Gram-positive bacteria specific binding compounds

Patent metadata

Field	Value
Publication number	US-9266943-B2
Application number	US-201314103715-A
Country	US
Kind code	B2
Filing date	Dec 11, 2013
Priority date	Jul 15, 2009
Publication date	Feb 23, 2016
Grant date	Feb 23, 2016

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 antibody or antigen-binding part thereof 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, wherein X is I or M.

2. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof has a heavy chain variable domain sequence comprising:
(a) framework 1 (FW1) which has the sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO: 38);
(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).

3. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof has a light chain variable domain sequence comprising:
(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).

4. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof has a heavy chain variable domain sequence comprising:
(a) framework 1 (FW1) which has the sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTLS (SEQ ID NO: 38);
(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 wherein the antibody or antigen-binding part thereof has a light chain variable domain sequence comprising:
(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 framework 4 (FW4) which has the sequence of FGQGTKLEIKRTV (SEQ ID NO: 54) or FGQGTKVEIKRTV (SEQ ID NO: 59).

5. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof comprises a light chain variable domain comprising a sequence of DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I (SEQ ID NO:11).

6. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof has a heavy chain variable domain sequence comprising:
(a) framework 1 (FW1) which has the sequence of 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).

7. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof has a heavy chain variable domain sequence comprising:
(a) framework 1 (FW1) which has the sequence of 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 wherein the antibody or antigen-binding part thereof has a light chain variable domain sequence comprising:
(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 framework 4 (FW4) which has the sequence of FGQGTKLEIKRTV (SEQ ID NO: 54) or FGQGTKVEIKRTV (SEQ ID NO: 59).

8. The antibody or antigen-binding part thereof of claim 1 wherein antibody or antigen-binding part thereof comprises:
(a) a heavy chain variable domain comprising a sequence of EVQLVESGGGLVQPGGSLRLSCAASGFTLSRFAMSWVRQAPGRGLEWVASINSG NNPYYARSVQYRFTVSRDVSQNTVSLQMNNLRAEDSATYFCAKDHPSSGWPTFD SWGPGTLVTVSS (SEQ ID NO:62) and
(b) a light chain variable domain comprising a sequence of DIQLTQSPSALPASVGDRVSITCRASENVGDWLAWYRQKPGKAPNLLIYKTSILES GVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYXRFPYTFGQGTKVEIKRTV, wherein X is I (SEQ ID NO:11).

9. The antibody or antigen-binding part thereof of claim 8 , further comprising a heavy chain constant domain comprising the sequence of: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP (SEQ ID NO:63).

10. The antibody or antigen-binding part thereof of claim 8 , further comprising a light chain constant domain comprising the sequence of: AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:64).

11. The antibody or antigen-binding part thereof of claim 8 , further comprising
(a) a heavy chain constant domain comprising the sequence of: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP (SEQ ID NO:63) and;
(b) a light chain constant domain comprising the sequence of: AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:64).

12. The antibody or antigen-binding part thereof of claim 8 , further comprising
(a) a heavy chain constant domain comprising the sequence of: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP (SEQ ID NO:63); and
(b) a light chain constant domain comprising the sequence of: AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFNRGEC (SEQ ID NO:65).

13. The antibody or antigen-binding part thereof of claim 8 , further comprising
(a) a heavy chain constant domain comprising the sequence of: CSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP (SEQ ID NO:66) and;
(b) a light chain constant domain comprising the sequence of: AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPCTKSFNRGEC (SEQ ID NO:65).

14. The antibody or antigen-binding part thereof of claim 8 , further comprising
(a) a heavy chain constant domain comprising the sequence of: CSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCP (SEQ ID NO:66) and;
(b) a light chain constant domain comprising the sequence of: AAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:64).

15. The antibody or antigen-binding part thereof of claim 1 wherein the antibody or antigen-binding part thereof is coupled to a cytotoxic agent.

16. The antibody or antigen-binding part

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

• A61P31/00

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

• A61P31/04

  Antibacterial agents · CPC title

• A61P37/06

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

• A61P37/04

  Immunostimulants · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title