Patents by Inventor Richard Jude Samulski

Richard Jude Samulski 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).

  • Publication number: 20030211614
    Abstract: The present invention relates to methods and compositions for increasing the production of high titre stocks of recombinant AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins. The methods and compositions of the invention are based on the observation that the low level expression of the AAV REP protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titre recombinant viral stocks. The invention encompasses recombinant AAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of novel stable cell lines capable of generating high titre rAAV vectors. The invention provides methods for regulating the expression of the AAV REP gene at the transcriptional and post-translational level.
    Type: Application
    Filed: September 30, 2002
    Publication date: November 13, 2003
    Applicants: The University of North Carolina at Chapel Hill, Cell Genesys, Inc.
    Inventors: Richard Jude Samulski, Xiao Xiao, Richard Snyder
  • Patent number: 6627617
    Abstract: The present invention provides temperature-sensitive (ts) adeno-associated virus (AAV) Rep78 and Rep68 proteins. In preferred embodiments, the ts AAV Rep78 and Rep68 proteins have missense mutations at amino acid positions 40, 42 and 44 that confer a temperature-sensitive phenotype. Also provided are nucleotide sequences and vectors encoding the inventive ts Rep proteins. In preferred embodiments, a hybrid adenovirus vector is provided that stably comprises a nucleotide sequence encoding a ts AAV Rep protein according to the invention. The present invention also provides methods of packaging AAV vectors and methods of ex vivo gene delivery using the ts Rep proteins of the invention. Further provided are cells containing the ts AAV Rep proteins, preferably stably integrated into the genome of the cell.
    Type: Grant
    Filed: September 29, 2000
    Date of Patent: September 30, 2003
    Assignee: University of North Carolina at Chapel Hill
    Inventors: Richard Jude Samulski, Denise Gavin, Nicholas Muzyczka, Corinne Abernathy, Daniel Pereira
  • Patent number: 6548286
    Abstract: The present invention relates to methods and compositions for increasing the production of high titre stocks of recombinant AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins. The methods and compositions of the invention are based on the observation that the low level expression of the AAV REP protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titre recombinant viral stocks. The invention encompasses recombinant AAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of novel stable cell lines capable of generating high titre rAAV vectors. The invention provides methods for regulating the expression of the AAV REP gene at the transcriptional and post-translational level.
    Type: Grant
    Filed: April 14, 1998
    Date of Patent: April 15, 2003
    Assignees: Cell Genesys, Inc., The University of North Carolina at Chapel Hill
    Inventors: Richard Jude Samulski, Xiao Xiao, Richard Snyder
  • Publication number: 20030053990
    Abstract: The present invention provides genetically-engineered parvovirus capsids and viruses designed to introduce a heterologous gene into a target cell. The parvoviruses of the invention provide a repertoire of vectors with altered antigenic properties, packaging capabilities, and/or cellular tropisms as compared with current AAV vectors.
    Type: Application
    Filed: July 26, 2002
    Publication date: March 20, 2003
    Applicant: University of North Carolina at Chapel Hill
    Inventors: Joseph E. Rabinowitz, Richard Jude Samulski, Weidong Xiao
  • Publication number: 20030032176
    Abstract: The present invention relates to a method for producing helper-free stocks of recombinant adeno-associated virus (rAAV) which can be used to efficiently and stably transduce foreign genes into host cells or organisms. The method comprises the cotransfection of eukaryotic cells with rAAV and with helper AAV DNA in the presence of helper virus (e.g. adenovirus or herpesvirus) such that the helper AAV DNA is not associated with virion formation. The crux of the invention lies in the inability of the helper AAV DNA to recombine with rAAV vector, thereby preventing the generation of wild-type virus.
    Type: Application
    Filed: September 24, 2002
    Publication date: February 13, 2003
    Applicant: THE TRUSTEES OF PRINCETON UNIVERSITY
    Inventors: Thomas E. Shenk, Richard Jude Samulski, Long-Sheng Chang
  • Publication number: 20030013197
    Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.
    Type: Application
    Filed: August 16, 2002
    Publication date: January 16, 2003
    Inventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
  • Patent number: 6491907
    Abstract: The present invention provides genetically-engineered parvovirus capsids and viruses designed to introduce a heterologous gene into a target cell. The parvoviruses of the invention provide a repertoire of vectors with altered antigenic properties, packaging capabilities, and/or cellular tropisms as compared with current AAV vectors.
    Type: Grant
    Filed: November 10, 1999
    Date of Patent: December 10, 2002
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: Joseph E. Rabinowitz, Richard Jude Samulski, Weidong Xiao
  • Patent number: 6489162
    Abstract: The present invention relates to a method for producing helper-free stocks of recombinant adeno-associated virus (rAAV) which can be used to efficiently and stably transduce foreign genes into host cells or organisms. The method comprises the cotransfection of eukaryotic cells with rAAV and with helper AAV DNA in the presence of helper virus (e.g. adenovirus or herpesvirus) such that the helper AAV DNA is not associated with virion formation. The crux of the invention lies in the inubility of the helper AAV DNA to recombine with rAAV vector, thereby preventing the generation of wild-type virus. In a specific embodiment of the invention, the vector comprises a recombinant AAV genome containing only the terminal regions of the AAV chromosome bracketing a non-viral gene, and the helper AAV DNA comprises a recombinant AAV genome containing that part of the AAV genome which is not present in the vector, and in which the AAV terminal regions are replaced by adenovirus sequences.
    Type: Grant
    Filed: February 19, 1998
    Date of Patent: December 3, 2002
    Assignee: The Trustees of Princeton University
    Inventors: Thomas E. Shenk, Richard Jude Samulski, Long-Sheng Chang
  • Patent number: 6458587
    Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.
