Devices and disposables for patient-specific cell therapy manufacturing

Patent metadata

Field	Value
Publication number	US-11933787-B2
Application number	US-202218083279-A
Country	US
Kind code	B2
Filing date	Dec 16, 2022
Priority date	Dec 7, 2007
Publication date	Mar 19, 2024
Grant date	Mar 19, 2024

Abstract

The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder ( 42 ), a pump ( 64 ) and a plurality of valves ( 1 - 11 ) configured to at least partially control fluid flow through a fluid circuitry and a separation column ( 40 ) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

First claim

The invention claimed is:

1. A closed automatic system for manufacturing a therapeutic cell population for administration to a patient in need thereof,
wherein the system comprises a single-use assembly that includes the following components:
(1) a sample processing unit that includes an input port operably connected to a sample chamber, wherein the sample chamber comprises ports to supply fresh media and gasses to support culture of a sample of cells in the chamber, and is configured to wash target cells and/or adjust volume of the sample as needed;
(2) a sample separation unit that includes a magnetic separation member, and
(3) fluid circuitry that interconnects the sample processing unit and the sample separation unit, so that cells can be caused to flow between the sample processing unit and the sample separation unit in either direction;
wherein the components of the assembly are constructed and arranged to receive a population of donor cells and to manufacture therefrom said therapeutic cell population by applying a process that comprises a plurality of steps selected from the following:
(a) positive or negative selection of a defined population of target cells using the magnetic separation member;
(b) activation or differentiation of cells by culturing with one or more cytokines or growth factors;
(c) transduction or transfection of cells by culturing with genetic material; and/or
(d) expansion of cells by culturing in fresh media before or after step (a);
and thereafter to wash and formulate the therapeutic cell population in an adjusted volume of injectable liquid;
wherein the system is closed and sterile, whereby said therapeutic cell population manufactured therewith is suitable for administration to a human patient;
wherein the single-use assembly is configured to be reversibly installed on a computer-controlled apparatus that operates the sample processing unit, the sample separation unit, and the fluid circuitry so as to manufacture the therapeutic cell population from the population of donor cells, after which the assembly maybe removed from the apparatus and replaced with another single-use assembly to process another population of donor cells.

2. The system of claim 1 , wherein the components of the single-use assembly are constructed and arranged for positive selection of target cells,
whereby target cells labeled with magnetic particles are retained in the magnetic separation member, while non-target cells that are not labeled with magnetic particles pass into a waste container.

3. The system of claim 1 , wherein the components of the single-use assembly are constructed and arranged for negative selection of target cells,
whereby non-target cells labeled with magnetic particles are retained in the magnetic separation member and discarded, while target cells that are not labeled with magnetic particles are retained.

4. The system of claim 1 , wherein the sample chamber comprises a plurality of layered surfaces that are configured so that cells can adhere to the surfaces when cultured in the chamber.

5. The system of claim 1 , wherein the sample chamber comprises a window or prism through which to monitor cells in the sample chamber during processing.

6. The system of claim 1 , wherein the sample processing unit is configured to remove unwanted cells by density separation.

7. The system of claim 1 , wherein the system further comprises said computer-controlled apparatus,
wherein the apparatus is configured to be reversibly installed with said single-use assembly, to operate the assembly to manufacture said therapeutic cell population from a population of donor cells, and to deliver the therapeutic cell population into a product collection container for administration to the patient.

8. The system of claim 7 , wherein the apparatus comprises a holder for the magnetic separation member, a pump operating on the fluid circuitry, and a plurality of valves that control flow through the fluid circuitry and the magnetic separation member of the single-use assembly.

9. The system of claim 7 , wherein the apparatus is controlled by a computer that is programmed to perform a plurality of said steps selected by an operator to manufacture said therapeutic cell population.

10. The system of claim 7 , wherein the computer is programmed to operate the apparatus to manufacture a genetically modified cell population from a donor cell population in the single-use assembly by performing the following steps:
(a) receive a sample of cells through the input port into the sample processing unit;
(b) prepare the sample of cells in the sample processing unit;
(c) transfer the prepared cells from the sample processing unit to the sample separation unit;
(d) separate the prepared cells into target cells and non-target cells in the sample separation unit using the magnetic separation member, allowing non-target cells to pass to a waste container,
(e) transfer the separated target cells back to the sample processing unit;
(f) combine and culture the target cells with genetic material in the sample chamber;

supplying gas and fresh media as needed so as to genetically modify the cells;
(g) process the genetically modified cells by washing and adjusting volume; and thereafter
(h) deliver the genetically modified cells as a therapeutic cell population to a product collection container.

11. A computer-controlled apparatus configured to be reversibly installed with a single-use assembly as put forth in claim 1 , and thereafter to operate the assembly to manufacture a therapeutic cell population for a human subject in need thereof by applying to a population of donor cells a process that comprises a plurality of said processing steps.

12. A method of using the system of claim 1 to manufacture a therapeutic cell population for administration to a patient in need thereof, the method comprising:
installing said single-use assembly on said computer controlled apparatus; and
directing the computer controlled apparatus to operate the single-use assembly to manufacture the therapeutic cell population from a population of donor cells.

13. The method of claim 12 , wherein the therapeutic cell population obtained thereby is genetically modified.

14. The method of claim 13 , wherein the system is directed to perform the following steps:
(a) receive a sample of cells through the input port into the sample processing unit;
(b) prepare the sample of cells in the sample processing unit;
(c) transfer the prepared cells from the sample processing unit to the sample separation unit;
(d) separate the prepared cells into target cells and non-target cells in the sample separation unit using the magnetic separation member, allowing non-target cells to pass to a waste container,
(e) transfer the separated target cells back to the sample processing unit;
(f) combine and culture the target cells with genetic material in the sample chamber;
supplying gas and fresh media as needed so as to genetically modify the cells;
(g) process the genetically modified cells by washing and adjusting volume; and thereafter
(h) deliver the genetically modified cells as the therapeutic cell population to a product collection container.

15. The method of claim 12 , wherein the therapeutic cell population has been enriched for cells that are CD34 positive, CD133 positive, CD14 positive, and/or CD8 negative.

16. The method of claim 12 , wherein the therapeutic cell population is a population of stem cells or progenitor grafts from cord blood, a dendritic cell vaccine, an expanded population of T helper cells

Assignees

• Miltenyi Biotec Bv & Co Kg

Inventors

• Miltenyi Stefan
• Schimmelpfennig Winfried
• Lantow Holger
• Neuschaefer Niklas Elmar
• Biehl Martin
• Kabaha Eiad
• Schulz Juergen

Classifications

• A61K40/418

  Antigens related to induction of tolerance to non-self · CPC title

• A61K40/416

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title

• A61K40/46

  Viral antigens · CPC title

• A61K40/42

  Cancer antigens · CPC title

• A61K40/24

  Antigen-presenting cells [APC] · CPC title