Modified botulinum neurotoxins

• US 7,491,799 B2
• Filed: 01/14/2004
• Issued: 02/17/2009
• Est. Priority Date: 07/21/2000
• Status: Expired due to Term

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Herrington, Todd M., Steward, Lance E., Aoki, Kei Roger, Fernandez-Salas, Ester
• Primary Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US10/757,077
• Publication Number:
  US 20040220386A1
• Time in Patent Office: 1,861 Days
• Field of Search: None
• US Class Current: 530/350
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/33 from Clostridium (G)
• CPC Class Codes: C07K 2319/01 containing a localisation/targetting motif

Abstract

Natural and modified neurotoxins and isolated neurotoxin compositions are described. The neurotoxins may include one or more structural modifications, wherein the structural modification(s) alters the biological persistence, such as the biological half-life and/or a biological activity of the modified neurotoxin relative to an identical neurotoxin without the structural modification(s). In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In some embodiments, methods of using the modified neurotoxin to treat conditions include treating various disorders, neuromuscular ailments and pain.

Claims

1. A modified botulinum neurotoxin type A, wherein the modification is one or more additional amino acid sequences comprising SEQ ID NO:

27 within the N-terminal 30 amino acids of a wild-type botulinum toxin type A light chain,

wherein the additional amino acid sequence comprising SEQ ID NO;

27 increases biological half-life of the modified botulinum neurotoxin type A relative to an identical botulinum neurotoxin type A without the additional amino acid sequence comprising SEQ ID NO;

27.

2. The modified botulinum neurotoxin type A of claim 1, further comprising a modification of adding one or more additional leucine-based motifs of SEQ ID NO:

18 within the C-terminal 50 amino acids of the wild-type botulinum toxin type A light chain,

wherein the additional leucine-based motif of SEQ ID NO;

18 increases biological half- life of the modified botulinum neurotoxin type A relative to an identical botulinum neurotoxin type A without the additional leucine-based motif.

3. The modified botulinum neurotoxin type A of claim 2, wherein the additional leucine-based motif is SEQ ID NO:

1, SEQ ID NO;

4, SEQ ID NO;

6, or SEQ ID NO;

13.