Single use tubing set for making genetically modified donor cells for reinfusion into a patient

Patent metadata

Field	Value
Publication number	US-11531031-B2
Application number	US-202217725509-A
Country	US
Kind code	B2
Filing date	Apr 20, 2022
Priority date	Dec 7, 2007
Publication date	Dec 20, 2022
Grant date	Dec 20, 2022

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 sterile single-use tubing set for preparing a cell population for therapy for a patient in need thereof,
wherein the tubing set comprises the following components:
(1) a sample processing unit that includes an input port operably connected to a sample chamber, wherein the sample chamber comprises additional ports to supply fresh media and gasses to support culture 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 cell separation column, and
(3) fluid circuitry that interconnects the sample processing unit and the sample separation unit, so that cells can flow between the sample processing unit and the sample separation unit in either direction;
wherein the components of the tubing set are constructed and arranged so that a user of the tubing set can prepare the cell population for human administration according to the following procedure:
(a) receive a sample of cells through the input port into the sample processing unit of the tubing set;
(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 column, 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 cellular product to a product collection container;
wherein the single use tube set constitutes a closed sterile system, whereby the cellular product delivered to the product collection container is suitable for administration to a human patient in need thereof;
wherein the single use tubing set is configured to be reversibly installed on an apparatus that operates the sample processing unit, the sample separation unit, and the fluid circuitry so as to process cells in the tubing set and deliver a cellular product to the product collection container, after which the tubing set is removed from the apparatus and replaced with another tubing set to process another sample of cells.

2. The tubing set 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.

3. The tubing set of claim 1 , wherein the sample chamber comprises a detection window or prism through which to monitor cells in the sample chamber during processing.

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

5. The tubing set of claim 1 , wherein the magnetic column and the fluid circuitry are arranged so that target cells labeled with magnetic particles can be retained in the separation column, while non-target cells that are not labeled with magnetic particles pass into the waste container.

6. The tubing set of claim 1 , wherein the magnetic column and the fluid circuitry are arranged so that non-target cells labeled with magnetic particles can be retained in the separation column, while target cells that are not labeled with magnetic particles pass to the sample processing unit.

7. The tubing set of claim 1 , wherein the apparatus upon which the tubing set is configured to be installed comprises a holder for the magnetic separation column, a pump operating on the fluid circuitry, and a plurality of valves that control flow through the fluid circuitry and the separation column of the tubing set.

8. The tubing set of claim 1 , installed on said apparatus so that the apparatus operates the sample processing unit, the sample separation unit, and the fluid circuitry to process a sample of cells and deliver a cellular product to the product collection container.

9. The tubing set installed on the apparatus as put forth in claim 8 , wherein the apparatus is operatively connected with and controlled by a computer that is programmed to cause the apparatus to operate the tubing set whereby a sample of cells is processed and a cellular product is delivered to the product collection container.

10. The tubing set installed on the apparatus as put forth in claim 8 , wherein the apparatus is configured to operate the tubing set 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 column, 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 cellular product to a product collection container.

11. An apparatus configured to be reversibly installed with a single use tubing set as put forth in claim 1 , and thereafter to operate the tubing set to prepare a sample of genetically modified cells for a human subject in need thereof according to said procedure.

12. The apparatus of claim 11 , operatively connected with and controlled by a computer that is programmed to cause the apparatus to operate the tubing set whereby a sample of cells is processed and a cellular product is delivered to the product collection container.

Assignees

• Miltenyi Biotec Bv & Co Kg
• Miltenyi Biotec Gmbh

Inventors

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

Classifications

• A61M2202/0071

  product to be retained or harvested, e.g. by pheresis · CPC title

• B01D21/262

  by using a centrifuge · CPC title

• B03C1/288

  disposed at the outer circumference of a recipient · CPC title

• C12N5/0018

  Culture media for cell or tissue culture (media for specific animal cell type C12N5/06) · CPC title

• B04B2005/0464

  with hollow or massive core in centrifuge bowl · CPC title