Claims for Patent: 9,624,260

Summary for Patent: 9,624,260

Title:	Process for isolation of plasma or serum proteins
Abstract:	The present invention provides a process for the isolation of one or more proteins) from a protein solution. The process comprising the steps of: a) providing a protein solution comprising one or more specific proteins) and having a preset pH and a preset ionic strength or conductivity, b) applying the protein solution to a packed bed or expanded bed column comprising an adsorbent, and c) obtaining one or more proteins) from the column; wherein the protein solution has been supplemented with an alcohol.
Inventor(s):	Lihme; Allan Otto Fog (Birkerod, DK)
Assignee:	Therapure Biopharma Inc. (Mississauga, Ontario, CA)
Application Number:	11/570,154
Patent Claims:	1. A process for the large-scale isolation of one or more proteins from a protein solution, wherein the protein solution is obtained from a source selected from the group consisting of human blood and a solution derived from human blood, and wherein the protein solution has not been supplemented with an alcohol, the process comprising the steps of: a) adjusting the pH of the solution to a pH in the range of 3 to 10; b) adjusting the ionic strength or conductivity of the protein solution to an ionic strength in the range of 0.0001 to 12 or a conductivity in the range of 0.01 to 1000 mS/cm; c) applying said protein solution to an adsorption column comprising an adsorbent, said adsorbent comprises a particle with at least one high density non-porous core, surrounded by a porous material, the adsorbent comprises a particle density of at least 1.5 g/ml and a mean volume particle diameter of at most 150 .mu.m, whereby one or more proteins are bound to the adsorbent; d) obtaining a non-bound material fraction from the column, which non-bound material fraction contains at least one non-bound protein; e) subjecting the adsorbent to at least one elution buffer to elute at least one of the proteins bound to the adsorbent, thereby obtaining a bound material fraction; and f) subjecting the non-bound material fraction to further processing to obtain at least one non-bound protein therefrom. 2. The process according to claim 1, wherein the proteins are human blood proteins from the human blood solution. 3. The process according to claim 1, further comprising at least one virus elimination treatment. 4. The process according to claim 3, wherein the at least one virus elimination treatment is performed prior to contacting the protein solution with the adsorbent. 5. The process according to claim 3, wherein the virus elimination treatment involves addition of detergent and/or an organic solvent to the protein solution. 6. The process according to claim 1, wherein the adsorbent comprises a functionalized matrix polymer carrying a plurality of covalently attached functional groups comprising an aromatic ring-system, a heteroaromatic ring-system or one or more acidic groups. 7. The process according to claim 2, wherein the human blood proteins are selected from the group consisting of albumin, IgG, IgA, IgM, IgD, IgE, alpha-1-proteinase inhibitor, blood pro-coagulation protein, blood anti-coagulation protein, anti-angiogenic protein, .alpha.-2-antiplasmin, C-1 esterase inhibitor, apolipoprotein, HDL, LDL, Fibronectin, beta-2-glycoprotein I, fibrinogen, plasminogen, plasmin, plasminogen activator, plasminogen inhibitor, plasma protease inhibitor, anti-thrombin III, streptokinase, inter-alpha-trypsin inhibitor, .alpha.-2-macroglobulin, amyloid protein, ferritin, pre-albumin, GC-globulin, haemopexin, C3-complement , transferrin, urokinase and .alpha.-1-acid-glycoprotein. 8. The process according to claim 1, wherein, after applying the protein solution to the adsorption column, one or more proteins are washed out as a non-bound protein with one or more washing buffers. 9. The process according to claim 1, wherein one non-bound protein is an alpha-1-proteinase inhibitor. 10. The process according to claim 1, wherein, prior to applying the protein solution to the adsorption column, the pH of the protein solution is adjusted to a pH in the range of pH 3.0 to pH 10.0. 11. The process according to claim 10, wherein the pH-value for capturing and for elution is maintained in the range of pH 3.0 to pH 10.0. 12. The process according to claim 1, wherein, prior to applying the protein solution to the adsorption column, the ionic strength is adjusted. 13. The process according to claim 1, wherein, prior to applying the protein solution to the adsorption column, the conductivity is adjusted. 14. The process according to claim 1, wherein the flow rate of the protein solution through the column is at least 2 cm/min. 15. The process according to claim 1, wherein the adsorbent has a dynamic binding capacity at 10% break-through for said at least one protein of at least 5 g per liter sedimented adsorbent. 16. The process according to claim 1, wherein at least 2 proteins are isolated from the protein solution, wherein the proteins are selected from the group consisting of albumin, IgG, IgA, IgM, IgD, IgE, alpha-1-proteinase inhibitor, blood pro-coagulation protein, blood anti-coagulation protein, anti-angiogenic protein, .alpha.