WO2023220336A1 - Méthodes, systèmes et appareil d'administration d'un traitement d'anticorps par perfusion - Google Patents

Méthodes, systèmes et appareil d'administration d'un traitement d'anticorps par perfusion Download PDF

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Publication number
WO2023220336A1
WO2023220336A1 PCT/US2023/021983 US2023021983W WO2023220336A1 WO 2023220336 A1 WO2023220336 A1 WO 2023220336A1 US 2023021983 W US2023021983 W US 2023021983W WO 2023220336 A1 WO2023220336 A1 WO 2023220336A1
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WIPO (PCT)
Prior art keywords
volume
solution
pump
patient
infusion
Prior art date
Application number
PCT/US2023/021983
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English (en)
Inventor
Regina E. Herzlinger
Original Assignee
Herzlinger Regina E
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US17/840,423 external-priority patent/US11806507B2/en
Application filed by Herzlinger Regina E filed Critical Herzlinger Regina E
Priority to US18/374,816 priority Critical patent/US20240050646A1/en
Publication of WO2023220336A1 publication Critical patent/WO2023220336A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/165—Filtering accessories, e.g. blood filters, filters for infusion liquids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/148—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags
    • A61M5/152—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons flexible, e.g. independent bags pressurised by contraction of elastic reservoirs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/36—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests with means for eliminating or preventing injection or infusion of air into body
    • A61M5/365—Air detectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/44—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for cooling or heating the devices or media
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/18—General characteristics of the apparatus with alarm
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/75—General characteristics of the apparatus with filters
    • A61M2205/7545—General characteristics of the apparatus with filters for solid matter, e.g. microaggregates

Definitions

  • the subject matter described herein relates to methods, systems, and apparatus for infusion of an antibody treatment to a patient, particularly for use in the treatment of a disease or condition.
  • mAb and pAb monoclonal and polyclonal antibody
  • injection i.e., one or multiple “shots” or injections of a relatively small volume of drug directly into a vein with a needle, or by intravenous “push,” IVP, i.e., rapid administration of a small volume of medication into the vein via a previously inserted intravenous catheter.
  • IVP intravenous “push,” IVP
  • mAb and pAb solutions that are of sufficiently high concentration to reasonably limit the number of injections required per patient per treatment may have unsuitably high viscosity. Such solutions require increased force and time required for subcutaneous injection or intramuscular injection.
  • Viscous formulations can result in increased pain upon injection, or may preclude this route of delivery.
  • High mAb concentration may also increase opalescence, which introduces a potential safety issue, because in opalescent solution is easily confused with turbid solutions that can result from protein aggregation or other particulate formation.
  • infusion is likely to be more effective.
  • mAbs and pAbs are infused in an out-patient setting, e.g., at a freestanding or hospital-based infusion center, a skilled nursing facility (SNF), or via in-home infusion.
  • SNF skilled nursing facility
  • Both infusion centers and in-home infusion require health care personnel to manage nursing assistance and supplies to support infusion therapy delivered in an Ambulatory Infusion Suite or in the home.
  • Ambulatory and home infusion resources are limited in capacity and human resources. Reducing the time necessary to complete each infusion would significantly reduce the person-hours of personnel resources needed and free up capacity.
  • a disposable infusion set for connection with the infusion device to facilitate delivery of a volume of solution composing one or more antibodies to the patient, e.g., wherein the disposable infusion set comprises a needle (e.g., straight steel needle), one or more lengths of tubing, and/or an adhesive support (e.g., to avoid dislodging of the needle). Also described therein is a filter for filtering out particles (e.g., monoclonal antibody aggregates and/or polyclonal antibody aggregates) from the volume of solution prior to (upstream of) delivery of the fdtered solution to the patient.
  • particles e.g., monoclonal antibody aggregates and/or polyclonal antibody aggregates
  • the filter has a size small enough (e.g., a mesh tight enough) to catch the particles (e.g., monoclonal antibody aggregates and/or polyclonal antibody aggregates) (e.g., wherein the filter has a size below 170 microns, e.g., below 150 microns, e.g., below 125 microns, e.g., below 100 microns, e.g., below 75 microns, e.g., below 50 microns, e.g., below 40 microns, e.g., below 30 microns, e.g., below 20 microns, e.g., below 10 microns, e.g., below 8 microns, e.g., below 5 microns, e.g., below 4 microns, e.g., below 2 microns, e.g., below 1 micron, e.g., below a mesh tight enough) to catch the particles
  • the tubing line(s) of the disposable infusion set has, collectively, no greater than 200 cc (cubic centimeters, cm 3 ), no greater than 150 cc, no greater than 100 cc, no greater than 50 cc, or no greater than 35 cc of dead space.
  • the tubing line(s) of the disposable infusion set has, collectively, no greater than 200 cc (cubic centimeters, cm 3 ), no greater than 150 cc, no greater than 100 cc, no greater than 50 cc, or no greater than 35 cc of combined total priming volume and dead space.
  • an infusion device e.g., a rapid infusion device, e.g., for the treatment of a disease or condition that requires one or more infusions of monoclonal and/or polyclonal antibodies.
  • the invention is directed to a method for administering an antibody treatment via an infusion device (e.g., a rapid infusion device), the method comprising: administering to a patient by intravenous infusion, using the infusion device, a volume of solution comprising one or more members selected from the group consisting of: (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), (ii) one or more antibody drug conjugates (ADCs), (iii) one or more lipid drug conjugates (LDCs), and (iv) intravenous immunoglobulin (IVIg), wherein the infusion device comprises: (a) a pump (e.g., a roller pump or centrifugal pump), and (b) a disposable infusion set (e.g., the disposable infusion set of any of the disclosed embodiments) comprising a tubing line or lines fluidly connecting an intravenous (IV) bag or other receptacle containing the volume
  • an infusion device
  • the method comprises performing a post infusion saline flush.
  • the disposable infusion set further comprises a filter (e.g., an inline filter), wherein the filter comprises a filter membrane material that provides very low protein binding (e.g., negligible binding of the one or more antibodies to the filter membrane).
  • the filter membrane material comprises polyethersulfone (PES).
  • PES polyethersulfone
  • the filter membrane material comprises cellulose acetate.
  • the filter membrane material comprises regenerated cellulose acetate.
  • the filter membrane material comprises nylon.
  • the pump administers the volume of solution to the patient at an infusion rate of at least 10 mL/min.
  • the pump administers the volume of solution to the patient at an infusion rate of at least 15 mL/min.
  • the pump administers the volume of solution to the patient at an infusion rate of at least 30 mL/min.
  • the pump administers the volume of solution to the patient at an infusion rate of at least 100 mL/min. [0017] In certain embodiments, the pump administers the volume of solution at a dosing rate of at least 35 mg of the one or more antibodies per minute.
  • the pump administers the volume of solution at a dosing rate of at least 35 mg of the one or more antibodies per minute and at a total antibody concentration of less than or equal to 20 mg/mL.
  • administration of the volume of solution to the patient is completed in no more than 30 minutes.
  • the volume of solution comprises an antibody treatment for the treatment of one or more members selected from the group consisting of cancer, a neurological disease, psoriasis, a respiratory disease, macular degeneration, cytokine release syndrome, Castelman disease, a disease caused by a pathogen, an organ transplant, and a tissue transplant.
