may optionally contain an additional lysine residue (K) immediately adjacent to the C-terminus of the CH3 domain sequence.

Claims

An antibody molecule that binds to Programmed Death Ligand 1 (PD-L1) and CD137.
(A) PD-L1 complementarity determining regions (CDR) -based antigen binding sites; and (b) CD137 antigen binding sites located in the CH3 domain of the antibody molecule, the CDR-based antigen binding sites being Kabat . By numbering
(I) SEQ ID NOs: 1, 2, 3, 4, 5 and 6 [E12v2];
(Ii) SEQ ID NOs: 1, 2, 3, 18, 19 and 20 [E05v2]; or (iii) SEQ ID NOs: 1, 2, 3, 18, 19 and 29 [G12v2], respectively;
Contains or contains CDRs 1 to 6 described in
The CDR-based antigen-binding sites are numbered by ImMunoGeneTics (IMGT).
(I) SEQ ID NOs: 7, 8, 9, 10, 11 and 6 [E12v2];
(Ii) SEQ ID NOs: 21, 8, 9, 22, 11 and 20 [E05v2]; or
(Iii) SEQ ID NOs: 21, 8, 9, 22, 11 and 29 [G12v2], respectively;
Including CDRs 1 to 6 described in
The CD137 antigen binding site comprises a first sequence and a second sequence located in the AB and EF structural loops of the CH3 domain, respectively, and the first and second sequences are SEQ ID NOs: 113 and 114 [, respectively. FS22-172-003], or having the sequences described in 79 and 80 [FS22-53-008],
Antibody molecule.

The antibody molecule
(I) SEQ ID NOs: 12 and 14 [E12v2], respectively;
(Ii) SEQ ID NOs: 23 and 25 [E05v2], respectively; or (iii) SEQ ID NOs: 23 and 30 [G12v2], respectively.
The antibody molecule according to claim 1, which comprises the VH domain and the VL domain according to claim 1.

The antibody molecule
(I) CDR1-6 [E12v2] according to SEQ ID NOs: 1, 2, 3, 4, 5 and 6 , respectively, by Kabat numbering ;
(Ii) VH and VL domains [E12v2] according to SEQ ID NOs: 7, 8, 9, 10, 11 and 6 [E12v2]; and / or ( iii ), respectively, according to IMGT numbering.
The antibody molecule according to claim 1 or 2.

(I) The first sequence is located between the 14th and 17th positions of the CH3 domain of the antibody molecule; and / or (ii) the second sequence is the CH3 of the antibody molecule. It is located between positions 91 and 99 of the domain; and the numbering of amino acid residues follows the IMGT numbering scheme.
The antibody molecule according to any one of claims 1 to 3.

The antibody molecule according to any one of claims 1 to 4, wherein the antibody molecule comprises the CH3 domain set forth in SEQ ID NO: 115 [FS22-172-003] or SEQ ID NO: 81 [FS22-53-008] .

The antibody molecule of claim 5, wherein the CH3 domain sequence further comprises a lysine residue (K) immediately adjacent to the C-terminus of the CH3 domain sequence.

The antibody molecule is an antibody:
(I) FS22-172-003-AA / E12v2 according to SEQ ID NOs: 134 and 17, respectively;
(Ii) FS22-172-003-AA / E05v2 according to SEQ ID NOs: 137 and 28, respectively;
(Iii) FS22-172-003-AA / G12v2 according to SEQ ID NOs: 140 and 33, respectively;
(Iv) FS22-053-008-AA / E12v2 according to SEQ ID NOs: 143 and 17, respectively;
(V) FS22-053-008-AA / E05v2 according to SEQ ID NOs: 146 and 28, respectively; or (vi) FS22-053-008-AA / G12v2 according to SEQ ID NOs: 149 and 33, respectively.
The antibody molecule according to any one of claims 1 to 6 , which comprises a heavy chain and a light chain of the above.

The antibody molecule according to any one of claims 1 to 7 , wherein the antibody molecule comprises a heavy chain and a light chain according to SEQ ID NOs: 134 and 17 [FS22-172-003-AA / E12v2], respectively.

The antibody molecule of claim 8, wherein the CH3 domain sequence of the heavy chain sequence further comprises a lysine residue (K) immediately adjacent to the C-terminus of the CH3 domain sequence.

(I) The antibody molecule is modified to reduce or suppress the binding of the CH2 domain of the antibody molecule to one or more Fcγ receptors.
(Ii) The antibody molecule does not bind to one or more Fcγ receptors and / or
(Iii) Binding of the antibody molecule to CD137 on immune cells and to PD-L1 bound to the surface of tumor cells causes clustering of CD137 on immune cells.
The antibody molecule according to any one of claims 1 to 8.

One or more nucleic acid molecules encoding the antibody molecule according to any one of claims 1 to 10.

One or more vectors comprising the one or more nucleic acid molecules of claim 11.

A recombinant host cell comprising the one or more nucleic acid molecules of claim 11 or the one or more vectors of claim 12.

10 . The method for producing the antibody molecule according to the above item.

A pharmaceutical composition comprising the antibody molecule according to any one of claims 1 to 10 and a pharmaceutically acceptable excipient.

A pharmaceutical composition for treating cancer in an individual , comprising the antibody molecule according to any one of claims 1 to 10.