-2-antiplasmin, C-1 esterase inhibitor, apolipoprotein, HDL, LDL, Fibronectin, beta-2-glycoprotein I, fibrinogen, plasminogen, plasmin, plasminogen activator, plasminogen inhibitor, plasma protease inhibitor, anti-thrombin III, streptokinase, inter-alpha-trypsin inhibitor, .alpha.-2-macroglobulin, amyloid protein, ferritin, pre-albumin, GC-globulin, haemopexin, C3-complement, transferrin, urokinase and .alpha.-1-acid-glycoprotein, and wherein the proteins are isolated in at least 2 fractions. 17. The process according to claim 16, wherein at least 2proteins are isolated from the protein solution, wherein the proteins are selected from the group consisting of .alpha.-1 proteinase inhibitor, IgG, human albumin, transferrin, thrombin, Factor II, Factor V, Factor VII, Factor VII, Factor IX, protein C, Protein S, .alpha.-1-acid-glycoprotein and fibrinogen, and wherein the proteins are isolated in at least 2fractions. 18. The process according to claim 1, wherein at least one of the proteins bound to the adsorbent comprises fibrinogen and wherein the at least one non-bound protein comprises Factor II, Factor V, Factor VII, Factor VIII, von Willebrand factor, Factor VIII - von Willebrand factor complex, Factor IX, Factor X, Factor XI, C1 inhibitor, protein C and/or Protein S. 19. The process according to claim 1, wherein the bound proteins are albumin and IgG and the non-bound protein is .alpha.-1-proteinase inhibitor. 20. The process according to claim 19, wherein albumin and IgG are isolated from the bound fraction by stepwise elution. 21. The process according to claim 1, wherein fibrinogen and IgG are bound to the adsorbent and simultaneously albumin may be obtained as non-bound material from the adsorbent. 22. The process according to claim 21, wherein fibrinogen and IgG may be obtained from the adsorbent by stepwise elution. 23. The process according to claim 1, wherein the bound proteins are fibrinogen, albumin and IgG and the non-bound protein is .alpha.-1-proteinase inhibitor. 24. Theprocess according to claim 23, wherein fibrinogen, albumin and IgG are obtained from the adsorbent by stepwise elution. 25. The process according to claim 1, wherein at least 2 of fibrinogen, albumin, and/or IgG are bound to the adsorbent and simultaneously .alpha.-1-acid glycoprotein is obtained as non-bound material from the adsorbent. 26. The process according to claim 25, wherein the at least 2of fibrinogen, albumin and/or IgG are obtained from the adsorbent by stepwise elution. 27. The process according to claim 1, wherein the bound proteins are at least 2 of fibrinogen, albumin and/or IgG and the non-bound proteins are .alpha.-1-acid glycoprotein and/or .alpha.-1-proteinase inhibitor. 28. The process according to claim 27, wherein the at least 2 of fibrinogen, albumin and/or IgG may be obtained from the adsorbent by stepwise elution. 29. A process for the large-scale isolation of one or more proteins from a protein solution, wherein the protein solution is obtained from a source selected from the group consisting of human blood and a solution derived from human blood, and wherein the protein solution has not been supplemented with an alcohol, said process comprising the steps of: a) adjusting the pH of the protein solution to a pH in the range of 3 to 10; b) adjusting the ionic strength or conductivity of the protein solution to an ionic strength in the range of 0.0001 to 12 or a conductivity in the range of 0.01 to 1000 mS/cm; c) applying the protein solution to an adsorption column comprising an adsorbent, wherein the adsorbent comprises a functionalised matrix polymer carrying a plurality of covalently attached functional groups comprising an aromatic or heteroaromatic ring-system and one or more acidic groups, whereby one or more proteins are bound to the adsorbent; d) obtaining a non-bound material fraction from the column, which non-bound material fraction contains at least one non-bound protein; e) subjecting the adsorbent to at least one elution buffer to elute at least one of the proteins bound to the adsorbent; and f) subjecting the non-bound material fraction to further processing to isolate at least one non-bound protein therefrom. 30. The process according to claim 29, further comprising at least one virus elimination treatment. 31. The process according to claim 29, wherein one of the non-bound proteins is .alpha.-1-proteinase inhibitor. 32. The process according to claim 29, wherein one of the bound proteins is human albumin. 33. The process according to claim 29, wherein one of the bound proteins is fibrinogen. 34. The process according to claim 29, wherein one of the bound proteins is transferrin. 35. The process according to claim 29, wherein one of the non-bound proteins is .alpha.-1-acid glycoprotein. 36. The process according to claim 29, wherein one of the non-bound proteins is a coagulation or anticoagulation factor. 