Abstract: The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens complexed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis.
Type:
Grant
Filed:
July 18, 1994
Date of Patent:
March 27, 2001
Assignee:
The Immune Response Corporation
Inventors:
Mark D. Howell, Steven W. Brostoff, Dennis J. Carlo
Abstract: In accordance with the present invention, there are provided novel isolated nucleic acids encoding ataxin-2-binding proteins (A2BPs), functional fragments thereof, vectors containing invention nucleic acids and recombinant cells transformed therewith, antisense-nucleic acids thereto. Also provided are novel isolated ataxin-2-binding proteins (A2BPs) having ability to bind to ataxin-2, methods for expression of A2BP, transgenic non-human mammals that express invention A2BP, anti-A2BP antibodies, and methods related thereto.
Abstract: The present invention provides methods based on serological and genetic markers for diagnosing clinical subtypes of Crohn's disease (CD) having characteristic responsiveness to anti-Th1 cytokine therapy. In the methods of the inventions the presence of perinuclear anti-neutrophil antibody (pANCA), the presence of the TNFa10b4c1d3e3 haplotype or the presence TNFa11b4c1d3e3 haplotype each are independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. In addition, the presence of the homozygous TNF-&bgr; 1111 haplotype involving the TNFc, aa13L, aa26 and NcoI loci is independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. The presence of speckling anti-pan polymorphonuclear antibody (SAPPA) is diagnostic of a clinical subtype of CD having a superior clinical response to anti-Th1 cytokine therapy.
Type:
Grant
Filed:
May 12, 1997
Date of Patent:
February 6, 2001
Assignee:
Prometheus Laboratories, Inc.
Inventors:
Scott E. Plevy, Stephan R. Targan, Kent Taylor, Mary J. Barry
Abstract: The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachment activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.
Abstract: The present invention provides a method of identifying a tumor homing molecule that homes to angiogenic vasculature by contacting a substantially purified NGR receptor with one or more molecules and determining specific binding of a molecule to the NGR receptor, where the presence of specific binding identifies the molecule as a tumor homing molecule that homes to angiogenic vasculature. The invention also provides a method of directing a moiety to angiogenic vasculature in a subject by administering to the subject a conjugate including a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. In addition, the invention provides a method of imaging the angiogenic vasculature of a tumor in a subject by administering to the subject a conjugate having a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor and detecting the conjugate.
Abstract: The present invention provides peptides having specificity for fibronectin-binding and vitronectin-binding integrins, and in particular for &agr;5&bgr;1 integrin. These peptides are characterized by having the ability to interfere with extracellular matrix protein binding to integrins; to block attachment of cells expressing these integrins to extracellular matrix proteins; and to promote cell attachment when coated onto a surface.
Abstract: The present invention provides a method of identifying a membrane dipeptidase (MDP)-binding homing molecule that selectively homes to lung endothelium. The method includes the steps of contacting MDP with one or more molecules; and determining specific binding of a molecule to the MDP, where the presence of specific binding identifies the molecule as a MDP-binding homing molecule that selectively homes to lung endothelium. Such MDP-binding homing molecules can be linked to a moiety and, when administered to a subject as a conjugate, can selectively direct the moiety to lung endothelium in the subject.
Type:
Grant
Filed:
February 26, 1999
Date of Patent:
January 16, 2001
Assignee:
The Burnham Institute
Inventors:
Daniel Rajotte, Renata Pasqualini, Erkki Ruoslahti
Abstract: The present invention provides a mammalian CD40-associated protein (CAP), a nucleic acid molecule encoding the CAP and antibodies specific for the CAP. The invention further provides a substantially purified human CAP-1 and a nucleic acid molecule encoding human CAP-1. The invention also provides screening assays for identifying an agent that effectively alters the association of a CAP with a second molecule, which can bind to the CAP. In addition, the invention provides methods for identify a CAP agonist or CAP antagonist that can increase or decrease, respectively, the level of expression of the CAP in a cell. Such an effective agent, agonist or antagonist can modulate a function of a cell such as a humoral immune response or cell growth. The invention also provides methods of detecting a CAP in a sample by detecting the CAP or a nucleic acid molecule encoding the CAP. Such methods can be used to diagnose a pathology that is characterized by an increased or decreased level of a CAP in a cell.
Abstract: Methods are provided for transplanting a histoincompatible organ allograft in a subject, methods for enhancing organ allograft survival in a subject, methods for reducing the amount of anti-HLA alloantibodies in a transplant candidate and methods to make candidate less susceptible to rejection.
Abstract: The present invention provides vaccines and a means of vaccinating a mammal so as to prevent or control specific T cell mediated pathologies or to treat the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the mammal in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis. The invention additionally provides a specific .beta.-chain variable region of the T cell receptor, designated V.beta.17, which is central to the pathogenesis of rheumatoid arthritis (RA).
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
December 12, 2000
Assignee:
The Immune Response Corporation
Inventors:
Mark D. Howell, Steven W. Brostoff, Dennis J. Carlo
Abstract: A composition comprising genetically altered human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% human myeloblasts and promyelocytes, which have been derived from neutrophil progenitor cells obtained from peripheral blood, bone marrow or cord blood, and less than about 5% colony forming units (CFU) of at least about 50 cells is provided. An alternative composition comprising genetically altered human neutrophil precursor cells, wherein the cellular component is comprised of at least about 16% CD15+CD11b- cells and less than about 5% colony forming units (CFU) of at least about 50 cells also is provided, wherein at least about 60% of the CD15+CD11b- cells are myeloblasts and promyelocytes.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
November 14, 2000
Assignee:
Nexell Therapeutics Inc.
