Neurotoxins exhibiting shortened biological activity

Patent metadata

Field	Value
Publication number	US-9827298-B2
Application number	US-201615342376-A
Country	US
Kind code	B2
Filing date	Nov 3, 2016
Priority date	Jul 2, 2009
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

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 feast one degradation signal in the light chain as well as vectors and host calls 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 method of weakening muscle strength and contraction for immobilization in connection with knee arthroplasty in a subject in need thereof, comprising a step of administering to the subject a therapeutically effective amount of a modified neurotoxin polypeptide which exhibits a reduced duration of a biological effect comprising at least one degradation signal in a light chain of a Clostridium botulinum serotype E (BoNT/E) neurotoxin polypeptide of SEQ ID NO: 10, wherein the at least one degradation signal in the light chain is at least one internally or terminally introduced E3 ligase recognition motif.

2. The method of claim 1 , wherein the modified neurotoxin polypeptide exhibits a reduced duration of the biological effect in a subject in comparison to the biological effect of an unmodified BoNT/E neurotoxin polypeptide in a subject.

3. The method of claim 1 , wherein the modified neurotoxin polypeptide is administered in an amount which is therapeutically effective to cause muscle paralysis in the subject.

4. The method of claim 1 , wherein the reduced duration of the biological effect in a subject persists less than 4, 3 or 2 weeks.

Assignees

• Merz Pharma Gmbh & Co Kgaa

Inventors

• Hofmann Fred
• FREVERT Jürgen

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

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61K8/64

  Proteins; Peptides; Derivatives or degradation products thereof · CPC title