EA043840B1 - SYSTEMS AND METHODS FOR PREPARATION OF PLATELETS - Google Patents

Description

Cross reference to related applications

This invention claims priority to US Provisional Application No. 62/276223, filed January 7, 2016, and 62/311373, filed March 21, 2016, each of which is incorporated herein by reference in its entirety.

Field of technology

The methods, systems and compositions described herein generally relate to the preparation of platelets. More specifically, the present invention relates to improved methods and systems for preparing apheresis platelet units suitable for infusion, and compositions containing such platelet units.

State of the art

The collection and processing of blood components play a critical role in healthcare worldwide, and millions of units of donated blood components are collected by blood banks every year. While some units of whole blood are collected from donors and used directly for transfusion, most collections are typically separated into the blood components of red blood cells, platelets, and plasma for more specific therapeutic uses. Separation can occur either after whole blood collection or at the time of collection if a suitable separation device system is used, such as an apheresis collection device. The individual blood components are then used to treat various medical needs and conditions based on therapeutic need.

Platelets play a key role in hemostasis, thrombus stability and retraction, as well as vascular repair and host defense against microbes. Various methods are used to collect and store blood platelets for clinical use. The collection of platelets from a unit of donated whole blood is usually carried out in the form of platelet concentrates (PCs) prepared using processing methods such as buffer layer or platelet plasma method, and such CTs can be combined to create a unit of platelets with sufficient therapeutic dosage for transfusion. In general, CT scans from four to six separate donors of compatible blood types should be combined to create one unit of platelets of sufficient therapeutic dose for transfusion.

Apheresis collection provides a method of obtaining platelet units of sufficient therapeutic strength from a single donor without the need for pooling and any associated risk of infusion recipient exposure to platelets from multiple donors. Apheresis platelet collection uses an automatic device that separates platelets from donor blood and returns the remaining blood components (e.g., red blood cells, plasma) to the donor during the donation process, apheresis platelet portions are usually based on certain donor parameters such as gender, physical size ( e.g., weight), hemoglobin level, platelet count on the day of donation, and frequency of donation, in part to ensure that only safe quantities are collected. With these parameters, apheresis platelet donation typically involves collecting from an individual donor a volume sufficient to obtain one, two, or three platelet units, each containing a specified minimum number (e.g., at least a minimum number) of platelets per unit to satisfy therapeutic dose with such unit or therapeutic dose criteria as are generally defined by government, regulatory, institutional, or accredited organization (e.g., industry) standards. Blood centers may further define their own apheresis platelet collection characteristics for single, double, and triple collections (e.g., split points), including, for example, the volume (e.g., number) of excess platelets compared to that required to satisfy government, regulatory, accredited organization standards. Typically, collecting platelets to achieve a given threshold for one, two, or three platelet units usually has a number of parameters that result in a distribution of platelet yield (e.g., a bell curve distribution), but they do not need to be collected in excess from the donor in apheresis methods except accounting for expected donor and/or process variability, collection time constraints (e.g., donor-based, blood center operations-based), digestion, and testing (e.g., Bac-T testing) as excess platelets are stored in one, two, or three units, but without additional value in terms of platelet production. Thus, even if a donor can safely donate a number of platelets by apheresis, such as 1.6 units of platelets or 2.8 units of platelets, there is usually no benefit or incentive for the blood center to collect that amount since the platelet units are ultimately received and donated doctor or hospital will be simply 1 or 2 units of platelets, respectively.

There remains a need for improved systems and methods that provide greater efficiency for collecting and preparing apheresis platelets, including pathogen-inactivated platelets, in order to more fully capture the overall potential for platelet unit acquisition, for example, in blood centers using apheresis platelet collection systems .

- 1 043840

Brief description of the invention

The methods, systems, and compositions described herein are useful for improving the collection and production of platelet units (e.g., apheresis-derived platelet units) suitable for infusion (e.g., into a subject), and compositions containing such platelet units, such as therapeutic platelet dosage units.

In one aspect, the present invention provides a method of obtaining a plurality of platelet units suitable for infusion (eg, suitable for infusion into a subject), comprising a) collecting a first portion of platelets by apheresis from a first donor, b) collecting a second portion of platelets by apheresis from a second donor, c ) combining a unit of platelets from a first donor and a unit of platelets from a second donor to obtain a pooled platelet preparation; and d) dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic doses, therapeutic dosage units), each in a separate container, the plurality of platelet units containing a greater number platelet units than the total number of platelet units that can be obtained from the first platelet unit and the second platelet unit without combining the first and second platelet units.

In some embodiments, the first platelet unit contains less than the number (eg, less than a minimum number, less than a minimum number) of platelets required to produce one unit of platelets. In some embodiments, the platelet unit contains a number (e.g., number) of platelets that is less than about 99, 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30 or about 25% of the number of platelets needed to produce one unit of platelets. In some embodiments, the platelet unit contains a number of platelets that is at least 10% of the number of platelets required to produce one platelet unit. In some embodiments, the platelet unit contains a platelet count that is from about 10 to about 98%, from about 15 to about 98%, from about 20 to about 98%, from about 25 to about 98%, from about 30 to about 98 %, from about 35 to about 98%, from about 40 to about 98%, or from about 50 to about 98% of the number of platelets required to produce one unit of platelets. In some embodiments, the platelet unit contains a platelet count that is about 98, 95, 90, 85, 80, 75, 70%, 65, 60, 55, 50, 45, 40, 35, 30, or about 25% of the platelet count required to obtain one unit of platelets. In some embodiments, collecting a first platelet from a first donor includes adjusting the platelet collection to obtain a first platelet containing less than about 99, 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50. 45, 40, 35, 30 or less than about 25% of the number of platelets required to produce one unit of platelets.

In some embodiments, the first platelet unit contains more than the number (e.g., more than the minimum number, greater than the minimum number) of platelets required to produce one unit of platelets, but less than the number (e.g., less than the minimum number, less than the minimum number ) platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain one unit of platelets.

In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain one unit of platelets. In some embodiments, collecting the first platelet from the first donor includes adjusting the platelet collection,

- 2 043840 to obtain a first portion of platelets containing at least about 125, 130, 135, 140,

145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce two units of platelets.

In some embodiments, the first batch of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain two units of platelets.

In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain two units of platelets. In some embodiments, collecting a first platelet from a first donor includes adjusting the platelet collection to obtain a first platelet containing at least about 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280 , 285, 290, or at least about 295% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the first batch of platelets contains from about 210 to about 298%, from about 215 to about 298%, from about 220 to about 298%, from about 225 to about 298%, from about 230 to about 298%, from about 235 to about 298%, about 240 to about 298%, about 245 to about 298%, or about 250 to about 298% of the number of platelets required to produce one unit of platelets.

In some embodiments, the first batch of platelets contains more platelets than the number required to produce three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets needed to produce three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain three

- 3,043,840 platelet units. In some embodiments, collecting a first platelet from a first donor includes adjusting the platelet collection to obtain a first platelet containing at least about 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380 , 385, 390, or at least about 395% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce three units of platelets. In some embodiments, the first batch of platelets contains from about 310 to about 398%, from about 315 to about 398%, from about 320 to about 398%, from about 325 to about 398%, from about 330 to about 398%, from about 335 to about 398%, about 340 to about 398%, about 345 to about 398%, or about 350 to about 398% of the number of platelets required to produce one unit of platelets.

In some embodiments, the second batch of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain one unit of platelets. In some embodiments, collecting a second platelet from a second donor includes adjusting the platelet collection to obtain a second platelet containing at least about 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180 , 185, 190, or about 195% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce two units of platelets. In some embodiments, collecting a second platelet unit from a second donor includes adjusting the platelet collection to obtain a second platelet unit containing a sufficient number of platelets to obtain two units of platelets, to obtain three units of platelets, to obtain four units of platelets, or to obtain five units of platelets after combining the first and second platelet units and dividing the resulting combined platelet preparation into a plurality of platelet units. In some embodiments, the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into two, three, four, or five platelet units. In some embodiments, collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain two units of platelets, to obtain three units of platelets, to obtain four units of platelets, or to obtain five units of platelets from the pooled preparation.

In some embodiments, the second batch of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, ranging from about 1.1 times to

- 4 043840 about 1.98 times, from about 1.15 times to about 1.98 times, from about 1.2 times to about 1.98 times, from about 1.25 times to about 1 .98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or from about 1.5 times to about 1.98 times the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, is from about 210 to about 298%, from about 215 to about 298%, from about 220 to about 298%, from about 225 to about 298%, from about 230 to about 298%, from about 235 to about 298%, from about 240 to about 298%, or from about 250 to about 298% of the number of platelets required to obtain one unit of platelets. In some embodiments, collecting a second platelet from a second donor includes adjusting the platelet collection to obtain a second platelet containing at least about 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280 , 285, 290, or about 295% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce three units of platelets. In some embodiments, collecting a second platelet unit from a second donor includes adjusting the platelet collection to obtain a second platelet unit containing a sufficient number of platelets to obtain three units of platelets, to obtain four units of platelets, to obtain five units of platelets, or to obtain six units of platelets after combining the first and second platelet units and dividing the resulting combined platelet preparation into a plurality of platelet units. In some embodiments, the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into three, four, five, or six platelet units. In some embodiments, collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain three units of platelets, to obtain four units of platelets, to obtain five units of platelets, or to obtain six units of platelets from the pooled preparation.

In some embodiments, the second batch of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain three units of platelets. In some embodiments, the number of platelets greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, is from about 1.1 times to about 1.98 times, from about 1.15 times to about 1.2 times to about 1.98 times about 1.25 times to about 1.3 times to about 1.98 times about 1.35 times to about 1.4 times to about 1.98 times or from about 1.5 times to about 1.98 times, about 1.98 times, about 1.98 times, 1.98 times the number of platelets needed to produce three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain three units of platelets. In some embodiments, implementation

- 5 043840 leniya the number of platelets greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, is from about 310 to about 398%, from about 315 to about 398%, from about 320 to about 398%, from about 325 to about 398%, from about 330 to about 398%, from about 335 to about 398%, from about 340 to about 398%, or from about 350 to about 398% of the number of platelets required to obtain one unit of platelets. In some embodiments, collecting a second platelet from a second donor includes adjusting the platelet collection to obtain a second platelet containing at least about 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380 , 385, 390, or about 395% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce four units of platelets. In some embodiments, collecting a second platelet unit from a second donor includes adjusting the platelet collection to obtain a second platelet unit containing a sufficient number of platelets to obtain four units of platelets, to obtain five units of platelets, or to obtain six units of platelets, to obtain seven units of platelets after pooling first and second portions of platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units. In some embodiments, the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into four, five, six, or seven platelet units. In some embodiments, collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain 4, 5, 6, or 7 platelet units from the pooled preparation.

In some embodiments, the first platelet unit contains less platelets than the number required to obtain one unit of platelets, and the second platelet unit contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two platelet units. In some embodiments, the first platelet unit contains less platelets than the number required to obtain one unit of platelets, and the second platelet unit contains more platelets than the number required to obtain two platelet units, but less than the number of platelets necessary to obtain three platelet units. In some embodiments, the first platelet unit contains less platelets than the number required to obtain one unit of platelets, and the second platelet unit contains more platelets than the number required to obtain three platelet units, but less than the number of platelets necessary to obtain four platelet units. In some embodiments, the pooled platelet preparation contains enough platelets to produce two units of platelets, to produce three units of platelets, or to produce four units of platelets. In some embodiments, the plurality of platelet units comprises 2, 3, or 4 platelet units.

In some embodiments, the first platelet unit contains more platelets than the number needed to obtain one platelet unit but less than the number of platelets needed to obtain two platelet units, and the second platelet unit contains more platelets than the number required to obtain one units of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the first platelet unit contains more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the second platelet unit contains more platelets than the number required to obtain two units. units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the first platelet unit contains more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the second platelet unit contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce three units of platelets, to produce four units of platelets, or to produce five units of platelets. In some embodiments, the plurality of platelet units comprises 3, 4, or 5 platelet units.

In some embodiments, the first platelet unit contains more platelets than the number needed to obtain two platelet units but less than the number of platelets needed to obtain three platelet units, and the second platelet unit contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the first portion of platelets contains more platelets than the number

- 6 043840 quantity required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, and the second portion of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the first platelet unit contains more platelets than the number needed to obtain three platelet units but less than the number of platelets needed to obtain four platelet units, and the second platelet unit contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce 5, 6, or 7 platelet units. In some embodiments, the plurality of platelet units comprises 5, 6, or 7 platelet units.

In some of the above embodiments, the method further includes collecting a third platelet portion by apheresis from a third donor, and combining the third platelet portion with the first and second platelet portions to produce a pooled platelet preparation, and dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container. wherein the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from the first platelet unit, the second platelet unit and the third platelet unit without combining the first, second and third platelet units. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets.

In some of the above embodiments, the second portion of platelets is collected in less than about (e.g., within) 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3, 2 hours or less than about 1 hour. hours from the moment of collecting the first portion of platelets. In some embodiments, the second batch of platelets is collected at approximately the same time (eg, overlapping collection time) as the first batch of platelets. In some embodiments, the second portion of platelets is collected for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days, or for about 1 day. the moment of collecting the first portion of platelets. In some embodiments, the second platelet unit is collected within 20 hours of the first platelet unit being collected. In some embodiments, the second platelet unit is collected within 12 hours of the first platelet unit being collected. In some embodiments, the second platelet unit is collected within 6 hours of the first platelet unit being collected. In some of the above embodiments, the third portion of platelets is collected in less than about (e.g., within) 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3, 2 hours or less than about 1 hour. hours from the moment of collecting the first portion of platelets. In some embodiments, the third batch of platelets is collected at approximately the same time (eg, overlapping collection time) as the first batch of platelets. In some embodiments, the third portion of platelets is collected for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days, or for about 1 day. the moment of collecting the first portion of platelets. In some embodiments, the third platelet unit is collected within 20 hours of the first platelet unit being collected. In some embodiments, the third portion of platelets is collected within 12 hours of the collection of the first portion of platelets. In some embodiments, the third platelet unit is collected within 6 hours of the first platelet unit being collected. In some embodiments, the first portion of platelets, the second portion of platelets, and the third portion of platelets are collected over a period (e.g., the same period) of about 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3. 2 or about 1 hour. In some embodiments, the first portion of platelets, the second portion of platelets, and the third portion of platelets are collected at approximately the same time (eg, overlapping collection times). In some embodiments, the first portion of platelets, the second portion of platelets, and the third portion of platelets are collected for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days. days or for about 1 day, for about 72 hours, for about 48 hours, for about 36 hours, for about 24 hours, for about 20 hours, for about 12 hours or for about 6 hours each from friend. In some of the above embodiments, the pooled platelet preparation contains platelets only from donors (e.g., the first donor, the second

- 7 043840 third donor, third donor) of the same ABO blood type.

In some of the above embodiments, the method further includes subjecting the first platelet portion, the second platelet portion, and/or the third platelet portion to a pathogen inactivation process. In some embodiments, the method further includes subjecting each of the first platelet portion and the second platelet portion to a pathogen inactivation process. In some embodiments, the method further includes subjecting each of the first platelet portion, the second platelet portion, and the third platelet portion to a pathogen inactivation process. In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting a unit of platelets or a pooled platelet preparation to a pathogen inactivation process includes treating the unit of platelets or a pooled platelet preparation with a pathogen inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen-inactivating compound is amotosalen.

In some of the above embodiments, the platelet units (e.g., each of the platelet units) in the plurality of platelet units comprise at least about 2.0x1011 platelets, at least about 2.2x1011, at least about 2.4x1011, at least about 2.5x1011, at least about 2.6x1011, at least about 2.7x1011, at least about 2.8x1011, at least about 2.9x1011, or at least about 3.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9.5x1011, at least about 10.0x1011, at least about 10, 5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011, or at least about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 6.1x1011, at least about 6.2x1011, at least about 6.3x1011, at least about 6.4 x 1011 or at least about 6.5 x 1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 9.2x1011, at least about 9.3x1011, at least about 9.4x1011, at least about 9.5 x 1011 or at least about 9.6 x 1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 12.3x1011, at least about 12.4x1011, at least about 12.5x1011, at least about 12.6 x 1011, at least about 12.7 x 1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 15.4x1011, at least about 15.5x1011, at least about 15.6x1011, at least about 15.7x1011, at least about 15.8x1011, at least about 16.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7.5x1011, about 8.0x1011, about 8. 5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12.5x1011, about 13.0x1011, about 13, 5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.0x1011 platelets, and the pooled platelet preparation contains at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least

- 8 043840 about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9.5x1011, at least about 10.0x1011, at least about 10.5x1011, at least at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011, or at least about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.0x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.0x1011 platelets, and the pooled platelet preparation contains about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7. 5x1011, about 8.0x1011, about 8.5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12, 5x1011, about 13.0x1011, about 13.5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.2x1011 platelets, and the pooled platelet preparation contains at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9, 5x1011, at least about 10.0x1011, at least about 10.5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011 or at least about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.2x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.2x1011 platelets, and the pooled platelet preparation contains about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7. 5x1011, about 8.0x1011, about 8.5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12, 5x1011, about 13.0x1011, about 13.5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.4x1011 platelets, and the pooled platelet preparation contains at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9, 5x1011, at least about 10.0x1011, at least about 10.5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011 or at least about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.4x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets. In some embodiments, each of the platelets contains at least about 2.4x1011 platelets, and the pooled platelet preparation contains about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7. 5x1011, about 8.0x1011, about 8.5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12, 5x1011, about 13.0x1011, about 13.5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.6x1011 platelets, and the pooled platelet preparation contains at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9, 5x1011, at least about 10.0x1011, at least about 10.5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011 or at least about 15.0x1011 platelets.

- 9 043840

In some embodiments, each of the platelets contains at least about 2.6x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets. In some embodiments, each of the platelets contains at least about 2.6x1011 platelets, and the pooled platelet preparation contains about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7. 5x1011, about 8.0x1011, about 8.5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12, 5x1011, about 13.0x1011, about 13.5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.8x1011 platelets, and the pooled platelet preparation contains at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9, 5x1011, at least about 10.0x1011, at least about 10.5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011 or at least about 15.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 2.8x1011 platelets, and the pooled platelet preparation contains less than about 16.0x1011, less than about 14.0x1011, or less than about 12.0x1011 platelets. In some embodiments, each of the platelets contains at least about 2.8x1011 platelets, and the pooled platelet preparation contains about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7. 5x1011, about 8.0x1011, about 8.5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12, 5x1011, about 13.0x1011, about 13.5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

In some of the above embodiments, the platelet units (eg, each platelet unit) in the plurality of platelet units comprise a therapeutic dose (eg, therapeutic dosage unit) of platelets suitable for infusion into a human subject (eg, in need of platelet infusion). In some embodiments, the therapeutic dose contains a minimum amount (e.g., at least a minimum number) of platelets, as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accredited organization (e.g., a government agency, a regulatory agency, institution and/or accredited organization responsible for donated blood products (e.g. donated platelets)). In some embodiments, platelet units are obtained in the country of a government agency, regulatory body, institution, and/or accredited organization that defines therapeutic platelet dose criteria. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or 100% of platelet units in a plurality of platelet units contain a minimum number of therapeutic dose platelets. In some embodiments, each of the platelet units in the plurality of platelet units contains a minimum number of therapeutic dose platelets. In some embodiments, the minimum number of platelets in a therapeutic dose is at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some of the above embodiments, tailoring platelet collection includes determining optimal platelet collection. In some embodiments, the optimal platelet collection is the maximum platelet collection (eg, the maximum that can be safely collected, the maximum in accordance with regulatory and/or industry standards or rules) that can be obtained from the donor. In some embodiments, the optimal platelet collection is less than the maximum platelet collection that can be collected from the donor, but greater than the platelet collection required for a certain number (eg, target number, desired number) of platelet units. In some embodiments, customizing the platelet collection includes providing entry (eg, programming) into the apheresis system. In some embodiments, adjusting platelet collection includes providing a batch volume to the apheresis system. In some embodiments, tailoring the platelet collection includes ensuring

- 10 043840 baking the duration of time for collecting platelets in the apheresis system. In some embodiments, tailoring platelet collection includes providing a batch volume and/or duration of time for platelet collection that influences (eg, accounts for) a change (eg, distribution) in actual platelet collections compared to target collections. In some embodiments, the first portion of platelets and the second portion of platelets are combined in a single container of a suitable size for the volume of the combined platelet preparation. In some embodiments, the first portion of platelets and the second portion of platelets have a suitable volume for treatment with a pathogen-inactivating compound. In some embodiments, the first portion of platelets and the second portion of platelets have a suitable volume and number of platelets (eg, platelet count) to be treated with a pathogen-inactivating compound. In some embodiments, the pooled platelet preparation has a suitable volume for treatment with a pathogen-inactivating compound. In some embodiments, the pooled platelet preparation has a suitable volume and number of platelets to be treated with a pathogen-inactivating compound.

In another aspect, this disclosure provides a method for obtaining a plurality of platelet units suitable for infusion (e.g., suitable for infusion into a subject), comprising a) maintaining a storage log of collected apheresis platelet preparations, wherein the storage log contains for each platelet preparation a unique identifier, the blood type of the donor , time of donation (e.g. date, time, date and time) and quantity (e.g. total platelet count, platelet count, platelet concentration and volume) of platelets in the preparation, b) identification of an available donor suitable for apheresis platelet donation, c) selection from the storage log of at least one (e.g., one or more) platelet preparation into storage, to be combined with platelets collected from an existing donor, d) collecting a new portion of platelets by apheresis from an existing donor, e) combining at least one selected platelet preparation and a new portion of platelets to obtain a pooled platelet preparation; and f) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units (eg, therapeutic doses, therapeutic dose units) containing a greater number of platelet units than the total number of units. platelets that can be obtained from at least one selected drug and a new batch of platelets without combining at least the first selected drug and a new batch of platelets. In some embodiments, the storage log further contains, for each platelet preparation, the gender of the donor and/or the volume of the platelet preparation. In some embodiments, the repository of apheresis-collected platelet preparations (eg, an existing repository) contains existing platelet preparations that have already been collected. In some embodiments, the list of apheresis-collected platelet preparations comprises platelet preparations collected from a given donor (eg, a donor present at a blood center), wherein the donor is not an existing donor. In some embodiments, platelet preparations collected from a given donor contain platelets collected at approximately the same time (eg, overlapping time) as platelet units collected by apheresis from an existing donor. In some embodiments, platelet preparations collected from a given donor contain platelets that will be collected from a given donor. In some embodiments, the existing donor is a new donor (eg, a donor who has not previously donated at the blood center, a donor whose history is not available at the blood center). In some embodiments, the existing donor is a previous donor (eg, a donor who was previously a donor at the blood center, a donor whose history is available at the blood center).

In some embodiments, the method further includes determining for an available donor one or more donor parameters selected from the group consisting of gender, physical size (e.g., weight, height), hemoglobin level, and platelet count (e.g., platelet count on day of donation, count platelets before donation). In some embodiments, the method further includes determining a maximum amount (eg, maximum safe amount, maximum volume, maximum number) of platelets that can be collected from an available donor by apheresis.

In some embodiments, the at least one selected platelet preparation contains less than the number (eg, less than a minimum number, less than a minimum number) of platelets required to produce one unit of platelets. In some embodiments, the at least one selected platelet preparation contains an amount (e.g., number) of platelets that is less than about 99, 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30 or less than about 25% of the number of platelets required to produce one unit of platelets. In some embodiments, the at least one selected platelet preparation contains a number of platelets that is at least 10% of the number of platelets required to produce one unit of platelets. In some embodiments, the at least one selected platelet preparation contains a number of platelets

- 11 043840 which is from about 10 to about 98%, from about 15 to about 98%, from about 20 to about 98%, from about 25 to about 98%, from about 30 to about 98%, from about 35 to about 98%, about 40 to about 98%, or about 50 to about 98% of the number of platelets required to produce one unit of platelets. In some embodiments, the at least one selected platelet preparation contains a platelet count that is about 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, or about 25 % of the number of platelets required to produce one unit of platelets.

In some embodiments, the at least one selected platelet preparation contains more than the number (e.g., greater than the minimum number, greater than the minimum number) of platelets required to produce one unit of platelets, but less than the number (e.g., less than the minimum number , less than the minimum number) of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being about 1.1 times,

1.2-fold, 1.9-fold, one more than

1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.95 times or about 1.98 times the platelet count , required for half a unit of platelets. In some embodiments, the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, is from about 1.1 times to about 1.98 times, from about 1.15 times to about 1.98 times, from about 1.2 times to about 1.98 times, from about 1.25 times to about 1.98 times, from about 1.3 times to about 1.98 -fold, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the platelet count, required to obtain one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain one unit of platelets.

In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain two units of platelets. In some embodiments, the at least one selected platelet preparation contains at least about 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, or about 295% of the platelet count , required to produce one unit of platelets, but less than the number of platelets required to produce three units

- 12 043840 platelets. In some embodiments, the at least one selected platelet preparation contains from about 225 to about 298%, from about 230 to about 298%, from about 235 to about 298%, from about 240 to about 298%, from about 245 to about 298 % or about 250 to about 298% of the number of platelets required to produce one unit of platelets.

In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets needed to produce three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain three units of platelets. In some embodiments, the at least one selected platelet preparation contains at least about 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, or about 395% of the platelet count , required to produce one unit of platelets, but less than the number of platelets required to produce four units of platelets. In some embodiments, the at least one selected platelet preparation contains from about 325 to about 398%, from about 330 to about 398%, from about 335 to about 398%, from about 340 to about 398%, from about 345 to about 398 % or about 350 to about 398% of the number of platelets required to produce one unit of platelets.

In some embodiments, the new supply of platelets contains less than the number (eg, less than the minimum number, less than the minimum number) of platelets required to produce one unit of platelets. In some embodiments, the new batch of platelets contains a number (e.g., number) of platelets that is less than about 99, 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30 or less than about 25% of the number of platelets required to produce one unit of platelets.

In some embodiments, the new supply of platelets contains a number of platelets that is at least 10% of the number of platelets required to produce one unit of platelets. In some embodiments, the new batch of platelets contains a platelet count that is from about 10 to about 98%, from about 15 to about 98%, from about 20 to about 98%, from about 25 to about 98%, from about 30 to about 98%, about 35 to about 98%, about 40 to about 98%, or about 50 to about 98% of the number of platelets required to produce one unit of platelets. In some embodiments, the new batch of platelets contains a platelet count that is about 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, or about 25% of the platelet count required to obtain one unit of platelets. In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing a number of platelets less than that required to obtain one unit of platelets.

In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to produce a batch containing less than about 99, 98, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35 , 30 or less than about 25% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing from about 10 to about 98%, from about 15 to about 98%, from about 20 to about 98%, from about 25 to about 98%, from about 30 to about 98%, from about 35 to about 98%, from about 40 to about 98%, or from about 50 to about 98% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to obtain one, two, three, four units of platelets after combining at least one selected platelet preparation and the new platelet unit and separating the resulting pooled platelet preparation into a plurality of platelet units. In some embodiments, the new platelet unit contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a pooled platelet preparation containing a sufficient number of platelets to separate into one, two, three, or four platelet units. In some embodiments, collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain one, two, three, or four units of platelets from the pooled preparation.

In some embodiments, the new supply of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15x to about 1.98x, about 1.2x to about 1.98x, about 1.25x to about 1.98x, about

1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about

1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to produce one unit of platelets. In some embodiments, the number of platelets is greater than that required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain one unit of platelets.

In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to produce a batch containing at least about 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, or about 195% of the number of platelets needed to produce one unit of platelets, but less than the number of platelets needed to produce two units of platelets. In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to produce a batch containing from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, about 135 to about 198%, about 140 to about 198%, about 145 to about 198%, or about 150 to about 198% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to obtain two, three, four, five units of platelets after combining at least one selected platelet preparation and the new platelet unit and separating the resulting pooled platelet preparation into a plurality of platelet units. In some embodiments, the new batch of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a combined platelet preparation containing a sufficient number of platelets to separate into two, three, four, or five platelet units. In some embodiments, collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain two, three, four, or five units of platelets from the pooled preparation.

