EP-4736892-A2 - METHODS FOR PREPARING PATHOGEN-INACTIVATED WHOLE BLOOD

Abstract

Provided are methods for preparing pathogen-inactivated whole blood and other pathogen-inactivated blood product compositions, as well as kits and compositions related thereto.

Inventors

• CAHYADI, Harry
• NORTH, ANNE
• VON GOETZ, Melissa
• ERICKSON, ANNA

Assignees

• Cerus Corporation

Dates

Publication Date

20260506

Application Date

20190920

Claims (17)

1. A kit for preparing a pathogen-inactivated whole blood composition, comprising: (a) a vascular access device for drawing whole blood from a donor; (b) a first container suitable for mixing the whole blood and a pathogen inactivation compound (PIC), wherein the first container comprises at least a first inlet and a first outlet ; (c) a first conduit extending between the vascular access device and the first container and providing a fluid communication path for transferring the whole blood from the donor into the first container; (d) a container containing a pathogen inactivation compound (PIC container); (e) a second conduit, wherein the second conduit: (i) is coupled or configured to be coupled at one end to the PIC container; (ii) is coupled to the first container, configured to be coupled to the first container, or configured to be coupled to the first conduit, thereby providing a fluid communication path between the PIC container and the first container; and (iii) further comprises a displacement device suitable for increasing the transfer of the PIC into the first container; and (f) an infusion line assembly for infusing a pathogen-inactivated whole blood composition into a subject.
2. The kit of claim 1, wherein: (a) the PIC container is configured to be coupled by a fluid communication path to the first container; or (b) the PIC container is coupled by a fluid communication path to the first container; or (c) the first container further comprises a second inlet and the PIC container is configured to be coupled by a fluid communication path to the second inlet of the first container; or (d) the first container further comprises a second inlet and the PIC container is coupled by a fluid communication path to the second inlet of the first container.
3. The kit of claim 1 or claim 2, further comprising a container containing a quencher (quencher container).
4. The kit of claim 3, wherein the quencher container: (a) is configured to be coupled by a fluid communication path to the first container, optionally wherein the quencher container is configured to be coupled to the first conduit or configured to be coupled by a fluid communication path to the second inlet of the first container; or (b) is coupled by a fluid communication path to the first container; optionally wherein the quencher container is coupled by a fluid communication path to the second inlet of the first container.
5. The kit of claim 3 or claim 4, wherein the second conduit is coupled at one end to the quencher container
6. The kit of claim 3 or claim 4, wherein the PIC container and the quencher container are the same container.
7. The kit of any one of claims 1-6, wherein the second conduit comprises at one end at least one adaptor for coupling a PIC container to the second conduit.
8. The kit of claim 7, wherein the second conduit comprises at one end a first adaptor for coupling a PIC container to the second conduit and a second adaptor for coupling a quencher container to the second conduit.
9. The kit of any one of claims 3-8, wherein the second conduit is configured to be coupled to the first conduit, providing a fluid communication path between the quencher container and the first container.
10. The kit of any one of claims 3-9, wherein the displacement device is further suitable for increasing the transfer of the quencher into the first container.
11. The kit of any one of claims 1-10, wherein the first container contains an anticoagulant.
12. The kit of any one of claims 1-11, further comprising a second container suitable for storing a pathogen-inactivated whole blood composition, wherein the second container comprises at least a first inlet and a first outlet.
13. The kit of claim 12, further comprising: (a) a third conduit extending between the first container and the second container and providing a fluid communication path for transferring a mixture comprising a whole blood composition and a PIC from the first container into the second container, optionally wherein the mixture further comprises a quencher if present; and/or (b) a third container suitable for storing a pathogen-inactivated whole blood composition, wherein the third container comprises at least a first inlet and a first outlet, and wherein the kit further comprises a fourth conduit extending between the second container and the third container and providing a fluid communication path for transferring a mixture comprising a whole blood composition and a PIC from the second container into the third container, optionally wherein the mixture further comprises a quencher if present.
14. The kit of claim 12 or claim 13, wherein the infusion line assembly is coupled to the second container; optionally wherein the infusion line assembly comprises a second vascular access device and an infusion line conduit extending between the first outlet of the second container and the second vascular access device, wherein the infusion line conduit provides a fluid communication path for sterilely transferring the pathogen-inactivated whole blood composition from the second container to the vascular access device.
