Covalently linked antigen-antibody conjugates

Patent metadata

Field	Value
Publication number	US-2020164064-A1
Application number	US-201916667464-A
Country	US
Kind code	A1
Filing date	Oct 29, 2019
Priority date	Jul 4, 2012
Publication date	May 28, 2020
Grant date	—

Abstract

Herein is reported a conjugate comprising an antigen and an antibody that specifically binds to the antigen wherein a covalent bond is formed between the antigen and an amino acid residue in the CDR2 of the antibody, an antibody comprising a cysteine residue at amino acid position 53 (according to Kabat) in the heavy chain CDR2 and uses thereof.

First claim

1 - 4 . (canceled)

5 : A conjugate comprising a hapten and an antibody that specifically binds to the hapten, wherein there is a covalent bond between the hapten and a cysteine residue in the heavy chain CDR2 of the antibody at position 52b or at position 53 according to the heavy chain variable domain numbering of Kabat.

6 : The conjugate according to claim 5 , wherein the covalent bond is a disulfide bond.

7 : The conjugate according to claim 5 , wherein the antibody is a bispecific antibody comprising a first binding specificity to a first antigen or a first hapten and a second binding specificity to a second antigen or a second hapten.

8 : The conjugate according to claim 5 , wherein the first binding specificity is to a hapten and a second binding specificity is to a non-hapten antigen.

9 : The conjugate according to claim 5 , wherein the antibody is a full length antibody.

10 : The conjugate according to claim 5 , wherein the antibody is a humanized antibody or a human antibody.

11 : The conjugate according to claim 5 , wherein the conjugate further comprises a therapeutic or detectable moiety.

12 : The conjugate according to claim 5 , wherein the hapten is selected from the group consisting of haptens comprising biotin, theophylline, digoxigenin, carborane, and fluorescein.

13 - 15 . (canceled)

16 : The conjugate of claim 5 , wherein the hapten is biotin and the antibody comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 57; a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 58; a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 59; a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 61; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 62; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 63.

17 : The conjugate of claim 16 , wherein the antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 64.

18 : The conjugate of claim 5 , wherein the hapten is theophylline and the antibody comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 89; a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 90; a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 91; a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 93; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 94; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 95.

19 : The conjugate of claim 18 , wherein the antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 92 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 96.

20 : The conjugate of claim 5 , wherein the hapten is fluorescein and the antibody comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 105; a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 106; a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 107; a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 109; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 110; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 111.

21 : The conjugate of claim 20 , wherein the antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 108 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 112.

22 : The conjugate of claim 5 , wherein the hapten is digoxigenin and the antibody comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 25; a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO 26; a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO 27; a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 29; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 30; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 31.

23 : The conjugate of claim 22 , wherein the antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 32.

24 : The conjugate of claim 5 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to a hapten and a second binding site that specifically binds to a cell surface marker.

25 : The conjugate of claim 16 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to a hapten and a second binding site that specifically binds to a cell surface marker.

26 : The conjugate of claim 16 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to biotin and a second binding site that specifically binds to a cell surface marker.

27 : The conjugate of claim 16 , wherein the antibody is humanized.

28 : The conjugate of claim 18 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to theophylline and a second binding site that specifically binds to a cell surface marker.

29 : The conjugate of claim 18 , wherein the antibody is humanized.

30 : The conjugate of claim 20 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to fluorescein and a second binding site that specifically binds to a cell surface marker.

31 : The conjugate of claim 20 , wherein the antibody is humanized.

32 : The conjugate of claim 22 , wherein the antibody is a multispecific antibody comprising a first binding site that binds to digoxigenin and a second binding site that specifically binds to a cell surface marker.

33 : The conjugate of claim 22 , wherein the antibody is humanized.

Assignees

• Hoffmann La Roche

Inventors

• Benz Joerg
• Brinkmann Ulrich
• Dengl Stefan
• Dziadek Sebastian
• Georges Guy
• Grote Michael
• Haas Alexander
• Hoffmann Eike

Classifications

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/24

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

• A61K47/6897 Primary

  Pre-targeting systems with two or three steps using antibody conjugates; Ligand-antiligand therapies · CPC title