In some embodiments, the new batch of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but

- 14 043840 less than the number of platelets required to obtain three units of platelets is about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1, 6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times, or about 1.98 times the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, about 1.35 times to about 1.98 times, about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to produce two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain two units of platelets. In some embodiments, the number of platelets is greater than that required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain two units of platelets. In some embodiments, the new supply of platelets contains at least about 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, or about 295% of the number of platelets required for obtaining one unit of platelets, but less than the number of platelets required to obtain three units of platelets.

In some embodiments, the new batch of platelets contains from about 210 to about 298%, from about 215 to about 298%, from about 220 to about 298%, from about 225 to about 298%, from about 230 to about 298%, from about 235 to about 298%, from about 240 to about 298%, from about 245 to about

298%, or about 250 to about 298% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing at least about 225, 230, 235, 240, 245, 250, 255, 260, 265, 270, 275, 280, 285, 290, or about 295% of the number of platelets needed to produce one unit of platelets, but less than the number of platelets needed to produce three units of platelets.

In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to produce a batch containing from about 210 to about 298%, from about 215 to about 298%, from about 220 to about 298%, from about 225 to about 298%, from about 230 to about 298%, about 235 to about 298%, about 240 to about 298%, about 245 to about 298%, or about 250 to about 298% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to produce three, four, five, six units of platelets after combining at least one selected platelet preparation and the new platelet unit and separating the resulting pooled platelet preparation into a plurality of platelet units. In some embodiments, the new batch of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a combined platelet preparation containing a sufficient number of platelets to separate into three, four, five, or six platelet units. In some embodiments, collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain three, four, five, or six units of platelets from the pooled preparation.

In some embodiments, the new batch of platelets contains more platelets than the number required to produce three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, about 1.1 times, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times, 1.95 times or about 1.98 times the platelet count required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being from about 1.1 times to about 1.98 times, from about 1. 15 times to about 1.98 times, about 1.2 times to about 1.98 times, about 1.25 times to about 1.98 times, about 1.3 times to about 1.98 times, from about 1.35 times to about 1.98 times, from

- 15 043840 about 1.4 times to about 1.98 times, or about 1.5 times to about 1.98 times the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, being about 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190 or about 195% of the number of platelets required to obtain three units of platelets. In some embodiments, the number of platelets is greater than that required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, is from about 110 to about 198%, from about 115 to about 198%, from about 120 to about 198%, from about 125 to about 198%, from about 130 to about 198%, from about 135 to about 198%, from about 140 to about 198%, or from about 150 to about 198% of the number of platelets required to obtain three units of platelets.

In some embodiments, the new supply of platelets contains at least about 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, or about 395% of the number of platelets required for obtaining one unit of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the new batch of platelets contains from about 310 to about 398%, from about 315 to about 398%, from about 320 to about 398%, from about 325 to about 398%, from about 330 to about 398%, from about 335 to about 398%, about 340 to about 398%, about 345 to about 398%, or about 350 to about 398% of the number of platelets required to produce one unit of platelets.

In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing at least about 325, 330, 335, 340, 345, 350, 355, 360, 365, 370, 375, 380, 385, 390, or about 395% of the number of platelets needed to produce one unit of platelets, but less than the number of platelets needed to produce three units of platelets. In some embodiments, collecting a new batch of platelets includes adjusting the platelet collection to produce a batch containing from about 310 to about 398%, from about 315 to about 398%, from about 320 to about 398%, from about 325 to about 398%, from about 330 to about 398%, about 335 to about 398%, about 340 to about 398%, about 345 to about 398%, or about 350 to about 398% of the number of platelets required to produce one unit of platelets. In some embodiments, collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to obtain four, five, six, or seven units of platelets after combining at least one selected platelet preparation and the new platelet unit and separating the resulting pooled platelet preparation into a plurality of platelet units. In some embodiments, the new batch of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a combined platelet preparation containing a sufficient number of platelets to separate into four, five, six, or seven platelet units. In some embodiments, collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain four, five, six, or seven units of platelets from the pooled preparation.

In some embodiments, the at least one selected platelet preparation contains fewer platelets than the number required to produce one unit of platelets, and the new unit of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets, required to obtain two units of platelets. In some embodiments, the at least one selected platelet preparation contains less platelets than the amount required to obtain one unit of platelets, and the new platelet unit contains more platelets than the amount required to obtain two units of platelets, but less than the number of platelets, required to obtain three units of platelets. In some embodiments, the at least one selected platelet preparation contains less platelets than the amount required to obtain one unit of platelets, and the new platelet unit contains more platelets than the amount required to obtain three units of platelets, but less than the number of platelets, required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce two, three, or four platelet units. In some embodiments, the plurality of platelet units comprises two, three, or four platelet units.

In some embodiments, the new platelet supply contains less platelets than the number required to obtain one unit of platelets, and the at least one selected platelet preparation contains more platelets than the amount required to obtain one unit of platelets, but less than the number of platelets, required to obtain two units of platelets. In some embodiments, the new batch of platelets contains

- 16 043840 lives of platelets is less than the number required to obtain one unit of platelets, and at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three platelet units. In some embodiments, the new platelet supply contains less platelets than the amount required to obtain one unit of platelets, and the at least one selected platelet preparation contains more platelets than the amount required to obtain three units of platelets, but less than the number of platelets, required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce two, three, or four platelet units. In some embodiments, the plurality of platelet units comprises two, three, or four platelet units.

In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, and the new unit of platelets contains more platelets than the number required to produce one unit of platelets, but less than the number of platelets required to produce two units of platelets. In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, and the new unit of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, and the new unit of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce three, four, or five platelet units. In some embodiments, the plurality of platelet units comprises three, four, or five platelet units.

In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, and the new platelet unit contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, and the new platelet unit contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the at least one selected platelet preparation contains more platelets than the number required to obtain three units of platelets but less than the number of platelets required to obtain four units of platelets, and the new platelet unit contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the pooled platelet preparation contains a sufficient number of platelets to produce five, six, or seven platelet units. In some embodiments, the plurality of platelet units comprises five, six, or seven platelet units.

In some embodiments, the method further includes identifying a second available donor suitable for platelet donation by apheresis, collecting a second new supply of platelets by apheresis from the second available donor, combining the second new supply of platelets with at least one selected drug and the new supply of platelets to obtain a pooled a platelet preparation and dividing the combined platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from at least one selected platelet preparation and a new platelet unit; and a second new portion of platelets without combining at least one selected platelet preparation and a new portion of platelets and a second new portion of platelets. In some embodiments, the method further includes subjecting at least one selected platelet preparation, a fresh platelet batch, and/or a second fresh platelet batch to a pathogen inactivation process. In some embodiments, the method further includes

- 17 043840 subjecting each of at least one selected platelet preparation and a new portion of platelets to a pathogen inactivation process. In some embodiments, the method further includes subjecting each of at least one selected platelet preparation, a fresh platelet batch, and a second fresh platelet batch to a pathogen inactivation process. In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting the at least one selected platelet preparation, a fresh platelet batch, a second fresh platelet batch, and/or a pooled platelet preparation to a pathogen inactivation process comprises treating the at least one selected platelet preparation, a fresh platelet batch, a second fresh platelet batch, and/ or a pooled platelet preparation to a pathogen-inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some embodiments, the method further includes collecting a third portion of platelets by apheresis from a third available donor, combining the third portion of platelets with at least one selected drug and a new portion of platelets to produce a pooled platelet preparation, and dividing the pooled platelet preparation into a plurality of platelet units, each in separate container, wherein the plurality of platelet units contains a greater number of platelet units than the total number of platelet units that can be obtained from the at least one selected platelet preparation and the new platelet unit and the third platelet unit without combining the at least one selected platelet preparation and the new portions of platelets and a third portion of platelets. In some embodiments, the method further includes subjecting at least one selected platelet preparation, a new platelet batch, and/or a third platelet batch to a pathogen inactivation process. In some embodiments, the method further includes subjecting each of the at least one selected platelet preparation and a new batch of platelets to a pathogen inactivation process. In some embodiments, the method further includes subjecting each of at least one selected platelet preparation, a fresh platelet batch, and a third platelet batch to a pathogen inactivation process. In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting the at least one selected platelet preparation, a fresh platelet batch, a third platelet batch, and/or a pooled platelet preparation to a pathogen inactivation process comprises treating the at least one selected platelet preparation, a fresh platelet batch, a third platelet batch, and/or a pooled platelet preparation. platelet preparation to a compound that inactivates pathogens. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some of the above embodiments, a new batch of platelets is collected in less than about (e.g., within) 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3, 2, or less than about 1 hour from the time of collection of at least one selected platelet preparation. In some embodiments, a new batch of platelets is collected for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days, or for about 1 day. the time of collection of at least one selected platelet preparation. In some embodiments, a new batch of platelets is collected at approximately the same time (eg, overlapping collection time) as at least one selected platelet preparation. In some embodiments, a new batch of platelets is collected within 20 hours of collection of at least one selected platelet preparation. In some embodiments, a new portion of platelets is collected within 12 hours of collection of at least one selected platelet preparation. In some embodiments, a new batch of platelets is collected within 6 hours of collection of at least one selected platelet preparation. In some of the above embodiments, the second new platelet batch (or third platelet batch) is collected in less than about (e.g., within) 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3, 2 or less than about 1 hour from the time of collection of at least one selected platelet preparation. In some embodiments, the second new batch of platelets is collected for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days, or for about 1 day. since now

- 18 043840 and collection of at least one selected platelet preparation. In some embodiments, a second new batch of platelets (or a third batch of platelets) is collected at approximately the same time (eg, overlapping collection time) as the at least one selected platelet preparation. In some embodiments, a second new platelet batch (third platelet batch) is collected within 20 hours of collection of at least one selected platelet preparation. In some embodiments, a second new batch of platelets (or a third batch of platelets) is collected within 12 hours of collection of the at least one selected platelet preparation. In some embodiments, a second new batch of platelets (or a third batch of platelets) is collected within 6 hours of collection of at least one selected platelet preparation. In some embodiments, a second new batch of platelets is collected within 24, 22, 20, 16, 12, 10, 8, 6, 5, 4, 3, 2, or about 1 hour from the time of collection of at least one selected platelet preparation and a new portions of platelets. In some embodiments, at least one selected platelet preparation, a fresh platelet batch, a second fresh platelet batch (or a third platelet batch) is collected over a period (e.g., the same period) of about 24, 22, 20, 16, 12, 10 . for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days or for about 1 day, for about 72 hours, for about 48 hours, for about 36 hours, within about 24 hours, within about 20 hours, within about 12 hours, or within about 6 hours of each other. In some embodiments, at least one selected platelet preparation, a fresh platelet batch, and a second new platelet batch (or a third platelet batch) are collected at approximately the same time (eg, overlapping collection time).

In some of the above embodiments, the pooled platelet preparation contains platelets (eg, at least one selected platelet preparation, a fresh platelet stock, a second fresh platelet stock, a third platelet stock) only from donors of the same ABO blood type.

In some of the above embodiments, the platelet units (e.g., each of the platelet units) in the plurality of platelet units comprise at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 6.2x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 9.3x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 12.4x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 15.5x1011 platelets.

In some of the above embodiments, the platelet units (eg, each platelet unit) in the plurality of platelet units comprise a therapeutic dose (eg, therapeutic dosage unit) of platelets suitable for infusion into a human subject (eg, in need of platelet infusion). In some embodiments, the therapeutic dose contains a minimum amount (e.g., at least a minimum number) of platelets, as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accredited organization (e.g., a government agency, a regulatory agency, institution and/or accredited organization responsible for donated blood products (e.g. donated platelets)). In some embodiments, platelet units are obtained in the country of a government agency, regulatory body, institution, and/or accredited organization that defines therapeutic platelet dose criteria. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or more of the platelet units in a plurality of platelet units contain the minimum number of therapeutic dose platelets. In some embodiments, each of the platelet units in the plurality of platelet units contains a minimum number of therapeutic dose platelets. In some variants

- 19 043840 the minimum number of platelets in a therapeutic dose is at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some of the above embodiments, tailoring platelet collection includes determining optimal platelet collection. In some embodiments, the optimal platelet collection is the maximum platelet collection (eg, the maximum that can be safely collected, the maximum in accordance with regulatory and/or industry standards or rules) that can be obtained from the donor. In some embodiments, tailoring platelet collection includes providing entry (eg, programming) into the apheresis system. In some embodiments, adjusting platelet collection includes providing a batch volume to the apheresis system. In some embodiments, adjusting platelet collection includes providing a length of time for platelet collection in the apheresis system. In some embodiments, tailoring platelet collection includes providing a batch volume and/or duration of time for platelet collection that influences (eg, accounts for) a change (eg, distribution) in actual platelet collections compared to target collections. In some embodiments, at least one selected platelet preparation and a new platelet supply are combined in a single container of a suitable size for the volume of the combined platelet preparation. In some embodiments, the at least one selected platelet preparation and the fresh platelet supply have a suitable volume for treatment with the pathogen-inactivating compound. In some embodiments, the at least one selected platelet preparation and the new platelet supply have a suitable volume and number of platelets (eg, platelet count) to be treated with a pathogen-inactivating compound. In some embodiments, the pooled platelet preparation has a suitable volume for treatment with a pathogen-inactivating compound. In some embodiments, the pooled platelet preparation has a suitable volume and number of platelets to be treated with a pathogen-inactivating compound.

In another aspect, this disclosure provides an infusionable unit of platelets prepared by any of the above methods.

In another aspect, the present invention provides a method of producing two or more platelet units (eg, therapeutic platelet dosage units), comprising: a) combining two or more donor platelet units obtained by apheresis to form a pooled platelet composition, b) subjecting the pooled composition to platelet pathogen inactivation process; and c) separating the combined platelet composition into two or more platelet units (eg, therapeutic platelet dosage units), each in a separate container. In some embodiments, the method is a method of producing three or more, four or more, five or more, six or more, or seven or more units of platelets. In some embodiments, the present invention provides a method of producing two or more therapeutic platelet dosage units (e.g., therapeutic platelet dosage units suitable for infusion into a subject), comprising a) combining two or more apheresis-derived platelet donor units to form a combined composition platelets, b) subjecting the pooled platelet composition to a pathogen inactivation process, and c) dividing the pooled platelet composition into two or more therapeutic platelet dosage units, each in a separate container. In some embodiments, the method is a method of producing three or more, four or more, five or more, six or more, or seven or more therapeutic platelet dosage units. In some embodiments, the therapeutic platelet dosage unit after step c) is greater than the number of therapeutic platelet dosage units that can be obtained from two or more apheresis-derived platelet donor units individually, without combining the two or more donor units.

In some embodiments, each platelet donor unit obtained by apheresis contains a number of platelets greater than needed to obtain one therapeutic platelet dosage unit, but less than the number of platelets required to obtain two therapeutic platelet dosage units. In some embodiments, each platelet donor unit obtained by apheresis contains a number of platelets greater than needed to obtain two therapeutic platelet dosage units, but less than the number of platelets required to obtain three therapeutic platelet dosage units. In some embodiments, each platelet donor unit obtained by apheresis contains more platelets than are needed to obtain

- 20 043840 three therapeutic platelet dosage units, but less than the number of platelets required to obtain four therapeutic platelet dosage units.

In some embodiments, two apheresis platelet donor units are combined, and each apheresis platelet donor unit contains more platelets than needed to produce one therapeutic platelet dosage unit, but less than the number of platelets needed to produce two therapeutic platelet dosage units. In some embodiments, each donor unit contains at least about 125%, at least about 130%, at least about 135%, at least about 140%, at least about 145%, or at least about 150% of the number of platelets required to produce one unit of platelets.

In some embodiments, each donor unit contains less than about 198% of the number of platelets required to obtain one unit of platelets. In some embodiments, two apheresis platelet donor units are combined, and each apheresis platelet donor unit contains more platelets than needed to produce two therapeutic platelet dosage units, but less than the number of platelets needed to produce three therapeutic platelet dosage units.

In some embodiments, each donor unit contains at least about 225%, at least about 230%, at least about 235%, at least about 240%, at least about 245%, or at least about 250% of the number of platelets required to produce one unit of platelets. In some embodiments, each donor unit contains less than about 298% of the number of platelets required to obtain one unit of platelets. In some embodiments, two apheresis platelet donor units are combined, and each apheresis platelet donor unit contains a number of platelets greater than needed to obtain three therapeutic platelet dosage units, but less than the number of platelets necessary to obtain four therapeutic platelet dosage units.

In some embodiments, each donor unit contains at least about 325%, at least about 330%, at least about 335%, at least about 340%, at least about 345%, or at least about 350% of the number of platelets required to produce one unit of platelets. In some embodiments, each donor unit contains less than about 398% of the number of platelets required to obtain one unit of platelets. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units (e.g., the first donor unit) contains more than the number of platelets required to produce one therapeutic platelet dosage unit, but less than the number of platelets, required to obtain two therapeutic platelet dosage units, and the other of the two donor units (e.g., the second donor unit) contains more than the number of platelets required to obtain two therapeutic platelet dosage units, but less than the number of platelets required to obtain three therapeutic platelet dosage units. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units contains more than the number of platelets required to obtain one therapeutic platelet dosage unit, but less than the number of platelets required to obtain two therapeutic dosage units platelets, and the other of the two donor units contains more than the number of platelets required to obtain three therapeutic platelet dosage units, but less than the number of platelets required to obtain four therapeutic platelet dosage units. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units contains more than the number of platelets required to obtain two therapeutic platelet dosage units, but less than the number of platelets required to obtain three therapeutic dosage units platelets, and the other of the two donor units contains more than the number of platelets required to obtain three therapeutic platelet dosage units, but less than the number of platelets required to obtain four therapeutic platelet dosage units. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units contains less than the number of platelets needed to produce one therapeutic platelet dosage unit, and the other of the two donor units contains more than the number of platelets needed to obtain one therapeutic platelet unit, but less than the number of platelets required to obtain two therapeutic platelet units. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units contains less than the number of platelets required to produce one therapeutic platelet dosage unit, and the other of the two donor units contains more than the number of platelets required to obtain two therapeutic platelet dosage units, but less than the number of platelets required to obtain three therapeutic platelet dosage units. In some embodiments, two platelet donor units obtained by apheresis are combined, and one of the two donor units contains less than the number of platelets needed to produce one therapeutic platelet dosage unit, and the other of the two donor units contains more than the number of platelets needed to obtain three therapeutic platelet dosage units, but less than the number of platelets required to obtain four therapeutic platelet dosage units.

In some embodiments, at least one of the two donor units contains at least about 125%, at least about 130%, at least about 135%, at least about 140%, at least about 145%, or at least at least about at least about 150% of the number of platelets required to produce one unit of platelets. In some embodiments, at least one of the two donor units contains at least about 225%, at least about 230%, at least about 235%, at least about 240%, at least about 245%, or at least at least about 250% of the number of platelets required to obtain one unit of platelets.

In some embodiments, at least one of the two donor units contains at least about 325%, at least about 330%, at least about 335%, at least about 340%, at least about 345%, or at least at least about 350% of the number of platelets required to obtain one unit of platelets. In some embodiments, the at least one donor unit contains less than about 98%, less than about 198%, less than about 298%, or less than about 398% of the number of platelets required to obtain one unit of platelets.

In some embodiments, at least one of two or more apheresis platelet donor units is selected from an apheresis-collected donor platelet unit storage log, wherein the storage log contains, for each platelet donor unit, a unique identifier, the donor's blood type, the time of donation, and number of platelets in the donor unit. In some embodiments, each of two or more donor platelet units obtained by apheresis is selected from a storage log. In some embodiments, two or more portions of platelets obtained by apheresis are combined for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days or within about 1 day from the moment of collection. In some embodiments, two or more apheresis-derived platelet donor units are combined within 20 hours of collection (eg, collection of each donor unit is completed). In some embodiments, two or more apheresis-derived platelet donor units are combined within 12 hours of collection (eg, collection of each donor unit is completed). In some embodiments, two or more apheresis-derived platelet donor units are combined within 6 hours of collection (eg, collection of each donor unit is completed). In some embodiments, two or more donor apheresis platelet units are obtained from donors of the same ABO blood type. In some embodiments, subjecting the pooled platelet composition to a pathogen inactivation process includes treating the pooled platelet composition with a pathogen inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some embodiments, two or more platelet units (e.g., each of two or more platelet units) contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some embodiments, each therapeutic platelet dosage unit contains at least 2.4x1011 platelets, at least 2.5x1011 platelets, at least 2.6x1011 platelets, at least 2.7x1011 platelets, at least 2.8x1011 platelets, at least 2.9x1011 platelets or at least about 3.0x1011 or more platelets. In some embodiments, each of the platelets contains at least about 3.0 x 1011 platelets, and the combined thrombus preparation

- 22043840 bocytes contain at least about 6.2x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 9.3x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 12.4x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 15.5x1011 platelets.

In some of the above embodiments, the platelet therapeutic unit contains a minimum number of platelets as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, institution, and/or accredited organization (e.g., government agency, regulatory agency, institution, and/or accredited organization responsible for donated blood products (e.g. donated platelets)). In some embodiments, the therapeutic platelet dosage units are obtained in the country of the government agency, regulatory body, institution, and/or accredited organization defining the criteria for the therapeutic platelet dosage unit. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or more of the therapeutic platelet dosage units contain the minimum platelet count of the therapeutic dosage unit. In some embodiments, each of the therapeutic platelet dosage units contains a minimum number of platelets of the therapeutic dosage unit. In some embodiments, the minimum platelet count per therapeutic dosage unit is at least about 2.0 x 1011 platelets, at least about

2.2 x 1011 platelets, at least about 2.4 x 1011 platelets, at least about

2.5 x 1011 platelets, at least about 2.6 x 1011 platelets, at least about

2.7 x 1011 platelets, at least about 2.8 x 1011 platelets, at least about

2.9 x 1011 platelets or at least about 3.0 x 1011 platelets.

In another aspect, the present invention provides a therapeutic platelet dosage unit prepared by any of the above methods.

In another aspect, the present invention provides a method for collecting a portion of platelets by apheresis from a donor, comprising a) maintaining a storage log of collected apheresis platelet preparations, wherein the storage log contains for each platelet preparation a unique identifier, the donor's blood type, the date of donation, and the number of platelets in the preparation, b) identifying a donor suitable for apheresis platelet donation, c) selecting from a repository log one or more platelet preparations suitable for combination with the new platelet collection collected by apheresis from the donor, d) determining the target volume of the new platelet supply, wherein the target volume optimizes the number of platelet units that can be obtained from a combination containing a new supply of platelets and one or more selected platelet preparations; and f) collecting the target volume of new platelets by apheresim from the donor. In some embodiments, determining a target platelet volume for the new platelet batch includes determining a target platelet yield for the new platelet batch. In some embodiments, the method further includes determining the length of time to collect a new batch of platelets by apheresis. In some embodiments, the method further includes f) combining one or more selected platelet preparations and a new portion of platelets to form a pooled platelet preparation, and g) dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic dosage units), each in a separate container. In some embodiments, each of the platelet units in the plurality of platelet units contains a therapeutic dose (eg, a therapeutic dose of platelets) suitable for infusion to a person in need thereof. In some embodiments, the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from the one or more selected platelet preparations and the fresh platelet unit without combining the one or more selected platelet preparations and the fresh platelet unit.

In some embodiments, each of the one or more selected platelet preparations contains a number of platelets less than that required to obtain one therapeutic dose. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to obtain one therapeutic dose, but less than the number of platelets necessary to obtain two therapeutic doses. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to obtain two therapeutic doses, but less than the number of platelets necessary to obtain three therapeutic doses. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to obtain three therapeutic doses, but less than the number of platelets necessary to obtain four therapeutic doses.

In some embodiments, the new platelet supply contains a number of platelets that are less than those required to obtain one therapeutic dose. In some embodiments, the new platelet supply contains more platelets than the number required to obtain one therapeutic dose, but less than the number of platelets required to obtain two therapeutic doses. In some embodiments, the new batch of platelets contains more platelets than the number required to obtain two therapeutic doses, but less than the number of platelets required to obtain three therapeutic doses.

In some embodiments, the new batch of platelets contains more platelets than the number required to obtain three therapeutic doses, but less than the number of platelets required to obtain four therapeutic doses.

In some embodiments, the one or more selected platelet preparation contains a number of platelets less than that required to produce one unit of platelets. In some embodiments, the target volume of the new platelet unit is a volume containing a sufficient number of platelets to produce two, three, or four platelet units after combining one or more selected platelet preparations and the new platelet unit and dividing the resulting combined platelet preparation into a plurality of platelet units. In some embodiments, the new platelet unit contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into two, three, or four platelet units. In some embodiments, collecting a new supply of platelets from a donor includes collecting enough platelets to obtain two, three, or four units of platelets from the pooled preparation.

In some embodiments, the one or more selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, one or more selected formulations contains at least about 125%, at least about 130%, at least about 135%, at least about 140%, at least about 145%, or at least about 150 % of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the target new platelet unit volume is a volume containing a sufficient number of platelets to produce two, three, four, or five platelet units after combining one or more selected platelet preparations and the new platelet unit and dividing the resulting combined platelet preparation into a plurality of platelet units . In some embodiments, the new platelet unit contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into two, three, four, or five platelet units. In some embodiments, collecting a new supply of platelets from a donor includes collecting enough platelets to obtain two, three, four, or five units of platelets from the pooled preparation.

In some embodiments, the one or more selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, one or more selected formulations contains at least about 225%, at least about 230%, at least about 235%, at least about 240%, at least about 245%, or at least about 250 % of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce three units of platelets. In some embodiments, the target new platelet unit volume is a volume containing a sufficient number of platelets to produce three, four, five, or six platelet units after combining one or more selected platelet preparations and the new platelet unit and dividing the resulting combined platelet preparation into a plurality of platelet units . In some embodiments, the new platelet unit contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a combined platelet preparation containing a sufficient number of platelets to separate into three, four, five, or six platelet units. In some embodiments, collecting a new supply of platelets from a donor includes collecting enough platelets to obtain three, four, five, or six units of platelets from the pooled preparation.

- 24 043840

In some embodiments, the one or more selected platelet preparation contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets. In some embodiments, one or more selected formulations contains at least about 325%, at least about 330%, at least about 335%, at least about 340%, at least about 345%, or at least about 350 % of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce four units of platelets. In some embodiments, the target volume of a new platelet unit is a volume containing a sufficient number of platelets to obtain four, to obtain five, to obtain six, or to obtain seven platelet units after combining one or more selected platelet preparations and the new platelet unit and separating the resulting combined platelet preparation into multiple platelet units. In some embodiments, the new batch of platelets contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into four, five, six, or seven platelet units. In some embodiments, collecting a new supply of platelets from a donor includes collecting enough platelets to obtain four, five, six, or seven units of platelets from the pooled preparation.

In some embodiments, each of the one or more selected platelet preparations and the new platelet supply contains more platelets than the number required to obtain one therapeutic dose, but less than the number of platelets required to obtain two therapeutic doses. In some embodiments, each of the one or more selected platelet preparations and the new platelet supply contains more platelets than the number required to obtain two therapeutic dosage units, but less than the number of platelets required to obtain three therapeutic platelet dosage units.

In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to receive one therapeutic dose but less than the number of platelets required to receive two therapeutic doses, and the new platelet unit contains less platelets than the amount required to receive one therapeutic dose. In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to obtain one therapeutic dose but less than the number of platelets required to obtain two therapeutic doses, and the new platelet unit contains more platelets than the amount required to obtain two therapeutic doses, but less than the amount required to obtain three therapeutic doses. In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to obtain one therapeutic dose but less than the number of platelets required to obtain two therapeutic doses, and the new platelet unit contains more platelets than the amount required to obtain three therapeutic doses, but less than the amount required to obtain four therapeutic doses.

In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to obtain two therapeutic doses but less than the number of platelets required to obtain three therapeutic doses, and the new platelet unit contains less platelets than the amount required to receive one therapeutic dose. In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to obtain two therapeutic doses but less than the number of platelets required to obtain three therapeutic doses, and the new platelet unit contains more platelets than the amount required to obtain one therapeutic dose, but less than the amount required to obtain two therapeutic doses. In some embodiments, one or more of the selected platelet preparations contains more platelets than the amount required to obtain two therapeutic doses but less than the number of platelets required to obtain three therapeutic doses, and the new platelet unit contains more platelets than the amount required to obtain three therapeutic doses, but less than the amount required to obtain four therapeutic doses.

In some embodiments, one or more platelet preparations and a fresh supply of platelets are combined for about 7 days, for about 6 days, for about 5 days, for about 4 days, for about 3 days, for about 2 days, or within about 1 day from the moment of collection. In some embodiments, one or more selected platelet preparations and a new platelet stock are combined within 20 hours of collection. In some variants

- 25 043840 implementation of one or more selected platelet preparation and a new portion of platelets are combined within 12 hours from the moment of collection. In some embodiments, one or more selected platelet preparations and a new platelet stock are combined within 6 hours of collection. In some embodiments, one or more of the selected platelet preparation and a fresh supply of platelets are obtained from donors of the same ABO blood type.

In some embodiments, the platelet units (e.g., each of the platelet units) in the plurality of platelet units comprises at least about 2.0x1011 at least about 2.2x1011 platelets, at least about 2.4x1011 at least about 2.5x1011 platelets, at least about 2.6x1011 at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, platelets, platelets, platelets, at least about 2.9x1011 platelets or at least about 3.0x1011 platelets. In some embodiments, each platelet unit contains at least 2.4x1011 platelets. In some embodiments, each platelet unit contains at least 2.6x1011 platelets. In some embodiments, each platelet unit contains at least 3.0x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 6.2x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 9.3x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 12.4x1011 platelets. In some embodiments, each of the platelets contains at least about 3.0x1011 platelets, and the pooled platelet preparation contains at least about 15.5x1011 platelets.

In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting the pooled platelet preparation to a pathogen inactivation process includes treating the pooled platelet preparation with a pathogen inactivating compound. In some embodiments, the method further includes subjecting each of the one or more selected platelet preparations and a new batch of platelets to a pathogen inactivation process. In some embodiments, subjecting one or more selected platelet preparation and a fresh platelet batch to a pathogen inactivation process comprises treating one or more selected platelet preparation and a fresh platelet batch with a pathogen inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some embodiments, platelet units contain a minimum number of platelets as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, institution, and/or accredited organization (e.g., government agency, regulatory agency, agency, and/or accredited organization responsible for donated blood products (e.g. donated platelets)). In some embodiments, the platelet units are obtained in the country of the government agency, regulatory body, institution, and/or accredited organization that defines the criteria for the platelet unit. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or more of platelet units contain a minimum number of platelet units. In some embodiments, each of the platelet units contains a minimum number of therapeutic dosage unit platelets. In some embodiments, the minimum platelet count per therapeutic dosage unit is at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In another aspect, the present invention provides a platelet unit suitable for infusion in a human, wherein the platelet unit is selected from a plurality of platelet units obtained by any of the above methods.

In another aspect, the present invention provides a therapeutic platelet dosage unit suitable for infusion into a subject comprising pooled platelets obtained by

- 26 043840 apheresis, from two or more donors, and wherein the pooled platelets obtained by apheresis have been treated with a pathogen-inactivating compound. In some embodiments, pooled apheresis platelets have been treated with a pathogen-inactivating compound prior to pooling. In some embodiments, pooled platelets obtained by apheresis were treated with a pathogen-inactivating compound after pooling. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen. In some embodiments, platelets obtained by apheresis are obtained from donors of the same ABO blood type. In some embodiments, platelets obtained by apheresis are obtained from donors of the same ABO blood type and Rh factor. In some embodiments, a therapeutic platelet dosage unit contains at least about

2.0x1011 platelets, at least about 2.2x1011 platelets, at least about

2.4 x 1011 platelets, at least about 2.5 x 1011 platelets, at least about

2.6 x 1011 platelets, at least about 2.7 x 1011 platelets, at least about

2.8 x 1011 platelets, at least about 2.9 x 1011 platelets, or at least about 3.0 x 1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 2.4 x 1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 2.6x1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 3.0x1011 platelets.

In some embodiments, a therapeutic platelet dosage unit contains a minimum amount (e.g., at least a minimum amount) of platelets, as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accredited organization (e.g., a government regulatory agency agency, institution and/or accredited organization responsible for donated blood products (eg, donated platelets)). In some embodiments, the platelet therapeutic unit is obtained in the country of the government agency, regulatory body, institution, and/or accredited organization defining the criteria for the platelet therapeutic unit.

In another aspect, the present invention provides a method of administering platelets to a subject in need thereof, comprising administering to the patient the aforementioned platelet unit or the aforementioned therapeutic platelet dosage unit.

In another aspect, the present invention provides a computerized method for optimizing platelet units (eg, platelet units for infusion), comprising: in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of a unit of platelets; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; determination based on the search results of the platelet portion volume; and providing a specific platelet unit volume that optimizes platelet units (eg, platelet units for infusion). In some embodiments, determining the platelet unit volume further includes determining the platelet yield (eg, target platelet yield) of the platelet unit. In some embodiments, determining the platelet unit volume further includes determining the duration of the platelet donation. In some embodiments, optimizing platelet units includes optimizing the number of platelet units that can be obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing excess platelets in a platelet unit (eg, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing or removing excess platelets (eg, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes improving or increasing the number of platelet units obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes increasing the efficiency of obtaining platelet units (eg, depending on the process for obtaining platelet blocks prior to optimization). In some embodiments, optimizing platelet units includes obtaining a target value (eg, number) of platelets per platelet unit.

- 27 043840

In some embodiments, at least one of the platelet unit and the plurality of platelet preparations comprises apheresis-derived platelets. In some embodiments, the platelet unit comprises platelets that are currently being collected from a donor or platelets that are to be collected from a donor. In some embodiments, one or more properties of the platelet unit include: blood type, time of donation (eg, date, time, date and time), number of platelets per unit volume, and, optionally, maximum volume of the platelet unit. In some embodiments, the blood type value includes one of: A, B, AB, or O.

In some embodiments, directing a search for a plurality of values associated with samples of a plurality of platelet preparations includes: obtaining one or more search criteria using one or more retrieved values associated with one or more properties of a platelet unit; indicating a search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria; and obtaining one or more potential platelet preparation samples from the plurality of platelet preparation samples, one or more potential platelet preparation samples having values that satisfy the one or more search criteria. In some embodiments, the search criteria include one or more threshold conditions of one or more of blood type, time of donation, platelet volume, and platelet count per unit volume. In some embodiments, obtaining one or more potential platelet preparation samples includes filtering samples of a plurality of platelet preparations based on one or more search criteria. In some embodiments, the representations of multiple platelet preparations include at least one of: platelet preparations being stored in a platelet preparation repository, platelet preparations being currently collected from a plurality of donors, and platelet preparations being collected from a plurality of donors.

In some embodiments, determining the volume of a platelet unit includes obtaining one or more values corresponding to one or more potential samples of platelet preparations obtained from the search results; obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units; determining, based on the one or more values corresponding to the one or more candidate platelet preparation samples, and the one or more criteria for the platelet units, one or more platelet preparations for selecting from the one or more candidate samples from the plurality of platelet preparations; and obtaining a platelet unit volume based on the particular platelet preparation. In some embodiments, providing the determined platelet unit volume includes at least one of: displaying the determined platelet unit volume on a computer system display; sending a notification indicating a certain volume of platelet portion; and providing a certain volume of platelet portions in the apheresis system. In some embodiments, determining the platelet unit volume further includes determining the platelet yield (eg, target platelet yield) of the platelet unit. In some embodiments, determining the platelet unit volume further includes determining the length of time of platelet donation. In some embodiments, providing a specified volume of platelet donation further includes at least one of: displaying the determined output volume and/or length of time of platelet donation on a computer system display; sending a notification specifying a specific volume and/or duration of platelet donation; and providing a specified volume and/or duration of time for platelet donation to the apheresis system.

In some embodiments, the method further includes combining a portion of platelets and one or more platelet preparations selected from samples of a plurality of platelet preparations to produce a pooled platelet preparation. In some embodiments, the method further includes dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic platelet dosage units), each in a separate container. In some embodiments, the platelet units (e.g., each of the platelet units) in the plurality of platelet units comprise at least about

2.0x1011 platelets, at least about 2.2x1011 platelets, at least about

2.4 x 1011 platelets, at least about 2.5 x 1011 platelets, at least about

2.6 x 1011 platelets, at least about 2.7 x 1011 platelets, at least about

2.8 x 1011 platelets, at least about 2.9 x 1011 platelets, or at least about 3.0 x 1011 platelets. In some embodiments, each platelet unit contains at least 2.4x1011 platelets. In some embodiments, each platelet unit contains at least 2.6x1011 platelets. In some embodiments, each platelet unit contains at least 3.0x1011 platelets. In some embodiments, one or more selected platelet preparations and a portion of platelets are combined during

- 28 043840 20 hours from the moment of collection. In some embodiments, one or more selected platelet preparation and platelet portion are combined within 12 hours of collection. In some embodiments, one or more selected platelet preparation and platelet portion are combined within 6 hours of collection. In some embodiments, one or more selected platelet preparation and platelet unit are obtained from donors of the same ABO blood type. In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting the pooled platelet preparation to a pathogen inactivation process includes treating the pooled platelet preparation with a pathogen inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some embodiments, the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from one or more selected platelet preparations and the platelet unit without combining the one or more selected platelet preparations and the platelet unit.

In some embodiments, each of the one or more selected platelet preparations contains a number of platelets less than that required to produce one unit of platelets. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, each of the one or more selected platelet preparations contains more platelets than the number required to produce three platelet units, but less than the number of platelets required to obtain four therapeutic platelet units.

In some embodiments, the new supply of platelets contains a number of platelets less than that required to produce one unit of platelets. In some embodiments, the platelet unit contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the platelet unit contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the platelet unit contains more platelets than the number required to produce three platelet units, but less than the number of platelets required to obtain four platelet units.

In some embodiments, each of the one or more selected platelet preparations and platelet units contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, each of the one or more selected platelet preparation and platelet unit contains more platelets than the number required to produce platelet units, but less than the number of platelets required to obtain platelet units. In some embodiments, the one or more selected platelet preparation contains more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the platelet unit contains fewer platelets than the number needed to receiving one unit of platelets. In some embodiments, the one or more selected platelet preparation contains more platelets than the number needed to produce one unit of platelets but less than the number of platelets needed to produce two units of platelets, and the platelet unit contains more platelets than the number needed to obtaining two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the one or more selected platelet preparation contains more platelets than the number needed to produce one unit of platelets but less than the number of platelets needed to produce two units of platelets, and the platelet unit contains more platelets than the number needed to obtaining three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the one or more selected platelet preparation contains more platelets than the amount required

- 29 043840 mine to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, and a unit of platelets contains fewer platelets than the number required to obtain one unit of platelets. In some embodiments, the one or more selected platelet preparation contains more platelets than the number needed to produce two units of platelets but less than the number of platelets needed to obtain three units of platelets, and the platelet unit contains more platelets than the number needed to obtaining one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the one or more selected platelet preparation contains more platelets than the number needed to produce two units of platelets but less than the number of platelets needed to obtain three units of platelets, and the platelet unit contains more platelets than the number needed to obtaining three units of platelets, but less than the number of platelets required to obtain four units of platelets.

In another aspect, the present invention provides a non-transitory computer-readable medium containing instructions stored thereon for optimizing platelet units (e.g., platelet units for infusion), the instructions executed by one or more processors of a computer system causing the computer system to obtain one or more values associated with one or more properties of a platelet unit; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; determining, based on the search results, the volume of a platelet portion; and providing a specific platelet unit volume that optimizes platelet units (eg, platelet units for infusion). In some embodiments, determining the volume of a platelet unit further includes determining a platelet yield (e.g., a target platelet yield) of the platelet unit and providing a determined platelet yield of the platelet unit, wherein the determined platelet yield of the platelet unit optimizes platelet units. In some embodiments, determining the platelet unit volume further includes determining the duration of the platelet donation and providing a certain duration of the platelet donation, wherein the determined duration of the platelet donation allows optimization of the platelet units.

In another aspect, the present invention provides a system for optimizing platelet units (eg, platelet infusion units) comprising one or more processors; and a memory containing instructions stored therein, wherein the instruction executed by the one or more processors causes the computer system to obtain one or more values associated with one or more properties of the platelet unit; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; determining, based on the search results, a platelet unit volume and providing a determined platelet unit volume that optimizes platelet units (eg, platelet units for infusion). In some embodiments, determining the volume of a platelet unit further includes determining the platelet yield (e.g., a target platelet yield) of the platelet unit and providing a certain platelet yield of the platelet unit, wherein the determined platelet yield of the platelet unit provides platelet optimization. In some embodiments, determining the platelet unit volume further includes determining the duration of the platelet donation and providing a certain duration of the platelet donation, wherein the determined duration of the platelet donation allows optimization of the platelet units. In some embodiments, the computer system is integrated with the apheresis system.

In another aspect, the present invention provides a computerized method for optimizing platelet units (eg, platelet units for infusion), comprising, in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of a first platelet preparation; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; selecting, based on the search results, a second platelet preparation from samples of the plurality of platelet preparations; and providing the selected second platelet preparation, wherein the selected second platelet preparation allows optimization of platelet units (eg, platelet units for infusion). In some embodiments, optimizing platelet units includes optimizing the number of platelet units that can be obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing excess platelets in a platelet unit (eg, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing or removing excess platelets (eg, depending on the process for obtaining platelet units prior to optimization). Somehow

- 30 043840 In many embodiments, optimizing platelet units involves improving or increasing the number of platelet units obtained (eg, from a platelet unit and a plurality of platelet preparations, depending on the platelet unit acquisition process prior to optimization). In some embodiments, optimizing platelet units includes increasing the efficiency of obtaining platelet units (eg, depending on the process of obtaining platelet blocks prior to optimization). In some embodiments, optimizing platelet units includes obtaining a target value (eg, number) of platelets per platelet unit.

In some embodiments, at least one of the first platelet preparation and the plurality of platelet preparations comprises platelets obtained by apheresis. In some embodiments, the first platelet preparation includes a platelet preparation stored in a platelet preparation inventory. In some embodiments, one or more properties of the first platelet preparation include blood type, time of donation (eg, date, time, date and time), volume, and number of platelets per unit volume. In some embodiments, the blood type value includes one of: A, B, AB, or O.

In some embodiments, directing a search for a plurality of values associated with samples of a plurality of platelet preparations includes obtaining one or more search criteria using one or more retrieved values associated with one or more properties of the first platelet preparation; indicating a search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria; and obtaining one or more potential platelet preparation samples from the plurality of platelet preparation samples, one or more potential platelet preparation samples having values that satisfy the one or more search criteria. In some embodiments, the search criteria include one or more threshold conditions of one or more of: blood type, time of donation, volume, and platelet count per unit volume. In some embodiments, obtaining one or more potential platelet preparation samples includes filtering samples of a plurality of platelet preparations based on one or more search criteria. In some embodiments, the representations of multiple platelet preparations include at least one of: platelet preparations are stored in a platelet preparation store, platelet preparations are currently being collected from a plurality of donors, and platelet preparations will be collected from a plurality of donors.

In some embodiments, selecting a second platelet preparation includes obtaining one or more values corresponding to one or more potential platelet preparation samples obtained from the search results; obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units; and selecting, based on the one or more values corresponding to the one or more candidate platelet preparation samples, and the one or more criteria for platelet units, a second platelet preparation from the one or more candidate platelet preparation samples. In some embodiments, providing the selected second platelet preparation includes at least one of: displaying the selected second platelet preparation on a computer system display; sending a notification providing the selected second platelet preparation; and providing identification of the selected second platelet preparation in the apheresis system.

In some embodiments, the method further includes combining the first platelet preparation and the selected second platelet preparation to produce a combined platelet preparation. In some embodiments, the method further includes dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic platelet dosage units), each in a separate container. In some embodiments, the platelet units (e.g., each of the platelet units) in the plurality of platelet units comprise at least about 2.0 x 1011 platelets, at least about

2.2 x 1011 platelets, at least about 2.4 x 1011 platelets, at least about

2.5 x 1011 platelets, at least about 2.6 x 1011 platelets, at least about

2.7 x 1011 platelets, at least about 2.8 x 1011 platelets, at least about

2.9 x 1011 platelets or at least about 3.0 x 1011 platelets. In some embodiments, each platelet unit contains at least 2.4 x 1011 platelets. In some embodiments, each platelet unit contains at least 2.6 x 1011 platelets. In some embodiments, each platelet unit contains at least 3.0x1011 platelets. In some embodiments, the first platelet preparation and the selected second platelet preparation are combined within 20 hours of collection. In some embodiments, the first platelet preparation and the selected second platelet preparation are combined within 12 hours of collection. In some embodiments, the first platelet preparation and the selected second platelet preparation are combined within 6 hours of collection. In some embodiments, the first platelet preparation and the second selected platelet preparation are obtained

- 31 043840 us from donors of the same ABO blood type. In some embodiments, the method further includes subjecting the pooled platelet preparation to a pathogen inactivation process. In some embodiments, subjecting the pooled platelet preparation to a pathogen inactivation process includes treating the pooled platelet preparation with a pathogen inactivating compound. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen.

In some embodiments, the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from the first platelet preparation and the selected second platelet preparation without combining the first platelet preparation and the selected second platelet preparation.

In some embodiments, the second selected platelet preparation contains a number of platelets less than that required to produce one unit of platelets. In some embodiments, the second selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the second selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, the second selected platelet preparation contains more platelets than the number required to obtain three platelet units, but less than the number of platelets necessary to obtain four therapeutic units of platelets.

In some embodiments, the first platelet preparation contains a number of platelets less than needed to produce one unit of platelets. In some embodiments, the first platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, the first platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. In some embodiments, the first platelet preparation contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets.

In some embodiments, the selected second platelet preparation and the first platelet preparation each contain more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, each of the selected second platelet preparation and the first platelet preparation contains more platelets than the number required to produce platelet units, but less than the number of platelets necessary to obtain platelet units. In some embodiments, the second selected platelet preparation contains more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the first platelet preparation contains less platelets than the number of platelets needed to receiving one unit of platelets. In some embodiments, the selected second platelet preparation contains more platelets than the number required to obtain one unit of platelets but less than the number of platelets necessary to obtain two units of platelets, and the first platelet preparation contains more platelets than the amount necessary to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the selected second platelet preparation contains more platelets than the number required to obtain one unit of platelets but less than the number of platelets necessary to obtain two units of platelets, and the first platelet preparation contains more platelets than the amount necessary to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. In some embodiments, the second selected platelet preparation contains more platelets than the number needed to obtain two units of platelets but less than the number of platelets needed to obtain three units of platelets, and the first platelet preparation contains less platelets than the number of platelets needed to receiving one unit of platelets. In some embodiments, the selected second platelet preparation contains more platelets than the amount required to obtain two units of platelets, but less than

- 32 043840 the number of platelets required to obtain three units of platelets, and the first platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. In some embodiments, the selected second platelet preparation contains more platelets than the number required to obtain two units of platelets but less than the number of platelets necessary to obtain three units of platelets, and the first platelet preparation contains more platelets than the amount necessary to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets.

In another aspect, the present invention provides a non-transitory computer-readable medium containing instructions stored thereon for optimizing platelet units (e.g., platelet units for infusion), the instructions executed by one or more processors of a computer system causing the computer system to obtain one or more values related to one or more properties of the first platelet preparation; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; selecting, based on the search results, a second platelet preparation from samples of the plurality of platelet preparations; and providing a selected second platelet preparation, wherein the selected second platelet preparation allows optimization of platelet units (eg, platelet units for infusion).

In another aspect, the present invention provides a system for optimizing platelet units (eg, platelet infusion units) comprising one or more processors; and a memory containing instructions stored therein, wherein the instruction executed by the one or more processors causes the computer system to obtain one or more values associated with one or more properties of the first platelet preparation; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; selecting, based on the search results, a second platelet preparation from samples of the plurality of platelet preparations; and providing a selected second platelet preparation, wherein the selected second platelet preparation allows optimization of platelet units (eg, platelet units for infusion). In some embodiments, the computer system is integrated with the apheresis system.

In another aspect, the present invention provides a processing unit for producing a plurality of platelet units from two or more platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject, the processing unit comprising: a) a first container that contains a pathogen inactivation compound (PIP) and is suitable for combining two or more platelets with a PIP; b) a second container connected to the first container, within which two or more platelet units mixed with CIP can be photochemically inactivated under sterile conditions, the volume of the two or more platelet units being sufficient to produce multiple platelet units; c) a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions; and d) two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions to provide multiple units platelets, wherein the plurality of platelet units contains a greater number of platelet units than the total number of platelet units, which can be obtained from two or more units without combining two or more units of platelets. In some embodiments, the SIP is psoralen. In some embodiments, the CIP is amotosalen. In some embodiments, the platelet units in the plurality of platelet units comprise a therapeutic dose of platelets.

In some embodiments, the processing unit comprises three or more third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the three or more third containers in sterile conditions to provide multiple units of platelets. In some embodiments, the treatment unit comprises three-thirds containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the three-third containers under sterile conditions to provide multiple platelet units. In some embodiments, the first container is suitable for sterile connection with the additional container. In some embodiments, the processing unit further comprises an additional container suitable for housing one or more of two or more portions of platelets, while additionally

- 33 043840 The body container is connected to the first container so that one or more portions of platelets from the additional container can be transferred from the additional container to the first container under sterile conditions. In some embodiments, the additional container is suitable for housing a portion of platelets obtained by apheresis. In some embodiments, the additional container is suitable for sterile connection with the second additional container. In some embodiments, the second additional container contains one or more of two or more platelet units, and wherein the additional container is suitable for sterile connection with the second additional container such that one or more platelet units of the second additional container can be transferred from the second additional container to additional container under sterile conditions.

In some embodiments, the processing unit further comprises a second additional container suitable for housing one or more of the two or more platelet units, wherein the second additional container is connected to the additional container such that one or more platelet units of the second additional container can be transferred from the second additional container. additional container into an additional container under sterile conditions. In some embodiments, the additional container is suitable for housing a platelet unit obtained by apheresis from a first donor, and wherein the second additional container is suitable for housing a platelet unit obtained by apheresis from a second donor.

In another aspect, the present invention provides a kit comprising (a) a processing unit and (b) instructions for operating the processing unit for producing a plurality of platelet units from two or more platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion subject, wherein the plurality of platelet units contains a greater number of platelets than the number of platelets that can be obtained from two or more units of platelets without combining the two or more units of platelets, and wherein the processing unit comprises 1) a first container that contains a compound for pathogen inactivation (PIP) and is suitable for combining two or more platelets with PIP; 2) a second container connected to the first container, within which two or more portions of platelets mixed with SIP can be photochemically inactivated under sterile conditions, the volume of the two or more portions of platelets being sufficient to produce multiple units of platelets; 3) a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions; and 4) two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions to provide multiple units platelets. In some embodiments, the kit contains instructions for operating a processing unit for producing a plurality of platelet units from two or more platelet concentrates, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject, wherein the plurality of platelet units contains a greater number of platelets than the number platelet, which can be obtained from two or more platelet concentrates without combining two or more platelet concentrates. In some embodiments, the kit contains instructions for operating a processing unit for producing a plurality of platelet units from two or more apheresis platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject, wherein the plurality of platelet units contains a larger number of platelets than the number of platelets that can be obtained from two or more apheresis platelet units without combining two or more apheresis platelet units. In some embodiments, the SIP is psoralen. In some embodiments, the CIP is amotosalen. In some embodiments, the platelet units in the plurality of platelet units comprise a therapeutic dose of platelets.

In some embodiments, the kit contains three or more third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the three or more third containers under sterile conditions for providing multiple units of platelets. In some embodiments, the kit comprises three-thirds containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the three-thirds containers under sterile conditions to provide multiple platelet units . In some embodiments, the first container is suitable for sterile connection with the additional container. In some embodiments, the kit further comprises an additional container suitable for housing one or more of two or more platelet units, wherein the additional container is connected to the first container so that one

- 34 043840 per or more additional container platelet units can be transferred from the additional container to the first container under sterile conditions. In some embodiments, the additional container is suitable for housing the platelet concentrate. In some embodiments, the additional container is suitable for housing a portion of platelets obtained by apheresis. In some embodiments, the additional container is suitable for sterile connection with the second additional container. In some embodiments, the second additional container contains one or more of two or more platelet units, and wherein the additional container is suitable for sterile connection with the second additional container such that one or more platelet units of the second additional container can be transferred from the second additional container to additional container under sterile conditions.

In some embodiments, the kit further comprises a second additional container suitable for housing one or more of the two or more platelet units, wherein the second additional container is connected to the additional container such that one or more platelet units of the second additional container can be transferred from the second additional container into an additional container under sterile conditions. In some embodiments, the additional container is suitable for containing platelet concentrate obtained from a first donor, and wherein the second additional container is suitable for containing platelet concentrate obtained from a second donor. In some embodiments, the additional container is suitable for housing a platelet unit obtained by apheresis from a first donor, and wherein the second additional container is suitable for housing a platelet unit obtained by apheresis from a second donor.

It should be understood that one, some, or all of the features of the various embodiments described herein may be combined to form other embodiments. These and other aspects will become apparent to one skilled in the art. These and other embodiments are further described in the following detailed description.

Description of graphic materials

In fig. 1 shows a method for producing three therapeutic units of platelets from two very large single apheresis units of platelets from a first donor and a second donor. Abbreviations: OB - very large unit; IP - pathogen inactivation.

In fig. 2 shows a method for producing five therapeutic units of platelets from two very large double apheresis units of platelets collected from a first donor and a second donor. Abbreviations: OB - very large unit; C - ordinary single.

In fig. 3 depicts a method for producing four therapeutic units of platelets from one very large double apheresis unit of platelets collected from a first donor and one very large single apheresis unit of platelets collected from a second donor. Abbreviations: OB - very large unit; C - ordinary single.

In fig. 4 shows a method for producing seven therapeutic units of platelets from two very large triple apheresis units of platelets collected from a first donor and a second donor. Abbreviations: OB - very large unit; C - ordinary single.

In fig. 5 depicts a method for producing six therapeutic units of platelets from one very large triple apheresis platelet unit collected from a first donor and one very large double apheresis unit of platelets collected from a second donor. Abbreviations: OB - very large unit; C - ordinary single.

In fig. 6 depicts a method for producing five therapeutic units of platelets from one very large triple apheresis unit of platelets collected from a first donor and one very large single apheresis unit of platelets collected from a second donor. Abbreviations: OB - very large unit; C - ordinary single.

In fig. 7 depicts a typical processing kit for use in producing pathogen-inactivated platelets in accordance with some embodiments. The dotted components depict one container of platelets (eg, donor platelets) sterilely connected to the processing kit. Abbreviations: SIP - pathogen inactivating compound; UAS is a device for adsorption of a compound.

In fig. 8 depicts a typical processing kit for use in producing pathogen-inactivated platelets in accordance with some embodiments. The dotted components depict two platelet containers (eg, first donor platelets, second donor platelets) sterilely connected to each other (eg, for pooling) and to a processing kit. Abbreviations: SIP - pathogen inactivating compound; UAS is a device for adsorption of a compound.

In fig. 9 depicts a system for optimizing platelet units for infusion.

Detailed description

The term pooled platelet preparation refers to a platelet preparation containing

- 35 043840 platelets obtained from more than one unit, such as an apheresis unit of platelets, and then combined (for example, in one container). As a rule, portions of platelets are obtained from different donors. Platelets may be pooled at any stage after donation and prior to therapeutic use, including, but not limited to, pooling before or after supplementation, before or after any storage period, and before or after any treatment and pathogen inactivation process. The platelets may be combined into any container suitable for platelet preparations and of sufficient size to accommodate the volume of platelets, for example, by sterilely joining the containers of two platelet preparations (eg, via a connecting tube) and transferring the platelets from one container to the other, or by sterilely joining the containers two platelet preparations with a third container (eg, via a connecting tube) and transferring the platelets to the third container.

