Abstract: The invention relates to antibodies, and antigen binding fragments thereof that potently neutralize infection of both RABV and non-RABV lyssaviruses. The invention also relates to antigenic sites to which the antibodies and antigen binding fragments bind, as well as to nucleic acids that encode and immortalized B cells and cultured plasma cells that produce such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies and antibody fragments of the invention in screening methods as well as in the diagnosis, prophylaxis and treatment of RABV infection and infection with non-RABV lyssaviruses.
Abstract: Methods for generating immune responses to Ebola virus antigens using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.
Abstract: Isolated, antigenic polypeptides including a pre-hairpin intermediate conformation of gp41 and vectors encoding such polypeptides are provided. Exemplary pre-hairpin intermediate conformations of gp41 include an oligomerization domain; a heptad repeat 2 motif; and a membrane-proximal external region, where the polypeptide lacks a heptad repeat 1 motif, and where the isolated, antigenic polypeptides elicit production of a broadly neutralizing antibody against HIV when injected into a subject. Antibodies that bind to a pre-hairpin intermediate conformation of gp41 and methods of making antibodies a that bind to pre-hairpin intermediate conformation of gp41 are also provided. Vaccines against a pre-hairpin intermediate conformation of gp41, as well as methods of treating subjects infected with HIV, preventing HIV infection, and inhibiting HIV-mediated activities are also provided. Methods of screening compounds that bind to an isolated, pre-hairpin intermediate conformation of gp41 are further provided.
Abstract: A platform enabling the manufacture of thermostable vaccines by incorporating recombinantly expressed, viral envelope proteins in their native conformation into ether glycerophospholipid nanodisc structures that simulate the natural environment of the envelope proteins. The ether glycerophospholipids include ether-linked hydrophobic side chains, and are derived from or modeled after those found in thermophile bacteria, which increase thermostability, thereby significantly enhancing the vaccine's potency, enabling the production of highly multivalent vaccines incorporating multiple variants of the viral antigen, and improving stability and shelf-life.
Abstract: A highly safe dengue vaccine was invented that induced a neutralizing antibody response against all of the four serotypes of dengue virus without developing more than a fixed level of viremia with single administration. A tetravalent dengue virus formulation is provided that is excellent in both efficacy (neutralizing antibody response) and safety (viremia).
Abstract: Provided are tri-specific fusion antibodies created to target multiple epitopes of the Human Immunodeficiency Virus (HIV). The fusion antibodies provide improved potency and breadth against HIV as compared to monospecific and bispecific antibodies, and additionally provide a high barrier against viral resistance. Also disclosed are pharmaceutical formulations and therapeutic methods utilizing such fusion proteins.
Type:
Grant
Filed:
June 2, 2016
Date of Patent:
May 19, 2020
Assignee:
The Rockefeller University
Inventors:
David Ho, Jian Yu, Xin Yao, Yaoxing Huang
Abstract: The invention provides a polypeptide comprising a single domain CD4, as well as a fusion protein comprising the single domain CD4 and one or more fusion partners. A nucleic acid encoding the polypeptide or fusion protein, as well as compositions or cells comprising the polypeptide, fusion protein, or nucleic acid also are provided.
Type:
Grant
Filed:
October 16, 2017
Date of Patent:
May 12, 2020
Assignee:
The United States of America, as represented by the Secretary, Department of Health and Human Services
Inventors:
Dimiter S. Dimitrov, Weizao Chen, Prabakaran Ponraj
Abstract: The present invention provides HIV-1 vaccine immunogens. Some of the immunogens contain a soluble gp140-derived protein that harbors a modified N-terminus of the HR1 region in gp41. Some of the immunogens contain an HIV-1 Env-derived trimer protein that is presented on a nanoparticle platform. The invention also provides methods of using the HIV-1 vaccine immunogens for eliciting an immune response or treating HIV infections.
Type:
Grant
Filed:
October 31, 2018
Date of Patent:
May 12, 2020
Assignee:
The Scripps Research Institute
Inventors:
Leopold Kong, Ian A. Wilson, Natalia De Val, Andrew B. Ward, Dennis Burton, Linling He, Jiang Zhu
Abstract: This disclosure is directed to compositions and methods for utilizing the boundaries of the C-terminal domains of Nucleoprotein from Zaire Ebola virus as highly stable recombinant protein antigens to generate antibodies for diagnosis and treatment of Ebola virus infection.
Type:
Grant
Filed:
October 16, 2015
Date of Patent:
May 5, 2020
Assignees:
University of Virginia Patent Foundation, The University of Chicago
Inventors:
Zygmunt S. Derewenda, Daniel A. Engel, Anthony Kossiakoff, Elena K. Davydova, Mateusz Jaskolowski
Abstract: Instead of generating immune responses to several HIV proteins and risk over activating more CD4+ T cells (easy targets for HIV-1 infection) as current candidate vaccines try to do, a lower magnitude, narrowly focused, well maintained virus specific CD8+ T cell response to multiple subtypes should destroy and eliminate a few founder viruses without inducing inflammatory responses that may activate more CD4+ T cells and provide more targets for HIV-1 virus infection. Specifically, described herein is a method that focuses the immune response to the 12 protease cleavage sites.
Abstract: The disclosure provides non-human primate-derived binding molecules, e.g., antibodies or antigen-binding fragments thereof, that can bind to orthologous epitopes found on two or more filovirus species or strains.
