Allergan, Inc.

Syntaxin Limited

Allergan Sales, Inc.

Ipsen Bioinnovation Limited

Invent Dcu Limited

Allergas, Inc.

Allegan Sales, Inc.

Kei Roger Aoki

Lance Steward

Ester Fernandez-Salas

Joseph Francis

Marcella A Gilmore

Shengwen Li

Keith Foster

John Andrew Chaddock

Sanjiv Ghanshani

Minglei Cui

Todd M Herrington

Stephen W Jenkins

Patton E Garay

Charles Penn

Dudley J Williams

Marc F Verhagen

Philip Marks

Patrick Stancombe

Joanne Wang

J Oliver Dolly

Lina Wong

Judith M Leon

Steven R Carlson

Michael W Grayston

Gregory F Brooks

Lance E Steward

Michael E Garst

Larry Allen Wheeler

D Dianne Hodges

George A Sachs

Wei-Jen Lin

Fernandez-Salas Ester

James Oliver Dolly

D Diane Hodges

Athena Faye Spanoyannis

Daniel W Gil

Mitchell F Brin

Birgitte P S Jacky

Shengwin Li

Ronald G Miller

Micheal W Grayston

Stephen Jenkins

Lina S Wong

The present specification discloses SNAP-25 compositions, methods of making &#x3b1;-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the Presidue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, &#x3b1;-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the Presidue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, methods of detecting BoNT/A activity, and methods of detecting neutralizing &#x3b1;-BoNT/A antibodies.

Immuno-based botulinum toxin serotype A activity assays

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell wherein the Targeting Moiety is selected from the group consisting of BAM, &#x3b2;-endorphin, bradykinin, substance P, dynorphin and/or nociceptin.

Non-cytotoxic protein conjugates

The specification discloses Clostridial toxins or Clostridial toxin chimeras comprising an inactivation cleavage site, polynucleotide molecules encoding such toxins or chimeras, compositions comprising such toxins or chimeras, and method of producing such toxins or chimeras.

Degradable clostridial toxins

The present specification discloses modified Clostridial toxins, compositions comprising such toxins and methods of treating urogenital-neurological disorders in a mammal using such modified Clostridial toxins and compositions.

Methods of treating urogenital-neurological disorders using modified Clostridial toxins

Degradable Clostridial toxins

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, &#x3b2;-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.

Fusion proteins

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

The present invention is directed to non-cytotoxic protein conjugates for inhibition or reduction of exocytic fusion in a nociceptive sensory afferent cell. The protein conjugates comprise: (i) a dynorphin Targeting Moiety (TM), wherein the TM is an agonist of a receptor present on a nociceptive sensory afferent cell, and wherein the receptor undergoes endocytosis to be incorporated into an endosome within the nociceptive sensory afferent cell; (ii) a non-cytotoxic protease or a fragment thereof, wherein the protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of the nociceptive sensory afferent cell; and (iii) a Translocation Domain, wherein the Translocation Domain translocates the protease or protease fragment from within the endosome, across the endosomal membrane, and into the cytosol of the nociceptive sensory afferent cell. Nucleic acid sequences encoding the protein conjugates, methods of preparing same and uses thereof are also described.

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing 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, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

Growing community of inventors

Coto de Caza, CA, United States of America

Kei Roger Aoki