Patents by Inventor Ronald T. Raines
Ronald T. Raines has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20160280701Abstract: Biheteroaryl dicarboxylates and esters, and salts thereof which are useful as modulators of CP4H activity and more particularly as inhibitors of CP4H. Compounds of formula: and salts thereof where: X is S, O, NH, or NR, where R is an alkyl group having 1-3 carbon atoms; R1 and R2 independently are —OR7, or —NHSO2R8, where R7 is selected from: hydrogen, alkyl, alkenyl, alkoxyalkyl, —R?—CO—R?, —R?—CO—O—R?, —CO—R?, —R?—O—CO—R?, —R?—CO—NR?, —CO—NR?, or —R?—O—CO—NR?, and R8 is selected from hydrogen, alkyl, aryl, arylalkyl; R3, R4 and R6 independently are hydrogen, alkyl, alkoxy, alkenyl, alkenoxy, halo alkyl, haloalkenyl, halogen, hydroxyl, hydroxyalkyl, hydroxyalkenyl, aryl, aryloxy, arylalkyl or arylalkyloxy; R5 is hydrogen, halogen, alkyl having 1-3 carbon atoms, or alkoxy having 1-3 carbon atoms; —R?— is a divalent straight chain or branched alkylene, and —R? is an alkyl, alkenyl, arylalkyl, or aryl group. Methods for inhibition of CP4H in vivo and in vitro.Type: ApplicationFiled: March 28, 2016Publication date: September 29, 2016Inventors: Ronald T. RAINES, James Vasta
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Publication number: 20160122366Abstract: Protease inhibitors, particularly aspartyl protease inhibitors, and more particularly HIV protease inhibitors which are boronated to enhance activity or to enhance entry into cells. Compounds, prodrugs and salts thereof of this invention contain phenylboronate groups, in particular p-B(OH)2-phenyl groups, benzoxaborole groups or borono-pyridyl groups or analogous groups in which the boronate group is protected.Type: ApplicationFiled: October 29, 2015Publication date: May 5, 2016Inventors: Ronald T. Raines, Ian Windsor, Michael Palte, John Lukesh
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Publication number: 20160083706Abstract: Cargo molecules carrying one or more phenylboronate moieties useful for cellular uptake of the cargo molecules. Phenylboronate can be ligated, crosslinked or otherwise bonded to the cargo molecules. Cargo molecules include peptides and proteins. The phenylboronate groups are optionally conjugated to the cargo molecule via linking moieties that can be selectively cleaved, such cleavable linkers can allow the phenylboronate groups to be removed from the cargo molecule after the boronated cargo molecule is introduced into the cell. The invention includes certain phenylboronates which are boronation reagents, certain boronated oligopeptides and certain boronated peptides and proteins. The invention also includes kits for enhancing cellular uptake of cargo molecules by boronation with one or more phenylboronates or boronated oligopeptides.Type: ApplicationFiled: December 2, 2015Publication date: March 24, 2016Inventors: Ronald T. RAINES, Gregory Ellis, Michael Palte
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Publication number: 20160075764Abstract: Novel collagen-mimetic peptides are disclosed comprising the formula (Xaa-Yaa-Gly)n, where the amino acid at one of the Xaa positions is substituted with a homocysteine residue. Also disclosed are multi-stranded novel collagen-mimetic peptides comprising a first strand as described above that is covalently bonded with a disulfide bridge to a second strand comprising the formula (Xaa-Yaa-Gly)m, where the amino acid at one of the Yaa positions is substituted with a cysteine residue. Disulfide formation between the terminal thiol sulfur of the homocysteine residue of the first strand and the terminal thiol sulfur of the cysteine residue of the second strand reveals unstrained bridges that enhance the structure and substantially improve the stability of collagen triple helices as compared to other possible disulfide or thioether bridges.Type: ApplicationFiled: September 11, 2015Publication date: March 17, 2016Inventors: Ronald T. Raines, Ismet C. Tanrikulu
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Publication number: 20160067342Abstract: Methods and reagents for enhancing cellular uptake of a cargo molecule by covalently bonding optionally-substituted fluorenyl groups to the cargo molecules, where cellular uptake includes at least partial uptake into the cytosol. Useful fluorenylation reagents include those of formula: and salts thereof where variables are as defined. Cargo molecules include peptides and proteins. Also provided are fluorenylated cargo molecules, including fluorenylated peptides and proteins.Type: ApplicationFiled: September 3, 2015Publication date: March 10, 2016Inventors: Ronald T. RAINES, Kristen A. ANDERSEN