  • the volume of solution comprises one or more antibody drug conjugates (ADCs) selected from the group consisting of ado-trastuzumab emtansine (e.g., KadcylaTM, manufactured by Genentech, Roche), brentuximab vedotin (e.g., AdcetrisTM, manufactured by Seattle Genetics, Millennium/Takeda), inotuzumab ozogamicin (e.g., BesponsaTM, manufactured by Pfizer Vyeth), gemtuzumab ozogamicin (e.g., MylotargTM, manufactured by Pfizer/Wyeth), Moxetumomab pasudotox (e.g., LumoxitiTM, manufactured by Astrazeneca), polatuzumab vedotin-piiq (e.g., PolivyTM, manufactured by Genentech, Roche), Enfortumab ve
  • ADCs antibody drug conjug
  • the volume of solution comprises an intravenous immunoglobulin (IVIg) [e.g, an intravenous immunoglobulin (IVIg) selected from the group consisting of Gammagard S/D (e.g., manufactured by Baxter/Hyland), Gammunex (e.g., manufactured by Bayer), Intratect (e.g., manufactured by Biotest Pharma), Kiovig (e.g., manufactured by Baxter), Octagam (e.g., manufactured by Octapharma), Pentaglobin (e.g., manufactured by Biotest Pharma), and Sandoglobulin (e.g., manufactured by CSL Behring)].
  • IIG intravenous immunoglobulin
  • the volume of solution comprises one or more monoclonal and/or polyclonal antibodies comprising one or more members selected from the group consisting of: pembrolizumab (e.g., Keytruda), nivolumab (e.g., Opdivo), bevacizumab (e.g., Avastin), ocrelizumab (e.g., Ocrevus), rituximab (e.g., Rituxan, e.g., MabThera), daratumumab (e.g., Darzalex), pertuzumab (e.g., Perjeta), trastuzumab (e.g., Herceptin), infliximab (e.g., Remicade), tocilizumab (e.g., Actemra/RoActemra), atezolizumab (e.g., Tecentriq), tositumom
  • pembrolizumab
  • the invention is directed to a method for administering an antibody treatment via an infusion device, the method comprising: administering to a patient by intravenous infusion, using the infusion device, a volume of solution comprising one or more members of the group consisting of: (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), (ii) one or more antibody drug conjugates (ADCs), (iii) one or more lipid drug conjugates (LDCs), and (iv) intravenous immunoglobulin (IVIg), wherein the infusion device comprises: (a) a pump which administers the volume of solution at a dosing rate of at least 35 mg of the one or more antibodies per minute and at a total antibody concentration of less than or equal to 20 mg/rnL, and (b) a disposable infusion set comprising: (A) a tubing line or lines fluidly connecting an intravenous (IV) bag or other receptacle containing
  • the volume of solution comprises an antibody treatment for the treatment of one or more members selected from the group consisting of cancer, a neurological disease, psoriasis, a respiratory disease, macular degeneration, cytokine release syndrome, Castelman disease, a disease caused by a pathogen, an organ transplant, and a tissue transplant.
  • the volume of solution comprises one or more antibody drug conjugates (ADCs) selected from the group consisting of ado-trastuzumab emtansine (e.g., KadcylaTM, manufactured by Genentech, Roche), brentuximab vedotin (e.g., AdcetrisTM, manufactured by Seattle Genetics, Millennium/Takeda), inotuzumab ozogamicin (e.g., BesponsaTM, manufactured by Pfizer/Wyeth), gemtuzumab ozogamicin (e.g., MylotargTM, manufactured by Pfizer/Wyeth), Moxetumomab pasudotox (e.g., LumoxitiTM, manufactured by Astrazeneca), polatuzumab vedotin-piiq (e.g., PolivyTM, manufactured by Genentech, Roche), Enfortumab
  • ADCs antibody drug conjugates
  • the volume of solution comprises an intravenous immunoglobulin (IVIg) (e.g., an intravenous immunoglobulin (IVIg) selected from the group consisting of Gammagard S/D (Baxter/Hyland), Gammunex (Bayer), Intratect (Biotest Pharma), Kiovig (Baxter), Octagam (Octapharma), Pentaglobin (Biotest Pharma), and Sandoglobulin (CSL Behring)).
  • IVIg intravenous immunoglobulin
  • IVIg selected from the group consisting of Gammagard S/D (Baxter/Hyland), Gammunex (Bayer), Intratect (Biotest Pharma), Kiovig (Baxter), Octagam (Octapharma), Pentaglobin (Biotest Pharma), and Sandoglobulin (CSL Behring)
  • the volume of solution comprises one or more monoclonal and/or polyclonal antibodies selected from the group consisting of: pembrolizumab (e.g., Keytruda), nivolumab (e.g., Opdivo), bevacizumab (e.g., Avastin), ocrelizumab (e.g., Ocrevus), rituximab (e.g., Rituxan, e.g., MabThera), daratumumab (e.g., Darzalex), pertuzumab (e.g., Perjeta), trastuzumab (e.g., Herceptin), infliximab (e.g., Remicade), tocilizumab (e.g., Actemra/RoActemra), atezolizumab (e g., Tecentnq), tositumomab-1131 (e.
  • pembrolizumab
  • the pump is capable of administering the volume of solution to the patient at a volume of at least 10 mL/min.
  • the pump is capable of administering the volume of solution to the patient at a volume of at least 15 mL/min.
  • the pump is capable of administering the volume of solution to the patient at an infusion rate of at least 30 mL/min.
  • the pump is capable of administering the volume of solution to the patient at an infusion rate of at least 100 mL/min.
  • administration of the volume of solution to the patient is completed in no more than 30 minutes.
  • the filter membrane material comprises poly ethersulfone (PES). [0035] In certain embodiments, the filter membrane material comprises cellulose acetate.
  • the filter membrane material comprises regenerated cellulose acetate.
  • the filter membrane material comprises nylon.
  • the filter has pore size below 170 pm.
  • the filter has pore size below 10 pm.
  • the filter has pore size below 2 pm.
  • the filter has pore size 0.2 pm.
  • the invention is directed to a disposable infusion set for use with an infusion device (e.g., a rapid infusion device) for administering to a patient by intravenous infusion a volume of solution comprising one or more members of the group consisting of: (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), (ii) one or more antibody drug conjugates (ADCs), (iii) one or more lipid drug conjugates (LDCs) and (iv) intravenous immunoglobulin (IVIg), the disposable infusion set comprising: (a) a tubing line or lines, and (b) a filter (e g., an inline filter), wherein the filter comprises a filter membrane material that provides very low protein binding (e.g., negligible binding of the one or more antibodies to the filter membrane).
  • an infusion device e.g., a rapid infusion device
  • ADCs antibody drug conjugates
  • LDCs lipid drug conjugates
  • the tubing line(s) have, collectively, no greater than 200 cc (cubic centimeters, cm 3 ) of a total priming volume plus dead space volume [e.g., no greater than 150 cc, no greater than 100 cc, no greater than 50 cc, or no greater than 35 cc of a total of priming volume plus dead space volume],
  • the filter membrane material comprises poly ethersulfone (PES). [0045] In certain embodiments, the filter membrane material comprises cellulose acetate.
  • the filter membrane material comprises regenerated cellulose acetate.
  • the filter membrane material comprises nylon.
  • the filter membrane has pore size less than 2 pm, or less than 1 pm, or less than 0.5 pm, or less than 0.3 pm (e.g., about 0.2 pm).
