Abstract: The invention relates to a transgenic non-human mammal whose cells express a constitutively active oncogenic mutant of the kinase-domain of the Raf-1 gene or a protein coded by a corresponding normal allele or derivative of the A, B or c-Raf-1 gene.
Abstract: A human keratinocyte cell line immortalized by at least one functional tumor gene of DNA viral origin characterized in that it is: (1) non-tumorigenic, (2) conserves the capacity for differentiation and for the expression of proteins and of enzymes expressed by normal differentiated keratinocytes even after an elevated number of passages in culture; and (3) forms a stratified and polarized epithelium having a stratum corneum ortho-keratinocyte, if cultivated in an organo-typical culture in a medium without serum and without a layer of nourishing cells. An improved process to immortalize human skin cells to obtain immortalized keratinocytes. Also, the use of keratinocytes for immunological, pharmacological, photo- and chemical-toxicological analyzes of skin reaction and for expression of heterologous genes and for the construction of artificial skin.
Abstract: Secretory gland cells, particularly pancreatic and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.
Type:
Grant
Filed:
January 4, 2001
Date of Patent:
May 20, 2003
Assignee:
The Regents of the University of California
Inventors:
Michael German, Ira D. Goldfine, Stephen S. Rothman
Abstract: The present invention relates to DNA constructs that alter the expression of a targeted gene in a cell when the DNA construct is homologously recombined with a target site within the chromosomal DNA of the cell, as well as to a cell into which has been incorporated a new transcription unit containing an exogenous regulatory sequence operatively linked to an endogenous gene of the cell's chromosomal DNA. These constructs and cells can be used in a method of altering expression of the targeted gene.
Type:
Grant
Filed:
May 14, 1999
Date of Patent:
May 20, 2003
Assignee:
Transkaryotic Therapies, Inc.
Inventors:
Douglas Treco, Michael W. Heartlein, Richard F Selden
Abstract: The present invention relates to a method for implanting producer cells into the mammalian brain. The producer cells are engineered with a retroviral based recombinant vector encoding a tumorcidal factor or susceptibility factor that confers on tumor cells sensitivity to chemotherapeutic or radiotherapeutic agents. Prior to transplantation into the mammalian brain, the producer cells are first cultured in vitro on a support matrix to increase the long-term viability of the transplanted cells and to provide long-term functional benefit.
Type:
Grant
Filed:
December 4, 2000
Date of Patent:
May 20, 2003
Assignees:
Titan Pharmaceuticals, Inc., New York University Medical Center
Abstract: Substantially purified stable human hypoxia-inducible factor-1&agr; (sHIF-1alpha) proteins and polynucleotides encoding stable human hypoxia-inducible factor-1&agr; proteins are provided. A method is provided for treating a hypoxia-related tissue damage in a subject by administering to the subject a therapeutically effective amount of a sHIF-1alpha protein or a nucleic acid encoding a stable HIF-1alpha protein. Formulations are provided for the administration of stable human hypoxia inducible factor-1&agr; (HIF-1alpha) polypeptide or a polynucleotide encoding stable human hypoxia inducible factor-1alpha (HIF-1alpha) to a patient having or at risk of having hypoxia- or ischemia-related tissue damage.
Type:
Grant
Filed:
August 25, 1999
Date of Patent:
May 13, 2003
Assignee:
The Johns Hopkins University School of Medicine
Abstract: This invention provides a novel purified mammalian protein designated FADD having the ability to bind the cytoplasmic region or domain of the Fas receptor. Also provided are nucleic acid molecules that encode the mammalian protein which binds the intracellular domain of Fas as well as methods for using the proteins and nucleic acid molecules.
Type:
Grant
Filed:
September 22, 1998
Date of Patent:
May 13, 2003
Assignee:
The Regents of the University of Michigan
Abstract: The present invention provides prophylactic and therapeutic methods of treating the ductal epithelium of an exocrine gland, in particular a mammary gland, for disease, in particular cancer. The methods comprise contacting the ductal epithelium of the exocrine gland with an epithelium-destroying gent, preferably by ductal cannulation, so as to realize a prophylactic or therapeutic effect.
Type:
Grant
Filed:
August 8, 2000
Date of Patent:
May 6, 2003
Assignee:
Johns Hopkins University School of Medicine
Abstract: The invention features p28 Bap31 polypeptides and nucleic acids. The invention also features methods for modulating apoptosis using these polypeptides and nucleic acids, and methods for identifying apoptosis-modulating compounds.
Type:
Grant
Filed:
September 10, 1999
Date of Patent:
May 6, 2003
Assignee:
McGill University
Inventors:
Gordon C. Shore, Florence W. H. Ng, Mai Nguyen, Philip E. Branton
Abstract: The present invention describes a recombinant adenoviral vector in which a single-chain antibody has been introduced into the minor capsid proteins, pIIha or pIX, so that the adenoviral vector can be targeted to a particular cell type. Additionally disclosed is a method of using the recombinant adenoviral vector in targeted gene therapy.
Abstract: The present invention relates to a new delivery system and method for producing same. The delivery system is a biphasic system of delivering charged macromolecules and comprises a negatively charged hydrophobic organic phase and a positively charged inorganic phase. The organic phase and the inorganic phase entrapping added macromolecules. The macromolecules are entrapped by electrostatic bonds between the organic phase, the inorganic phase and the macromolecules. The method for producing the delivery system comprises the steps of contacting together and mixing a negatively charged organic phase, a charged macromolecule and positively charged inorganic phase.