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Publication number: 20160052878Abstract: Catalysts of protein-disulfide isomerization of formula: where R1 is hydrogen or —COR4, where R4 is an optionally substituted aliphatic group or an optionally substituted aryl group; R2 is hydrogen or —CO—R5, where R5 is alkyl having 1-8 carbon atoms, an alkenyl having 3-8 carbon atoms or a phenyl, benzyl, phenethyl or naphthyl group; and R3 is hydrogen or alkyl group having 1-3 carbon atoms. Protein folding buffers comprising one or more of the above compounds. Method of catalyzing, in vivo or in vitro, the isomerization of disulfide linkages in a protein or peptide employing above catalysts. Method of forming, in vivo or in vitro, disulfide linkages in a protein or peptide employing above catalysts.Type: ApplicationFiled: August 19, 2015Publication date: February 25, 2016Inventors: Ronald T. Raines, John C. Lukesh, III
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Patent number: 9255260Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.Type: GrantFiled: July 18, 2014Date of Patent: February 9, 2016Assignees: Wisconsin Alumni Research Foundation, The Regents of the University of CaliforniaInventors: Ronald T. Raines, Julie C. Mitchell, Thomas J. Rutkoski
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Publication number: 20160024122Abstract: Methods for enhancing cellular uptake of cargo molecules by boronating the cargo molecule, particularly with one or more phenylboronic acid groups. Boronation reagents for reversible boronation of cargo molecules, particularly, cargo molecules having one or more amino groups are provided.Type: ApplicationFiled: July 27, 2015Publication date: January 28, 2016Inventors: Ronald T. RAINES, Thomas P. SMITH
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Patent number: 9234191Abstract: Cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex are disclosed. Also disclosed is the 3-D structure of the hRI.RNase 1 complex and methods for designing and using the RNase 1 variants.Type: GrantFiled: October 4, 2013Date of Patent: January 12, 2016Assignee: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, George N. Phillips, Jr., R. Jeremy Johnson, Jason G. McCoy
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Patent number: 9234048Abstract: Methods for enhancing cellular uptake of cargo molecules by boronating the cargo molecule, particularly with one or more phenylboronic acid groups. Cellular uptake includes at least partial uptake into the cytosol. Boronation includes ligating, crosslinking or otherwise bonding one or more phenylboronic acids substituted to contain a reactive group to a cargo molecule. Boronation also includes ligating, crosslinking or otherwise bonding a phenylboronated oligopeptide to a cargo molecule. The phenylboronate groups are optionally conjugated to the cargo molecule via linking moieties that can be selectively cleaved, such cleavable linkers can allow the phenylboronate groups to be removed from the cargo molecule after the boronated cargo molecule is introduced into the cell. The invention includes certain phenylboronates which are boronation reagents, certain boronated oligopeptides and certain boronated peptides and proteins.Type: GrantFiled: January 18, 2013Date of Patent: January 12, 2016Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Ronald T. Raines, Gregory Ellis, Michael Palte
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Publication number: 20150307544Abstract: Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention can be employed to regulate protein function in proteins in which a sulfhydryl group is associated with biological activity. Reducing agents of this invention can prevent inactivation of a given protein or enhance activation of a given protein or other biological molecule in vitro and/or in vivo. Reducing agents of this invention can prevent or reduce oxidation of cysteine residues in proteins and prevent the formation of reduced activity protein dimers (or other oligomers). Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents.Type: ApplicationFiled: July 7, 2015Publication date: October 29, 2015Inventors: Ronald T. RAINES, John LUKESH
