Abstract: Compositions and methods for treating ocular cancer are provided. The composition is a subconjunctival formulation of nutlin-3 and its analogs. The composition provides for methods of treating ocular cancer, including retinoblastoma. The formulation has high penetration into ocular tissue with low toxicity.
Type:
Application
Filed:
September 27, 2011
Publication date:
May 10, 2012
Applicant:
St. Jude Children's Research Hospital
Inventors:
Michael A. Dyer, Jean-Christophe Marine, Aart Gerrit Jochemsen, R. Kip Guy
Abstract: Two mechanisms are provided for improving the expression of Factor IX in gene therapy vectors. The first is the use of a specific Factor IX polynucleotide coding sequence designed for optimal expression. The second is the use of transcriptional regulatory regions minimized in size so that they can be used to express Factor IX, as well as any other gene of interest, in a size-constrained environment such as in a self complementary gene therapy vector system.
Abstract: Compositions and methods are provided for generating T cells having a regulatory phenotype from conventional T (Tconv) cells. Such compositions and methods include culturing isolated, naïve Tconv cells with an effective amount of interleukin-35 (IL-35) until the cells have the regulatory phenotype. Also provided are methods to treat subject having or susceptible to having various disorders including, for example, immune system disorders with the T cells having the regulatory phenotype.
Abstract: The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.
Type:
Grant
Filed:
June 1, 2005
Date of Patent:
February 28, 2012
Assignees:
Mount Sinai School of Medicine, St. Jude Children's Research Hospital, The United States of America as represented by The Secretary of Agriculture
Inventors:
Peter Palese, Adolfo Garcia-Sastre, Richard J. Webby, Juergen A. Richt, Robert G. Webster, Kelly M. Lager
Abstract: Polynucleotides encoding a mutant human carboxylesterase enzyme and polypeptides encoded by the polynucleotides which are capable of metabolizing a prodrug and inactive metabolites thereof to active drug are provided. Compositions and methods for sensitizing cells to a prodrug agent, inhibiting cell growth, treating drug addiction, and facilitating the metabolism of an organophosphate with this enzyme are also provided. In addition, a screening assay for identification of drugs activated by this enzyme is described.
Type:
Grant
Filed:
February 4, 2011
Date of Patent:
February 28, 2012
Assignees:
St. Jude Children's Research Hospital, The University of North Carolina
Inventors:
Philip M. Potter, Monika Weirdl, Matthew R. Redinbo
Abstract: The present invention relates to novel methods for preferentially activating and expanding NK cells. The methods utilize the stimulatory effects of IL-15 and CD137 ligand to preferentially expand and activate NK cells in a mixed cell culture comprising NK cells.
Abstract: Two mechanisms are provided for improving the expression of Factor IX in gene therapy vectors. The first is the use of a specific Factor IX polynucleotide coding sequence designed for optimal expression. The second is the use of transcriptional regulatory regions minimized in size so that they can be used to express Factor IX, as well as any other gene of interest, in a size-constrained environment such as in a self complementary gene therapy vector system.
Abstract: Compositions and methods for the diagnosis and treatment of a cancer that is resistant to at least one anaplastic lymphoma kinase (ALK) kinase inhibitor are provided herein. The present invention is based on the discovery of mutations within ALK that confer resistance to at least one ALK kinase inhibitor. Polynucleotides and polypeptides having at least one ALK inhibitor resistance mutation are provided and find use in methods and compositions useful in the diagnosis, prognosis, and/or treatment of diseases associated with aberrant ALK activity, more particularly, those that are resistant to at least one ALK kinase inhibitors. Methods and compositions are also provided for the identification of agents that can inhibit the kinase activity and/or reduce the expression level of the ALK resistance mutants.
Type:
Application
Filed:
April 15, 2010
Publication date:
October 20, 2011
Applicant:
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
Inventors:
STEPHAN W. MORRIS, QIN JIANG, Xiaoli Cui, Liquan Xue
Abstract: The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuraminidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus.
Abstract: Two mechanisms are provided for improving the expression of Factor IX in gene therapy vectors. The first is the use of a specific Factor IX polynucleotide coding sequence designed for optimal expression. The second is the use of transcriptional regulatory regions minimized in size so that they can be used to express Factor IX, as well as any other gene of interest, in a size-constrained environment such as in a self complementary gene therapy vector system.
Abstract: The present invention is a method for enhancing recombinant antibody production by co-expressing in a host cell a recombinant antibody and ERp23 protein, which facilitates oxidative folding and stability of the recombinant antibody thereby enhancing production.
Abstract: The present invention relates to novel methods for preferentially activating and expanding NK cells. The methods utilize the stimulatory effects of IL-15 and CD137 ligand to preferentially expand and activate NK cells in a mixed cell culture comprising NK cells.
Abstract: Polynucleotides encoding a mutant human carboxylesterase enzyme and polypeptides encoded by the polynucleotides which are capable of metabolizing a prodrug and inactive metabolites thereof to active drug are provided. Compositions and methods for sensitizing cells to a prodrug agent, inhibiting cell growth, treating drug addiction, and facilitating the metabolism of an organophosphate with this enzyme are also provided. In addition, a screening assay for identification of drugs activated by this enzyme is described.
