# US 11,439,739 B2 · Cartridge and method for increasing myocardial function > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,739 B2 - Document ID: US11439739B2 - Status: Granted - Kind: B2 - Application number: 16/935,992 - Filed: 2020-07-22 - Published: 2021-05-13 - Granted: 2022-09-13 - Earliest claimed: 2012-01-09 - Assignees: SeaStar Medical, Inc. - Applicants: SeaStar Medical, Inc. - Inventors: H. David Humes; Deborah A. Buffington - Web page: https://patentgrep.com/patent/US11439739B2 ## CPC - A61M 1/3486: {Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents} - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/194: having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid - A61M 1/16: with membranes - A61M 1/1625: {Dialyser of the outside perfusion type, i.e. blood flow outside hollow membrane fibres or tubes} - A61M 1/34: Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration - A61M 1/3472: {with treatment of the filtrate} - A61M 1/3489: {by biological cells, e.g. bioreactor} - A61M 1/3666: {Cardiac or cardiopulmonary bypass, e.g. heart-lung machines} - A61M 1/3679: {by absorption (A61M1/3675 takes precedence)} - A61M 1/3687: {Chemical treatment (A61M1/3675 takes precedence)} - A61M 1/3689: {by biological cells} - A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - B01D 61/20: Accessories; Auxiliary operations - A61M 1/3623: {Means for actively controlling temperature of blood} - A61M 1/3672: {Means preventing coagulation} - A61M 2202/0427: Platelets; Thrombocytes - A61M 2202/0439: White blood cells; Leucocytes - A61M 2205/126: with incorporated membrane filters - A61M 2210/125: Heart - 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)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract The present invention relates to a cytopheretic cartridge for use in treating and/or preventing inflammatory conditions that affect myocardial function and to related methods. The cartridge can be used in treating a subject with myocardial dysfunction, such as a subject with chronic heart failure and/or acute decompensated heart failure. ## Claims ### Claim 1 A method of increasing myocardial function in a subject with chronic heart failure, the method comprising: (a) extracorporeally sequestering activated leukocytes and/or activated platelets present in blood from the subject in a cartridge, the cartridge comprising: (i) a rigid housing defining an inner volume (IV), a fluid inlet port and a fluid outlet port, wherein the inner volume is in fluid flow communication with the fluid inlet port and the fluid outlet port, and (ii) a solid support disposed within the housing and defining a fluid contacting surface with a surface area (SA) capable of sequestering activated leukocytes and/or activated platelets, if present in blood entering the housing via the fluid inlet port, and the blood is introduced into the housing via the fluid inlet port under conditions that permit sequestration of the activated leukocytes and/or activated platelets on the fluid contacting surface of the solid support; and (b) treating the leukocytes and/or platelets sequestered in step (a) to inhibit release of a pro-inflammatory substance or to deactivate the leukocytes and/or platelets thereby to increase myocardial function of the subject when compared to the myocardial function of the subject prior to treatment, wherein the myocardial function is selected from the group consisting of left ventricular ejection fraction, cardiac output, systemic vascular resistance, left ventricular stroke volume, aortic pressure, left ventricular pressure, peak rate of change of left ventricular pressure during isovolumic contraction and relaxation, left ventricular end-diastolic pressure, myocardial oxygen consumption, and coronary flow reserve. ### Claim 2 (depends on 1) The method of claim 1, wherein the cartridge provided in step (a) has an SA/IV ratio greater than 25 cm′. ### Claim 3 (depends on 1) The method of claim 1, wherein the cartridge provided in step (a) has an SA/IV ratio ranging from 25 cm−1 to 2,000 cm−1. ### Claim 4 (depends on 1) The method of claim 1, wherein the cartridge provided in step (a) has an SA/IV ratio no greater than 80 cm−1. ### Claim 5 (depends on 1) The method of claim 1, wherein the solid support is disposed within the housing at a packing density ranging from 20% to 65%. ### Claim 6 (depends on 1) The method of claim 1, wherein the solid support comprises a fiber. ### Claim 7 (depends on 1) The method of claim 1, wherein