Patents Examined by Karen M. Hauda
  • Patent number: 6428782
    Abstract: The present invention features a method of inducing donor-specific tolerance in a host. Tolerogenic treatments of the present invention may be administered to a host prior to transplantation of donor-derived materials. The tolerogenic treatment involves (1) administering an immunosuppressive agent to a host mammal in a non-myeloablative regimen sufficient to decrease, but not necessarily to eliminate, the host mammal's functional T lymphocyte population; (2) infusing donor antigens from a non-syngeneic donor into the host mammal; (3) eliminating those host T lymphocytes responding to the infused donor antigens using a non-myeloablative dose of lymphocytotoxic or tolerizing agent; and (4) administering donor hematopoietic cells to the host mammal. Donor lymphoid cells used for cell therapy of a host mammal can be depleted of host specific immunological reactivity by methods essentially similar to those use for tolerizing a host mammal prior to transplantation.
    Type: Grant
    Filed: December 31, 1998
    Date of Patent: August 6, 2002
    Assignee: Hadasit Medical Research Services and Development Ltd.
    Inventors: Shimon Slavin, Tatyana Prigozhina
  • Patent number: 6365151
    Abstract: A cellular immunogen is provided for immunizing a host against the effects of the product of a target proto-oncogene, where the overexpression of the target proto-oncogene is associated with a malignancy. The cellular immunogen comprises host cells which have been transfected with at least one transgene construct comprising a transgene cognate to the target proto-oncogene and a strong promoter to drive the expression of the transgene in the transfected cells. The transgene encodes a gene product which induces host immunoreactivity to host self-determinants of the product of the target proto-oncogene gene. The transgene may comprise, for example, wild-type or mutant retroviral oncogene DNA cognate to the target proto-oncogene; or wild-type or mutant proto-oncogene DNA of a species different from the host species. The cellular immunogen may be prepared from biopsied host cells, e.g. skin fibroblasts, which are stably or transiently transfected with the transgene construct containing the cognate transgene.
    Type: Grant
    Filed: October 7, 1998
    Date of Patent: April 2, 2002
    Assignee: Philadelphia Health and Educational Corporation
    Inventors: Michael S Halpern, James M England
  • Patent number: 6340673
    Abstract: The present invention relates to methods of treatment of programmed cell death (apoptosis) through the use of the HSV-1 gene &ggr;134.5 or the product of its expression, ICP34.5. The gene and its expression have been demonstrated to be required for HSV-1 neurovirulence, and in particular, to act as an inhibitor of neuronal programmed cell death which allows for viral replication. Use of the gene therapy, or the protein itself, can be expected to result in inhibition of programmed cell death in various neurodegenerative diseases. This invention also relates to novel vectors for gene therapy, including modified herpes virus. Methods are presented for conducting assays for substances capable of mimicing, potentiating or inhibiting the expression of &ggr;134.5 or the activity of ICP34.5. Also, methods are disclosed for the treatment of tumorogenic diseases, including cancer, and for treatment of herpes and other viral infections using inhibitors of &ggr;134.5 expression or ICP34.5 activity.
    Type: Grant
    Filed: April 1, 1999
    Date of Patent: January 22, 2002
    Assignee: Arch Development Corporation
    Inventors: Bernard Roizman, Joany Chou
  • Patent number: 6331525
    Abstract: A molecular complex comprising a gene encoding interferon releasably linked to a conjugate of a nucleic acid binding agent and a ligand which binds to a component on the surface of a cell. In a preferred embodiment, the gene encodes human IFN-&agr;, IFN-&bgr;, or IFN-&ggr;. The complex can be used to obtain targeted expression of interferon in selected cells either in vivo or in vitro.
    Type: Grant
    Filed: August 23, 1999
    Date of Patent: December 18, 2001
    Assignee: The Immune Response Corporation
    Inventors: Henry C. Chiou, Dennis J. Carlo
  • Patent number: 6329347
    Abstract: The present invention relates to a composition and method useful for treating cancer in the urinary bladder. The present invention particularly relates to a composition comprising a Mycobacterium phlei deoxyribonucleic acid (M-DNA)-Mycobacterium phlei cell wall complex (MCC), wherein the M-DNA is preserved and complexed on the Mycobacterium phlei cell wall, and a pharmaceutically acceptable carrier. The MCC composition inhibits proliferation of and induces apoptosis in cancer cells in the urinary bladder and stimulates the responsive cells of the immune system to produce cytokines and reactive oxygen species. Methods of making MCC and methods of using MCC also are disclosed.
    Type: Grant
    Filed: August 5, 1998
    Date of Patent: December 11, 2001
    Assignee: Bioniche Life Sciences Inc.
