Patents Assigned to Barofold, Inc.
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Publication number: 20160002285Abstract: The present invention provides methods for reducing and/or evaluating the immunogenic potential of a therapeutic protein preparation. The present invention further provides pharmaceutical compositions of therapeutic proteins and methods of treatment with the same, the compositions having low immunogenic potential and/or improved efficacy. The invention achieves these goals by evaluating therapeutic protein preparations for subvisible protein particulates, which can contribute significantly to the overall immunogenic potential of the protein preparation. Further, by maintaining the content of such subvisible protein particulates to below an immunogenic threshold level, the resulting pharmaceutical composition is less likely to result in a loss of tolerance (e.g., upon repeated administration), thereby improving both the safety and efficacy profile of the therapeutic.Type: ApplicationFiled: February 21, 2014Publication date: January 7, 2016Applicants: Barofold, Inc., The Regents of the University of Colorado, A Body CorporateInventors: Matthew B. Seefeldt, Theodore W. Randolph, Amber Haynes Fradkin, John F. Carpenter
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Publication number: 20140302589Abstract: The invention provides methods and systems for production of recombinant protein, and particularly, for production of recombinant protein from inclusion bodies. For example, in one aspect, the method comprises providing a protein preparation comprising inclusion bodies, preparing an inclusion body dispersion, and exposing the protein preparation to high pressure in a pressure vessel, to disaggregate and refold the inclusion body protein.Type: ApplicationFiled: May 30, 2014Publication date: October 9, 2014Applicant: Barofold, Inc.Inventors: Matthew Seefeldt, Eliana Gomez
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Patent number: 8802828Abstract: Methods for refolding antibodies, particularly monoclonal antibodies, from aggregated and/or denatured preparations by subjecting the antibody preparation to high hydrostatic pressure are provided. Refolded preparations of antibodies produced by the methods described herein are also provided.Type: GrantFiled: February 27, 2012Date of Patent: August 12, 2014Assignee: Barofold, Inc.Inventors: Matthew B. Seefeldt, Robert Nelson, Theodore W. Randolph, Lyndal K. Hesterberg
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Patent number: 8710197Abstract: The present disclosure provides an effective method for the refolding of denatured proteins in solution so that properly folded, biologically active protein in solution is recovered in high yield. The refolding takes place at pressures between about 0.25 kbar to about 3.5 kbar, advantageously at about 1.5 kbar to about 3 kbar. Typically a chaotropic agent is present at a concentration which is not effective for denaturing protein at atmospheric pressure, and optionally, oxidation-reduction reagents can be incorporated in the refolding solution so that native intramolecular disulfide bonds can be formed where that is desired. The method is applicable to substantially all proteins, especially after solubilization and/or denaturation of insoluble protein aggregates, inclusion bodies, or abnormal oligomeric (soluble) aggregates.Type: GrantFiled: November 5, 2010Date of Patent: April 29, 2014Assignee: Barofold, Inc.Inventors: Theodore W. Randolph, John F. Carpenter, Richard St. John
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Patent number: 8697848Abstract: The present invention provides methods for reducing and/or evaluating the immunogenic potential of a therapeutic protein preparation. The present invention further provides pharmaceutical compositions of therapeutic proteins and methods of treatment with the same, the compositions having low immunogenic potential and/or improved efficacy. The invention achieves these goals by evaluating therapeutic protein preparations for subvisible protein particulates, which can contribute significantly to the overall immunogenic potential of the protein preparation. Further, by maintaining the content of such subvisible protein particulates to below an immunogenic threshold level, the resulting pharmaceutical composition is less likely to result in a loss of tolerance (e.g., upon repeated administration), thereby improving both the safety and efficacy profile of the therapeutic.Type: GrantFiled: July 19, 2011Date of Patent: April 15, 2014Assignees: The Regents of the University of Colorado, Barofold, Inc.Inventors: Matthew Seefeldt, Theodore W. Randolph, Amber Haynes Fradkin, John Carpenter
