Pilus, Fimbria, Or Adhesin Patents (Class 424/242.1)
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Patent number: 10329598Abstract: Methods and kits for preparing nucleic acid fragments from a sample of purified nucleic acid are provided. Alternatively, chromatin or other long polymers can be sheared with similar methods and kits.Type: GrantFiled: August 3, 2015Date of Patent: June 25, 2019Assignee: LIFE TECHNOLOGIES CORPORATIONInventors: Vladimir I. Bashkirov, Umberto Ulmanella, Robert G. Eason, Bradford J. Taft
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Patent number: 8431139Abstract: The invention provides proteins from group B streptococcus (Streptococcus agalactiae) and group A streptococcus (Streptococcus pyogenes), including amino acid sequences and the corresponding nucleotide sequences. Data are given to show that the proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics. The proteins are also targets for antibiotics.Type: GrantFiled: May 16, 2006Date of Patent: April 30, 2013Assignees: Novartis Vaccines and Diagnostics, Inc., J. Craig Venter InstituteInventors: John Telford, Vega Masignani, Maria Scarselli, Guido Grandi, Herve Tettelin, Claire Fraser
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Patent number: 8399000Abstract: The invention described herein relates to a Haemophilus influenzae (H. influenzae) regulon encoding type IV pili. In particular, the invention relates to type pili from nontypeable H. influenzae (NTHi) and from H. influenzae strains a, b, c, e and f. The invention provides isolated H. influenzae pilus polynucleotides and polypeptides encoded by the polynucleotides as well as polynucleotides and polypeptides encoded by the polynucleotides involved in the assembly/disassembly of the structure. The invention also relates to uses of these polynucleotides and/or polypeptides including methods for eliciting an immune response to H. influenzae and methods of treating and preventing H. influenzae related pathological conditions.Type: GrantFiled: January 12, 2011Date of Patent: March 19, 2013Assignee: Nationwide Children's Hospital, Inc.Inventors: Lauren O. Bakaletz, Robert S. Munson, Jr.
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Patent number: 8137679Abstract: A microbial adherence inhibitor specific to lactic acid producing microorganisms, in the form of fowl egg antibodies is disclosed, along with the method of making it and methods of using it. The inhibitor functions by substantially preventing the attachment or adherence of colony-forming immunogens in the fermentators. The inhibitor is made by inoculating female birds with the immunogen, allowing time for an immune response in the female bird and then harvesting the eggs that contain antibodies to the immunogen. The egg contents can be dried or used as a liquid and added to the media in the fermentators. Dependent upon the particular immunogen with which the female bird is inoculated, the egg antibody will specifically bind to the specific immunogen. When bacteria such as Lactobacillus spp. infect fermentation systems, they will further reduce alcohol conversion efficiency. Colony forming immunogens such as Lactobacillus spp.Type: GrantFiled: January 12, 2009Date of Patent: March 20, 2012Assignee: Camas IncorporatedInventors: Peter Nash, Bradley M. Mitteness
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Publication number: 20120064105Abstract: The present invention relates to engineered Clostridium difficile type IV pilin (tfp) genes, type IV pilin proteins which can serve as a diagnostic marker for identification of patients infected with C. difficile, and vaccines comprising type IV pilin proteins, antigenic fragments and variants thereof for therapeutic interventions.Type: ApplicationFiled: May 20, 2010Publication date: March 15, 2012Applicant: University of Maryland, BaltimoreInventor: Michael Donnenberg
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Patent number: 8062644Abstract: Disclosed herein are various genes that can be included in immunogenic compositions specific for pathogenic E. coli strains. The genes are from uropathogenic strains but are absent from non-pathogenic strains, and their encoded proteins have cellular locations which render them accessible to the immune system.Type: GrantFiled: February 17, 2006Date of Patent: November 22, 2011Assignee: Novartis Vaccines & Diagnostics SRL.Inventors: Mariagrazia Pizza, Laura Serino, Francesco Berlanda Scorza, Danilo Gomes Moriel, Maria Rita Fontana
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Patent number: 8003112Abstract: This disclosure relates to vaccine formulations comprising an immunogenic composition for inducing antibodies to both S. pneumoniae and N. meningitides in a subject. In a preferred aspect, the immunogenic composition comprises covalently conjugated recombinant PsaA (“rPsaA”) from S. pneumoniae and capsular polysaccharide from N. meningitidis serogroup C. This disclosure further relates to methods for producing the immunogenic composition as well as methods for their use.Type: GrantFiled: April 16, 2009Date of Patent: August 23, 2011Assignees: Howard University, The United States of America as represented by the Secretary, Department of Health and Human Services; National Institutes of Health, Office of Technology TransferInventors: Stanley Shih-Peng Tai, Che-Hung Robert Lee
