Abstract: The present invention related to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.
Abstract: The present invention relates to a pharmaceutical composition representing a novel immunomodulating principle comprising bacterial endotoxin, fetal hemoglobin or more particularly a heme-free derivative or the ?-chain thereof, and optionally, components which are present in the fetal liver in addition to HbF. The composition is delivered to humans in a pharmaceutically acceptable carrier and/or diluent. In accordance with the present invention it was surprisingly found that endotoxin and fetal hemoglobin partial structures display a pronounced synergistic biomedical activity. The biomedical effect of fetal hemoglobin and its partial structures is surprisingly not based on a classical hemoglobin function as an oxygen transporter but related to a modulation of endotoxin-mediated bioactivity. This biomedical activity is surprisingly also observed after oral application of the composition.
Type:
Grant
Filed:
February 18, 2004
Date of Patent:
June 28, 2011
Inventors:
Otto Westphal, Josette Westphal, legal representative, Alexander Westphal, legal representative, Thierry Walli, Reginald Gorczynski, Silke Muller, Jean-Pierre Mach, Alfred Hartman, Wolfgang Bessler, Petra Hofmann, Ulrich Zahringer, Christian Alexander, Ulrich vor dem Esche, Artur J. Ulmer, Antonio Verdini
Abstract: A pharmaceutical preparation comprising one of the botulinum neurotoxins from Clostridium botulinum of types A, B, C, D, E, F or G or a mixture of two or more of these neurotoxins, wherein the neurotoxin or the mixture of neurotoxins is free of the complexing proteins which naturally form the botulinum neurotoxin complexes together with the neurotoxins.
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:
July 30, 2008
Date of Patent:
June 14, 2011
Assignee:
Allergan, Inc.
Inventors:
J. Oliver Dolly, Yan Li, Kuo Chion Chan
Abstract: The present invention provides compositions including siderophore receptor polypeptides from gram negative microbes, and preferably, lipopolysaccharide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions, including inducing the production of antibody in an animal.
Abstract: The present invention provides compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccarhide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions, including inducing the production of antibody in an animal.
Abstract: Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 ?M, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 ?M of SSCrFCES inhibits the LPS-induced secretion of hTNF-? and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B.
Abstract: The present invention relates to a composition for eliciting a specific cytotoxic T lymphocyte (CTL) response against T cell epitopes in a mammal, which comprises a compound provoking lymphocytopenia, a molecule having selective affinity for professional antigen presenting cells (APC), wherein said molecule is associated to said T cell epitope, and optionally, a pharmaceutical acceptable carrier. Advantageously, the composition further contains an adjuvant. Said composition may be used in anti-infections and anti-cancer therapies.
Abstract: A composition and method for enhancing immune response in a living organism is disclosed. In particular, the present disclosure provides an adjuvant peptide for use in raising an immune response to an antigen. The adjuvant peptide is selected from a group of peptides with an HIV-related sequence. Additionally, the adjuvant peptide can comprise a fusion-protein that acts as a mucosal adjuvant. The adjuvant peptide can be transformed into one or more living cells, such that the mucosal adjuvant can be produced in living cells and then administered by systemic, mucosal or epidermal delivery.
Type:
Grant
Filed:
September 16, 2008
Date of Patent:
April 19, 2011
Assignee:
Arizona Board of Regents, Acting For and on Behalf of Arizona State University
Inventors:
Tsafrir S. Mor, Nobuyuki Matoba, Charles J. Arntzen
Abstract: A method for stimulating the immune response to a vaccine applied to a mammalian subject includes the step of administering to the subject an effective amount of EtxB or a molecule having substantially equivalent activity, free from whole toxin and not linked to an antigen.
Type:
Grant
Filed:
May 10, 1999
Date of Patent:
March 29, 2011
Assignee:
Trident Pharmaceuticals, Inc.
Inventors:
Timothy Raymond Hirst, Neil Andrew Williams, Andrew Morgan, Andrew Douglas Wilson, Lucy Amber Bird
Abstract: Methods for treating gastric disorders, such as GERD and delayed gastric emptying, by intramuscular administration of a botulinum toxin to a head, neck and/or shoulder muscle of a patient with a gastric disorder.
Abstract: The invention provides a chimeric peptide or mixture of chimeric peptides that can be formulated as an immunizing composition and used in a method for immunization of a mammal against an internal peptide cleavage product derived from a precursor or mature protein, for which the peptide cleavage product and the precursor or mature protein are self molecules. The chimeric peptide or peptides have an end-specific B cell epitope from a naturally-occurring internal peptide cleavage product of a precursor or mature protein, as a free N- or C-terminus, fused with or without spacer residues to a T helper cell epitope derived from a living source different from that of the internal peptide cleavage product.
