Patents by Inventor John R. Mascola
John R. Mascola 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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Publication number: 20200123236Abstract: The present disclosure relates to multispecific antibodies targeting the human immunodeficiency virus-1 (HIV-1) envelope, methods for their production, pharmaceutical compositions containing said antibodies and uses thereof in treatment and prevention of HIV infection.Type: ApplicationFiled: October 17, 2017Publication date: April 23, 2020Inventors: Javier Guenaga, Yuxing Li, James Steinhardt, John R. Mascola
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Publication number: 20200054765Abstract: Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.Type: ApplicationFiled: October 21, 2019Publication date: February 20, 2020Inventors: Zhi-Yong YANG, Gary J. NABEL, Ling XU, Ronnie WEI, Huawei QIU, Jochen BENINGA, Jochen KRUIP, Ercole RAO, Wulf Dirk LEUSCHNER, Christian BEIL, Christian LANGE, Mark CONNORS, John R. MASCOLA, Richard A. KOUP, Jinghe HUANG, Nicole A. DORIA-ROSE, Tongqing ZHOU, Peter D. KWONG, Young Do KWON, Amarendra PEGU, Mangaiarkarasi ASOKAN
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Publication number: 20190374633Abstract: The present invention relates to a vaccine for Zika virus, the vaccine comprising Zika virus membrane and envelope proteins. More specifically, the vaccine comprises nucleic acid molecules encoding modified Zika virus membrane and/or envelope proteins. When introduced into a cell, the encoded proteins are produced, which results in the production of a virus-like particle capable of eliciting an immune response against Zika virus.Type: ApplicationFiled: July 28, 2017Publication date: December 12, 2019Inventors: Barney S. GRAHAM, Theodore C. PIERSON, Kimberly A. DOWD, John R. MASCOLA, Wing-pui KONG, Sung-youl KO, Eun Sung YANG, Wei SHI, Lingshu WANG, Christina R. DEMASO, Rebecca S. PELC, Adrian CREANGA, Julie LEDGERWOOD, Leda R. CASTILHO
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Publication number: 20190314490Abstract: Vaccines that elicit broadly protective anti-influenza antibodies. Some vaccines comprise nanoparticles that display HA trimers from influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to the stem region of an influenza HA protein. The fusion proteins self-assemble to form the HA-displaying nanoparticles. The vaccines comprise only the stem region of an influenza HA protein joined to a trimerization domain. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.Type: ApplicationFiled: June 27, 2019Publication date: October 17, 2019Inventors: John R. MASCOLA, Jeffrey C. BOYINGTON, Hadi M. YASSINE, Peter D. KWONG, Barney S. GRAHAM, Masaru KANEKIYO
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Patent number: 10363301Abstract: Vaccines that elicit broadly protective anti-influenza antibodies. Some vaccines comprise nanoparticles that display HA trimers from influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to the stem region of an influenza HA protein. The fusion proteins self-assemble to form the HA-displaying nanoparticles. The vaccines comprise only the stem region of an influenza HA protein joined to a trimerization domain. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.Type: GrantFiled: May 27, 2015Date of Patent: July 30, 2019Assignee: The United States of America as represented by the Secretary, Department of Health and Human ServicesInventors: John R. Mascola, Jeffrey C. Boyington, Hadi M. Yassine, Peter D. Kwong, Barney S. Graham, Masaru Kanekiyo
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Publication number: 20190192651Abstract: Vaccines that elicit broadly protective anti-influenza antibodies. The vaccines comprise nanoparticles that display HA trimers from Group 2 influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to stabilized stem regions of Group 2 influenza virus HA proteins. The fusion proteins self-assemble to form the HA-displaying nanoparticles. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.Type: ApplicationFiled: September 1, 2017Publication date: June 27, 2019Inventors: Jeffrey C. BOYINGTON, Barney S. GRAHAM, John R. MASCOLA, Hadi M. YASSINE, Kizzmekia S. CORBETT, Syed M. MOIN, Lingshu WANG, Masaru KANEKIYO