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Publication number: 20110189236Abstract: Provided herein are methods and compositions for the display of polypeptides of interest on the tip of pili of Gram-positive bacteria. According to the present invention, the polypeptide of interest is amino terminal to a Gram-positive bacterial pilus tip protein or an active variant or fragment thereof, wherein the active variant or fragment comprises a cleaved cell wall sorting signal (CWSS) motif. The Gram-positive bacterium displaying a polypeptide of interest on the tip of pili that are disclosed herein are useful, for example, in methods for immunizing a subject with an antigen and methods for removing contaminants from a composition.Type: ApplicationFiled: May 8, 2009Publication date: August 4, 2011Applicant: EMORY UNIVERSITYInventors: June Scott, Dorothea Zahner, Bernard Quigley
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Patent number: 7939087Abstract: The invention provides proteins from group B streptococcus (Streptococcus agalactiae) and group A streptococcus (Streptococcus pyogenes), including amino acid sequences and the corresponding nucleotide sequences. Data are given to show that the proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics. The proteins are also targets for antibiotics.Type: GrantFiled: October 29, 2001Date of Patent: May 10, 2011Assignee: Novartis Vaccines and Diagnostics, Inc.Inventors: John Telford, Vega Masignani, Maria Scarselli, Guido Grandi, Herve Tettelin, Claire Fraser
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Publication number: 20110097360Abstract: Polypeptides from Streptococcus pneumoniae are described. In some aspects the polypeptides include pili polypeptides from a second pili island (pilus II island (INV1 04B)) identified in Streptococcus pneumoniae isolate INV1 04. In other aspects the polypeptides include pili polypeptides and non-pilus polypeptides from Streptococcus pneumoniae strains 23F, INV200, and OXC141 that are absent from Streptococcus pneumoniae isolate INV104. The polypeptides, including fragments and variants thereof, may be used in immunogenic compositions for prophylactic or therapeutic immunization against Streptococcus pneumoniae. The polypeptides are also disclosed to be used in compositions useful for the production of antibodies and immunostimulants. Also presented are methods of inhibiting Streptococcus pneumoniae, methods of treating Streptococcus pneumoniae infection, methods of identifying inhibitors of Streptococcus pneumoniae and methods for diagnosing/detecting Streptococcus pneumoniae infection.Type: ApplicationFiled: May 23, 2008Publication date: April 28, 2011Inventors: Claudio Donati, Vega Masignani, Marirosa Mora, Monica Moschioni
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Patent number: 7919104Abstract: Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of Streptococcus pneumoniae, and related methods and compositions. P4 peptide mimetics having a conformational structure identical or similar to the conformation of P4 (e.g., SEQ ID NO: 1 and SEQ ID NO:2) are provided. An antibody that specifically binds to the epitope defined by the disclosed peptides is provided. A P4-specific antibody is PsaA-specific since P4 defines an epitope specific for PsaA. Immunogenic compositions comprising the peptide of SEQ ID NO: 1 and a pharmaceutical carrier or the peptide of SEQ ID NO:2 and a pharmaceutical carrier are also provided. Methods of using the peptides and antibodies of the invention are provided.Type: GrantFiled: July 29, 2005Date of Patent: April 5, 2011Assignee: The United States of America as represented by the Department of Health and Human Services, Centers for Disease Control and PreventionInventors: Edwin W. Ades, Jacquelyn S. Sampson, Sandra Steiner, George M. Carlone, Joseph J. Caba, GowriSankar Rajam
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Patent number: 7893237Abstract: The invention described herein relates to a Haemophilus influenzae (H. influenzae) regulon encoding type IV pili. In particular, the invention relates to type IV pili from nontypeable H. influenzae (NTHi) and from H. influenzae strains a, b, c, e and f. The invention provides isolated H. influenzae pilus polynucleotides and polypeptides encoded by the polynucleotides as well as polynucleotides and polypeptides encoded by the polynucleotides involved in the assembly/disassembly of the structure. The invention also relates to uses of these polynucleotides and/or polypeptides including methods for eliciting an immune response to H. influenzae and methods of treating and preventing H. influenzae related pathological conditions.Type: GrantFiled: January 7, 2008Date of Patent: February 22, 2011Assignee: Nationwide Children's Hospital, Inc.Inventors: Lauren O. Bakaletz, Robert S. Munson, Jr.
