JP2024001073A5

JP2024001073A5 -

Info

Publication number: JP2024001073A5
Application number: JP2023165289A
Authority: JP
Filing date: 2023-09-27
Publication date: 2024-04-24

Claims

(a) a complementarity determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:23;
(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO:24;
(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 25;
(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO:26;
(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:27; and
(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10
2. An anti-glycoed MUC1 antibody or antigen-binding fragment comprising:

(a) a complementarity determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:28;
(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO:29;
(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 25;
(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO:30;
(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:9; and
(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 31
2. An anti-glycoed MUC1 antibody or antigen-binding fragment comprising:

(a) a complementarity determining region (CDR) H1 comprising the amino acid sequence of SEQ ID NO:5;
(b) CDR-H2 comprising the amino acid sequence of SEQ ID NO:6;
(c) CDR-H3 comprising the amino acid sequence of SEQ ID NO:7;
(d) CDR-L1 comprising the amino acid sequence of SEQ ID NO:8;
(e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:9; and
(f) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 10
2. An anti-glycoed MUC1 antibody or antigen-binding fragment comprising:

The anti-glycoMUC1 antibody or antigen-binding fragment of any one of claims 1 to 3, which is a chimeric or humanized antibody.

The anti-glycoMUC1 antibody or antigen-binding fragment of any one of claims 1 to 4, comprising a VH and a VL.

VH and VL,
(a) the VH comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:3 and the VL comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:4; or
(b) the VH comprises an amino acid sequence having at least 97% sequence identity to SEQ ID NO:3, and the VL comprises an amino acid sequence having at least 97% sequence identity to SEQ ID NO:4; or
(c) the VH comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:3, and the VL comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO:4; or
(c) the VH comprises an amino acid sequence having 100% sequence identity to SEQ ID NO:3, and the VL comprises an amino acid sequence having 100% sequence identity to SEQ ID NO:4;
The anti-glycoMUC1 antibody or antigen-binding fragment according to any one of claims 1 to 5.

(a) It is multivalent,
(b) in the form of a single chain variable fragment (scFv); or
(c) in the form of a multispecific antibody;
The anti-glycoMUC1 antibody or antigen-binding fragment according to any one of claims 1 to 6.

The anti-glycoMUC1 antibody or antigen-binding fragment according to claim 7, which is in the form of a multispecific antibody and is a bispecific antibody that binds to a glycoMUC1 epitope (hereinafter referred to as the "first epitope") and a second epitope different from the first epitope.

The anti-glycoMUC1 antibody or antigen-binding fragment of claim 8, wherein the bispecific antibody is a CrossMab.

The CrossMab ^ＦＡＢFAB , CrossMab ^{ＶＨ－ＶＬVH-VL} Or CrossMab ^{ＣＨ１－ＣＬCH1-CL} 10. The anti-glyco-MUC1 antibody or antigen-binding fragment of claim 9,

The anti-glycoMUC1 antibody or antigen-binding fragment of claim 8, wherein the second epitope is a MUC1 epitope that is overexpressed on cancer cells compared to normal cells.

The anti-glycoMUC1 antibody or antigen-binding fragment of claim 8, wherein the second epitope is a T cell epitope.

The anti-glycoMUC1 antibody or antigen-binding fragment of claim 12, wherein the T cell epitope is a human CD3 epitope.

The anti-glycoMUC1 antibody or antigen-binding fragment of claim 13, wherein the human CD3 epitope comprises a CD3 gamma epitope, a CD3 delta epitope, a CD3 epsilon epitope, or a CD3 zeta epitope.

A fusion protein comprising the anti-glycoed MUC1 antibody or antigen-binding fragment of any one of claims 1 to 14 operably linked to at least a second amino acid sequence.

The fusion protein of claim 15, wherein the second amino acid sequence is a fusion peptide, and the fusion peptide is a CD28-CD3-zeta fusion peptide or a 4-1BB (CD137)-CD3-zeta fusion peptide.

A chimeric antigen receptor (CAR) comprising an anti-glyco-MUC1 antibody or antigen-binding fragment in the form of an scFv according to claim 7.

The CAR of claim 17, comprising, in order from amino terminus to carboxy terminus, a human CD8 leader peptide, the scFv, a human CD8 hinge domain, a human CD8 transmembrane domain, and a CD3-zeta signaling domain.

An antibody-drug conjugate comprising the anti-glycoed MUC1 antibody or antigen-binding fragment of any one of claims 1 to 14 conjugated to a cytotoxic agent.

A nucleic acid comprising a coding region for the anti-glycoed MUC1 antibody or antigen-binding fragment of any one of claims 1 to 14.

A vector comprising the nucleic acid of claim 20.

A host cell engineered to express a nucleic acid comprising the coding region for the anti-glycoed MUC1 antibody or antigen-binding fragment of any one of claims 1 to 14.

A pharmaceutical composition for treating cancer, comprising an anti-glycoed MUC1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 14, a fusion protein according to claim 15 or 16, a CAR according to claim 17 or 18, an antibody-drug conjugate according to claim 19, a nucleic acid according to claim 20, a vector according to claim 21, or a host cell according to claim 22.

21. A pharmaceutical composition for use in the manufacture of a medicament for treating cancer, comprising an anti-glycoed MUC1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 14, a fusion protein according to claim 15 or 16, a CAR according to claim 17 or 18, an antibody-drug conjugate according to claim 19, a nucleic acid according to claim 20, a vector according to claim 21, or a host cell according to claim 22.

25. The pharmaceutical composition of claim 23 or 24, wherein the cancer is breast cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer, esophageal cancer, or colorectal cancer.

1. A method for detecting cancer in a biological sample, comprising:
(a) contacting a biological sample with an anti-glycoed MUC1 antibody or antigen-binding fragment thereof according to any one of claims 1 to 14; and
(b) detecting binding of said anti-glycoed MUC1 antibody or antigen-binding fragment.
The method includes: