Patents by Inventor Leslie P. Nagata
Leslie P. Nagata 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).
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Patent number: 8501157Abstract: A CDR grafted humanized recombinant antibody against infection from Venezuelan equine encephalitis virus (VEEV) comprises a human Ig framework having CDRs from murine mAb 1A4A1 VH and VL. DNA sequences, expression vectors incorporating such sequences and transformed host cells are also provided. Also provided are pharmaceutical compositions and methods of prophylaxis and treatment against VEEV infection using the humanized recombinant antibodies of the invention.Type: GrantFiled: November 3, 2008Date of Patent: August 6, 2013Assignee: Her Majesty the Queen in right of Canada as represented by The Ministry of National DefenceInventors: Wei-Gang Hu, Leslie P. Nagata
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Publication number: 20130058971Abstract: This invention addresses how to rapidly prevent alphavirus-induced encephalitides before and after exposure to alphaviruses. The invention discloses a single dose administration of two types of recombinant viral vectors: one expressing interferon and another expressing the structural proteins of alphaviruses or a single dose administration of the recombinant viral vector co-expressing both interferon and the structural proteins of alphaviruses. This invention can be used to prevent humans from alphavirus-induced encephalitides in the event of a bioterrorism attack or biowarfare in which alphaviruses such as Venezuelan (VEEV), eastern (EEEV) and western (WEEV) equine encephalitis viruses are deliberately released to humans, a natural outbreak of alphaviruses, and an accidental exposure to alphaviruses in laboratory.Type: ApplicationFiled: August 1, 2012Publication date: March 7, 2013Applicant: HER MAJESTY THE QUEEN, IN RIGHT OF CANADA, AS REPRESENTED BY THE MINISTER OF NATIONAL DEFENCEInventors: Josh Qiaohua Wu, Leslie P. Nagata
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Patent number: 8303947Abstract: This invention addresses how to rapidly prevent alphavirus-induced encephalitides before and after exposure to alphaviruses. The invention discloses a single dose administration of two types of recombinant viral vectors: one expressing interferon and another expressing the structural proteins of alphaviruses or a single dose administration of the recombinant viral vector co-expressing both interferon and the structural proteins of alphaviruses. This invention can be used to prevent humans from alphavirus-induced encephalitides in the event of a bioterrorism attack or biowarfare in which alphaviruses such as Venezuelan (VEEV), eastern (EEEV) and western (WEEV) equine encephalitis viruses are deliberately released to humans, a natural outbreak of alphaviruses, and an accidental exposure to alphaviruses in laboratory.Type: GrantFiled: August 24, 2009Date of Patent: November 6, 2012Assignee: Her Majesty the Queen in right of Canada, as represented the Minister of National DefenceInventors: Josh Qiaohua Wu, Leslie P. Nagata
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Publication number: 20100247532Abstract: A CDR grafted humanized recombinant antibody against infection from Venezuelan equine encephalitis virus (VEEV) comprises a human Ig framework having CDRs from murine mAb 1A4A1 VH and VL. DNA sequences, expression vectors incorporating such sequences and transformed host cells are also provided. Also provided are pharmaceutical compositions and methods of prophylaxis and treatment against VEEV infection using the humanized recombinant antibodies of the invention.Type: ApplicationFiled: November 3, 2008Publication date: September 30, 2010Applicant: HER MAJESTY THE QUEEN IN RIGHT OF CANADA AS REPRESInventors: Wei-Gang Hu, Leslie P. Nagata
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Publication number: 20100047274Abstract: This invention addresses how to rapidly prevent alphavirus-induced encephalitides before and after exposure to alphaviruses. The invention discloses a single dose administration of two types of recombinant viral vectors: one expressing interferon and another expressing the structural proteins of alphaviruses or a single dose administration of the recombinant viral vector co-expressing both interferon and the structural proteins of alphaviruses. This invention can be used to prevent humans from alphavirus-induced encephalitides in the event of a bioterrorism attack or biowarfare in which alphaviruses such as Venezuelan (VEEV), eastern (EEEV) and western (WEEV) equine encephalitis viruses are deliberately released to humans, a natural outbreak of alphaviruses, and an accidental exposure to alphaviruses in laboratory.Type: ApplicationFiled: August 24, 2009Publication date: February 25, 2010Inventors: Josh Qiaohua Wu, Leslie P. Nagata