Abstract: The invention overcomes the deficiencies of the prior art by providing antibody compositions having improved affinities for Bacillus anthracis antigens. The compositions have important thereapeutic and diagnostic applications, including treatment or detection of infection by Bacillus anthracis.
Type:
Grant
Filed:
July 12, 2005
Date of Patent:
March 8, 2011
Assignee:
The Board of Regents of The University of Texas System
Inventors:
Barrett R. Harvey, George Georgiou, Brent L. Iverson
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
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:
March 14, 2007
Date of Patent:
March 1, 2011
Assignee:
Syntaxin, Ltd
Inventors:
Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster, John Chaddock, Philip Marks, J. Mark Sutton, Patrick Stancombe, Jonathan Wayne
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
Abstract: This invention relates to the stabilization of a bacterial ADP-ribosylating exotoxin class protein (bARE), a method for analysing a bARE class protein, a method for the stabilization of the bARE class bacterial protein, compositions comprising a stabilized bARE protein, compositions comprising a substantially integral bARE class protein and immunogenic composition formulations incorporating same.
Abstract: The present invention pertains to pharmaceutical compositions which comprise a botulinum neurotoxin from Clostridium botulinum, the neurotoxin being free of the complexing proteins naturally present in the botulinum neurotoxin complex or being chemically modified or being modified by genetic manipulation. Moreover the pharmaceutical compositions of the instant invention have good stability and are advantageously formulated free of human serum albumin.
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: A protein toxin named Aeromonas salmonicida exoenzyme T (AexT), which belongs to the family of ADP-ribosylating toxins, is disclosed as is a novel Calcium (or other cation concentration) dependent promoter of A. salmonicida. Also disclosed are diagnostic, preventive, and therapeutic techniques, including the preparation of bacterin vaccines based on AexT for inducing immunity against A. salmonicida infections.
Type:
Grant
Filed:
July 8, 2009
Date of Patent:
December 14, 2010
Assignee:
Universitat Bern
Inventors:
Joachim Frey, Peter Kuhnert, Julian C. Thornton, Tracy A. Thornton, legal representative, Michael A. Kuzyk, Jan Burian, Martin Braun
Abstract: The invention provides compositions and methods for the treatment of diseases associated with amyloid deposits of A? in the brain of a patient, such as Alzheimer's disease. Such methods entail administering an immunogenic fragment of A?, lacking a T-cell epitope, capable of inducing a beneficial immune response in the form of antibodies to A?. In another aspect, the immunogenic fragment of A? is capable of elevating plasma A? levels. The immunogenic fragments comprise linear or multivalent peptides of A?. Pharmaceutical compositions comprise the immunogenic fragment chemically linked to a carrier molecule which may be administered with an adjuvant.
Type:
Grant
Filed:
May 1, 2006
Date of Patent:
December 14, 2010
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Victor M. Garsky, Joseph G. Joyce, Paul M. Keller, Gene Kinney, Xiaoping Liang, John W. Shiver
Abstract: A method for treating a mammary gland disorder, including hyperplastic, hypertonic, cystic and/or neoplastic mammary gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted breast tissue.
Abstract: The invention provides humanized antibodies that specifically bind to, and preferably, neutralize, verotoxin II (VT2). The antibodies are useful for treating patients suffering from, or at risk of suffering, toxic effects of verotoxin.
Type:
Grant
Filed:
May 19, 1999
Date of Patent:
December 7, 2010
Assignees:
Teijin Limited, PDL Biopharma, Inc.
Inventors:
Yoh-Ichi Matsumoto, Atsuchi Imaizumi, Tsuyoshi Kimura, Tae Takeda, Yoshifumi Takeda, legal representative, Man Sung Co, Maximiliano Vasquez
Abstract: A method of temporarily elevating the eyebrow position and softening undesirable glabellar muscle activity to affect a more desirable appearance. In a broad aspect the invention comprises injecting small quantities of botulinum toxin (BTX) equivalent in activity to 0.001 to 1.0 Units of botulinum toxin A, dissolved in 10 to 50 microliters microdroplets of injectable saline carrier, and injected 0.5 to 1.0 millimeters below the skin surface to treat the septal and orbital orbicularis oculi muscles, on each side of a patient's face. In sufficient numbers, injected microdroplets of BTX are able to selectively weaken these muscles. This method preferably also includes using microdroplets of BTX to treat: a) the depressor supercilii muscle, on each side; b) the procerus muscle; c) the corrugator supercilii muscle, on each side; and d) the inferior limit of the frontalis muscle where it meets the superior aspect of the orbital portion of the orbicularis oculi muscle.
