Abstract: Provided is an agent which is useful for diagnosis, prevention, and treatment of various diseases induced by an oxidative stress. Disclosed are secreted eIF5A protein and a pharmaceutical containing the same.
Abstract: Provided herein is a method of reversing or preventing a target cell's resistance to a death receptor agonist. Also provided are methods of screening for biomarkers resistance of and monitoring resistance to death receptor agonists. Also provided are methods of selectively inducing apoptosis in a target cell, treating a subject with cancer, autoimmune or inflammatory diseases, comprising administering compositions provided herein. Further provided are compositions comprising agents that modulate CARD containing proteins.
Abstract: Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic. acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.
Type:
Grant
Filed:
June 8, 2011
Date of Patent:
June 11, 2013
Assignee:
Washington University
Inventors:
William G. Hawkins, Dirk Spitzer, Richard S. Hotchkiss
Abstract: Methods of treatment using Fzd8 extracellular domains (ECDs), Fzd8 ECD fusion molecules, and/or antibodies that bind Fzd8 are provided. Such methods include, but are not limited to, methods of treating obesity and obesity-related conditions. Fzd8 ECDs and Fzd8 ECD fusion molecules are also provided. Polypeptide and polynucleotide sequences, vectors, host cells, and compositions comprising or encoding such molecules are provided. Methods of making and using Fzd8 ECDs, Fzd8 ECD fusion molecules, and antibodies that bind Fzd8 are also provided.
Type:
Grant
Filed:
June 27, 2011
Date of Patent:
April 30, 2013
Assignee:
Five Prime Therepeutics, Inc.
Inventors:
Thomas Brennan, Ernestine Lee, Steven Smith
Abstract: The present invention relates to nucleotide sequences of vertebrate Delta genes, and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof. In a specific embodiment, the vertebrate Delta protein is a human protein. The invention further relates to fragments (and derivatives and analogs thereof) of Delta which comprise one or more domains of the Delta protein, including but not limited to the intracellular domain, extracellular domain, DSL domain, domain amino-terminal to the DSL domain, transmembrane region, or one or more EGF-like repeats of a Delta protein, or any combination of the foregoing. Antibodies to Delta, its derivatives and analogs, are additionally provided. Methods of production of the Delta proteins, derivatives and analogs, e.g., by recombinant means, are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are provided.
Type:
Grant
Filed:
October 10, 2006
Date of Patent:
April 9, 2013
Assignees:
Imperial Cancer Research Technology, Ltd., Yale University
Inventors:
David Ish-Horowicz, Domingos Manuel Pinto Henrique, Julian Hart Lewis, Spyridon Artavanis-Tsakonas, Grace E. Gray
Abstract: Isolated human antibodies or antigen-binding fragments thereof, which specifically bind to human RANKL and block hRANKL binding to a RANK receptor, are provided. The antibodies are useful in preventing or treating disorders and/or diseases, which are associated with RANKL/RANK interactions, including bone disorders or cancer.
Type:
Grant
Filed:
August 19, 2009
Date of Patent:
April 9, 2013
Assignee:
Regeneron Pharmaceuticals, Inc.
Inventors:
Joel H. Martin, Aris N. Economides, Regina Raz
Abstract: The invention relates to the field of recombinant antibodies for use in human cancer therapy. More specifically the invention provides compositions or mixtures of antibodies capable of binding human EGFR. Antibody compositions with 3 or more antibodies showed synergy in reduction of proliferation of representative cancer cell lines. Advantageous results have also been obtained with a composition comprising two different chimeric anti-hEGFR antibodies which show a new mechanism of action based on rapid and efficient receptor internalisation, induction of terminal differentiation and subsequent tumour eradication in an animal model. The antibodies of the invention can be manufactured in one bioreactor as a polyclonal antibody.
Type:
Grant
Filed:
November 12, 2010
Date of Patent:
April 9, 2013
Assignee:
Symphogen A/S
Inventors:
Mikkel Wandahl Pedersen, Lucilla Steinaa, Allan Jensen, Klaus Koefoed, Per-Johan Meijer, Robert Carlsson, Charles Pyke, Lars Sogaard Nielsen
Abstract: The invention provides a polypeptide having a sequence of amino acids consisting of IXDFGLAKL (SEQ ID NO: 1), as well as a nucleic acid encoding the polypeptide, vector comprising the nucleic acid, cell comprising the vector, and compositions thereof. The invention also provides a method of inducing a T-cell response in a patient with epithelial cancer, and a method inhibiting epithelial cancer, wherein the methods comprise administering the composition of the invention. The invention further provides a method of stimulating a cell with the inventive polypeptide and a cell so stimulated.
Type:
Grant
Filed:
December 2, 2010
Date of Patent:
February 5, 2013
Assignee:
University of Pittsburgh—of the Commonwealth System of Higher Education
Inventors:
Robert L. Ferris, Pedro Andrade, Andres Lopez-Albaitero
Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to ErbB2, preferably human ErbB2. In another embodiment, the antibodies or antigen-binding portions thereof inhibit ErbB2. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins or portions thereof derived from human anti-ErbB2 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-ErbB2 antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.
