Abstract: The present invention relates to methods of introducing one or more cysteine residues into a polypeptide which permit the stabilization of the polypeptide by formation of at least one bond, preferably a disulfide bond, between different domains of the polypeptide. The invention also relates to polypeptides containing such introduced cysteine residue(s), nucleic acids encoding such polypeptides and pharmaceutical compositions comprising such polypeptides or nucleic acids. The invention also relates to vectors, viral particles and host cells containing such nucleic acids, and methods of using them to produce the polypeptides of the invention. Exemplified polypeptides include plasma proteins, including hepatocyte growth factor activator and plasma hyaluronin binding protein, as well as blood coagulation factors, such as Factor VIII, Factor V, Factor XII and prothrombin.
Type:
Grant
Filed:
January 25, 2007
Date of Patent:
April 19, 2011
Assignee:
The Scripps Research Institute
Inventors:
John H. Griffin, Andrew J. Gale, Elizabeth D. Getzoff, Jean-Luc Pellequer
Abstract: The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying the optimum probe attachment site. Biosensors are provided having environmentally sensitive dyes that can locate specific biomolecules within living cells and detect chemical and physiological changes in those biomolecules as the living cell is moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, the environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound.
Type:
Grant
Filed:
May 5, 2005
Date of Patent:
June 29, 2010
Assignee:
The Scripps Research Institute
Inventors:
Klaus M. Hahn, Alexei Toutchkine, Rajeev Muthyala, Vadim Kraynov, Steven J. Bark, Dennis R. Burton, Chester Chamberlain
Abstract: The invention describes recombinant fusion proteins containing Wee1 protein sequences involved in checkpoint regulation of cell cycle, nucleic acid molecules that encode the fusion protein, and methods using the proteins for screening for compounds which modulate Wee1 or Cds1 function.
Type:
Grant
Filed:
February 25, 2003
Date of Patent:
June 5, 2007
Assignee:
The Scripps Research Institute
Inventors:
Paul Russell, Michael N. Boddy, Beth Furnari
Abstract: Human Borna disease virus (BDV) nucleic acids and polypeptides are described from three psychiatric patients. The human BDV-derived nucleic acids and polypeptides are useful in both DNA- and protein-based assays to detect human BDV in a subject, particularly the detection of BDV nucleic acids, BDV polypeptides and BDV antibodies generated in response to BDV infection.
Abstract: A modified factor VIIa is provided. The modified factor has increased amidolytic activity in the absence of T.F. and a higher affinity for T.F. when compared to the native factor VIIa but does not have substantially altered proteolytic activity when bound to T.F. Nucleic acid molecules that encode the factor, expression vectors that contain the nucleic acid molecules, cells that contain the nucleic acid molecules, and cells transformed with the expression vector are also provided. In a preferred embodiment, the modified factor is a human factor VIIa.
Abstract: The present invention discloses deoxyribonucleic acid enzymes—catalytic or enzymatic DNA molecules—capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.
Abstract: Diagnostic systems, methods, polypeptides and antibodies for detecting the presence of C-terminal hGPIIb fragment of the platelet receptor GPIIb-IIIa in a body fluid sample are disclosed.
Type:
Grant
Filed:
September 3, 2004
Date of Patent:
October 17, 2006
Assignee:
The Scripps Research Institute
Inventors:
Mark H. Ginsberg, Andrew L. Frelinger, III, Edward F. Plow
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:
October 18, 2002
Date of Patent:
October 10, 2006
Assignee:
The Scripps Research Institute
Inventors:
Angray Kang, Carlos F. Barbas, III, Richard A. Lerner
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 as antibody Fv heterodimers in combinatorial libraries, and uses thereof.
Type:
Grant
Filed:
August 14, 2002
Date of Patent:
July 18, 2006
Assignee:
The Scripps Research Institute
Inventors:
Kim D. Janda, Peter Wirsching, Richard A. Lerner, Changshou Gao
Abstract: The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules with one or more accessory molecules. The matrices are used to activate naive CD4+T cells as well as shift the ongoing activation state into a preferred differentiated population of either Th1 or Th2 cells.