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Patent number: 7815911Abstract: Compositions and methods for treating a Yersinia pestis (Y. pestis) infection are provided. Compositions and methods of for inducing an immune response in a subject are provided. Composition can include a YadC polypeptide.Type: GrantFiled: October 10, 2007Date of Patent: October 19, 2010Assignee: University of Kentucky Research FoundationInventors: Susan C. Straley, Brian S. Murphy, Stanislav Forman, Christine R. Wulff, Robert D. Perry, Tanya Myers-Morales
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Patent number: 7794731Abstract: The invention provides a fusion protein comprising a flagellin adjuvant and a Yersinia pestis antigen. Also provided are compositions comprising a flagellin adjuvant and a Yersinia pestis antigen. The invention also discloses methods of making a fusion protein comprising a flagellin adjuvant and a Yersinia pestis antigen. The invention further provides pharmaceutical formulations and methods for inducing an immune response against Yersinia pestis.Type: GrantFiled: December 16, 2005Date of Patent: September 14, 2010Assignee: Wake Forest University Health SciencesInventors: Steven B. Mizel, Anna Nichole Honko
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Publication number: 20100074923Abstract: Presented are methods of isolation of pili and pilus-like structures from Gram-positive bacteria including Streptococcus pneumoniae and compositions that include such isolated pili. These compositions are useful as immunogenic compositions for the production of antibodies and immunostimulation. Also presented are methods of inhibiting Streptococcus pneumoniae, and methods of identifying inhibitors of Streptococcus pneumoniae.Type: ApplicationFiled: March 26, 2009Publication date: March 25, 2010Inventors: Antonello COVACCI, Markus HILLERINGMANN, Ilaria FERLENGHI
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Patent number: 7527802Abstract: A vaccine delivered by transcutaneous immunization provides an effective treatment against infections by pathogens such as, for example, enterotoxigenic Escherichia coli (ETEC) and/or for symptoms of diarrheal disease caused thereby. For example, one, two, three, four, five or more antigens derived from ETEC and capable of inducing an antigen-specific immune response (e.g., toxins, colonization or virulence factors) and one or more optional adjuvant (e.g., whole bacterial ADP-ribosylating exotoxins, B subunits or toxoids thereof, detoxified mutants and derivatives thereof) are used to manufacture vaccines or to induce systemic and/or mucosal immunity.Type: GrantFiled: February 13, 2002Date of Patent: May 5, 2009Assignee: The United States of America as represented by the Secretary of the ArmyInventors: Gregory M. Glenn, Frederick J. Cassels
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Patent number: 7501131Abstract: The invention described herein relates to a Haemophilus influenzae (H. influenzae) regulon encoding type IV pili. In particular, the invention relates to type IV pili from nontypeable H. influenzae (NTHi) and from H. influenzae strains a, b, c, e and f. The invention provides isolated H. influenzae pilus polynucleotides and polypeptides encoded by the polynucleotides as well as polynucleotides and polypeptides encoded by the polynucleotides involved in the assembly/disassembly of the structure. The invention also relates to uses of these polynucleotides and/or polypeptides including methods for eliciting an immune response to H. influenzae and methods of treating and preventing H. influenzae related pathological conditions.Type: GrantFiled: December 21, 2004Date of Patent: March 10, 2009Assignee: Nationwide Children's Hospital, Inc.Inventors: Lauren O. Bakaletz, Robert S. Munson, Jr.