    Type: Grant
    Filed: March 21, 2001
    Date of Patent: October 1, 2002
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
  • Publication number: 20020136710
    Abstract: Primary receptors and co-receptors for adeno-associated virus (AAV) attachment to and infection of target cells are described. Such receptors can be used to facilitate AAV attachment to and infection of cells, e.g., for gene therapy. Methods for purification and/or concentration of AAV are also described. Methods of facilitating or enhancing AAV infection of a cell are also provided. Also described are methods of inhibiting or preventing infection of AAV into a cell. Cell samples may be screened for permissiveness for AAV attachment and infection by detecting the presence or abundance of cellular receptors that mediate attachment and/or infection of AAV into the cell. Formulations and kits for mediating AAV attachment to, and infection of, cells are also provided herein.
    Type: Application
    Filed: March 20, 2002
    Publication date: September 26, 2002
    Applicant: The University
    Inventors: Richard Jude Samulski, Candace Summerford
  • Patent number: 6410300
    Abstract: Primary receptors and co-receptors for adeno-associated virus (AAV) attachment to and infection of target cells are described. Such receptors can be used to facilitate AAV attachment to and infection of cells, e.g., for gene therapy. Methods for purification and/or concentration of AAV are also described. Methods of facilitating or enhancing AAV infection of a cell are also provided. Also described are methods of inhibiting or preventing infection of AAV into a cell. Cell samples may be screened for permissiveness for AAV attachment and infection by detecting the presence or abundance of cellular receptors that mediate attachment and/or infection of AAV into the cell. Formulations and kits for mediating AAV attachment to, and infection of, cells are also provided herein.
    Type: Grant
    Filed: January 11, 1999
    Date of Patent: June 25, 2002
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: Richard Jude Samulski, Candace Summerford
  • Publication number: 20010039044
    Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.
    Type: Application
    Filed: March 21, 2001
    Publication date: November 8, 2001
    Inventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
  • Publication number: 20010016355
    Abstract: The invention relates to the production of AAV capsids which may be used to transfer native or heterologous molecules into appropriate host cells. The capsid proteins can be expressed from a recombinant virus, expression vector, or from a cell line that has stably integrated the AAV capsid genes or coding sequences. The invention further provides for the production of AAV capsids in vitro from the AAV capsid proteins and the construction of packaged capsids in vitro. The invention further provides for the production of AAV capsids that have been genetically engineered to express heterologous epitopes of clinically important antigens to elicit an immune response.
    Type: Application
    Filed: December 22, 2000
    Publication date: August 23, 2001
    Applicant: University of Pittsburgh
    Inventors: Richard Jude Samulski, Forrest K. Ferrari
  • Patent number: 6268213
    Abstract: The subject invention concerns a recombinant adeno-associated virus vector characterized as being capable of delivering and expressing at least one mammalian gene into a genome of a mammalian host cell such that the expression of the gene is regulated in a tissue specific manner by cis-acting regulatory and promoter elements of the gene. A method of using this recombinant adeno-associated virus vector for therapeutic purposes is also provided.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 31, 2001
    Inventors: Richard Jude Samulski, Christopher E. Walsh, Arthur W. Nienhuis, Johnson M. Liu, Jeffrey L. Miller
  • Patent number: 6204059
    Abstract: The invention relates to the production of AAV capsids which may be used to transfer native or heterologous molecules into appropriate host cells. The capsid proteins can be expressed from a recombinant virus, expression vector, or from a cell line that has stably integrated the AAV capsid genes or coding sequences. The invention further provides for the production of AAV capsids in vitro from the AAV capsid proteins and the construction of packaged capsids in vitro. The invention further provides for the production of AAV capsids that have been genetically engineered to express heterologous epitopes of clinically important antigens to elicit an immune response.
    Type: Grant
    Filed: June 30, 1994
    Date of Patent: March 20, 2001
    Assignee: University of Pittsburgh
    Inventors: Richard Jude Samulski, Forrest K. Ferrari
  • Patent number: 6093570
    Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 25, 2000
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
  • Patent number: 6057152
    Abstract: The present invention relates to a system for replication and encapsidation of recombinant DNA fragments into virus particles comprised of adenovirus associated viral (AAV) capsid proteins. The invention provides an means of obtaining recombinant viral stocks that may be used to treat patients suffering from genetic diseases.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: May 2, 2000
    Assignee: University of Pittsburgh
    Inventors: Richard Jude Samulski, Xiao Xiao
  • Patent number: 6040183
    Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: March 21, 2000
    Assignee: University of North Carloina at Chapel Hill
    Inventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
  • Patent number: 5869305
    Abstract: The present invention relates to a system for replication and encapsidation of recombinant DNA fragments into virus particles comprised of adenovirus associated viral (AAV) capsid proteins. The invention provides a means of obtaining recombinant viral stocks that may be used to treat patients suffering from genetic diseases.
    Type: Grant
    Filed: May 15, 1995
    Date of Patent: February 9, 1999
    Assignee: The University of Pittsburgh
    Inventors: Richard Jude Samulski, Xiao Xiao
  • Patent number: 5863541
    Abstract: The invention relates to the production of AAV capsids which may be used to transfer native or heterologous molecules into appropriate host cells. The capsid proteins can be expressed from a recombinant virus, expression vector, or from a cell line that has stably integrated the AAV capsid genes or coding sequences. The invention further provides for the production of AAV capsids in vitro from the AAV capsid proteins and the construction of packaged capsids in vitro. The invention further provides for the production of AAV capsids that have been genetically engineered to express heterologous epitopes of clinically important antigens to elicit an immune response.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: January 26, 1999
    Assignee: University of Pittsburgh
    Inventors: Richard Jude Samulski, Forrest K. Ferrari