The term pathogen inactivation process means a method useful for inactivating pathogens that may be present in a platelet acquisition such as platelet donation, it being understood that the process does not necessarily completely inactivate all pathogens that may be present, but substantially reduces the number of pathogens to significantly reduce risk of transfusion-related illness. Pathogen inactivation can be analyzed by measuring the amount of infectious pathogen (eg, viral or bacterial particles) in a specified volume, and the level of inactivation is usually expressed as the log reduction in pathogen infectivity or the log reduction in titer. Methods for analyzing the logarithmic reduction in titer and measuring it during pathogen inactivation are known in the art. When the inactivation process is tested against a variety of pathogens, the reduction in the identified active pathogen is at least about 1 log, at least about 2 log, at least about 3 log, at least about 4 log, or at least about 5 log titer reduction . Various methods for inactivating pathogens are known in the art and can be used in the methods of this disclosure, including, for example, commercially available pathogen inactivation processes such as the INTERCEPT blood system (Cerus Corp), Mirasol (TerumoBCT), and Theraflex (MacoPharma). In some embodiments, the method of inactivating pathogens may include treatment with a pathogen-inactivating compound.

The term pathogen-inactivating compound means any suitable compound, such as a small organic compound, that can be used to inactivate a pathogen that may be present in a platelet-containing blood product. A photoactivatable pathogen-inactivating compound is a suitable compound that requires some level of light in order to sufficiently inactivate the pathogen. Such compounds are preferred for inactivating pathogens in platelets because they provide control over the inactivation process. Such photoactivated pathogen-inactivating compounds described herein include psoralens, isoalcoxazines, alloxazines, phthalocyanines, phenothiazines and porphyrins, these terms being understood to cover a general class of compounds, i.e. the basic compound and its suitable derivatives. For example, psoralens or psoralen usually describes the psoralen core compound and any derivative thereof (e.g. amotosalen), isoalloxazins or isoalloxazine usually describes the isoalloxazine core and any derivative thereof (e.g. riboflavin), etc. Such derivatives include the structure of the main compound, as well as additional substituents on the core. Descriptions of such compounds include any salts thereof.

The term amotosalen means the compound 3-(2-aminoethoxymethyl)-2,5,9-trimethylfuro[3,2q]chromene-7-one and any salts thereof. The compound may also be referred to as 4'-(4-amino-2-oxa)butyl4,5',8-trimethylpsoralen. The compound may also be referred to as 3-[(2-aminoethoxy)methyl]-2,5,9trimethyl-7H-furo[3,2-g][1]benzopyran-7-one. When platelet inactivation involves the addition of amotosalen HCl (the HCl salt of amotosalen) to a unit of platelets, removal of this compound from a unit of platelets is not limited to the removal of amotosalen HCl, since amotosalen may be present in the solution as other salts or as a free base. As used in the methods described herein, removal of amotosalen means removal of the compound in any form, for example, as a free base or as any salt, as measured by the assays described herein.

Apheresis platelet collection.

Certain aspects of the present invention provide systems and methods associated with improvements (e.g., providing greater efficiency) in the collection and production of platelet units (e.g., apheresis platelet units), including pathogen-inactivated platelets, such as, for example, in blood centers, using apheresis collection systems for platelet portions. A particular benefit, among other things, provided by the improvement disclosed herein is the ability to obtain an increased number of platelet units (e.g., platelet units suitable for infusion) without increasing the number of platelet units or donors required, apheresis typically refers to an automated blood collection device which uses a centrifugal or filtration compartment to automatically remove whole blood from a donor, separate whole blood into blood components, collect specific components (such as platelets), and return the remainder of the whole blood and remaining uncollected blood components to the donor.

Plateletpheresis is the collection of platelets using such an automated device to separate blood cells, resulting in a high yield of platelets (eg, apheresis platelets) from a single donor. Some automated blood cell separation devices are capable of collection procedures not only for single platelet units, but also for double and triple platelet units. Apheresis collection devices are well known in the art, with several such devices being commercially available, including, for example, the Amicus™ system (Fenwal, Inc), the Trima Accel® system (Terumo BCT), and the mobile system

MCS®+ 9000 (Haemonetics, Inc).

Apheresis platelet units are typically based on certain donor parameters, such as, for example, gender, physical size (eg, weight), hemoglobin level, platelet count on the day of donation, pre-donation history, and frequency of donation, in part to ensure that only a safe number of platelets are collected. Any or all of these parameters may be entered into the computer system and/or apheresis collection device. With these parameters, apheresis platelet donation typically involves collecting from an individual donor a volume sufficient to provide one, two, or three platelet units (e.g., therapeutic dosage units), each containing a specified minimum amount (e.g., at least a minimum number) of platelets per unit to satisfy a therapeutic dose with such unit or therapeutic dose criteria as are generally determined by government, regulatory, institutional, or accredited organization (e.g., industry) standards. Non-limiting examples of such standards include, for example, those specified by the FDA, EDQM, AABB, PMDA, TGA and SFDA. The specified minimum, for example, may vary depending on the country. In some embodiments, platelet units may contain at least about 2.0x1011, at least about 2.2x1011, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets , at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, at least about 3.0x1011 platelets. Typically, the platelet count can be determined for each platelet unit, for example, based on the number of donor platelets and information on the volume collected, or alternatively, checking the units after collection. Preferably, each unit of platelets will contain the specified minimum number of platelets; however, determining the platelet count for each unit may not be an absolute requirement, and some platelet units in a plurality of platelet units may have less than a certain platelet count.

The present invention may, in certain embodiments, be extended in various ways to platelets collected from a donor (e.g., platelet units, platelet preparations), such as, for example, platelet units or platelet preparations that have already been collected (e.g., collected and stored), with or without further processing (eg, leukofiltration, pathogen inactivation), platelet units or platelet preparations that are currently being collected from a donor, and/or platelet units or platelet preparations that are to be collected from a donor (eg, a donor who has been identified , given donor). Typically, reference to platelet units or platelet preparations collected from a donor precedes any step of pooling or combining with additional platelets (eg, from another donor, such as a second donor or third donor) that may provide the pooled platelet preparation.

In some embodiments of the present invention, platelets collected from a donor by apheresis may contain less than the number (e.g., less than a minimum number, less than a minimum number, less than 100%) of platelets required to produce one platelet unit (e.g., a therapeutic dosage unit). For example, a unit of platelets may contain platelets in an amount that is less than about 99%, less than about 98%, less than about 97%, less than about 95%, less than about 90%, less than about 85%, less than about 80%, less than about 75%, less than about 70%, less than about 65%, less than about 60%, less than about 55%, less than about 50%, less than about 45%, less than about 40% , less than about 35%, less than about 30%, or less than about 25% of the number of platelets required to produce one unit of platelets. Such platelet units may contain a minimum amount of platelets, such as at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50% or more of the number of platelets required to obtain one unit of platelets. Alternatively or additionally, the platelet unit may contain a platelet count that is from about 10 to about 98%, from about 10 to about 95%, from about 10 to about 90%, 15 to about 98%, from about 15 to about 95% , from about 15 to about 90%, 20 to about 98%,

- 37 043840 from about 20 to about 95%, from about 20 to about 90%, 25 to about 98%, from about 25 to about 95%, from about 25 to about 90%, 30 to about 98%, from about 30 to about 95%, from about 30 to about 90%, from about 35 to about 98%, from about 35 to about 95%, from about 35 to about 90%, 40 to about 98%, from about 40 to about 95% , from about 40 to about 90%, 50 to about 98%, from about 50 to about 95%, or from about 50 to about 90% of the number of platelets required to produce one unit of platelets. In some embodiments, the platelet unit contains a platelet count that is from about 98 to about 95%, from about 90 to about 85%, from about 80 to about 75%, from about 70 to about 65%, from about 60 to about 55 %, about 50 to about 45%, about 40 to about 35%, or about 30 to about 25% of the number of platelets required to produce one unit of platelets.

In some embodiments, platelets obtained from a donor by apheresis may contain more than the number (e.g., more than a minimum number, more than a minimum number) of platelets required to produce one unit of platelets, but less than the number (e.g., less minimum number, less than the minimum number) of platelets required to obtain two units of platelets. For example, a unit of platelets containing more than the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, may contain platelets in an amount that is about 1.1 times, about 1 ,15 times, about 1.2 times, about 1.25 times, about 1.3 times, about 1.35 times, about 1.4 times, about 1.45 times, about 1, 5 times, about 1.6 times, about 1.7 times, about 1.8 times, about 1.9 times, about 1.95 times, or about 1.98 times the number of platelets needed to obtain one unit of platelets. Alternatively or in addition, a unit of platelets containing more than the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets, may contain platelets in an amount that is 1.1 times up to about 1.98 times, about 1.1 times to about 1.95 times, about 1.1 times to about 1.9 times, about 1.15 times to about 1.98 times multiple, about 1.15 times to about 1.95 times, about 1.15 times to about 1.9 times, about 1.2 times to about 1.98 times, about 1 .2 times to about 1.95 times, about 1.2 times to about 1.9 times, about 1.25 times to about 1.98 times, about 1.25 times to about 1.95 times, about 1.25 times to about 1.9 times, about 1.3 times to about 1.98 times, about 1.3 times to about 1.95 times multiple, about 1.3 times to about 1.9 times, about 1.35 times to about 1.98 times, about 1.35 times to about 1.95 times, about 1 .35 times to about 1.9 times, about 1.4 times to about 1.98 times, about 1.4 times to about 1.95 times, about 1.4 times to about 1.9-fold, about 1.5-fold to about 1.98-fold, about 1.5-fold to about 1.95-fold, or about 1.5-fold to about 1.9-fold a multiple of the number of platelets required to obtain one unit of platelets. Alternatively or additionally, a unit of platelets containing more platelets than the number of platelets required to produce one unit of platelets, but less than the number of platelets required to produce two units of platelets, may contain platelets in an amount of about 105%, about 110%, about 115%, about 120%, about 125%, about 130%, about 135%, about

140%, about 145%, about 150%, about 155%, about 160%, about 165%, about 170%, about 175%, about

180%, about 185%, about 190%, about 195%, or about 198% of the number of platelets required to produce one unit of platelets. Alternatively or additionally, a unit of platelets containing more platelets than the number of platelets required to produce one unit of platelets but less than the number of platelets required to produce two units of platelets may contain platelets in an amount of from about 110 to about 198%, from about 110 to about 195%, from about 110 to about from about 115 to about from about 120 to about from about 125 to about from about 130 to about from about 135 to about from about 140 to about

190%, from about 115

190%, from about 120

190%, from about 125

190%, from about 130

190%, from about 135

190%, from about 140 to about 198%, from about to about 198%, from about to about 198%, from about to about 198%, from about to about 198%, from about to about 198%, from about

115 to about 195%,

120 to about 195%,

125 to about 195%,

130 to about 195%,

135 to about 195%,

140 to about 195%,

150 to about 195% or

190%, about 150 to about 198%, from about 150 to about 190% of the number of platelets required to produce one unit of platelets.

In some embodiments, platelets obtained from a donor by apheresis may contain more than the number (e.g., more than a minimum number, more than a minimum number) of platelets required to obtain two units of platelets, but less than the number (e.g., less minimum number, less than the minimum number) of platelets required to obtain three units of platelets. For example, a unit of platelets containing more than the number of platelets required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, may contain platelets in an amount that is about 1.1- multiple, about 1.15 times, about 1.2 times, about 1.25 times, about 1.3 times, about 1.35 times, about 1.4 times, about 1.45 times , about 1.5 times, about 1.6 times, about 1.7 times, about 1.8 times, about 1.9 times, about 1.95 times or about 1.98 times from the number of platelets required to produce two units of platelets. Alternatively or in addition, a unit of platelets containing more than the number of platelets required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, may contain platelets in an amount that is 1.1 times up to about 1.98 times, about 1.1 times to about 1.95 times, about 1.1 times to about 1.9 times, about 1.15 times to about 1.98 times multiple, about 1.15 times to about 1.95 times, about 1.15 times to about 1.9 times, about 1.2 times to about 1.98 times, about 1 .2 times to about 1.95 times, about 1.2 times to about 1.9 times, about 1.25 times to about 1.98 times, about 1.25 times to about 1.95 times, about 1.25 times to about 1.9 times, about 1.3 times to about 1.98 times, about 1.3 times to about 1.95 times multiple, about 1.3 times to about 1.9 times, about 1.35 times to about 1.98 times, about 1.35 times to about 1.95 times, about 1 .35 times to about 1.9 times, about 1.4 times to about 1.98 times, about 1.4 times to about 1.95 times, about 1.4 times to about 1.9-fold, about 1.5-fold to about 1.98-fold, about 1.5-fold to about 1.95-fold, or about 1.5-fold to about 1.9-fold multiple of the number of platelets required to obtain two units of platelets. Alternatively or additionally, a unit of platelets containing more platelets than the number of platelets required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, may contain platelets in an amount of about 105%, about 110%, about 115%, about 120%, about 125%, about 130%, about 135%, about 140%, about 145%, about 150%, about 155%, about 160%, about 165%, about 170%, about 175%, about 180 %, about 185%, about 190%, about 195%, or about 198% of the number of platelets required to obtain two units of platelets. Alternatively or additionally, a unit of platelets containing more platelets needed to produce two units of platelets, but less than the number of platelets needed to obtain three units of platelets, may contain platelets in an amount of from about 110 to about 198%, from about 110 to about 198% platelets. about 195%, about 110 to about 190%, about 115 to about 198%, about 115 to about 195%, about 115 to about 190%, about 120 to about 198%, about 120 to about 195 %, from about 120 to about 190%, from about 125 to about 198%, from about 125 to about 195%, from about 125 to about 190%, from about 130 to about 198%, from about 130 to about 195%, from about 130 to about 190%, from about 135 to about 198%, from about 135 to about 195%, from about 135 to about 190%, from about 140 to about 198%, from about 140 to about 195%, from about 140 to about 190%, about 150 to about 198%, about 150 to about 195%, or about 150 to about 190% of the number of platelets required to obtain two units of platelets.

In some embodiments, platelets obtained from a donor by apheresis may contain more than the number (e.g., more than a minimum number, more than a minimum number) of platelets required to obtain three units of platelets, but less than the number (e.g., less minimum number, less than the minimum number) of platelets required to obtain four units of platelets. For example, a unit of platelets containing more than the number of platelets required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, may contain platelets in an amount that is about 1.1 times, about 1 ,15 times, about 1.2 times, about 1.25 times, about 1.3 times, about 1.35 times, about 1.4 times, about 1.45 times, about 1, 5 times, about 1.6 times, about 1.7 times, about 1.8 times, about 1.9 times, about 1.95 times, or about 1.98 times the number of platelets needed to obtain three units of platelets. Alternatively or in addition, a unit of platelets containing more than the number of platelets required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets, may contain platelets in an amount that is 1.1 times up to about 1.98 times, about 1.1 times to about 1.95 times, about 1.1 times to about 1.9 times, about 1.15 times to about 1.98 times multiple, about 1.15 times to about 1.95 times, about 1.15 times to about 1.9 times, about 1.2 times to about 1.98 times, about 1 .2 times to about 1.95 times, about 1.2 times to about 1.9 times, about 1.25 times to about 1.98 times, about 1.25 times to about 1.95 times, about 1.25 times to about 1.9 times, about 1.3 times to about 1.98 times, about 1.3 times to about 1.95 times multiple, from about 1.3 times to about 1.9 times, from about 1.35 times

- 39 043840 to about 1.98 times, from about 1.35 times to about 1.95 times, from about 1.35 times to about 1.9 times, from about 1.4 times to about 1.98 times, about 1.4 times to about 1.95 times, about 1.4 times to about 1.9 times, about 1.5 times to about 1.98 times , from about 1.5 times to about 1.95 times, or from about 1.5 times to about 1.9 times the number of platelets required to obtain three units of platelets. Alternatively or additionally, a unit of platelets containing more platelets required to produce three units of platelets, but less than the number of platelets required to obtain four units of platelets, may contain platelets in an amount of about 105%, about 110%, about 115%, about 120%, about 125%, about 130%, about 135%, about 140%, about 145%, about 150%, about 155%, about 160%, about 165%, about 170%, about 175%, about 180 %, about 185%, about 190%, about 195%, or about 198% of the number of platelets required to obtain three units of platelets. Alternatively or additionally, a unit of platelets containing more platelets needed to produce three units of platelets but less than the number of platelets needed to produce four units of platelets may contain from about 110 to about 115 from about 120 from about 125 from about 130 from about 135 from about 140 platelets in quantities from about 110 to about 198%, from about 110 to about 195%, to about 190%, from about 115 to about 198%, to about 190%, from about 120 to about 198 %, to about 190%, from about 125 to about 198%, to about 190%, from about 130 to about 198%, to about 190%, from about 135 to about 198%, to about 190%, from about 140 to about 198%, to about 190%, from about 150 to about 198%, from about 115 from about 120 from about 125 from about 130 from about 135 from about 140 about 150 to to about 195%, to about 195%, to about 195%, up to about 195%, up to about 195%, up to about 195%, about 195%, or from about 150 to about 190% of the number of platelets required to obtain three units of platelets.

In some or all of the above-described embodiments, when the unit contains more than the number of platelets needed to obtain a specific (e.g., target, desired) number of platelet units (e.g., one unit of platelets, two units of platelets, three units of platelets), the number of platelets , greater than required to obtain a specific number of units, refers to a portion containing a number of platelets greater than the quantity required to obtain a specific number of units after applying a factor to any losses of platelets from processing, sampling (e.g., sampling for testing) and/or inactivation of pathogens. In some or all of the above-described embodiments, when the unit contains less than the number of platelets needed to obtain a specific (e.g., target, desired) number of platelet units (e.g., one unit of platelets, two units of platelets, three units of platelets), the number of platelets , less than required to obtain a specific number of units, refers to a portion containing a number of platelets less than the amount required to obtain a specific number of units after applying a factor to any losses of platelets from processing, sampling (e.g., sampling for testing ) and/or inactivation of pathogens. In some embodiments, the unit may contain a number of platelets greater than, but less than, required to obtain a specified number of platelet units (e.g., one platelet unit, two platelet units, three platelet units) prior to any of the processing, sampling, and/or pathogen inactivation than the number of platelets required to obtain the same number of platelet units after any of the processing, sampling, and/or pathogen inactivation.

Preparation of platelet units.

In some aspects, the present invention provides methods typically associated with producing multiple platelet units, such as, for example, multiple platelet units or two or more therapeutic platelet units. For example, in one aspect, the present invention provides a method of obtaining a plurality of platelet units suitable for infusion, comprising a) collecting a first portion of platelets by apheresis from a first donor, b) collecting a second portion of platelets by apheresis from a second donor, c) pooling a portion of platelets from a first donor. a donor and a portion of a second donor's platelets to produce a pooled platelet preparation; and d) dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic doses, therapeutic dosage units), each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total the number of platelet units that can be obtained from the first platelet unit and the second platelet unit without combining the first and second platelet units.

In another aspect, the present invention also provides a method for obtaining a plurality of platelet units suitable for infusion, comprising a) maintaining a storage log of collected apheresis platelet preparations, wherein the storage log contains for each platelet preparation a unique identifier, donor blood type, time of donation, and platelet count. in the preparation, b) identification of an available donor suitable for apheresis platelet donation,

- 40 043840

c) selecting from the storage log at least one platelet preparation into storage for combination with platelets collected from an existing donor, d) collecting a new portion of platelets by apheresis from an existing donor, e) combining at least one selected platelet preparation and a new portion of platelets for obtaining a pooled platelet preparation; and f) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from at least one selected preparation and a new portions of platelets without combining at least the first selected drug and a new portion of platelets.

In another aspect, the present invention also provides a method of producing two or more therapeutic platelet dosage units, comprising a) combining two or more donor platelet units obtained by apheresis to form a pooled platelet composition, b) subjecting the pooled platelet composition to a pathogen inactivation process, and c ) dividing the combined platelet composition into two or more therapeutic platelet dosage units, each in a separate container. In some embodiments, the therapeutic platelet dosage unit after step c) is greater than the number of therapeutic platelet dosage units that can be obtained from two or more apheresis-derived platelet donor units individually, without combining the two or more donor units.

In another aspect, the present invention provides a method for collecting a portion of platelets by apheresis from a donor, comprising a) maintaining a storage log of collected apheresis platelet preparations, wherein the storage log contains for each platelet preparation a unique identifier, the blood type of the donor, the date of donation, and the number of platelets in the preparation , b) identifying a donor suitable for apheresis platelet donation, c) selecting from the storage register one or more platelet preparations suitable for combination with the new platelet portion collected by apheresis from the donor, d) determining the target volume of the new platelet portion, whereby the target volume optimizes the number of platelet units that can be obtained from a combination containing a new supply of platelets and one or more selected platelet preparations; and f) collecting the target volume of new platelets by apheresim from the donor. In some embodiments, the method further includes f) combining one or more selected platelet preparations and a new portion of platelets to form a pooled platelet preparation, and g) dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic dosage units), each in a separate container. In some embodiments, the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from the one or more selected platelet preparations and the new platelet unit without combining the one or more selected platelet preparations and the new platelet unit.

In another aspect, the present invention provides a computerized method for optimizing platelet units (eg, platelet units for infusion), comprising, in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of a platelet unit; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; determination based on the search results of the volume of platelet portion; and providing a specific platelet unit volume that optimizes platelet units (eg, platelet units for infusion). In some embodiments, optimizing platelet units includes optimizing the number of platelet units that can be obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing excess platelets in a platelet unit (eg, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing or removing excess platelets (eg, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes improving or increasing the number of platelet units obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes increasing the efficiency of obtaining platelet units (eg, depending on the process for obtaining platelet blocks prior to optimization). In some embodiments, optimizing platelet units includes obtaining a target value (eg, number) of platelets per platelet unit. In some embodiments, at least one of the platelet unit and the plurality of platelet preparations comprises apheresis-derived platelets. In some embodiments, the platelet unit comprises platelets that are currently being collected from a donor or platelets that are to be collected from a donor. In some embodiments, one or

- 41 043840 more properties of the platelet unit include: blood type, time of donation (for example, date, time, date and time), number of platelets per unit volume and, if necessary, the maximum volume of the platelet unit. In some embodiments, the blood type value includes one of: A, B, AB, or O.

In some embodiments, platelet unit optimization may be performed using quantitative approaches. For example, using a quantitative approach, a search for multiple values associated with samples of multiple platelet preparations can be performed against stored platelet preparation data. In some examples, the stored platelet product data may be dynamic, such that it continuously changes as new units are received from donors (eg, new platelet units) and platelet products (eg, old platelet units) are no longer available or suitable for use in optimization platelet units (eg, were used for infusion, became expired). In some embodiments, platelet unit optimization is performed for each platelet unit (eg, for a new platelet unit). In some embodiments, platelet unit optimization is performed at time intervals, such as, for example, an interval of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 24 , 36, 48, 60, 72, or 96 hours. In some embodiments, the quantitative approach may use regression and/or time series analysis to forecast or predict available platelet products to optimize platelet units. Examples of time series analysis include autoregressive integrated moving average, the Holt-Winter family of exponential smoothing models, neural network models, and the like.

In some embodiments, platelet unit optimization may be performed using qualitative approaches. For example, using a qualitative approach, searching for multiple values associated with samples of multiple platelet preparations can be performed using expert judgment or assumptions to control with or without the entire actual platelet preparation data. A qualitative approach allows platelet optimization in situations where the entire platelet preparation record may not be available or may only be partially available. Assumptions can be made using empirical data from platelet preparations and/or linear or nonlinear regression models. Various models that can be used to optimize platelet units include, for example, exponential smoothing model (exponentially reduces the weight of past data), autoregressive, moving averages, autoregressive average, or Box-Jenkins predictive models (uses past variable behavior to select the best forecasting model).

In some embodiments, directing a search for a plurality of values associated with samples of a plurality of platelet preparations includes obtaining one or more search criteria using one or more retrieved values associated with one or more properties of a platelet unit; instructing to search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria and obtaining one or more candidate samples of platelet preparations from the samples of the plurality of platelet preparations, one or more candidate samples of platelet preparations having values that satisfy one or more search criteria. In some embodiments, the search criteria include one or more threshold conditions of one or more of: blood type, time of donation, platelet volume, and platelet count per unit volume. In some embodiments, obtaining one or more potential platelet preparation samples includes filtering samples of a plurality of platelet preparations based on one or more search criteria. In some embodiments, the representations of multiple platelet preparations include at least one of: platelet preparations being stored in a platelet preparation store, platelet preparations being currently collected from a plurality of donors, and platelet preparations being collected from a plurality of donors.

Various search algorithms can be used to find multiple values associated with samples of multiple platelet preparations. The search algorithm retrieves information stored with data structures such as linked lists, arrays, search trees, hash tables, etc. The search algorithm may include one or more exhaustive search algorithms, heuristic search algorithm, simulated annealing, Taboo search, A commands, genetic programming, tree search algorithm (depth search, width search), combinatorial search (minimax algorithm, pruning alpha-beta), graph search algorithm (Dijkstra's algorithm, Kruskal's algorithm, nearest neighbor algorithm, Prim's algorithm) or the like. It will be understood that any desired algorithm can be used to perform searches for multiple values associated with samples of multiple platelet preparations.

In some embodiments, determining the volume of a platelet unit includes: obtaining one or more values corresponding to one or more potential samples of platelet preparations obtained from the search results; obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units; Determining, based on one or more values corresponding to one or more candidate samples of platelet preparations, and one or more criteria for platelet units, one or more platelet preparations for selecting from one or more candidate samples from a plurality of platelet preparations, and obtaining a platelet unit volume based on a specific platelet preparation. In some embodiments, providing the determined platelet unit volume includes at least one of: displaying the determined platelet unit volume on a computer system display; sending a notification indicating the determining volume of a portion of platelets; and providing a certain volume of platelet portions in the apheresis system. In some embodiments, the method further includes combining a portion of platelets and one or more platelet preparations selected from samples of a plurality of platelet preparations to produce a pooled platelet preparation. In some embodiments, the method further includes dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic platelet dosage units), each in a separate container.

In some embodiments, various sorting algorithms can be used to identify one or more platelet preparations. In some examples, the sort algorithm may include one or more of insertion sort, selection sort, merge sort, heapsort, quicksort, bubble sort, descending offset sort, comb sort, counting sort, grouping sort, radix sort, timsort algorithm, cubesort, binary tree sort, loop sort, patient sort, thread sort, etc. The sorting may be based on search results that include one or more samples of potential platelet products and based on one or more criteria for platelet units. The one or more criteria may include, for example, threshold conditions of one or more of: blood type, time of donation, volume, and platelet count per unit volume; and can provide optimization of platelet units. For example, the criteria may reduce the loss of platelet units. The sorting results may identify one or more platelet preparations to obtain platelet unit volume. For example, the triage results may identify a top list of platelet preparations that meet the criteria with an acceptable level of confidence (eg, a confidence level above a given threshold). Thus, platelet unit volume can be determined based on these platelet preparations identified by the sorting results.

In yet another aspect, the present invention provides a computerized method for optimizing platelet units (eg, platelet units for infusion), comprising, in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of the first drug platelets; indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations; selecting, based on the search results, a second platelet preparation from the samples of the plurality of platelet preparations; and providing a selected second platelet preparation, wherein the selected second platelet preparation allows optimization of platelet units (eg, platelet units for infusion). In some embodiments, optimizing platelet units includes optimizing the number of platelet units that can be obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing excess platelets in a platelet unit (eg, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes reducing or removing excess platelets (eg, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes improving or increasing the number of platelet units obtained (eg, from a unit of platelets and a plurality of platelet preparations, depending on the process of obtaining platelet units prior to optimization). In some embodiments, optimizing platelet units includes increasing the efficiency of obtaining platelet units (eg, depending on the process for obtaining platelet blocks prior to optimization). In some embodiments, optimizing platelet units includes obtaining a target value (eg, number) of platelets per platelet unit. In some embodiments, at least one of the first platelet preparation and the plurality of platelet preparations comprises platelets obtained by apheresis. In some embodiments, the first platelet preparation includes a platelet preparation stored in a platelet preparation inventory. In some embodiments, one or more properties of the first platelet preparation include: blood type, time of donation (eg, date, time, date and time), volume, and number of platelets per unit volume. In some embodiments, the blood type value includes one of: A, B, AB, or O.

- 43 043840

In some embodiments, directing a search for a plurality of values associated with samples of a plurality of platelet preparations includes obtaining one or more search criteria using one or more retrieved values associated with one or more properties of the first platelet preparation; indicating a search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria; and obtaining one or more potential platelet preparation samples from the plurality of platelet preparation samples, one or more potential platelet preparation samples having values that satisfy the one or more search criteria. In some embodiments, the search criteria include one or more threshold conditions of one or more of: blood type, time of donation, volume, and platelet count per unit volume. In some embodiments, obtaining one or more potential platelet preparation samples includes filtering samples of a plurality of platelet preparations based on one or more search criteria. In some embodiments, the representations of multiple platelet preparations include at least one of: platelet preparations are stored in a platelet preparation store, platelet preparations are currently being collected from a plurality of donors, and platelet preparations will be collected from a plurality of donors.

In some embodiments, selecting a second platelet preparation includes: obtaining one or more values corresponding to one or more potential platelet preparation samples obtained from the search results; obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units; and selecting, based on the one or more values corresponding to the one or more candidate platelet preparation samples, and the one or more criteria for the platelet units, a second platelet preparation from the one or more candidate platelet preparation samples. In some embodiments, providing the selected second platelet preparation includes at least one of: displaying the selected second platelet preparation on a computer system display; sending a notification providing the selected second platelet preparation; and providing identification of the selected second platelet preparation in the apheresis system. In some embodiments, the method further includes combining the first platelet preparation and the selected second platelet preparation to produce a combined platelet preparation. In some embodiments, the method further includes dividing the pooled platelet preparation into a plurality of platelet units (eg, therapeutic platelet dosage units), each in a separate container.

In any or all of the above aspects and/or embodiments, when two or more portions of platelets/platelet preparation are combined to form a combined platelet preparation, each of the portions of platelets/platelet preparations may contain an amount (e.g., number) of platelets that is similar or different from another, as above. For example, one of the platelet units (e.g., the first platelet unit) may contain a number of platelets less than needed to produce one unit of platelets, and another platelet unit (e.g., a second platelet unit) may contain more platelets than needed to obtain one unit of platelets, but less than the number of platelets needed to produce two units of platelets. Alternatively, one unit of platelets may contain fewer platelets than the number required to obtain one unit of platelets, and a second unit of platelets may contain more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three platelet units. Alternatively, one of the platelet units may contain less platelets than the number required to obtain one unit of platelets, and the other platelet unit may contain more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets. Alternatively, one of the platelet units may contain more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the other unit of platelets may contain more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets (see, for example, Fig. 1). Alternatively, one of the platelet units may contain more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the other unit of platelets may contain more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets (see, for example, Fig. 3). Alternatively, one of the platelet units may contain more platelets than the number needed to obtain one unit of platelets but less than the number of platelets needed to obtain two units of platelets, and the other unit of platelets may contain more platelets than the number needed to

- 44 043840 obtaining three units of platelets, but less than the number of platelets required to obtain four units of platelets (see, for example, Fig. 6). Alternatively, one of the platelet units may contain more platelets than the number needed to obtain two units of platelets but less than the number of platelets needed to obtain three units of platelets, and the other unit of platelets may contain more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets (see, for example, Fig. 2). Alternatively, one of the platelet units may contain more platelets than the number needed to obtain two units of platelets but less than the number of platelets needed to obtain three units of platelets, and the other unit of platelets may contain more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets (see, for example, Fig. 5). Alternatively, one of the platelet units may contain more platelets than the number needed to obtain three units of platelets but less than the number of platelets needed to obtain four units of platelets, and the other unit of platelets may contain more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets (see, for example, Fig. 4).

The present invention also contemplates that in any or all aspects and/or embodiments, the pooled platelet preparation may contain more than two portions of platelets/platelet preparations (eg, a third portion of platelets, a second new portion of platelets). For example, in some embodiments, the method further includes collecting a third portion of platelets by apheresis from a third donor, combining the third portion of platelets with the first portion of platelets and a second portion of platelets to produce a pooled platelet preparation, and dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container. wherein the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from the first platelet unit, the second platelet unit and the third platelet unit without combining the first, second and third platelet units. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. In some embodiments, the third portion of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets required to obtain four units of platelets.

In some embodiments, the method further includes identifying a second available donor suitable for platelet donation by apheresis, collecting a second new supply of platelets by apheresis from the second available donor, combining the second new supply of platelets with at least one selected drug and the new supply of platelets to obtain a pooled a platelet preparation and dividing the combined platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from the at least one selected platelet preparation and the new platelet unit; and a second new portion of platelets without combining at least one selected platelet preparation and a new portion of platelets and a second new portion of platelets.

In some embodiments, the method further includes collecting a third portion of platelets by apheresis from a third available donor, combining the third portion of platelets with at least one selected drug and a new portion of platelets to produce a pooled platelet preparation, and dividing the pooled platelet preparation into a plurality of platelet units, each in separate container, wherein the plurality of platelet units contains a greater number of platelet units than the total number of platelet units that can be obtained from the at least one selected platelet preparation and the new platelet unit and the third platelet unit without combining the at least one selected platelet preparation and the new portions of platelets and a third portion of platelets. In some embodiments, the method further includes subjecting at least one selected platelet preparation, a new platelet batch, and/or a third platelet batch to a pathogen inactivation process.

In some of the above embodiments, the pooled platelet preparation contains platelets only from donors (eg, first donor, second donor, third donor) of the same ABO blood type. In some of the above embodiments, the pooled platelet preparation contains platelets only from donors (eg, first donor, second donor, third donor) of the same ABO blood type and Rh factor.

- 45 043840

In general, when combining two or more units of platelets and/or platelet preparations, it is preferable that the units of platelets and/or platelet preparations be obtained from units relatively close in time, such as, for example, obtained within about 24 hours, within about 18 hours, within about 12 hours, or within about 6 hours of each other. Thus, in some embodiments, the time of donation (eg, date, time, date and time) may be important information that must be recorded and/or associated with platelet donation and/or platelet receipt. The donation time may, in certain embodiments, indicate the start time of the apheresis platelet collection and/or the time of completion of the apheresis platelet collection. In addition, the donation time may be, for example, an exact time (e.g., to the nearest minute) or a time rounded to an increment of time, such as 15 minutes in advance or 1 hour in advance, or time within a time range such as 15 minutes an interval or period of time or a 1-hour interval or period of time. In some of the above embodiments, platelet units and/or platelet preparations are collected within less than about (e.g., within) 24 hours, less than about 22 hours, less than about 20 hours, less than about 16 hours, less than about 12 hours, less than about 10 hours, less than about 8 hours, less than about 6 hours, less than about 5 hours, less than about 4 hours, less than about 3 hours, less than about 2 hours or less than about 1 hour. In some embodiments, the second batch of platelets is collected at approximately the same time (eg, overlapping collection time) as the first batch of platelets. In some embodiments, platelet units and/or platelet preparations are collected at approximately the same time (eg, overlapping collection times). In some embodiments, platelet units and/or platelet preparations are collected over a period (e.g., the same period) of about 24 hours, about 22 hours, about 20 hours, about 16 hours, about 12 hours, about 10 hours, about 8 hours h, about 6 h, about 5 h, about 4 h, about 3 h, about 2 h or about 1 h.

The pooled platelet preparation in any of the above embodiments may contain, for example, at least about 5.0x1011, at least about 5.5x1011, at least about 6.0x1011, at least about 6.5x1011, at least about 7.0x1011, at least about 7.5x1011, at least about 8.0x1011, at least about 8.5x1011, at least about 9.0x1011, at least about 9.5x1011, at least about 10, 0x1011, at least about 10.5x1011, at least about 11.0x1011, at least about 11.5x1011, at least about 12.0x1011, at least about 12.5x1011, at least about 13.0x1011, at least about 13.5x1011, at least about 14.0x1011, at least about 14.5x1011, or at least about 15.0x1011 platelets. In some embodiments, the pooled platelet preparation may contain, for example, less than about 16.0x1011, less than about 15.0x1011, less than about 14.0x1011, less than about 13.0x1011, or less than about 12.0x1011 platelets. In some embodiments, the pooled platelet preparation may contain, for example, about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011, about 7.5x1011, about 8.0x1011, about 8. 5x1011, about 9.0x1011, about 9.5x1011, about 10.0x1011, about 10.5x1011, about 11.0x1011, about 11.5x1011, about 12.0x1011, about 12.5x1011, about 13.0x1011, about 13, 5x1011, about 14.0x1011, about 14.5x1011 or about 15.0x1011 platelets.

Platelet Processing and Processing Units and Kits Processing of platelets as described herein may involve the use of a blood product container or blood product bag systems that are well known in the art. In general, such systems may contain more than one plastic container, typically plastic bags, with the bags being integrally connected by plastic tubing. Some of the containers described herein include those plastic bags that are known for storing and processing blood products, including platelet products. Blood bags can generally be designed to hold various volumes of fluid, including, but not limited to, volumes from 50 ml to 2 L, for example up to 350 ml capacity, up to 450 ml capacity, up to 500 ml capacity, up to 1 L capacity, capacity up to 1.5 l or capacity up to 2 l. It is understood that when the method refers to a bag, it includes any such plastic bags used in the handling of blood products. If such bags are called a pool bag, a mixing bag, a removal bag, a product bag, a storage bag, or a lighting bag, it will be understood that these bags are typical blood product processing bags, or similar in nature to such bags. Plastic bags suitable for use in accordance with this invention include, for example, those containing PL2410, as well as other suitable plastics known in the art. Plastic bag materials include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics and the like.

As described herein, where the presence of a tube is described as a connection, for example two packages, for example, for combining and/or a set for processing, it is understood that the tube may be connected at some point between them with another connection component between the two packages . For example, a disposal bag connected to a food bag by a tube contains in place at

- 46 043840 tube fastenings, filter between two bags, i.e. the tube is separated by a filter so that fluid flows from one bag to the other through the tube and filter. In one example, the tube connecting the disposal bag and the product bag may include a filter for removing any particulate matter from the fluid flowing from the disposal device into the product bag, i.e. the tube is split or interrupted by a filter between packets. These filters are designed to remove any small particles that may be removed from the removal device while still allowing platelets to pass through the filter. A tube between the bags allows liquid to flow from one bag to another, which can be blocked to prevent flow until needed, for example, as part of a treatment, liquid in one bag can be blocked from flowing into the next bag until needed. until it is needed for the next step in the process. Since such an openable seal, such as a clip, plug, valve, or the like, is contained in or on the pouch connecting tube, the pouches on which the clip, plug, valve, or the like is located. can be selectively opened as needed, for example to transfer liquid from one bag to another. In some embodiments, the tubing between the bags contains a rupture seal, such as a rupture valve, once the rupture seal is broken, the blood product solution is allowed to flow between the bags through the pipe. It is understood that the breakable seal is contained in the connection between the containers so that the sterility of the system is maintained. It is also understood that the tube containing the filter or rupture seal comprises, at a point where the tube may be interrupted by the filter or seal, for example, a tube extends from one bag and is connected to the filter or seal (the incoming portion of the tube), and the tube extends from the other part of the filter or seal to another package (outgoing part of the tube). In such a configuration, fluid flows from the first package through the inlet portion of the tube, through the filter or seal, and through the outlet portion of the tube and into the other package.

Different bags in the blood product bag system can be used for different stages of the process (see, for example, FIGS. 7, 8). For example, a pouch system to be used to inactivate pathogens in a platelet preparation may comprise a container with a pathogen-inactivating compound contained within, a pouch for receiving a platelet unit (e.g., a unit of platelets), and a pathogen-inactivating compound (e.g., a light pouch) , a platelet unit illumination bag, if the pathogen inactivation method includes illumination (for example, an illumination bag and typically the same platelet unit receiving bag and a pathogen inactivating compound), a pathogen inactivating compound removal bag, and/ or by-products thereof from a processed platelet unit (eg, a removal bag, a compound adsorption device - CAD), and one or more bags for containing the final platelet product, i.e., for example, a therapeutic dosage unit that has a concentration of an inactivating compound and/or its by-products, reduced to a desired concentration that is ready for use or can be stored for later use (eg, as a grocery bag, storage bag). Each bag in the system is usually made of plastic. For example, a container for containing a solution of a pathogen-inactivating compound can be made of a suitable plastic such as PL2411 (Baxter Healthcare) or other plastics such as polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, and the like. This container is also wrapped in a material that is impervious to light at a wavelength that activates a photoactivatable pathogen-inactivating compound (eg, a suitable plastic such as PL2420, Baxter Healthcare). The illumination package for a photoactivatable pathogen-inactivating compound requires a transparent, durable thermoplastic material that is translucent to light of a selected wavelength. Suitable plastics that are translucent to light in the UVA wavelength range include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, or other mixtures of thermoplastic polymers. Such suitable plastics include PL2410 (Baxter Healthcare) and PL732 (Baxter Healthcare). Similar materials can be used to make the disposal bag and food bag. Product bags include, for example, those made from PL2410. Suitable pouch materials are discussed, for example, in PCT Publication No. WO 2003/078023 and US Pat. No. 7,025,877, the disclosures of which are incorporated herein by reference as they relate to such pouch materials and related materials. In all cases, the materials used in the preparation of the processing kit must be sterilizable by known methods, such as steam and gamma or electron beam radiation used to ensure the sterility of the processing kit. While these are exemplary pouch materials described herein, the methods are applicable to methods using any suitable pouch material that would be readily available to one of ordinary skill in the art and can also be used with containers other than pouches. The bags used for illumination, removal and storage are also designed to allow gases such as oxygen and carbon dioxide to move in and out of the blood bag so that the platelets in them have sufficient oxygen and carbon dioxide levels during processing and storage.

Some aspects of the present invention relate to treatment kits. The processing kits of the present invention may find use, among other things, in the preparation of multiple platelet units suitable for infusion, for example, as described herein. Any of the exemplary components, such as bags and tubes described above, may find use in treatment kits according to the present invention.

In some embodiments presented herein, processing units are used to produce multiple platelet units suitable for infusion. In some embodiments, the processing units include a first container that contains a pathogen inactivation compound (PIC) and is suitable for combining two or more portions of platelets with the PIC; a second container connected to the first container, within which two or more units of platelets mixed with CIP can be photochemically inactivated (e.g., as above) under sterile conditions (in some embodiments, the volume of the two or more units of platelets is sufficient to produce multiple units platelets); a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions (eg, to reduce the concentration of a pathogen-inactivating compound); and two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions. In some embodiments, the containers are connected by a sterile fluid path containing a tube (eg, sterile tubing). Thus, the processing units are configured to provide a plurality of pathogen-inactivated platelets suitable for infusion, such as, for example, a plurality of platelet units containing a greater number of platelet units than the total number of platelet units, which can be obtained from two or more portions without pooling two or more platelets. In some embodiments, the volume of one or more platelet units is sufficient to produce a plurality of platelet units such that the processing units are configured to process a plurality of pathogen-inactivated platelet units suitable for infusion into a subject. In some such embodiments, the UAS of the present invention comprises a container (eg, a UAS container, a bag) containing two or more UAS plates (eg, plates containing adsorbent particles). In some embodiments, the treatment unit comprises three or more (e.g., three) third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to three or more more than a third of the container under sterile conditions. In some embodiments, the processing units are suitable (eg, configured) for sterile communication with one or more additional containers that are suitable for containing one or more units of platelets (for example, the content includes combining two or more units of platelets), wherein after connecting the additional container(s) to the processing unit, one or more of the platelet portions can be transferred from the additional container to the processing unit under sterile conditions. For example, in some embodiments, the processing units include a first container suitable for sterile connection with a secondary container. In such a processing unit comprising a first container suitable for sterile connection to the additional container, after connecting the additional container to the first container, one or more portions of platelets can be transferred from the additional container to the first container under sterile conditions. In some embodiments, the processing units comprise an additional container suitable for housing one or more platelet units (e.g., wherein the contents include combining two or more platelet units), wherein the additional container is connected to the first container such that the one or more platelet units can be transferred from the additional container to the first container under sterile conditions. For example, an additional container may be suitable for housing a portion of platelets obtained by apheresis. In some embodiments, the additional container is suitable for sterile connection with the second additional container. In some embodiments, the processing units comprise a plurality of additional containers coupled to each other, wherein at least one of the additional containers is coupled to the first container and wherein portions of platelets may be mixed or combined together in at least one of the additional containers. For example, additional containers may be suitable for mixing platelets from apheresis units from multiple donors.

Further non-limiting examples of processing setups are shown in FIGS. 7 and 8. An exemplary processing setup 700 is shown in FIG. 7. In some embodiments, installation 700 includes an optional package 702 containing donor platelets. Treatment unit 700 includes a container 704 (e.g., a first container) that contains a pathogen inactivating compound (PIC, e.g., psoralen) and is sterilely connected to an additional container (e.g., a pouch) 702 (e.g., an additional container) and connected to a container (eg, bag) 706 to enable provision of the donor platelets to the SIP and sterile transfer of the donor platelets to the photochemical inactivation container 706 (eg, a second container). Processing unit 700 further includes a UAS (eg, UAS container, UAS bag) 708 connected to the container 706 via sterile tubing 720, allowing the transfer of donor platelets after photochemical inactivation into the UAS. The UAS 708 contains two plates, 710 and 712, each of which removes or reduces the concentration of a pathogen-inactivating compound. Advantageously, this makes it possible to inactivate the pathogen in a larger number or volume of donor platelets. For example, in some embodiments, 710 and 712 may comprise adsorbent particles contained in a pouch and/or matrix (eg, as described below) that bind and/or otherwise adsorb a pathogen-inactivating compound. Processing unit 700 further includes sterile tubing 722, a three-way adapter 724, and three additional sterile tubing (e.g., tubing 726) that connects UAS 708 to platelet unit containers (e.g., bags) 714, 716, and 718 (e.g., three-thirds containers). Advantageously, this configuration allows increased numbers of platelet units (eg, in bags 714, 716, and 718) to be obtained from donor platelets (eg, if donor platelets 702 are derived from apheresis units).

An alternative configuration for processing unit 700 is shown in FIG. 8. Instead of being sterilely connected to a bag 702 containing donor platelets, container 704 is sterilely connected to two containers 730a and 730b (eg, first and second additional containers) containing donor platelets (eg, first donor platelets, second donor platelets). 730a and 730b are sterilely connected to each other (eg, for pooling) via sterile tubing 732. Advantageously, this configuration provides a pooled platelet preparation that can be subjected to pathogen inactivation and subsequently separated into more individual platelet units (eg, 714, 716, and 718).

Some aspects of the present invention also apply to kits. For example, the present invention provides a kit comprising (a) a processing unit (e.g., the aforementioned processing unit) and (b) instructions for operating the processing unit for producing a plurality of platelet units from two or more portions of platelets, each of the portions of platelets is pathogen-inactivated and suitable for infusion into a subject, wherein the plurality of platelet units contains a greater number of platelets than the number of platelets that can be obtained from two or more units of platelets without combining two or more units of platelets, and wherein the processing unit comprises 1) a first container that contains a pathogen inactivation compound (PIC) and is suitable for combining two or more portions of platelets with a PIC; 2) a second container connected to the first container, within which two or more portions of platelets mixed with SIP can be photochemically inactivated under sterile conditions, the volume of the two or more portions of platelets being sufficient to produce multiple units of platelets; 3) a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions; and 4) two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions to provide multiple units platelets. In some embodiments, the kit contains instructions for operating a processing unit for producing a plurality of platelet units from two or more apheresis platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject, wherein the plurality of platelet units contains a larger number of platelets than the number of platelets that can be obtained from two or more apheresis platelet units without combining two or more apheresis platelet units. In some embodiments, the kit contains three or more (e.g., three) third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the three third containers in under sterile conditions to provide multiple platelet units.

In some embodiments, the first container is suitable for sterile connection with an additional container suitable for housing one or more of two or more units of platelets (for example, units of platelets obtained by apheresis), such that one or more units of platelets of the additional container can be transferred from additional container into the first container under sterile conditions. In some embodiments, the additional container is suitable for sterile connection with the second additional container. In some embodiments, the second additional container contains one or more of two or more

- 49 043840 units of platelets, and wherein the additional container is suitable for sterile connection with the second additional container, so that one or more units of platelets of the second additional container can be transferred from the second additional container to the additional container under sterile conditions. In some embodiments, the platelet units in the plurality of platelet units comprise a therapeutic dose of platelets.

In some embodiments, instructions for use of a multiunit platelet processing kit from two or more platelet units provide a minimum and/or maximum platelet count (eg, a combined platelet count) from two or more platelet units suitable for combining with a CIP. In some embodiments, instructions for use of a kit for processing multiple platelet units of two or more platelet units provide a minimum and/or maximum volume (eg, a combined volume) for two or more platelet units suitable for combining with the SIP. In some embodiments, the minimum platelet count is about 4.5x1011, about 5.0x1011, about 5.5x1011, about 6.0x1011, about 6.5x1011, about 7.0x1011 platelets. In some embodiments, the maximum platelet count is about 15.0x1011, about 14.0x1011, about 13.0x1011, about 12.0x1011, about 11.0x1011 platelets. In some embodiments, the minimum platelet count is about 4.0x1011 platelets, the maximum platelet count is about 13.0x1011 platelets. In some embodiments, the minimum platelet count is about 5.0x1011 platelets, the maximum platelet count is about 12.0x1011 platelets. In some embodiments, the minimum platelet count is about 6.0x1011 platelets, the maximum platelet count is about 12.0x1011 platelets. In some embodiments, the minimum platelet volume is about 360 mL, about 380 mL, about 400 mL, about 420 mL, about 440 mL, about 460 mL, about 480 mL, or about 500 mL. In some embodiments, the maximum platelet volume is about 750 ml, about 700 ml, about 675 ml, about 650 ml, about 625 ml, or about 600 ml. In some embodiments, the minimum platelet volume is about 400 mL and the maximum platelet volume is about 700 mL. In some embodiments, the minimum platelet volume is about 420 mL and the maximum platelet volume is about 650 mL. In some embodiments, the minimum platelet volume is about 440 mL and the maximum platelet volume is about 625 mL.

Inactivation of pathogens.

Blood products, including platelet-containing blood products, may contain pathogens or may be contaminated with pathogens during processing. Thus, it is desirable to subject such blood products to a pathogen inactivation process to reduce the risk of transfusion-transmitted diseases. Various processes and methods have been analyzed to reduce the risk of transmission of transfusion diseases in blood products containing platelets. In addition to screening and detection of pathogens and subsequent disposal of contaminated blood products, processes are available that include treatments to inactivate pathogens (ie, pathogen inactivation) that may be present. Ideally, this process results in the inactivation of a wide range of pathogens, such as viruses, bacteria and parasites, that may be present in the blood product. In some preferred embodiments, pathogen inactivation methods require adding an amount of a pathogen inactivating compound to the platelet preparation (eg, to treat the platelet preparation). For example, inactivation of pathogens may involve adding a small molecule compound that inactivates various pathogens, with a preferred method including adding a photosensitizer that, when activated by illumination using light of suitable wavelengths, will inactivate various pathogens that may be present. Two preferred methods that are commercially available involve adding amotosalen or riboflavin to platelets followed by illumination with ultraviolet light. Other methods include illumination with ultraviolet light without the addition of a photosensitizer, as well as illumination with other photoactive compounds, including psoralen derivatives other than amotosalen, isoalloxazines other than riboflavin, alloxazines, dyes such as phthalocyanines, phenothiazine dyes (eg, methylene blue, Azur-B , azure-C, thionine, toluidine blue), porphyrin derivatives (eg, dihematoporphyrin ester, hematoporphyrin derivatives, benzoporphyrin derivatives, alkyl-substituted sapphirin) and merocyanine 540 (Prodouz et al., Blood Cells, 1992, 18(1):101-14 ; Sofer, Gail, BioPharm, August 2002). Other pathogen inactivation systems include, for example, those described in PCT publications WO 2012/071135; WO 2012/018484; WO 2003/090794; WO 2003/049784; WO 98/18908; WO 98/30327; WO 96/08965; WO 96/39815; WO 96/39820; WO 96/40857; WO 93/00005; US Patent Application No. US 20050202395 and US Patent Nos. 8,296,071 and 6,548,242, the disclosure of which is incorporated herein by reference as they relate to the inactivation of pathogens in blood products. In some embodiments, the pathogen-inactivating compound is a photoactive compound that inactivates

- 50 043840 pathogen selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen. When addition of a compound to platelets is used to inactivate pathogens, whether the method requires illumination or not, in some cases it is desirable to remove any residual pathogen inactivating compound or byproduct thereof.

The methods for inactivating pathogens and removing the pathogen-inactivating compound as described herein are applicable to any platelet preparations, regardless of whether the platelet preparations contain individual portions of platelets (eg, apheresis-collected platelets) or pooled platelet preparations. These methods typically provide a platelet preparation that is either about 85 to 100% plasma or has some platelet supplement solution, typically in the range of 50 to 95% platelet supplement solution, with the remainder effectively being plasma, i.e. e. plasma ranging from 5 to 50%. It should be understood that a solution of a pathogen inactivating compound may be added during a pathogen inactivating treatment since the pathogen inactivating compound is typically not combined in solid form but is dissolved in a solution (eg, amotosalen is an HCl salt dissolved in saline). Thus, in some cases, when a platelet preparation is designated as being about 100% plasma, it is understood that this means that the platelet supplement solution is not contained in the platelet unit. If such a platelet preparation of about 100% plasma is processed to inactivate pathogens, some volume of the pathogen inactivating compound solution will be included in the final product, as well as some volume of the anticoagulant used to collect the blood for platelet isolation. Although the plasma is partially diluted with any amount of anticoagulant and the solution that was used to contain the pathogen-inactivating compound, the resulting platelet preparation containing the pathogen-inactivating compound may be said to contain about 100% plasma or may be referred to as about 85 to 100% plasma (usually less than 5-15% of the volume will contain the solution used to deliver the pathogen inactivating compound). Platelet preparations can also be prepared using an amount of platelet supplement solution, which can, for example, be added after concentrating the platelets, removing a portion of the plasma from the supernatant, and adding the desired amount of platelet supplement solution to the platelet preparation. Platelet supplement is added to provide the desired percentage of platelet supplement solution. This platelet preparation is usually adjusted so that the plasma content is from 5 to 50%, with the remainder of the solution being a platelet supplement solution, i.e. 50 to 95% platelet supplement solution. When amounts of plasma and platelet supplement solutions are described, it is understood that, as with platelet preparations described as being within about 100% plasma, some volume of the solution containing the pathogen-inactivating compound may be included in the platelet unit containing the compound , inactivating pathogens. Although the solution was diluted partially with whatever amount of solution was used to contain the pathogen-inactivating compound, it is understood that, for example, a platelet preparation designated as containing 35% plasma and 65% platelet solution may refer to the relative amounts of plasma and platelet solution before adding the solution, containing a compound that inactivates pathogens.

