Methods directed to crystalline biomolecules
AssigneeAmgen Inc.
InventorsRizwan Sharnez, William Trieu, Marc A. Caporini, Ron C. Kelly, Neill Burt, Laura Nicholson, Twinkle R. Christian
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Abstract
Disclosed herein are methods of preparing a composition comprising crystalline biomolecules, for example, crystalline antibodies. In exemplary embodiments, the method comprises forming a fluidized bed of crystalline biomolecules using, for example, a counter-flow centrifuge to exchange buffer and/or to concentrate the crystalline biomolecules in a solution. Also provided are methods of detecting crystalline biomolecules and/or amorphous biomolecules in a sample.
Claims10
A method of preparing a composition comprising crystalline biomolecules, comprising:
- a) forming a fluidized bed of crystalline biomolecules in a rotating chamber comprising an inlet and an outlet, wherein the fluidized bed is created by rotating the chamber about a substantially horizontal axis to create a centrifugal force (Fcentrifugal) in said chamber, flowing a first stream of a first solution through the inlet in a direction opposite to the direction of the Fcentrifugal and at a first flow rate (FR1) having a force (FFR1) which counter balances Fcentrifugal, and collecting the first solution from the chamber while substantially maintaining the formation of the fluidized bed of crystallized biomolecules;
- b) performing step (i), (ii), or (iii):
- i. flowing a second stream of a second solution to replace the first stream of the first solution while substantially maintaining the formation of the fluidized bed of crystallized biomolecules;
- ii. concentrating the crystallized biomolecules within a region of the chamber by changing FR1 to a second flow rate (FR2) having a force (FFR2) which is less than Fcentrifugal or by increasing the speed of rotation of the chamber to increase Fcentrifugal to a level which is greater than FFR1;
- iii. a combination of step (i) and step (ii);
- and
- c) flowing a second stream into the chamber through the outlet in a direction which is parallel to the direction of the Fcentrifugal to crystalline remove the crystalline biomolecules from the chamber.
Dependencies are inferred from the claim text.