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Patent number: 7622111Abstract: Construction of a recombinant gene fusion encoding a human IgG1 heavy chain constant region and a single-chain variable fragment antibody of 1A4A1 monoclonal antibody is disclosed. The recombinant antibody of the present invention confers human immune effector functions on murine antibodies. After expression in bacteria as inclusion bodies, the recombinant antibody was purified and refolded in vitro. The recombinant soluble antibody retains high antigen-binding affinity to VEE and possesses some human IgG crystallizable fragment domain functions. On non-reducing gel electrophoresis analysis, disulfide bond formation was found in the hinge region of the recombinant antibody. The present invention shows that the recombinant antibody is in a native, functionally active form and it provides the basis to characterize the recombinant antibody for efficacy in vivo.Type: GrantFiled: March 5, 2003Date of Patent: November 24, 2009Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National DefenceInventors: Leslie P. Nagata, R. Elaine Fulton, Weigang Hu, Azhar Z. Alvi
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Publication number: 20090117105Abstract: A CDR grafted humanized rAb comprises a human Ig framework having CDRs from murine mAb 1A4A1 VH and VL. DNA sequences and vectors incorporating such sequences are also provided as are pharmaceutical preparations and methods of using the humanized rAbs.Type: ApplicationFiled: November 1, 2007Publication date: May 7, 2009Applicant: Her Majesty The Queen in Right of Canada as Represented by the Minister of National DefenceInventors: Wei-Gang Hu, Leslie P. Nagata
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Patent number: 7527796Abstract: A recombinant gene encoding a single-chain variable fragment (scFv) antibody against Venezuelan equine encephalitis virus (VEE) being cloned into a prokaryotic T7 RNA polymerase-regulated expression vector was disclosed. A streptavidin-binding peptide (SBP) sequence fused to a 6His tag is then attached downstream to the scFv gene. The recombinant fusion protein is expressed in bacteria and then purified by immobilized metal affinity chromatography. ELISA and Western blotting results revealed that the fusion protein not only retained VEE antigen binding and specificity properties similar to those of its parent native monoclonal antibody, but also possessed streptavidin-binding activity. This discovery obviates the need for chemical biotinylation of antibodies and the risk associated with antibody denaturation and provides a stable and reproducible reagent for rapid and efficient immunoassay of VEE.Type: GrantFiled: February 24, 2004Date of Patent: May 5, 2009Assignee: Her Majesty the Queen in Right of Canada, as represented by the Minister of National DefenceInventors: R. Elaine Fulton, Leslie P. Nagata, Azhar Z. Alvi, Weigang Hu
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Patent number: 7309566Abstract: A genetically biotinylated single chain fragment variable (scFv) antibody against Venezuelan equine encephalitis virus (VEE) being applied in a system consisting of an immunofiltration-enzyme assay (IFA) with a light addressable potentiometric sensor (LAPS) for the rapid identification of VEE is disclosed. The IFA entails formation of an immunocomplex sandwich consisting of VEE, biotinylated antibody, fluoresceinated antibody and streptavidin, capturing the sandwich by filtration on biotinylated membrane, and detecting the sandwich by anti-fluorescein urease conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies is investigated and optimized. The IFA/LAPS assay sensitivity was approximately equal to that of a conventional enzyme-linked immunosorbant assay utilizing polystyrene plates and a chromogenic substrate, however, less time and effort were required for performance of the IFA/LAPS assay.Type: GrantFiled: March 24, 2004Date of Patent: December 18, 2007Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National DefenseInventors: R. Elaine Fulton, Leslie P. Nagata, Azhar Z. Alvi, Weigang Hu
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Construction and characterization of monoclonal antibodies against western equine encephalitis virus
Patent number: 7276334Abstract: Construction and characterization of mouse monoclonal antibodies against western equine encephalitis virus (WEE) for potential use in detection, diagnosis, and immunotherapy are disclosed. Antibodies were prepared from hybridoma cells and further characterized by ELISAs, Western blotting, isotyping, and immunoprecipitation. The antibodies were also tested for cross-reactivity to other alphaviruses, such as Sindbis virus (SIN), Venezuelan equine encephalitis virus (VEE), and eastern equine encephalitis (EEE). All antibodies bound to WEE antigen in ELISAs, whereas only a subgroup of antibodies was found to be active in Western blotting and immunoprecipitations. A subset of antibodies was found to cross-react with other alphaviruses, such as SIN, VEE, and EEE.Type: GrantFiled: June 24, 2004Date of Patent: October 2, 2007Assignee: The Minister of Defence, Goverment of CanadaInventor: Leslie P. Nagata -
Patent number: 7223409Abstract: This invention relates to the development of a mammalian expression vector, under which expression of the structural genes of western equine encephalitis virus have been placed under the control of an eucaryotic promoter. When the recombinant vector is administered to mammalian cell culture or using a cell-free transcription/translation system, in vitro, authentic structural proteins of western equine encephalitis virus are produced as verified by reactivity with monoclonal antibodies developed to western equine encephalitis virus. When the recombinant DNA molecule is administered in vivo, a protective immune response is induced, thereby enhancing protection of the individual against subsequent infection by western equine encephalitis virus. In a similar manner, DNA vaccines to related alphaviruses (Venezuelan and eastern equine encephalitis viruses) could also be developed.Type: GrantFiled: August 20, 2004Date of Patent: May 29, 2007Assignee: The Minister of National Defence, Government of CanadaInventors: Leslie P. Nagata, Jonathon P. Wong
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Publication number: 20040229216Abstract: A genetically biotinylated single chain fragment variable (scFv) antibody against Venezuelan equine encephalitis virus (VEE) being applied in a system consisting of an immunofiltration-enzyme assay (IFA) with a light addressable potentiometric sensor (LAPS) for the rapid identification of VEE is disclosed. The IFA entails formation of an immunocomplex sandwich consisting of VEE, biotinylated antibody, fluoresceinated antibody and streptavidin, capturing the sandwich by filtration on biotinylated membrane, and detecting the sandwich by anti-fluorescein urease conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies is investigated and optimized. The IFA/LAPS assay sensitivity was approximately equal to that of a conventional enzyme-linked immunosorbant assay utilizing polystyrene plates and a chromogenic substrate, however, less time and effort were required for performance of the IFA/LAPS assay.Type: ApplicationFiled: March 24, 2004Publication date: November 18, 2004Inventors: R. Elaine Fulton, Leslie P. Nagata, Azhar Z. Alvi, Weigang Hu
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Construction and characterization of monoclonal antibodies against western equine encephalitis virus
Publication number: 20040229220Abstract: Construction and characterization of mouse monoclonal antibodies against western equine encephalitis virus (WEE) for potential use in detection, diagnosis, and immunotherapy are disclosed. Antibodies were prepared from hybridoma cells and further characterized by ELISAs, Western blotting, isotyping, and immunoprecipitation. The antibodies were also tested for cross-reactivity to other alphaviruses, such as Sindbis virus (SIN), Venezuelan equine encephalitis virus (VEE), and eastern equine encephalitis (EEE). All antibodies bound to WEE antigen in ELISAs, whereas only a subgroup of antibodies was found to be active in Western blotting and immunoprecipitations. A subset of antibodies was found to cross-react with other alphaviruses, such as SIN, VEE, and EEE.Type: ApplicationFiled: June 24, 2004Publication date: November 18, 2004Inventor: Leslie P. Nagata -
Construction and characterization of monoclonal antibodies against western equine encephalitis virus
Patent number: 6812329Abstract: Construction and characterization of mouse monoclonal antibodies against western equine encephalitis virus (WEE) for potential use in detection, diagnosis, and immunotherapy are disclosed. Antibodies were prepared from hybridoma cells and further characterized by ELISAs, Western blotting, isotyping, and immunoprecipitation. The antibodies were also tested for cross-reactivity to other alphaviruses, such as Sindbis virus (SIN), Venezuelan equine encephalitis virus (VEE), and eastern equine encephalitis (EEE). All antibodies bound to WEE antigen in ELISAs, whereas only a subgroup of antibodies was found to be active in Western blotting and immunoprecipitations. A subset of antibodies was found to cross-react with other alphaviruses, such as SIN, VEE, and EEE.Type: GrantFiled: February 27, 2001Date of Patent: November 2, 2004Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National DefenceInventor: Leslie P. Nagata -
Patent number: 6800289Abstract: This invention relates to the development of a mammalian expression vector, under which expression of the structural genes of western equine encephalitis virus have been placed under the control of an eucaryotic promoter. When the recombinant vector is administered to mammalian cell culture or using a cell-free transcription/translation system, in vitro, authentic structural proteins of western equine encephalitis virus are produced as verified by reactivity with monoclonal antibodies developed to western equine encephalitis virus. When the recombinant DNA molecule is administered in vivo, a protective immune response is induced, thereby enhancing protection of the individual against subsequent infection by western equine encephalitis virus. In a similar manner, DNA vaccines to related alphaviruses (Venezuelan and eastern equine encephalitis viruses) could also be developed.Type: GrantFiled: December 21, 2001Date of Patent: October 5, 2004Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National DefenceInventors: Leslie P. Nagata, Jonathon P. Wong
