Abstract: Single chain, monomeric polypeptide gene switches are provided. The gene switches include ligand binding domains and at least one functional domain. Preferred functional domains are DNA binding domains and transcriptional regulating domains. Methods of regulating gene function using the switches are also provided.
Type:
Application
Filed:
July 18, 2001
Publication date:
November 14, 2002
Applicant:
The Scripps Research Institute
Inventors:
Carlos F. Barbas, Roger Beerli, Ulrich Schopfer
Abstract: The present invention contemplates therapeutic compositions containing a fibrinogen homolog capable of binding to endothelial cells in an RGD-independent manner that inhibits fibrinogen binding to endothelial cells. Also described are therapeutic compositions containing an ICAM-1 homolog capable of binding to fibrinogen in an RGD-independent manner that inhibits fibrinogen binding to endothelial cells. Methods of inhibiting endothelial cell and fibrinogen mediated inflammation within a patient by administering a homolog of this invention are also contemplated.
Type:
Application
Filed:
July 24, 2001
Publication date:
November 14, 2002
Applicant:
The Scripps Research Institute
Inventors:
Dario C. Altieri, Lucia R. Languino, George B. Thornton
Abstract: The present invention provides a novel method for the identification and clonal isolation of antibodies that bind to unique epitopes. The method is based on the use of antibodies as solid phase capture reagents to bind a known capture antibody epitope, thereby precluding the capture antibody epitope from being presented to a population of antibodies to be screened. The method is particularly suited for screening libraries of cloned antibodies, such as phage display combinatorial antibodies. An antibody specific for herpes simplex virus (HSV), was employed as a model for the assay.
Type:
Application
Filed:
February 19, 2002
Publication date:
November 14, 2002
Applicant:
The Scripps Research Institute, a California Corporation
Inventors:
Dennis R. Burton, Roberto Burioni, R. Anthony Williamson, Pietro P. Sanna
Abstract: The present invention relates generally to nucleic acids encoding a novel neuropeptide designated cortistatin. The cortistatin nucleic acids, proteins and polypeptides thereof along with anti-cortistatin antibodies are useful in both screening methods, diagnostic methods and therapeutic methods related to modulation of sleep and disorders thereof.
Type:
Grant
Filed:
May 15, 1997
Date of Patent:
November 12, 2002
Assignee:
The Scripps Research Institute
Inventors:
J. Gregor Sutcliffe, Luis De Lecea, Steven J. Henriksen, George R. Siggins
Abstract: Methods and products for targeting delivery vectors, such as adenoviral gene delivery particles, to selected cell types are provided. The methods rely on targeting by a bifunctional molecule that specifically complexes with a protein on the vector particle surface and with targeted cell surface proteins. The targeted cell surface proteins are any that activate the phosphatidylinositol-3-OH kinases. The bifunctional molecules, compositions, kits, and methods of preparation and use of the vector/bifunctional molecules for gene therapy are provided.
Abstract: Polypeptides that contain from 2 to 12 zinc finger-nucleotide binding regions that bind to nucleotide sequences of the formula (ANN)2-12 are provided. Polynucleotides that encode such polypeptides and methods of regulating gene expression with such polypeptides and polynucleotides are also provided.
Abstract: Processes for the preparation of modified proteins comprising the coupling of a first peptide segment having a haloacyl group at the N-terminus thereof with a second peptide sequent having a carbonylthiol group at the C-terminus thereof are disclosed. Novel modified proteins produced by the process are also disclosed.
Type:
Grant
Filed:
December 29, 1998
Date of Patent:
November 5, 2002
Assignee:
The Scripps Research Institute
Inventors:
Stephen B. H. Kent, Martina Schnolzer-Rackwitz
Abstract: The immunoglobulins of the present invention are useful therapeutic immunoglobulins against mucosal pathogens such as S. mutans. The immunoglobulins contain a protection protein that protects the immunoglobulins in the mucosal environment.
Abstract: The invention describes the display of exogenous polypeptides on filamentous phage using a fusion between the exogenous polypeptide and phage pVII or pIX proteins. In particular, phage particles and phagemid vectors are described for expression and display of heterodimeric proteins such a antibody Fv heterodimers in combinatorial libraries, and uses thereof.
Type:
Grant
Filed:
May 25, 1999
Date of Patent:
October 29, 2002
Assignee:
The Scripps Research Institute
Inventors:
Kim D. Janda, Peter Wirsching, Richard A. Lerner, Changshou Gao
Abstract: Filamentous phage comprising a matrix of cpvIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.
Type:
Grant
Filed:
December 4, 2000
Date of Patent:
October 22, 2002
Assignee:
The Scripps Research Institute
Inventors:
Angray Kang, Carlos Barbas, Richard A. Lerner
Abstract: Hydroxyazepanes display inhibitory activity with respect to glycosidase, with Ki values from-moderate to low micromolar range. Benzyl and 3,6-dibenzyl derivatives of hydroxyazepanes display inhibitory activity with respect to HIV protease. These compounds are synthesized either by chemoenzymatic or chemical methodologies.
Abstract: Materials and methods of activating T lymphocytes with specificity for particular antigenic peptides are described, as well as the use of activated T lymphocytes in vitro for the treatment of a variety of disease conditions. In particular, a synthetic antigen presenting matrix for activating T lymphocytes to a specific peptide is described.
