Patents by Inventor Mavis Agbandje-McKenna
Mavis Agbandje-McKenna 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: 20160369298Abstract: Disclosed are compositions and methods for producing modified adeno-associated virus (AAV) cap genes and combinatorial libraries of chimeric AAV vectors and virions; selecting for virions displaying cell-specific tropisms; and, in certain embodiments, producing helper vectors containing one or more modified AAV cap genes. The synthetic combinatorial AAV capsid libraries of the invention are useful in introducing into selected target host cells one or more nucleic acid molecules. The viral vectors and genetic constructs disclosed herein are also useful in a variety of diagnostic and/or therapeutic gene-therapy regimens.Type: ApplicationFiled: September 26, 2014Publication date: December 22, 2016Inventors: Damien Marsic, Sergei Zolotukhin, Mavis Agbandje-McKenna
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Publication number: 20160361439Abstract: Disclosed are capsid-mutated rAAV vectors and methods for their use in gene therapy, and particularly for use in delivering therapeutic transgenes to treat a variety of mammalian diseases and disorders, including dysfunctions and abnormal conditions of the human eye. VP3 capsid proteins comprising a modification of one or more of the surface-exposed tyrosine residues are disclosed, and in particular, VP3 capsid protein comprising tyrosine-to-phenylalanine mutations at positions corresponding to Y444F, Y500F, and Y730F of the wild-type AAV2 sequence. Also provided are rAAV virions and viral particles that comprise such a mutated AAV capsid protein and a nucleic acid molecule that expresses one or more selected therapeutic or reporter transgenes in one or more mammalian cells of interest. Advantageously, the capsid-mutated rAAV vectors and virions disclosed herein afford improved transduction efficiency in a variety of cells, tissues and organs of interest, when compared to their unmodified (i.e.Type: ApplicationFiled: August 24, 2016Publication date: December 15, 2016Inventors: Mavis AGBANDJE-MCKENNA, William W. HAUSWIRTH, Arun SRIVASTAVA, Li ZHONG
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Publication number: 20160333372Abstract: Disclosed are next-generation multi-mutated capsid protein-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using these high transduction efficiency vector constructs in a variety of therapeutic applications including, inter alia, as delivery agents for the treatment or amelioration of one or more diseases or abnormal conditions in an affected mammal using in vivo and/or ex situ viral vector-based gene therapy protocols. Also disclosed are large-scale production methods for the multi-mutated, capsid-modified rAAV expression vectors, viral particles, and infectious virions, as well as use of the disclosed compositions in the manufacture of medicaments for use in a variety of in vitro and/or in vivo therapeutic methodologies.Type: ApplicationFiled: May 21, 2014Publication date: November 17, 2016Applicant: University of Florida Research Foundation, Inc.Inventors: Arun Srivastava, Li Zhong, Sergei Zolotukhin, George Vladimirovich Aslanidi, Mavis Agbandje-McKenna, Kim M. Van Vliet
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Publication number: 20160289275Abstract: A modified adeno-associated virus (AAV) capsid protein comprising at least one non-native amino acid that confers to the modified AAV particles new properties, such as increased transduction efficiency and reduced immunogenicity. These modified AAV proteins and particles are particularly useful for gene therapy and the treatment of various diseases and conditions.Type: ApplicationFiled: April 6, 2016Publication date: October 6, 2016Inventors: John A. Chiorini, Sandra Wainer, Mavis Agbandje-McKenna, Sujata Halder
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Publication number: 20160106865Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.Type: ApplicationFiled: September 8, 2015Publication date: April 21, 2016Applicant: University of Florida Research Foundation, Inc.Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Patent number: 9157098Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.Type: GrantFiled: April 2, 2013Date of Patent: October 13, 2015Assignee: University of Florida Research Foundation, Inc.Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Publication number: 20150133530Abstract: The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.Type: ApplicationFiled: May 15, 2013Publication date: May 14, 2015Applicant: University of Florida Research Foundation, Inc.Inventors: Arun Srivastava, George Vladimirovich Aslanidi, Kim M. Van Vliet, Mavis Agbandje-Mckenna
