Anti-cd70 antibody and application thereof

Patent metadata

Field	Value
Publication number	US-2023257472-A1
Application number	US-202118013231-A
Country	US
Kind code	A1
Filing date	Jun 29, 2021
Priority date	Jun 30, 2020
Publication date	Aug 17, 2023
Grant date	—

Abstract

The present invention relates to an anti-CD70 antibody and an application thereof. Specifically, the present disclosure relates to an anti-CD 70 antibody, which comprises a light chain variable region and a heavy chain variable region of the antibody, and a use as a drug.

First claim

1 . An anti-CD70 antibody comprising a heavy chain variable region and a light chain variable region, wherein:
i) the heavy chain variable region comprises an HCDR1 and an HCDR3 set forth in SEQ ID NO: 15 and SEQ ID NO: 17, respectively, and an HCDR2 set forth in SEQ ID NO: 54 or SEQ ID NO: 16; and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 set forth in SEQ ID NO 18, SEQ ID NO 19 and SEQ ID NO 20, respectively; ii) the heavy chain variable region comprises an HCDR1 and an HCDR3 set forth in SEQ ID NO: 9 and SEQ ID NO: 11, respectively, and an HCDR2 set forth in SEQ ID NO: 10 or SEQ ID NO: 42; and the light chain variable region comprises an LCDR1 and an LCDR3 set forth in SEQ ID NO: 12 and SEQ ID NO: 14, respectively, and an LCDR2 set forth in SEQ ID NO: 13 or SEQ ID NO: 43; or iii) the heavy chain variable region comprises an HCDR1 and an HCDR3 set forth in SEQ ID NO: 21 and SEQ ID NO: 23, respectively, and an HCDR2 set forth in SEQ ID NO: 22 or SEQ ID NO: 71; and the light chain variable region comprises an LCDR1 and an LCDR3 set forth in SEQ ID NO: 24 and SEQ ID NO: 25, respectively, and an LCDR2 set forth in SEQ ID NO: 13 or SEQ ID NO: 43; preferably, i) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 set forth in SEQ ID NO: 15, SEQ ID NO: 54 and SEQ ID NO: 17, respectively; and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 set forth in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively; ii) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 set forth in SEQ ID NO: 9, SEQ ID NO: 42 and SEQ ID NO: 11, respectively; and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 set forth in SEQ ID NO: 12, SEQ ID NO: 43 and SEQ ID NO: 14, respectively; or iii) the heavy chain variable region comprises an HCDR1, an HCDR2 and an HCDR3 set forth in SEQ ID NO: 21, SEQ ID NO: 71 and SEQ ID NO: 23, respectively; and the light chain variable region comprises an LCDR1, an LCDR2 and an LCDR3 set forth in SEQ ID NO: 24, SEQ ID NO: 43 and SEQ ID NO: 25, respectively.

2 . The anti-CD70 antibody according to claim 1 , wherein the antibody is a murine antibody, a chimeric antibody or a humanized antibody.

