Anti-CD3 antibodies, anti-CD123 antibodies and bispecific antibodies specifically binding to CD3 and/or CD123

Patent metadata

Field	Value
Publication number	US-10906978-B2
Application number	US-201815943685-A
Country	US
Kind code	B2
Filing date	Apr 2, 2018
Priority date	Jan 23, 2015
Publication date	Feb 2, 2021
Grant date	Feb 2, 2021

Abstract

The present invention concerns antibody-like binding protein specifically binding to CD3 and binding specifically to at least one further antigen, for example CD123. The present invention also concerns antibody-like binding protein specifically binding to CD123 and binding specifically to at least one further antigen. The invention further concerns anti-CD3 antibodies and anti-CD123 antibodies. The invention also relates to pharmaceutical compositions comprising the antibody-like binding protein, anti-CD3 antibodies or anti-CD123 antibodies of the invention, and their use to treat cancer. The invention further relates to isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibody-like binding protein, anti-CD3 or anti-CD123 antibody and the use of said anti-CD123 antibody as a diagnostic tool.

First claim

The invention claimed is:

1. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 388; and a second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 390.

2. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 391; and a second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 393.

3. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein the first polypeptide chain comprises a structure represented by the formula [I]:
V D1 -L 1 -V D2 -L 2 -C L   [I]

and the second polypeptide chain comprises a structure represented by the formula [II]:
V D3 -L 3 -V D4 -L 4 -C H1   [II]

wherein:
V D1 is a light chain variable domain of a first immunoglobulin;
V D2 is a light chain variable domain of a second immunoglobulin;
V D3 is a heavy chain variable domain of the second immunoglobulin;
V D4 is a heavy chain variable domain of the first immunoglobulin;
C L is a light chain constant domain of an immunoglobulin;
C H1 is a C H1 heavy chain constant domain of an immunoglobulin; and
L 1 , L 2 , L 3 , and L 4 are amino acid linkers;

wherein the first polypeptide chain and the second polypeptide chain form a cross-over light chain-heavy chain pair; and
wherein V D1 comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence of WAS, and a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379;
V D2 comprises a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11;
V D3 comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, and a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8; and
V D4 comprises a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

4. The antibody-like binding protein of claim 3 , wherein:
L 1 comprises an amino acid sequence as set forth in SEQ ID NO: 389;
L 2 comprises an amino acid sequence as set forth in SEQ ID NO: 389; and
L 3 and L 4 are 0 amino acids in length.

5. The antibody-like binding protein of claim 3 , wherein:
V D1 comprises an amino acid sequence as set forth in SEQ ID NO: 385;
V D2 comprises an amino acid sequence as set forth in SEQ ID NO: 141;
V D3 comprises an amino acid sequence as set forth in SEQ ID NO: 138;
V D4 comprises an amino acid sequence as set forth in SEQ ID NO: 383;
C L comprises an amino acid sequence as set forth in SEQ ID NO: 310; and
C H1 comprises an amino acid sequence as set forth in SEQ ID NO: 313.

6. The antibody-like binding protein of claim 3 , wherein:
(a) the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 388, or
an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 388, which comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence WAS, a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379, a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11; and

(b) the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO: 390, or
an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO: 390, which comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8, a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

7. The antibody-like binding protein of claim 3 , wherein the second polypeptide chain further comprises a Fc domain (“Fc”).

8. The antibody-like binding protein of claim 3 , wherein the first polypeptide chain further comprises a Fc domain (“Fc”).

9. An antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein the first polypeptide chain comprises a structure represented by the formula [IV]:
V D1 -L 1 -V D2 -L 2 -C L -L 5 -Fc 2   [IV]

and the second polypeptide chain comprises a structure represented by the formula [III]:
V D3 -L 3 -V D4 -L 4 -C H1 -Fc  [III]

wherein:
V D1 is a light chain variable domain of a first immunoglobulin;
V D2 is a light chain variable domain of a second immunoglobulin;
V D3 is a heavy chain variable domain of the second immunoglobulin;
V D4 is a heavy chain variable domain of the first immunoglobulin;
C L is a light chain constant domain of an immunoglobulin;
C H1 is a C H1 heavy chain constant domain of an immunoglobulin;
Fc is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of a first immunoglobulin;
Fc 2 is the immunoglobulin hinge region and CH 2 , CH 3 immunoglobulin heavy chain constant domains of a second immunoglobulin; and
L 1 , L 2 , L 3 , L 4 , and L 5 are amino acid linkers;

wherein the first polypeptide chain of formula [IV] and the second polypeptide chain of formula [III] form a cross-over light chain-heavy chain pair; and
wherein V D1 comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO: 378, a CDR2-L comprising an amino acid sequence of WAS, and a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO: 379;
V D2 comprises a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO: 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO: 11;
V D3 comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO: 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO: 7, and a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO: 8; and
V D4 comprises a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO: 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO: 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO: 382.

10. The antibody-like binding protein of claim 9 , wherein:
L 1 comprises an amino acid sequence as set forth in SEQ ID NO: 389;
L 2 comprises an amino acid sequence as set forth in SEQ ID NO: 389; and
L 3 , L 4 , and L 5 are 0 amino acids in length.

11. The antibody-like binding protein of claim 9 , wherein:
Fc comprises an amino acid sequence as set forth in SEQ ID NO: 394; and
Fc 2 comp

Assignees

• Sanofi Sa

Inventors

• Albrecht Jana
• Barriere Cédric
• Beil Christian
• Beninga Jochen
• Carrez Chantal
• Guerif Stéphane
• Kroll Katja
• Lange Christian
• Lemoine Cendrine
• Leuschner Wulf-Dirk
• Rao Ercole
• Schneider Marion
• Wetzel Marie-Cécile
• Wonerow Peter

Classifications

• G01N33/5759 Primary

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

• C07K2317/31

  multispecific · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title