Some pathogen inactivation methods may require the use of a removal device, e.g. devices for reducing the concentration of a pathogen-inactivating compound, such as a small organic compound, for example, a platelet-inactivating compound and its by-products, when producing platelets, while substantially maintaining the desired biological activity of the platelets. In some embodiments, the removal device is referred to as a compound absorption device (CAD) and may comprise a container (eg, a CAS container, a CAS bag) containing one or more materials, such as, for example, adsorbent particles, and which is suitable for in order to also contain a platelet preparation in which it is necessary to reduce the concentration of the pathogen-inactivating compound and its by-products. Such a removal device is usually intended for use in batch mode, i.e. the device is placed in contact with the plates and continues contact with the removal device, such as by shaking, allowing platelets to be substantially completely dissolved in contact with the removal device during contact, resulting in decreased levels of the pathogen inactivating compound. Such batch devices entail the use of an adsorbent particle that binds a pathogen-inactivating compound and can be used either by adding the adsorbent particles directly to a platelet container (eg, a bag) after illumination, or by transferring the platelets to a bag containing the adsorbent particles with subsequent illumination and further mixing of the platelets for a certain period of time while the platelet preparations are in contact with the removal device. Although loose adsorbent particles can be used as a removal device, such particles

- 51 043840 may be contained in a mesh bag, such as a polyester or nylon mesh bag, which allows the platelet solution to contact the adsorbent particles upon contact with the particles within the bag. Alternatively, the adsorbent particles may be immobilized in a matrix, wherein the immobilized matrix may be located directly in the blood bag used for batch disposal, or may be similarly located in a bag. In some cases, the removal device comprises porous adsorbent particles in an amount sufficient to reduce the pathogen-inactivating compound to a desired concentration, the adsorbent particles having an affinity for the pathogen-inactivating compound, it being understood that such adsorbent particles may be selected to better adsorb the compound or compounds to be removed with minimal impact on components that should not be removed or damaged by contact with the adsorbent particle. A variety of adsorbent particles are known, including typically those made from any natural or synthetic material capable of reacting with the compounds being removed, including particles made from natural materials such as activated carbon, silica, diatomaceous earth and cellulose, and synthetic materials. , such as hydrophobic resins, hydrophilic resins or ion exchange resins. Such synthetic resins include, for example, carbonaceous materials, polystyrene, polyacrylic, polyacrylic ether, cation exchange resin and polystyrene divinylbenzene. Detailed descriptions of such removal devices suitable for use in the methods described herein can be found in PCT Publications No. WO 96/40857, WO 98/30327,

WO 99/34914 and WO 2003/078023, the disclosure of which is incorporated herein by reference to the discussion of such devices for removing and adsorbent particles and other materials used to prepare such devices. Examples of adsorbent particles include, but are not limited to, Amberlite (Rohm and Haas) XAD-2, XAD-4, XAD-7, XAD-16, XAD-18, XAD-1180, XAD-1600, XAD-2000, XAD- 2010; Amberchrom (Toso Haas) CG-71m, CG-71c, CG-161m, CG161c; Diaion Sepabeads (Mitsubishi Chemicals) HP20, SP206, SP207, SP850, HP2MG, HP20SS, SP20MS; Dowex (Dow Chemical) XUS-40285, XUS-40323, XUS-43493 (also called Optipore V493 (dry form) or Optipore L493 (hydrated form)), Optipore V503, Optipore SD-2; Hypersol Macronet (Purolite) MN-100, MN-102, MN-150, MN-152, MN-170, MN-200, MN-202, MN-250, MN-252, MN-270, MN-300, MN -400, MN-500, MN-502, Purosorb (Purolite) PAD 350, PAD 400, PAD 428, PAD 500, PAD 550, PAD 600, PAD 700, PAD 900 and PAD 950. The material used to form the immobilized matrix is includes a low melting polymer such as nylon, polyester, polyethylene, polyamide, polyolefin, polyvinyl alcohol, ethylene vinyl acetate or polysulfone. In one example, the adsorbent particles immobilized in the matrix are in the form of a sintered medium. While it is understood that the methods and devices described herein cover removal devices known in the art, such methods and devices may be illustrated using a device for removing amotosalen-inactivated platelet product, as is commercially available. Such a removal device comprises Hypersol Macronet MN-200 adsorbent contained in a sintered matrix, the sintered matrix containing PL2410 plastic as a binder. In one embodiment, the removal device comprises Hypersol Macronet MN-200 adsorbent in a sintered matrix containing PL2410, with Hypersol Macronet MN-200 present in an amount of about 5-50 g, about 5-10 g, about 10-15 g, about 15-20 g, about 20-25 g, about 25-30 g, about 30-35 g, about 35-40 g, about 40-45 g or about 45-50 g dry weight equivalent.

Because different resins may require different processing when used to make removal devices useful in the methods and devices described herein, a comparison of the amounts of adsorbent resins described herein, unless otherwise noted, is a comparison of the dry weight of the resin . For example, resins are dried to <5% water before processing, and the adsorbent dry weight equivalent is used to compare the amount of resin used. For example, Hypersol Macronet MN-200 is treated to stabilize the adsorbent or what is commonly referred to as wetting the adsorbent so that it can be directly used in contact with the platelet unit. Such a wettable sample may contain, for example, about 50% glycerol or other suitable wetting agent. In some embodiments, the adsorbent resin is a polystyrene divinyl benzene resin. In some embodiments, the polystyrene divinyl benzene resin is Hypersol Macronet MN-200. In some embodiments, the adsorbent is contained in a sintered matrix, wherein the sintered matrix contains a PL2410 binder. In some embodiments, Hypersol Macronet MN-200 adsorbent is contained in a sintered matrix to provide a disposal device.

Platelet units.

The present invention also provides platelet units suitable for infusion (eg, infusion into a human subject), such as, for example, a platelet unit selected from a plurality of platelet units obtained by any of the methods of this disclosure. The platelet units (e.g., each platelet unit) in the plurality of platelet units contain a therapeutic dose (e.g., a therapeutic dosage unit) of platelets suitable for infusion

- 52 043840 to a human subject (for example, requiring platelet infusion). In some embodiments, the therapeutic dose contains a minimum amount (e.g., at least a minimum number) of platelets, as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accredited organization (e.g., a government agency, a regulatory agency, institution and/or accredited organization responsible for donated blood products (e.g. donated platelets)). In some embodiments, platelet units are obtained in the country of a government agency, regulatory body, institution, and/or accredited organization that defines therapeutic platelet dose criteria. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99% or more of the platelet units in a plurality of platelet units contain the minimum number of therapeutic dose platelets. In some embodiments, each of the platelet units in the plurality of platelet units contains a minimum number of therapeutic dose platelets. In some embodiments, the minimum platelet count in a therapeutic dose is at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about

2.5 x 1011 platelets, at least about 2.6 x 1011 platelets, at least about

2.7 x 1011 platelets, at least about 2.8 x 1011 platelets, at least about

2.9 x 1011 platelets or at least about 3.0 x 1011 platelets. In some embodiments, the platelet units in the plurality of platelet units comprise at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about

2.4 x 1011 platelets, at least about 2.5 x 1011 platelets, at least about

2.6 x 1011 platelets, at least about 2.7 x 1011 platelets, at least about

2.8 x1011 platelets, at least about 2.9x1011 platelets or at least about

3.0x1011 or more platelets. In some embodiments, each of the platelet units in the plurality of platelet units comprises at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets. In some embodiments, at least 75% of the platelet units in the plurality of platelet units contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about

2.5 x 1011 platelets, at least about 2.6 x 1011 platelets, at least about

2.7 x 1011 platelets, at least about 2.8 x 1011 platelets, at least about

2.9 x 1011 platelets or at least about 3.0 x 1011 or more platelets. In some embodiments, at least 80% of the platelet units in the plurality of platelet units contain at least about 2.0 x 1011 platelets, at least about 2.2 x 1011 platelets, at least about 2.4 x 1011 platelets, at least about 2 5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets . In some embodiments, at least 85% of the platelet units in the plurality of platelet units contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets. In some embodiments, at least 90% of the platelet units in the plurality of platelet units contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about

2.5 x 1011 platelets, at least about 2.6 x 1011 platelets, at least about

2.7 x 1011 platelets, at least about 2.8 x 1011 platelets, at least about

2.9 x 1011 platelets or at least about 3.0 x 1011 or more platelets. In some embodiments, at least 95% of the platelet units in the plurality of platelet units contain at least about 2.0 x 1011 platelets, at least about 2.2 x 1011 platelets, at least about 2.4 x 1011 platelets, at least about 2 or

- 53 043840 at least about 3.0 x 1011 or more platelets. In some embodiments, at least 98% of the platelet units in the plurality of platelet units contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets. In some embodiments, at least 99% of the platelet units in the plurality of platelet units contain at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets.

In another aspect, the present invention provides a therapeutic platelet dosage unit suitable for infusion into a subject comprising pooled apheresis platelets from two or more donors, wherein the pooled apheresis platelets have been treated with a pathogen-inactivating compound. In some embodiments, pooled apheresis platelets have been treated with a pathogen-inactivating compound prior to pooling. In some embodiments, pooled platelets obtained by apheresis were treated with a pathogen-inactivating compound after pooling. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen . In some embodiments, the pathogen inactivating compound is amotosalen. In some embodiments, platelets obtained by apheresis are obtained from donors of the same ABO blood type. In some embodiments, platelets obtained by apheresis are obtained from donors of the same ABO blood type and Rh factor. In some embodiments, a therapeutic platelet dosage unit contains at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2 .6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 2.4 x 1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 2.6x1011 platelets. In some embodiments, a therapeutic platelet dosage unit contains at least 3.0x1011 platelets. In some embodiments, the therapeutic platelet dosage unit contains a minimum amount (e.g., at least a minimum amount) of platelets, as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accredited organization (e.g., a government regulatory agency agency, institution and/or accredited organization responsible for donated blood products (eg, donated platelets)). In some embodiments, the therapeutic platelet dosage unit is obtained in the country of the government agency, regulatory body, institution, and/or accredited organization defining the criteria for the therapeutic platelet dosage unit.

This disclosure also provides a method of administering platelets to a subject in need thereof (eg, a human subject), comprising administering the aforementioned platelet unit or the aforementioned therapeutic platelet dosage unit to the patient. Systems In other aspects, the present invention provides computer-based methods and systems for optimizing platelet units for infusion. In fig. 9 illustrates an exemplary system 100 for optimizing blood infusion (eg, optimizing platelet units for infusion), consistent with some embodiments of the present invention. In some embodiments, optimization includes optimizing the number of platelet units that can be obtained, for example, from a unit of platelets and a plurality of platelet preparations (eg, a platelet preparation store), depending on the process for obtaining platelet units prior to optimization. In some embodiments, optimization includes reducing excess platelets in a platelet unit (eg, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimization includes reducing or removing excess platelets (eg, depending on the process for obtaining platelet units prior to optimization). In some embodiments, optimization includes improving or increasing the number of platelet units obtained, obtained from, for example, a platelet unit and a plurality of platelet preparations (eg, a platelet preparation store), depending on the platelet unit acquisition process prior to optimization. In some embodiments, optimization includes increasing the efficiency of obtaining platelet units (eg, depending on the process for obtaining platelet blocks prior to optimization). In some embodiments, optimization includes obtaining a target value (eg, number) of platelets per platelet unit.

As shown in FIG. 9, system 100 may include a computer system 101, input devices 104, output devices 105, devices 109, apheresis system 110, and blood collection system 111. It should be understood that one or more components of system 100 may be separate systems or may be integrated systems. systems. In some embodiments, the computer system 101 may include one or more central processing units (CPU or processor(s)) 102. The processor(s) 102 may include at least one data processor for executing software components to carry out user- or system-generated requests. . The user may include the person using the device, such as those included in this invention, or the device itself. The processor may include specialized processors such as integrated system (bus) controllers, memory management units, floating point units, graphics processors, digital signal processing units, etc. The processor may include a microprocessor such as an AMD Athlon, Duron or Opteron, an ARM application, embedded or ruggedized processors, IBM PowerPC, Intel's Core, Itanium, Xeon, Celeron or other processor lines, etc. Processor 102 may be implemented using mainframe, distributed processor, multi-core, parallel, network, or other architectures. In some embodiments, embedded technologies such as application specific integrated circuits (ASICs), digital signal processors (DSPs), field programmable gate arrays (FPGAs), etc. may be used.

The processor(s) 102 may be positioned in communication with one or more input/output (I/O) devices via an input/output interface 103. The I/O interface 103 may use communication protocols/methods such as, but not limited to, audio, analog, digital, mono acoustic, RCA, stereo, IEEE-1394, serial bus, universal serial bus (USB), infrared, PS/2, BNC, coaxial, component, composite, digital visual interface (DVI), high-definition multimedia interface ( HDMI), RF antennas, S-Video, VGA, IEEE 802.11 a/b/g/n/x, Bluetooth, cellular (e.g., Code Division Multiple Access (CDMA), High Speed Packet Access (HSPA+), Global System for Mobile communications (GSM), long-term development system (LTE), WiMax, etc.), etc.

Using the input/output interface 103, the computer system 101 can communicate with one or more input/output devices. For example, input device 104 may be an antenna, keyboard, mouse, joystick, (infrared) remote control, camera, card reader, fax machine, key, biometric reader, microphone, touch screen, touch pad, trackball, sensor (e.g. , accelerometer, light sensor, GPS, gyroscope, proximity sensor, etc.), stylus, scanner, storage device, transceiver, video device/source, visors, electric pointing devices, etc. Output device 105 may be a printer, facsimile machine, video display (eg, cathode ray tube (CRT), liquid crystal display (LCD), light emitting diode (LED), plasma, etc.), audio speaker, etc. In some embodiments, the transceiver 106 may be located in connection with the processor(s) 102. The transceiver may facilitate various types of wireless transmission or reception. For example, the transceiver may include an antenna operably coupled to the transceiver chip (e.g., Texas Instruments WiLink WL1283, Broadcom BCM4750IUB8, Infineon Technologies X-Gold 618-PMB9800, or the like), providing communication via IEEE 802.11a/b/g/ n, Bluetooth, FM, GPS, 2G/3G HSDPA/HSUPA, etc.

In some embodiments, the processor(s) 102 may be located in communication with the communications network 108 via a network interface 107. The network interface 107 may communicate with the communications network 108. The network interface 107 may use connection protocols, including, but not limited to, a direct connection protocol, Ethernet (Local Area Networking Standard) (e.g. 10/100/1000 Base T twisted pair), Transmission Control Protocol/Internet Protocol (TCP/IP), Relay Ring Protocol, IEEE 802.11a/b/g/n/x etc. The communications network 108 may include, but is not limited to, point-to-point, local area network (LAN), wide area network (WAN), wireless network (eg, using a wireless application protocol), the Internet, etc. Using network interface 107 and communications network 108, computer system 101 can communicate with devices 109. These devices can include, but are not limited to, personal computer(s), server(s), fax machines, printers, scanners, various mobile devices such as cell phones, smartphones (for example, iPhone from

- 55 043840

Apple, Blackberry, Android phones, etc.), tablet computers, e-readers (Amazon

Kindle, Nook, etc.), laptops, notebooks, game consoles (Microsoft Xbox, Nintendo DS, Sony PlayStation, etc.) or the like. In some embodiments, computer system 101 may itself implement one or more of these devices.

In some embodiments, using the network interface 107 and the communications network 108, the computer system 101 may communicate with the apheresis system 110, the blood collection system 111, or any other medical systems. Computer system 101 may communicate with these systems to obtain data for optimizing blood infusion (eg, optimizing platelet units for infusion). The computer system 101 may also be integrated with these imaging systems.

In some embodiments, processor 102 may be positioned in communication with one or more storage devices (e.g., RAM 113, ROM 114, etc.) via storage interface 112. The storage interface may be connected to storage devices, including, but not limited to, disks memory, removable disk drives, etc., using communication protocols such as Serial Data Interface (SATA), Integrated Storage Interface (IDE), IEEE-1394, Universal Serial Bus (USB), Fiber Channel, Interface small computer systems (SCSI), etc. The memory devices may further comprise a drum drive, a magnetic disk drive, a magneto-optical drive, an optical drive, a redundant array of independent disks (RAID), solid-state storage devices, flash devices, solid-state drives, etc.

Memory devices may store a collection of program or database components, including, but not limited to, operating system 116, user interface application 117, infusion algorithms 118, infusion data 119, criteria data 120, user/application data 121 (e.g., any variable data or records data discussed in this disclosure), etc. The operating system 116 may facilitate resource management and operation of the computer system 101. Examples of operating systems include, but are not limited to, OS X from Apple Macintosh, Unix, Unix-like system distributions (for example, Berkeley Software Distribution (BSD), FreeBSD, NetBSD, OpenBSD, and etc.), Linux distributions (for example, Red Hat, Ubuntu, Kubuntu, etc.), IBM OS/2, Microsoft Windows (XP, Vista/7/8, etc.), iOS from Apple, Android from Google, Blackberry OS, etc. The user interface 117 may facilitate the display, execution, interaction, manipulation, or operation of software components using text or graphical means. For example, user interfaces may provide computer interface elements on a display system operably connected to the computer system 101, such as cursors, icons, checkboxes, menus, scrollers, windows, widgets, etc. Graphical user interfaces (GUIs) may be used, including, but not limited to, Aqua of the Apple Macintosh operating system, IBM OS/2, Microsoft Windows (e.g. Aero, Metro, etc.), Unix X-Windows, web interface libraries ( for example ActiveX, Java, Javascript, AJAX, HTML, Adobe Flash, etc.) or the like.

In some embodiments, computer system 101 may implement infusion algorithms 118. Computer system 101 may also store infusion data 119 and criteria data 120. For example, memory 115 and/or a frame buffer (not shown) may be used to store infusion data 119.

In some embodiments, the computer system 101 may store user/application data 121, such as data, variables and parameters, as described in this disclosure, and a database 124. The database 124 may contain data associated with materials (e.g., platelet preparations) stored in a platelet storage facility (eg, platelet preparation storage facility). Database 124 may be internal or external to computer system 101. Such databases may be implemented as fault-tolerant, relational, scalable, secure databases such as Oracle or Sybase. Alternatively, such databases can be implemented using standardized data structures such as array, hash, linked list, structure, structured text file (eg XML), table or as object-oriented databases (eg using ObjectStore , Poet, Zope, etc.). Such databases may be aggregated or distributed, sometimes among various computer systems discussed above in this disclosure. It should be understood that the structure and operation of any computer or database component can be combined, combined, or distributed in any operating combination.

Disclosed embodiments describe systems and methods for optimizing blood infusion (eg, optimizing platelet units for infusion). The illustrated components and steps are provided to explain the illustrated exemplary embodiments, and it is expected that ongoing technological developments will change the way specific functions are performed. These examples are presented herein for purposes of illustration and not limitation. In addition, the boundaries of the functional building blocks have been arbitrarily defined herein for ease of description. Alternative boundaries may be defined as long as the specified functions and their

- 56 043840 relationships will be properly carried out. The alternatives (including equivalents, extensions, variations, deviations, etc., described herein) will be apparent to those skilled in the relevant art(s) based on the data provided herein. Such alternatives fall within the scope and spirit of the disclosed embodiments. In addition, the words containing, having, consisting of and including and other similar forms must be equivalent in meaning and open-ended in the sense that the item or items following one of these words is not an exhaustive enumeration of such item or items or is limited only the listed item or items.

It should be noted that, while references are made to specific computing paradigms and software tools herein, the computer program instructions, embodiments of which may be implemented, may correspond to any of a variety of programming languages, software tools, and data formats, and be stored in any type of volatile or a non-transitory, non-transitory computer-readable storage medium or storage device, and may be performed in accordance with a variety of computing models, including, for example, a client-server model, a peer-to-peer model, on a stand-alone computing device, or in accordance with a distributed computing model in which various functions can performed or used in different places. Additionally, references to specific algorithms in this document are provided as examples only. Suitable alternatives or more recent developments known to those skilled in the art may be used without departing from the scope of the subject matter of this invention.

Those skilled in the art will also appreciate that changes in form and details of the implementations described herein may be made without departing from the scope of the present invention. In addition, although various advantages, aspects and objects are described with reference to various implementations, the scope of the present invention should not be limited by reference to such advantages, aspects and objects. Rather, the scope of the present invention should be determined by reference to the appended claims.

The invention is further illustrated by the following examples, which should not be construed as limiting the invention in scope or spirit to the specific methods described therein.

Examples

Example 1. Apheresis platelet collection.

Donor(s) suitable for apheresis platelet donation were identified and platelets were collected using a validated device with apheresis collection procedures known in the art. More specifically, in one example, platelet portions were collected by apheresis using the AMICUS™ system (Fenwal, Inc., Lake Zurich, IL). Genetics, weight, height, hematocrit, and preliminary platelet count were determined for available donors, and donors were referred for single, double, or triple apheresis collection to obtain 1, 2, or 3 platelet units, each containing at least the number of platelets in accordance with applicable FDA regulatory standards. apheresis collections, adjusted for potential losses (eg, processing losses) and blood center split ranges, were >3.1 x 1011 platelets for single, >6.2 x 1011 platelets for double, and >9.6 x 1011 platelets for triple. Appropriate ranges for such divisions can also be represented, for example, as >3.1x1011 to <6.2x1011 platelets for a single, >6.2x1011 to <9.6x1011 platelets for a double, and >9.6x1011 to <12. 8x1011 platelets for triple.

In table Figure 1 shows the donor characteristics and target platelet collection (target platelet yield) to prepare the specified platelet quantities for each of the 12 donors. Generation of apheresis platelet units by standard methods as single, double, or triple targets resulted in 23 platelet units from 12 donors.

- 57 043840

Table 1

Apheresis platelet collections

Donor Floor Weight (pounds) Height (inches) pre-calculation Target output Products 1 M 185 7 5 375 10, 96 3 2 M 167 71 257 7.20 2 3 M 170 7 0 246 6, 38 2 4 AND 202 6 6 433 10.50 3 5 AND 165 63 309 7.80 2 6 M 210 7 0 309 8.75 2 7 M 175 72 205 5.21 1 8 AND 165 64 441 7.00 2 9 AND 135 67 220 4.50 1 10 m 212 7 3 234 8.00 2 eleven m 140 67 190 4.86 1 12 m 155 6 6 362 9, 15 2

Among these twelve donors, platelet collections for donors Nos. 6, 7, 11 and 12 may be categorized as extra-large collections, as provided in one embodiment of the present invention, in which each contains excess amounts of platelets, in which case more than 50% of platelets in excess of the number separating platelets, but less than the number of platelets, to achieve the next higher level of separation to obtain an additional unit of platelet product (eg, based on platelet units containing at least 3x1011). For example, donor #6, with 8.75x1011 platelets, exceeded the yield of >6.2x1011 for double collection, but it was less than 9.6x1011 platelets for triple collection (eg, very large double). Similarly, donor #11, with 4.86x1011 platelets, exceeded the yield of >3.1x1011 for a single collection, but it was less than >6.2x1011 platelets for a double collection (eg, very large single).

Example 2. Obtaining an increased number of platelet units.

As described in one embodiment of the present invention, the methods provided herein provide a method for producing multiple platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from the same apheresis portions of platelets without using the disclosed methods. More specifically, in one example, an increased number of platelet units are obtained from the 12 donors of Example 1 and Table. 1. After collection, the following pairs of platelet portions were combined:

Donors No. 7 and 11 each contain more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets.

Donors No. 6 and 12 each contain more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets.

After pooling pairs of platelet units, the pooled platelet preparations were divided into three platelet units (in cases No. 7 and 11) and five platelet units (in cases No. 6 and 12). Together with units (eg, non-combined units) from the remaining eight donors from the table. 1 these methods provided an increase in the number of platelet apheresis units, with 25 platelet units obtained compared to 23 platelet units that would have resulted (e.g.

- 58 043840 based on platelet units having 3x1011). Thus, an increase in platelet receipt of almost 9% is based on this description without additional donors or platelet units.

Likewise, alternative combinations of platelet units can be combined to achieve and increase the number of finished platelet units. For example, after collection, the following pairs of platelet portions were combined.

Donors No. 6 and 7 contained more platelets than the amount required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets, No. 7 contained more platelets than the amount required to obtain one unit of platelets, but less than the number of platelets needed to produce two units of platelets.

Donors No. 11 and 12 with No. 12 contained more platelets than the amount required to obtain two units of platelets but less than the number of platelets required to obtain three units of platelets, No. 11 contained more platelets than the amount required to obtain one unit platelets, but less than the number of platelets required to obtain two units of platelets.

After pooling pairs of platelet units, the pooled platelet preparations were divided into four platelet units (in cases Nos. 6 and 7) and four platelet units (in cases Nos. 11 and 12). Together with units (eg, non-combined units) from the remaining eight donors from the table. 1, these methods again provided an increase in the number of apheresis platelet units, with 25 platelet units obtained compared to the 23 platelet units that would have resulted (eg, based on platelet units having 3x1011). Analysis of a significantly larger data set of apheresis platelet units provides the opportunity to further highlight the improved acquisition of multiple platelet units, with significantly more platelet units being obtained in accordance with the methods of the present invention compared to existing conventional apheresis collection methods for preparing platelet units.

Example 3: Inactivation of pathogens.

The methods described in Example 2 may further include the step of inactivating the pathogen. More specifically, in one embodiment, apheresis-collected platelets are individually subjected to a pathogen inactivation process with a pathogen-inactivating compound using the commercially available INTERCEPT® Platelet Blood System (Cerus Corporation, Concord, Calif.) according to the manufacturer's instructions. After inactivation of pathogens in platelet units from donors 6, 7, 11, and 12, platelet units were pooled in pairs as above, and the pooled platelet preparations were divided into three platelet units. Each of the other eight platelet units was similarly subjected to a pathogen inactivation process, providing multiple pathogen-inactivated platelet units.

Alternatively, pooled platelet preparations were individually subjected to a pathogen inactivation process with a pathogen inactivating compound using the commercially available INTERCEPT® Platelet Blood System in conjunction with a processing unit such as that depicted in FIG. 7 or 8.

In another example, pools of two apheresis platelet batches (n=6) were prepared containing between approximately 10.2 x 1011 and 11.8 x 1011 platelets in approximately 623-648 ml of a 35% plasma platelet supplement/65% PAS-3 solution. Pooled apheresis platelets were subjected to photochemical pathogen inactivation with amotosalen and UVA using a processing kit as provided herein (see, e.g., FIGS. 7 and 8) to generate three platelet units, at least 3x1011 platelets from each from two apheresis donor portions. Units were assessed on day 7 post-donation for product dosing and maintenance of volume, pH, and in vitro platelet quality parameters (e.g., function) correlated with in vivo platelet survival and recovery (e.g., pH, lactate normalization, ATP, morphological assessment, ESC and HSR (Hypersensitivity Reaction) and found to meet EDQM (European Directorate for the Quality of Medicines and Healthcare) requirements and to be within the ranges for platelet units from single donors and to be pathogen inactivated using the commercially available INTERCEPT® Platelet Blood System .

Example 4 Obtaining a further increased number of platelet units.

The methods for obtaining platelets described herein can be further improved by analyzing increased collection of apheresis platelets from available donors. For example, in one embodiment, the maximum platelet yield is determined for the above twelve donors based on previously described donor characteristics. In addition to the previous target product and target products reproduced below from the table. 1, the maximum platelet yield is also shown in the following table. 2, as well as additional target maximum product quantities that can be achieved by collecting as many platelets as possible.

- 59 043840

table 2 Donor Floor Weight Height Pre-count Target exit Target products Maxi- small exit Max pro- duct 1 M 185 75 375 10.96 3 11.74 3 2 M 167 71 257 7.20 2 9.39 2 3 M 170 70 246 6, 38 2 8, 16 2 4 AND 202 66 433 10, 50 3 11.52 3 5 AND 165 63 309 7, 80 2 9, 09 2 6 M 210 70 309 8.75 2 11.56 3 7 m 175 72 205 5.21 1 7.21 2 8 and 165 64 441 7.00 2 9, 90 3 9 and 135 67 220 4.50 1 6, 05 1 10 m 212 73 234 8.00 2 9.49 2 eleven m 140 67 190 4, 86 1 5, 81 1 12 m 155 66 3 62 9, 15 2 9, 83 3

As shown in table. 2, four additional platelet units can be obtained by increasing the apheresis collection to the maximum number indicated, increasing the total number to 27 platelet units compared to 23 units with the previous collection values. In addition, as provided herein, many more platelet units can be obtained from the same twelve donors based on the maximum sets and methods described previously in Example 2. More specifically, after collection for maximum yield, the following pairs of platelet units were pooled :

Donors No. 9 and 11 each contain more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets.

