Allergan, Inc.

Syntaxin Limited

Ipsen Bioinnovation Limited

Other

Irvine, Inc.

Health Protection Agency

The Secretary of State for Health

Secretary of State for Health and Social Care

Lance Steward

Kei Roger Aoki

Ester Fernandez-Salas

Joseph Francis

Marcella A Gilmore

Shengwen Li

Sanjiv Ghanshani

Keith Foster

John Andrew Chaddock

Todd M Herrington

Charles Penn

K Roger Aoki

Marc F Verhagen

Dudley J Williams

Philip Marks

Patrick Stancombe

Wei-Jen Lin

J Oliver Dolly

Yi Liu

Linh Q Le

Athena Spanoyannis

Melvin S Oka

Patrick Michael Hughes

Futian Liu

Xiaojie Yu

Joanne Wang

George A Sachs

Fernandez-Salas Ester

Roger Kei Aoki

Guang Wei Lu

Shiazah Z Malik

Dean G Stathakis

Amy Brideau-Andersen

Peter James

Ronald G Miller

Shengwin Li

Sheshadri Neervannan

Birgitte Ps Jacky

Edward C Hsai

Single chain polypeptide fusion protein, comprising: a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin targeting moiety; a protease cleavage site; a translocation domain; a first spacer located between the non-cytotoxic protease and the protease cleavage site; and a second spacer located between the galanin targeting moiety and the translocation domain.

Fusion proteins comprising a non-cytotoxic protease, a translocation domain, and a targeting moiety that binds a galanin receptor and methods for treating, preventing or ameliorating pain using such fusion proteins

Microneedle arrays for introducing an active ingredient through a skin surface of a subject can include a base layer, a plurality of microneedles projecting from the base layer, and an active ingredient. Each of the microneedles comprises an elongate body having a proximal portion and a distal portion, in which the proximal portion is attached to the base layer. Each of the microneedles comprises at least one dissolvable polymer. The active ingredient is incorporated in the elongate body, and the active ingredient is present only in the distal portion and at least internally in the distal portion.

Microneedle array with active ingredient

Methods for treating melanin-related afflictions of the skin, such as hyperpigmentation, are provided. The methods comprise administering a composition comprising BoNT/DC.

Botulinum neurotoxin for treatment of disorders associated with melanocyte hyperactivity and/or excess melanin

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 expression constructs comprising single-chain proteins comprising a di-chain loop region comprising an exogenous protease cleavage site and a protease that can cleave the exogenous protease cleavage site located within the di-chain loop, cell compositions comprising such expression construct, and intracellular methods of converting the single-chain protein into its di-chain form.

Methods of intracellular conversion of single-chain proteins into their di-chain form

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.

Use of a therapeutic molecule, for the treatment of specific pain conditions, wherein the therapeutic molecule is 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, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the Targeting Moiety; and a translation 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.

Treatment of pain

Growing community of inventors

Irvine, CA, United States of America

Lance Steward