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Patent number: 7501132Abstract: The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from Streptococcus pneumoniae. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention further provides monoclonal antibodies which selectively bind PsaA. In addition, peptides are provided that immunospecifically bind to the monoclonal antibodies of the invention, and that are immunogenic against Streptococcus pneumoniae infection. Additionally, multiple antigenic peptides that provide protection against S. pneumoniae challenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies.Type: GrantFiled: June 6, 2005Date of Patent: March 10, 2009Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Edwin W. Ades, Scott E. Johnson, Danny L. Jue, Jacquelyn S. Sampson, George M. Carlone
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Patent number: 7479283Abstract: An acellular vaccine is provided which in use provides protection against Bordetella pertussis infections. The vaccine is based on the synergistic combination of two antigenes from B. pertussis, the 69 kDa, and the filamentous haemagglutinin antigens.Type: GrantFiled: May 25, 1995Date of Patent: January 20, 2009Assignee: UCB Pharma LimitedInventor: Pavel Novotny
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Patent number: 7404961Abstract: This invention relates to amino acid sequences from within a consensus peptide of the formula: VEKNITVTASVDPTIDLLQADGSALPSAVALTYSPA (SEQ ID. NO: 1) Eight mer peptides from within the consensus peptide were tested against an antibody raised to the consensus peptide. Studies relating to antibody raised to denatured proteins from the natural organisms producing the family of proteins were also useful and showed particular value of some sequences. A sequence of the formula ASVDPTIDLLQA (SEQ ID NO: 2) was identified thereby. An enlarge sequence of the formula TVTASVDPTIDLLQAD (SEQ ID NO: 3) is also especially interesting as are intermediate sequences such as sequences VTASVDPTIDLLQAD (SEQ ID NO: 4), TASVDPTIDLLQAD (SEQ ID NO: 5), and TASVDPTIDLLQA (SEQ ID NO: 6) as being binding sites for antibodies raised to the denatured proteins.Type: GrantFiled: January 12, 2004Date of Patent: July 29, 2008Assignee: The United States of America as represented by the Secretary of the ArmyInventors: Frederick J. Cassels, Lawrence Loomis-Price
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Publication number: 20080138356Abstract: The present invention relates to pili obtained from Mycobacterium tuberculosis, methods of producing the pili and the use of the pili for inducing an immune response against Mycobacterium tuberculosis. The present invention also provides proteins and peptides which are constituents of the pili. Antibodies which bind to the pili are also provided.Type: ApplicationFiled: February 9, 2005Publication date: June 12, 2008Applicant: The AZ Bd of Regents on Behalf of the Univ. of AZInventors: Richard L. Friedman, Jorge A. Giron, Christopher J. Alteri
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Publication number: 20080112982Abstract: Disclosed are compositions and methods relating to bacterial flagella and uses thereof.Type: ApplicationFiled: June 12, 2007Publication date: May 15, 2008Inventor: Kelly T. Hughes
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Patent number: 7314625Abstract: The invention provides chimeric proteins comprising a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, wherein the Type IV loop sequence is inserted within the non-toxic Pseudomonas exotoxin A. The invention also provides polynucleotides encoding the chimeric proteins, and compositions comprising the polynucleotides or the chimeric proteins. The invention also provides methods for using the chimeric proteins, polynucleotides and compositions of the invention.Type: GrantFiled: December 20, 2001Date of Patent: January 1, 2008Assignee: The United States as represented by the Secretary of the Department of Health and Human ServicesInventor: David J. FitzGerald
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Patent number: 7279169Abstract: Mucosal DTPa vaccines, especially intranasal vaccines, comprising (a) a diphtheria antigen, a tetanus antigen and an acellular pertussis antigen, and (b) a detoxified mutant of cholera toxin (CT) or E. coli heat labile toxin (LT). Component (b) acts as a mucosal adjuvant. The acellular pertussis antigen preferably comprises pertussis holotoxin (PT) and filamentous haemagglutinin (FHA) and, optionally, pertactin. The mucosally-delivered combined DTPa formulation is capable of generating a level of protection against B. pertussis infection equivalent to that observed by alum-adjuvanted parenteral administration.Type: GrantFiled: September 28, 2000Date of Patent: October 9, 2007Assignee: Novartis Vaccines and Diagnostics SRLInventors: Rino Rappuoli, Mariagrazia Pizza