Type:
Grant
Filed:
October 27, 2015
Date of Patent:
April 7, 2020
Assignees:
INTEGRATED BIOTHERAPEUTICS, INC., THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Inventors:
Mohammad Javad Aman, Frederick Wayne Holtsberg, Sven G. Enterlein, Katie A. Howell, Zhen-Yong Keck, Steven K. H. Foung
Abstract: Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is a common human, human-like, or humanized light chain. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.
Type:
Grant
Filed:
April 27, 2016
Date of Patent:
March 31, 2020
Assignee:
Merus N.V.
Inventors:
Ton Logtenberg, Mark Throsby, Robert A. Kramer, Rui Daniel Pinto, Cornelis A. Dekruif, Erwin Houtzager
Abstract: Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) potent VRC01-like (PVL) antibodies targeted to gp120 having an amino acid substitution at a residue in the anti-CD4 binding site PVL antibody that is equivalent to Phe43 in CD4, these antibodies having improved potency and breadth.
Type:
Grant
Filed:
December 21, 2017
Date of Patent:
March 17, 2020
Assignees:
California Institute of Technology, The Rockefeller University
Inventors:
Ron Diskin, Pamela J. Bjorkman, Michel C. Nussenzweig, Johannes Scheid
Abstract: The present invention relates, in general, to human immunodeficiency virus (HIV), and, in particular, to a method of inducing neutralizing antibodies to HIV and to compounds and compositions suitable for use in such a method.
Type:
Grant
Filed:
June 26, 2017
Date of Patent:
March 17, 2020
Assignee:
DUKE UNIVERSITY
Inventors:
Barton F. Haynes, S. Munir Alam, Hua-Xin Liao
Abstract: This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebolavirus (EBOV) or Marburg virus (MARV).
Type:
Grant
Filed:
October 31, 2016
Date of Patent:
March 10, 2020
Assignees:
THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES, GLAXOSMITHKLINE BIOLOGICALS SA
Inventors:
Nancy J. Sullivan, Gary J Nabel, Clement Asiedu, Cheng Cheng, Alfredo Nicosia, Riccardo Cortese, Virginia Ammendola, Stefano Colloca
Abstract: The present invention relates to an improved filovirus vaccine comprising a recombinant modified vaccinia virus Ankara-based (MVA-based) vaccine against filovirus infection and to related products, methods and uses. Specifically, the present invention relates to genetically engineered (recombinant) MVA and FPV vectors comprising at least one heterologous nucleotide sequence encoding an antigenic determinant of a Marburg virus (MARV) or Ebola virus glycoprotein. Specifically, the invention relates to recombinant MVA comprising Ebola virus glycoprotein and virion protein 40. The invention also relates to products, methods and uses thereof as well as prime/boost regimens of MVA and genetically engineered (recombinant) FPV, e.g., suitable to induce a protective immune response in a subject.
Type:
Grant
Filed:
September 3, 2015
Date of Patent:
March 3, 2020
Assignee:
Bavarian Nordic A/S
Inventors:
Ariane Volkmann, Robin Steigerwald, Hubertus Hochrein, Ulrike Dirmeier, Henning Lauterbach, Jürgen Hausmann Hausmann
Abstract: This invention relates to the use of antibody therapy as a treatment substitute, or for treatment interruption, to treat HIV-1 infected patients. Specifically, the present invention relates to the use of antibody therapy, such as PRO 140 monoclonal anti-body therapy, as a monotherapy for treatment of HIV-1 infected patients.
Type:
Grant
Filed:
August 20, 2015
Date of Patent:
February 18, 2020
Assignee:
Cytodyn Inc.
Inventors:
Robert T. Schooley, Nader Z. Pourhassen
Abstract: The invention provides a method for determining whether a human immunodeficiency virus is resistance to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.
Abstract: A method for detecting HIV infection in a mammal is disclosed. The method contains the steps of isolating exosomes from a urine sample of a mammal and detecting the presence of HIV-specific biomarker in said isolated exosomes. A method for diagnosing a mammal with an HIV-associated disease, in particular, HIV-associated nephropathy is also disclosed.
Type:
Grant
Filed:
October 2, 2009
Date of Patent:
January 28, 2020
Assignee:
MOREHOUSE SCHOOL OF MEDICINE
Inventors:
Gale W. Newman, Mike Powell, Akins Doherty, Chamberlain Obialo, Claudette Mitchell-Ali, Khalid Bashir, Mafuz Khan
Abstract: The present invention relates anti-HIV therapies and prophylaxis. Specifically, the invention relates to broadly neutralizing antibodies against HIV-1, nucleic acids encoding these antibodies, vectors comprising the nucleic acids and cells and pharmaceutical compositions Comprising said vectors and/or antibodies. The present invention also relates to use of the antibodies and/or vectors for the treatment and/or prevention of HIV-1 infection in a subject. Furthermore, the invention also relates to a kit containing the antibodies of the invention.
Type:
Grant
Filed:
February 27, 2015
Date of Patent:
December 31, 2019
Assignees:
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, CENTRE FOR THE AIDS PROGRAMME OF RESEARCH IN SOUTH AFRICA, UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG, NATIONAL HEALTH LABORATORY SERVICE
Inventors:
Chaim Aryeh Schramm, Jason Gorman, John Mascola, Lawrence Stewart Shapiro, Lynn Morris, Nicole Amy Doria-Rose, Penelope Linda Moore, Peter Dak Pin Kwong, Salim Safurdeen Abdool Karim