  • the disposable infusion set is configured (e.g., and approved) for use with a rapid infusion device (e.g., an infusion device capable of an infusion rate of at least 2 mL/min, e.g., at least 10 mL/min, e.g., at least 20 mL/min, e.g., at least 30 mL/min, e.g., at least 50 mL/min, e.g., at least 75 mL/min, e.g., at least 100 mL/min, e g., at least 150 mL/min, e.g., at least 200 mL/min, e.g., at least 250 mL/min, e.g., at least 300 mL/min, e.g., at least 400 mL/min, e.g., at least 500 mL/min; e.g., an infusion device capable of infusion rates
  • a rapid infusion device
  • the disposable infusion set does not include a coarse (e g., with pore size greater than 100 pm or greater than 200 pm, e.g., 250 pm) filter (e g., a blood filter, e.g., a filter that does not provide very low protein binding, e.g., a filter that is not made of PES or cellulose acetate).
  • a coarse filter e.g., with pore size greater than 100 pm or greater than 200 pm, e.g., 250 pm
  • a blood filter e.g., a filter that does not provide very low protein binding, e.g., a filter that is not made of PES or cellulose acetate.
  • the tubing line or lines fluidly connect: (i) an intravenous (IV) bag or other receptacle containing the volume of solution to a pump capable of administering the volume of solution to the patient at a flow rate faster (e.g., substantially faster) than by gravity alone (e.g., faster than a gravity drip device); and/or (ii) the pump to the patient.
  • the filter provides for retention of bacteria and/or fungi, and/or wherein the filter provides for elimination of air from the solution passing therethrough.
  • the invention is directed to a disposable infusion set for use with an infusion device (e.g., a rapid infusion device) for administering to a patient by intravenous infusion a volume of solution comprising one or more members of the group consisting of: (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), (ii) one or more antibody drug conjugates (ADCs), (iii) one or more lipid drug conjugates (LDCs) and (iv) intravenous immunoglobulin (IVIg), the disposable infusion set comprising a tubing line or lines fluidly connecting an intravenous (IV) bag or other receptacle containing the volume of solution to a pump, and/or a pump to the patient, wherein the tubing line(s) have, collectively, no greater than 200 cc (cubic centimeters, cm 3 ) of a total priming volume plus dead space volume [e.g., no
  • the tubing line(s) have, collectively, no greater than 50 cc (cubic centimeters, cm 3 ) of a total priming volume plus dead space volume.
  • the disposable infusion set is configured (e.g., and approved) for use with a rapid infusion device (e.g., an infusion device capable of an infusion rate of at least 2 mL/min, e.g., at least 10 mL/min, e.g., at least 20 mL/min, e.g., at least 30 mL/min, e.g., at least 50 mL/min, e.g., at least 75 mL/min, e.g., at least 100 mL/min, e.g., at least 150 mL/min, e.g., at least 200 mL/min, e.g., at least 250 mL/min, e.g., at least 300 mL/min, e.g., at least 400 mL/min, e.g., at least 500 mL/min; e.g., an infusion device capable of infusion rates
  • a rapid infusion device
  • the volume of solution comprises an antibody treatment for the treatment of one or more members selected from the group consisting of cancer, a neurological disease, psoriasis, a respiratory disease, macular degeneration, cytokine release syndrome, Castelman disease, a disease caused by a pathogen, an organ transplant, and a tissue transplant.
  • the volume of solution comprises one or more antibody drug conjugates (ADCs) selected from the group consisting of ado-trastuzumab emtansine (e.g., KadcylaTM, manufactured by Genentech, Roche), brentuximab vedotin (e.g., AdcetrisTM, manufactured by Seattle Genetics, Millennium/Takeda), inotuzumab ozogamicin (e.g., BesponsaTM, manufactured by Pfizer/Wyeth), gemtuzumab ozogamicin (e.g., MylotargTM, manufactured by Pfizer/Wyeth), Moxetumomab pasudotox (e.g., LumoxitiTM, manufactured by Astrazeneca), polatuzumab vedotin-piiq (e.g., PolivyTM, manufactured by Genentech, Roche), Enfortumab
  • ADCs antibody drug conjugates
  • the volume of solution comprises an intravenous immunoglobulin (I VIg) [e.g, an intravenous immunoglobulin (I VIg) selected from the group consisting of Gammagard S/D (e.g., manufactured by Baxter/Hyland), Gammunex (e.g., manufactured by Bayer), Intratect (e.g., manufactured by Biotest Pharma), Kiovig (e.g., manufactured by Baxter), Octagam (e.g., manufactured by Octapharma), Pentaglobin (e.g., manufactured by Biotest Pharma), and Sandoglobulin (e.g., manufactured by CSL Behring)].
  • I VIg intravenous immunoglobulin
  • the volume of solution comprises one or more monoclonal and/or polyclonal antibodies comprising one or more members selected from the group consisting of: pembrolizumab (e.g., Keytruda), nivolumab (e.g., Opdivo), bevacizumab (e.g., Avastin), ocrelizumab (e.g., Ocrevus), rituximab (e.g., Rituxan, e.g., MabThera), daratumumab (e.g., Darzalex), pertuzumab (e.g., Perjeta), trastuzumab (e.g., Herceptin), infliximab (e.g., Remicade), tocilizumab (e.g., Actemra/RoActemra), atezolizumab (e.g., Tecentriq), tositumom
  • pembrolizumab
  • the invention is directed to an infusion device (e.g., a rapid infusion device) for administering to a patient by intravenous infusion a volume of solution comprising one or more members selected from the group consisting of: (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), (ii) one or more antibody drug conjugates (ADCs), (iii) one or more lipid drug conjugates (LDCs), and (iv) intravenous immunoglobulin (IVIg), the infusion device comprising: (a) a pump (e.g., a roller pump or centrifugal pump), and (b) a disposable infusion set (e.g., the disposable infusion set of any of the disclosed embodiments) comprising a tubing line or lines fluidly connecting an intravenous (IV) bag or other receptacle containing the volume of solution to the pump, and/or the pump to the patient, the tubing line(s)
  • the device further comprises a filter (e.g., an inline filter), wherein the filter comprises a filter membrane material that provides very low protein binding (e.g., negligible binding of the one or more antibodies to the filter membrane).
  • a filter e.g., an inline filter
  • the filter comprises a filter membrane material that provides very low protein binding (e.g., negligible binding of the one or more antibodies to the filter membrane).
  • FIG. 1 shows a system and device for administering a monoclonal and/or polyclonal antibody solution via rapid infusion, according to an illustrative embodiment.
  • FIG. 2 shows another system and device for administering a monoclonal and/or polyclonal antibody solution via rapid infusion, according to an illustrative embodiment.
  • FIG. 3 shows a method of using devices for administering a monoclonal and/or polyclonal antibody solution via rapid infusion, according to an illustrative embodiment.
  • FIG. 4 depicts an illustrative disposable infusion set manufactured by Belmont Medical Technologies (3-Spike Disposable Set) (400), originally designed for rapid delivery of warmed blood, e.g., via the FMS 2000 rapid infusion device, with noted design modifications to make the disposable set compatible for use with an infusion device (e g., a rapid infusion device) for infusion of an antibody treatment to a patient, according to illustrative embodiments of the present disclosure.
  • Belmont Medical Technologies 3-Spike Disposable Set
  • FIG. 5 depicts the illustrative disposable infusion set of FIG. 4, with notations depicting priming volume and dead space.
  • FIG. 6 depicts the illustrative disposable infusion set of FIG. 4 and 5, modified to remove an unnecessary chamber and superfluous tubing, for purposes of infusion of an antibody treatment to a patient, according to illustrative embodiments of the present disclosure.
