Abstract: The present invention provides novel rotavirus reassortants, vaccines employing the novel reassortants and methods for their preparation and administration. One such reassortant contains the gene encoding the v.p.7 neutralization antigen of a human rotavirus. Another reassortant contains the gene encoding the v.p.4 neutralization antigen of a human rotavirus. The remaining genes are provided solely from the bovine rotavirus WC3 strain, or from both the human and bovine strains.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
May 12, 1998
Assignees:
The Wistar Institute of Anatomy & Biology, The Children's Hospital of Philadelphia
Inventors:
H. Fred Clark, Paul Offit, Stanley A. Plotkin
Abstract: Improved vaccine compositions and methods of making same are provided, which vaccines are characterized by an antigen from a pathogen and an effective adjuvanting amount of Interleukin-12. These IL-12 adjuvanted vaccines are capable of increasing the vaccinated host's cell mediated immune response to provide an increased and protective immune response to the pathogen. Also disclosed are methods for vaccinating hosts by administering a vaccine containing an antigen from a pathogenic microorganism and co-administering an adjuvanting amount of IL-12. Vaccines or therapeutic compositions directed against a cancer may also be adjuvanted with IL-12 according to this invention.
Type:
Grant
Filed:
March 25, 1996
Date of Patent:
March 3, 1998
Assignees:
The Trustees of the University of Pennsylvania, The Wistar Institute of Anatomy & Biology
Abstract: A partial murine cDNA clone, a human cDNA clone, and a partial human genomic clone, each encoding a Box-dependent myc-interacting polypeptide termed Bin1, are provided. Also provided are methods of using the nucleic acid sequences, polypeptides, and antibodies directed against same in the diagnosis and treatment of cancers and hyperplastic disease states.
Type:
Grant
Filed:
May 24, 1996
Date of Patent:
March 3, 1998
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
George C. Prendergast, Daitoku Sakamuro
Abstract: The present invention provides p53 proteins with altered tetramerization domains that retain wild-type p53 function, and the ability to form tetramers and have at least one of the following characteristics: (1) do not hetero-oligomerize with wild-type p53 or tumor-derived p53 mutants, and (2) restricted DNA binding specificity from an alteration in the way that the tetramerization domain orients the DNA binding domains of a p53 tetramer relative to one another. The invention also provides nucleic acids encoding the above proteins and methods of enhancing the cellular response to DNA damaging agents, treating diseases characterized by abnormal cell proliferation, and inducing immune tolerance to facilitate transplants and treatment of autoimmune disease, by administration of proteins of the invention or nucleic acid sequences encoding the proteins of the invention.
Type:
Grant
Filed:
April 28, 1995
Date of Patent:
February 24, 1998
Assignee:
The Wistar Institute of Anatomy & Biology
Abstract: The present invention provides compositions and methods for targeting recombinant retroviral particles specifically to cells of interest for delivery of desired therapeutic or toxic agents. The invention provides chimeric nucleotide constructs, chimeric proteins formed of a selected viral envelope gene from which a selected sequence has been deleted and into which has been inserted all or an effective portion of a heterologous ligand, said ligand or portion thereof capable of binding to a selected receptor, recombinant viral particles formed of the chimeric proteins, a biological mediator for delivery to the target cell; and retroviral gag and pol proteins. The lack of retroviral nucleic acid renders the viral particle replication defective and non-pathogenic.
Type:
Grant
Filed:
November 4, 1993
Date of Patent:
February 3, 1998
Assignees:
The Wistar Institute of Anatomy & Biology, The Trustees of the University of Pennsylvania
Inventors:
David Weiner, William Williams, David N. Levy
Abstract: The invention provides a modified human cytotoxic T cell line, which is characterized by dual activity in vitro and in vivo against malignant cells and virus-infected cells. Also provided are effective and safe methods for use of the modified cells in adoptive therapy of cancer and untreatable vital diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the cytokine stimulated, irradiated TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine and feline malignancies.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
December 30, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Daniela Santoli, Giovanni Rovera, Alessandra Cesano
Abstract: A method of vaccinating a human or animal against rabies is provided by administering a replication defective recombinant adenovirus containing a complete deletion of its E1 gene and at least a partial deletion of its E3 gene, said virus containing in the site of the E1 deletion a sequence comprising a non-adenovirus promoter directing the replication and expression of DNA encoding a rabies virus G protein, which, when administered to the animal or human in said recombinant virus, elicits a substantially complete protective immune response against rabies virus.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
December 16, 1997
Assignees:
The Wistar Institute of Anatomy & Biology, The Trustees of the University of Pennsylvania
Abstract: The present invention provides a novel monoclonal antibody, mAb C1.7, and its antigenic receptor, p38, which is an NK cell and CD8.sup.+ T cell activating structure. Methods of using these compositions to identify and monitor the course of a disease, as well as for therapeutic purposes, are disclosed.
Type:
Grant
Filed:
September 16, 1994
Date of Patent:
November 18, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Nicholas M. Valiante, Giorgio Trinchieri
Abstract: The invention provides a modified human cytotoxic T cell line TALL-104, which is characterized by dual activity in vitro and in vivo against tumor cells and virus-infected cells. Also provided are effective and safe methods for use of the modified TALL-104 cells in adoptive therapy of cancer and untreatable viral diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the modified TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine lymphoma and feline leukemias.
