Issued Patents

PCT

PCT-Related Patents

 US Patents

 Rapid cryobaric sterilization and vaccine preparation

  • Authors: Laugharn, J., D. Bradley, and R. Hess
  • Date Awarded: 08/07/2001
  • Patent Number: US 6,270,723
  • Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -20o C to about 95o C.). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, the decontamination of military devices, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

Rapid cryobaric sterilization and vaccine preparation

  • Authors: Laugharn, J.A., D.W. Bradley, R.A. Hess
  • Date Awarded: 2/24/2004
  • Patent Number: US 6,696,019
  • Abstract: The invention is based on the discovery that biological and non-biological materials can be sterilized, decontaminated, or disinfected by repeatedly cycling between relatively high and low pressures. Pressure cycling can be carried out at low, ambient, or elevated temperatures (e.g., from about -40o C to about 95o C., or intermediate ranges). New methods based on this discovery can have applications in, for example, the preparation of vaccines, the sterilization of blood plasma or serum, plant, animal, and human tissue, sputum, urine, feces, water, and ascites, the decontamination of military devices, food and beverage production, and the disinfection of medical equipment. The new methods can also be incorporated into production processes or research procedures.

 Pressure-enhanced extraction and purification

  • Authors: James A. Laugharn, Robert Hess, and Feng Tao
  • Date Awarded: 12/01/2009
  • Patent Number: US 7,626,017 B2
  • Abstract: Methods for cell lysis and purification of biological materials, involving subjecting a sample to high pressure. Also featured is an apparatus for practicing the methods.

 High pressure sample containment system for electromagnetic measurements

  • Authors: Ting, E., A. Lazarev
  • Date Awarded: 09/20/2016
  • Patent Number: US 9,448,291
  • Abstract: The present invention is related to systems and methods for chemical and biological analysis and, in particular, to systems, apparatus, and methods of sample conditioning and analysis.

Extraction and partitioning of molecules

  • Authors: Lazarev, A., V. Gross
  • Date Awarded: 10/04/2016
  • Patent Number: US 9,458,190
  • Abstract: Methods of extracting a component of interest from a plurality of components are described.

Flow-through High Hydrostatic Pressure Microfluidic Sample Preparation Device and Related Methods Therefor

  • Authors: Ting, Edmund, Y., Lazarev, Alexander
  • Date Awarded: June 12, 2018
  • Patent Number: US 9995661
  • Abstract: Described herein is a sample preparation device including a sample delivery source, an inline means of transferring the sample from the sample source into a deformable channel within a pressure vessel, and out of the channel into downstream analysis components, a deformable channel disposed within the pressure vessel, the deformable channel having an inlet end and an outlet end fluidly connectable to high pressure valves and a means to measure the fluid pressure within the deformable channel, an external source of a controlled pressurized fluid fluidly connectable to the pressure vessel and a controller system that monitors and controls the sample fluid pressure by control of the external pressure vessel fluid.

Japanese Patents

Extraction and partitioning of molecules

  • Authors: Lazarev, A., V. Gross
  • Date Awarded: 08/01/2014
  • Patent Number: 5587770
  • Abstract: The present invention relates to the extraction and distribution of a molecule which were improved by the pressure.

Chinese Patents

System for High Pressure, High Shear Processing of Fluids

  • Author: Ting, Edmund, Y.
  • Date Awarded: 11/30/2016
  • Patent Number: ZL 2016 2 0243518.2
  • Abstract: A method for high fluid shear processing of a fluid uses an isolator that has a first sub-chamber for containing a first fluid and a second sub-chamber for containing a second fluid defined by a separator positioned in the chamber and movable between a first end of the chamber and a second end of the chamber. The two sub-chambers are in pressure communication with each other but are not in fluid communication with each other. A first fluid is pumped at an ultrahigh pressure into the first-sub chamber, and the pressure in the first sub-chamber causes a second fluid to be processed to be discharged from the second sub-chamber into a processing valve. A system is also provided for performing the steps of this method.

