Neurotoxins exhibiting shortened biological activity

Patent metadata

Field	Value
Publication number	US-9511114-B2
Application number	US-201514886485-A
Country	US
Kind code	B2
Filing date	Oct 19, 2015
Priority date	Jul 2, 2009
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a Neurotoxin polypeptide exhibiting a reduced duration of biological effect in a subject, wherein the polypeptide comprises at least one degradation signal in the light chain as well as vectors and host cells comprising the polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising the polynucleotides and polypeptides as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

First claim

The invention claimed is:

1. A composition comprising a modified Clostridium botulinum neurotoxin serotype E (BoNT/E) polypeptide exhibiting a reduced duration of muscle paralysis in a subject, wherein the modified BoNT/E polypeptide comprises at least one degradation signal in the light chain of a BoNT/E polypeptide, wherein the degradation signal in the light chain of the modified BoNT/E polypeptide is selected from:
a) at least one internally or terminally introduced PEST motif;
b) at least one internally or terminally introduced E3 ligase recognition motif;
c) an N-terminal oligo-lysine residue;
d) an N-terminally linked ubiquitin;
e) a substitution of the N-terminal proline with a basic amino acid;
f) substitutions of surface displayed amino acid residues with lysine; and
g) a substitution of the N-terminal praline with a basic amino acid in combination with substitutions of surface displayed amino acid residues with lysine; and
one or more pharmaceutically acceptable carriers.

2. The composition of claim 1 , wherein the duration of the muscle paralysis in a subject persists less than 4, 3 or 2 weeks.

3. The composition of claim 1 , wherein the light chain of the modified BoNT/E polypeptide exhibiting a reduced duration of muscle paralysis in a subject is a modified form of a light chain from wild-type BoNT/E, wherein the wild-type BoNT/E comprises the amino acid sequence of SEQ ID NO:10.

4. The composition of claim 1 which is in the form of a cosmetic composition.

5. The composition of claim 1 comprising one or more drugs in addition to the modified BoNT/E polypeptide.

Assignees

• Merz Pharma Gmbh & Co Kgaa

Inventors

• Hofmann Fred
• Frevert Jurgen

Classifications

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• C12Y304/24069

  Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title