Abstract: The invention includes liquid formulations of botulinum toxin that are stable to storage in liquid form at standard refrigerator temperatures for at least 1-2 years and to storage at higher temperatures for at least 6 months. The invention also includes methods of treatment using such formulations for various therapeutic and cosmetic purposes.
Abstract: Animal protein-free, solid-form Clostridial toxin pharmaceutical compositions comprising a Clostridial toxin active ingredient and at least two excipients.
Abstract: Methods of using clostridial toxins and other biological agents to treat rosacea in humans is provided. The disclosed methods provide beneficial effects in humans.
Abstract: A Clostridial toxin pharmaceutical composition comprising a Clostridial toxin, such as a botulinum toxin, wherein the Clostridial toxin present in the pharmaceutical composition is stabilized by a non-protein excipient such as a polyvinylpyrrolidone, a disaccharides, a trisaccharide, a polysaccharide, an alcohol, a metal, an amino acid, a surfactant and/or a polyethylene glycol.
Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.
Type:
Grant
Filed:
March 14, 2006
Date of Patent:
March 6, 2012
Assignee:
Allergan, Inc.
Inventors:
Lance E. Steward, Ester Fernandez-Salas, Joseph Francis, Shengwen Li, Marcella A. Gilmore, Kei R. Aoki
Abstract: Mutants of cholesterol-dependent cytolysins comprising at least one amino acid substitution in at least one of Loop 1, Loop 2, or Loop 3 of Domain 4, nucleic acids encoding such polypeptide mutants, and compositions and vaccines comprising such polypeptide mutants.
Type:
Grant
Filed:
April 14, 2008
Date of Patent:
March 6, 2012
Assignee:
The Board of Regents of the University of Oklahoma
Abstract: The present invention provides MSCRAMM® proteins from S. aureus which are putative highly-expressed antigens from methicillin-resistant S. aureus, including communit-associated MRSA (CA-MRSA), and these antigens can thus be utilized in methods of generating antibodies capable of binding these antigens which can be useful in methods of treating or preventing infection from MRSA. The present invention is directed to these proteins, antibodies capable of binding these proteins, methods of generating said antibodies, nucleic acids coding for said proteins, and pharmaceutical compositions or vaccines which include the proteins or antibodies of the present invention in combination with a pharmaceutically acceptable vehicle, carrier or excipient.
Type:
Grant
Filed:
February 22, 2007
Date of Patent:
February 28, 2012
Assignee:
The Texas A&M University System
Inventors:
Magnus Hook, Maria Labandeira-Rey, Gabriela M. Bowden
Abstract: Various nucleic acid-based matrixes are provided, comprising nucleic acid monomers as building blocks, as well as nucleic acids encoding proteins, so as to produce novel biomaterials. The nucleic acids are used to form dendrimers that are useful as supports, vectors, carriers or delivery vehicles for a variety of compounds in biomedical and biotechnological applications. In particular, the macromolecules may be used for the delivery of drugs, genetic material, imaging components or other functional molecule to which they can be conjugated. An additional feature of the macromolecules is their ability to be targeted for certain organs, tumors, or types of tissues. Methods of utilizing such biomaterials include delivery of functional molecules to cells.
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 22, 2008
Date of Patent:
February 21, 2012
Assignee:
Allergan, Inc.
Inventors:
J. Oliver Dolly, Yan Li, Kuo Chion Chan
Abstract: This invention relates to a mutant E. coli heat-labile enterotoxin (LT) subunit A that can be used as an adjuvant. This subunit A mutant contains an amino acid substitution at a position corresponding to position 61 of a wild-type LT. An LT containing this mutated subunit A exhibits reduced toxicity compared to its wild type counterpart.
Abstract: Methods of treating one or more autoimmune disorders include a step of administering a Clostridial neurotoxin, such as a botulinum toxin, to a patient that has an autoimmune disorder. In one aspect, a method includes a step of administering the neurotoxin to the thymus gland or near the thymus gland of the patient. In another aspect, a method includes a step of administering the neurotoxin in combination with administering a cytokine inhibitor to the patient. Compositions are also described.
Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.
Abstract: This invention provides Pseudomonas exotoxin A-like chimeric immunogens that include a non-native epitope in the Ib domain of Pseudomonas exotoxin. Methods of eliciting an immune response using these immunogens also are provided.
Type:
Grant
Filed:
December 20, 2007
Date of Patent:
January 10, 2012
Assignee:
The United States of America as represented by the Secretary of the Department of Health and Human Services
Abstract: A method for treating an rheumatoid arthritis in a mammalian subject in need of same wherein the method comprises: administering to the mammalian subject an agent capable of modulating a ganglioside GM-1 associated activity in an amount effective to treat the disease.
Type:
Application
Filed:
June 27, 2011
Publication date:
January 5, 2012
Applicant:
Trident Pharmaceuticals, Inc.
Inventors:
Neil A. Williams, Timothy R. Hirst, Toufic O. Nashar
Abstract: This invention relates to a mutant E. coli heat-labile enterotoxin (LT) subunit A that can be used as an adjuvant. This subunit A mutant contains an amino acid substitution at a position corresponding to position 61 of a wild-type LT. An LT containing this mutated subunit A exhibits reduced toxicity compared to its wild type counterpart.
Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.
Abstract: The present invention provides a Mycoplasma pneumoniae community acquired respiratory distress syndrome (CARDS) toxin, biologically active fragments/domains of the CARDS toxin, antibodies to the CARDS toxin and nucleic acids encoding the CARDS toxin. Also provided are methods of diagnosing, treating and/or preventing infection by Mycoplasma pneumoniae using the compositions provided herein.
Type:
Grant
Filed:
November 4, 2009
Date of Patent:
January 3, 2012
Assignee:
Board of Regents, The University of Texas System
Inventors:
Joel Barry Baseman, Thirumalai Rengasamy Kannan
Abstract: A method is disclosed for blocking or reducing physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.
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 15, 2008
Date of Patent:
December 6, 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
Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.
Abstract: Compositions useful for detecting Clostridial toxin activity comprising a cell that contains an exogenous Clostridial toxin substrate which comprises a fluorescent member, a membrane targeting domain and a Clostridial toxin recognition sequence comprising a cleavage site, where the cleavage site intervenes between the fluorescent member and the membrane targeting domain; and methods useful for determining Clostridial toxin activity using such Clostridial toxin substrates.
Type:
Grant
Filed:
April 4, 2006
Date of Patent:
November 29, 2011
Assignee:
Allergan, Inc.
Inventors:
Ester Fernandez-Salas, Lance E. Steward, Kei Roger Aoki
Abstract: The present invention related to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.
Type:
Grant
Filed:
October 27, 2007
Date of Patent:
November 22, 2011
Assignee:
The Regents of the University of Colorado
Abstract: The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.
Type:
Application
Filed:
April 15, 2011
Publication date:
November 17, 2011
Applicants:
Services, National Institutes of Health, Office of Technology Transfer
Inventors:
Stephen H. Leppla, Shi-Hui Liu, Thomas H. Bugge
Abstract: Methods for treating obsessions and compulsions by local administration of a Clostridial toxin. The obsessions or compulsions can be eye poking, body rocking, finger biting, counting, checking and related disorders treated by low dose, intramuscular administration of a botulinum toxin.
Abstract: The present invention related to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.
Type:
Grant
Filed:
October 1, 2008
Date of Patent:
November 15, 2011
Assignee:
The Regents of the University of Colorado, a body corporate
Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.
Type:
Grant
Filed:
March 14, 2006
Date of Patent:
November 8, 2011
Assignee:
Allergan, Inc.
Inventors:
Lance E. Steward, Ester Fernandez-Salas, Joseph Francis, Shengwen Li, Marcella A. Gilmore, Kei Roger Aoki
Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is an adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.
