Fusion protein comprising anti-mesothelin antibody, anti-CD3 antibody or anti-EGFR antibody, bispecific or trispecific antibody comprising same, and uses thereof

Patent metadata

Field	Value
Publication number	US-12534518-B2
Application number	US-201917439974-A
Country	US
Kind code	B2
Filing date	Dec 16, 2019
Priority date	Mar 29, 2019
Publication date	Jan 27, 2026
Grant date	Jan 27, 2026

Abstract

A fusion protein including a fragment of an anti-mesothelin antibody, an anti-CD3 antibody or an anti-EGFR antibody; a bispecific antibody that is specific to mesothelin and CD3; a trispecific antibody that is specific to mesothelin, CD3 and EGFR are provided. The fusion protein is effective in treating cancer. The bispecific or trispecific antibody can be prepared in a high yield and with high purity, and has excellent tumor killing and growth inhibitory effects, and thus can be effectively used in cancer treatment.

First claim

The invention claimed is:

1 . A multispecific antibody, comprising a first protein and a second protein,
wherein the first protein is the first fusion protein of Structural Formula 1; and wherein the second protein is a second fusion protein of Structural Formula 2 or a third fusion protein of Structural Formula 3:
N′-A-B-L1-C-D-L2-E-F-L3-G-H-L4-I-C′  [Structural Formula 1]

wherein N′ is the N-terminus of the first fusion protein, C′ is the C-terminus of the first fusion protein, A is a light chain variable domain of an antibody that specifically binds to mesothelin (anti-mesothelin antibody), comprising light chain CDR1 of SEQ ID NO: 25, light chain CDR2 of SEQ ID NO: 26, and light chain CDR3 of SEQ ID NO: 27, B is a light chain constant domain of the anti-mesothelin antibody, C is a heavy chain variable domain of the anti-mesothelin antibody, comprising heavy chain CDR1 of SEQ ID NO: 28, heavy chain CDR2 of SEQ ID NO: 29, and heavy chain CDR3 of SEQ ID NO: 30, D is a CH1 domain in heavy chain constant domains of the anti-mesothelin antibody, E is a light chain variable domain of an antibody that specifically binds to CD3 (anti-CD3 antibody), comprising light chain CDR1 of SEQ ID NO: 31, light chain CDR2 of SEQ ID NO: 32, and light chain CDR3 of SEQ ID NO: 33, F is a light chain constant domain of the anti-CD3 antibody, G is a heavy chain variable domain of the anti-CD3, the domain including heavy chain CDR1 of SEQ ID NO: 34, heavy chain CDR2 of SEQ ID NO: 35, and heavy chain CDR3 of SEQ ID NO: 36, H is a CH1 domain in heavy chain constant domains of the anti-CD3 antibody, I is an Fc region or a variant thereof, and each of L1, L2, L3, and L4 is a peptide linker; and
N′-A-B-L1-C-D-L5-J-C′  [Structural Formula 2]

wherein N′ is the N-terminus of the second fusion protein, C′ is the C-terminus of the second fusion protein, A, B, L1, C, and D are the same as defined above with respect to Structural Formula 1; J is an Fc region or a fragment thereof, and L5 is a peptide linker; and
N′-K-M-L6-N-O-L7-P-C′  [Structural Formula 3]

wherein N′ is the N-terminus of the first fusion protein, C′ is the C-terminus of the first fusion protein, K is a light chain variable domain of an antibody that specifically binds to EGFR (anti-EGFR antibody), comprising light chain CDR1 of SEQ ID NO: 37, light chain CDR2 of SEQ ID NO: 38, and light chain CDR3 of SEQ ID NO: 39, M is a light chain constant domain of the anti-EGFR antibody, N is a heavy chain variable domain of the anti-EGFR antibody, comprising heavy chain CDR1 of SEQ ID NO: 40, heavy chain CDR2 of SEQ ID NO: 41, and heavy chain CDR3 of SEQ ID NO: 42, O is a CH1 domain in heavy chain constant domains of the anti-EGFR antibody, P is an FC region or a fragment thereof, and each of L6 and L7 is a peptide linker.

2 . The multispecific antibody of claim 1 , wherein the multispecific antibody is a bispecific antibody comprising the first fusion protein and the second fusion protein, wherein a knob modification is included in I of the first fusion protein and a hole modification is included in J of the second fusion protein; or a hole modification is included in I of the first fusion protein and a knob modification is included in J of the second fusion protein.

3 . The multispecific antibody of claim 1 , wherein the multispecific antibody is a trispecific antibody comprising the first fusion protein and the third fusion protein, wherein a knob modification is included in I of the first fusion protein and a hole modification is included in P of the third fusion protein; or a hole modification is included in I of the first fusion protein and a knob modification is included in P of the third fusion protein.

4 . A pharmaceutical composition comprising, as an active ingredient, the multispecific antibody of claim 1 .

5 . A method for treating cancer in a subject in need thereof, comprising administering, to the subject, a therapeutically effective amount of the pharmaceutical composition of claim 4 .

Assignees

• Green Cross Corp
• Mogam Inst Biomedical Res

Inventors

• Lim Yangmi
• Lee Shinai
• Won Jonghwa
• Park Yong-Yea
• Yoon Aerin
• Lee Sua
• Lim Okjae
• Lim Sojung
• Kim Munkyung

Classifications

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/522

  CH1 domain · CPC title