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Patent number: 10273291Abstract: Antibody VRC01 represents a human immunoglobulin that neutralizes—˜90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains.Type: GrantFiled: March 23, 2012Date of Patent: April 30, 2019Assignees: Duke University, THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES OFFICE OF TECHNOLOGY TRANSFER, NATIONAL INSTITUTES OF HEALTHInventors: John R. Mascola, Gary Nabel, Barton F. Haynes, Xueling Wu, Thomas B. Kepler, Peter Kwong
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Publication number: 20190054182Abstract: Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, where in a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.Type: ApplicationFiled: October 24, 2016Publication date: February 21, 2019Applicants: Sanofi, The USA, as Represented by the Secretary, Department of Health and Human ServicesInventors: Zhi-Yong YANG, Gary J. NABEL, Ling XU, Ronnie WEI, Huawei QIU, Jochen BENINGA, Jochen KRUIP, Ercole RAO, Wulf Dirk LEUSCHNER, Christian BEIL, Christian LANGE, Mark CONNORS, John R. MASCOLA, Richard A. KOUP, Jinghe HUANG, Nicole A. DORIA-ROSE, Tongqing ZHOU, Peter D. KWONG, Young Do KWON, Amarendra PEGU, Mangaiarkarasi ASOKAN
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Publication number: 20180360948Abstract: The present invention relates, in general, to HIV-1 and, in particular, to broadly neutralizing HIV-1 antibodies, and to HIV-1 immunogens and to methods of using such immunogens to induce the production of broadly neutralizing HIV-1 antibodies in a subject (e.g., a human).Type: ApplicationFiled: January 8, 2018Publication date: December 20, 2018Inventors: Barton F. HAYNES, Hua-Xin LIAO, Rebecca M. LYNCH, Tongqing ZHOU, Feng GAO, Scott BOYD, George M. SHAW, Beatrice H. HAHN, Thomas B. KEPLER, Bette T. KORBER, Peter KWONG, John R. MASCOLA
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Patent number: 10047148Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.Type: GrantFiled: September 8, 2017Date of Patent: August 14, 2018Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Mark Connors, Jinghe Huang, Leo B. Laub, Peter Kwong, Gary Nabel, John R. Mascola, Baoshan Zhang, Rebecca S. Rudicell, Ivelin Georgiev, Yongping Yang, Jiang Zhu, Gilad Ofek
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Publication number: 20180002406Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.Type: ApplicationFiled: September 8, 2017Publication date: January 4, 2018Applicant: The United States of America, as represented by the Secretary, Department of Health and HumanInventors: Mark Connors, Jinghe Huang, Leo B. Laub, Peter Kwong, Gary Nabel, John R. Mascola, Baoshan Zhang, Rebecca S. Rudicell, Ivelin Georgiev, Yongping Yang, Jiang Zhu, Gilad Ofek
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Patent number: 9783595Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.Type: GrantFiled: August 2, 2016Date of Patent: October 10, 2017Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Mark Connors, Jinghe Huang, Leo B. Laub, Peter Kwong, Gary Nabel, John R. Mascola, Baoshan Zhang, Rebecca S. Rudicell, Ivelin Georgiev, Yongping Yang, Jiang Zhu, Gilad Ofek
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Publication number: 20170202946Abstract: Vaccines that elicit broadly protective anti-influenza antibodies. Some vaccines comprise nanoparticles that display HA trimers from influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to the stem region of an influenza HA protein. The fusion proteins self-assemble to form the HA-displaying nanoparticles. The vaccines comprise only the stem region of an influenza HA protein joined to a trimerization domain. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.Type: ApplicationFiled: May 27, 2015Publication date: July 20, 2017Inventors: John R. MASCOLA, Jeffrey C. BOYINGTON, Hadi M. YASSINE, Peter D. KWONG, Barney S. GRAHAM, Masaru KANEKIYO
