Back to results
US 6,596,172 B1Granted
Purification of biological substances
OwnerHenry B. Kopfinventor
Life of this patent
Estimating the term…
Abstract
A process and apparatus for purifying one or more target substances from a source liquid, employing one or more cross-flow filter elements, and one or more types of chromatography resins, in combination, to provide purification with advantageous yield, product purity, and cost- and time-efficiency.
Claims61
A process for purifying one or more target substances from a source liquid, said process comprising:
- (a) contacting the source liquid with one or more chromatography resins;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the resins to bind a predetermined fraction of the target substance(s);
- (c) circulating the chromatography resin(s) in a cross-flow filter wherein one or more of the following steps is performed:
- (i) separating unbound substances from the chromatography-resin-bound target substance(s) by concentration and/or diafiltration;
- (ii) eluting the target substance(s) from the chromatography resin(s);
- and
- (iii) separating the target substance(s) from the chromatography resin(s) by concentration and/or diafiltration;
- (d) recovering the target substance(s);
- and
- (e) optionally concentrating and/or diafiltering the target substance(s).
7 more elements
A process for purifying one or more target substances from a source liquid, said process comprising:
- (a) contacting the source liquid with a chromatography resin;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the chromatography resin to bind a predetermined fraction of target substance(s);
- (c) circulating the chromatography resin in a cross-flow filter wherein one or more of the following steps is performed:
- (i) separating unbound substances from the chromatography-resin-bound target substance(s) by concentration and/or diafiltration;
- (ii) eluting the target substance(s) from the chromatography resin;
- and
- (iii) separating the target substance(s) from the chromatography resin by concentration and/or diafiltration;
- (d) recovering the target substance(s);
- and
- (e) optionally concentrating and/or diafiltering the target substance(s).
7 more elements
A process for depleting one or more contaminants from a source liquid, said process comprising:
- (a) contacting the source liquid with one or more chromatography resins;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the resins to bind a predetermined fraction of the contaminant(s);
- (c) circulating the chromatography resin(s) in a cross-flow filter wherein the unbound substances are separated from the chromatography-resin-bound contaminant(s) by concentration and/or diafiltration.
A process for depleting one or more target substances from a source liquid, said process comprising:
- (a) contacting the source liquid with a chromatography resin;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the resins to bind a predetermined fraction of one or more contaminants;
- (c) circulating the chromatography resin in a cross-flow filter to separate unbound substances from the chromatography-resin-bound target substance(s) by concentration and/or diafiltration.
A process for depleting one or more contaminants from a source liquid, said process comprising:
- (a) contacting the source liquid with one or more chromatography resins;
- (b) maintaining the contact for a sufficient period of time under conditions suitable for the resins to bind a predetermined fraction of one or more contaminant(s);
- (c) circulating the chromatography resin(s) in a cross-flow filter wherein one or more of the following steps is performed:
- (i) separating unbound substances from the chromatography-resin-bound contaminant(s) by concentration and/or diafiltration;
- (ii) recovering the contaminant(s)-depleted source liquid;
- and
- (iii) optionally concentrating and/or diafiltering of the source liquid.
4 more elements
A process for depleting one or more contaminants from a source liquid, said process comprising:
- (a) contacting the source liquid with a chromatography resin;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the resins to bind a predetermined fraction of one or more contaminant(s);
- (c) circulating the chromatography resin in a cross-flow filter to separate unbound substances from the chromatography-resin-bound contaminant(s) by concentration and/or diafiltration;
- (d) recovering the contaminant(s)-depleted source liquid;
- and
- (e) optionally concentrating and/or diafiltration of the source liquid.
3 more elements
A method of purifying a liquid comprising one or more target substances, the method comprising
- (a) contacting the liquid with a chromatography resin to bind the target substance(s) thereto;
- and
- (b) cross-flow filtering the target substance(s)-bound chromatography resin under elution conditions to recover a filtrate comprising the target substance(s).
A method of purifying a liquid purifying comprising one or more target substance(s), the method comprising the steps of contacting the liquid with a chromatography resin to bind one or more non-target substances thereto, and cross-flow filtering the non-target substance(s)-bound chromatography resin under concentration and/or diafiltration conditions to recover a filtrate comprising the target substance(s).
A method of purifying one or more target substances from a source liquid comprising one or more bioactive contaminants, the method comprising the steps of:
- (a) contacting the source liquid with a chromatography resin;
- (b) maintaining the contact for a sufficient period of time and under conditions suitable for the resin to bind a predetermined fraction of the target substance(s);
- (c) circulating the chromatography resin in a cross-flow filter wherein one or more of more of the following steps is performed:
- (i) concentration and/or diafiltration of the chromatography resin;
- (ii) elution of the target substance(s) from the chromatography resin;
- and
- (iii) separation of the target substance(s) from the chromatography resin by concentration and/or diafiltration;
- (d) recovering the target substance(s);
- (e) optionally concentrating the target substance(s);
- and
- (f) inactivating the bioactive contaminant(s) during said method.
