Tangential flow filtration process and apparatus

• US 5,490,937 A
• Filed: 07/06/1994
• Issued: 02/13/1996
• Est. Priority Date: 09/17/1990
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: van Reis, Robert D.
• Primary Examiner(s): SPEAR JR, FRANK
• Application Number:
  US08/271,223
• Time in Patent Office: 587 Days
• Field of Search: 210/637, 210/641, 210/137, 210/321.65, 210/651, 210/109, 210/321.84
• US Class Current: 210/637
• CPC Class Codes: B01D 61/145 Ultrafiltration
• CPC Class Codes: B01D 61/146 comprising multiple ultrafiltration steps
• CPC Class Codes: B01D 61/147 Microfiltration
• CPC Class Codes: C07K 1/34 by filtration, ultrafiltration or reverse osmosis
• CPC Class Codes: C12M 23/58 Reaction vessels connected in series or in parallel combinations of bioreactors with other apparatus, C12M43/00
• CPC Class Codes: C12M 47/02 Separating microorganisms from the culture medium; Concentration of biomass separating microorganisms from their culture media C12N1/02
• CPC Class Codes: C12M 47/10 Separation or concentration of fermentation products bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02

Abstract

Processes and apparati are provided for separating species of interest from a mixture containing them which comprises subjecting the mixture to tangential-flow filtration, wherein the filtration membrane preferably has a pore size that retains species with a size up to about 10 microns, and the flux is maintained at a level ranging from about 5 % up to 100 % of transition point flux.

Claims

1. A process for separating species of interest having a molecular weight of about 1 to 1000 kDa from a mixture, which process comprises filtering the mixture by tangential-flow filtration through a filtration membrane having a pore size that separates said species of interest from the mixture, while maintaining flux at a level ranging from about 5 to 100% of transition point flux in the pressure-dependent region of the flux versus TMP curve, whereby the species of interest are selectively separated from the mixture, and wherein transmembrane pressure decreases or remains approximately constant as the filtration progresses.

2. The process of claim 1 wherein the flux is from about 50 to 100% of the transition point flux.

3. The process of claim 1 wherein the flux is from about 75 to 100% of the transition point flux.

4. The process of claim 1 wherein the mixture is undiluted.

6. The process of claim 1 wherein transmembrane pressure decreases as the filtration progresses.

7. The process of claim 1 wherein transmembrane pressure remains approximately constant as the filtration progresses.

8. The process of claim 1 wherein the species of interest are biological entities selected from the group consisting of proteins, polypeptides, amino acids, colloids, mycoplasm, endotoxins, viruses, carbohydrates, RNA, and DNA.

9. The process of claim 8 wherein the species of interest are proteins or polypeptides.

10. The process of claim 1 wherein the species of interest are less than ten times larger or smaller in molecular weight than the other species of interest of the mixture.

11. The process of claim 1 wherein transmembrane pressure is held substantially constant along the membrane at a level no greater than the transmembrane pressure at the transition point of the filtration.

5. The process of claim l wherein retentate from the filtration is recycled to a tank containing the mixture to be separated and the process is repeated.

12. A process for separating at least two proteins or polypeptides from each other that are contained in a mixture, wherein the proteins or polypeptides differ from each other in molecular weight by less than ten fold, which process comprises filtering the mixture by tangential-flow filtration through a filtration membrane having a pore size that separates the polypeptides or proteins from the mixture, while maintaining flux at a level ranging from about 5 to 100% of transition point flux in the pressure-dependent region of the flux versus TMP curve, whereby the proteins or polypeptides are selectively separated from the mixture, and wherein transmembrane pressure decreases or remains approximately constant as the filtration progresses.