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Patent number: 9090662Abstract: Dithioamine reducing agents useful for the reduction of disulfide bonds. The reducing agents of this invention are useful, for example, to reduce disulfide bonds, particularly in proteins, or to prevent the formation of disulfide bonds, particularly in proteins and other biological molecules. Reducing agents of this invention are useful and suitable for application in a variety of biological applications, particularly as research and synthetic reagents. The invention provides S-acylated dithioamines which can be selectively activated reducing agents by removal of the S-acyl groups enzymatically or chemically. The invention further provides dithiane precursors of thioamino reducing agents. The invention provides dithioamine reducing agents, S-acylated dithioamines and dithianes which are immobilized on surfaces, including among others, glass, quartz, microparticles, nanoparticles and resins.Type: GrantFiled: February 15, 2013Date of Patent: July 28, 2015Assignee: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, John Lukesh
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Patent number: 9085590Abstract: Di- and trivalent protecting groups for organoboronic acids including phenyl boronic acids, benzoxaboroles and benzoxaborins, which are prepared from precursor compounds of formula I: where: R1 is a methyl, ethyl or a —(CH2)n—OH group, where n is 2 or 3; R2 and R3 are independently methyl or ethyl groups; R4 and R5 are independently halogens or hydrogens; R6 and R7 are independently hydrogens, halogens, or nitro groups; and R8 and R9 are independently hydrogens, halogens or nitro groups or R8 and R9 together with a portion of the naphthalene ring form a 5-member ring, where when R1 is —CH2—CH2—OH then the protecting group is a trivalent protecting group. Also provided are protected organoboronic acids including protected phenyl boronic acids, benzoxaboroles and benzoxaborins. Also provides are methods for conducting reactions employing protected organoboronic acids.Type: GrantFiled: March 14, 2014Date of Patent: July 21, 2015Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATIONInventors: Ronald T. Raines, Brett VanVeller, Matthew Aronoff
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Patent number: 8962001Abstract: A class of anionic oligomers and polymers that function for inhibition of nucleases, particularly RNase. Specific inhibitors include mixtures of oligomers of vinyl sulfate. Methods for inhibition or inactivation of one or more nucleases in vitro which comprises the step of contacting the one or more nucleases in a biological medium with one or more of the anionic oligomeric or polymeric inhibitors of this invention. Kits for carrying out a biological procedure, biological reaction and/or a biological assay containing one or more inhibitors of this invention. The use of oligomers and/or polymers of this invention as additives in buffers or reagents. The inhibitors of the invention can also be attached to surfaces to provide for removal of nucleases from media, solutions or other liquids in contact with the solid.Type: GrantFiled: June 10, 2013Date of Patent: February 24, 2015Assignee: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, Bryan D. Smith, Matthew B. Soellner, David M. Lynn
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Publication number: 20140275601Abstract: Di- and trivalent protecting groups for organoboronic acids including phenyl boronic acids, benzoxaboroles and benzoxaborins, which are prepared from precursor compounds of formula I: where: R1 is a methyl, ethyl or a —(CH2)n—OH group, where n is 2 or 3; R2 and R3 are independently methyl or ethyl groups; R4 and R5 are independently halogens or hydrogens; R6 and R7 are independently hydrogens, halogens, or nitro groups; and R8 and R9 are independently hydrogens, halogens or nitro groups or R8 and R9 together with a portion of the naphthalene ring form a 5-member ring, where when R1 is —CH2—CH2—OH then the protecting group is a trivalent protecting group. Also provided are protected organoboronic acids including protected phenyl boronic acids, benzoxaboroles and benzoxaborins. Also provides are methods for conducting reactions employing protected organoboronic acids.Type: ApplicationFiled: March 14, 2014Publication date: September 18, 2014Applicant: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, Brett VanVeller, Matthew Aronoff