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Patent number: 7208574Abstract: A polypeptide, called Tir (for translocated intimin receptor, which is secreted by attaching and effacing pathogens, such as the enteropathogenic (EPEC) and enterohemorrhagic (EHEC) E. coli. These bacterial pathogens inserts their own receptors into mammalian cell surfaces, to which the bacterial pathogen then adheres to trigger additional host signaling events and actin nucleation. Diagnosis of disease caused by pathogenic E. coli can be performed by the use of antibodies which bind to Tir to detect the protein or the use of nucleic acid probes for detection of nucleic acids encoding Tir polypeptide. Isolated nucleic acid sequences encoding Tir polypeptide, Tir peptides, a recombinant method for producing recombinant Tir, antibodies which bind to Tir, and a kit for the detection of Tir-producing E. coli are provided. A method of immunizing a host with Tir to induce a protective immune response to Tir or a second polypeptide of interest is also provided.Type: GrantFiled: November 10, 1998Date of Patent: April 24, 2007Assignee: The University of British ColumbiaInventors: B. Brett Finlay, Brendan Kenny, Rebekah DeVinney, Markus Stein
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Patent number: 7135175Abstract: Compositions for eliciting an immune response against Gram-negative bacterial infections and methods of making such compositions are provided. The composition comprises glycosylated pilin, the pilin being glycosylated with the O-antigen of a target Gram-negative bacteria of interest. Methods of eliciting an immune response by administration of such compositions are also provided.Type: GrantFiled: July 29, 2005Date of Patent: November 14, 2006Assignee: Duquesne University of the Holy GhostInventor: Paul A. Castric
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Patent number: 7132101Abstract: Compositions for eliciting an immune response against Gram-negative bacterial infections and methods of making such compositions are provided. The composition comprises glycosylated pilin, the pilin being glycosylated with the O-antigen of a target Gram-negative bacteria of interest. Methods of eliciting an immune response by administration of such compositions are also provided.Type: GrantFiled: February 27, 2002Date of Patent: November 7, 2006Assignee: Duquesne University of the Holy GhostInventor: Peter A. Castric
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Patent number: 7025971Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.Type: GrantFiled: March 6, 2001Date of Patent: April 11, 2006Assignees: Washington University, SIGA Pharmaceuticals, Inc.Inventors: Scott Hultgren, Meta Kuehn, Zheng Xu, Derek Ogg, Mark Harris, Matti Lepisto, Charles Hal Jones, Jan Kihlberg
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Patent number: 6902736Abstract: Compositions comprising products of the csa operon, an isolated nucleic acid encoding the csa operon or functional fragments thereof, purified polypeptide products of the csa operon or functional fragments thereof, methods of eliciting an immune response to these products, and methods of producing products of the csa operon are disclosed herein.Type: GrantFiled: April 20, 2001Date of Patent: June 7, 2005Assignee: University of Maryland, BaltimoreInventors: Zeev Altboum, Myron M. Levine, Eileen M. Barry
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Patent number: 6872398Abstract: The present invention relates to a broadly reactive vaccine against Gram-negative bacteria which is composed of a biological glycan-pilus conjugate. The conjugate core is a common pilus type to which is attached the glycan of choice in vivo. Pooling of these bioconjugates produces a multivalent vaccine. These pili give high bronchial titers when delivered by the intranasal route. Mice vaccinated with pure glycosylated P. aeruginosa strain 1244 pili in this manner are protected against respiratory challenge with P. aeruginosa strain 1244. The present invention further relates to a DNA and amino acid sequence of a new gene, pilO, which is capable of glycosylating pilin of Gram-negative bacteria and uses thereof.Type: GrantFiled: June 23, 1999Date of Patent: March 29, 2005Assignee: The United States of America as represented by the Secretary of the ArmyInventors: Peter Castric, Alan S. Cross, Jerald C. Sadoff
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Patent number: 6767545Abstract: A composition and method for treating or preventing infection by Pseudomonas aeruginosa is disclosed. The composition includes a P. aeruginosa pilin peptide modified to prevent oligomerization of the pilin. The method involves administered the composition to a person infected with Pseudomonas are at risk of such infection.Type: GrantFiled: May 24, 2001Date of Patent: July 27, 2004Assignee: Governors of the University of AlbertaInventors: Randall T. Irvin, Randy J. Read, Bart Hazes, Wah Y. Wong, Sastry A. Parimi, Linda M. G. Glasier