8 more elements
A process for purifying one or more target substances from a source liquid comprising the target substance(s) together with one or more viral species, the process comprising:
- (a) contacting the source liquid with a viral inactivation agent to inactivate the viral species;
- (b) contacting the source liquid with a chromatography resin;
- (c) incubating the source liquid with the chromatography resin for a sufficient contact time to bind a desired fraction of the target substance(s);
- (d) circulating the chromatography resin in a cross-flow filter apparatus wherein one or more of the following steps is performed:
- (i) concentrating the chromatography resin and separating one or more contaminants from the chromatography-resin-bound target substance(s) by diafiltration in a filter comprising a membrane effective to retain the resin and pass species that are not bound to the resin;
- (ii) eluting the target substance(s) from the chromatography resin by contact with an elution membrane effective to retain the resin and pass the target substance(s);
- and
- (iii) separating the target substance(s) from the chromatography resin by diafiltration;
- (e) recovering the target substance(s);
- and
- (f) optionally concentrating the target substance(s).
8 more elements
A process for purifying one or more target substances from a source liquid containing the target substance(s), the process comprising:
- (a) contacting the source liquid with a chromatography resin;
- (b) circulating the chromatography resin in at least one cross-flow filter apparatus wherein one or more of the following steps is performed:
- (i) optionally concentrating the target substance(s) and chromatography resin in the source liquid by tangential flow filtration;
- (ii) diafiltering the chromatography resin in a filter comprising a membrane effective to retain the resin and pass species that are not bound to the resin;
- (iii) eluting the target substance(s) from the chromatography resin by contact with an elution membrane effective to retain the resin and pass the target substance(s);
- (iv) separating the target substance(s) from the chromatography resin by concentration and/or diafiltration of the resin recovering the target substance(s);
- and
- (v) optionally concentrating the target substance(s).
5 more elements
A method of separating a liquid in a separation system, the method comprising:
- (a) providing a bioreactor, a chromatographic resin reservoir, a first cross-flow filtration module, a second cross-flow filtration module, and a third cross-flow filtration module;
- (b) clarifying perfusate of the bioreactor in the first cross-flow filtration module to yield a permeate;
- (c) flowing the permeate to the chromatographic resin reservoir;
- (d) flowing chromatographic resin and permeate to the second cross-flow filtration module for concentration, diafiltration and elution to yield an eluate;
- and
- (e) flowing the eluate to the third cross-flow filtration module for concentration and diafiltration therein.
3 more elements
A method of separating a liquid in a separation system, the method comprising:
- (a) providing a bioreactor, a chromatographic resin reservoir, a first cross-flow filtration module, and a second cross-flow filtration module;
- (b) optionally, clarifying the fluid from the bioreactor;
- (c) flowing the fluid to the chromatographic resin reservoir;
- (d) flowing chromatographic resin and fluid to the first cross-flow filtration module for concentration and/or diafiltration and elution to yield an eluate;
- and
- (e) flowing the eluate to the second cross-flow filtration module for concentration and/or diafiltration therein.
3 more elements
A method for purifying multiple target substances from a source liquid comprising said target substances, utilizing multiple cross-flow filters and multiple chromatography resins the method comprising:
- (a) contacting the source liquid with a first chromatography resin;
- (b) circulating the first chromatography resin across a first cross-flow filter wherein the following steps are performed:
- (i) optionally, concentrating a first target substance and the first chromatography resin in the source liquid by tangential flow filtration;
- (ii) diafiltering the first chromatography resin in a filter comprising a membrane effective to retain the resin and pass species that are not bound to the resin;
- (iii) eluting the first target substance from the chromatography resin by contact with an elution membrane effective to retain the resin and pass the target substance;
- (c) separating the first target substance from the first chromatography resin by concentration and/or diafiltration of the first resin recovering the first target substance;
- and
- (d) optionally, concentrating the first target substance;
- (e) contacting the permeate of the first cross-flow filter with a second chromatography resin to isolate a second target substance;
- (f) circulating the second chromatography resin across a second cross-flow filter wherein one or more of the following steps is performed:
- (i) optionally concentrating the second target substance and the second chromatography resin in the permeate of the first cross-flow filter by tangential flow filtration;
- (ii) diafiltering the second chromatography resin in a filter comprising a membrane effective to retain the resin and pass species that are not bound to the resin;
- (iii) eluting the second target substance from the second chromatography resin by contact with an elution membrane effective to retain the resin and pass the second target substance;
- (g) separating the second target substance from the second chromatography resin by concentration and/or diafiltration of the second resin recovering the second target substance;
- and
- (h) optionally concentrating the second target substance;
- and
- (i) sequentially repeating steps sequence of steps (e), (f), (g), and (h) with the permeate generated by the previous cross-flow filter with a subsequent chromatography resin until all the desired target substances are obtained.
15 more elements
Dependencies are inferred from the claim text.