Antibody binding to bcma and use thereof

Patent metadata

Field	Value
Publication number	US-2025034268-A1
Application number	US-202218716203-A
Country	US
Kind code	A1
Filing date	Dec 7, 2022
Priority date	Dec 7, 2021
Publication date	Jan 30, 2025
Grant date	—

Abstract

Provided are an antibody having an improved affinity for specifically binding to BCMA, an antibody further comprising a P329G mutation, and a conjugate, a fusion, a bispecific antibody or a pharmaceutical composition comprising the antibody. In addition, further provided are a nucleic acid encoding the antibody, a host cell comprising the nucleic acid, and a method for preparing the antibody. The present invention also relates to the therapeutic and diagnostic use of the antibody binding to BCMA.

First claim

What is claimed is:

1 . An antibody that specifically binds to BCMA or antigen-binding fragment thereof, comprising
(a) three CDRs in the amino acid sequence of heavy chain variable region shown in SEQ ID NO: 27 and three CDRs in the amino acid sequence of light chain variable region shown in SEQ ID NO: 36; or variants with a single CDR or several CDRs not exceeding 2 or 1 amino acid change per CDR region within the six CDR regions; (b) three CDRs in the amino acid sequence of heavy chain variable region shown in SEQ ID NO: 45 and three CDRs in the amino acid sequence of light chain variable region shown in SEQ ID NO: 54; or variants with a single CDR or several CDRs not exceeding 2 or 1 amino acid change per CDR region within the six CDR regions; (c) three CDRs in the amino acid sequence of heavy chain variable region shown in SEQ ID NO: 81 and three CDRs in the amino acid sequence of light chain variable region shown in SEQ ID NO: 90; or variants with a single CDR or several CDRs not exceeding 2 or 1 amino acid change per CDR region within the six CDR regions; or (d) three CDRs in the amino acid sequence of heavy chain variable region shown in SEQ ID NO: 99 and three CDRs in the amino acid sequence of light chain variable region shown in SEQ ID NO: 108; or variants with a single CDR or several CDRs not exceeding 2 or 1 amino acid change per CDR region within the six CDR regions; wherein the amino acid change is the addition, deletion or substitution of amino acid.

2 . An antibody that specifically binds to BCMA or antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, wherein
(a) the heavy chain variable region comprises HCDR1 shown in GSIVSSSYYWT (SEQ ID NO: 19), or a variant of the HCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR2 shown in SISIAGSTYYNPSLKS (SEQ ID NO: 20), or a variant of the HCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR3 shown in ARDRGDTILDV (SEQ ID NO: 21), or a variant of the HCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; the light chain variable region comprises LCDR1 shown in RASQSISRYLN (SEQ ID NO: 28), or a variant of the LCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; LCDR2 shown in AASSLQS (SEQ ID NO: 29), or a variant of the LCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; and LCDR3 shown in QQKYFDIT (SEQ ID NO: 30), or a variant of the LCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; (b) the heavy chain variable region comprises HCDR1 shown in GSIVSSSYYWT (SEQ ID NO: 37), or a variant of the HCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR2 shown in SISIAGSTYYNPSLKS (SEQ ID NO: 38), or a variant of the HCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR3 shown in ARDRGDQILDV (SEQ ID NO: 39), or a variant of the HCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; the light chain variable region comprises LCDR1 shown in RASQSISRYLN (SEQ ID NO: 46), or a variant of the LCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; LCDR2 shown in AASSLQS (SEQ ID NO: 47), or a variant of the LCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; and LCDR3 shown in QQKYFDIT (SEQ ID NO: 48), or a variant of the LCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; (c) the heavy chain variable region comprises HCDR1 shown in GTFSNDVIS (SEQ ID NO: 73), or a variant of the HCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR2 shown in VIIPIFGIANYAQKFQG (SEQ ID NO: 74), or a variant of the HCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR3 shown in ARGRGYYSSWLLDI (SEQ ID NO: 75), or a variant of the HCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; the light chain variable region comprises LCDR1 shown in QASQDITNYLN (SEQ ID NO: 82), or a variant of the LCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; LCDR2 shown in DASNLET (SEQ ID NO: 83), or a variant of the LCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; and LCDR3 shown in QQAFDLIT (SEQ ID NO: 84), or a variant of the LCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; or (d) the heavy chain variable region comprises HCDR1 shown in GTFSNDVIS (SEQ ID NO: 91), or a variant of the HCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR2 shown in VIIPIFGIANYAQKFQG (SEQ ID NO: 92), or a variant of the HCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; HCDR3 shown in ARGRGYYSSWLHDI (SEQ ID NO: 93), or a variant of the HCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; the light chain variable region comprises LCDR1 shown in QASQDITNYLN (SEQ ID NO: 100), or a variant of the LCDR1 with no more than 2 amino acid changes or no more than 1 amino acid change; LCDR2 shown in DASNLET (SEQ ID NO: 101), or a variant of the LCDR2 with no more than 2 amino acid changes or no more than 1 amino acid change; and LCDR3 shown in QQAFDLIT (SEQ ID NO: 102), or a variant of the LCDR3 with no more than 2 amino acid changes or no more than 1 amino acid change, according to Kabat numbering; wherein the amino acid change is the addition, deletion or substitution of amino acid.