  • FIG. 7 depicts a rapid infusion pump running at 30 mL/min after one minute of infusion of a “dead space” experiment, using the disposable infusion set of FIG. 6, according to an illustrative embodiment.
  • FIG. 8 depicts the rapid infusion pump of FIG. 7 at 1 minute 24 sec when the dye is exiting the patient line.
  • systems, architectures, devices, methods, and processes of the claimed invention encompass variations and adaptations developed using information from the embodiments described herein. Adaptation and/or modification of the systems, architectures, devices, methods, and processes described herein may be performed, as contemplated by this description.
  • Headers are provided for the convenience of the reader - the presence and/or placement of a header is not intended to limit the scope of the subject matter described herein.
  • FIG. 1 shows an example of a rapid infusion system 100, in accordance with an illustrative embodiment of the invention.
  • the rapid infusion system 100 includes an intravenous (IV) bag or other receptacle 110 containing a volume of drug solution to be administered to the patient. Elements of the rapid infusion system 100 are connected by tubing lines (e.g., a disposable set designed for one-time use).
  • the drug solution is drawn from the IV bag or other receptacle 110 with pump 120 (e.g., a roller pump or centrifugal pump).
  • Element 130 is a heater (which in some embodiments, may be optional) or other temperature control device.
  • element 130 may optionally include one or more of a rate control device (e g., a pressure-regulating valve 135, a pressure responsive valve 135, or the like), one or more sensors 140, and/or feedback circuitry 145.
  • a rate control device e g., a pressure-regulating valve 135, a pressure responsive valve 135, or the like
  • sensors 140 e.g., a pressure sensor 140
  • feedback circuitry 145 e.g., a pressure responsive valve 135, or the like
  • Heating element 130 may alternatively or additionally include an air venting mechanism 150.
  • element 130 includes (or is) a filter 155 for filtering out particles (e.g., monoclonal antibody aggregates and/or polyclonal antibody aggregates) from the volume of solution prior to (upstream of) delivery of the filtered solution to the patient.
  • the filter 155 has a size small enough (e.g., a mesh tight enough) to catch the particles (e.g., monoclonal antibody aggregates and/or polyclonal antibody aggregates).
  • the filter 155 has a size below 170 microns (e.g., below 150 microns, e.g., below 125 microns, e.g., below 100 microns, e.g., below 75 microns, e.g., below 50 microns, e.g., below 40 microns, e.g., below 30 microns, e.g., below 20 microns, e.g., below 10 microns, e.g., below 8 microns, e.g., below 5 microns, e.g., below 4 microns, e.g., below 2 microns, e.g., below 1 micron, e.g., below 0.7 micron, e.g., below 0.5 micron, e.g., below 0.3 micron, e.g., about 0.2 m).
  • a size below 170 microns e.g., below 150 microns,
  • a standard filter size for blood administration is generally 170-260 microns, which is designed to trap fragments of cells, clots, or particulate matter that may develop as a result of blood product storage.
  • particulate matter from antibody solutions is smaller (e.g., and/or the solution viscosity is less than that of blood), so a filter that traps smaller particles may be advantageously used for certain embodiments described herein.
  • the rapid infusion system 100 may include (e.g., as part or all of element 130, or as a separate element) an alarm 160 that identifies air or any other blockage in the line.
  • the rapid infusion system 100 may include (e g , as part or all of element 130, or as a separate element) an alarm 160 that identifies when a flow rate is above or below' a prescribed rate.
  • element 130 is positioned between element 110 (TV bag or other receptacle) and the pump 120.
  • element 130 i.e., the heating element
  • Element 130 may have one or more components, any one or more of which may be in a different position with respect to other elements of the system than pictured in FIG. 1 (e.g., one or more elements of 130, e.g., a filter, may be positioned between IV bag 110 and pump 120, ahead of the pump, or may be part of the intravenous (IV) bag or other receptacle 110).
  • one or more elements of 130 e.g., a filter
  • IV bag 110 e.g., a filter
  • FIG. 2 shows an example of a rapid infusion system 200, in accordance with an illustrative embodiment of the present disclosure.
  • the rapid infusion system 200 shown in FIG. 2 includes an elastomeric medicine ball 210 (also known as a “homeball,” “ball pump,” and/or “grenade pump”).
  • the elastomeric medicine ball 210 may be used for drug delivery in place of the reservoir 110, pump 120, heating element 130, and/or other components illustrated in FIG. 1 and described above.
  • the system 200 may be used for administering rapid infusion to patients in their own homes, for example.
  • Elastomeric medicine balls 210 are considered pumps, but they do not typically operate with electricity. Elastomeric pumps use pressure created by an elastomeric layer molded into the inside of the medicine ball 210 to infuse its fluid contents into a patient.
  • the system 200 includes a pump line 230 that is configured to connect to a patient IV line 260 (that may be already installed (i.e., pre-installed) in the patient, or alternatively may be installed at the time of treatment).
  • the patient IV line 260 Prior to connection with the pump line 230, the patient IV line 260 may be flushed with saline solution (for example, via syringe 225) to ensure no clogs in the system 200, and then subsequently sanitized with alcohol wipes, especially at device access port (or hub) 250 (where contaminants could potentially enter the patient IV line 260).
  • a pump line cap 240 can then be removed and the pump line 230 can be fluidly connected (for example, by inserting and twisting) into hub 250.
  • clamp 220 can be removed from the pump line 230, and the drug will begin flowing into the patient via the patient IV line 260.
  • the elastomeric medicine ball 210 may be pre-filled with drug product (i.e., drug solution) and may be pre- pressunzed. Once the clamp 220 is removed, the pressure within the elastomeric medicine ball 210 gradually forces the drug solution out of the elastomeric medicine ball 210, through the pump line 230 and patient IV line 260, and into the patient.
  • drug product i.e., drug solution
  • the delivery process for a single administration can take as long as 90 minutes, but is preferably a shorter time period, for example, administration is completed in no more than 30 minutes (e.g., no more than 25 minutes, e.g., no more than 20 minutes, e.g., no more than 15 minutes, e.g., no more than 10 minutes, e.g., no more than 5 minutes).
  • Elastomer balls generally have a flow restrictor 265 to control the accuracy of the rate of flow.
  • the flow restrictor 265 may be, for example, a steel cannula or a glass capillary molded into system tubing or located inside the elastomeric reservoir.
  • Standard elastomer balls generally provide a flow rate of up to about 250 mL/hr (about 4.17 mL/min).
  • elastomer balls may be engineered to permit higher flow rate, for example, flow rate substantially faster than IV flow by gravity alone (e.g., the elastomer ball system provides a flow rate of at least 10 mL/min, or at least 15 mL/min, or at least 20 mL/min, or at least 25 mL/min, or at least 30 mL/min, or at least 35 mL/min, or at least 40 mL/min, or at least 45 mL/min, or at least 50 mL/min).
  • Total drug delivery volumes per elastomeric medicine ball 210 may range up to about 500 mL (e.g., the total volume may be about 50 mL, about 100 mL, about 150 mL, about 250 mL, about 350 mL, about 450 mL, about 500 mL, or within ⁇ 50 mL ranges of each of these figures).
  • a patient IV line 260 can be installed in each arm (or, alternatively, in one or more other locations of the body), each patient IV line 260 connecting to a separate elastomeric medicine ball 210.
