Therapeutic Monoclonal Antibodies that Neutralize Botulinum Neurotoxins

Patent metadata

Field	Value
Publication number	US-2016168265-A1
Application number	US-201514873071-A
Country	US
Kind code	A1
Filing date	Oct 1, 2015
Priority date	Mar 22, 2007
Publication date	Jun 16, 2016
Grant date	—

Abstract

This invention provides antibodies that specifically bind to and typically neutralize botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/E, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof and/or other antibodies that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

First claim

1 .- 31 . (canceled)

32 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds an epitope of a Botulinum neurotoxin (BoNT), wherein the antibody or antigen-binding fragment comprises:
a V H CDR1 comprising the amino acid sequence of SEQ ID NO:83, a V H CDR2 comprising the amino acid sequence of SEQ ID NO:85, a V H CDR3 comprising the amino acid sequence of SEQ ID NO:87, a V L CDR1 comprising the amino acid sequence of SEQ ID NO:187, a V L CDR2 comprising the amino acid sequence of SEQ ID NO:189, and a V L CDR3 comprising the amino acid sequence of SEQ ID NO:191; or a V H CDR1 comprising the amino acid sequence of SEQ ID NO:125, a V H CDR2 comprising the amino acid sequence of SEQ ID NO:127, a V H CDR3 comprising the amino acid sequence of SEQ ID NO:129, a V L CDR1 comprising the amino acid sequence of SEQ ID NO:229, a V L CDR2 comprising the amino acid sequence of SEQ ID NO:231, and a V L CDR3 comprising the amino acid sequence of SEQ ID NO:233.

33 . A composition comprising the isolated antibody or antigen-binding fragment of claim 32 and a pharmaceutically acceptable carrier.

34 . The isolated antibody or antigen-binding fragment of claim 32 , wherein said antibody is a humanized antibody.

35 . The isolated antibody or antigen-binding fragment of claim 32 , wherein said antibody is a human antibody.

36 . The isolated antigen-binding fragment of claim 32 , wherein said antigen-binding fragment is a single chain Fv (scFv), Fab, (Fab′) 2 or (scFv′) 2 .

37 . The isolated antibody or antigen-binding fragment of claim 32 , wherein said antibody is an IgG.

38 . A method of specifically binding a Botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 32 .

39 . A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 33 .

40 . The isolated antibody or antigen-binding fragment of claim 32 , wherein said antibody comprises:
a V H CDR1 comprising the amino acid sequence of SEQ ID NO:83, a V H CDR2 comprising the amino acid sequence of SEQ ID NO:85, a V H CDR3 comprising the amino acid sequence of SEQ ID NO:87, a V L CDR1 comprising the amino acid sequence of SEQ ID NO:187, a V L CDR2 comprising the amino acid sequence of SEQ ID NO:189, and a V L CDR3 comprising the amino acid sequence of SEQ ID NO:191.

41 . The isolated antibody or antigen-binding fragment of claim 40 , wherein said antibody comprises:
a heavy chain comprising the amino acid sequence of SEQ ID NO:40; a light chain comprising the amino acid sequence of SEQ ID NO:55; or a heavy chain comprising the amino acid sequence of SEQ ID NO:40 and a light chain comprising the amino acid sequence of SEQ ID NO:55.

42 . A composition comprising the isolated antibody or antigen-binding fragment of claim 41 and a pharmaceutically acceptable carrier.

43 . The isolated antibody or antigen-binding fragment of claim 41 , wherein said antibody is a humanized antibody.

44 . The isolated antibody or antigen-binding fragment of claim 41 , wherein said antibody is a human antibody.

45 . The isolated antigen-binding fragment of claim 41 , wherein said antigen-binding fragment is a single chain Fv (scFv), Fab, (Fab′) 2 or (scFv′) 2 .

46 . The isolated antibody or antigen-binding fragment of claim 41 , wherein said antibody is an IgG.

47 . A method of specifically binding a Botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 41 .

48 . A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 42 .

49 . The isolated antibody or antigen-binding fragment of claim 32 , wherein said antibody comprises:
a V H CDR1 comprising the amino acid sequence of SEQ ID NO:125, a V H CDR2 comprising the amino acid sequence of SEQ ID NO:127, a V H CDR3 comprising the amino acid sequence of SEQ ID NO:129, a V L CDR1 comprising the amino acid sequence of SEQ ID NO:229, a V L CDR2 comprising the amino acid sequence of SEQ ID NO:231, and a V L CDR3 comprising the amino acid sequence of SEQ ID NO:233.

50 . The isolated antibody or antigen-binding fragment of claim 49 , wherein said antibody comprises:
a heavy chain comprising the amino acid sequence of SEQ ID NO:46; a light chain comprising the amino acid sequence of SEQ ID NO:61; or a heavy chain comprising the amino acid sequence of SEQ ID NO:46 and a light chain comprising the amino acid sequence of SEQ ID NO:61.

51 . A composition comprising the isolated antibody or antigen-binding fragment of claim 50 and a pharmaceutically acceptable carrier.

52 . The isolated antibody or antigen-binding fragment of claim 50 , wherein said antibody is a humanized antibody.

53 . The isolated antibody or antigen-binding fragment of claim 50 , wherein said antibody is a human antibody.

54 . The isolated antigen-binding fragment of claim 50 , wherein said antigen-binding fragment is a single chain Fv (scFv), Fab, (Fab′) 2 or (scFv′) 2 .

55 . The isolated antibody or antigen-binding fragment of claim 50 , wherein said antibody is an IgG.

56 . A method of specifically binding a Botulinum neurotoxin in a mammal, said method comprising administering to said mammal the isolated antibody or antigen-binding fragment of claim 50 .

57 . A kit for specifically binding a Botulinum neurotoxin, said kit comprising:
a composition according to claim 51 .

Assignees

• Univ California

Inventors

• Marks James D
• Geren Isin N
• Garcia Maria Consuelo
• Lou Jianlong
• Razai Ali

Classifications

• C07K2317/51

  Complete heavy chain or Fd fragment, i.e. VH + CH1 · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/1282 Primary

  Clostridium (G) · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• A61P31/04

  Antibacterial agents · CPC title