37. The process according to claim 36, wherein the coagulation or anti-coagulation factor is selected from the group consisting of Factor II, Factor V, Factor VII, Factor VIII, von Willebrand factor, Factor VIII - von Willebrand factor complex, Factor IX, Factor X, Factor XI, C1 inhibitor, protein C and Protein S. 38. A process for the large-scale isolation of one or more proteins from a protein solution, wherein the protein solution is obtained from a source selected from the group consisting of human blood and a solution derived from human blood, and wherein the protein solution has not been supplemented with an alcohol, said process comprising the steps of: a) providing a protein solution comprising one or more proteins obtained from a source selected from the group consisting of human blood or a solution derived from human blood, the protein solution having a preset pH and a preset ionic strength or conductivity; b) contacting the protein solution with an adsorbent, wherein the adsorbent comprises a particle with at least one high density non-porous core, surrounded by a porous material, whereby one or more proteins is bound to the adsorbent; c) subjecting the adsorbent to an elution buffer to elute at least one of the proteins bound to the adsorbent; and d) subjecting the adsorbent to one or more additional elution buffers to elute one or more remaining proteins bound to the adsorbent. 39. The process according to claim 38, further comprising at least one virus elimination treatment. 40. The process according to claim 38, wherein one of the proteins isolated from the protein solution is an .alpha.-1-proteinase inhibitor. 41. The process according to claim 38, wherein one of the proteins isolated from the protein solution is human albumin. 42. The process according to claim 38, wherein one of the proteins isolated from the protein solution is fibrinogen. 43. The process according to claim 38, wherein one of the proteins isolated from the protein solution is transferrin. 44. The process according to claim 38, wherein one of the proteins isolated from the protein solution is .alpha.-1- acid-glycoprotein. 45. The process according to claim 38, wherein one of the proteins isolated from the protein solution is a coagulation or anticoagulation factor. 46. The process according to claim 45, wherein the coagulation or anti-coagulation factor is selected from the group consisting of Factor II, Factor V, Factor VII, Factor VIII, von Willebrand factor, Factor VIII - von Willebrand factor complex, Factor IX, Factor X, Factor XI, C1 inhibitor, protein C and Protein S. 47. The process according to claim 1, wherein the protein solution is serum and/or plasma. 48. The process according to claim 2, wherein the human blood proteins are human plasma proteins or human serum proteins. 49. The process according to claim 16, wherein 3 proteins are isolated from the protein solution, and wherein the 3 proteins are isolated in 3 fractions. 50. The process according to claim 16, wherein 4 proteins are isolated from the protein solution, and wherein the 4 proteins are isolated in 4 fractions. 51. The process according to claim 16, wherein 5 proteins are isolated from the protein solution, and wherein the 5 proteins are isolated in 5 fractions. 52. The process according to claim 16, wherein 6 proteins are isolated from the protein solution, and wherein the 6 proteins are isolated in 6 fractions. 53. The process according to claim 17, wherein 3 proteins are isolated from the protein solution, and wherein the 3 proteins are isolated in 3 fractions. 54. The process according to claim 17, wherein 4 proteins are isolated from the protein solution, and wherein the 4 proteins are isolated in 4 fractions. 55. The process according to claim 17, wherein 5 proteins are isolated from the protein solution, and wherein the 5 proteins are isolated in 5 fractions. 56. The process according to claim 17, wherein 6 proteins are isolated from the protein solution, and wherein the 6 proteins are isolated in 6 fractions. 57. The process according to claim 25, wherein fibrinogen, albumin and IgG are bound to the adsorbent. 58. The process according to claim 27, wherein fibrinogen, albumin and IgG are bound to the adsorbent. 59. The process according to claim 5, wherein the detergent and/or organic solvent is selected from the group consisting of polysorbate detergents, octylphenol ethoxylate detergents, and tri-n-butyl phosphate. 60. The process of claim 1, wherein the human blood comprises human plasma or serum. 61. The process of claim 7 wherein the blood pro-coagulation protein or anti-coagulation protein is selected from the group consisting of Factor II, Factor V, Factor VII, Factor VIII, von Willebrand factor, Factor VIII - von Willebrand factor complex, Factor IX, Factor X, Factor XI, C1 inhibitor, protein C and Protein S. 62. The process of claim 16 wherein the blood pro-coagulation protein or anti-coagulation protein is selected from the group consisting of Factor II, Factor V, Factor VII, Factor VIII, von Willebrand factor, Factor VIII - von Willebrand factor complex, Factor IX, Factor X, Factor XI, C1 inhibitor, protein C and Protein S.

Details for Patent 9,624,260

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	January 16, 1978		2024-06-07
Octapharma Pharmazeutika Produktionsges.m.b.h.	OCTAPLAS	pooled plasma (human), solvent/detergent treated	For Injection	125416	January 17, 2013		2024-06-07