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Patent number: 6737063Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. Also provided are methods for vaccination of mammalian species, especially human patients, with variants of the E. coli FimH protein, said variants being derived from different strains of E. coli, and to production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A plasmid-based method of producing polypeptides, especially fused polypeptides, such as the complex of a bacterial chaperone and a bacterial adhesin, is also disclosed.Type: GrantFiled: July 6, 2001Date of Patent: May 18, 2004Assignee: MedImmune, Inc.Inventors: Solomon Langermann, Andrew Revel, Christine Auguste, Jeanne Burlein
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Patent number: 6696065Abstract: A multi-component vaccine composition is described comprising acellular pertussis vaccine components, diphtheria toxoid, tetanus toxoid and inactivated poliovirus. The composition also may contain a conjugate of a capsular polysaccharide on Haemophilus influenzae type b and tetanus toxoid or diphtheria toxoid, which may be reconstituted from a lyophilized state by the other component. The administration of the multiple component vaccine resulted in no diminution of the immunogenicity of any component as a result of interference by other components of the vaccine.Type: GrantFiled: July 2, 1996Date of Patent: February 24, 2004Assignee: Aventis Pastuer LimitedInventors: Raafat E. F. Fahim, Larry U. L. Tan, Luis Barreto, John Thipphawong, Gail E. D. Jackson
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Patent number: 6660261Abstract: The invention concerns a Bordetella strain deficient in the production of toxin and expressing a hybrid protein comprising at least part of the filamentous hemagglutin (FHA) and at least part of a protein heterologous to FHA. The gene coding for the toxin has been eliminated, or at least partially deleted or mutated so as to produce an inactive toxin. This strain can be used as vaccine. The invention also concerns liposomes containing at least part of the FHA protein and at least one protein heterologous to the FHA protein, and the use of FHA for the stimulation of immune responses.Type: GrantFiled: September 16, 1999Date of Patent: December 9, 2003Assignee: Institut Pasteur de LilleInventors: Nathalie Mielcarek, Camille Locht, Gilles Riveau, Odile Poulain-Godefroy, André Capron
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Patent number: 6562349Abstract: It has been discovered that a vaccine comprised of fimbrin, a filamentous protein derived from the bacterial surface appendages of non-typable Haemophilus influenzae is useful in studying, preventing or reducing the severity of, otitis media. The gene sequence of the DNA coding for fimbrin and the amino acid sequence of fimbrin have also been determined. Vectors containing DNA coding for fimbrin have also been developed, and transformants have been prepared which contain such vectors and which express such DNA and provide a source of pure fimbrin.Type: GrantFiled: November 29, 1999Date of Patent: May 13, 2003Assignee: The Ohio State University Research FoundationInventors: Pappachan E. Kolattukudy, Lauren O. Bakaletz, Tatiana Sirakova
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Patent number: 6548265Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.Type: GrantFiled: March 7, 2001Date of Patent: April 15, 2003Assignees: Washington University, Siga Pharmaceuticals, Inc.Inventors: Scott Hultgren, Meta Kuehn, Zheng Xu, Derek Ogg, Mark Harris, Matti Lepisto, Charles Hal Jones, Jan Kihlberg
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Patent number: 6500434Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.Type: GrantFiled: April 23, 1999Date of Patent: December 31, 2002Assignee: MedImmune, Inc.Inventors: Solomon Langermann, Scott J. Hultgren, Jerome S. Pinkner, Christine Gale Auguste