Type:
Grant
Filed:
November 17, 2000
Date of Patent:
July 11, 2006
Assignee:
The Scripps Research Institute
Inventors:
Susan R. Webb, Ola Wingvist, Lars Karlsson, Michael R. Jackson, Per A. Peterson
Abstract: Compositions comprising OB-R agonists and methods of treatment for conditions such as systemic inflammatory response syndrome are provided. One suitable OB-R agonist ligand is recombinant human OB protein, also known as leptin. Also provided are methods and compositions for the treatment of obesity and OB resistance. Assay methods and kits relating to these conditions are also included.
Abstract: The present invention describes methods for producing antibody libraries, and particularly for increasing antibody library diversity by inducing mutagenesis within the CDR regions of immunoglobulin heavy or light chains that are displayed on the surface of filamentous phage particles comprising the library. The invention also describes oligonucleotides useful for increasing the library diversity, and universal light chains useful in the library production methods.
Type:
Grant
Filed:
July 5, 2000
Date of Patent:
June 27, 2006
Assignee:
The Scripps Research Institute
Inventors:
Carlos F. Barbas, Dennis R. Burton, Richard A. Lerner
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:
Grant
Filed:
February 19, 2002
Date of Patent:
June 13, 2006
Assignee:
The Scripps Research Institute
Inventors:
Dennis R. Burton, Roberto Burioni, R. Anthony Williamson, Pietro P. Sanna
Abstract: The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin ?v?5 antagonists. The ?v?5-mediated angiogenesis is correlated with exposure to cytokines including vascular endothelial growth factor, transforming growth factor-? and epidermal growth factor. Inhibition of ?v?5-mediated angiogenesis is particularly preferred in vascular endothelial ocular neovascular diseases, in tumor growth and in inflammatory conditions, using therapeutic compositions containing ?v?5 antagonists.
Type:
Grant
Filed:
May 30, 1997
Date of Patent:
May 30, 2006
Assignee:
The Scripps Research Institute
Inventors:
Peter C. Brooks, David A. Cheresh, Martin Friedlander
Abstract: The invention relates to compositions useful for the production of transgenic plants. In particular, the invention relates to Cassava vein mosaic virus (CsVMV) promoter sequences and expression cassettes containing CsVMV promoter sequences. The invention describes nucleic acid molecules, vectors and transgenic plants containing promoters derived from CsVMV promoter that are operatively linked to heterologous DNA sequences, and methods for producing transgenic plants containing these promoters.
Type:
Grant
Filed:
June 20, 1997
Date of Patent:
May 30, 2006
Assignee:
The Scripps Research Institute
Inventors:
Bertrand Verdaguer, Alexandre de Kochko, Roger N. Beachy, Claude Fauguet
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:
Grant
Filed:
July 18, 2001
Date of Patent:
March 14, 2006
Assignee:
The Scripps Research Institute
Inventors:
Carlos F. Barbas, III, Roger Beerli, Ulrich Schopfer
Abstract: The present invention describes methods for producing binding sites on polypeptides, and particularly for producing binding sites within the CDR regions of immunoglobulin heavy or light chains that are displayed on the surface of filamentous phage particles. The invention also describes oligonucleotides useful for preparing the binding sites, and human monoclonal antibodies produced by the present methods.
Type:
Grant
Filed:
February 2, 1994
Date of Patent:
October 18, 2005
Assignee:
The Scripps Research Institute
Inventors:
Carlos F. Barbas, III, Richard A. Lerner
Abstract: The present invention provides novel glycoluril derivatives for use as core molecules in combinatorial chemistry. Core molecules of the present invention can contain from one to six building blocks. Preferred building blocks are substituted amine radicals. Combinatorial libraries containing such core molecules are also provided.
Abstract: The present invention provides a process for making an in vivo model of human leukemia. The process includes the steps of: pre-conditioning an immunodeficient rodent by administering to the rodent a sub-lethal dose of irradiation and injecting the rodent with an effective pre-conditioning amount of human fetal cord blood mononuclear cells; maintaining the rodent for from about 5 to 10 days; and injecting the rodent with an effective engrafting amount of primary human leukemia cells. An in vivo and in vitro model of human leukemia are also provided.