Abstract: A method for treating a mammary gland disorder, including hyperplastic, hypertonic, cystic and/or neoplastic mammary gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted breast tissue.
Abstract: The invention relates to the use of a pre-synaptic neuromuscular blocking substance for preparing a medicament intended to treat a gland, organ or duct obstructed by a naturally formed stone. This method can be applied notably for salivary gland, gall bladder, kidney or pancreas stones.
Abstract: The present invention provides PE CD4+ T-cell epitopes, as well as novel variants that exhibit reduced immunogenic responses, as compared to the parental PE. The present invention further provides DNA molecules that encode novel PE variants, host cells comprising DNA encoding novel PE variants, as well as methods for making PEs less immunogenic. In addition, the present invention provides various compositions that comprise these PE variants that are less immunogenic than wild-type PEs.
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: Methods and compositions for immediately immunizing an individual against any molecule or compound are provided. The present invention is directed to an immunity linker with at least two sites; (1) at least one first binding site that binds to an immune response component in an individual, and (2) at least one second binding site that binds specifically to a desired compound or molecule, the target. The second binding sites are preferably thiolated aptamers that have the benefit of increased stability, resistance to degradation and longer circulating half life. Methods of making and using pharmaceutical compositions including immunity linker molecules having a thiolated aptamer are also provided.
Type:
Application
Filed:
May 5, 2010
Publication date:
November 11, 2010
Inventors:
KARY B. MULLIS, JEEVALATHA VIVEKANANDA, JOHNATHAN LLOYD KIEL, RONALD M. COOK
Abstract: The present composition combines an RNAIII-inhibiting peptide (RIP) with an antimicrobial peptide, such as a cathelicidin, that is capable of binding and neutralizing lipidic and polyanionic components of bacterial cell envelope. In another embodiment, the RIP is combined with an antibiotic, with or without an antimicrobial peptide. The present composition is advantageously used in a method of treatment of bacterial sepsis.
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: Botulinum toxin, or other neuromuscular inhibitors, injected into the lower leg muscle of infants, less than a year old, with idiopathic clubfoot is shown to be an effective therapy in correcting this physical deformity. Following a protocol of manipulations, castings, and injections, clubfoot is effectively treated, and surgical treatment procedures can be avoided.
Abstract: The present invention provides a vaccine composition comprising the B subunit of Shiga toxin or an immunologically functional equivalent thereof which is able to bind the Gb3 receptor, complexed with at least one first antigen, and further comprising at least one second antigen (which may be the same or different as the first antigen) and an adjuvant.
Abstract: Method for alleviating testicular pain in a patient in need thereof. The method can comprise the step of locally administering a neurotoxin (e.g., a botulinum toxin) to at least one anatomical site selected from the group consisting of a testicle and a tissue associated with the testicle of the patient.
Abstract: This invention features a composition that includes a multiple-cell organism for use as food for an aquatic animal (e.g., a fish or a shrimp), and a single-cell organism fed to, and as a result, bioencapsulated by, the multiple-cell organism. The single-cell organism has been transformed to express a recombinant antigen that induces an immune response in the aquatic animal.
Type:
Grant
Filed:
October 21, 2004
Date of Patent:
October 5, 2010
Assignee:
Academia Sinica
Inventors:
Huey-Lang Yang, John Han-You Lin, James Chein-Chih Yu
Abstract: The present invention relates to a hybrid bacterial toxin subunit, to a hybrid bipartite bacterial toxin and to nucleic acid molecules comprising a nucleotide sequence encoding such bacterial toxins. Furthermore, the invention relates to vaccines comprising bacterial toxins and to their use in vaccines. Finally, the invention relates to methods for the preparation of such vaccines and to the use of such bacterial toxins for the manufacture of such vaccines.
Abstract: Compositions comprising a Neisserial antigen and a detoxified ADP-ribosylating toxin are provided. These compositions have been found useful for mucosal immunization, particularly for nasal immunization against Neisseria meningitidis.
Abstract: A composition for treating a subject is provided. The composition includes a pentameric secretory IgM therapeutic. Formulating agents are mixed with the pentameric secretory IgM to yield a dosing form of a capsule, tablet, and a suppository. A process for manufacturing a medicament for the treatment of C. difficile associated disease in a human is also provided that the modification of pentameric IgM with secretory component to form a pentameric secretory IgM therapeutic. The pentameric secretory IgM therapeutic is then mixed with formulating agents to create a capsule, tablet, 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.