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Patent number: 6471966Abstract: Fimbriae adhesins have a molecular weight of 2×105 and 2×107 Da, and are comprised of 90-95% protein and 1-3% sugar. Type 1 fimbriae include five different protein fractions of 14-20 kDa, most of which are associated with carbohydrates. Type P fimbriae also include five different protein fractions of 14-20 kDa, and one of the majority proteins is associated with carbohydrates. The process of the invention comprises: culturing E. coli strains CECT 4484 and CECT 4485; collecting the sediment by centrifugation and resuspending it in physiological saline followed by homogenization; centrifuging the homogenate and collecting the supernatant; precipitating the supernatant with saline, reconstituting the precipitate and dialyzing the solution; treating the dialyzate with sodium deoxycholate and, subjecting the product to two successive chromatographies with Sephacryl S-200 and Sepharose 4B. The product is used for treatment and prevention of infections of the urinary tract caused by fimbriated E. coli.Type: GrantFiled: August 4, 1998Date of Patent: October 29, 2002Assignee: Industrial Farmaceutica y de Especialidades, S.A.Inventors: Ricardo Palacios Pelaez, Alberto Martinez Garate, Jorge Martinez Quesada
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Publication number: 20020146428Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.Type: ApplicationFiled: March 7, 2001Publication date: October 10, 2002Inventors: Scott Hultgren, Meta Kuehn, Zheng Xu, Derek Ogg, Mark Harris, Matti Lepisto, Charles Hal Jones, Jan Kihlberg
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Publication number: 20020142008Abstract: A method of producing pili and vaccines containing pili are described using bacteria that express at least one immunogenic peptide in a PapA region that does not normally contain such a peptide.Type: ApplicationFiled: April 12, 2001Publication date: October 3, 2002Inventors: Peter O'Hanley, Kenneth Denich, M. Alexander Schmidt
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Patent number: 6420127Abstract: Novel methods for the treatment and/or prophylaxis of diseases caused by tissue-adhering bacteria are disclosed. By interacting with periplasmic molecular chaperones it is achieved that the assembly of pili is prevented or inhibited and thereby the infectivity of the bacteria is diminished. Also disclosed are methods for screening for drugs as well as methods for the de novo design of such drugs, methods which rely on novel computer drug modelling methods involving an approximative calculation of binding free energy between macromolecules. Finally, novel pyranosides which are believed to be capable of interacting with periplasmic molecular chaperones are also disclosed.Type: GrantFiled: October 10, 1996Date of Patent: July 16, 2002Assignees: Washington University, Siga Pharmaceuticals, Inc.Inventors: Scott Hultgren, Meta Kuehn, Zheng Xu, Derek Ogg, Mark Harris, Matti Lepisto, Charles Hal Jones, Jan Kihlberg
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Publication number: 20020086037Abstract: A protein construct comprising a pilus protein portion, preferably a structurally stabilized pilus-protein, and an additional, or effector, portion other than a pilus protein or chaperone and wherein said effector portion serves to stabilize the pilus protein portion and to confer a therapeutic activity, such as vaccine activity or anti-microbial or anticancer activity, on the protein construct is disclosed. Such effector portion commonly comprises a donor strand complementary segment capable of structurally stabilizing a pilus protein subunit and attaching the auxiliary portion to said subunit to form the pilus protein analog of the invention. Methods of using said protein constructs are also disclosed as well as the formation and use of analogs comprising fragments of a pilus protein linked to effector components to produce immunogenic and/or therapeutic activity.Type: ApplicationFiled: December 28, 2001Publication date: July 4, 2002Inventors: Scott J. Hultgren, Solomon Langermann, Frederic G. Sauer
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Publication number: 20020054888Abstract: A method of producing pili and vaccines containing pili is described using bacteria harboring mutations that facilitate detachment of pili from the bacteria. Wild type pili have known immunoprotective effects in treating urinary tract infections. The mutant pili produced by this method are also shown to have such immunoprotective effects. Therefore, the pili may be used to make vaccines for treating urinary tract infections.Type: ApplicationFiled: April 12, 2001Publication date: May 9, 2002Inventors: Peter O'Hanley, Kenneth Denich
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Patent number: 6342233Abstract: A composition and method for treating or preventing infection by Pseudomonas aeruginosa is disclosed. The composition includes a P. aeruginosa pilin peptide modified to prevent oligomerization of the pilin. The method involves administered the composition to a person infected with Pseudomonas are at risk of such infection.Type: GrantFiled: June 11, 1999Date of Patent: January 29, 2002Assignee: Governors of the University of AlbertaInventors: Randall T. Irvin, Randy J. Read, Bart Hazes, Wah Y. Wong, Sastry A. Parimi, Linda M. G. Glasier