JPWO2020132190A5

JPWO2020132190A5 -

Info

Publication number: JPWO2020132190A5
Application number: JP2021536072A
Authority: JP
Publication date: 2022-12-16

Claims

An isolated antibody that binds to human MUC18 that binds to the same epitope on human MUC18 as the reference antibody that is CL070325.

(a) a heavy chain variable region ( _VH ) comprising heavy chain complementarity determining region 1 (HC CDR1), heavy chain complementarity determining region 2 (HC CDR2), and heavy chain complementarity determining region 3 (HC CDR3); and (b) a light chain variable region (V _L ) comprising light chain CDR1 (LC CDR1), light chain CDR2 (LC CDR2), and light chain CDR3 (LC CDR3);
including
wherein HC CDR1, HC CDR2 and HC CDR3 are collectively at least 85% identical to HC CDR1, HC CDR2 and HC CDR3 of the reference antibody and/or LC CDR1, LC CDR2 and LC 2. The isolated antibody of claim 1, wherein CDR3 is, collectively, at least 85% identical to LC CDRl, LC CDR2, and LC CDR3 of the reference antibody.

_VH is
(a) contains the same HC CDR1, HC CDR2 and HC CDR3 as the reference antibody and/or V _L contains the same LC CDR1, LC CDR2 and LC CDR3 as the reference antibody and/or
(b) comprises HC CDR1, HC CDR2, and HC CDR3 that collectively contain up to 5 amino acid residue variations compared to the HC CDR1, HC CDR2, and HC CDR3 of the reference antibody; and/or 2. VL comprises LC _CDR1 , LC CDR2, and LC CDR3 that collectively contain up to 5 amino acid residue variations compared to LC CDR1, LC CDR2, and LC CDR of the reference antibody. An isolated antibody as described in .

The _VH is at least 85% identical to the _VH of the reference antibody and/or the _VL is at least 85% identical to the _VL of the reference antibody and optionally the same _VH and/or to the reference antibody or the isolated antibody of any one of claims 1-3 , comprising the same _VL as the reference antibody.

(a) specifically binds to human MUC18 and/or
(b) cross-reacts with human MUC18 and non-human MUC18, optionally the non-human MUC18 is primate MUC18, and/or
(c) is a human, humanized, or chimeric antibody,
optionally comprising a V _H set forth in SEQ ID NO: 1 and/or a V _L set forth in SEQ ID NO: 2,
The antibody according to any one of claims 1-4 .

(a) a full-length antibody or an antigen-binding fragment thereof, optionally the antibody is an IgG molecule, or
(b) is a single chain antibody;
An isolated antibody according to any one of claims 1-5 .

A nucleic acid or set of nucleic acids that collectively encode the anti-MUC18 antibody of any one of claims 1-6 .

A vector or set of vectors comprising a nucleic acid according to claim 7 , optionally an expression vector.

9. A host cell containing the vector or set of vectors of claim 8 .

(i) an extracellular domain comprising an antigen-binding fragment that binds to MUC18;
(ii) a transmembrane domain, and (iii) one or more intracellular signaling domains ,
Optionally:
(a) the antigen-binding fragment is a single-chain antibody fragment (scFv), optionally the scFv is represented in claim 6(b); and/or
(b) the transmembrane domain comprises a transmembrane domain derived from a CD28 or CD8 receptor, and/or
(c) the one or more intracellular signaling domains comprise signaling domains from CD3ζ, and/or
(d) the one or more intracellular signaling domains comprise a costimulatory signaling domain, optionally the costimulatory signaling domain is 4-1BB, CD7, CD27, CD28, CD40, OX40, ICOS, GITR, HVEM, TIM1 , or from the LFA-1 receptor,
Chimeric antigen receptor.

11. A nucleic acid comprising a nucleotide sequence encoding the chimeric antigen receptor of claim 10 , or a vector comprising said nucleic acid .

12. A host cell expressing a chimeric receptor according to claim 10 or 11 , optionally an immune cell, eg the immune cell is a T cell.

(i) an antibody according to any one of claims 1 to 6 , a nucleic acid or set of nucleic acids according to any one of claims 7 or 12, or a host cell according to claims 9 or 13 ; and (ii) a pharmaceutically acceptable carrier ,
Optionally for use in a method of reducing the number of MUC18 ⁺ cells comprising administering an effective amount of the pharmaceutical composition to a subject in need thereof, e.g., having or suspected of having cancer of the pharmaceutical composition.

A method of detecting the presence of MUC18 ⁺ cells, comprising:
i. contacting a sample suspected of having MUC18 ⁺ cells with an antibody according to any one of claims 1 to 6 , wherein the antibody is conjugated with a labeling agent, and
ii. detecting the presence of MUC18 ⁺ cells in the sample based on binding of the antibody to cells in the sample.

(a) culturing the cells of claim 9 and
(b) collecting antibodies, antigen-binding fragments thereof, from said cultured cells or culture medium;
A method of making the antibody, or antibody-binding fragment thereof, of any one of claims 1-6, comprising: