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KR-20260067373-A - High-viscosity ultrafiltration/dialysis filtration and single-pass tangential flow filtration processes

KR20260067373AKR 20260067373 AKR20260067373 AKR 20260067373AKR-20260067373-A

Abstract

The present disclosure provides high-viscosity ultrafiltration/dialysis filtration (UF/DF) and single-pass tangential flow filtration (SPTFF) processes used in the purification of polypeptides. A method for purifying polypeptides from polypeptide formulations may comprise the following steps in order: a) applying the polypeptide formulation to one or more purification processes and recovering a first resulting pool having a viscosity of about 5-40 cP; and b) applying the pool recovered from step a) to an SPTFF operation involving the use of a membrane having either or both of a serial membrane and/or parallel membrane configuration and recovering a second resulting pool having an operating viscosity of about 41-400 cP, wherein i) the operating temperature is about 15-55°C and ii) the feed flux is about 5-50 L/ m² /hr (LMH).

Inventors

  • 새킷, 벤자민 마크
  • 케바, 제임스 제이.

Assignees

  • 제넨테크, 인크.

Dates

Publication Date
20260512
Application Date
20240906
Priority Date
20230908

Claims (20)

  1. A method for purifying a polypeptide from a polypeptide preparation, comprising the following steps in order: a) applying a polypeptide formulation to one or more purification processes and recovering a first result pool having a viscosity of about 5-40 cP; and b) applying the pool recovered from step a) to a single-pass tangential flow filtration (SPTFF) operation and recovering a second resulting pool having an operating viscosity of about 41-400 cP, Here, i) The operating temperature is approximately 15-55℃, and ii) The feed fluid flux is approximately 5-50 L/ m² /hr(LMH).
  2. A method according to claim 1, wherein the viscosity of the first recovered pool in step a) is 10-35 cP.
  3. A method according to claim 1 or 2, wherein in step b) the STPFF operation involves the use of a serial membrane configuration.
  4. A method according to any one of claims 1 to 3, wherein in step b) the STPFF operation involves the use of a parallel membrane configuration.
  5. A method according to claim 3 or 4, wherein in step b) the SPTFF operation involves the use of both serial membrane configurations and parallel membrane configurations.
  6. A method according to any one of paragraphs 3 to 5, wherein in step b), the membrane composition is 1:1:1, 1:1:1:1, 2:1:1, or 2:2:1:1.
  7. A method according to any one of paragraphs 3 to 6, wherein in step b), the membrane composition comprises at least one of a 10 kD membrane and a 30 kD membrane.
  8. A method according to any one of claims 3 to 7, wherein in step b), the membrane composition comprises at least one of a narrow channel membrane and a wide channel membrane.
  9. A method according to any one of claims 1 to 8, wherein in step a), the polypeptide formulation is formulated in a viscosity-reducing excipient.
  10. A method according to any one of claims 1 to 9, wherein in step b), the operating temperature is about 15-50℃ or about 30-50℃.
  11. A method according to any one of claims 1 to 10, wherein in step b), the supply liquid flux is about 5-25 LMH or about 25-50 LMH.
  12. A method according to any one of claims 1 to 11, wherein in step b), the working viscosity is about 200-400 cP or about 200-300 cP.
  13. A method according to any one of claims 1 to 12, wherein in step b), the residual liquid pressure is about 5-20 psi.
  14. A method according to any one of claims 1 to 13, wherein one or more purification processes of step a) include ultrafiltration.
  15. A method according to any one of claims 1 to 14, wherein one or more purification processes of step a) include at least two ultrafiltration operations.
  16. A method according to any one of claims 1 to 15, wherein one or more purification processes of step a) include dialysis filtration.
  17. A method according to any one of paragraphs 1 through 16, wherein step a) comprises the following i) A step of applying a polypeptide preparation to an ultrafiltration operation up to a first target concentration, ii) a step of applying the polypeptide preparation to a dialysis filtration operation for buffer exchange, and iii) A step of applying the polypeptide preparation to a second ultrafiltration operation to a second target concentration and recovering a first result pool with a viscosity of 5-40 cP.
  18. In paragraph 17, the method in which the first target concentration is 5-80 g/L.
  19. In paragraph 17 or 18, the buffer exchange is a method of 6-12 times exchange.
  20. A method according to any one of claims 17 to 19, wherein the second target concentration is 100-150 g/L or 100-200 g/L.