  • the elastomeric medicine ball 210 is calibrated according to the inherent back pressure or resistance in the pump line 230, patient IV line 260, and patient himself / herself, the elastomeric medicine ball 210 generally would not be used in connection with, for example, the fluid heater 130 (shown in FIG. 1).
  • each elastomeric medicine ball 210 should be removed from the refrigerator with enough time to warm up to room temperature (for example, 10-30 minutes, or about 10-20 minutes) prior to use. However, care should be taken not to expose each elastomeric medicine ball 210 to room temperature for a prolonged period of time, to avoid spoiling and/or breakdown of the drug product.
  • the system 200 may include one or more elastomeric medicine balls 210 that use only the pressure within each elastomeric medicine ball 210, and not gravity or a separate pump, for drug delivery.
  • patients have the ability to move around and carry the one or more elastomeric medicine balls 210 with them (for example, in a pocket or pockets, etc.) as the drug is flowing.
  • each elastomeric medicine ball 210 will be fully deflated, and the pump line 230 can be removed from the device access port 250 (or hub 250). The elastomeric medicine ball 210, pump line 230, clamp 220, and cap 240 can then be disposed of.
  • post treatment flushing of the patient IV line 260 should be performed to ensure any drug solution still in the patient IV line at the end of treatment in pushed through the patient IV line 260 into the patient.
  • final (i.e., post flushing) sterilization of the hub or device access port 250 should be performed, and the device access port should be capped after sterilization.
  • heparin may be administered before and/or after the final flushing to avoid clotting, depending on the patient needs.
  • the system 200 shown in FIG. 2 may also include a heating element in fluid communication with the drug IV line 230 (i.e., downstream of the ball pump 210) to more rapidly heat the infusate.
  • the system 200 may also include an additional pump fluidly upstream of the heating element in order to overcome any addition flow restriction or pressure drop introduced by the heating element.
  • FIG. 3 illustrates a method 300 for systems 100 and/or 200, according to aspects of the present embodiments.
  • the method 300 for system 200 may include using a syringe 225 and flushing the intravenously-attached system at port 250 with saline.
  • a solution flow rate may be determined according to various embodiments of system 100 and may be controlled using a flowcontrolling device 120.
  • an initial solution flow rate may be determined according to various embodiments of system 200 and may be controlled using a flowcontrolling device 210.
  • the initial solution flow rate may be 50 mg/hr, 100 mg/hr, or from about 25 mg/hr to about 75 mg/hr, or in other embodiments from about 75 mg/hr to about 125 mg/hr.
  • the flow rate may then be increased in increments of about 25 mg/hr, 50 mg/hr, and/or 100 mg/hr, at time intervals of about 1 minute, 2 minutes, 5 minutes, 10 minutes, 15 minutes, 20, minutes, and/or 30 minutes, to a maximum flow rate of about 400 mg/hr, or from about 300 mg/hr to about 450 mg/hr, or from about 250 mg/hr to about 500 mg/hr, or from about 150 mg/hr to about 450 mg/hr.
  • a solution temperature may be determined according to various embodiments of system 100 and a solution temperature may be set using an optional temperature-controlling device 130.
  • a solution temperature may be determined according to various embodiments of system 200 and a solution temperature may be set by equilibrating a solution to an ambient temperature or physiologically-relevant temperature.
  • step 308 rapid infusion is started by flowing a solution at an initial flow rate determined by various embodiments of the invention.
  • step 310 the patient is monitored and graded for infusion-related reactions (IRR).
  • IRR infusion-related reactions
  • a solution flow rate is maintained, increased, or decreased based on IRR grading and according to various embodiments of the present invention.
  • solution flow rate may be maintained for a patient presenting no IRR or presenting a minor IRR after an initial solution flow and being treated using an embodiment of system 100 or an embodiment of system 200.
  • solution flow rate may be increased for a patient presenting no IRR or presenting a minor IRR after an initial solution flow and being treated using an embodiment of system 100 or an embodiment of system 200.
  • solution flow rate may be increased for a patient presenting no IRR or presenting a minor IRR after an initial solution flow and being treated using an embodiment of system 100 or an embodiment of system 200.
  • a solution may be continued to flow at a flow rate previously determined in method 300 for a time period sufficient for providing disease therapy.
  • the method 300 may include monitoring for air and/or blockage in the system (for example, with or without the air of alarm 160) during the entire period of time that solution is flowing (i.e., steps 308-314 in FIG. 3).
  • a volume of therapeutic solution may be loaded into any device or devices (for example, 110, 210, 225) as needed according to aspects of the present disclosure.
  • FIG. 4 depicts an illustrative disposable infusion set manufactured by Belmont Medical Technologies (3-Spike Disposable Set) (400), originally designed for rapid delivery of warmed blood, with noted design modifications to make the disposable set compatible for use with an infusion device (e g., a rapid infusion device) for infusion of an antibody treatment to a patient.
  • an infusion device e g., a rapid infusion device
  • an inline filter for example, a 0.2 pm poly ethersulfone (PES) inline filter
  • PES poly ethersulfone
  • the inline filter (420) may be positioned, for example, at the connection to a patient line extension (430), as pictured, though other positions may be chosen, and a patient line extension may not be needed.
  • the added inline filter (420) also provides air venting.
  • the circular heat exchanger portion shown in FIG. 4, with high surface area stainless steel rings may be removed, e.g., where no heating of the delivered solution is required.
  • a pressure chamber and air detector is pictured to the left of the circular heat exchanger portion in FIG. 4, with the fluid path splitting into an infuse line extending from the air detector to the patient line extension (430), and a recirculate line extending below the heat exchanger portion and back up.
  • the modified design (for delivery of an antibody treatment) need not include a recirculate line, and, in certain embodiments, the pressure chamber and/or air detector is/are not needed or is/are positioned elsewhere in the disposable set.
  • the disposable set pictured in FIG. 4 has connections between a heat exchanger, reservoir, and patient line. Where a heat exchanger and/or reservoir is/are not needed, further modifications of this arrangement can be made to adapt the set for use with infusion of treatment solutions.
  • non-PES coarse blood filters such as used with the 120 mL reservoir chamber 410 for infusion of blood or plasma (the original purpose of rapid infusion devices) may clog if used to filter antibody infusions, e.g., solutions of monoclonal and/or polyclonal antibodies (mAbs and/or pAbs), antibody drug conjugates (ADCs), lipid drug conjugates (LDCs), and/or intravenous immunoglobulin (IVIg).
  • mAbs and/or pAbs monoclonal and/or polyclonal antibodies
  • ADCs antibody drug conjugates
  • LDCs lipid drug conjugates
  • IVIg intravenous immunoglobulin
  • An example of a PES filter suitable to filter antibody infusions which can be integrated as an inline filter 420 in the disposable filter set 400 of FIG 4, is the Sterifix® 0.2 pm infusion filter manufactured by B.
  • the inline filter 420 provides retention of undesired particles, bacteria, and fungi, and provides for elimination of air, while avoiding binding of antibodies.
  • the filter has a Supor® membrane made of PES with effective filtration area of 10 cm2.
  • Other non-PES filters can potentially bind antibodies, e.g., monoclonal antibodies (mAbs), from the treatment solution such that it is retained in the filter rather than being delivered to the patient.
  • mAbs monoclonal antibodies
  • Another filter membrane material that provides very low protein binding is cellulose acetate, and hence, in certain embodiments, may be used for mAbs delivery via infusion (e.g., rapid infusion). Regenerated cellulose has low protein binding but higher than PES and cellulose acetate.