15. The kit of any one of claims 1-14, wherein: (a) the PIC comprises a functional group which is, or which forms, a reactive electrophilic group; and/or (b) the PIC comprises a nucleic acid binding ligand.
16. The kit of any one of claims 3-15, wherein: (a) the quencher comprises a thiol group, wherein the thiol is capable of reacting with a reactive electrophilic group of the PIC; and/or (b) the quencher is glutathione or a pharmaceutically acceptable salt thereof.
17. The kit of claim 1, wherein the displacement device is an air displacement device; optionally wherein the displacement device includes a sample diversion pouch, a syringe, a rubber bulb, a flexible container, or a cartridge; optionally wherein the displacement device is an air pillow or sampling pouch.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the priority benefit of U.S. Provisional Application No. 62/734,117, filed September 20, 2018, the disclosure of which is incorporated herein by reference in its entirety. TECHNICAL FIELD The present disclosure relates to pathogen-inactivated whole blood and improved methods and kits for preparing pathogen-inactivated whole blood and other blood product compositions. BACKGROUND Pathogen inactivation (PI) technologies increasingly are being used to treat blood products to help mitigate the risk of transfusion transmitted infection and complications arising from donor leukocytes. At least three PI technologies available commercially in certain countries utilize ultraviolet light, either in the presence or absence of a pathogen inactivation compound (e.g., photosensitizer), for treatment of one or more blood products, such as plasma, platelets, red blood cells and/or whole blood (see e.g., Schubert, 2018; Schlenke, 2014; Prowse 2013). Such PI technologies include, for example, the amotosalen/UV based INTERCEPT® system (Cerus), the riboflavin/UV based Mirasol® system (TerumoBCT) and the UVC light only based Theraflex® system (Macopharma). At least one other PI technology in late stage clinical development for treatment of red blood cells (RBCs) also targets nucleic acids, by utilizing frangible pathogen-inactivation compounds (e.g., S-303), but without the need for ultraviolet light (Henschler 2011). Exemplary frangible PI compounds are described in more detail in U.S. Patents 6,093,725 and 6,514,987. The INTERCEPT® Blood System for RBCs utilizes the frangible nucleic acid targeted alkylator compound S-303 (e.g., amustaline) for pathogen inactivation. Amustaline is a modular compound comprising an acridine anchor (e.g., intercalator that targets nucleic acids), an effector (e.g., bis alkylator group that reacts with nucleophiles such as DNA bases) and a linker (e.g., small flexible carbon chain that contains a labile ester bond that can hydrolyze at neutral pH). The anchor targets nucleic acids of pathogens and cells by intercalating into helical regions, with the effector rapidly (e.g., minutes) reacting with nucleic acid bases to form mono adducts and then cross links that block replication. Within hours, the linker can hydrolyze, resulting in the dissociation of the anchor from the effector. The INTERCEPT® Blood System for RBCs further includes a quencher, such as for example glutathione (GSH), to reduce non-specific binding of amustaline (Henschler 2011; US Patent No. 8,900,805). Following mixing of a donor RBC unit, amustaline, GSH and a processing solution, the admixture is transferred to an incubation bag, incubated at room temperature for 18-24 hours for pathogen inactivation and amustaline hydrolysis, and then centrifuged, with the solution containing residual non-hydrolyzed amustaline, GSH, processing solution subsequently removed and replaced with a red blood cell additive solution prior to storage. PI treatment with the pathogen inactivation compound amustaline and GSH also has been demonstrated for whole blood units. However, for whole blood PI treatment, similar post-incubation steps of centrifugation and solution replacement with fresh additive solution as used for treatment of red blood cells cannot be performed, and therefore residual non-hydrolyzed amustaline and GSH is not removed or reduced by such solution replacement step, which may preclude the use of the PI treated whole blood units for infusion into a subject if the residual amustaline remains above certain concentrations in treated units. Additionally, volume limitations for amustaline and GSH addition to whole blood for pathogen inactivation compared to red blood cell treatment processes may affect dosing and benefit from processing kits modifications that better facilitate transfer of compounds. Finally, current pathogen inactivation technologies, including the amustaline/GSH system, may have certain limitations for use, particularly in geographic areas which can lack access to suitable facilities, and in war zones where blood components are not easily available or treatable. PI technologies generally require suitable power sources and equipment for one or more processing steps, including for example an illumination device to provide ultraviolet light exposure during processing (e.g., amotosalen/UV and riboflavin/UV systems) and/or devices for other processing steps, such as for example, the use of sterile docking (e.g., tubing welding) devices to connect blood product containing bags to a PI system (e.g., to a kit, to a processing set) and/or centrifuges, incubators, rockers, agitators or other equipment. Therefore, modifications to PI technologies and related processing kits that could lead to further improvements in the pathogen inactivation of blood products (e.g., whole blood) are desirable, such as by reducing residual levels of PI compounds in treated products, im