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Patent number: 8834918Abstract: A composition for delivery of a molecule into a cell is provided. The composition includes a protein transduction domain that is conjugated to the molecule which is incorporated into a multilayered film. Preferably, the protein transduction domain is a cationic protein transduction domain. More preferably, the cationic protein transduction domain is nonaarginine, and the multilayered film includes polyelectrolyte multilayers. When the composition is presented to a cell, the multilayered film dissolves or erodes in physiological media, and the molecule is delivered into the cell.Type: GrantFiled: January 22, 2008Date of Patent: September 16, 2014Assignee: Wisconsin Alumni Research FoundationInventors: David M. Lynn, Ronald T. Raines, Christopher M. Jewell, Stephen M. Fuchs, Ryan M. Flessner
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Patent number: 8802413Abstract: This invention relates to altered forms of members of the RNase A superfamily. An RNase A can be modified to be cytotoxic by altering its amino acid sequence so that it is not bound easily by the ribonuclease inhibitor while still retaining catalytic properties. While earlier work had identified some modifications to RNase A that would result in cytotoxicity, the use of the FADE algorithm for molecular interaction analysis has led to several other locations that were candidates for modification. Some of those modifications did result in RNase A variants with increase cytotoxicity.Type: GrantFiled: August 30, 2013Date of Patent: August 12, 2014Assignee: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, Julie C. Mitchell, Thomas J. Rutkoski
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Publication number: 20140220651Abstract: High-yielding method for chemical hydrolysis of lignocellulose into monosaccharides. The process of the invention can additionally be applied to cellulose, xylan and related biomass polysaccharides, such as galactan, mannan, or arabinan. The method is employed for hydrolysis of a biomass polysaccharide substrate. The process is carried out in an ionic liquid in which cellulose is soluble in the presence of catalytic acid at a temperature sufficiently high to initiate hydrolysis. Water is added to the reaction mixture after initiation of hydrolysis at a rate controlled to avoid precipitation yet avoid undesired sugar dehydration products such as HMF. Hydrolysis product is useful as feedstock for fermentations including fermentation processes for ethanol, butanol and other fuels.Type: ApplicationFiled: April 10, 2014Publication date: August 7, 2014Applicant: Wisconsin Alumni Research FoundationInventors: Ronald T. RAINES, Joseph B. BINDER
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Patent number: 8722878Abstract: High-yielding method for chemical hydrolysis of lignocellulose into monosaccharides. The process of the invention can additionally be applied to cellulose, xylan and related biomass polysaccharides, such as galactan, mannan, or arabinan. The method is employed for hydrolysis of a biomass polysaccharide substrate. The process is carried out in an ionic liquid in which cellulose is soluble in the presence of catalytic acid at a temperature sufficiently high to initiate hydrolysis. Water is added to the reaction mixture after initiation of hydrolysis at a rate controlled to avoid precipitation yet avoid undesired sugar dehydration products such ad HMF. Hydrolysis product is useful as feedstock for fermentations including fermentation processes for ethanol, butanol and other fuels.Type: GrantFiled: June 24, 2010Date of Patent: May 13, 2014Assignee: Wisconsin Alumni Research FoundationInventors: Ronald T. Raines, Joseph B. Binder
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Patent number: 8697062Abstract: The present invention relates generally to conjugates of human ribonucleases and water-soluble polymers, compositions comprising the conjugates and methods of using the same. In particular, the present invention provides conjugates of human ribonucleases and one or more water-soluble polymer compositions (e.g., to increase serum half-life and a pharmacokinetic profile, in vivo biological activity, stability, and/or reduce host immune response to the protein in vivo) as well as methods of using the conjugates in the therapy, treatment, and/or prevention of disease (e.g., cancer).Type: GrantFiled: October 8, 2008Date of Patent: April 15, 2014Assignee: Quintessence Biosciences, Inc.Inventors: Ronald T. Raines, Thomas J. Rutkoski, John A. Kink, Laura E. Strong