  • Nylon has low to moderate protein binding, and cellulose nitrate has high protein binding.
  • the infusion device (e.g., rapid infusion device) includes a disposable set with a sterile fluid path intended for single-use, with standard luer connectors for connection to a standard catheter and a pressure-regulating valve (PRV) at the input to protect the disposable set and the patient from unintended exposure to high pressure applied to the intravenous (IV) line, wherein the PRV may allow an increase of flow from a low level to a higher level by application of a pressure (e.g., up to 300 mmHg), but will prevent pressure higher than this from reaching the set or IV line distal to it.
  • the infusion device also includes a check valve at the output to prevent back flow.
  • drug administration is simplified by provision of a portable infusion system (e.g., a portable rapid infusion system) with disposable tubing lines already attached, e.g., where the entire infusion system, pump included, is designed for a single use.
  • a portable infusion system e.g., a portable rapid infusion system
  • disposable tubing lines already attached e.g., where the entire infusion system, pump included, is designed for a single use.
  • Further simplification may be possible by providing the IV bag (or other receptacle) pre- loaded with drug solution (e.g., pre-made drug solution) in the appropriate amount and at the appropriate concentration (e g., all in a self-contained kit).
  • drug solution e.g., pre-made drug solution
  • concentration e.g., all in a self-contained kit
  • the invention is directed to a disposable infusion set for use with an infusion device (e.g., a rapid infusion device) for administering by intravenous infusion a volume of solution comprising one or more antibodies [e.g., (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs) and/or (n) one or more antibody drug conjugates (ADCs) and/or (iii) one or more lipid drug conjugates (LDCs) and/or (iv) intravenous immunoglobulin (IVIg)] to a patient, the disposable infusion set comprising a tubing line or lines and a filter (e.g., an inline filter), wherein the filter comprises a filter membrane that provides very low protein binding (e.g., negligible binding of the one or more antibodies to the filter membrane).
  • an infusion device e.g., a rapid infusion device
  • ADCs antibody drug conjugates
  • LDCs lipid drug conjugates
  • the filter membrane comprises polyethersulfone (PES).
  • the filter membrane comprises cellulose acetate.
  • the filter membrane has pore size less than 2 pm, or less than 1 pm, or less than 0.5 pm, or less than 0.3 pm, or about 0.2 pm.
  • the disposable infusion set is configured (e.g., and approved) for use with a rapid infusion device (e.g., an infusion device capable of an infusion rate of at least 2 mL/min, e.g., at least 10 mL/min, e.g., at least 20 mL/min, e.g., at least 30 mL/min, e.g., at least 50 mL/min, e.g., at least 75 mL/min, e.g., at least 100 mL/min, e.g., at least 150 mL/min, e.g., at least 200 mL/min, e.g., at least 250 mL/min, e.g., at least 300 mL/min, e.g., at least 400 mL/min, e.g., at least 500 mL/min; e.g., an infusion device capable of infusion rates
  • a rapid infusion device
  • the disposable infusion set does not include a coarse (e g., with pore size greater than 100 pm or greater than 200 pm, e.g., 250 pm) filter (e g., a blood filter, e.g., a filter that does not provide very low protein binding, e.g., a filter that is not made of PES or cellulose acetate).
  • a coarse filter e.g., with pore size greater than 100 pm or greater than 200 pm, e.g., 250 pm
  • a blood filter e.g., a filter that does not provide very low protein binding, e.g., a filter that is not made of PES or cellulose acetate.
  • the tubing line or lines fluidly connect (i) an intravenous (IV) bag or other receptacle containing the volume of solution to a pump capable of administering the volume of solution to the patient at a flow rate faster (e.g., substantially faster) than by gravity alone (e.g., faster than a gravity drip device) and/or (ii) the pump to the patient.
  • IV intravenous
  • a pump capable of administering the volume of solution to the patient at a flow rate faster (e.g., substantially faster) than by gravity alone (e.g., faster than a gravity drip device) and/or (ii) the pump to the patient.
  • the tubing line or lines (and/or pump surfaces that come into contact with the pumped fluid) is/are constructed of a medical-grade plastic such as polyvinyl chloride (PVC), polyethylene, a thermoplastic elastomer (TPE), nylon, and/or silicone.
  • a medical-grade plastic such as polyvinyl chloride (PVC), polyethylene, a thermoplastic elastomer (TPE), nylon, and/or silicone.
  • the filter provides for retention of bacteria and/or fungi, and/or wherein the filter provides for elimination of air from the solution passing therethrough.
  • the invention is directed to an infusion device (e.g., a rapid infusion device) for administering by intravenous infusion a volume of solution comprising one or more antibodies [e.g., (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs) and/or (ii) one or more antibody drug conjugates (ADCs) and/or (iii) one or more lipid drug conjugates (LDCs) and/or (iv) intravenous immunoglobulin (IVIg)] to a patient
  • the rapid infusion device comprising: a pump (e.g., a roller pump or centrifugal pump); and a disposable infusion set (e.g., any of the disposable infusion sets described herein) comprising a tubing line or lines and a filter (e.g., an inline filter), wherein the filter comprises a filter membrane that provides very low protein binding (e g., negligible binding of the one
  • the invention is directed to a method for administering an antibody treatment via an infusion device (e.g., a rapid infusion device), the method comprising: administering by intravenous infusion a volume of solution comprising one or more antibodies [e.g., (i) one or more monoclonal and/or polyclonal antibodies (mAbs and/or pAbs) and/or (ii) one or more antibody drug conjugates (ADCs) and/or (iii) one or more lipid drug conjugates (LDCs) and/or (iv) intravenous immunoglobulin (IVIg)] to a patient using an infusion device (e.g., a rapid infusion device), wherein the infusion device comprises a pump (e.g., a roller pump or centrifugal pump) and a disposable infusion set (e.g., the disposable infusion set of any of the embodiments described herein) comprising a tubing line or lines and a filter (e.g.
  • a pump e
  • the one or more monoclonal and/or polyclonal antibodies comprises a monoclonal and/or polyclonal antibody (or cocktail of antibodies) for the treatment of one or more members selected from the group consisting of cancer (e.g., colorectal, lung, glioblastoma, kidney, breast, stomach, esophageal, cervical, or ovarian cancer, or multiple myeloma, soft tissue sarcoma, lymphoma, melanoma, neuroblastoma, or leukemia), a neurological disease or condition ⁇ e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD); Duchene’s muscular dystrophy (DMD); multiple sclerosis (MS); myasthenia gravis; migraine; migraine and cluster headache; neuromyelitis optica spectrum disorder (NMOSD); idiopathic inflammatory myopathies (IIM); immune-related peripheral neuropathies (multifocal motor neuropathy (MMN), anti-mye
  • cancer e.g.
  • the one or more monoclonal and/or polyclonal antibodies comprises a member selected from the group consisting of the following: an antiinflammatory (e.g., infliximab, adalimumab, basiliximab, daclizumab, or omalizumab); an anti-cancer (e g., gemtuzumab, alemtuzumab, rituximab, trastuzumab, nimotuzumab, cetuximab, or bevacizumab & ranibizumab); an anti-cancer and anti-viral (e.g., bavituximab); palivizumab; and abciximab.