the SA of the cartridge provided in step (a) ranges from 0.1 m2 to 5.0 m2. ### Claim 8 (depends on 1) The method of claim 1, wherein the inner volume ranges from 15 cm3 to 120 cm3. ### Claim 9 (depends on 1) The method of claim 1, further comprising permitting the blood to exit the cartridge via the fluid outlet port at a flow rate ranging from 10 cm3/minute to 8,000 cm3/minute. ### Claim 10 (depends on 1) The method of claim 1, wherein fluid flow within the cartridge is in a direction substantially parallel to the solid support. ### Claim 11 (depends on 1) The method of claim 1, wherein, in step (b), the leukocytes and/or platelets are treated with a calcium chelating agent. ### Claim 12 (depends on 11) The method of claim 11, wherein the calcium chelating agent is citrate. ### Claim 13 (depends on 11) The method of claim 11, wherein the calcium chelating agent is introduced into the blood from the subject prior to step (a). ### Claim 14 (depends on 11) The method of claim 11, wherein the leukocytes and/or platelets from the subject are treated over a period of at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, or at least 12 hours. ### Claim 15 (depends on 11) The method of claim 11, wherein the leukocytes and/or platelets from the subject are treated over a period of 2 to 48 hours, 2 to 24 hours, 2 to 12 hours, 4 to 48 hours, 4 to 24 hours, or 4 to 12 hours. ### Claim 16 (depends on 1) The method of claim 1, wherein the subject has myocardial dysfunction secondary to inflammatory cell penetration of heart tissue. ### Claim 17 (depends on 1) The method of claim 1, wherein the subject has received a heart transplant. ### Claim 18 (depends on 1) The method of claim 1, wherein the increased myocardial function is maintained for at least 6 hours after termination of the treating in step (b). ### Claim 19 (depends on 18) The method of claim 18, wherein the increased myocardial function is maintained for at least 24 hours after termination of the treating in step (b). ### Claim 20 (depends on 1) The method of claim 1, wherein the solid support comprises a membrane. ### Claim 21 A method of increasing myocardial function in a subject with chronic heart failure, the method comprising: (a) extracorporeally sequestering activated leukocytes and/or activated platelets present in blood from the subject; and (b) treating the leukocytes and/or platelets sequestered in step (a) to inhibit release of a pro-inflammatory substance or to deactivate the leukocytes and/or platelets thereby to increase myocardial function of the subject when compared to the myocardial function of the subject prior to treatment, wherein the myocardial function is selected from the group consisting of left ventricular ejection fraction, cardiac output, systemic vascular resistance, left ventricular stroke volume, aortic pressure, left ventricular pressure, peak rate of change of left ventricular pressure during isovolumic contraction and relaxation, left ventricular end-diastolic pressure, myocardial oxygen consumption, and coronary flow reserve. ### Claim 22 (depends on 21) The method of claim 21, wherein, in step (b), the leukocytes and/or platelets are treated with a calcium chelating agent. ### Claim 23 (depends on 22) The method of claim 22, wherein the calcium chelating agent is citrate. ### Claim 24 (depends on 22) The method of claim 22, wherein the calcium chelating agent is introduced into the blood from the subject prior to step (a). ### Claim 25 (depends on 22) The method of claim 22, wherein leukocytes and/or platelets from the subject are treated over a period of at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, or at least 12 hours. ### Claim 26 (depends on 22) The method of claim 22, wherein leukocytes and/or platelets from the subject are treated over a period of 2 to 48 hours, 2 to 24 hours, 2 to 12 hours, 4 to 48 hours, 4 to 24 hours, or 4 to 12 hours. ### Claim 27 (depends on 22) The method of claim 22, wherein the increased myocardial function is maintained for at least 6 hours after termination of the treatment in step (b). ### Claim 28 (depends on 22) The method of claim 22, wherein the increased myocardial function is maintained for at least 24 hours after termination of the treatment in step (b). ### Claim 29 (depends on 22) The method of claim 22, wherein, in step (a), the activated leukocytes and/or activated platelets are sequestered by introducing the blood into a cartridge comprising (i) a rigid housing defining an inner volume (IV), a