Abstract: Methods and compositions are provided for the enhanced production of bacterial toxins in large-scale cultures. Specifically, methods and compositions for reducing bacterial toxin expression inhibitors are providing including, but not limited to, addition of toxin expression inhibitor binding compounds, culture media having reduced concentrations of toxin inhibitor metabolic precursors and genetically modified toxogenic bacteria lacking enzymes required to metabolize the toxin inhibitor metabolic precursors.
Type:
Grant
Filed:
November 1, 2005
Date of Patent:
September 7, 2010
Assignees:
Baxter International Inc., Bacter Healthcare S.A.
Inventors:
Milan S. Blake, John A. Bogdan, Jr., Javier Nazario-Larrieu
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 Clostridial toxin pharmaceutical composition comprising a Clostridial toxin, such as a botulinum toxin and a polysaccharide, such as a hydroxyethyl starch, wherein the pharmaceutical composition has a reduced toxicity. The Clostridial toxin pharmaceutical composition can be essentially free of any blood or serum derived proteins, filtrates or fractions.
Abstract: The present invention describes the adjuvant activity of mutants of LT-IIa and LT-IIb enterotoxin which lack ganglioside binding activity. The adjuvant activity of the LT-IIb(T13I) mutant is comparable to that of the wild type LT-IIb. The adjuvant activity of LT-IIa(T34I) mutant is also described which exhibits a late onset adjuvant activity. These mutants are useful for enhancing immune response to antigens.
Type:
Grant
Filed:
November 5, 2008
Date of Patent:
August 17, 2010
Assignee:
The Research Foundation of State University of New York
Inventors:
Terry D. Connell, Michael W. Russell, Hesham Nawar, Sergio Arce
Abstract: The present invention provides a method for treating pain in a subject in need of treatment, by administering to the subject a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat pain in the subject. Also disclosed is a method for treating opioid-withdrawal effects in a subject in need of treatment, by the administration to the subject of a non-opioid agent in combination with a selective excitatory-opioid-receptor inactivator, in amounts effective to treat opioid-withdrawal effects in the subject. Finally, the present invention provides a pharmaceutical composition comprising a non-opioid agent and a selective excitatory-opioid-receptor inactivator, and a pharmaceutically-acceptable carrier.
Abstract: The present invention provides a vaccine composition comprising a non-live vector which targets the MHC class I pathway derived from a bacterial toxin or an immunologically functional derivative thereof but excluding those which bind the Gb3 receptor complexed with at least one first antigen and further comprising at least one second antigen (which may be the same or different as the first antigen) and an adjuvant.
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:
November 8, 2002
Date of Patent:
July 27, 2010
Assignee:
The United States of America as represented by the Department of Health and Human Services
Inventors:
Joseph Shiloach, Stephen H. Leppla, Delia M. Ramirez, Rachel Schneerson, John B. Robbins, S. Dana Hsu, Mary Jo Rosovitz
Abstract: This invention relates to the use of a composition comprising a polysaccharide and a botulinum toxin for reducing a skin wrinkle. In some embodiments, the polysaccharide comprises disaccharides. In some embodiments, the average molecular weight of a disaccharide unit of the polysaccharide is between about 345 D and about 1,000 D.
Abstract: Pharmaceutical compositions for transdermal administration of neurotoxins to a patient include a neurotoxin, such as a botulinum toxin, and an enhancing agent that facilitates absorption of the neurotoxin through the skin of the patient and does not eliminate the bioactivity associated with the neurotoxin. The pharmaceutical compositions are topically applied on a patient, and may be provided in a transdermal patch.
Abstract: Methods are disclosed herein for treating depression in the subject. A method includes the use of Botulinum toxin to cause paralysis of a facial muscle, such as the depressor anguli oris, procerus, frontalis, orbicularis oculi, or corrugator supercilii muscle to treat depression in the subject.
Abstract: This invention relates to conjugates of the Vi polysaccharide of S. typhi with the carrier Pseudomonas aeruginosa recombinant exoprotein A (rEPA), and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, S. typhi bacterial infections. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies against S. typhi and are useful to prevent and/or treat illnesses caused by S. typhi.
Type:
Grant
Filed:
March 20, 2007
Date of Patent:
July 13, 2010
Assignee:
The United States of America as represented by the Department of Health and Human Services
Inventors:
Zuzana Kossaczka, Shousun Chen Szu, John B. Robbins, Rachel Schneerson, Joseph Shiloach