3 . The antibody that specifically binds to BCMA or antigen-binding fragment thereof according to claim 2 , comprising a heavy chain variable region and a light chain variable region, wherein
(a) the heavy chain variable region comprises HCDR1 shown in GSIVSSSYYWT (SEQ ID NO: 19); HCDR2 shown in SISIAGSTYYNPSLKS (SEQ ID NO: 20); and HCDR3 shown in ARDRGDTILDV (SEQ ID NO: 21); the light chain variable region comprises LCDR1 shown in RASQSISRYLN (SEQ ID NO: 28); LCDR2 shown in AASSLQS (SEQ ID NO: 29); and LCDR3 shown in QQKYFDIT (SEQ ID NO: 30); (b) the heavy chain variable region comprises HCDR1 shown in GSIVSSSYYWT (SEQ ID NO: 37); HCDR2 shown in SISIAGSTYYNPSLKS (SEQ ID NO: 38); and HCDR3 shown in ARDRGDQILDV (SEQ ID NO: 39); the light chain variable region comprises LCDR1 shown in RASQSISRYLN (SEQ ID NO: 46); LCDR2 shown in AASSLQS (SEQ ID NO: 47); and LCDR3 shown in QQKYFDIT (SEQ ID NO: 48); (c) the heavy chain variable region comprises HCDR1 shown in GTFSNDVIS (SEQ ID NO: 73); HCDR2 shown in VIIPIFGIANYAQKFQG (SEQ ID NO: 74); HCDR3 shown in ARGRGYYSSWLLDI (SEQ ID NO: 75); the light chain variable region comprises LCDR1 shown in QASQDITNYLN (SEQ ID NO: 82); LCDR2 shown in DASNLET (SEQ ID NO: 83); and LCDR3 shown in QQAFDLIT (SEQ ID NO: 84); or (d) the heavy chain variable region comprises HCDR1 shown in GTFSNDVIS (SEQ ID NO: 91); HCDR2 shown in VIIPIFGIANYAQKFQG (SEQ ID NO: 92); HCDR3 shown in ARGRGYYSSWLHDI (SEQ ID NO: 93); the light chain variable region comprises LCDR1 shown in QASQDITNYLN (SEQ ID NO: 100); LCDR2 shown in DASNLET (SEQ ID NO: 101); and LCDR3 shown in QQAFDLIT (SEQ ID NO: 102).

4 . The antibody that specifically binds to BCMA or antigen-binding fragment thereof according to any of claims 1 to 3 , comprising a heavy chain variable region and a light chain variable region, wherein
(a) the heavy chain variable region comprises a sequence shown in SEQ ID NO: 27 or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity thereto, and the light

Assignees

• Innovent Biologics Suzhou Co Ltd

Inventors

• Wei Huafeng
• Xu Dan
• Darowski Diana Binia
• Prinz Bianka
• Boland Nadthakarn
• Geoghegan James

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K2317/92

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

• C07K14/7051

  T-cell receptor (TcR)-CD3 complex · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title