Donors No. 2 and 5 each contain more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets.

After pooling pairs of platelet units, the pooled platelet preparations were divided into three platelet units (in cases No. 9 and 11) and five platelet units (in cases No. 2 and 5). Together with units (e.g., pooled units) from the remaining eight donors, these methods provided an increase in the number of apheresis platelet units, with 29 platelet units obtained compared to 23 platelet units from the pooled apheresis collection and production methods or 27 platelet units from the pooled apheresis collection at maximum yield (eg, based on platelet units having 3x1011). Analysis of a significantly larger data set of apheresis platelet units provides the opportunity to further highlight the improved acquisition of multiple platelet units, with significantly more platelet units being obtained in accordance with the methods of the present invention compared to existing conventional apheresis collection methods for preparing platelet units.

As described in Example 3, these platelet portions may be subjected to a pathogen inactivation process prior to pooling or, alternatively, after pooling by treating the pooled platelet preparation with a pathogen inactivation process.

- 60 043840

Example 5: Preparing platelet units from storage and new units.

This disclosure also provides further improved methods for producing multiple platelet units suitable for infusion. More specifically, in one embodiment, a storage log of platelet preparations collected via apheresis is maintained. Next table 3 illustrates the sample storage log for such platelet preparations and includes for each platelet preparation a unique identifier, the ABO blood type of the donor, the time of donation, and the number of platelets (x1011) in the preparation.

Table 3

Apheresis platelet storage

Identification kator Pre- ΆΒΟ date Time strictly count Platelet Products 15072347 IN July 23 2015 16:33 375 10.96 3 15072348 ABOUT July 23 2015 16:42 257 7.20 2 15072349 0 July 23 2015 16:55 246 6.38 2 15072201 A July 22 2015 10:42 433 10.50 3 15072202 15072203 AB A July 22 2015 July 22 2015 10:58 11:26 309 309 7.80 2 8.75 2 15072204 IN July 22 2015 11:32 205 5.21 1 15072205 ABOUT July 22 2015 11:48 441 7.00 2 15072206 AB July 22 2015 12:14 220 4.50 1 15072207 A 2 2 Jul i 2015 12:22 234 8.00 2 15072208 A 2 2 Jul i 2015 12:59 190 4.86 1 July 22 15072209 O 13:16 362 9.15 2 2015 An available type A blood donor suitable for apheresis platelet donation was identified and a storage platelet preparation (#15072208, extra large single) was selected from the storage register to be combined with platelets collected from the available donor. A new batch of platelets with a target platelet yield of 5.10 x 1011 (very large single) was collected via apheresis from an available donor and combined with the selected platelet preparation (e.g., over 6 hours), yielding a pooled platelet preparation containing approx.

- 61 043840

9.86x1011 platelets. The pooled platelet preparation is divided into three platelet units, which is a greater number of platelet units than the two platelet units that can be obtained from the selected platelet preparation and a new portion of platelets without pooling them, as provided in this disclosure. Likewise, additional new platelet units can be collected and pooled and combined with other platelet preparations, for example, a new very large single unit type A blood platelet in combination with platelet preparation 15072203 from storage and obtaining a pooled platelet preparation containing sufficient platelets to production of 4 units of platelets, a new very large double unit of blood with platelet type B blood for combining with platelet storage preparation 15072204 and producing a pooled platelet preparation containing enough platelets to form 4 units of platelets, and a new very large double unit of type O platelets for combining with platelet preparation 15072209 from storage to produce a combined platelet preparation containing a sufficient number of platelets to produce 5 platelet units to further increase the number of platelet units that can be obtained. For example, in the above scenario illustrated in this example, the 23 possible units from storage could be combined with four new units of platelets that would otherwise provide 6 new units of platelets using conventional methods to instead prepare 33 full units of platelets (e.g. content 3x1011 per unit) based on the methods of this disclosure. A pathogen inactivation process such as that described in Example 3 (e.g., photochemical inactivation of pathogens using amotosalen and UVA and a treatment unit as shown in FIGS. 7 and 8) can optionally be performed before combining or, alternatively, after combining by exposure on pooled platelet preparations by the process of pathogen inactivation.

All references, including publications, patent applications and patents, cited herein are incorporated herein by reference to the same extent as if each reference had been individually and specifically stated to be incorporated by reference and set forth in their entirety herein .

When used herein (especially within the scope of the appended claims), the singular forms include plural references unless the context clearly indicates otherwise. The terms containing, having, including and consisting of are to be construed as open-ended terms (i.e., meaning including, but not limited to), unless otherwise noted. Where an open term is used to describe a function or element, it is specifically contemplated that the term of the closed term may be used in place of the open term without departing from the spirit and scope of the invention. The calculation of value ranges in this document is simply intended to be used as a shorthand method for individually addressing each individual value falling within the range unless otherwise noted, and each individual value is included in the description as if it were separately presented herein. All methods described herein may be performed in any suitable order, unless otherwise indicated herein or otherwise clearly contrary to the context. The use of any and all examples or exemplary language (such as such) presented herein is intended merely to better illuminate the description and does not constitute a limitation on the scope of the description unless otherwise stated. No language in the specification should be construed as indicating any non-borrowed element as essential to the practice of the methods, systems, and compositions described herein.

Preferred embodiments are described herein. Variations of these preferred embodiments may become apparent to those skilled in the art upon reading the foregoing description. It is expected that those skilled in the art will be able to use such variations as necessary and to implement the methods, systems and compositions described herein other than as specifically described herein. Accordingly, the methods, systems and compositions described herein include all modifications and equivalents of the subject matter set forth in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations is covered by the description unless otherwise indicated herein or otherwise clearly contrary to the context.

List of embodiments.

Embodiment 1. A method for producing a plurality of platelet units suitable for infusion, comprising:

a) collection of the first portion of platelets by apheresis from the first donor,

b) collection of a second portion of platelets by apheresis from a second donor,

c) combining the platelet portion of the first donor and the platelet portion of the second donor to obtain a pooled platelet preparation; and

- 62 043840

d) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that could be obtained from the first platelet unit and the second platelet unit without combining the first and second unit platelets.

Embodiment 2. The method of Embodiment 1, wherein collecting the first platelet from the first donor includes adjusting the platelet collection to obtain a first platelet containing less than about 98% of the number of platelets required to obtain one unit of platelets.

Embodiment 3. The method of Embodiment 1, wherein the first portion of platelets contains less than the number of platelets required to obtain one unit of platelets.

Embodiment 4. The method of Embodiment 1, wherein collecting the first platelet from the first donor includes adjusting the platelet collection to obtain a first platelet containing at least about 125% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets.

Embodiment 5. The method of Embodiment 1, wherein the first portion of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets.

Embodiment 6. The method of Embodiment 5, wherein the first portion of platelets contains from about 125 to about 198% of the number of platelets required to produce one unit of platelets.

Embodiment 7. The method of Embodiment 1, wherein collecting the first platelet from the first donor includes adjusting the platelet collection to obtain a first platelet containing at least about 225% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain three units of platelets.

Embodiment 8. The method of Embodiment 1, wherein the first portion of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets.

Embodiment 9. The method of Embodiment 8, wherein the first portion of platelets contains from about 125 to about 198% of the number of platelets required to obtain two units of platelets.

Embodiment 10. The method of Embodiment 8, wherein the first portion of platelets contains from about 225 to about 298% of the number of platelets required to produce one unit of platelets.

Embodiment 11. The method of Embodiment 1, wherein collecting the first portion of platelets from the first donor includes adjusting the platelet collection to obtain a first portion of platelets containing at least about 325% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain four units of platelets.

Embodiment 12. The method of Embodiment 1, wherein the first portion of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets.

Embodiment 13. The method of Embodiment 12, wherein the first portion of platelets contains from about 125 to about 198% of the number of platelets required to obtain three units of platelets.

Embodiment 14. The method of Embodiment 12, wherein the first portion of platelets contains from about 325 to about 398% of the number of platelets required to produce one unit of platelets.

Embodiment 15. The method of any one of embodiments 1-14, wherein collecting a second platelet from a second donor includes adjusting the platelet collection to obtain a second platelet containing at least about 125% of the number of platelets needed to obtain one unit of platelets, but less than the number of platelets needed to produce two units of platelets.

Embodiment 16. The method of any one of embodiments 1-14, wherein the second portion of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets.

- 63 043840

Embodiment 17. The method of Embodiment 16, wherein the second unit of platelets contains from about 125 to about 198% of the number of platelets required to produce one unit of platelets.

Embodiment 18. The method of any one of embodiments 1-14, wherein collecting a second platelet from a second donor includes adjusting the platelet collection to obtain a second platelet containing at least about 225% of the number of platelets needed to obtain one unit of platelets, but less than the number of platelets needed to produce three units of platelets.

Embodiment 19. The method of any one of embodiments 1-14, wherein the second portion of platelets contains more platelets than the amount required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets.

Embodiment 20. The method of Embodiment 19, wherein the second portion of platelets contains from about 125 to about 198% of the number of platelets required to obtain two units of platelets.

Embodiment 21. The method of Embodiment 19, wherein the second unit of platelets contains from about 225 to about 298% of the number of platelets required to produce one unit of platelets.

Embodiment 22. The method of any one of Embodiments 1-14, wherein collecting a second portion of platelets from a second donor includes adjusting the platelet collection to obtain a second portion of platelets containing at least about 325% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets needed to produce four units of platelets.

Embodiment 23. The method of any one of embodiments 1-14, wherein the second portion of platelets contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four units of platelets.

Embodiment 24. The method of Embodiment 23, wherein the second portion of platelets contains from about 125 to about 198% of the number of platelets required to obtain three units of platelets.

Embodiment 25. The method of Embodiment 23, wherein the second unit of platelets contains from about 325 to about 398% of the number of platelets required to produce one unit of platelets.

Embodiment 26. The method of Embodiment 2 or Embodiment 3, wherein collecting a second platelet batch from a second donor includes adjusting the platelet collection to obtain a second platelet batch containing a sufficient number of platelets to obtain two units of platelets after combining the first and second batches platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 27. The method of Embodiment 2 or Embodiment 3, wherein the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into two platelet units.

Embodiment 28. The method of Embodiment 2 or Embodiment 3, wherein collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain two units of platelets from the pooled preparation.

Embodiment 29. The method as in any one of Embodiments 4-6, wherein collecting a second portion of platelets from a second donor includes adjusting the platelet collection to obtain a second portion of platelets containing a sufficient number of platelets to obtain three units of platelets after combining the first and second portions platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 30. The method of any one of embodiments 4-6, wherein the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into three platelet units.

Embodiment 31. The method as in any one of embodiments 4-6, wherein collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain three units of platelets from the pooled preparation.

Embodiment 32. The method as in any one of Embodiments 7-10, wherein collecting a second portion of platelets from a second donor includes adjusting the platelet collection to obtain a second portion of platelets containing a sufficient number of platelets to obtain five units of platelets after combining the first and second portions. platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units.

- 64 043840

Embodiment 33. The method of any one of embodiments 7-10, wherein the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into five platelet units.

Embodiment 34. The method of any one of embodiments 7-10, wherein collecting a second portion of platelets from a second donor includes collecting enough platelets to obtain five platelet units from the pooled preparation.

Embodiment 35. The method as in any one of embodiments 11-14, wherein collecting a second platelet batch from a second donor includes adjusting the platelet collection to obtain a second platelet batch containing a sufficient number of platelets to produce seven units of platelets after combining the first and second batches platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 36. The method of any one of embodiments 11-14, wherein the second portion of platelets contains a sufficient number of platelets that, when combined with the first portion of platelets, produces a pooled platelet preparation containing a sufficient number of platelets to separate into seven platelet units.

Embodiment 37. The method of any one of embodiments 11-14, wherein collecting a second portion of platelets from a second donor comprises collecting enough platelets to obtain seven units of platelets from the pooled preparation.

Embodiment 38. The method of any one of embodiments 15-17, wherein the first portion of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets, and the second platelet supply contains more platelets than the number needed to produce one unit of platelets, but less than the number of platelets needed to produce two units of platelets.

Embodiment 39. The method of Embodiment 38, wherein the pooled platelet preparation contains a sufficient number of platelets to produce three units of platelets.

Embodiment 40: The method of Embodiment 38 or Embodiment 39, wherein the plurality of platelet units comprises three platelet units.

Embodiment 41. The method of any one of embodiments 18-21, wherein the first portion of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets, and the second platelet supply contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets.

Embodiment 42. The method of Embodiment 41, wherein the pooled platelet preparation contains a sufficient number of platelets to produce five units of platelets.

Embodiment 43: The method of Embodiment 41 or Embodiment 42, wherein the plurality of platelet units comprises five platelet units.

Embodiment 44. The method as in any one of Embodiments 1-43, further comprising collecting a third portion of platelets by apheresis from a third donor, combining the third portion of platelets with the first and second portions of platelets to produce a pooled platelet preparation, and dividing the pooled platelet preparation into a plurality of platelet units. each in a separate container, wherein the plurality of platelet units contains a greater number of platelet units than the total number of platelet units that can be obtained from the first platelet unit, the second platelet unit and the third platelet unit without combining the first, second and third platelet units.

Embodiment 45. The method according to any one of embodiments 1-44, characterized in that the second portion of platelets is collected within 20 hours from the time of collection of the first portion of platelets.

Embodiment 46. The method according to embodiment 45, characterized in that the second portion of platelets is collected within 12 hours from the time of collection of the first portion of platelets.

Embodiment 47. The method according to embodiment 46, characterized in that the second portion of platelets is collected within 6 hours from the time of collection of the first portion of platelets.

Embodiment 48. The method according to embodiment 44, characterized in that the third portion of platelets is collected within 12 hours from the time of collection of the first portion of platelets.

Embodiment 49. The method of any one of embodiments 1-48, wherein the pooled platelet preparation contains platelets only from donors of the same ABO blood type.

Embodiment 50. The method as in any one of Embodiments 1-49, further

- 65 043840 comprising subjecting each of the first portion of platelets and the second portion of platelets to a pathogen inactivation process.

Embodiment 51. The method of Embodiment 44 further comprising subjecting each of the first platelet portion, the second platelet portion, and the third platelet portion to a pathogen inactivation process.

Embodiment 52. The method of any one of embodiments 1-49, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process.

Embodiment 53. The method of any one of embodiments 50-52, wherein subjecting the portion of platelets or pooled platelet preparation to a pathogen inactivation process comprises treating the portion of platelets or pooled platelet preparation with a pathogen-inactivating compound.

Embodiment 54. The method of Embodiment 53, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540.

Embodiment 55. The method of Embodiment 54, wherein the pathogen-inactivating compound is psoralen.

Embodiment 56. The method of Embodiment 55, wherein the pathogen inactivating compound is amotosalen.

Embodiment 57. The method of any one of embodiments 1-56, wherein the platelet units in the plurality of platelet units contain a therapeutic dose of platelets suitable for infusion into a human subject.

Embodiment 58. The method of Embodiment 57, wherein the therapeutic dose of platelets contains a minimum number of platelets as determined by the criteria of a government agency, regulatory body, institution, and/or accredited organization.

Embodiment 59. The method of any one of embodiments 1-58, wherein each unit of platelets contains at least about 2.4 x 1011 platelets.

Embodiment 60. The method of Embodiment 59, wherein each platelet unit contains at least about 2.6x1011 platelets.

Embodiment 61. The method of Embodiment 60, wherein each unit of platelets contains at least about 3.0 x 1011 platelets.

Embodiment 62. The method of any one of embodiments 26-28, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

Embodiment 63. The method of Embodiment 62, wherein the pooled platelet preparation contains at least about 6.2 x 1011 platelets.

Embodiment 64. The method of any one of embodiments 29-31, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

Embodiment 65. The method of Embodiment 65, wherein the pooled platelet preparation contains at least about 9.3 x 1011 platelets.

Embodiment 66. The method of any one of embodiments 26-34, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

Embodiment 67. The method of Embodiment 66, wherein the pooled platelet preparation contains at least about 15.5x1011 platelets.

Embodiment 68. The method as in any one of Embodiments 2, 4, 7, 11, 15, 18, 22, 26, 29, 32, and 35, wherein tailoring platelet collection includes determining optimal platelet collection.

Embodiment 69. The method of any one of Embodiments 2, 4, 7, 11, 15, 18, 22, 26, 29, 32, and 35, wherein adjusting the platelet collection includes providing entry into the apheresis system.

Embodiment 70. The method as in any one of Embodiments 2, 4, 7, 11, 15, 18, 22, 26, 29, 32, and 35, wherein the platelet collection adjustment includes the volume of the portion in the apheresis system.

Embodiment 71. The method of any one of embodiments 1-70, characterized in that the first portion of platelets and the second portion of platelets are combined in a single container of a suitable size for the volume of the combined platelet preparation.

Embodiment 72. A method for producing a plurality of platelet units suitable for infusion, comprising:

- 66 043840

a) maintaining a storage log of platelet preparations collected by apheresis, wherein the storage log contains for each platelet preparation a unique identifier, the donor’s blood type, the time of donation and the number of platelets in the preparation,

b) identification of an available donor suitable for apheresis platelet donation,

c) selecting from the storage log at least one platelet preparation in the storage to be combined with platelets collected from an existing donor,

d) collecting a new portion of platelets by apheresis from an existing donor,

e) combining at least one selected platelet preparation and a new portion of platelets to obtain a pooled platelet preparation; and

f) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from the at least one selected preparation and a new portion of platelets without pooling at least the first drug chosen and a new portion of platelets.

Embodiment 73. The method of Embodiment 72, wherein the storage of apheresis-collected platelet preparations contains existing platelet preparations that have already been collected.

Embodiment 74. The method of Embodiment 72, wherein the apheresis-collected platelet preparation storage contains one or more apheresis-collected platelet preparations from one or more given donors, wherein one or more of the given donors are not available donors.

Embodiment 75. The method of any one of embodiments 72-74, wherein the at least one selected platelet preparation contains a number of platelets less than that required to produce one unit of platelets.

Embodiment 76. The method of any one of embodiments 72-74, wherein the at least one selected platelet preparation contains more platelets than the number needed to produce one unit of platelets, but less than the number of platelets needed to produce two platelet units.

Embodiment 77. The method of any one of embodiments 72-74 and 76, wherein the at least one selected platelet preparation contains at least about 125% of the number of platelets required to produce one unit of platelets, but less than the number platelets required to produce two units of platelets.

Embodiment 78. The method of Embodiment 76, wherein the at least one selected platelet preparation contains from about 125 to about 198% of the number of platelets required to produce one unit of platelets.

Embodiment 79. The method of any one of embodiments 72-74, wherein the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three platelet units.

Embodiment 80. The method of any one of embodiments 72-74 and 79, wherein the at least one selected platelet preparation contains at least about 225% of the number of platelets required to produce one unit of platelets, but less than the number platelets required to produce three units of platelets.

Embodiment 81. The method of Embodiment 80, wherein the at least one selected platelet preparation contains from about 225 to about 298% of the number of platelets required to produce one unit of platelets.

Embodiment 82. The method of Embodiment 80, wherein the at least one selected platelet preparation contains from about 125 to about 198% of the number of platelets required to obtain two units of platelets.

Embodiment 83. The method of any one of embodiments 72-74, wherein the at least one selected platelet preparation contains more platelets than the number required to obtain three units of platelets, but less than the number of platelets necessary to obtain four platelet units.

Embodiment 84. The method of any one of embodiments 72-74 and 83, wherein the at least one selected platelet preparation contains at least about 325% of the number of platelets required to produce one unit of platelets, but less than the number platelets required to produce four units of platelets.

Embodiment 85. The method of Embodiment 84, wherein the at least one selected platelet preparation contains from about 325 to about 398% of the number of platelets required to produce one unit of platelets.

Embodiment 86. The method of Embodiment 83, wherein the at least one selected platelet preparation contains from about 125 to about 198% of the number of platelets required to produce three units of platelets.

Embodiment 87. The method of any one of embodiments 72-86, wherein collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing at least about 125% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets needed to produce two units of platelets.

Embodiment 88. The method as in any one of embodiments 72-86, wherein the new batch of platelets contains more platelets than the number required to produce one unit of platelets, but less than the number of platelets required to produce two units of platelets.

Embodiment 89. The method of Embodiment 88, wherein the new batch of platelets contains from about 125 to about 198% of the number of platelets required to produce one unit of platelets.

Embodiment 90. The method of any one of embodiments 72-86, wherein collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing at least about 225% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets needed to produce three units of platelets.

Embodiment 91. The method as in any one of embodiments 72-86, wherein the new batch of platelets contains more platelets than the number required to produce two units of platelets, but less than the number of platelets required to obtain three units of platelets.

Embodiment 92. The method of Embodiment 91, wherein the new batch of platelets contains from about 125 to about 198% of the number of platelets required to produce two units of platelets.

Embodiment 93. The method of Embodiment 91, wherein the new batch of platelets contains from about 225 to about 298% of the number of platelets required to produce one unit of platelets.

Embodiment 94. The method of any one of embodiments 72-86, wherein collecting a new batch of platelets includes adjusting the platelet collection to obtain a batch containing at least about 325% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets needed to produce four units of platelets.

Embodiment 95. The method as in any one of embodiments 72-86, wherein the new batch of platelets contains more platelets than the number required to produce three units of platelets, but less than the number of platelets required to obtain four units of platelets.

Embodiment 96. The method of Embodiment 95, wherein the new batch of platelets contains from about 125 to about 198% of the number of platelets required to produce three units of platelets.

Embodiment 97. The method of Embodiment 95, wherein the new batch of platelets contains from about 325 to about 398% of the number of platelets required to produce one unit of platelets.

Embodiment 98. The method of Embodiment 75, wherein collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to produce two units of platelets after combining at least one selected platelet preparation and a new portions of platelets and dividing the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 99. The method of Embodiment 75, wherein the new unit of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a combined platelet preparation containing a sufficient number of platelets to separate into two platelet units.

Embodiment 100. The method of Embodiment 75, wherein collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain two units of platelets from the pooled preparation.

Embodiment 101. The method as in any one of embodiments 76-78, wherein collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to produce three units of platelets after combining at least one selected platelet preparation and a new portion of platelets and dividing the resulting combined platelet preparation into

- 68 043840 many platelet units.

Embodiment 102. The method as in any one of Embodiments 76-78, wherein the new batch of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a pooled platelet preparation containing a sufficient number of platelets to separate into three platelet units.

Embodiment 103. The method of any one of embodiments 76-78, wherein collecting a new batch of platelets from an existing donor includes collecting enough platelets to obtain three units of platelets from the pooled preparation.

Embodiment 104. The method as in any one of embodiments 79-82, wherein collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to produce five units of platelets after combining at least one selected a platelet preparation and a new portion of platelets and dividing the resulting combined platelet preparation into a plurality of platelet units.

Embodiment 105. The method of any one of Embodiments 79-82, wherein the fresh platelet unit contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a pooled platelet preparation containing a sufficient number of platelets to separate into five platelet units.

Embodiment 106. The method of any one of embodiments 79-82, wherein collecting a new batch of platelets from an existing donor includes collecting enough platelets to obtain five units of platelets from the pooled preparation.

Embodiment 107. The method as in any one of embodiments 83-86, wherein collecting a new platelet unit from an existing donor includes adjusting the platelet collection to obtain a platelet unit containing a sufficient number of platelets to produce seven platelet units after combining at least one selected platelet preparation and new platelet units and dividing the resulting combined platelet preparation into a plurality of platelet units.

Embodiment 108. The method of any one of Embodiments 83-86, wherein the new batch of platelets contains a sufficient number of platelets that, when combined with at least one selected platelet preparation, provides a pooled platelet preparation containing a sufficient number of platelets to separate into seven platelet units.

Embodiment 109. The method of any one of embodiments 83-86, wherein collecting a new batch of platelets from an existing donor includes collecting enough platelets to obtain seven units of platelets from the pooled preparation.

Embodiment 110. The method of Embodiment 88 or Embodiment 89, wherein the at least one selected platelet preparation contains more platelets than the number needed to produce one unit of platelets, but less than the number of platelets needed to produce two units of platelets, and the new supply of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets.

Embodiment 111. The method of Embodiment 110, wherein the pooled platelet preparation contains a sufficient number of platelets to produce three units of platelets.

Embodiment 112: The method of Embodiment 110 or Embodiment 111, wherein the plurality of platelet units comprises three platelet units.

Embodiment 113. The method of any one of embodiments 91-93, wherein the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets, and the new supply of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets.

Embodiment 114. The method of Embodiment 113, wherein the pooled platelet preparation contains a sufficient number of platelets to produce five units of platelets.

Embodiment 115: The method of Embodiment 113 or Embodiment 114, wherein the plurality of platelet units comprises five platelet units.

- 69 043840

Embodiment 116. The method as in any one of Embodiments 72-115, further comprising identifying a second available donor suitable for apheresis platelet donation, collecting a second new portion of platelets by apheresis from the second available donor, combining the second new portion of platelets with at least one the selected preparation and a new portion of platelets to obtain a pooled platelet preparation; and dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from at least one selected platelet preparation and a new portion of platelets and a second new portion of platelets without combining at least one selected platelet preparation and a new portion of platelets and a second new portion of platelets.

Embodiment 117. The method as in any one of embodiments 72-116, wherein a new portion of platelets is collected within 12 hours of collection of at least one selected platelet preparation.

Embodiment 118. The method of Embodiment 117, wherein the second new batch of platelets is collected within 12 hours of the collection of at least one selected platelet preparation and the new platelet batch.

Embodiment 119. The method of any one of embodiments 72-118, wherein the pooled platelet preparation contains platelets only from donors of the same ABO blood type.

Embodiment 120. The method of any one of embodiments 72-119, further comprising subjecting each of the at least one selected platelet preparation and a fresh batch of platelets to a pathogen inactivation process.

Embodiment 121. The method of Embodiment 116, further comprising subjecting each of the at least one selected platelet preparation, a fresh platelet batch, and a second fresh platelet batch to a pathogen inactivation process.

Embodiment 122. The method of Embodiment 120 or Embodiment 121, wherein subjecting each of the at least one selected platelet preparation, a fresh platelet batch, and a second fresh platelet batch to a pathogen inactivation process comprising treating each of the at least one selected platelet preparation, a new portion of platelets, and a second new portion of platelets with a pathogen-inactivating compound.

Embodiment 123. The method of any one of embodiments 72-119, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process.

Embodiment 124. The method of Embodiment 123, wherein subjecting the pooled platelet preparation to a pathogen inactivation process comprises treating the pooled platelet preparation with a pathogen inactivating compound.

Embodiment 125. The method of Embodiment 122 or Embodiment 124, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine. 540.

Embodiment 126. The method of Embodiment 125, wherein the pathogen-inactivating compound is psoralen.

Embodiment 127. The method of Embodiment 126, wherein the pathogen-inactivating compound is psoralen.

Embodiment 128. The method of any one of embodiments 72-127, wherein the platelet units in the plurality of platelet units contain a therapeutic dose of platelets suitable for infusion into a human subject.

Embodiment 129. The method of Embodiment 128, wherein the therapeutic dose of platelets contains a minimum number of platelets as determined by the criteria of a government agency, regulatory body, institution, and/or accredited organization.

Embodiment 130. The method of any one of embodiments 72-129, wherein each platelet unit contains at least about 2.4 x 1011 platelets.

Embodiment 131. The method of Embodiment 130, wherein each unit of platelets contains at least about 2.6 x 1011 platelets.

Embodiment 132. The method of Embodiment 131, wherein each unit of platelets contains at least about 3.0 x 1011 platelets.

Embodiment 133. The method of any one of embodiments 98-100, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

- 70 043840

Embodiment 134. The method of Embodiment 133, wherein the pooled platelet preparation contains at least about 6.2 x 1011 platelets.

Embodiment 135. The method of any one of embodiments 101-103, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

Embodiment 136. The method of Embodiment 135, wherein the pooled platelet preparation contains at least about 9.3 x 1011 platelets.