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Publication number: 20040005333Abstract: Construction of a recombinant gene fusion encoding a human IgG1 heavy chain constant region and a single-chain variable fragment antibody of 1A4A1 monoclonal antibody is disclosed. The recombinant antibody of the present invention confers human immune effector functions on murine antibodies. After expression in bacteria as inclusion bodies, the recombinant antibody was purified and refolded in vitro. The recombinant soluble antibody retains high antigen-binding affinity to VEE and possesses some human IgG crystallizable fragment domain functions. On non-reducing gel electrophoresis analysis, disulfide bond formation was found in the hinge region of the recombinant antibody. The present invention shows that the recombinant antibody is in a native, functionally active form and it provides the basis to characterize the recombinant antibody for efficacy in vivo.Type: ApplicationFiled: March 5, 2003Publication date: January 8, 2004Inventors: Leslie P. Nagata, R. Elaine Fulton, Weigang Hu, Azhar Z. Alvi
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Publication number: 20030143201Abstract: This invention relates to the development of a mammalian expression vector, under which expression of the structural genes of western equine encephalitis virus have been placed under the control of an eucaryotic promoter. When the recombinant vector is administered to mammalian cell culture or using a cell-free transcription/translation system, in vitro, authentic structural proteins of western equine encephalitis virus are produced as verified by reactivity with monoclonal antibodies developed to western equine encephalitis virus. When the recombinant DNA molecule is administered in vivo, a protective immune response is induced, thereby enhancing protection of the individual against subsequent infection by western equine encephalitis virus. In a similar manner, DNA vaccines to related alphaviruses (Venezuelan and eastern equine encephalitis viruses) could also be developed.Type: ApplicationFiled: December 21, 2001Publication date: July 31, 2003Inventors: Leslie P. Nagata, Jonathon P. Wong
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Patent number: 6544958Abstract: The present invention relates to novel ribonucleotide oligonucleotides (RNOs) that are specifically designed to inhibit viral replication. The RNOs are capable of binding to both the negative and positive strands of influenza RNA segments, thereby inhibiting the virus' ability to produce various viral components, thus inhibiting viral propagation, and effectively killing the virus at the intracellular sites of infection in the respiratory tract. The RNOs provided may act independently, or in combination to optimize their antiviral activity. In addition, the RNOs provided may be formulated in liposomes, which facilitate their therapeutic delivery to intracellular sites of infection, and additionally increase antiviral efficacies.Type: GrantFiled: March 26, 2001Date of Patent: April 8, 2003Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National Defence of Her Majesty's Canadian GovernmentInventors: Jonathan P. H. Wong, Leslie P. Nagata
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Publication number: 20030008000Abstract: DNA vaccination using plasmid encoding the hemagglutinin (HA) gene of influenza virus to induce long-lasting protective immunity against respiratory infection is disclosed. Efficacy of DNA vaccines is shown using a lethal influenza infection model in mice by employing liposomes as carriers. Mice immunized intranasally or intramuscularly with liposome-encapsulated pCI plasmid endcoding HA (pCI-HA10) are completely protected against an intranasal 5 LD50 influenza virus challenge. Mice immunized with liposome-encapsulated pCI-HA10, but not naked pCI-HA10, by intranasal administration are found to produce high titers of serum IgA. The present invention shows that DNA vaccines encapsulated in liposomes are efficacious in inducing complete protective immunity against respiratory influenza virus infection.Type: ApplicationFiled: March 7, 2002Publication date: January 9, 2003Inventors: Jonathan P. Wong, Leslie P. Nagata
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Construction and characterization of monoclonal antibodies against western equine encephalitis virus
Publication number: 20020141997Abstract: Construction and characterization of mouse monoclonal antibodies against western equine encephalitis virus (WEE) for potential use in detection, diagnosis, and immunotherapy are disclosed. Antibodies were prepared from hybridoma cells and further characterized by ELISAs, Western blotting, isotyping, and immunoprecipitation. The antibodies were also tested for cross-reactivity to other alphaviruses, such as Sindbis virus (SIN), Venezuelan equine encephalitis virus (VEE), and eastern equine encephalitis (EEE). All antibodies bound to WEE antigen in ELISAs, whereas only a subgroup of antibodies was found to be active in Western blotting and immunoprecipitations. A subset of antibodies was found to cross-react with other alphaviruses, such as SIN, VEE, and EEE.Type: ApplicationFiled: February 27, 2001Publication date: October 3, 2002Applicant: The Minister of National DefenceInventor: Leslie P. Nagata