Type:
Grant
Filed:
January 18, 1995
Date of Patent:
November 4, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Daniela Santoli, Giovanni Rovera, Alessandra Cesano
Abstract: The present invention provides novel human polynucleotide sequences and the recombinant human DRADA proteins encoded thereby and methods of use thereof.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
October 14, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Abstract: Methods of determining whether a tumor is an alveolar rhabdomyosarcoma tumor by detecting the presence of a DNA sequence of a chimeric gene that is generated by translocation of a portion of human chromosome 2 and a portion of human chromosome 13 are disclosed. In addition, diagnostic kits to practice methods of determining whether a tumor is an alveolar rhabdomyosarcoma tumor are disclosed. Isolated nucleic acid molecules which comprise nucleotide sequences that are complementary to at least a portion of human chromosome 2 or a portion of human chromosome 13 are disclosed.
Type:
Grant
Filed:
October 25, 1994
Date of Patent:
July 22, 1997
Assignees:
Children's Hospital of Philadelphia, Trustees of The University of Pennsylvania, The Wistar Institute of Anatomy and Biology
Inventors:
Frederic G. Barr, Beverly S. Emanuel, Naomi Galili
Abstract: The present invention provides novel human polynucleotide sequences and the recombinant human double-stranded RNA adenosine deaminase enzyme (DRADA) proteins encoded thereby and methods of use thereof.
Type:
Grant
Filed:
July 25, 1994
Date of Patent:
July 1, 1997
Assignee:
The Wistar Institute of Anatomy & Biology
Abstract: The present invention provides three unique monoclonal antibodies directed against a portion of the Wilms' tumor antigen, and methods of use therefor in detecting, monitoring and diagnosing malignancies characterized by over-expression or inappropriate expression of the WT 1 protein.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
May 27, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Meenhard Herlyn, Jennifer Morris, Frank J. Rauscher, III, Ulrich Rodeck
Abstract: The present invention provides novel rotavirus reassortants, vaccines employing the novel reassortants and methods for their preparation and administration. One such reassortant contains the gene encoding the v.p.7 neutralization antigen of a human rotavirus. Another reassortant contains the gene encoding the v.p.4 neutralization antigen of a human rotavirus. The remaining genes are provided solely from the bovine rotavirus WC3 strain, or from both the human and bovine strains.
Type:
Grant
Filed:
December 9, 1994
Date of Patent:
May 6, 1997
Assignees:
The Wistar Institute of Anatomy and Biology, The Children's Hospital of Philadelphia
Inventors:
H. Fred Clark, Paul Offit, Stanley A. Plotkin
Abstract: Three unique monoclonal antibodies, each having an epitope located in amino acids 1-181 of the WT1 tumor protein, and the hybridomas which secrete them have been constructed. These monoclonal antibodies are useful in the detection, monitoring, and diagnosis of malignancies characterized by inappropriate expression of the WT1 protein.
Type:
Grant
Filed:
April 28, 1994
Date of Patent:
April 22, 1997
Assignee:
The Wistar Institute of Anatomy & Biology
Inventors:
Meenhard Herlyn, Jennifer Morris, Frank J. Rauscher, III, Ulrich Rodeck
Abstract: The present invention refers generally to a novel human cytopathic rotavirus of serotype 3 (HCR3A) and to its use as a vehicle for the expression of human rotavirus genes. The invention also relates to novel rotavirus reassortants, vaccines employing the novel rotavirus and its reassortants and methods for their preparation and administration.
Type:
Grant
Filed:
May 1, 1991
Date of Patent:
March 11, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Abstract: A partial murine cDNA clone and a human cDNA clone, each encoding a c-Myc interacting polypeptide termed MIP-99, are provided. Also provided are methods of using the nucleic acid sequences, polypeptides, and antibodies directed against same in the diagnosis and treatment of cancers and hyperplastic disease states.
Type:
Grant
Filed:
May 5, 1995
Date of Patent:
February 25, 1997
Assignee:
The Wistar Institute of Anatomy & Biology
Inventors:
George C. Prendergast, Daitoku Sakamuro
Abstract: The present invention provides a non-defective adenovirus recombinant expression system for the expression of the HCMV gB subunit and for the expression of non-structural immediate-early exon 4 proteins, said recombinant HCMV-expressing adenovirus being useful as a vaccine.
Type:
Grant
Filed:
April 21, 1995
Date of Patent:
January 7, 1997
Assignee:
The Wistar Institute of Anatomy and Biology
Inventors:
Stanley A. Plotkin, Robert P. Ricciardi, Ewa Gonczol
Abstract: A recombinant antibody capable of binding to two different antigenic sites, contains Fab fragments from the same or, preferably, different antibodies, which are brought into association by complementary interactive domains which have been inserted into a region of the antibody heavy chain constant region.
Type:
Grant
Filed:
May 27, 1994
Date of Patent:
December 10, 1996
Assignee:
The Wistar Institute of Anatomy & Biology
Abstract: The present invention provides p53 proteins with altered tetramerization domains that retain wild-type p53 function, and the ability to form tetramers and have at least one of the following characteristics: (1) do not hetero-oligomerize with wild-type p53 or tumor-derived p53 mutants, and (2) restricted DNA binding specificity from an alteration in the way that the tetramerization domain orients the DNA binding domains of a p53 tetramer relative to one another. The invention also provides nucleic acids encoding the above proteins and methods of enhancing the cellular response to DNA damaging agents, treating diseases characterized by abnormal cell proliferation, and inducing immune tolerance to facilitate transplants and treatment of autoimmune disease, by administration of proteins of the invention or nucleic acid sequences encoding the proteins of the invention.
Type:
Grant
Filed:
November 28, 1994
Date of Patent:
November 12, 1996
Assignee:
The Wistar Institute of Anatomy and Biology