Plasma Technologies, LLC

Dennis Curtin

Eugene J Zurlo

Kurt L Brillhart

Peter Radtke

Allan L Louderback

Klaus Peter Radtke

David P Nowotnik

Matthew Whelihan

Ryan Dorfman

Gene Zurlo

Charles M Heldebrant

Charles Heldebrant

Eugene Zurlo

Allan Louderback

PHD Charles Heldebrant

David Peter Nowotnik

Methods of producing multiple protein products from blood-based materials including alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins are described herein. The inventive methods include steps of: salt fractionation, chromatography, ultrafiltration, diafiltration, solvent-detergent treatment, and sterile filtration. Advantageously, the inventive methods are simple and produce alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins in high yields. The sequence of process steps can be selected to obtain multiple products from various in-process materials, such as supernatants, pastes, chromatography flow-though, and chromatography washes.

Methods for extracting proteins from a blood-based material

Systems and methods are described in which proteins are isolated from complex solution using successive chromatographic separations that retain the protein of interest in the flow-through. At least one of the chromatography media used is selected to be capable of interacting with both contaminants and the protein of interest, however capacity of this media is selected such that the protein of interest is displaced and remains in the flow-through.

Compositions and methods for isolating proteins

Methods are provided for isolation of immunoglobulin G (IgG) from plasma, where IgG is initially fractioned by salt precipitation, followed by successive ion exchange steps in which IgG appears in unbound, flow-through fractions of the ion exchange steps. Some embodiments employ successive anion exchange steps. Other embodiments employ an anion exchange step followed by application of flow-through of the anion exchange step to a cation exchange step, with IgG collected in flow-through fractions from the cation exchange step. IgG is collected at high yield (typically about 75% or greater) and high purity. Avoidance of binding and elution from chromatography media simplifies processing and scale up without sacrificing IgG quality or yield.

Systems and methods for process scale isolation of immunoglobulin G

Methods for isolating proteins from solution by precipitation and compositions generated thereby are provided. A nonvolatile precipitation agent is added to an aqueous protein solution at a low concentration. Water is then removed from the resulting solution until the precipitant and the protein content of the solution increase to a concentration that provides the desired segregation of proteins between supernatant and precipitate. Additional water can be removed from the supernatant to provide additional fractionation. Water can be removed by evaporation (e.g. under reduced pressure) and/or diafiltration.

Compositions and methods for high efficiency protein precipitation

Compositions of the inventive concept provide a therapeutic protein with less than 2% contamination by the therapeutic protein in denatured form. Such compositions provide enhanced specific activity and improved stability on storage and/or in serum than corresponding therapeutic protein preparations resulting from conventional isolation methods.

Therapeutic protein compositions and methods

Compositions and methods are provided that simplify isolation of proteins of interest from serum or plasma. Finely divided silica or a similar lipid/lipoprotein binding solid is used in combination with a protein precipitating agent to generate a solution that includes the protein of interest and that can be applied to chromatography media without resulting in significant fouling of the media. The method is particularly suitable for isolation of immunoglobulin G.

Compositions and methods for simplified high efficiency isolation of proteins

A method of producing protein products including alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins from plasma includes steps of: (1) adding a salt to the blood product to produce a first intermediate, wherein the salt comprises between 11-13 wt % of the first intermediate; (2) separating the first intermediate to produce a first supernatant and a first paste; (3) adding a salt to the first intermediate to produce a second intermediate, wherein the salt comprises between 21-23 wt % of the second intermediate; (4) separating the second intermediate to produce a second supernatant and a second paste; (5) separating a third intermediate from the second supernatant by affinity chromatography; and (6) separating the third intermediate by ion exchange chromatography to produce an eluate containing the protein product. Advantageously, the inventive methods are simple and produce alpha-1-proteinase inhibitor, gamma globulin, albumin, and other proteins in high yields.

Methods for extracting A1P1 and albumin from blood plasma

Methods for isolating proteins from solution by precipitation are provided. A nonvolatile precipitation agent is added to an aqueous protein solution at a low concentration. Water is then removed from the resulting solution until the precipitant and the protein content of the solution increase to a concentration that provides the desired segregation of proteins between supernatant and precipitate. Additional water can be removed from the supernatant to provide additional fractionation. Water can be removed by evaporation (e.g. under reduced pressure) and/or diafiltration.

Methods for extracting proteins from blood plasma

The instant invention provides novel and effective methods of isolating alpha-1-antitrypsin from cryo-poor plasma and formulating it into therapeutic products. This invention achieves higher yields and a superior quality of alpha-1-antitrypsin. Alpha-1-antitrypsin is isolated from cryo-poor plasma, using one or more salts selected from a group comprising sodium citrate, sodium acetate, sodium gluconate, ammonium sulfate, sodium chloride, sodium sulfate and ammonium chloride in two fractionation steps, followed by diafiltration to remove those salts employed.

Ultra-high yield of alpha-1-anti-trypsin

An efficacious large-scale alcohol-free plasma fractionation production process which produces a high-yielding, non-denatured, double viral-inactivated intravenous human immune gamma globulin (IgG) product. The process employs sodium citrate in two initial fractionation steps, followed by diafiltration to remove sodium citrate.

Ultra-high yield intravenous immune globulin preparation

An efficacious large-scale alcohol-free plasma fractionation production process which produces a high-yielding, non-denatured, double viral-inactivated intravenous human immune gamma globulin (IgG) product. The process employs one or more salts from a group of salts comprising sodium citrate, sodium acetate, sodium gluconate, ammonium sulfate, sodium chloride, sodium sulfate and ammonium chloride in two initial fractionation steps, followed by diafiltration to remove those salts employed. A process which employs alcohol via the process of the disclosed inventive method is also disclosed.

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Plattsburgh, NY, United States of America

Dennis Curtin