    Inventors: Nigel C. Phillips, Mario C. Filion
  • Patent number: 6329171
    Abstract: The present invention relates to a newly identified human ubiquitin protease belonging to the family of mammalian deubiquitinating enzymes. The invention also relates to polynucleotides encoding the ubiquitin protease. The invention further relates to methods using the ubiquitin protease polypeptides and polynucleotides as a target for diagnosis and treatment in ubiquitin-mediated or -related disorders. The invention further relates to drug-screening methods using the ubiquitin protease polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the ubiquitin protease polypeptides and polynucleotides. The invention further relates to procedures for producing the ubiquitin protease polypeptides and polynucleotides.
    Type: Grant
    Filed: September 30, 1999
    Date of Patent: December 11, 2001
    Assignee: Millennium Pharmaceuticals, Inc.
    Inventor: Rosana Kapeller-Libermann
  • Patent number: 6326357
    Abstract: The present invention relates to a composition and method useful for stimulating the immune system and for inhibiting proliferation of and inducing apoptosis in responsive cells of an animal. The present invention further relates to a composition comprising a Mycobacterium phlei deoxyribonucleic acid (M-DNA)-Mycobacterium phlei cell wall complex (MCC), wherein the Mycobacterium phlei-DNA is preserved and complexed on the Mycobacterium phlei cell wall, and a pharmaceutically acceptable carrier. MCC stimulates responsive cells of the immune system to produce cytokines and reactive oxygen species and inhibits proliferation of and induces apoptosis in responsive cells, including cancer cells, in an animal. Methods of making MCC and methods of using MCC also are disclosed.
    Type: Grant
    Filed: August 5, 1998
    Date of Patent: December 4, 2001
    Assignee: Bioniche Life Sciences Inc.
    Inventors: Nigel C. Phillips, Mario C. Filion
  • Patent number: 6307122
    Abstract: Immunocompromised or immunosuppressed non-primate chimeric mammalian hosts comprising a neuronal graft in the eye are provided for studying various events associated with humans. Particularly, the chimeric host may have solely human fetal neuronal xenografts or other fetal xenografts with other tissue, where the various tissues may be studied as to their response to a variety of agents, their response to pathogens or other diseased states, or their response to agents for the treatment of the various indications.
    Type: Grant
    Filed: October 23, 1992
    Date of Patent: October 23, 2001
    Inventors: Leon G. Epstein, Manuel Del Cerro, Benjamin M. Blumberg
  • Patent number: 6303331
    Abstract: The invention relates generally to compositions of and methods for obtaining and using a polypeptide other than BCL-2 that affects programmed vertebrate cell death. The invention relates as well to polynucleotides encoding those polypeptides, recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant polypeptides. The invention further provides methods for using the isolated, recombinant polypeptides in assays designed to select and improve substances capable of altering programmed cell death for use in diagnostic, drug design and therapeutic applications.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: October 16, 2001
    Assignees: Arch Development Corporation, The Regent of the University of Michigan
    Inventors: Craig B. Thompson, Lawrence H. Boise, Gabriel Nuñez
  • Patent number: 6299858
    Abstract: The present invention provides methods of screening an agent for activity using teleosts. Methods of screening an agent for angiogenesis activity, toxic activity and an effect cell death activity in teleosts are provided.
    Type: Grant
    Filed: February 22, 1999
    Date of Patent: October 9, 2001
    Assignee: Phylonix Pharmaceuticals, Inc.
    Inventors: George N. Serbedzija, Carlos Semino, Deanna Frost
  • Patent number: 6300129
    Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.
    Type: Grant
    Filed: December 2, 1996
    Date of Patent: October 9, 2001
    Assignee: GenPharm International
    Inventors: Nils Lonberg, Robert M. Kay
  • Patent number: 6297219
    Abstract: A method for the direct in vivo transformation of cells in and surrounding a solid tumor is disclosed. This method is based on the site-specific delivery of proteins to solid tumors and to tissue surrounding the solid tumor by direct injection of a nucleic acid sequence. In particular, this method is directed to site-specific delivery of nucleic acids encoding major histocompatibility proteins, cytokines, and toxins to a solid tumor. This technique provides for the transfer of vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of disease.
    Type: Grant
    Filed: July 8, 1997
    Date of Patent: October 2, 2001
    Assignee: The Regents of the University of Michigan
    Inventors: Elizabeth G. Nabel, Gary J. Nabel
  • Patent number: 6294384
    Abstract: The present invention is directed to an isoform of the p53 tumor suppressor and to polynucleotides that encode this isoform. The isoform may be used as a marker to indicate that cardiac cells have experienced hypoxia, as would occur during a myocardial infarction. In addition, vectors encoding the isoform may be transfected into cells as a means of regulating proliferation.
    Type: Grant
    Filed: October 7, 1999
    Date of Patent: September 25, 2001
    Assignee: The Brigham and Women's Hospital Inc.
