Gram-positive bacteria specific binding compounds

Patent metadata

Field	Value
Publication number	US-9688745-B2
Application number	US-201514981643-A
Country	US
Kind code	B2
Filing date	Dec 28, 2015
Priority date	Jul 15, 2009
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

The present invention provides improved binding compounds capable of specifically binding Gram-positive bacteria. Binding compounds are provided that are fully human, enabling therapeutic applications in human individuals.

First claim

We claim:

1. An isolated recombinant antibody producing cell capable of producing the antibody or a functional part thereof wherein said antibody or functional part thereof comprises a heavy chain variable domain and a light chain variable domain comprising:
(a) a heavy chain CDR1 sequence RFAMS (SEQ ID NO:1), and
(b) a heavy chain CDR2 sequence SINNGNNPYYARSVQY (SEQ ID NO:2), and
(c) a heavy chain CDR3 sequence DHPSSGWPTFDS (SEQ ID NO:3), and
(d) a light chain CDR1 sequence RASENVGDWLA (SEQ ID NO:4), and
(e) a light chain CDR2 sequence KTSILES (SEQ ID NO:5), and
(f) a light chain CDR3 sequence QHYXRFPYT (SEQ ID NO:6), wherein X is I or M.

2. The cell of claim 1 , wherein X in SEQ ID NO:6 is I.

3. The cell of claim 1 , wherein X in SEQ ID NO:6 is M.

4. The cell of claim 1 , wherein the heavy chain variable domain comprises:
(a) framework 1 (FW1) which has the sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO: 38) or EVQLVESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO:61);
(b) framework 2 (FW2) which has the sequence of WVRQAPGRGLEWVA (SEQ ID NO:40);
(c) framework 3 (FW3) which has the sequence of RFTVSRDVSQNTVSLQMNNLRAEDSATYFCAK (SEQ ID NO:42); and
(d) framework 4 (FW4) which has the sequence of WGPGTLVTVSS (SEQ ID NO:44).

5. The cell of claim 1 , wherein the light chain variable domain comprises:
(a) framework 1 (FW1) which has the sequence of DIQLTQSPSALPASVGDRVSITC (SEQ ID NO: 48);
(b) framework 2 (FW2) which has the sequence of WYRQKPGKAPNLLIY (SEQ ID NO:50);
(c) framework 3 (FW3) which has the sequence of GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC (SEQ ID NO:52); and
(d) framework 4 (FW4) which has the sequence of FGQGTKLEIKRTV (SEQ ID NO: 54) or FGQGTKVEIKRTV (SEQ ID NO: 59).

6. The cell of claim 1 , wherein the heavy chain variable domain comprises:
(a) framework 1 (FW1) which has the sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO:38) or EVQLVESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO:61);
(b) framework 2 (FW2) which has the sequence of WVRQAPGRGLEWVA (SEQ ID NO:40);
(c) framework 3 (FW3) which has the sequence of RFTVSRDVSQNTVSLQMNNLRAEDSATYFCAK (SEQ ID NO:42); and
(d) framework 4 (FW4) which has the sequence of WGPGTLVTVSS (SEQ ID NO:44), and the light chain variable domain comprises:
(a) framework 1 (FW1) which has the sequence of DIQLTQSPSALPASVGDRVSITC (SEQ ID NO:48);
(b) framework 2 (FW2) which has the sequence of WYRQKPGKAPNLLIY (SEQ ID NO:50);
(c) framework 3 (FW3) which has the sequence of GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC (SEQ ID NO:52); and
(d) framework 4 (FW4) which has the sequence of FGQGTKLEIKRTV (SEQ ID NO: 54) or FGQGTKVEIKRTV (SEQ ID NO: 59).

7. The cell of claim 1 , wherein the heavy chain variable domain amino acid sequence comprises: EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7).

8. The cell of claim 1 , wherein the heavy chain variable domain amino acid sequence comprises: EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9).

9. The cell of claim 1 , wherein the light chain variable domain amino acid sequence comprises: DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I or M (SEQ ID NO:8).

10. The cell of claim 9 , wherein X in SEQ ID NO:8 is I.

11. The cell of claim 1 , wherein the light chain variable domain amino acid sequence comprises: DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRA, wherein X is I or M (SEQ ID NO:10).

12. The cell of claim 11 , wherein X in SEQ ID NO:10 is M.

13. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I or M (SEQ ID NO:11).

14. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I or M (SEQ ID NO:8).

15. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRA, wherein X is I or M (SEQ ID NO:10).

16. The cell of claim 15 , wherein X in SEQ ID NO:10 is M.

17. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:9); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I or M (SEQ ID NO:11).

18. The cell of claim 17 , wherein X in SEQ ID NO:11 is M.

19. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRTV, wherein X is I or M (SEQ ID NO:8).

20. The cell of claim 19 , wherein X in SEQ ID NO:8 is I.

21. The cell of claim 1 , wherein
(a) the heavy chain variable domain amino acid sequence comprises EVQLLESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINNGNNPYYA RSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFDSWGPGTLVTVSS (SEQ ID NO:7); and
(b) the light chain variable domain amino acid sequence comprises DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKLEIKRA, wherein X is I or M (SEQ ID NO:10).

22. The cell of claim 1 , wherein the antibody comprises:
(a) a heavy chain comprising a sequence of SEQ ID NO: 55 and
(b) a light chain comprising a sequence of SEQ ID NO: 57.

23. An isolated recombinant antibody producing cell capable of producing the antibody or functional part thereof wherein said antibody or functional part thereof comprises a heavy chain variable domain and a light chain variable domain comprising:
(a) a heavy chain CDR1 sequence RFAMS (SEQ ID NO:1), and
(b) a heavy chain CDR2 sequence SINSGNNPYYARSVQY (SEQ ID NO:60), and
(c) a heavy chain CDR3 sequence DHPSSGWPTFDS (SEQ ID NO:3), and
(d) a light chain CDR1 sequence RASENVGDWLA (SEQ ID NO:4), and
(e) a light chain CDR2 sequence KTSILES (SEQ ID NO:5), and
(f) a light chain CDR3 sequence QHYXRFPYT (SEQ ID NO:6), wherein X is I or M.

24. The cell of

Assignees

• Genentech Inc
• Aimm Therapeutics Bv

Inventors

• Beaumont Tim
• Kwakkenbos Mark Jeroen
• Brown Eric J
• Morisaki John Hiroshi
• Hazenbos Wouter L W
• Mariathasan Sanjeev
• Kajihara Kimberly
• Xia Yi

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title