Patents by Inventor Lance E. Steward

Lance E. Steward has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • FRET protease assays for clostridial toxins
    Patent number: 8013113
    Abstract: The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
    Type: Grant
    Filed: November 17, 2009
    Date of Patent: September 6, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Kei Roger Aoki
  • Nucleic acids encoding chimera botulinum toxin type E
    Patent number: 8008465
    Abstract: The present invention relates to a toxin comprising a modified light chain of a botulinum toxin type E, wherein the modified light chain comprises amino acid sequence PFVNKQFN (SEQ ID NO: 120) at the N-terminus, and amino acid sequence xExxxLL (SEQ ID NO: 112) at the C-terminus, wherein x is any amino acid.
    Type: Grant
    Filed: January 8, 2010
    Date of Patent: August 30, 2011
    Assignee: Allergan, Inc.
    Inventors: Ester Fernandez-Salas, Lance E. Steward, Todd Herrington, K. Roger Aoki
  • Fret protease assays for clostridial toxins
    Patent number: 8003753
    Abstract: The present invention provides clostridial toxin substrates useful in assaying for the protease activity of any clostridial toxin, including botulinum toxins of all serotypes as well as tetanus toxins. A clostridial toxin substrate of the invention contains a donor fluorophore; an acceptor having an absorbance spectrum overlapping the emission spectrum of the donor fluorophore; and a clostridial toxin recognition sequence that includes a cleavage site, where the cleavage site intervenes between the donor fluorophore and the acceptor and where, under the appropriate conditions, resonance energy transfer is exhibited between the donor fluorophore and the acceptor.
    Type: Grant
    Filed: November 17, 2009
    Date of Patent: August 23, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Kei Roger Aoki
  • Degradable clostridial toxins
    Patent number: 7998489
    Abstract: The specification discloses modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; polynucleotide molecules encoding modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; and method of producing modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain.
    Type: Grant
    Filed: August 15, 2008
    Date of Patent: August 16, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester G. Fernandez-Salas, Marcella A. Gilmore, Joseph Francis, Shengwen Li, Kei Roger Aoki
  • Assays of molecular or subcellular interactivity using depolarization after resonance transfer energy (DARET)
    Patent number: 7998749
    Abstract: The present invention provides a method of determining the proximity, or changes in the proximity of two or more molecular features labeled with fluorophores able to undergo DARET. In preferred embodiments the change in proximity of molecular features in a sample is correlated with changes in the fluorescence polarization of the sample, and may be monitored in real time.
    Type: Grant
    Filed: October 11, 2006
    Date of Patent: August 16, 2011
    Assignee: Allergan, Inc.
    Inventors: Marcella A. Gilmore, Dudley J. Williams, Lance E. Steward, Kei Roger Aoki
  • Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for clostridial toxin target cells
    Patent number: 7993656
    Abstract: The invention provides modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain, a translocation facilitating domain and an altered target domain; polynucleotide molecules encoding such modified Clostridial toxins; and methods of producing such modified Clostridial toxins.
    Type: Grant
    Filed: July 11, 2007
    Date of Patent: August 9, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Joseph Francis, Ester G. Fernandez-Salas, Marcella A. Gilmore, Shengwen Li, Kei Roger Aoki
  • Modified Clostridial Toxins Comprising an Integrated Protease Cleavage Site-Binding Domain
    Publication number: 20110189162
    Abstract: The present specification discloses modified Clostridial toxins, compositions comprising an integrated protease cleavage site-binding domain, polynucleotide molecules encoding such modified Clostridial toxins and compositions comprising di-chain forms of such modified Clostridial toxins.
    Type: Application
    Filed: December 16, 2010
    Publication date: August 4, 2011
    Applicant: ALLERGAN, INC.
    Inventors: Sanjiv Ghanshani, Linh Q. Le, Yi Liu, Lance E. Steward
  • Botulinum Neurotoxin Serotype B Activatable Botulinum Neurotoxin Serotype Bs
    Publication number: 20110111479
    Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins comprising a Clostridial toxin substrate cleavage site located in the di-chain loop region; and method of producing modified Clostridial toxins comprising Clostridial toxin substrate cleavage site located within the di-chain loop region.