    Inventors: Giorgio Dell'Acqua, Michael J. Mann, Victor J. Dzau
  • Patent number: 6284880
    Abstract: The toxicity problems which occur when foreign material is introduced into higher eukaryotic cells, particularly during transfection with DNA, are countered by causing gene products to be expressed in the cell, which block the apoptosis triggered by the transfection process, and/or by treating the cells with anti-inflammatory substances. Preferably, Bcl-2, E1B 19K or an anti-apoptotically active gene of chicken adenovirus CELO is used as the anti-apoptosis gene whilst the inflammatory substance used is adenovirus VA1, which is introduced into the cell in the form of VA1-DNA. Using these methods, long-lasting gene expression can be achieved.
    Type: Grant
    Filed: February 14, 1997
    Date of Patent: September 4, 2001
    Assignee: Boehringer Ingelheim International GmbH
    Inventors: Matthew Cotten, Adam Baker, Susanna Chiocca
  • Patent number: 6284740
    Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.
    Type: Grant
    Filed: November 18, 1997
    Date of Patent: September 4, 2001
    Assignee: Amgen Inc.
    Inventors: William J. Boyle, David L. Lacey, Frank J. Calzone, Ming-Shi Chang
  • Patent number: 6284742
    Abstract: A gene delivery vector used to generate genetically modified dendritic cells and B-cells central to the immune system. As a result, genetic modification of cells bearing the CD40 target antigen on its surface can be used to modulate immunity. Previously, both dendritic cells and B-cells have been resistant to gene transfer. The present invention serves to mediate dramatic enhancements in gene transfer to these cell types. Simultaneous with gene transfer, the vector system described herein matures dendritic cells and B-cells to a more potent immunoregulatory status. This invention provides technology for genetic manipulation of dendritic cells and B-cells.
    Type: Grant
    Filed: September 28, 1999
    Date of Patent: September 4, 2001
    Assignee: UAB Research Foundation
    Inventors: David T. Curiel, Bryan Walter Tillman
  • Patent number: 6284540
    Abstract: A novel growth factor, artemin, which belongs to the GDNF/neurturin/persephin family of growth factors, is disclosed. The human and mouse amino sequences have been identified. Human and mouse artemin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using artemin, methods for detecting artemin gene alterations and methods for detecting and monitoring patient levels of artemin are provided.
    Type: Grant
    Filed: December 24, 1998
    Date of Patent: September 4, 2001
    Assignee: Washington University
    Inventors: Jeffrey D. Milbrandt, Robert H. Baloh
  • Patent number: 6277594
    Abstract: A neurogenesis inducing gene coding for the following protein (a) or (b): (a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2 (b) a protein which consists of the amino acid sequence shown in SEQ ID NO: 2 having deletion, substitution or addition of at least one amino acid and which has neurogenesis inducing activity.
    Type: Grant
    Filed: September 28, 1998
    Date of Patent: August 21, 2001
    Assignee: The Institute of Physical and Chemical Research
    Inventors: Katsuhiko Mikoshiba, Jun Aruga, Takeharu Nagai, Katsunori Nakata
  • Patent number: 6274788
    Abstract: The present invention relates to a bicistronic DNA construct comprising X-myc transgene. In particular, the present invention relates to a bicistronic X15-myc transgene capable of expressing truncated X protein and a full-length murine c-myc protein. More particularly, the present invention relates to a bicistronic DNA construct being an X15-myc transgene for use in the production of transgenic animal model systems for human hepatocellular carcinoma and transgenic animal model systems so produced. The invention is based partially on the discovery that in susceptible transgenic mice that carry a bicistronic X-myc transgene there is an accelerated formation of liver tumors involving all lobes.
    Type: Grant
    Filed: February 2, 1999
    Date of Patent: August 14, 2001
    Assignees: International Centre for Genetic Engineering and Biotechnology, National Institute of Immunology
    Inventors: Vjay Kumar, Mahavir Singh, Satish Totey, Rajesh Anand
  • Patent number: 6274338
    Abstract: Isolated nucleic acid molecules encoding human c-Maf, and isolated c-Maf proteins, are provided. The invention further provides antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals carrying a human c-Maf transgene. The invention further provides human c-Maf fusion proteins and anti-human c-Maf antibodies. Methods of using the human c-maf compositions of the invention are also disclosed, including methods for detecting human c-Maf activity in a biological sample, methods of modulating human c-Maf activity in a cell, and methods for identifying agents that modulate the activity of human c-Maf.
    Type: Grant
    Filed: May 27, 1998
    Date of Patent: August 14, 2001
    Assignee: President and Fellows of Harvard College
    Inventors: Laurie H. Glimcher, John Douhan, III