Method for the crystallization of human serum albumin
First Claim
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1. A crystalline human albumin product comprising at least a portion of the material resulting from a process of:
- a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a first phosphate mixture to said albumin containing fluid until the concentration of said phosphate mixture is in the range of 2.4-2.6 molar;
c) providing a first filtering of said albumin containing solution so as to form a resultant crystallizing batch solution to remove impurities;
d) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 15°
C.;
e) allowing the human albumin in said crystallizing batch solution to crystallize;
f) adding more of said first phosphate mixture to said crystallizing batch solution sufficient to achieve a concentration of at most 3.0 molar;
g) making a first separation of albumin crystals from any remaining fluid;
h) suspending the albumin crystals from said first separation of albumin crystals in a second phosphate mixture wherein said second phosphate mixture has a concentration of 2.7-3.0 M;
i) heating the crystal suspension from said first separation of albumin crystals up to temperature in the range of 40-50°
C. in order to dissolve the crystals, j) providing a second filtering to the dissolved crystal suspension from said first separation of albumin crystals;
k) cooling the resultant dissolved crystal suspension from said first separation of albumin crystals to a temperature of at most 15°
C.; and
l) allowing albumin crystals to form form the resultant cooled crystal suspension;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given human albumin containing feedstream.
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Abstract
The present invention relates to the purification and production of human albumin from various sources through crystallization and repeated crystallization. Basic features of the invented process include providing specific reaction conditions and precipitating reagents to maximize albumin crystallization. Solubility diagrams are utilized as the basis for process control of the invented method. The current invention specifically controls phosphate concentration, pH and temperature to precisely guide crystallization kinetics and crystal yield.
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Citations
184 Claims
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1. A crystalline human albumin product comprising at least a portion of the material resulting from a process of:
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a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a first phosphate mixture to said albumin containing fluid until the concentration of said phosphate mixture is in the range of 2.4-2.6 molar;
c) providing a first filtering of said albumin containing solution so as to form a resultant crystallizing batch solution to remove impurities;
d) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 15°
C.;
e) allowing the human albumin in said crystallizing batch solution to crystallize;
f) adding more of said first phosphate mixture to said crystallizing batch solution sufficient to achieve a concentration of at most 3.0 molar;
g) making a first separation of albumin crystals from any remaining fluid;
h) suspending the albumin crystals from said first separation of albumin crystals in a second phosphate mixture wherein said second phosphate mixture has a concentration of 2.7-3.0 M;
i) heating the crystal suspension from said first separation of albumin crystals up to temperature in the range of 40-50°
C. in order to dissolve the crystals,j) providing a second filtering to the dissolved crystal suspension from said first separation of albumin crystals;
k) cooling the resultant dissolved crystal suspension from said first separation of albumin crystals to a temperature of at most 15°
C.; and
l) allowing albumin crystals to form form the resultant cooled crystal suspension;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given human albumin containing feedstream. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 168, 169)
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45. A method of producing crystalline human albumin comprising:
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a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a first phosphate mixture to said albumin containing fluid until the concentration of said phosphate mixture is in the range of 2.4-2.6 molar;
c) providing a first filtering of said albumin containing solution so as to form a resultant crystallizing batch solution to remove impurities;
d) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 15°
C.;
e) allowing the human albumin in said crystallizing batch solution to crystallize;
f) adding more of said first phosphate mixture to said crystallizing batch solution sufficient to achieve a concentration of at most 3.0 molar;
g) making a first separation of albumin crystals from any remaining fluid;
h) suspending the albumin crystals from said first separation of albumin crystals in a second phosphate mixture wherein said second phosphate mixture has a concentration of 2.7-3.0 M;
i) heating the crystal suspension from said first separation of albumin crystals up to temperature in the range of 40-50°
C. in order to dissolve the crystals,j) providing a second filtering to the dissolved crystal suspension from said first separation of albumin crystals;
k) cooling the resultant dissolved crystal suspension from said first separation of albumin crystals to a temperature of at most 15°
C.; and
l) allowing albumin crystals to form form the resultant cooled crystal suspension;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given human albumin containing feedstream. - View Dependent Claims (46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87)
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88. A human albumin product comprising at least a portion of the material resulting from a process of:
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a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a first phosphate mixture to said albumin containing fluid until the concentration of said phosphate mixture is in the range of 2.6-3.0 molar and the pH is in the range of 6.1-6.3;
c) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 15°
C.;
d) allowing the human albumin in said crystallizing batch solution to crystallize; and
e) separating the albumin crystals from any remaining fluid;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given human albumin containing feedstream. - View Dependent Claims (89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 144, 145, 170, 171)
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128. A human albumin product comprising at least a portion of the material resulting from a process of:
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a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a first phosphate mixture to said albumin containing fluid until the concentration of said phosphate mixture is at most 2.6 molar and the pH is in the range of 6.1-6.3;
c) providing a first filtering of said albumin containing solution so as to form a resultant crystallizing batch solution to remove impurities;
d) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 15°
C.;
e) adding more of said first phosphate mixture to said crystallizing batch solution sufficient to achieve a concentration of at most 3.0 molar;
f) allowing the human albumin in said crystallizing batch solution to crystallize; and
g) separating the albumin crystals from any remaining fluid;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given feedstream. - View Dependent Claims (129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 172, 173)
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174. A method of producing crystalline human albumin comprising:
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a) concentrating an albumin containing fluid until said fluid has at least 15 grams of albumin per liter of solution;
b) adding a sufficient amount of a first chemical modifying agent to said albumin containing fluid;
c) providing a first filtering of said albumin containing solution so as to form a resultant crystallizing batch solution to remove impurities;
d) cooling the resultant filtrate of said crystallizing batch solution to a temperature of at most 20°
C.;
e) allowing the human albumin in said crystallizing batch solution to crystallize;
f) adding more of said first chemical modifying agent to said crystallizing batch solution sufficient to achieve a concentration of at most 3.0 molar;
g) making a first separation of albumin crystals from any remaining fluid;
h) suspending the albumin crystals from said first separation of albumin crystals in a second chemical modifying agent;
i) heating the crystal suspension from said first separation of albumin crystals up to temperature in the range of 40-50°
C. in order to dissolve the crystals,j) providing a second filtering to the dissolved crystal suspension from said first separation of albumin crystals;
k) cooling the resultant dissolved crystal suspension from said first separation of albumin crystals to a temperature of at most 15°
C.; and
l) allowing albumin crystals to form form the resultant cooled crystal suspension;
wherein the application of these specific steps allows the purification and crystallization of human albumin from a given human albumin containing feedstream. - View Dependent Claims (175, 176, 177, 178, 179, 180, 181, 182, 183, 184)
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Specification