Type:
Application
Filed:
February 4, 2011
Publication date:
July 7, 2011
Applicants:
St. Jude Children's Research Hospital, The University of North Carolina at Chapel Hill
Inventors:
Philip M. Potter, Monika Weirdl, Matthew R. Redinbo
Abstract: This disclosure relates to amides, aryl sulphonamides, aryl ureas, and ?,?-diketones derivatives useful as carboxylesterase esterase inhibitors. The disclosure is also directed to the use of these compounds as selective human intestinal carboxylesterase inhibitors and insect carboxylesterase inhibitors. The disclosure is also directed to pharmaceutical compositions and pesticide formulations containing these compounds, and to methods for treating or ameliorating the toxic effects following administration of drugs such as cancer therapy drugs, treating or ameliorating the effects of a drug overdose, and to the use of the compounds for increasing the effectiveness of insecticides and pesticides.
Type:
Grant
Filed:
February 15, 2008
Date of Patent:
July 5, 2011
Assignee:
St. Jude Children's Research Hospital
Inventors:
Philip Michael Potter, Janice Louise Hyatt, Christopher Lee Morton, Paul P. Beroza, Komath V. Damoradan
Abstract: The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuraminidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus.
Abstract: The immunogenicity of the influenza virus hemagglutinin (HA) molecule may be increased by substitutions of amino acids in the HA sequence. The substitution of specific HA residues, such as asparagine at position 223 of H5 HA, increase the sensitivity of the hemagglutinin inhibition (HI) assay by altering receptor specificity and/or antibody-antigen binding. HA molecules containing such substitutions will be useful in the development of diagnostic reference viruses and improved influenza vaccines.
Type:
Application
Filed:
December 9, 2010
Publication date:
May 5, 2011
Applicant:
St. Jude Children's Research Hospital
Inventors:
Erich Hoffmann, Aleksandr S. Lipatov, Richard J. Webby, Elena A. Govorkova, Robert G. Webster
Abstract: The present invention includes methods of identifying and/or isolating stem cells based on expression of BCRP. The present invention also describes methods of obtaining and/or using cell populations enriched for stem cells. In addition, methods are provided for diagnosing and/or prognosing leukemia, particularly human acute myelogenous leukemia (AML), through assaying for BCRP expression in leukemic cells.
Abstract: Polynucleotides encoding a mutant human carboxylesterase enzyme and polypeptides encoded by the polynucleotides which are capable of metabolizing a prodrug and inactive metabolites thereof to active drug are provided. Compositions and methods for sensitizing cells to a prodrug agent, inhibiting cell growth, treating drug addiction, and facilitating the metabolism of an organophosphate with this enzyme are also provided. In addition, a screening assay for identification of drugs activated by this enzyme is described.
Type:
Grant
Filed:
June 20, 2007
Date of Patent:
March 15, 2011
Assignees:
St. Jude Children's Research Hospital, The University of North Carolina at Chapel Hill
Inventors:
Philip M. Potter, Monika Weirdl, Matthew R. Redinbo
Abstract: This invention provides isolated nucleic acids encoding polypeptides comprising amino acid sequences of streptococcal matrix adhesion (Ema) polypeptides. The invention provides nucleic acids encoding Group B streptococcal Ema polypeptides EmaA, EmaB, EmaC, EmaD and EmaE. The present invention provides isolated polypeptides comprising amino acid sequences of Group B streptococcal polypeptides EmaA, EmaB, EmaC, EmaD and EmaE, including analogs, variants, mutants, derivatives and fragments thereof. Ema homologous polypeptides from additional bacterial species, including S. pneumoniae, S. pyogenes, E. faecalis and C. diptheriae are also provided. Antibodies to the Ema polypeptides and immunogenic fragments thereof are also provided. The present invention relates to the identification and prevention of infections by virulent forms of streptococci.
Type:
Grant
Filed:
December 7, 2009
Date of Patent:
February 22, 2011
Assignees:
University of Utah Research Foundation, St. Jude Children's Research Hospital
Abstract: A panel of IgG1 human monoclonal antibodies (HMAbs) identified by hemagglutination inhibition (HI) assay has been produced from peripheral B cells of an individual immunized with prototype H5N1 vaccine. Sequence analysis of antibody clones showed three clusters of different HMAbs as represented by HMAbs designated as BF1-1, BF1-19 and BF1-10. BF1-1 and BF1-10 have distinct CDR 1, 2 and 3 regions of both heavy and light chains. BF1-19 has the same heavy chain as BF1-1 but the light chain of BF1-10. Antibody binding affinity, KD, studies showed all three HMAbs ranging from at least about 10?8 to at least about 10?9. In vivo protection studies showed that these antibodies afforded significant protection against infection. These findings demonstrate that the antibodies of the invention are cross-neutralizing and therapeutic.
Type:
Grant
Filed:
June 16, 2008
Date of Patent:
February 1, 2011
Assignees:
The Board of Trustees of the Leland Stanford Junior University, St. Jude Children's Research Hospital
Inventors:
Steven Foung, Zhen-Yong Keck, Richard Webby