Inventors:
James G. Bender, Phillip B. Maples, Stephen Smith, Kristen L. Unverzagt, Dennis E. Van Epps
Abstract: The present invention relates to novel tetrahydro-quinoline compounds of the following formula, libraries containing such compounds, and to the generation of such combinatorial libraries composed of such compounds: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and Y have the meanings provided.
Abstract: The instant invention is directed to a single, selectively N-alkylated compound and libraries of such compounds as set forth in Formula I. Furthermore, the instant invention is directed to methods of effecting analgesia, a decrease in the postprandial rise in the blood glucose levels of a mammal after ingestion of a carbohydrate load by said mammal, and treating microbial infections, utilizing such a single compound of Formula I in conjunction with a pharmaceutically-acceptable carrier. Also, the instant invention is directed to methods for selective alkylation, positional scanning and iterative synthetic and screening technologies.
Type:
Grant
Filed:
July 1, 1999
Date of Patent:
November 7, 2000
Assignee:
Trega Biosciences, Inc.
Inventors:
Barbara Dorner, John M. Ostresh, Colette T. Dooley, Richard A. Houghten, Jutta Eichler
Abstract: The present invention provides an analytical test device for conducting assays of biological fluids. Methods for carrying out the assays with the disclosed analytical test device are also provided.
Abstract: The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.
Abstract: The present invention provides a substantially pure C2GnT-M polypeptide or a functional fragment or derivative thereof, wherein C2GnT-M is characterized as a polypeptide having core 2, core 4 and I branching .beta.-1.fwdarw.6-N-acetylglucosaminyltransferase activities. The invention also provides a substantially pure C2GnT-M peptide, wherein the peptide is immunogenic. Also provided is a method of modifying an acceptor molecule by contacting the acceptor molecule with a substantially pure C2GnT-M polypeptide or a functional fragment under conditions that allow addition of core 2, core 4 or I GlcNAc linkages to the acceptor molecule, and an acceptor molecule produced by the method. Also provided is a substantially pure nucleic acid molecule having substantially the nucleic acid sequence designated SEQ ID NO: 1, or the complement thereof.
Abstract: The present invention provides a mammalian artificial chromosome (MAC), comprising a centromere and a unique cloning site, said MAC containing less than 0.1% of the DNA present in a normal haploid genome of the mammalian cell from which the centromere was obtained. The invention further provides a MAC, wherein the unique cloning site is a nucleic acid sequence encoding a selectable marker. The invention also provides methods of preparing a MAC. In addition, the invention provides methods of stably expressing a selectable marker in a cell, comprising introducing a MAC containing the selectable marker into the cell. The invention also provides a cell containing a MAC expressing an exogenous nucleic acid sequence and a transgenic mammal expressing a selectable marker.
Type:
Grant
Filed:
February 17, 1998
Date of Patent:
October 17, 2000
Assignee:
The Regents of the University of California
Abstract: The invention provides compositions of a non-adenoviral vector containing a polynucleotide sequence encoding adenoviral pTP operationally linked domain. The invention also provides compositions of an adenoviral pTP binding domain. The invention also provides methods for increasing the expression of a polynucleotide by expressing the polynucleotide in a non-adenoviral vector containing an adenoviral pTP binding domain in the presence of adenoviral pTP. The invention additionally provides methods to increase expression of a heterologous polynucleotide in an individual by obtaining cells from the individual, genetically altering the cells to express a non-adenoviral vector containing an adenoviral pTP binding domain and a gene encoding pTP and readministering the genetically altered cells to the individual.
Abstract: The present invention provides substantially purified nucleic acid molecules encoding Bax inhibitor protein-1 (BI-1; SEQ ID NO: 1) or Bax inhibitor protein-2 (BI-2; SEQ ID NO: 4), nucleic acid molecules complementary thereto (SEQ ID NO: 2 and SEQ ID NO: 5, respectively), portions of such nucleic acid molecules, vectors containing the nucleic acid molecules, and host cells containing the vectors. The invention also provides methods of using such nucleic acid molecules to identify the presence of a nucleic acid molecule encoding a Bax inhibitor protein in a sample or to increase or decrease the level of expression of a Bax inhibitor protein in a cell. In addition, the invention provides substantially purified BI-1 (SEQ ID NO: 3) and BI-2 (SEQ ID NO: 6) polypeptides, portions of such polypeptides, and antibodies specific for BI-1 or BI-2.
Abstract: The invention relates to melanocortin receptor ligands and methods of using the ligands to alter or regulate the activity of a melanocortin receptor. The invention further relates to tetrahydroisoquinoline aromatic amines that function as melanocortin receptor ligands and as agents for controlling cytokine-regulated physiologic processes and pathologies, and combinatorial libraries thereof.
Type:
Grant
Filed:
April 28, 1999
Date of Patent:
October 3, 2000
Inventors:
Amaresh Basu, Timothy C. Gahman, Beverly E. Girten, Michael C. Griffith, Curtis C. Hecht, John S. Kiely, Sandra R. Slivka