fluid inlet port and a fluid outlet port, wherein the inner volume is in fluid flow communication with the fluid inlet port and the fluid outlet port, and (ii) a solid support disposed within the housing and defining a fluid contacting surface with a surface area (SA) capable of sequestering activated leukocytes and/or platelets, if present in the blood entering the housing via the fluid inlet port, wherein the blood is introduced into the housing via the fluid inlet port under conditions that permit sequestration of the activated leukocytes and/or platelets on the fluid contacting surface of the solid support. ### Claim 30 (depends on 29) The method of claim 29, wherein the cartridge provided in step (a) has an SA/IV ratio in a range of from 25 cm−1 to 1,500 cm−1. ### Claim 31 (depends on 30) The method of claim 30, wherein the SA/IV ratio is in a range of from 80 cm−1 to 1,500 cm−1. ### Claim 32 (depends on 29) The method of claim 29, wherein the cartridge provided in step (a) has an SA/IV ratio is no greater than 80 cm−1. ### Claim 33 (depends on 29) The method of claim 29, wherein the solid support is disposed within the housing at a packing density in a range from 20% to 65%. ### Claim 34 (depends on 29) The method of claim 29, wherein the solid support comprises a membrane. ### Claim 35 (depends on 29) The method of claim 29, wherein the solid support comprises a fiber. ### Claim 36 (depends on 29) The method of claim 29, wherein the SA of the cartridge provided in step (a) is in a range of from 0.1 m2 to 5.0 m2. ### Claim 37 (depends on 29) The method of claim 29, further comprising permitting the blood to exit the cartridge via the fluid outlet port at a flow rate in a range of 10 cm3/minute to 8,000 cm3/minute. ### Claim 38 (depends on 29) The method of claim 29, wherein fluid flow within the cartridge is in a direction substantially parallel to the solid support. ### Claim 39 A method of treating a subject having or at risk of developing an inflammatory condition, wherein the inflammatory condition is chronic heart failure (CHF), the method comprising: (a) providing a cartridge comprising (i) a rigid housing defining an inner volume (IV), a fluid inlet port and a fluid outlet port, wherein the inner volume is in fluid flow communication with the fluid inlet port and the fluid outlet port; and (ii) a fluid permeable solid support disposed within the housing and defining a fluid contacting surface with a surface area (SA) capable of sequestering an activated leukocyte, if present in blood entering the housing via the fluid inlet port, wherein the cartridge has an SA/IV ratio of no greater than 80 cm−1; and (b) introducing blood from the subject into the housing via the fluid inlet port under conditions that permit sequestration of the activated leukocyte on the fluid contacting surface of the solid support. ### Claim 40 (depends on 39) The method of claim 39, further comprising (c) treating the leukocyte sequestered in step (b) to reduce in the subject the risk of developing inflammation associated with the inflammatory condition or to alleviate inflammation associated with the inflammatory condition. ### Claim 41 (depends on 40) The method of claim 40, further comprising the step of returning the leukocyte and/or the platelet produced in step (c) back to the subject. ### Claim 42 (depends on 40) The method of claim 40, wherein, in step (c), the leukocyte and/or the platelet is treated with a calcium chelating agent. ### Claim 43 (depends on 42) The method of claim 42, wherein the calcium chelating agent is citrate. ### Claim 44 (depends on 42) The method of claim 42, wherein the solid support comprises a membrane. ### Claim 45 (depends on 42) The method of claim 42, wherein the solid support comprises a fiber. ### Claim 46 (depends on 42) The method of claim 42, wherein the SA of the cartridge provided in step (a) is in a range of from 0.1 m2 to 10.0 m2. ### Claim 47 (depends on 42) The method of claim 42, wherein the SA of the cartridge provided in step (a) is in a range of from 0.1 m2 to 5.0 m2. ### Claim 48 (depends on 42) The method of claim 42, wherein the inner volume is in a range of from 10 cm3 to 150 cm3. ### Claim 49 (depends on 42) The method of claim 42, wherein the inner volume is in a range of from 20 cm−1 to 80 cm3. ### Claim 50 (depends on 49) The method of claim 49, further comprising permitting the blood to exit the cartridge via the fluid outlet port at a flow rate in a range of 10 cm3/minute to 8,000 cm−1/minute.