3 . The anti-CD70 antibody according to claim 1 , wherein the antibody is a humanized antibody, wherein the humanized antibody comprises a framework region or a framework region variant of a human antibody, wherein the framework region variant has up to 11 amino acid back mutations relative to a light chain framework region and/or a heavy chain framework region of the human antibody;
preferably, the humanized antibody comprises: a) a heavy chain variable region comprising an HCDR1 and an HCDR3 set forth in SEQ ID NO: 15 and SEQ ID NO: 17, respectively, and an HCDR2 set forth in SEQ ID NO: 54 or SEQ ID NO: 16; and a light chain variable region comprising an LCDR1, an LCDR2 and an LCDR3 set forth in SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 20, respectively; wherein the light chain variable region comprises a light chain framework region variant of the human antibody comprising one or more amino acid back mutations selected from the group consisting of 38R, 43S, 69R, 70Q and 71Y relative to the light chain framework region of the human antibody, and/or the heavy chain variable region comprises a heavy chain framework region variant of the human antibody comprising one or more amino acid back mutations selected from the group consisting of 2I, 24T, 46K, 72E and 82a N relative to the heavy chain framework region of the human antibody; or b) a heavy chain variable region comprising an HCDR1 and an HCDR3 set forth in SEQ ID NO: 9 and SEQ ID NO: 11, respectively, and an HCDR2 set forth in SEQ ID NO: 10 or SEQ ID NO: 42; and a light chain variable region comprising an LCDR1 and an LCDR3 set forth in SEQ ID NO: 12 and SEQ ID NO: 14, respectively, and an LCDR2 set forth in SEQ ID NO: 13 or SEQ ID NO: 43; wherein the heavy chain variable region comprises a heavy chain framework region variant of the human antibody comprising one or more amino acid back mutations selected from the group consisting of 4M, 37I, 38K, 48I, 67A, 69L, 71A, 73R, 78A, 80L and 94T relative to the heavy chain framework region of the human antibody; and/or the light chain variable region comprises a light chain framework region variant of the human antibody comprising one or more amino acid back mutations selected from the group consisting of 5S and 70N relative to the light chain framework region of the human antibody; or c) a heavy chain variable region comprising an HCDR1 and an HCDR3 set forth in SEQ ID NO: 21 and SEQ ID NO: 23, respectively, and an HCDR2 set forth in SEQ ID NO: 22 or SEQ ID NO: 71; and a light chain variable region comprising an LCDR1 and an LCDR3 set forth in SEQ ID NO: 24 and SEQ ID NO: 25, respectively, and an LCDR2 set forth in SEQ ID NO: 13 or SEQ ID NO: 43; wherein the heavy chain variable region comprises a heavy chain framework region variant of the human antibody comprising one or more amino acid back mutations selected from the group consisting of 27D, 30P, 37L, 38K, 48I, 66K, 67A, 69L and 82a N relative to the heavy chain framework region of the human antibody, and/or the light chain variable region comprises a light chain framework region variant of the human antibody comprising a 49S amino acid back mutation relative to the light chain framework region of the human antibody.

4 . The anti-CD70 antibody according to claim 1 , wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein:
d) the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 5, 44, 45, 46, 51, 52 or 53, and/or the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 6, 47, 48, 49 or 50; or e) the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 3, 26, 27, 28, 29, 30, 31, 34, 35, 36, 37, 38 or 39, and/or the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 4, 32, 33, 40, or 41; or f) the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 7, 55, 56, 57, 58, 59, 60, 63, 64, 65, 66, 67 or 68, and/or the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8, 61, 62, 69 or 70; preferably, the anti-CD70 antibody comprises a heavy chain variable region and a light chain variable region, wherein: (g) the heavy chain variable region is set forth in SEQ ID NO: 44, 45, 46, 51, 52 or 53; and the light chain variable region is set forth in SEQ ID NO: 47, 48, 49 or 50; or h) the heavy chain variable region is set forth in SEQ ID NO: 26, 27, 28, 29, 30, 31, 34, 35, 36, 37, 38 or 39; and the light chain variable region is set forth in SEQ ID NO: 32, 33, 40 or 41; or (i) the heavy chain variable region is set forth in SEQ ID NO: 5; and the light chain variable region is set forth in SEQ ID NO: 6; or (j) the heavy chain variable region is set forth in SEQ ID NO: 3; and the light chain variable region is set forth in SEQ ID NO: 4; or (k) the heavy chain variable region is set forth in SEQ ID NO: 7; and the light chain variable region is set forth in SEQ ID NO: 8; or l) the heavy chain variable region is set forth in SEQ ID NO: 55, 56, 57, 58, 59, 60, 63, 64, 65, 66, 67 or 68; and the light chain variable region is set forth in SEQ ID NO: 61, 62, 69 or 70; and more preferably, the anti-CD70 antibody comprises a heavy chain variable region and a light chain variable region as shown below, wherein: (n) the heavy chain variable region is set forth in SEQ ID NO:

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Sun Le
• Ye Xin
• Chen Yuxiao
• Jin Xinsheng
• Tao Weikang

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/92

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

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title