JPWO2019161443A5

JPWO2019161443A5 -

Info

Publication number: JPWO2019161443A5
Application number: JP2020544005A
Authority: JP
Publication date: 2022-03-02
Anticipated expiration: 2039-02-20

Claims

An anti-lambda myeloma antigen (LMA) -binding protein with an antigen-binding domain,
The antigen-binding domain preferentially binds to LMA on a free lambda light chain and comprises a heavy chain variable region ( _VH ) and a light chain variable region ( _VL ).
The _VH comprises complementarity determining regions (CDRs) 1 as shown in SEQ ID NO: 1, CDR2 as shown in SEQ ID NO: 2, and CDR3 as shown in SEQ ID NO: 3 .
The anti-lambda myeloma antigen binding, wherein the _VL comprises CDR1 as set forth in SEQ ID NO: 6, CDR2 as set forth in SEQ ID NO: 7, and CDR3 as set forth in SEQ ID NO: 8 or SEQ ID NO: 13. protein.

The binding protein according to claim 1, wherein the VH comprises _the amino acid sequence shown in SEQ ID NO: 5.

The V _ＬL The binding protein according to claim 1 or 2, wherein the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 15.

The V _ＬL The binding protein according to claim 1 or 2, wherein the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 10.

An anti-LMA binding protein having an antigen-binding domain, wherein the antigen-binding domain binds to LMA and contains _VH and _VL .
-The V _H comprises CDR1 as shown in SEQ ID NO: 61, CDR2 as shown in SEQ ID NO: 62, and CDR3 as shown in SEQ ID NO: 63, wherein the _VL is SEQ ID NO: 66 or SEQ ID NO. Containing CDR1, as shown in SEQ ID NO: 67 or SEQ ID NO: 72, and CDR3 as shown in SEQ ID NO: 68 or SEQ ID NO: 73.
The anti-LMA binding protein.

The V _ＨH The binding protein according to claim 5, wherein the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 65.

The V _ＬL 5. The binding protein of claim 5 or 6, wherein the binding protein comprises the amino acid sequence set forth in any one of SEQ ID NOs: 70 or 75.

An anti-LMA binding protein having an antigen-binding domain, wherein the antigen-binding domain binds to LMA and contains a heavy chain variable region ( _VH ) and a light chain variable region ( _VL ).
-The V _H comprises the amino acid sequence set forth in SEQ ID NO: 5, and the _VL comprises the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 15.
-The V _H comprises the amino acid sequence set forth in SEQ ID NO: 65, and the _VL comprises the amino acid sequence set forth in SEQ ID NO: 70 or SEQ ID NO: 75.
The anti-LMA binding protein.

The binding protein according to any one of claims 5 to 8 , wherein the binding protein specifically binds to LMA.

The binding protein according to any one of claims 1 to 9 , which is an antibody.

The binding protein according to any one of claims 1 to 9 , wherein the _VE and _VL are single polypeptide chains.

(I) Single-chain Fv fragment (scFv),
(Ii) Dimer scFv (di-scFv),
(Iii) Trimer scFv (tri-scFv),
(Iv) One of (i), (ii), or (iii) linked to the constant region, Fc, or heavy chain constant domain _CH 2 and / or _CH 3 of the antibody. The binding protein according to claim 11 .

The binding protein according to any one of claims 1 to 9 , wherein V _H and _VL are separate polypeptide chains.

(I) Diabody,
(Ii) Triabody,
(Iii) Tetra body,
(Iv) Fab,
(V) F (ab') ₂ ,
(Vi) Fv,
(Vi) One of (i)-(vi) linked to the constant region, Fc, or heavy chain constant domain _CH 2 and / or _CH 3 of the antibody, or.
(Viii) The binding protein according to claim 13 , which is an intact antibody.

A nucleic acid encoding a binding protein, as defined in any one of claims 1-14 .

An isolated or recombinant cell expressing the binding protein as defined in any one of claims 1-14 or the nucleic acid as defined in claim 15 .

A composition comprising a pharmaceutical carrier and a binding protein as defined in any one of claims 1-14 .

Use of the binding protein or composition of claim 17 as defined in any one of claims 1-14 in the manufacture of a pharmaceutical for treating LMA-expressing cancer.

The binding protein or composition of claim 17 as defined in any one of claims 1-14 for use in the treatment of LMA-expressing cancer.

Use as defined in claim 18 or 19 , wherein the LMA-expressing cancer is multiple myeloma, Waldenström macroglobulinemia, diffuse large B-cell lymphoma (DLBCL), POEMS syndrome, or amyloidosis.