Immuno imaging agent for use with antibody-drug conjugate therapy

Patent metadata

Field	Value
Publication number	US-9989524-B2
Application number	US-201414173656-A
Country	US
Kind code	B2
Filing date	Feb 5, 2014
Priority date	Feb 5, 2013
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The invention relates to a companion diagnostic antibody-like binding protein based on the humanized monoclonal antibody, DS6, to be used as diagnostic tool for in vivo detection and quantification of the tumor-associated MUC1-sialoglycotope, CA6.

First claim

The invention claimed is:

1. An antibody-like binding protein that specifically binds CA6, wherein the antibody-like binding protein comprises two polypeptides having structures represented by the formulas [I] and [II] below:
V L1 -L 1 -V L2 -C L   [I]

V H1 -L 2 -V H2 -C H1   [II]

wherein:
V L1 is an immunoglobulin light chain variable domain comprising SEQ ID NO: 2;
V L2 is an immunoglobulin light chain variable domain comprising SEQ ID NO: 2;
V H1 is an immunoglobulin heavy chain variable domain comprising SEQ ID NO: 8;
V H2 is an immunoglobulin heavy chain variable domain comprising SEQ ID NO: 8;
C L is an immunoglobulin light chain constant domain;
C H1 is an immunoglobulin C H1 heavy chain constant domain;
L 1 and L 2 are amino acid linkers; and
wherein the polypeptides of formula I and the polypeptides of formula II form a bivalent monospecific tandem immunoglobulin antibody-like binding protein.

2. The antibody-like binding protein of claim 1 , wherein L 1 is GGGGS (SEQ ID NO: 15) or GGGGSGGGGS (SEQ ID NO: 3).

3. The antibody-like binding protein of claim 1 , wherein L 2 is GGGGS (SEQ ID NO: 15) or GGGGSGGGGS (SEQ ID NO: 3).

4. The antibody-like binding protein of claim 1 , wherein L 1 and L 2 are identical.

5. The antibody-like binding protein of claim 1 , wherein V L1 and V L2 domains are identical.

6. The antibody-like binding protein of claim 1 , wherein V H1 and V H2 are identical.

7. The antibody-like binding protein of claim 1 , wherein the polypeptide of formula [I] comprises SEQ ID NO: 1.

8. The antibody-like binding protein of claim 1 , wherein the polypeptide of formula [II] comprises SEQ ID NO: 7.

9. The antibody-like binding protein of claim 1 , further comprising a tag.

10. The antibody-like binding protein of claim 9 , wherein the tag is 6x-Histidine, biotin, MYC, V5, FLAG, MBP, or glutathione-S-transferase, or HA.

11. The antibody-like binding protein of claim 10 , wherein the tag is a 6x-Histidine tag.

12. The antibody-like binding protein of claim 1 , further comprising at least one radiolabel, imaging agent, therapeutic agent, or diagnostic agent.

13. The antibody-like binding protein of claim 12 , wherein the radiolabel, imaging agent, therapeutic agent, or diagnostic agent is 110 In, 111 In, 177 Lu, 18 F, 52 Fe, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 86 Y, 90 Y, 89 Zr, 94 Tc, 94 Tc, 99m Tc, 120 I, 123 I, 124 I, 125 I, 131 I, 154-158 Gd, 32 P, 11 C, 13 N, 15 O, 186 Re, 188 Re, 51 Mn, 52m Mn, 55 Co, 72 As, 75 Br, 76 Br, 82m Rb, 83 Sr.

14. The antibody-like binding protein of claim 12 , wherein the radiolabel, imaging agent, therapeutic agent, or diagnostic agent comprises one or more agents for magnetic resonance imaging (MRI); positron emission tomography (PET); single photon emission tomography (SPECT); optical imaging, computed tomography (CT); ultrasound, X-ray, or photoacoustic imaging.

15. A method for making an antibody-like binding protein that specifically binds CA6, comprising expressing in a cell one or more nucleic acid molecules encoding polypeptides having structures represented by the formulas [I] and [II] below:
V L1 -L 1 -V L2 -C L   [I]

V H1 -L 2 -V H2 -C H1   [II]

wherein:
V L1 is an immunoglobulin light chain variable domain comprising SEQ ID NO: 2;
V L2 is an immunoglobulin light chain variable domain comprising SEQ ID NO: 2;
V H1 is an immunoglobulin heavy chain variable domain comprising SEQ ID NO: 8;
V H2 is an immunoglobulin heavy chain variable domain comprising SEQ ID NO: 8;
C L is an immunoglobulin light chain constant domain;
C H1 is an immunoglobulin C H1 heavy chain constant domain;
L 1 and L 2 are amino acid linkers; and
wherein the polypeptides of formula I and the polypeptides of formula II form a bivalent monospecific tandem immunoglobulin antibody-like binding protein.

16. The method of claim 15 , wherein said antibody-like binding protein is an antibody-like binding protein further comprises a tag.

17. The method of claim 16 , wherein the tag is 6x-Histidine, biotin, MYC, V5, FLAG, MBP, glutathione-S-transferase, or HA.

18. The method of claim 17 , wherein the tag is a 6x-Histidine tag.

19. The antibody-like binding protein of claim 1 , wherein C L is a human IGKC immunoglobulin light chain constant domain.

20. The antibody-like binding protein of claim 1 , wherein C H1 is a human immunoglobulin C H1 heavy chain constant domain.

21. The antibody-like binding protein of claim 15 , wherein C L is a human IGKC immunoglobulin light chain constant domain.

22. The antibody-like binding protein of claim 15 , wherein C H1 is a human immunoglobulin C H1 heavy chain constant domain.

Assignees

• Sanofi Sa

Inventors

• Kruip Jochen
• Sarkar Susanta K
• Gebauer Mathias
• Lange Christian
• Focken Ingo

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• A61K51/1027

  against receptors, cell-surface antigens or cell-surface determinants · CPC title

• C07K16/3092 Primary

  against tumour-associated mucins · CPC title