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Patent number: 8329878Abstract: The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. In particular, the present invention provides for the use of agitation, high temperature, “stepped” depressurization, dialysis and dilution under pressure to increase the speed and extent of aggregate dissolution and protein refolding.Type: GrantFiled: April 17, 2009Date of Patent: December 11, 2012Assignee: Barofold Inc.Inventors: Theodore W. Randolph, John F. Carpenter, Richard J. St. John, Jonathan N. Webb
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Publication number: 20120070406Abstract: The present invention provides methods for reducing and/or evaluating the immunogenic potential of a therapeutic protein preparation. The present invention further provides pharmaceutical compositions of therapeutic proteins and methods of treatment with the same, the compositions having low immunogenic potential and/or improved efficacy. The invention achieves these goals by evaluating therapeutic protein preparations for subvisible protein particulates, which can contribute significantly to the overall immunogenic potential of the protein preparation. Further, by maintaining the content of such subvisible protein particulates to below an immunogenic threshold level, the resulting pharmaceutical composition is less likely to result in a loss of tolerance (e.g., upon repeated administration), thereby improving both the safety and efficacy profile of the therapeutic.Type: ApplicationFiled: July 19, 2011Publication date: March 22, 2012Applicants: The Regents of the University of Colorado, A Body Corporate, Barofold, Inc.Inventors: Matthew SEEFELDT, Theodore W. RANDOLPH, Amber Haynes FRADKIN, John CARPENTER
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Patent number: 7829681Abstract: Described herein are methods for the solubilization and proteolytic cleavage of fusion protein aggregates, including autocatalytic fusion proteins, at pressures greater than atmospheric pressure to yield soluble target polypeptides.Type: GrantFiled: April 7, 2008Date of Patent: November 9, 2010Assignee: Barofold Inc.Inventors: Matthew B. Seefeldt, Lyndal K. Hesterberg, Theodore W. Randolph, John F. Carpenter
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Patent number: 7767795Abstract: The present disclosure provides an effective method for the refolding of denatured proteins in solution so that properly folded, biologically active protein in solution is recovered in high yield. The refolding takes place at pressures between about 0.25 kbar to about 3.5 kbar, advantageously at about 1.5 kbar to about 3 kbar. Typically a chaotropic agent is present at a concentration which is not effective for denaturing protein at atmospheric pressure, and optionally, oxidation-reduction reagents can be incorporated in the refolding solution so that native intramolecular disulfide bonds can be formed where that is desired. The method is applicable to substantially all proteins, especially after solubilization and/or denaturation of insoluble protein aggregates, inclusion bodies, or abnormal oligomeric (soluble) aggregates.Type: GrantFiled: January 27, 2006Date of Patent: August 3, 2010Assignee: BaroFold Inc.Inventors: Theodore W. Randolph, John F. Carpenter, Richard St. John
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Publication number: 20100112660Abstract: The present invention provides an effective method for derivatization of proteins using hydrostatic pressure to reversibly perturb the native conformation of a protein such that a normally buried functional group on the protein, such as an amino acid residue, or a ligand or cofactor associated with the protein, is exposed and available for derivatization by a polymer molecule or a cytotoxic agent. The methods described herein do not require use of chaotropes, changes in pH, changes in temperature, or genetic modification of the native primary sequence of the protein and are applicable to substantially all proteins.Type: ApplicationFiled: May 29, 2009Publication date: May 6, 2010Applicant: BaroFold, Inc.Inventor: Mary S. Rosendahl
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Patent number: 7538198Abstract: The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. In particular, the present invention provides for the use of agitation, high temperature, “stepped” depressurization, dialysis and dilution under pressure to increase the speed and extent of aggregate dissolution and protein refolding.Type: GrantFiled: April 29, 2003Date of Patent: May 26, 2009Assignee: Barofold, Inc.Inventors: Theodore W. Randolph, John F. Carpenter, Richard J. St. John, Jonathan N. Webb