Description

High-viscosity ultrafiltration/dialysis filtration and single-pass tangential flow filtration processes Cross-reference regarding related applications This application claims priority to U.S. provisional application serial number 63/581,474 filed September 8, 2023, the entire contents of which are incorporated herein by reference. field The present disclosure provides high-viscosity ultrafiltration/dialysis filtration (UF/DF) and single-pass tangential flow filtration (SPTFF) processes used in the purification of polypeptides. Background Technology Single-pass Tangential Flow Filtration (SPTFF) enables new technologies and advancements in protein purification, supporting increased productivity across the biotherapeutic manufacturing industry. SPTFF systems differ from conventional UFDF systems in terms of reduced membrane area, smaller process volume, and shorter operation times. These differences may also apply to operating temperatures and the application of multiple stages of ultrafiltration. Furthermore, while initial process concentration is related to process control, typical multi-pass UFDF operations are minimally affected by initial concentration. SPTFF increases protein solution concentration by removing buffer solution as it passes through a semipermeable membrane while retaining the product. Protein concentration is a key process parameter determining ocular and subcutaneous administration capabilities. However, viscosity increases exponentially with increasing protein concentration, resulting in high pressure within the supply channel and low flux at the membrane boundary. Consequently, high viscosity limits the maximum protein concentration achievable with TFF-based ultrafiltration. All references cited in this specification, including patent applications and publications, are incorporated by reference in their entirety. summation An SPTFF process developed under operating conditions that minimize feed channel pressure and operating viscosity is ideal for achieving maximum protein concentration. Systems and methods for high-viscosity ultrafiltration/dialysis filtration (UF/DF) and SPTFF processes used for the purification of polypeptides are disclosed herein. Systems and methods disclosed herein may include an SPTFF operation following one or more purification processes. One or more purification processes may include ultrafiltration and dialysis filtration. One or more purification processes may produce a pool with a viscosity of about 5-40 cP, which may then be applied to an SPTFF operation. An SPTFF operation may include producing a resulting pool with an operating viscosity of about 41-400 cP using a membrane in one or both of a serial and/or parallel configuration. According to one embodiment, a method for purifying a polypeptide from a polypeptide preparation comprises the following steps in order: a) applying the polypeptide preparation to one or more purification processes and recovering a first resulting pool having a viscosity of about 5-40 cP; and b) applying the pool recovered from step a) to a single-pass tangential flow filtration (SPTFF) operation and recovering a second resulting pool having an operating viscosity of about 41-400 cP, wherein i) the operating temperature is about 15-55°C and ii) the feed flux is about 5-50 L/ m² /hr (LMH). In some embodiments of the method, the viscosity of the first recovered pool in step a) is 10-35 cP. In some embodiments of the method, the STPFF operation in step b) involves the use of a serial membrane configuration. In some embodiments of the method, the STPFF operation in step b) involves the use of a parallel membrane configuration. In some embodiments of the method, the SPTFF operation in step b) involves the use of both serial membrane configurations and parallel membrane configurations. In some embodiments of the method, in step b), the membrane configuration is any one of 1:1:1, 1:1:1:1, 2:1:1, or 2:2:1:1. In some embodiments of the method, in step b), the membrane configuration comprises at least one of a 10 kD membrane and a 30 kD membrane. In some embodiments of the method, in step b), the membrane configuration includes at least one of a narrow channel membrane and a wide channel membrane. In some embodiments of the method, in step a), the polypeptide formulation is formulated in a viscosity-reducing excipient. In some embodiments of the method, the operating temperature in step b) is about 15-50°C or about 30-50°C. In some embodiments of the method, the feed flux in step b) is about 5-25 LMH or about 25-50 LMH. In some embodiments of the method, the working viscosity in step b) is about 200-400 cP or about 200-300 cP. In some embodiments of the method, the residual liquid pressure in step b) is about 5-20 psi. In some embodiments of the method, one or more purification processes of step a) include ultrafiltration. In some embodiments of the method, one or more purification processes of step a) include at least two ultrafiltration