    Type: Application
    Filed: August 30, 2010
    Publication date: May 12, 2011
    Applicant: ALLERGAN, INC.
    Inventors: LANCE E. STEWARD, MELVIN S. OKA
  • Optimizing Expression of Active Botulinum Toxin Type E
    Publication number: 20110111483
    Abstract: Nucleic acid molecules that comprise modified open reading frames providing increased expression of the encoded active BoNT/E in a heterologous cell, expression constructs and cells comprising such nucleic acid molecules and methods useful for expressing the encoding active BoNT/E from such nucleic acid molecules, expression constructs and cells.
    Type: Application
    Filed: October 14, 2010
    Publication date: May 12, 2011
    Applicant: ALLERGAN, INC.
    Inventors: LANCE E. STEWARD, MARCELLA A. GILMORE, ESTER G. FERNANDEZ-SALAS, SHENGWEN LI, RONALD G. MILLER, KEI ROGER AOKI
  • Multivalent Clostridial Toxins
    Publication number: 20110070621
    Abstract: The present invention is directed to multivalent Clostridial toxin comprising more than one binding domain directed to a cell surface molecule of a target cell. Such modified toxins are useful as therapeutic compositions to prevent exocytosis and secretion by the target cell. Conditions in which such compositions may be useful include, without limitation, disorders of the sensory or motor nervous system, acute or chronic pain, cancer, pancreatitis, hyperhydrosis, glandular disorders, viral infections, cystic fibrosis and the like. The invention is also directed to methods of using and administering such a composition, and methods of treating a given condition using such a composition.
    Type: Application
    Filed: September 16, 2010
    Publication date: March 24, 2011
    Applicant: ALLERGAN, INC.
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Joseph Francis, Shengwen Li, Marcella A. Gilmore, Kei Roger Aoki
  • Activatable clostridial toxins
    Patent number: 7897157
    Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.
    Type: Grant
    Filed: August 27, 2007
    Date of Patent: March 1, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Joseph Francis, Ester Fernandez-Salas, Sanjiv Ghanshani, Marcella A. Gilmore, Shengwen Li, J. Oliver Dolly, Kei Roger Aoki
  • POST-TRANSLATIONAL MODIFICATIONS AND CLOSTRIDIAL NEUROTOXINS
    Publication number: 20110046356
    Abstract: The present invention discloses modified neurotoxins with altered biological persistence. In one embodiment, the modified neurotoxins are derived from Clostridial botulinum toxins. Such modified neurotoxins may be employed in treating various conditions, including but not limited to muscular disorders, hyperhidrosis, and pain.
    Type: Application
    Filed: January 17, 2007
    Publication date: February 24, 2011
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Athena Spanoyannis, K. Roger Aoki, Wei-Jen Lin
  • Post-translational modifications and Clostridial neurotoxins
    Patent number: 7893202
    Abstract: The present invention discloses modified neurotoxins with altered biological persistence. In one embodiment, the modified neurotoxins are derived from Clostridial botulinum toxins. Such modified neurotoxins may be employed in treating various conditions, including but not limited to muscular disorders, hyperhidrosis, and pain.
    Type: Grant
    Filed: January 17, 2007
    Date of Patent: February 22, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Athena Spanoyannis, K. Roger Aoki, Wei-Jen Lin
  • Degradable clostridial toxins
    Patent number: 7892565
    Abstract: The specification discloses modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; polynucleotide molecules encoding modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain; and method of producing modified Clostridial toxins comprising a PAR ligand domain, a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and a Clostridial toxin binding domain.
    Type: Grant
    Filed: September 1, 2005
    Date of Patent: February 22, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester G. Fernandez-Salas, Marcella A. Gilmore, Joseph Francis, Shengwen Li, Kei Roger Aoki
  • Post-translation modification and clostridial neurotoxins
    Patent number: 7888469
    Abstract: The present invention discloses modified neurotoxins with altered biological persistence. In one embodiment, the modified neurotoxins are derived from Clostridial botulinum toxins. Such modified neurotoxins may be employed in treating various conditions, including but not limited to muscular disorders, hyperhidrosis, and pain.