Type:
Grant
Filed:
October 30, 2000
Date of Patent:
April 22, 2003
Assignee:
Universite de Montreal
Inventors:
Youssef Elazhary, Boby Makabi-Panzu, David John Hurley, Sylvette Laurent
Abstract: A hydrophilic therapeutic agent is prepared in storage-stable form, suitable for administration to a patient. The agent is formulated with a hydrophobically-derivatized carbohydrate, making use of ion-pair formation to form a solution of the agent and carbohydrate.
Abstract: Devices useful in the delivery of DNA encoding neurotrophic agents, anti-fibrotic agents, and related compositions are disclosed herein for use in the treatment of central and/or peripheral nervous system injury. Methods of making and using the disclosed devices and DNA are also described. In various embodiments, the invention also discloses compositions and devices that may further include a targeting agent, such as a polypeptide that is reactive with an FGF receptor (e.g., bFGF), or another ligand that binds to cell surface receptors on neuronal cells, or a support cell. The invention also discloses methods of promoting neuronal survival and regeneration via transfection of an axon as it grows through a device or composition of the present invention, or via transfection of a repair cell.
Type:
Grant
Filed:
October 23, 1998
Date of Patent:
April 22, 2003
Assignees:
University of Birmingham, King's College, Selective Genetics, Inc.
Inventors:
Andrew Baird, Ana Maria Gonzalez, Ann Logan, Martin Berry
Abstract: The invention generally relates to targeted gene therapy using recombinant vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional vectors and methods for using them. Such vectors are able to selectively replicate in a target tissue to provide a therapeutic benefit from the presence of the vector per se or from heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits transcription of the gene by means of the transcriptional regulatory sequence with this vector, therefore, a target tissue can be selectively treated.
Type:
Grant
Filed:
December 15, 1998
Date of Patent:
April 22, 2003
Assignee:
Genetic Therapy, Inc.
Inventors:
Paul L. Hallenbeck, Yung-Nien Chang, Yawen L. Chiang
Abstract: The invention provides a method of radiosensitizing a tumor in a subject by contacting the tumor with a cytokine or a nucleic acid molecule encoding a cytokine. The invention also provides a method of radiosensitizing a tumor in a subject by administering, at a site other than the tumor, a cell genetically modified to express a cytokine. The invention further provides a method of reducing the severity of a cancer in a subject by administering a cytokine at the site of the tumor or by immunizing the subject at a site other than the tumor with tumor cells genetically modified to express a cytokine, and treating the tumor with radiotherapy.
Type:
Grant
Filed:
March 24, 2000
Date of Patent:
April 22, 2003
Assignee:
The Regents of the University of California
Abstract: The invention relates to a method of identifying nuclear receptor controlled genes in specific tissues. In particular, the method also provides a method of activating PPAR&ggr; nuclear receptor controlled target genes in vivo in a tissue-specific manner.
Abstract: A previously unknown histone acetylase inhibitor, 6-(1,3-Dioxo-1H, 3H-benzo[de]isoquinolin-2-yl)-hexanoic acid hydroxyamide, termed “scriptaid,” can be used to enhance transcription. Scriptaid can be added to transactivation assays, or can be used, for example, to increase production of therapeutic polypeptides in vitro and in vivo.
Abstract: The present invention is directed to methods of sensitizing a human tumor cell with adenovirus E1A. The methods involve treating a human tumor cell by, first, introducing into the tumor cell nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cell, and then either contacting the E1A expressing tumor cell with a chemotherapeutic agent or irradiating the E1A-expressing tumor cell. The invention also provides methods of enhancing a subject's response to chemotherapy or irradiation by introducing into a subject's tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cells and finally, administering either a chemotherapeutic agent or irradiation. The invention also provides a method of treating cancer.
Abstract: The invention provides methods and compositions of selectively disrupting mitotic function in a target cell demonstrating undesirable mitotic function. Suitable target cells include mammalian, plant and bacterial cells, which cells may be in vitro or in situ. The general methods involve introducing into the target cell an effective amount of a peptide comprising contiguous acidic amino acids, such as Asp or Glu, whereby the undesirable mitotic function of the cell is selectively disrupted. In particular embodiments, the peptide comprises a Gm2S-1 peptide, particularly a lunasin and/or alisin peptide. The peptide may be introduced by transfecting the cell with a nucleic acid encoding the peptide.
Type:
Grant
Filed:
March 21, 2000
Date of Patent:
April 8, 2003
Assignee:
The Regents of the University of California
Abstract: Disclosed is substantially pure DNA encoding mammalian IAP polypeptides; substantially pure polypeptides; and methods of using such DNA to express the IAP polypeptides in cells and animals to inhibit apoptosis. Also disclosed are conserved regions characteristic of the IAP-family and primers and probes for the identification and isolation of additional IAP genes. In addition, methods for treating diseases and disorders involving apoptosis are provided.
Type:
Grant
Filed:
December 1, 1998
Date of Patent:
April 1, 2003
Assignee:
Aegera Therapeutics Inc.
Inventors:
Robert G. Korneluk, Alexander E. MacKenzie, Stephen Baird, Peter Liston