Anti-cldn18.2 antibodies and diagnostic uses thereof
AssigneeAntengene Biologics Limited
InventorsJishun CHEN, Peng CHEN, Bing HOU, Bo SHAN
Life of this patent
Estimating the term…
Abstract
The present disclosure provides anti-CLDN18.2 antibodies or antigen-binding fragments thereof, pharmaceutical com-position comprising the same and the uses thereof (e.g., diagnostic use).
Claims72
An antibody or antigen-binding fragment thereof which specifically binds to CLDN18.2, comprising:
- one, two or three heavy chain complementarity determining regions (HCDR1, HCDR2 and/or HCDR3) contained within a heavy chain variable (VH) region sequence as set forth in SEQ ID NO:
- 7;
- and/or
- one, two or three light chain complementarity determining regions (LCDR1, LCDR2 and/or LCDR3) contained within a light chain variable (VL) region sequence as set forth in SEQ ID NO:
- 8.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising one, two or three of LCDR1, LCDR2 and LCDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 4, 5 and 6.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising:
- i. a HCDR1 comprising an amino acid sequence as set forth in SEQ ID NO:
- 1;
- ii. a HCDR2 comprising an amino acid sequence as set forth in SEQ ID NO:
- 2;
- and
- iii. a HCDR3 comprising an amino acid sequence as set forth in SEQ ID NO:
- 3.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising:
- i. a LCDR1 comprising an amino acid sequence as set forth in SEQ ID NO:
- 4;
- ii. a LCDR2 comprising an amino acid sequence as set forth in SEQ ID NO:
- 5;
- and
- iii. a LCDR3 comprising an amino acid sequence as set forth in SEQ ID NO:
- 6.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising:
- a HCDR1 comprising an amino acid sequence as set forth in SEQ ID NO:
- 1,
- a HCDR2 comprising an amino acid sequence as set forth in SEQ ID NO:
- 2,
- a HCDR3 comprising an amino acid sequence as set forth in SEQ ID NO:
- 3,
- a LCDR1 comprising an amino acid sequence as set forth in SEQ ID NO:
- 4,
- a LCDR2 comprising an amino acid sequence as set forth in SEQ ID NO:
- 5,
- and a LCDR3 comprising an amino acid sequence as set forth in SEQ ID NO:
- 6.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising a VH region having an amino acid sequence as set forth in SEQ ID NO:
- 7, or a homologous sequence thereof having at least 80% sequence identity to SEQ ID NO:
- 7.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising a VL region having an amino acid sequence as set forth in SEQ ID NO:
- 8, or a homologous sequence thereof having at least 80% sequence identity to SEQ ID NO:
- 8.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, comprising a VH region having an amino acid sequence as set forth in SEQ ID NO:
- 7 and a VL region having an amino acid sequence as set forth in SEQ ID NO:
- 8.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, further comprising one or more amino acid residue substitutions or modifications yet retains specific binding affinity to CLDN18.2.
The antibody or antigen-binding fragment thereof of the preceding claims, further comprising one or more non-natural amino acid (NNAA) substitutions.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, having one or more properties selected from the group consisting of:
- a) having substantially no cross-reactivity to human CLDN18.1;
- b) having substantially no cross-reactivity to human CLDN18.1 as measured by ELISA, FACS or IHC;
- c) having substantially no cross-reactivity to human CLDN18.1 peptide fragment within the amino acid sequence of STQDLYDNPVTSVFQYEGLWRSC (SEQ ID NO:
- 14) as measured by ELISA;
- d) being capable of specifically binding to an epitope within the amino acid sequence of TQDLYNNPVTAVFNYQGLWRSC (SEQ ID NO:
- 13) as measured by ELISA;
- e) being capable of specifically binding to an epitope within the amino acid sequence of human CLDN18.2 expressed in cells as measured by FACS assay;
- and
- f) being capable of specifically binding to human CLDN18.2 expressed in a cancer cell (e.g., a gastric cancer cell, a colon cancer cell, a hepatocellular carcinoma cell, an ovarian cancer cell, a cholangiocarcinoma cell, a pancreatic cancer cell, a breast cancer cell) as measured by IHC.
An antibody or antigen-binding fragment thereof, which competes for binding to CLDN18.2 with the antibody or antigen-binding fragment thereof of any one of the preceding claims.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, which is a chimeric, a humanized or a human antibody or an antigen-binding fragment thereof.
The antibody or an antigen-binding fragment thereof of any one of the preceding claims, which is a monoclonal antibody, a bispecific antibody, a multi-specific antibody, a recombinant antibody, a chimeric antibody, a humanized antibody, a labeled antibody, a bivalent antibody, an anti-idiotypic antibody, a fusion protein, a dimerized or polymerized antibody, or a modified antibody (e.g., glycosylated antibody).
The antibody or antigen-binding fragment thereof of any one of the preceding claims, which is a diabody, a Fab, a Fab′, a F(ab′) 2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv) 2, a bispecific dsFv (dsFv-dsFv′), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), a camelized single domain antibody, a nanobody, a domain antibody, or a bivalent domain antibody.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, further comprising an Fc region, optionally an Fc region of human immunoglobulin (Ig), or optionally an Fc region of human IgG.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, wherein the light chain is a λ light chain or a k light chain.
The antibody or antigen-binding fragment thereof of any one of the preceding claims, which is linked to one or more conjugate moieties.
Dependencies are inferred from the claim text.