Fusion proteins

Patent metadata

Field	Value
Publication number	US-9243301-B2
Application number	US-201213419381-A
Country	US
Kind code	B2
Filing date	Mar 13, 2012
Priority date	Jun 1, 2006
Publication date	Jan 26, 2016
Grant date	Jan 26, 2016

Abstract

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment can cleave a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a Targeting Moiety that can bind to a Binding Site on the nociceptive sensory afferent, which Binding Site can undergo endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, which is located between the non-cytotoxic protease and the Targeting Moiety; and a translocation domain that can translocate the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; wherein the Targeting Moiety is BAM, β-endorphin, bradykinin, substance P, dynorphin and/or nociceptin. Nucleic acid sequences encoding the fusion proteins, methods of preparing same and uses thereof are also described.

First claim

The invention claimed is:

1. A method of treating or ameliorating pain in a subject, comprising administering to said subject a therapeutically effective amount of a polypeptide fusion protein comprising:
a. a non cytotoxic protease, or a fragment thereof, which protease or protease fragment cleaves a protein of the exocytic fusion apparatus of a nociceptive sensory afferent;
b. a Targeting Moiety that binds to a Binding Site on the nociceptive sensory afferent, which Binding Site endocytoses to be incorporated into an endosome within the nociceptive sensory afferent;
c. a protease cleavage site at which site the fusion protein is cleavable by a protease,
wherein the protease cleavage site is located between the non cytotoxic protease or fragment thereof and the Targeting Moiety;
d. a translocation domain that translocates the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent;

wherein the Targeting Moiety is selected from the group consisting of BAM, β endorphin, bradykinin, substance P, dynorphin and/or nociception;
wherein said polypeptide fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 24, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 111, 112, 113, 115, 116, 120, 121, 124, 125, 126, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, and/or 157.

2. A method according to claim 1 , wherein the pain is chronic pain selected from neuropathic pain, inflammatory pain, headache pain, somatic pain, visceral pain, and referred pain.

Assignees

• Foster Keith
• Chaddock John
• Marks Philip
• Stancombe Patrick
• Aoki Kei Roger
• Francis Joseph
• Steward Lance
• Allergan Inc
• Ipsen Bioinnovation Ltd

Inventors

• Foster Keith
• Chaddock John
• Marks Philip
• Stancombe Patrick
• Aoki Kei Roger
• Francis Joseph
• Steward Lance

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07K2319/06

  containing a lysosomal/endosomal localisation signal · CPC title

• C12N15/62

  DNA sequences coding for fusion proteins · CPC title