  • an antiinflammatory e.g., infliximab, adalimumab, basiliximab, daclizumab, or omalizumab
  • an anti-cancer e.g., gemtuzumab, alemt
  • the method is performed for the treatment of COVID- 19 (i.e., caused by the virus SARS-CoV-2)
  • the one or more monoclonal and/or polyclonal antibodies comprises one or more members selected from the group consisting of bamlanivimab (aka LY-CoV555, Eli Lilly); bamlanivimab and etesevimab antibody cocktail (aka LY-CoV555 (bamlanivimab) + JS016 (etesevimab) antibody cocktail, Eli Lilly); casirivimab and imdevimab antibody cocktail (aka REGN-COV2 aka REGEN-COVTM aka
  • REGN10933 + REGN10987 aka Ronapreve, Regeneron, Roche
  • gimsilumab Roivant Sciences
  • tocilizumab aka Actemra, Genentech
  • COVI-GUARDTM (STI-1499) and/or COVI-AMGTM (STI-2020)
  • regdanvimab aka Regkirona (Celltiion); sotrovimab (aka VIR-7831 aka Xevudy) and/or VIR-7832, Vir Biotechnology); and tixagevimab and cilgavimab antibody cocktail (aka Evusheld, AstraZeneca)] .
  • the method is performed for the treatment of a neurological disease or condition ⁇ e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD); Duchene’s muscular dystrophy (DMD); multiple sclerosis (MS); myasthenia gravis; migraine; migraine and cluster headache; neuromyelitis optica spectrum disorder (NMOSD); idiopathic inflammatory myopathies (IIM); immune-related peripheral neuropathies (multifocal motor neuropathy (MMN), anti-myelin associate glycoprotein (anti-MAG) neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP)); or a neurooncological condition (e.g., malignant glioma or recurrent glioblastoma) ⁇ [e.g., wherein the one or more monoclonal antibodies comprises one or more members selected from the group consisting of aducanumab (Biogen Inc ), gantenerumab (Chugai Pharmaceutical Co., Ltd., Hoffmann-La
  • the one or more monoclonal antibodies comprises one or more members selected from the group consisting of: pembrolizumab (Keytruda), manufactured by Merck for treatment of cancer; nivolumab (Opdivo), manufactured by Bristol Myers Squibb, for various forms of cancer; bevacizumab (Avastin), manufactured by Roche, for colorectal, lung, glioblastoma, kidney, cervical, and/or ovarian cancer; ocrelizumab (Ocrevus), manufactured by Roche, for relapsing or primary progressive multiple sclerosis; rituximab (Rituxan), manufactured by Roche, Pharmstandard, for various autoimmune diseases and cancers; daratumumab (Darzalex), manufactured by Janssen (Johnson & Johnson), for multiple myeloma; pertuzumab (Peg eta), manufactured by Roche, for HER2 -positive breast cancer; trastuzumab
  • the method is performed for the treatment of an organ and/or tissue transplant patient [e.g., wherein the one or more polyclonal and/or monoclonal antibodies comprises one or more members selected from the group consisting of antithymocyte globulin [rabbit] (Thymoglobulin, Sanofi), lymphocyte immune globulin, antithymocyte globulin [equine] sterile solution (Atgam, Pfizer), alemtuzumab (Sanofi), rituximab (Amgen Inc), alpha- 1 antitrypsin, and a double antibody conjugate that is an anti- CD3 and anti-CD7 agent].
  • antithymocyte globulin [rabbit] (Thymoglobulin, Sanofi)
  • lymphocyte immune globulin lymphocyte immune globulin
  • antithymocyte globulin [equine] sterile solution Atgam, Pfizer
  • alemtuzumab Sanofi
  • the volume of solution being rapidly infused to the patient comprises one or more antibody drug conjugates (ADCs) and/or lipid drug conjugates (LDCs) [lipoidal prodrug - bioactive molecules covalently or non-covalently linked with lipids like fatty acids, glycerides, or phospholipids].
  • ADCs antibody drug conjugates
  • LDCs lipid drug conjugates
  • ADCs examples include the following: ado-trastuzumab emtansine (KadcylaTM, manufactured by Genentech, Roche), brentuximab vedotin (AdcetrisTM, manufactured by Seattle Genetics, Millennium/Takeda), inotuzumab ozogamicin (BesponsaTM, manufactured by Pfizer/Wyeth), gemtuzumab ozogamicin (MylotargTM, manufactured by Pfizer/Wyeth), Moxetumomab pasudotox (LumoxitiTM, manufactured by Astrazeneca), polatuzumab vedotin-piiq (PolivyTM, manufactured by Genentech, Roche), Enfortumab vedotin (PadcevTM, manufactured by Astellas/Seattle Genetics), Sacituzumab govitecan (Trodelvy, manufactured by Immunomedics),
  • the volume of solution being rapidly infused to the patient comprises an immunoglobulin (IVIg) preparation.
  • IVIG preparations include the following: Gammagard S/D (Baxter/Hyland), Gammunex (Bayer), Intratect (Biotest Pharma), Kiovig (Baxter), Octagam (Octapharma), Pentaglobin (Biotest Pharma), and Sandoglobulin (CSL Behring).
  • the infusion device for which the disposable infusion set is designed to be used is a rapid infusion device, though in other embodiments, the infusion device is not a rapid infusion device.
  • Examples of commercially available rapid infusion systems include the Hotline HL-1200A Rapid Infuser Infusion Pump (capable of infusion rates from 30 mL/min to 1100 mL/min, with maximum rate of 1400 mL/min) (Smiths Group Pic, London, UK); the Belmont® Rapid Infuser RI-2 (capable of infusion rates from 2.5 mL/min to 1000 mL/min), the FMS2000, the buddyTM and the buddy liteTM portable IV & infusion pump (Belmont Medical Technologies, Billerica, MA); LifeFlow Rapid Fluid Infuser, and LifeFlow Plus Rapid Fluid and Blood Infuser (capable of 500 rnL of fluid in less than 2 min, 20G IV catheter, or 274 mL/min via 18ga catheter) (410 Medical, Durham, NC); Thermacor 1200 (capable of infusion rates from 10 mL/hour to 1200 mL/min) (Smisson-Cartledge Biomedical, Macon, GA); The Warrior lite, W
  • the portable Belmont® buddyTM system is designed for flow rates up to 100 mL/min for crystalloids at 20 °C and up to 50 rnL/min for packed red cells at 10 °C.
  • the portable, battery powered buddy liteTM system is designed for maximum flow rates of 50-80 mL/min, depending on the input temperature.
  • Pressurized devices for massive transfusion of blood include the Belmont Rapid Infuser RI-2 which can deliver a flow rate of more than 750 mL/minute (e.g., up to 1500 mL/minute); the Level 1 h-1200 Fast Flow Fluid Warmer which can infuse fluids at flows of up to 600 mL/min.
  • Many of the above devices include a flow control system and/or other flow and/or metering control devices, such as pressure-regulating valves (PRVs) and/or pressure-responsive valves, to control the specific flow rate of a liquid delivered to the patient and/or to ensure the flow stays below a predetermined maximum flow rate and/or above a predetermined minimum flow rate.
  • PRVs pressure-regulating valves
  • these flow control devices and/or systems may allow the operator to establish an initial lower flow rate, then increase to a safe higher flow rate if no serious IRRs are observed in the patient.
  • Rapid infusion systems are not currently used for administration of drugs. Rapid infusion systems include those described in any of the following U.S. patents and published patent application, the disclosures of which are incorporated herein by reference: U.S. Patent Nos. 5,319,170; 6,175,688; 6,236,809; 6,480,257; 7,819,875; 9,737,672; 10,293,099; and 10,485,936; and U.S. Patent Application Publication No. 2009/0192446 (U.S. Patent Application No. 12/228,618).