Type:
Grant
Filed:
August 2, 2007
Date of Patent:
January 8, 2013
Assignee:
MedImmune Limited
Inventors:
Susan Ann Cartlidge, Jianying Dong, Mark Hickinson, Ian Foltz, Jaspal Singh Kang
Abstract: Disclosed herein are antigen-binding molecules, such as antibodies, that specifically recognize a portion of the EGFR C-terminal (intracellular) regulatory domain that interacts with one or more regulatory molecules (such as Suppressor of Cytokine Signaling (“SOCS”) proteins). In certain normal or neoplastic cells and/or tissues, this region is inaccessible to the disclosed antigen-binding molecules. Thus, such antigen-binding molecules are useful at least to interrogate the regulated state of EGFR, predict the response of a cancer patient to EGFR inhibitor therapies, and/or predict the aggressiveness of neoplasms.
Type:
Grant
Filed:
July 11, 2008
Date of Patent:
December 11, 2012
Assignee:
Ventana Medical Systems, Inc.
Inventors:
William C. Powell, Linda Willoughby Kivi, Patrick C. Roche, Gary Gooch, Fabien Gaire
Abstract: The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.
Type:
Grant
Filed:
July 29, 2010
Date of Patent:
December 11, 2012
Assignees:
3M Innovative Properties Company, Trustees of Dartmouth
Inventors:
Randolph J. Noelle, Cory L. Ahonen, Ross M. Kedl
Abstract: The invention provides human monoclonal antibodies or fragments thereof, that specifically bind to CXCR4. Disclosed are methods of use of such antibodies for the treatment and/or prevention of a CXCR4 disease or disorder such as cancer and X4-tropic HIV-1 infection Also provided are methods of use of such antibodies and antibody fragments for the treatment or prevention of cancer metastasis. The invention provides methods of mobilizing CD34+stem cells from the bone marrow and methods of blocking chemotaxis of CXCR4-expressing cells in response to SDF-1. Also provided are methods of use of the antibodies and fragments thereof for the prevention or treatment of graft-versus-host disease. Finally, the invention provides methods of inhibiting new tumor blood vessel formation and/or tumor cell angiogenesis.
Abstract: Fusion proteins which act on the TWEAK and TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, as well as other diseases such as alloimmune diseases and cancer.
Type:
Grant
Filed:
August 11, 2011
Date of Patent:
December 11, 2012
Assignee:
The Trustees of the University of Pennsylvania
Abstract: The present invention relates to novel Death Domain Containing Receptor-4 (DR4) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR4 proteins. DR4 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR4 activity and methods for using DR4 polynucleotides and polypeptides. The invention also relates to the treatment of diseases associated with reduced or increased levels of apoptosis using antibodies specific for DR4, which may be agonists and/or antagonists of DR4 activity.
Type:
Grant
Filed:
January 18, 2008
Date of Patent:
December 11, 2012
Assignees:
Human Genome Sciences, Inc., The Regents of the University of Michigan
Inventors:
Jian Ni, Craig A. Rosen, James G. Pan, Reiner L. Gentz, Vishva M. Dixit
Abstract: An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.
Type:
Grant
Filed:
October 10, 2011
Date of Patent:
December 11, 2012
Assignee:
The UAB Research Foundation
Inventors:
Tong Zhou, Kimihisa Ichikawa, Robert P. Kimberly, William J. Koopman
Abstract: The present invention provides fusion proteins comprising an extracellular domain of a VEGF receptor and a death ligand. The fusion proteins bind to VEGF and to death receptors on tumor cells thereby inhibiting VEGF activation of VEGF receptors and inducing apoptosis in the tumor cells. Fusion proteins of the present invention are useful for inducing apoptosis and cytotoxic effects in cells, treating cancer and diseases or disorders related to unregulated angiogenesis and/or vasculogenesis. Thus, this invention further provides methods for treating angiogenesis related diseases using the fusion proteins, polynucleotides encoding the fusion proteins, vectors containing the polynucleotides, pharmaceutical compositions and kits containing the fusion proteins or the polynucleotides encoding the fusion proteins.
Type:
Grant
Filed:
August 15, 2006
Date of Patent:
December 4, 2012
Assignee:
The Regents of the University of California
Abstract: A method to determine the utility of small molecules as functional replacements (mimetics) for protein receptor ligands is described. The method uses cellular biological assays on a systematic array of compounds, comprising known protein receptor ligands and other biologically active molecules to determine if a proposed small molecule is a functional equivalent of a receptor ligand, having therapeutic utility as a pharmaceutically relevant and useful agent either alone or in combination with other molecules. Furthermore, the invention provides for a method for the treatment of cancer comprising administering a combination of ET-18-O-CH3 and an anti-cancer agent.
Abstract: A method of inhibiting apoptosis in a cell includes administering to a cell an effective amount of a cell penetrating peptide (CPP), wherein the CPP consists of about 5 to about 41 amino acids and is substantially homologous to a portion of the C-terminal region of IFN?R2.