    Type: Grant
    Filed: January 17, 2007
    Date of Patent: February 15, 2011
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Athena Spanoyannis, K. Roger Aoki, Wei-Jen Lin
  • Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity
    Patent number: 7846722
    Abstract: Clostridial toxin substrates comprising a lanthanide donor complex, an acceptor, and a Clostridial toxin recognition sequence including a cleavage site; methods for determining the activity of a Clostridial toxin from a test sample using such Clostridial toxin substrates; cell compositions comprising such Clostridial toxin substrates and a Clostridial toxin receptor; and methods for determining the activity of a Clostridial toxin from a test sample using such cell compositions.
    Type: Grant
    Filed: May 25, 2007
    Date of Patent: December 7, 2010
    Assignee: Allergan, Inc.
    Inventors: Dudley J. Williams, Marcella A. Gilmore, Lance E. Steward, Marc Verhagen, Kei Roger Aoki, Ester Fernandez-Salas
  • GFP-SNAP25 fluorescence release assay for botulinum toxin protease activity
    Patent number: 7838260
    Abstract: The present invention provides a nucleic acid molecule which contains a nucleotide sequence encoding a SNAP-25 substrate which includes (i) a green fluorescent protein; (ii) a first partner of an affinity couple; and (iii) a portion of SNAP-25 that includes a BoNT/A, BoNT/C1 or BoNT/E recognition sequence containing a cleavage site, where the cleavage site intervenes between the green fluorescent protein and the first partner of the affinity couple. Further provided herein is a nucleic acid molecule which contains a nucleotide sequence encoding a tagged toxin substrate which includes (i) a fluorescent protein; (ii) a first partner of an affinity couple; and (iii) a clostridial toxin recognition sequence containing a cleavage site, where the cleavage site intervenes between the fluorescent protein and the first partner of the affinity couple.
    Type: Grant
    Filed: January 24, 2008
    Date of Patent: November 23, 2010
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Marcella A. Gilmore, Kei R. Aoki
  • Methods of Activating Clostridial Toxins
    Publication number: 20100286371
    Abstract: The specification discloses modified Clostridial toxins comprising an exogenous Clostridial toxin di-chain loop protease cleavage site located within the di-chain loop region; polynucleotide molecules encoding such modified Clostridial toxins; method of producing such modified Clostridial toxins, method of activating such modified Clostridial toxins and methods of activating recombinantly-expressed Clostridial toxins.
    Type: Application
    Filed: June 27, 2008
    Publication date: November 11, 2010
    Inventors: Marc F. Verhagen, Dean G. Stathakis, Lance E. Steward
  • CLOSTRIDIAL NEUROTOXIN COMPOSITIONS AND MODIFIED CLOSTRIDIAL NEUROTOXINS
    Publication number: 20100280222
    Abstract: Natural and modified neurotoxins and isolated neurotoxin compositions are described. The neurotoxins may include one or more structural modifications, wherein the structural modification(s) alters the biological persistence, such as the biological half-life and/or a biological activity of the modified neurotoxin relative to an identical neurotoxin without the structural modification(s). In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In another embodiment, methods of using the modified neurotoxin to treat conditions include treating various disorders, neuromuscular aliments and pain.
    Type: Application
    Filed: January 5, 2007
    Publication date: November 4, 2010
    Inventors: Lance E. Steward, Ester Fernandez-Salas, Todd Herrington, Kei Roger Aoki
  • Optimizing expression of active Botulinum Toxin type E
    Patent number: 7825233
    Abstract: Nucleic acid molecules that comprise modified open reading frames providing increased expression of the encoded active BoNT/E in a heterologous cell, expression constructs and cells comprising such nucleic acid molecules and methods useful for expressing the encoding active BoNT/E from such nucleic acid molecules, expression constructs and cells.
    Type: Grant
    Filed: June 9, 2005
    Date of Patent: November 2, 2010
    Assignee: Allergan, Inc.
    Inventors: Lance E. Steward, Marcella A. Gilmore, Ester G. Fernandez-Salas, Shengwen Li, Ronald G. Miller, Kei Roger Aoki