  • a rapid infusion device does not need a drip chamber to gauge flow rates, since a software-controlled pump is used to administer the fluids.
  • a rapid infusion device provides for administration of mAbs with reduced agitation of the mAbs and infusate, as compared to administration by drip IV. The reduced agitation can help avoid problems due to mAbs instability, aggregation, and protein unfolding, potentially improving efficacy.
  • the infusion device comprises an elastomeric (e.g., ball) pump, wherein the pump comprises the receptacle containing the volume of solution, and wherein the tubing line or lines fluidly connect (e.g., directly or indirectly) the pump (and, therefore, the receptacle containing the volume of solution) to the patient via the abovedescribed disposable infusion set, for intravenous delivery of the volume of solution to the patient.
  • the pump comprises the receptacle containing the volume of solution
  • the tubing line or lines fluidly connect (e.g., directly or indirectly) the pump (and, therefore, the receptacle containing the volume of solution) to the patient via the abovedescribed disposable infusion set, for intravenous delivery of the volume of solution to the patient.
  • the infusion device/system may include an intravenous (IV) bag or other receptacle containing a volume of drug solution to be administered to the patient. Elements of the infusion device are connected by tubing lines of a disposable set designed for one-time use.
  • the drug solution is draw n from the IV bag or other receptacle with a pump (e.g., an elastomeric (e.g., ball) pump, a roller pump, or a centrifugal pump).
  • the infusion device may optionally include a heater or other temperature control device.
  • the infusion device may optionally include one or more of a rate control device (e g., a pressure-regulating valve, a pressure responsive valve, or the like), one or more sensors, and/or feedback circuitry .
  • a rate control device e g., a pressure-regulating valve, a pressure responsive valve, or the like
  • the heating element may alternatively or additionally include an air venting mechanism.
  • the air venting mechanism is part of the filter (e.g., inline filter).
  • FIG. 5 depicts the illustrative disposable infusion set of FIG. 4, with notations depicting priming volume and dead space.
  • FMS2000 disposable bag could result in under-dosed infusions if they are infused using the pump without a post infusion saline flush.
  • the Belmont pump stops infusing once the disposable bag is mostly emptied and air is detected at the inlet of the machine, yet, fluid still remains inside the disposable when the pump stops.
  • the remaining fluid in the “dead space” contains some of the required dose necessary to complete the pharmaceutical treatment. The patient will be left under-dosed should the medicated fluid in the “dead space” not be pushed into the patient.
  • FIG. 6 depicts the illustrative disposable infusion set of FIGs. 4 and 5, modified to remove an unnecessary chamber and superfluous tubing, for purposes of infusion of an antibody treatment to a patient, according to illustrative embodiments of the present disclosure.
  • the modified design eliminates 162 cc of priming fluid that would be needed for blood infusions, but is unnecessary for mAbs delivery.
  • the unneeded chamber and filter (410) is replaced with minimal tubing and a spike, in this example.
  • the priming volume of the system is 242 cc, which includes a dead volume of only 80 cc as there is a vent at the top of the chamber to empty the camber and associated tubing of 162 cc.
  • the pump will stop once the disposable bag is emptied, as detected when air is sensed at the top of the tubing located within the pump housing.
  • 80 cc of fluid the so-called “dead space”
  • This volume of fluid contains some of the dose needed to complete the procedure, potentially leaving the patient under-dosed if not flushed.
  • FIGs. 7 and 8 to quantify mixing and/or diffusion with a post-infusion saline flush.
  • the protocol for the infusion test is as follows: [0125] Materials:
  • a goal is to reduce the time and resources required for infusion of mAbs and similar medications, thus, the experiment was performed at a 30 mL/min flow rate, a rate that is considerably faster than typical mAb infusions (e g., Rituxan is infused at 0.2 mL/min - 6.6 mL/min per the IFU).
  • the amount of fluid within the ringed portion of the disposable was measured at 80 cc (“dead space”) and the amount of fluid within the recirculation line was measured at between 9 and 16 cc (average of 12.5 cc), where the 12.5 cc is a portion of the 80 cc dead space.
  • the Belmont system purges air that has collected in the air collection chamber by closing the infusion line and opening the recirculation line. Air is purged from the air collection chamber to ensure that no air is infused into the patient. Thus, upon completion of the mAb infusion, it is not expected to be able to flush the recirculation line without further mixing and infusion of additional saline.

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  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne des méthodes, des systèmes et un appareil pour administrer un traitement d'anticorps par l'intermédiaire d'un dispositif de perfusion, par exemple, un dispositif de perfusion rapide, par exemple, pour le traitement d'une maladie ou d'un état pathologique qui nécessite une ou plusieurs perfusions d'anticorps monoclonaux et/ou polyclonaux.
PCT/US2023/021983 2020-12-22 2023-05-12 Méthodes, systèmes et appareil d'administration d'un traitement d'anticorps par perfusion WO2023220336A1 (fr)

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US202263341928P 2022-05-13 2022-05-13
US63/341,928 2022-05-13
US202263343963P 2022-05-19 2022-05-19
US63/343,963 2022-05-19
US17/840,423 US11806507B2 (en) 2020-12-22 2022-06-14 Methods, systems, and apparatus for administering an antibody treatment via infusion
US17/840,423 2022-06-14
US202363457898P 2023-04-07 2023-04-07
US63/457,898 2023-04-07

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020016570A1 (en) * 1996-02-28 2002-02-07 Cartledge Richard G. Rapid infusion system
US8372045B2 (en) * 2004-11-19 2013-02-12 Curlin Medical Inc. Controlled-volume infusion device
WO2015133972A1 (fr) * 2014-03-07 2015-09-11 Agency For Science, Technology And Research Appareil et procédés permettant le fractionnement de produits biologiques
US20170058044A1 (en) * 2007-03-14 2017-03-02 Ganymed Pharmaceuticals Ag Monoclonal Antibodies for Treatment of Cancer
WO2021097220A1 (fr) * 2019-11-15 2021-05-20 Seagen Inc. Méthodes de traitement du cancer du sein her2 positif avec du tucatinib en combinaison avec un conjugué médicament-anticorps anti-her2
WO2022140463A1 (fr) * 2020-12-22 2022-06-30 Herzlinger Regina E Procédés, systèmes et appareil d'administration d'un traitement d'anticorps monoclonal et/ou polyclonal par perfusion rapide

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020016570A1 (en) * 1996-02-28 2002-02-07 Cartledge Richard G. Rapid infusion system
US8372045B2 (en) * 2004-11-19 2013-02-12 Curlin Medical Inc. Controlled-volume infusion device
US20170058044A1 (en) * 2007-03-14 2017-03-02 Ganymed Pharmaceuticals Ag Monoclonal Antibodies for Treatment of Cancer
WO2015133972A1 (fr) * 2014-03-07 2015-09-11 Agency For Science, Technology And Research Appareil et procédés permettant le fractionnement de produits biologiques
WO2021097220A1 (fr) * 2019-11-15 2021-05-20 Seagen Inc. Méthodes de traitement du cancer du sein her2 positif avec du tucatinib en combinaison avec un conjugué médicament-anticorps anti-her2
WO2022140463A1 (fr) * 2020-12-22 2022-06-30 Herzlinger Regina E Procédés, systèmes et appareil d'administration d'un traitement d'anticorps monoclonal et/ou polyclonal par perfusion rapide

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