Abstract: The present invention relates to isolated immunogenic polypeptides and their use. In one aspect, the isolated immunogenic polypeptide includes a scaffold polypeptide having a hairpin loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond. The scaffold polypeptide directs self-assembly with two other of the scaffold polypeptides to form a trimeric structure, which constrains the one or more epitopes to a conformation that is (i) substantially similar to one or more native pathogen epitopes in trimeric conformation and (ii) capable of binding an antibody reactive to the one or more native pathogen epitopes in trimeric conformation. Another aspect relates to an isolated immunogenic polypeptide that includes a scaffold polypeptide having a native loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond.
Type:
Grant
Filed:
September 5, 2017
Date of Patent:
February 25, 2020
Assignees:
New York University, Molsoft LLC, Icahn School of Medicine at Mount Sinai
Inventors:
Maxim Totrov, Xunqing Jiang, Ruimin Pan, Susan Zolla-Pazner, Xiangpeng Kong
Abstract: The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.
Type:
Grant
Filed:
September 28, 2011
Date of Patent:
January 3, 2017
Assignees:
New York University, University of Massachusetts, Molsoft LLC
Abstract: Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely related E. coli enterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.
Type:
Grant
Filed:
August 20, 2008
Date of Patent:
February 24, 2015
Assignees:
New York University, Molsoft LLC, University of Massachusetts
Inventors:
Susan Zolla-Pazner, Miroslaw K. Gorny, Timothy J. Cardozo, Xiang-peng Kong, Ruben Abagyan, Maxim Totrov, Shan Lu, Abraham Pinter
Abstract: The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.
Type:
Application
Filed:
September 28, 2011
Publication date:
October 31, 2013
Applicants:
NEW YORK UNIVERSITY, UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY, UNIVERSITY OF MASSACHUSETTS, MOLSOFT LLC
Inventors:
Timothy Cardozo, Xian-peng Kong, Susan Zolla-Pazner, Abraham Pinter, Chavdar Krachmarov, Shan Lu, Shixia Wang, Maxim Totrov
Abstract: A method of identification of compounds that modulate thyroid hormone activity, and the use of such compounds and compositions thereof for such purposes are disclosed. The compounds may be selected from the group consisting of: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of conditions that are causally related to aberrant thyroid hormone activity, such as hyperthyroidism and thyrotoxicosis.
Type:
Grant
Filed:
April 18, 2008
Date of Patent:
March 12, 2013
Assignees:
Molsoft LLC, New York University School of Medicine
Inventors:
Herbert H. Samuels, Ruben Abagyan, Matthieu Schapira, Maxim Totrov, Bruce M. Raaka, Stephen R. Wilson, Li Fan, Zhiguo Zhou
Abstract: A structured document file which includes graphical and non graphical information. The graphical information includes the vector and coordinate description of a representation of at least one three dimensional object and at least one of the following group of view attributes or features: rotation, translation, view angle, lighting, colors, specific graphical representations, labels and parameters. The vector and coordinate description are stored with or independently from the one or more view attributes or features and the vector and coordinate description and the one or more view attributes are stored in a single file which can be accessed and viewed by a structured document viewer. Related authoring tools and viewers are also disclosed.
Type:
Application
Filed:
December 28, 2010
Publication date:
April 28, 2011
Applicant:
MOLSOFT LLC
Inventors:
Ruben ABAGYAN, Eugene RAUSH, Maxmin TOTROV, Levon BUDAGYAN, Andrew J. W. Orry
Abstract: A structured document file which includes graphical and non graphical information. The graphical information includes the vector and coordinate description of a representation of at least one three dimensional object and at least one of the following group of view attributes or features: rotation, translation, view angle, lighting, colors, specific graphical representations, labels and parameters. The vector and coordinate description are stored with or independently from the one or more view attributes or features and the vector and coordinate description and the one or more view attributes are stored in a single file which can be accessed and viewed by a structured document viewer. Related authoring tools and viewers are also disclosed.
Type:
Grant
Filed:
July 14, 2006
Date of Patent:
February 1, 2011
Assignee:
Molsoft LLC
Inventors:
Ruben Abagyan, Eugene Raush, Maxim Totrov, Levon Budagyan, Andrew J. W. Orry
Abstract: Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely related E. coli enterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.
Type:
Application
Filed:
August 20, 2008
Publication date:
April 16, 2009
Applicants:
New York University, Molsoft LLC, University of Massachusetts, University of Medicine and Dentistry of New Jersey
Inventors:
Susan ZOLLA-PAZNER, Miroslaw K. Gorny, Timothy J. Cardozo, Xiang-peng Kong, Ruben Abagyan, Maxim Totrov, Shan Lu, Abraham Pinter
Abstract: A structured document file which includes graphical and non graphical information. The graphical information includes the vector and coordinate description of a representation of at least one three dimensional object and at least one of the following group of view attributes or features: rotation, translation, view angle, lighting, colors, specific graphical representations, labels and parameters. The vector and coordinate description are stored with or independently from the one or more view attributes or features and the vector and coordinate description and the one or more view attributes are stored in a single file which can be accessed and viewed by a structured document viewer. Related authoring tools and viewers are also disclosed.