Type:
Application
Filed:
October 9, 2009
Publication date:
November 3, 2011
Inventors:
Frank Alexis, Matteo Iannacone, Jinjin Shi, Pamela Basto, Elliott Ashley Moseman, Ulrich von Andrian, Robert S. Langer, Omid C. Farokhzad, Elena Tonti
Abstract: The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.
Type:
Grant
Filed:
February 9, 2009
Date of Patent:
November 1, 2011
Assignee:
Anjin Group, Inc.
Inventors:
Robert J. Harrison, Johanna C. Vanderspek
Abstract: The invention relates to improved methods of producing and recovering B. anthracis protective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, B. anthracis bacterial infections and which are useful to prevent and/or treat illnesses caused by B. anthracis, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.
Type:
Grant
Filed:
June 15, 2010
Date of Patent:
October 25, 2011
Assignee:
The United States of America as represented by the Department of Health and Human Services
Inventors:
Stephen H. Leppla, Yogendra Singh, Kurt Klimpel, Rachel Schneerson, John B. Robbins
Abstract: Methods of using clostridial toxins and other biological agents to thin skin and control fine wrinkles in humans are provided. In preferred embodiments the methods provide beneficial effects in humans.
Abstract: The invention relates to a process for the production of a vaccine against bacterial pathogens which produce an AB toxin, like Clostridium, comprising (a) culturing the pathogen under conditions where the AB toxin is produced, and harvesting the culture (b) cleaving the AB toxin enzymatically in vitro, preferably using inositol hexaphosphate as a co-factor, and (c) combining the composition of step (b) with a pharmaceutically acceptable carrier.
Abstract: The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.
Abstract: Methods for treating conditions in an animal or human subject. The conditions may be pain, skeletal muscle conditions, smooth muscle conditions, glandular conditions and cosmetic conditions. The methods comprise the step of administering a Clostridium neurotoxin component or Clostridium neurotoxin component encoding DNA to the subject using a needleless syringe.
Abstract: A composition for treating a subject is provided. The composition includes antigen specific dimeric secretory IgA and pentameric IgM therapeutic. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided that the modification of antigen specific dimeric secretory IgA and pentameric IgM with secretory component to form a antigen specific dimeric secretory IgA and pentameric secretory IgM therapeutic. The antigen specific dimeric secretory IgA and the pentameric secretory IgM therapeutic is then mixed with formulating agents to create a capsule, tablet, liquid or suppository dosing form. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating. A method of C. difficile treatment with the therapeutic is also provided that is amenable to supplementation with concurrent or prior antibiotic administration.
Type:
Grant
Filed:
June 13, 2008
Date of Patent:
September 20, 2011
Inventors:
Michael R. Simon, Stephanie M. Chervin, Stephen C. Brown
Abstract: The specification discloses modified Clostridial toxins comprising a Clostridial toxin enzymatic domain, a Clostridial toxin translocation domain and an enhanced Clostridial toxin binding domain; polynucleotide molecules encoding such modified Clostridial toxins; and method of producing such modified Clostridial toxins.
Type:
Grant
Filed:
August 15, 2008
Date of Patent:
September 20, 2011
Assignee:
Allergan, Inc.
Inventors:
Lance E. Steward, Ester Fernandez-Salas, Joseph Francis, Shengwen Li, Marcella A. Gilmore, Kei Roger Aoki
Abstract: Agents for treating pain, methods for producing the agents and methods for treating pain by administration to a patient of a therapeutically effective amount of the agent. The agent can include a clostridial neurotoxin, or a component or fragment or derivative thereof, attached to a targeting moiety, wherein the targeting moiety is selected from a group consisting of transmission compounds which can be released from neurons upon the transmission of pain signals by the neurons, and compounds substantially similar to the transmission compounds.