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Patent number: 9012224Abstract: The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.Type: GrantFiled: January 3, 2011Date of Patent: April 21, 2015Assignees: The University of North Carolina at Chapel Hill, The University of Florida Research FoundationInventors: Dawn E. Bowles, Chengwen Li, Joseph E. Rabinowitz, Josh Grieger, Mavis Agbandje-McKenna, Richard Jude Samulski
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Publication number: 20140341852Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations containing them. Also provided are methods of preparing and using the disclosed capsid-protein-mutated rAAV constructs in a variety of diagnostic and therapeutic modalities, including, inter alia, as mammalian cell-targeting delivery agents, and as human gene therapy vectors. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.Type: ApplicationFiled: March 14, 2014Publication date: November 20, 2014Applicant: University of Florida Research Foundation, Inc.Inventors: Arun Srivastava, George V. Aslanidi, Sergei Zolotukhin, Mavis Agbandje-McKenna, Kim M. Van Vliet, Li Zhong, Lakshmanan Govindasamy
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Patent number: 8802440Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.Type: GrantFiled: March 29, 2013Date of Patent: August 12, 2014Assignee: University of Florida Research Foundation, Inc.Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Publication number: 20140093533Abstract: Various aspects of the invention provide for capsids, parvovirus capsids, hybrid parvovirus capsids, parvovirus vectors, hybrid parvovirus vectors, hybrid parvovirus particles and parvovirus particles containing polypeptides in which the sequence YCDGFYACYMDV (SEQ ID NO: 3) has been substituted into the VP2 loop of the B19 capsid protein. Polypeptides in which the sequence YCDGFYACYMDV (SEQ ID NO: 3) has been substituted into the VP2 loop of the B19 capsid protein are also provided (e.g., SEQ ID NO: 2). Other aspects of the invention provide capsids, parvovirus capsids, hybrid parvovirus capsids, parvovirus vectors, hybrid parvovirus vectors, hybrid parvovirus particles and parvovirus particles containing a polypeptide comprising SEQ ID NO: 2. Also provided in various aspects of the invention are pharmaceutical compositions and methods of delivering therapeutic agents and/or reporter peptides/proteins to target cells.Type: ApplicationFiled: May 18, 2012Publication date: April 3, 2014Applicant: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.Inventors: Kirsten Ariane Kelley Weigel-Van Aken, Mavis Agbandje-McKenna
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Publication number: 20140050701Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using novel capsid-protein-mutated rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more symptoms of disease or abnormal conditions via in situ and/or ex vivo mammalian gene therapy methods. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.Type: ApplicationFiled: May 21, 2013Publication date: February 20, 2014Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Publication number: 20130310443Abstract: The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.Type: ApplicationFiled: March 15, 2013Publication date: November 21, 2013Inventors: ARUN SRIVASTAVA, GEORGE VLADIMIROVICH ASLANIDI, KIM M. VAN VLIET, MAVIS AGBANDJE-MCKENNA
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Patent number: 8445267Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.Type: GrantFiled: April 8, 2008Date of Patent: May 21, 2013Assignee: University of Florida Research Foundation, Inc.Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Publication number: 20110104119Abstract: The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.Type: ApplicationFiled: January 3, 2011Publication date: May 5, 2011Inventors: Dawn E. Bowles, Chengwen Li, Joseph E. Rabinowitz, Josh Grieger, Mavis Agbandje-McKenna, Richard Jude Samulski
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Patent number: 7892809Abstract: The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.Type: GrantFiled: December 15, 2005Date of Patent: February 22, 2011Assignees: The University of North Carolina at Chapel Hill, The University of Florida Research FoundationInventors: Dawn E. Bowles, Chengwen Li, Joseph E. Rabinowitz, Josh Grieger, Mavis Agbandje-McKenna, Richard Jude Samulski
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Publication number: 20100104561Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.Type: ApplicationFiled: April 8, 2008Publication date: April 29, 2010Applicant: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.Inventors: Li Zhong, Sergei Zolotukhin, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Arun Srivastava
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Publication number: 20080269149Abstract: The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.Type: ApplicationFiled: December 15, 2005Publication date: October 30, 2008Inventors: Dawn E. Bowles, Chengwen Li, Joseph E. Rabinowitz, Josh Grieger, Mavis Agbandje-McKenna, Richard Jude Samulski