Ultrahigh Pressure Compact Valve with Throttling Capability

  • Authors: Edmund Y. Ting, Alexander Lazarev, and Ma Jun
  • Date Awarded: 8/15/2017
  • Patent Number: ZL 201621148183.2
  • Abstract: The utility model relates to a be superhigh pressure compact valve with throttle ability, one of them plant high -pressure valve include the pole with be used for help open under the high pressure with the variable force generator of the control of shut -off valve. Mobilizable round pin between position and the closed position is being opened including having the casing that provides the cavity that the fluid feeds through between first port and second port to the high- pressure valve in the cavity. The first end of pole is coupled round pin and the second end of pole coupled the variable force generator. The pole around pivot turning point pivot. Couple the controller of variable force generator, the controller is configured as the adjustment and is applied by the variable force generator power on the second end of pole is with control the round pin is in open the position with motion between the closed position.

Press-enhanced Extraction and Partitioning of Molecules

  • Authors: Lazarev, Alexander; Gross, Vera
  • Date Awarded: 10/27/2017
  • Patent Number: ZL 20088010044.1
  • Abstract: Abstract: Methods of extracting a component of interest from a plurality of components are described.

Taiwan Patents

Extraction and Partitioning of Molecules

  • Authors: Lazarev, Alexander; Gross, Vera
  • Award Date: 9/11/207
  • Patent Number: I598359
  • Abstract: Abstract: Methods of extracting a component of interest from a plurality of components are described.

Barofold-Related Patents

US Patents

High pressure refolding of protein aggregates and inclusion bodies 

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. 
  • Date Awarded: 12/3/2002
  • Patent Number: 6,489,450
  • Abstract: 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.

High pressure refolding of protein aggregates and inclusion bodies 

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. 
  • Date Awarded: 6/20/2006
  • Patent Number: 7,064,192
  • Abstract: 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.

High pressure refolding of protein aggregates and inclusion bodies 

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. 
  • Date Awarded: August 3, 2010
  • Patent Number: 7,767,795
  • Abstract: 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.

 Methods for protein refolding

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. (San Francisco, CA), Webb; Jonathan N. (Zionsville, IN)
  • Date Awarded: 5/26/2009
  • Patent Number: 7,538,198
  • Abstract: The present invention relates generally to the field of protein biochemistry. More particularly, it concerns improved methods for the renaturation and refolding of polypeptides aggregates. 

Use of hydrostatic pressure to inhibit and reverse protein aggregation and facilitate protein refolding

  • Authors: Robinson; Anne Skaja (Kennett Square, PA), Robinson; Clifford R. (Kennett Square, PA), Foguel; Debora (Copa Cabana, BR), Silva; Jerson Lima (Copa Cabana, BR)
  • Date Awarded: 11/102009
  • Patent Number: 7,615,617
  • A novel approach is described for reversing aggregation and increasing refolding by application of hydrostatic pressure. A protein of interest in an aggregated, or inclusion body, or other non-native or inactive state is subjected to high hydrostatic pressure. This treatment denatures the protein to states (or conformations) competent for refolding and results in increased formation of native protein once pressure is released. The technique can facilitate conversion non-native proteins, including inclusion bodies and aggregates to native proteins without addition of chaotropic agents, changes in buffer, or large-scale dilution of reagents required for traditional refolding methods.

Methods for protein refolding

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. (San Francisco, CA), Webb; Jonathan N. (Zionsville, IN)
  • Date Awarded: 12/11/12
  • Patent Number: 8,329,878
  • Abstract: The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. 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.

Method for reducing immunogenicity of therapeutic protein compositions 

  • Authors: Seefeldt; Matthew (Denver, CO), Randolph; Theodore W. (Niwot, CO), Fradkin; Amber Haynes (Golden, CO), Carpenter; John (Denver, CO)
  • Date Awarded: 4/15/14
  • Patent Number: 8,697,848
  • Abstract: 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.

European Patents

High pressure refolding of protein aggregates and inclusion bodies 

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. 
  • Date Awarded: 07/09/1999
  • Patent Number: EP1095056
  • Country: EPO
  • 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.

Improved methods for protein refolding

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. (San Francisco, CA), Webb; Jonathan N. (Zionsville, IN)
  • Date Awarded: 03/26/2008
  • Patent Number: DE60133426
  • Country: Germany
  • Abstract: The present invention discloses improved methods of disaggregating protein aggregates, and refolding denatured proteins, using high pressure. 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

Improved protein disaggregation and refolding using high pressure

  • Authors: Randolph; Theodore W. (Niwot, CO), Carpenter; John F. (Littleton, CO), St. John; Richard J. (San Francisco, CA), Webb; Jonathan N. (Zionsville, IN)
  • Date Awarded: 03/26/08
  • Patent Number: EP1424789
  • Country: EPO
  • Abstract: 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.