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
Type:
Grant
Filed:
January 27, 2009
Date of Patent:
September 13, 2011
Assignees:
Syntaxin Limited, The Health Protection Agency
Inventors:
Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, John Sutton, Patrick Stancombe, Jonathan Wayne
Abstract: Animal product free (APF) media and processes for the culture and fermentation of botulinum toxin producing Clostridium botulinum bacteria. The botulinum toxin obtained can be used for formulating and compounding botulinum toxin pharmaceutical compositions. The APF media can contain significantly reduced levels of meat or dairy by-products and use non-animal based products instead of the animal-derived products. Preferably, the APF media used are substantially free or free of animal derived products.
Abstract: A single polypeptide is provided which comprises first and second domains. The first domain enables the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis, and the second domain enables the polypeptide to be translocated into a target cell or increases the solubility of the polypeptide, or both. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.
Type:
Grant
Filed:
February 11, 2009
Date of Patent:
September 6, 2011
Assignees:
Syntaxin, Ltd., Health Protection Agency
Inventors:
Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, J. Mark Sutton, Patrick Stancombe, Jonathan Wayne
Abstract: Combination vaccines for treating or preventing Neisseria meningitidis infection are described. The vaccines include Neisseria meningitidis serogroup B proteoliposomic vesicles and Neissera meningitidis serogroup C conjugated oligosaccharides.
Type:
Grant
Filed:
May 28, 1999
Date of Patent:
August 30, 2011
Assignees:
Novartis AG, Statens Institutt for Folkehelse
Inventors:
Dan M. Granoff, Howard Raff, Ingeborg S. Aaberge, Bjorn Haneberg, Johan Holst
Abstract: The present invention relates to the field of vaccines, and in particular vaccines comprising antigens of low isoelectric point at pH 7.0, in particular the capsular polysaccharide or oligosaccharide of H. influenzae B (PRP). Immunogenic compositions and methods of making such compositions are presented in which the PRP is surprisingly protected from immune interference by adding a polyanionic polymer (such as PLG-poly-L-glutamic acid) to the composition.
Abstract: Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.
Abstract: Various improvements to vaccines that include a serogroup C meningococcal conjugate antigen, including: (a) co-administration with acellular B. pertussis antigen; (b) co-administration with an inactivated poliovirus antigen; (c) supply in a kit together with a separate pneumococcal conjugate component, which may be in a liquid form; and (d) use in combination with a pneumococcal conjugate antigen but without an aluminum phosphate adjuvant. A kit may have: (a) a first immunogenic component that comprises an aqueous formulation of a conjugated capsular saccharide from Streptococcus pneumoniae; (b) a second immunogenic component that comprises a conjugated capsular saccharide from Neisseria meningitidis serogroup C.
Abstract: A mucosal vaccine for the prevention or treatment of microbial infections is described that is capable of inducing vaccine antigen-specific immune responses in an organism without the addition of a mucosal adjuvant. The mucosal vaccine comprises a composite of a nanogel comprising a hydrophilic polysaccharide having a cationic functional group and a hydrophobic cholesterol added thereto as a side chain and a vaccine antigen. The vaccine is administered via a mucosal route.
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 22, 2008
Date of Patent:
August 23, 2011
Assignee:
Allergan, Inc.
Inventors:
J. Oliver Dolly, Yan Li, Kuo Chion Chan
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
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
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 18, 2008
Date of Patent:
July 26, 2011
Assignee:
Allergan, Inc.
Inventors:
J. Oliver Dolly, Yan Li, Kuo Chion Chan
Abstract: Botulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the sphenopalatine ganglion. Exemplary delivery is carried out by way of injection.
Abstract: The invention features a polypeptide complex synthesized by bacteria of the genus Clostridia that contains the serotype E botulinum neurotoxin and five neurotoxin associated polypeptides having molecular weights of about 118, 80, 65, 40, and 18 kDa, respectively. The complex is useful in the treatment of diseases or conditions that are caused by excessive release of acetylcholine from presynaptic nerve terminals.