Type:
Grant
Filed:
September 8, 1997
Date of Patent:
October 8, 2002
Assignee:
The Scripps Research Institute
Inventors:
Zeling Cai, Jonathan Sprent, Anders Brunmark, Michael Jackson, Per A. Peterson, Alain Luxembourg, Didier J. Leturcq, Ann M. Moriarty
Abstract: Potent inhibitors of fatty acid amide hydrolase (FAAH) are constructed having Ki's below 200 pM and activities 102-103 times more potent than the corresponding trifluoromethyl ketones. The potent inhibitors combine several features, viz.: 1.) an &agr;-keto heterocylic head group; 2.) a hydrocarbon linkage unit employing an optimal C12-C8 chain length; and 3.) a phenyl or other &pgr;-unsaturation corresponding to the arachidonyl &Dgr;8.9/&Dgr;11.12 and/or oleyl &Dgr;9.10 positions. A preferred &agr;-keto heterocylic head group is &agr;-keto N4 oxazolopyridine, with incorporation of a second weakly basic nitrogen. Fatty acid amide hydrolase is an enzyme responsible for the degradation of oleamide (an endogenous sleep-inducing lipid) and anandamide (an endogenous ligand for cannabinoid receptors).
Abstract: The present invention contemplates therapeutic compositions containing a fibrinogen homolog capable of binding to endothelial cells in an RGD-independent manner that inhibits fibrinogen binding to endothelial cells. Also described are therapeutic compositions containing an ICAM-1 homolog capable of binding to fibrinogen in an RGD-independent manner that inhibits fibrinogen binding to endothelial cells. Methods of inhibiting endothelial cell and fibrinogen mediated inflammation within a patient by administering a homolog of this invention are also contemplated.
Type:
Application
Filed:
July 24, 2001
Publication date:
September 19, 2002
Applicant:
The Scripps Research Institute
Inventors:
Dario C. Altieri, Lucia R. Languino, George B. Thornton
Abstract: An improved method for the simultaneous sequence-specific identification of mRNAs in a mRNA population allows the visualization of nearly every mRNA expressed by a tissue as a distinct band on a gel whose intensity corresponds roughly to the concentration of the mRNA. In general, the method comprises the formation of cDNA using anchor primers to fix a 3′-endpoint, producing cloned inserts from the cDNA in a vector containing a bacteriophage-specific promoter for subsequent RNA synthesis, generating linearized fragments of the cloned inserts, preparing cRNA, transcribing cDNA from the cRNA using a set of primers, and performing PCR using a 3′-primer whose sequence is derived from the vector and a set of 5′-primers that is derived from the primers used for transcription of cDNA from cRNA. The method can identify changes in expression of mRNA associated with the administration of drugs or with physiological or pathological conditions.
Abstract: This invention provides hybridoma cell lines producing monoclonal antibodies which inhibit CD14 mediated cell activation. Monoclonal antibodies produced by these cell lines also are provided. The antibodies are useful for the detection of the presence of cell surface and soluble CD14 in a sample. Chimeric and CDR grafted antibodies generated from the above monoclonal antibodies are further provided. Pharmaceutical compositions containing the above biological compositions are provided. These are useful to treat and prevent disorders with CD14 mediated cell activation, such as sepsis.
Type:
Grant
Filed:
October 13, 1998
Date of Patent:
September 3, 2002
Assignee:
The Scripps Research Institute
Inventors:
Didier J. Leturcq, Ann M. Moriarty, Richard J. Ulevitch, Peter S. Tobias, John C. Mathison
Abstract: Epothilone A, epothilone B, analogs of epothilone and libraries of epothilone analogs are synthesized. Epothilone A and B are known anticancer agents that derive their anticancer activity by the prevention of mitosis through the induction and stabilization of microtubulin assembly. The analogs of epothilone are novel. Several of the anlogs are demonstrated to have a superior cytotoxic activities as compared to epothilone A or epothilone B as demonstrated by their enhanced ability to induce the polymerization and stabilization of microtubules.
Type:
Grant
Filed:
September 4, 1997
Date of Patent:
August 27, 2002
Assignee:
The Scripps Research Institute
Inventors:
Kyriacos C. Nicolaou, Yun He, Sacha Ninkovic, Joaquin Pastor, Frank Roschangar, Francisco Sarabia, Hans Vallberg, Dionisios Vourloumis, Nicolas Winssinger, Zhen Yang, N. Paul King, M. Ray Finlay
Abstract: Methods are provided for deuteration, tritiation, dedeuteration or detritiation of a carbonyl compound. A catalytic antibody that catalyzes an aldol addition reaction is contacted with a carbonyl compound to exchange at least one hydrogen atom of the carbonyl compound with a deterium or tritium atom of an isotopically enriched water molecule, or to exchange at least one deuterium or tritium atom of the carbonyl compound with a hydrogen atom. The aldol addition reaction may be between an aliphatic ketone donor and an aldehyde acceptor. Isotopically enriched water molecules include deuterium hydrogen oxide, dideuterium oxide, tritium hydrogen oxide, ditritium oxide and deuterium tritium oxide. The catalytic antibody may be that secreted by hybridoma 38C2 (ATCC HB 12005) or 33F12 (ATCC HB 12004).
Abstract: The present invention encompasses novel mammalian cell cycle checkpoint genes/DNA repair genes, cDNA or genomic DNA, isolated nucleic acids corresponding thereto, expression vectors comprising said nucleic acids, host cells transformed with said expression vectors, pharmaceutical compositions and the formulation of such compositions comprising said nucleic acids or proteins expressed therefrom, methods for treating a cell using such nucleic acids, proteins or pharmaceutical compositions, and the use of such nucleic acids or proteins in formulating a pharmaceutical preparation.
Type:
Grant
Filed:
September 14, 2000
Date of Patent:
August 27, 2002
Assignees:
The Scripps Research Institute, Janssen Pharmaceutica N.V.
Inventors:
Paul R. Russell, Jorge E. Vialard, Michael N. Boddy, Paul A. Shanahan, Antonia Lopez-Girona, Cecile-Marie D. D. Denis