Regulation of specific spinal neurons regulating pain transmission via chimeric toxins

Patent metadata

Field	Value
Publication number	US-10022450-B2
Application number	US-201615241221-A
Country	US
Kind code	B2
Filing date	Aug 19, 2016
Priority date	Mar 8, 2013
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

A chimeric toxin is disclosed comprising a peptide ligand specifically targeting neurons involved in pain processing; and a clostridial neurotoxin light chain, wherein the ligand is linked to the light chain. The methods of preparing such chimeric toxin and the method of using the chimeric toxin to regulate pain transmission are also disclosed.

First claim

We claim:

1. A method for inhibiting pain transmission in a patient in need thereof, the method comprising the step of
administering to said patient a formulation comprising an effective amount of a chimeric toxin of a chimeric toxin comprising
(i) a peptide ligand specifically targeting neurons involved in pain processing, wherein the ligand is Substance P (SEQ ID NO:1); and
(ii) a clostridial neurotoxin light chain,

wherein the ligand is linked to the light chain to form a chimeric toxin, and wherein the chimeric toxin does not comprise a translocation domain.

2. The method of claim 1 , wherein the formulation is delivered into lumbar intrathecal puncture space.

3. The method of claim 2 , wherein the formulation is in a water based isotonic vehicle prepared freshly prior to the administration.

4. The method of claim 1 , wherein the effective amount is in the range of 5 to 10000 U typically delivered in a volume of 1 mL.

5. The method of claim 4 , wherein the effective amount is in the range of 0.005 to 1000 micrograms of the ligand.

6. The method of claim 5 , wherein the effective amount is 0.5 micrograms.

7. The method of claim 1 , wherein the pain arises from cutaneous injury and inflammation, musculoskeletal injury and inflammation, visceral inflammation or injury, peripheral nerve injury as caused by chemicals, metabolic disease, physical injury, and mixtures thereof.

Assignees

• Wisconsin Alumni Res Found
• Univ California

Inventors

• Johnson Eric A
• Pellett Sabine
• Tepp William H
• Yaksh Tony L
• Marino Marc
• Xu Qinghao

Classifications

• C07K14/72

  for hormones {(for neuromediators C07K14/70571)} · CPC title

• C12Y304/24069

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

• C07K2319/55

  containing a fusion with a toxin, e.g. diphteria toxin · CPC title

• C07K2319/01

  containing a localisation/targetting motif · CPC title

• C07K7/22

  {Tachykinins, e.g.} Eledoisins {, Substance P}; Related peptides · CPC title