# US 2021/0330874 A1 · Multicolumn Blood Plasma Immunomodulating Agents Rebalancing System

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0330874 A1
- Document ID: US20210330874A1
- Status: Published application
- Kind: A1
- Application number: 17/236,888
- Filed: 2021-04-21
- Published: 2021-10-28
- Earliest claimed: 2020-04-23
- Assignees: Thompson Oncology Devices LLC
- Applicants: Thompson Oncology Devices LLC
- Inventors: Joel Wallace Graff; Christopher Armstrong Kay; Randall Jay Daughenbaugh
- Web page: https://patentgrep.com/patent/US20210330874A1

## CPC

- A61M 1/3496: {Plasmapheresis; Leucopheresis; Lymphopheresis (A61M1/3472 takes precedence)}
- A61M 1/3403: {Regulation parameters}
- A61M 1/3486: {Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents}
- A61M 1/362: {changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity}
- A61M 2202/0415: Plasma
- A61M 2202/0445: Proteins
- A61M 2205/0238: the material being a coating or protective layer
- A61M 2230/06: Heartbeat rate only
- A61M 2230/20: Blood composition characteristics
- A61M 2230/30: Blood pressure (A61M2230/04 takes precedence)
- A61M 2230/42: Rate
- A61M 2230/50: Temperature
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

Generally, a blood plasma immunomodulating agent rebalancing system. In particular, a blood plasma sTNFR and cytokine rebalancing system and methods of rebalancing sTNFR and cytokines in the blood plasma of a subject during plasmapheresis.

## Claims

### Claim 1

An apparatus, comprising:
a plasmapheresis device;
a valved conduit adapted to receive blood plasma from said plasmapheresis device, said valved conduit including:
a valve assembly operable to direct said blood plasma to a soluble TNF receptors removal medium or operable to direct said blood plasma to a cytokine removal medium, said valve assembly operable to direct said blood plasma passed through said TNF receptors removal medium to said subject or operable to direct said blood plasma passed through said cytokine removal medium to said subject,
wherein said soluble TNF receptor removal medium adapted to remove soluble TNF receptors in blood plasma of a subject,
wherein said cytokine removal medium adapted to remove cytokines in said blood plasma of said subject, whereby said apparatus rebalances levels of said soluble TNF receptors and said cytokines toward normative levels in said blood plasma of said subject.

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein said soluble TNF receptors removal medium comprises a plurality of TNF-α muteins immobilized on an extracorporeal biocompatible solid support.

### Claim 3 (depends on 2)

The apparatus of claim 2, where said plurality of TNF-α muteins are covalently attached to said extracorporeal biocompatible solid support.

### Claim 4 (depends on 3)

The apparatus of claim 3, wherein said extracorporeal biocompatible solid support contained in a first column fluidically coupled to said valved conduit.

### Claim 5 (depends on 3)

The apparatus of claim 3, wherein said extracorporeal biocompatible solid support contained in a first reactor fluidically coupled to said valved conduit.

### Claim 6 (depends on 2)

The apparatus of claim 2, wherein each of said plurality of TNF-α muteins immobilized on the extracorporeal biocompatible solid support have a single binding site capable of selectively binding to one of said soluble TNF receptors with an affinity sufficient to deplete the soluble TNF receptors from the biological fluid.

### Claim 7 (depends on 2)

The apparatus of claim 2, wherein said plurality of TNF-α muteins comprises one or more of: TNF-α mutein 1, TNF-α mutein 2, TNF-α mutein 3, TNF-α mutein 4, TNF-α mutein 5, TNF-α mutein 6, and combinations thereof.

### Claim 8 (depends on 2)

The apparatus of claim 2, wherein said plurality of TNF-α muteins is selected from the group of TNF-α muteins consisting of: TNF-α mutein 1, TNF-α mutein 2, TNF-α mutein 3, TNF-α mutein 4, TNF-α mutein 5, TNF-α mutein 6, and combinations thereof.

### Claim 9 (depends on 1)

The apparatus of claim 1, wherein said soluble TNF receptors comprise soluble TNF receptors type 1 or soluble TNF receptors type 2.

### Claim 10 (depends on 9)

The apparatus of claim 9, wherein said soluble TNF receptors comprises soluble TNF receptor type 1 and soluble TNF receptor type 2.

### Claim 11 (depends on 1)

The apparatus of claim 1, wherein said cytokine removal medium non-specifically binds said cytokines.

### Claim 12 (depends on 11)

The apparatus of claim 11, wherein said cytokine removal medium adsorbs cytokines of less than 50 kDa.

### Claim 13 (depends on 12)

The apparatus of claim 12, wherein said cytokines of less than 50 kDa include one or more of IL-6, IL-10, HMGB-1, IL-8, IL-18, MCP-1, IL-2, IL-1β and S100B.

### Claim 14 (depends on 11)

The apparatus of claim 11, wherein said cytokine removal medium which non-specifically binds said cytokines comprises a polystyrene-divinylbenzene copolymer beads with a biocompatible polyvinylpyrrolidone coating.

### Claim 15 (depends on 14)

The apparatus of claim 14, wherein said a polystyrene-divinylbenzene copolymer beads with said biocompatible polyvinylpyrrolidone coating comprises CYTOSORB copolymer beads.

### Claim 16 (depends on 11)

The apparatus of claim 11, wherein said cytokine removal medium which non-specifically binds said cytokines comprises a 2-methacryloyloxyethyl phosphorylcholine bead.

### Claim 17 (depends on 16)

The apparatus of claim 16, wherein said 2-methacryloyloxyethyl phosphorylcholine bead comprises MEDASORB beads.

### Claim 18 (depends on 1)

The apparatus of claim 1, wherein said a valve assembly manually operated by a user of said apparatus to direct said blood plasma to said soluble TNF receptor removal medium or to direct said blood plasma to said cytokine removal medium.

### Claim 19 (depends on 18)

The apparatus of claim 18, wherein said user operates said valve assembly between said soluble TNF receptor removal medium and said cytokine removal medium based on monitoring one or more measurable variables of said subject indicative of levels of cytokine activity.

### Claim 20 (depends on 19)

The apparatus of claim 19, where said measurable variables of said subject include one or more of temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, white blood cell count, cardiac output, lactate level, interleukin-6, interleukin-10, and TNF-α.

### Claim 21 (depends on 1)

The apparatus of claim 1, further comprising:
one or more sensors which correspondingly generate a sensor signal which varies based on change in a measurable variable indicative of levels of cytokine activity in said blood plasma of said subject;
a controller which operates to:
convert said sensor signal to a measured value of said measurable variable;
compare said measured value to pre-selected threshold value of said measured variable of cytokine activity in said blood plasma of said subject;
identify said measured value in excess of said pre-selected threshold value of said measured variable of cytokine activity in said blood plasma of said subject;
actuate said valve assembly to direct said blood plasma to said cytokine removal medium to decrease levels of said cytokines in said blood plasma of said subject.

### Claim 22 (depends on 19)

The apparatus of claim 19, wherein said controller actuates said valve assembly to direct said blood plasma to said soluble TNF receptor removal medium to decrease levels of said soluble TNF receptor in said blood plasma which increases levels of and said cytokines in said blood plasma of said subject.

### Claim at position 23

23-32. (canceled)