# US 11,439,956 B2 · Method for processing solutions of biomolecules

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- Number: US 11,439,956 B2
- Document ID: US11439956B2
- Status: Granted
- Kind: B2
- Application number: 16/864,234
- Filed: 2020-05-01
- Published: 2020-08-27
- Granted: 2022-09-13
- Earliest claimed: 2016-01-07
- Assignees: Fujifilm Diosynth Biotechnologies UK Limited
- Applicants: Fujifilm Diosynth Biotechnologies UK Limited
- Inventors: Charles Heise; Tibor Nagy
- Web page: https://patentgrep.com/patent/US11439956B2

## CPC

- B01D 61/18: Apparatus therefor
- B01D 61/146: {comprising multiple ultrafiltration steps}
- B01D 61/16: Feed pretreatment
- B01D 61/20: Accessories; Auxiliary operations
- C07K 1/145: {by extraction or solubilisation}
- C12N 15/1017: {by filtration, e.g. using filters, frits, membranes}
- B01D 61/22: Controlling or regulating
- B01D 2313/18: Specific valves
- B01D 2313/19: Specific flow restrictors
- B01D 2313/243: Pumps
- B01D 2315/10: Cross-flow filtration
- B01D 2315/16: Diafiltration
- B01D 2317/022: Reject series
- B01D 2319/022: Reject series
- B01D 2321/2016: Static mixers; Turbulence generators
- B01D 2321/2066: Pulsated flow
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Apparatus for in-line liquid exchanging a biomolecule-containing liquid is provided. The apparatus comprises a means for mixing at least two liquids comprising a multiple inlet flow-controller, the means for mixing also comprising an outlet in fluid connection with a tangential flow filtration device configured in single-pass mode.

## Claims

### Claim 1

Apparatus for in-line liquid exchanging a biomolecule-containing liquid comprising a means for mixing comprising a multiple inlet flow-controller further comprising two or more variable flow inlet valves for mixing at least two liquids, wherein the variable flow inlet valves are controlled to be cycled between a position achieving a first, relatively low flow rate wherein the liquid remains able to flow, or flow is prevented and at least a second, higher flow rate, the means for mixing also comprising an outlet in fluid connection with a tangential flow filtration device configured in single-pass mode.

### Claim 2 (depends on 1)

The apparatus according to claim 1, wherein the variable flow inlet valves are intermittent flow valves.

### Claim 3

Apparatus for liquid exchanging a biomolecule-containing liquid comprising:
a) a multiple inlet flow-controller comprising:
i) a first inlet for a first liquid medium comprising a biomolecule;
ii) at least a second inlet for a second liquid medium;
iii) an outlet in fluid connection with a tangential flow filtration device; and
b) a means for imparting flow of the liquids through the flow-controller and the tangential flow filtration device, and
c) a means for controlling the flow through the tangential flow filtration device such that the flow is cycled between a position achieving a first, relatively low flow rate wherein the liquid remains able to flow, or flow is prevented and at least a second, higher flow rate.

### Claim 4 (depends on 3)

The apparatus according to claim 3, further comprising a second multiple inlet flow-controller comprising:
i) a first inlet in fluid connection with the retentate from the tangential flow filtration device;
ii) a second inlet for a third liquid medium; and
iii) an outlet in fluid connection with a second tangential flow filtration device.

### Claim 5 (depends on 4)

The apparatus according to claim 4, wherein the second multiple inlet flow-controller functions as a restrictor.

### Claim 6 (depends on 5)

The apparatus according to claim 5, wherein the second multiple inlet flow-controller further comprises two or more variable flow inlet valves.

### Claim 7 (depends on 1)

A method for the preparation of a biomolecule, which comprises processing a liquid medium comprising the biomolecule by liquid exchange employing an apparatus according to claim 1, wherein at least 10 cycles are employed, the cycle frequency is less than 100 Hz, and the processing comprises buffer exchange.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the cycle frequency is from 0.05 to 0.5 Hz.