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Publication number: 20160362478Abstract: Described herein are methods of generating a protein binding domain that specifically binds to gp120 in a specific conformational state, comprising contacting gp120 with a CD4-mimetic compound, thereby forming gp120 in the specific conformational state; and generating antibodies to gp120 in the specific conformation state. Relatedly, the disclosure also describes methods of neutralizing HIV-1, comprising contacting HIV-1 with an effective amount of a CD4-mimetic compound, thereby forming HIV-1 having gp120 in a specific conformational state; and contacting the HIV-1 in the specific conformational state with an antibody.Type: ApplicationFiled: February 10, 2015Publication date: December 15, 2016Inventors: Joseph SODROSKI, Navid MADANI, Amy M. PRINCIOTTO, Arne SCHON, Judith M. LaLONDE, Ernesto FREIRE, Amos B. SMITH, Richard T. WYATT, Jongwoo PARK, Joel R. COURTER, David M. JONES, Wayne A. HENDRICKSON, Xueling WU, Matthew LE-KHAC, Peter D. KWONG, Young Do KWON, John R. MASCOLA
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Publication number: 20160333076Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.Type: ApplicationFiled: August 2, 2016Publication date: November 17, 2016Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Mark Connors, Jinghe Huang, Leo B. Laub, Peter Kwong, Gary Nabel, John R. Mascola, Baoshan Zhang, Rebecca S. Rudicell, Ivelin Georgiev, Yongping Yang, Jiang Zhu, Gilad Ofek
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Patent number: 9475862Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.Type: GrantFiled: November 7, 2012Date of Patent: October 25, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Mark Connors, Jinghe Huang, Leo B. Laub, Peter Kwong, Gary Nabel, John R. Mascola, Baoshan Zhang, Rebecca S. Rudicell, Ivelin Georgiev, Yongping Yang, Jiang Zhu, Gilad Ofek
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Patent number: 9403763Abstract: Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gp120, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD-556.Type: GrantFiled: December 14, 2012Date of Patent: August 2, 2016Inventors: Joseph Sodroski, Judith M. LaLonde, Amos B. Smith, III, Peter D. Kwong, Young Do Kwon, David M. Jones, Alexander W. Sun, Joel R. Courter, Takahiro Soeta, Toyoharu Kobayashi, Amy M. Princiotto, Xueling Wu, John R. Mascola, Arne Schon, Ernesto Freire, Navid Madani, Matthew Le-Khac, Wayne A. Hendrickson, Jongwoo Park
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Patent number: 9175070Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.Type: GrantFiled: September 24, 2010Date of Patent: November 3, 2015Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, University of WashingtonInventors: John R. Mascola, Richard T. Wyatt, Xueling Wu, Yuxing Li, Carl-Magnus Hogerkorp, Mario Roederer, Zhi-yong Yang, Gary J. Nabel, Peter D. Kwong, Tongqing Zhou, Mark Connors, William R. Schief
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Publication number: 20150044137Abstract: Neutralizing antibodies that specifically bind to HIV-1 gp120 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.Type: ApplicationFiled: March 15, 2013Publication date: February 12, 2015Inventors: John R. Mascola, Rebecca M. Lynch, Xueling Wu, Mark Connors, Tongqing Zhou, Joseph Casazza, Peter D. Kwong
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Publication number: 20140350113Abstract: Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gp120, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD-556.Type: ApplicationFiled: December 14, 2012Publication date: November 27, 2014Inventors: Joseph Sodroski, Judith M. LaLonde, Amos B. Smith, III, Peter D. Kwong, Young Do Kwon, David M. Jones, Alexander W. Sun, Joel R. Courter, Takahiro Soeta, Toyoharu Kobayashi, Amy M. Princiotto, Xueling Wu, John R. Mascola, Ame Schon, Emesto Freire, Navid Madani, Matthew Le-Khac, Wayne A. Hendrickson