Embodiment 137. The method of any one of embodiments 98-106, wherein each unit of platelets contains a therapeutic dose equal to at least about 3x1011 platelets.

Embodiment 138. The method of Embodiment 137, wherein the pooled platelet preparation contains at least about 15.5 x 1011 platelets.

Embodiment 139. The method as in any one of embodiments 87, 90, 94, 98, 101, 104, 107, wherein tailoring platelet collection includes determining optimal platelet collection.

Embodiment 140. The method as in any one of embodiments 87, 90, 94, 98, 101, 104, 107, wherein adjusting the platelet collection includes providing entry into the apheresis system.

Embodiment 141. The method as in any one of embodiments 87, 90, 94, 98, 101, 104, 107, wherein the platelet collection adjustment includes the batch volume in the apheresis system.

Embodiment 142. The method of any one of embodiments 72-141, wherein the at least one selected platelet preparation and the new platelet supply are combined in a single container of a suitable size for the volume of the combined platelet preparation.

Embodiment 143. An infusionable platelet unit prepared by the method of any one of Embodiments 1-143.

Embodiment 144: A method of producing two or more therapeutic platelet dosage units, comprising:

a) combining two or more donor platelet units obtained by apheresis to form a pooled platelet composition,

b) subjecting the combined platelet composition to a pathogen inactivation process; and

c) dividing the combined platelet composition into two or more therapeutic platelet dosage units, each in a separate container.

Embodiment 145. The method of Embodiment 144, wherein the therapeutic platelet unit after step c) is greater than the number of therapeutic platelet units that can be obtained from two or more donor platelet units obtained by apheresis, individually, without combining two or more donor units.

Embodiment 146. The method of Embodiment 144 or Embodiment 145, wherein the two platelet donor units obtained by apheresis and each donor unit contains a number of platelets greater than needed to produce one therapeutic platelet dosage unit, but less than the number of platelets required to obtain two therapeutic platelet dosage units.

Embodiment 147. The method of Embodiment 146, wherein each donor unit contains about 125% of the number of platelets required to obtain one unit of platelets.

Embodiment 148. The method of Embodiment 144 or Embodiment 145, wherein the two apheresis platelet donor units and each donor unit contain a number of platelets greater than that required to produce two therapeutic platelet dosage units, but less than than the number of platelets required to obtain three therapeutic platelet dosage units.

Embodiment 149. The method of Embodiment 148, wherein each donor unit contains about 225% of the number of platelets required to obtain one unit of platelets.

Embodiment 150. The method as in any one of embodiments 144-149, wherein at least one of the two or more apheresis-collected donor platelet units is selected from a storage log of apheresis-collected donor platelet units, wherein the storage log contains: Each platelet donor unit has a unique identifier, the donor's blood type, the time of donation, and the number of platelets in the donor unit.

Embodiment 151. The method of Embodiment 150, wherein each of the two or more donor platelet units obtained by apheresis is selected from a magazine.

- 71 043840 storage.

Embodiment 152. The method of any one of embodiments 144-151, wherein two or more apheresis platelet donor units are combined within 12 hours of collection.

Embodiment 153. The method of any one of embodiments 144-151, wherein the two or more donor units of apheresis platelets are obtained from donors of the same ABO blood type.

Embodiment 154. The method of any one of embodiments 144-153, wherein subjecting the pooled platelet composition to a pathogen inactivation process comprises treating the pooled platelet composition with a pathogen-inactivating compound.

Embodiment 155. The method of Embodiment 154, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540.

Embodiment 156. The method of Embodiment 155, wherein the pathogen-inactivating compound is psoralen.

Embodiment 157 The method of Embodiment 156, wherein the pathogen inactivating compound is psoralen.

Embodiment 158. The method of any one of embodiments 144-157, wherein each therapeutic platelet dosage unit contains at least 2.4 x 1011 platelets.

Embodiment 159. The method of Embodiment 158, wherein each therapeutic platelet dosage unit contains at least 2.6x1011 platelets.

Embodiment 160. The method of Embodiment 159, wherein each therapeutic platelet dosage unit contains at least 3.0x1011 platelets.

Embodiment 161. A therapeutic platelet dosage unit prepared by the method of any one of embodiments 144-160.

Embodiment 162. A method for collecting a portion of platelets by apheresis from a donor, comprising:

a) maintaining a repository log of platelet preparations collected by apheresis, wherein the repository log contains for each platelet preparation a unique identifier, the donor's blood type, the date of donation and the number of platelets in the preparation,

b) identification of a donor suitable for apheresis platelet donation,

c) selecting from the storage log one or more platelet preparations suitable for combination with a new portion of platelets collected by apheresis from the donor,

d) determining a target volume of the new platelet supply, wherein the target volume optimizes the number of platelet units that can be obtained from the combination containing the new platelet supply and one or more selected platelet preparations; And

e) collection of the target volume of a new portion of platelets by apheresim from the donor.

Embodiment 163. The method of Embodiment 162, further comprising:

f) combining one or more of the selected platelet preparation and a new portion of platelets to obtain a pooled platelet preparation; and

g) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container.

Embodiment 164. The method of Embodiment 163, wherein each of the platelet units in the plurality of platelet units contains a therapeutic dose suitable for infusion into a human subject.

Embodiment 165. The method of Embodiment 163 or Embodiment 164, wherein the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from one or more selected platelet preparations and a fresh platelet unit without pooling. one or more selected platelet preparations and a new supply of platelets.

Embodiment 166. The method of any one of embodiments 162-165, wherein the one or more selected platelet preparation contains a number of platelets less than that required to produce one unit of platelets.

Embodiment 167. The method of Embodiment 166, wherein the target volume of the new platelet unit is a volume containing a sufficient number of platelets to produce two units of platelets after combining one or more selected platelet preparations and the new unit of platelets and separating the resulting combined preparation. 72 043840 platelet rate for many platelet units.

Embodiment 168. The method of Embodiment 166, wherein the new unit of platelets contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into two platelet units.

Embodiment 169. The method of Embodiment 166, wherein collecting a new supply of platelets from a donor includes collecting enough platelets to obtain two units of platelets from the pooled preparation.

Embodiment 170. The method of any one of embodiments 162-165, wherein the one or more selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units. platelets.

Embodiment 171. The method of Embodiment 167, wherein the one or more selected platelet preparation contains at least about 125% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to obtain two units. platelets.

Embodiment 172. The method of Embodiment 170 or Embodiment 171, wherein the target new platelet volume is a volume containing enough platelets to produce three units of platelets after combining one or more selected platelet preparations and the new platelet batch and separating the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 173. The method of Embodiment 170 or Embodiment 171, wherein the new unit of platelets contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into three units. platelets.

Embodiment 174. The method of Embodiment 170 or Embodiment 171, wherein collecting a new supply of platelets from a donor includes collecting enough platelets to obtain three units of platelets from the pooled preparation.

Embodiment 175. The method of any one of embodiments 162-165, wherein the one or more selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units. platelets.

Embodiment 176. The method of Embodiment 175, wherein the one or more selected platelet preparation contains at least about 225% of the number of platelets required to produce one unit of platelets, but less than the number of platelets required to obtain three units. platelets.

Embodiment 177. The method of Embodiment 175 or Embodiment 176, wherein the target new platelet volume is a volume containing enough platelets to produce five units of platelets after combining one or more selected platelet preparations and the new platelet batch and separating the resulting pooled platelet preparation into a plurality of platelet units.

Embodiment 178. The method of Embodiment 175 or Embodiment 176, wherein the new unit of platelets contains a sufficient number of platelets that, when combined with one or more selected platelet preparations, provides a pooled platelet preparation containing a sufficient number of platelets to separate into five units platelets.

Embodiment 179. The method of Embodiment 175 or Embodiment 176, wherein collecting a new batch of platelets from a donor includes collecting enough platelets to obtain five units of platelets from the pooled preparation.

Embodiment 180. The method of Embodiment 164 or Embodiment 165, wherein each of the one or more selected platelet preparations and the fresh platelet supply contains more platelets than the number required to obtain one therapeutic dose, but less than the number of platelets required to obtain two therapeutic doses.

Embodiment 181. The method of Embodiment 164 or Embodiment 165, wherein each of the one or more selected platelet preparations and the fresh platelet supply contains more platelets than the amount required to produce two therapeutic dosage units, but less than the amount platelets required to obtain three therapeutic platelet dosage units.

- 73 043840

Embodiment 182. The method as in any one of embodiments 163-182, wherein one or more of the selected platelet preparation and a new portion of platelets are combined within 12 hours of collection.

Embodiment 183. The method as in any one of embodiments 163-182, wherein one or more of the selected platelet preparation and the fresh platelet supply are obtained from donors of the same ABO blood type.

Embodiment 184. The method of any one of embodiments 163-182, wherein each unit of platelets contains at least 2.4 x 1011 platelets.

Embodiment 185. The method of Embodiment 184, wherein each platelet unit contains at least 2.6x1011 platelets.

Embodiment 186. The method of Embodiment 185, wherein each platelet unit contains at least 3.0x1011 platelets.

Embodiment 187. The method of any one of embodiments 163-186, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process.

Embodiment 188. The method of Embodiment 187, wherein subjecting the pooled platelet preparation to a pathogen inactivation process comprises treating the pooled platelet preparation with a pathogen inactivating compound.

Embodiment 189. The method of any one of embodiments 163-186, further comprising subjecting each of the one or more selected platelet preparations and a fresh batch of platelets to a pathogen inactivation process.

Embodiment 190. The method of Embodiment 189, wherein subjecting the one or more selected platelet preparation and the fresh platelet batch to a pathogen inactivation process comprises treating the one or more selected platelet preparation and the fresh platelet batch with a pathogen inactivating compound.

Embodiment 191. The method of any one of embodiments 187-190, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine. 540.

Embodiment 192. The method of Embodiment 191, wherein the pathogen-inactivating compound is psoralen.

Embodiment 193. The method of Embodiment 192, wherein the pathogen-inactivating compound is psoralen.

Embodiment 194. A platelet unit suitable for infusion in a human, selected from a plurality of platelet units obtained by the method of any one of embodiments 163-193.

Embodiment 195: A therapeutic platelet dosage unit suitable for infusion into a subject comprising pooled apheresis platelets from two or more donors, and wherein the pooled apheresis platelets have been treated with a pathogen-inactivating compound.

Embodiment 196. The therapeutic dosage unit of Embodiment 195, wherein the pooled platelets obtained by apheresis have been treated with a pathogen-inactivating compound prior to pooling.

Embodiment 197 The therapeutic platelet dosage unit of Embodiment 195, wherein the pooled platelets obtained by apheresis are treated with a pathogen-inactivating compound after pooling.

Embodiment 198. The therapeutic platelet dosage unit of any one of embodiments 195-197, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin and merocyanine 540.

Embodiment 199. The therapeutic platelet dosage unit of Embodiment 198, wherein the pathogen inactivating compound is psoralen.

Embodiment 200. The therapeutic platelet dosage unit of Embodiment 199, wherein the pathogen inactivating compound is amotosalen.

Embodiment 201. The therapeutic platelet dosage unit of any one of embodiments 195-200, wherein the platelets obtained by apheresis are obtained from donors of the same ABO blood type.

Embodiment 202. The therapeutic platelet dosage unit of any one of embodiments 195-201, wherein the therapeutic dosage unit comprises

- 74 043840 at least 2.4x1011 platelets.

Embodiment 203. The therapeutic platelet dosage unit of embodiment 202, wherein the therapeutic dosage unit contains at least 2.6x1011 platelets.

Embodiment 204. The therapeutic platelet dosage unit of embodiment 203, wherein the therapeutic dosage unit contains at least 3.0 x 1011 platelets.

Embodiment 205: A method of infusing platelets into a subject in need thereof, comprising infusing the subject with a platelet unit of Embodiment 143 or Embodiment 194 or a therapeutic platelet dosage unit of any of Embodiments 161 and 195-204.

Embodiment 206: A computerized method for optimizing platelet units for infusion, comprising:

in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of a unit of platelets;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

determining, based on the search results, a platelet unit volume and providing a specific platelet unit volume that optimizes platelet units.

Embodiment 207. The method of embodiment 206, wherein at least one of the platelet unit and the plurality of platelet preparations comprises platelets obtained by apheresis.

Embodiment 208. The method of Embodiment 206 or Embodiment 207, wherein the platelet unit comprises platelets that are currently being collected from a donor or platelets that are to be collected from a donor.

Embodiment 209. The method as in any one of embodiments 206-208, wherein the one or more properties of the platelet unit include blood type, time of donation, number of platelets per unit volume, and, optionally, a maximum volume of the platelet unit.

Embodiment 210. The method of Embodiment 209, wherein the blood type value includes one of A, B, AB, or O.

Embodiment 211. The method as in any one of embodiments 206-210, characterized in that the instruction to search for a plurality of values associated with samples of a plurality of platelet preparations includes:

obtaining one or more search criteria using one or more obtained values associated with one or more properties of the platelet unit;

instructing to search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria and obtaining one or more candidate samples of platelet preparations from the samples of the plurality of platelet preparations, one or more candidate samples of platelet preparations having values that satisfy one or more search criteria.

Embodiment 212. The method of Embodiment 211, wherein the search criteria include one or more threshold conditions of one or more of: blood type, donation time, platelet volume, and platelet count per unit volume.

Embodiment 213. The method of embodiment 211 or 212, wherein obtaining one or more potential platelet preparation samples comprises filtering the plurality of platelet preparation samples based on one or more search criteria.

Embodiment 214. The method as in any one of embodiments 206-213, wherein the representations of the plurality of platelet preparations include at least one of: platelet preparations stored in a platelet preparation repository, platelet preparations currently being collected from a plurality of donors, and platelet preparations will be collected from many donors.

Embodiment 215. The method according to any of embodiments 206-214, characterized in that determining the volume of a portion of platelets includes:

obtaining one or more values corresponding to one or more potential platelet preparation samples obtained from the search results;

obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units;

determination, based on one or more values corresponding to one or more samples of potential platelet products, and one or more criteria for platelet units, one

- 75 043840 or more platelet preparations for selecting from one or more potential samples from a plurality of platelet preparations; and obtaining a platelet unit volume based on the particular platelet preparation.

Embodiment 216. The method as in any one of embodiments 206-215, wherein providing a specified volume of platelet unit comprises at least one of:

displaying a certain volume of platelet portion on the computer system display;

sending a notification indicating the determining volume of a portion of platelets; and providing a certain volume of platelet portions in the apheresis system.

Embodiment 217. The method of any one of embodiments 206-216, further comprising combining a portion of platelets and one or more platelet preparations selected from samples of a plurality of platelet preparations to produce a pooled platelet preparation.

Embodiment 218 The method of embodiment 217 further comprising dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container.

Embodiment 219. A non-transitory computer readable medium containing instructions stored thereon for optimizing platelet units for infusion, the instructions executed by one or more processors of the computer system causing the computer system to:

obtaining one or more values associated with one or more properties of the platelet unit;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

determining, based on the search results, a platelet unit volume and providing a specific platelet unit volume that optimizes platelet units.

Embodiment 220: A system for optimizing platelet units for infusion, comprising:

one or more processors and a memory containing instructions stored therein, wherein the instruction executed by the one or more processors causes the computer system to:

obtaining one or more values associated with one or more properties of the platelet unit;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

determining, based on the search results, a platelet unit volume and providing a specific platelet unit volume that optimizes platelet units.

Embodiment 221. The system of embodiment 220, wherein the computer system is integrated with the apheresis system.

Embodiment 222: A computerized method for optimizing platelet units for infusion, comprising:

in a computer system comprising one or more processors and memory, obtaining one or more values associated with one or more properties of the first platelet preparation;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

selecting, based on the search results, a second platelet preparation from samples of the plurality of platelet preparations and providing the selected second platelet preparation, wherein the selected second platelet preparation allows optimization of the platelet units.

Embodiment 223. The method of Embodiment 222, wherein at least one of the first platelet preparation and the plurality of platelet preparations comprises platelets obtained by apheresis.

Embodiment 224. The method of Embodiment 222 or 223, wherein the first platelet preparation includes a platelet preparation stored in a platelet preparation inventory.

Embodiment 225. The method of any one of embodiments 222-224, wherein one or more properties of the first platelet preparation include blood type, time of donation, volume, and number of platelets per unit volume.

Embodiment 226. The method of Embodiment 225, wherein the blood type value includes one of A, B, AB, or O.

Embodiment 227. The method of any one of embodiments 222-226, characterized in that the instruction to search for multiple values associated with samples of multiple platelet preparations includes:

obtaining one or more search criteria using one or more obtained values associated with one or more properties of the first platelet preparation;

indicating a search for a plurality of values associated with samples of the plurality of platelet preparations based on one or more search criteria; and obtaining one or more potential platelet preparation samples from the plurality of platelet preparation samples, one or more potential platelet preparation samples having values that satisfy the one or more search criteria.

Embodiment 228. The method of Embodiment 227, wherein the search criteria include one or more threshold conditions of one or more of: blood type, time of donation, volume, and platelet count per unit volume.

Embodiment 229. The method of embodiment 227 or 228, wherein obtaining one or more potential platelet preparation samples includes filtering the plurality of platelet preparation samples based on one or more search criteria.

Embodiment 230. The method as in any one of embodiments 222-229, wherein the representations of the plurality of platelet preparations include at least one of: platelet preparations stored in a platelet preparation repository, platelet preparations currently being collected from a plurality of donors, and platelet preparations will be collected from many donors.

Embodiment 231. The method of any one of embodiments 222-230, wherein the selection of the second platelet preparation includes:

obtaining one or more values corresponding to one or more potential platelet preparation samples obtained from the search results;

obtaining one or more criteria for platelet units, wherein the criteria for platelet units allow optimization of the platelet units; and selecting, based on the one or more values corresponding to the one or more candidate platelet preparation samples, and the one or more criteria for the platelet units, a second platelet preparation from the one or more candidate platelet preparation samples.

Embodiment 232. The method of any one of embodiments 222-231, wherein providing the selected second platelet preparation comprises at least one of:

displaying the selected second platelet preparation on the display of the computer system; and sending a notification providing the selected second platelet preparation; and providing identification of the selected second platelet preparation in the apheresis system.

Embodiment 233. The method of any one of embodiments 222-232, further comprising combining the first platelet preparation and the selected second platelet preparation to produce a combined platelet preparation.

Embodiment 234 The method of embodiment 233 further comprising dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container.

Embodiment 235. A non-transitory computer readable medium containing instructions stored thereon for optimizing platelet units for infusion, the instructions executed by one or more processors of the computer system causing the computer system to:

obtaining one or more values associated with one or more properties of the first platelet preparation;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

selecting, based on the search results, a second platelet preparation from samples of the plurality of platelet preparations and providing the selected second platelet preparation, wherein the selected second platelet preparation allows optimization of the platelet units.

Embodiment 236: A system for optimizing platelet units for infusion, comprising:

one or more processors and a memory containing instructions stored therein, wherein the instruction executed by the one or more processors causes the computer system to:

obtaining one or more values associated with one or more properties of the first platelet preparation;

indicating a search based on the obtained one or more values, a plurality of values associated with samples of a plurality of platelet preparations;

selecting, based on the search results, a second platelet preparation from samples of a plurality of platelet preparations; and providing a selected second platelet preparation, wherein the selected second platelet preparation allows optimization of the platelet units.

Embodiment 237. The system of embodiment 236, wherein the computer system is integrated with the apheresis system.

Embodiment 238. The method of any one of embodiments 217, 218, 233, and 234, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process.

Embodiment 239 The method of Embodiment 238, wherein subjecting the pooled platelet preparation to a pathogen inactivation process comprises treating the pooled platelet preparation with a pathogen inactivating compound.

Embodiment 240. The method of Embodiment 239, wherein the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540.

Embodiment 241 The method of embodiment 240, wherein the pathogen-inactivating compound is psoralen.

Embodiment 242. The method of Embodiment 241, wherein the pathogen-inactivating compound is psoralen.

Embodiment 243: A processing unit for producing a plurality of platelet units from two or more platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject, the processing unit comprising:

a) a first container that contains a pathogen inactivation compound (PIC) and is suitable for combining two or more portions of platelets with a PIC;

b) a second container connected to the first container, within which two or more platelet units mixed with CIP can be photochemically inactivated under sterile conditions, the volume of the two or more platelet units being sufficient to produce multiple platelet units;

c) a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions; And

d) two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions to provide multiple platelet units wherein the plurality of platelet units contains a greater number of platelet units than the total number of platelet units that can be obtained from two or more units without combining two or more units of platelets.

Embodiment 244. The treatment unit of Embodiment 243, comprising three or more third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to three or more more than a third of the container under sterile conditions to provide multiple units of platelets.

Embodiment 245. The processing unit of Embodiment 243 or Embodiment 244 further comprising an additional container suitable for housing one or more of two or more platelet units, wherein the additional container is connected to the first container such that the one or more platelet units additional container can be transferred from the additional container to the first container under sterile conditions.

Embodiment 246. The processing unit of Embodiment 245, wherein the additional container is suitable for housing a portion of platelets obtained by apheresis.

Embodiment 247: The processing unit of Embodiment 245 or Embodiment 246, wherein the additional container is suitable for sterile connection with the second additional container.

Embodiment 248. The processing unit of Embodiment 247, wherein the second additional container contains one or more of two or more portions of platelets, and wherein the additional container is suitable for sterile connection with the second additional container such that the one or more portions platelets from the second additional container can be transferred from the second additional container to the additional container under sterile conditions.

Embodiment 249: The processing unit of any one of embodiments 245-248, further comprising a second additional container suitable

- 78 043840 for housing one or more of two or more platelet units, wherein the second additional container is connected to the additional container so that one or more platelet units of the second additional container can be transferred from the second additional container to the additional container under sterile conditions.

Embodiment 250. The processing unit as in any one of embodiments 247-249, wherein the additional container is suitable for accommodating the apheresis platelet portion from the first donor, and wherein the second additional container is suitable for accommodating the apheresis platelet portion from the second donor.

Embodiment 251. The treatment unit of any one of embodiments 243-250, wherein the SIP is psoralen.

Embodiment 252. The treatment unit of Embodiment 251, wherein the SIP is amotosalen.

Embodiment 253. A kit comprising (a) a processing unit and (b) instructions for operating the processing unit for producing a plurality of platelet units from two or more platelet units, each of the platelet units being pathogen-inactivated and suitable for infusion into a subject wherein the plurality of platelet units contains a greater number of platelets than the number of platelets that can be obtained from two or more units without combining the two or more units of platelets, and wherein the processing unit comprises:

1) a first container that contains a pathogen inactivation compound (PIC) and is suitable for combining two or more portions of platelets with a PIC;

2) a second container connected to the first container, within which two or more portions of platelets mixed with SIP can be photochemically inactivated under sterile conditions, the volume of the two or more portions of platelets being sufficient to produce multiple units of platelets;

3) a compound absorption device (CAD) coupled to a second container such that two or more photochemically inactivated platelet units can be transferred from the second container to the compound absorption device under sterile conditions; And

4) two or more third containers, each of which is connected to the compound absorption device such that two or more photochemically inactivated platelet units can be transferred from the compound absorption device to the two or more third containers under sterile conditions to provide multiple platelet units .

Embodiment 254. The kit of Embodiment 253, wherein the treatment unit comprises three or more third containers, each of which is connected to a compound absorption device such that two or more photochemically inactivated platelet portions can be transferred from the compound absorption device. absorption of the compound into three or more thirds of the container under sterile conditions to provide multiple platelet units.

Embodiment 255. The kit of Embodiment 253 or Embodiment 254, wherein the processing unit further comprises an additional container suitable for housing one or more of two or more portions of platelets, wherein the additional container is connected to the first container such that one or more additional container platelet portions may be transferred from the additional container to the first container under sterile conditions.

Embodiment 256. The kit of Embodiment 255, wherein the additional container is suitable for containing a portion of platelets obtained by apheresis.

Embodiment 257: The kit of Embodiment 255 or 256, wherein the additional container is suitable for sterile connection with the second additional container.

Embodiment 258. The kit of Embodiment 257, wherein the second additional container contains one or more of two or more platelet units, and wherein the additional container is suitable for sterile connection with the second additional container such that the one or more platelet units of the second additional container can be transferred from the second additional container to the additional container under sterile conditions.

Embodiment 259. The method as in any one of embodiments 255-258, wherein the processing unit further comprises a second additional container suitable for housing one or more of the two or more portions of platelets, the second additional container being connected to the additional container, such that one or more portions of platelets from the second additional container can be transferred from the second additional container to the additional container under sterile conditions.

Embodiment 260. The kit as in any one of embodiments 257-259, wherein the additional container is suitable for containing a portion of platelets obtained by apheresis from the first donor, and wherein the second additional container is suitable for containing

-

Claims (26)

a portion of platelets obtained by apheresis from a second donor. Embodiment 261. The kit as in any one of embodiments 253-260, wherein the SIP is psoralen. Embodiment 262. The kit of Embodiment 261, wherein the SIP is amotosalen. Embodiment 263: The treatment unit of any one of embodiments 243252 or the kit of any of embodiments 253-262, wherein the platelet units in the plurality of platelet units each contain a therapeutic dose of platelets. CLAIM 1. A method of producing a plurality of platelet units, each unit containing a therapeutic dose of platelets suitable for infusion into a human subject, comprising: a) maintaining a repository log of platelet preparations collected by apheresis, the repository log containing for each platelet preparation a unique identifier, the donor's blood type, the time of donation and the number of platelets in the preparation; b) identification of an available donor suitable for apheresis platelet donation; c) selecting from the storage log at least one preparation of platelets in the storage from the first donor to be combined with platelets collected from an existing donor, wherein the first donor is different from the existing donor; d) collecting a new portion of platelets by apheresis from an existing donor, e) combining at least one selected platelet preparation from the stock of apheresis platelet preparations and a new supply of platelets to obtain a pooled platelet preparation; and f) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from at least one selected preparation from the stock of apheresis platelet preparations , and a new portion of platelets from an existing donor without combining at least the first selected drug and a new portion of platelets. 2. The method of claim 1, wherein the at least one selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. 3. The method of claim 1, wherein the at least one selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. 4. The method of claim 1, wherein the at least one selected platelet preparation contains more platelets than the number required to produce three units of platelets, but less than the number of platelets required to obtain four units of platelets. 5. The method according to any one of claims 1 to 4, wherein collecting a new platelet unit comprises adjusting the platelet collection to obtain a batch containing at least about 125% of the number of platelets required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. 6. The method according to any one of claims 1 to 4, wherein the new batch of platelets contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets required to obtain two units of platelets. 7. The method according to any one of claims 1 to 4, wherein the new batch of platelets contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets required to obtain three units of platelets. 8. The method of claim 2, wherein collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain three units of platelets from the pooled preparation. 9. The method of claim 3, wherein collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain five units of platelets from the pooled preparation. 10. The method of claim 4, wherein collecting a new supply of platelets from an existing donor includes collecting enough platelets to obtain seven units of platelets from the pooled preparation. 11. The method according to claim 5 or 6, wherein the plurality of platelet units comprises three platelet units. 12. The method according to any one of claims 1 to 11, further comprising identifying a second available donor suitable for platelet donation by apheresis, collecting a second new portion of platelets by apheresis from the second available donor, combining the second new portion of platelets with at least one selected drug from a stock of platelet preparations obtained by apheresis and a new portion of platelets from an existing donor to obtain a pooled preparation - 80 043840 platelets and dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, the plurality of platelet units containing a greater number of platelet units than the total number of platelet units that can be obtained from at least one selected platelet preparation and a new portion platelets and a second new batch of platelets without combining at least one selected platelet preparation and a new batch of platelets and a second new batch of platelets. 13. The method according to any one of claims 1 to 12, further comprising subjecting each of at least one selected platelet preparation and a new portion of platelets to a pathogen inactivation process. 14. The method of claim 13, wherein subjecting each of the at least one selected platelet preparation and the fresh platelet batch to a pathogen inactivation process, comprising treating each of the at least one selected platelet preparation and the fresh platelet batch with a pathogen inactivating compound. 15. The method according to any one of claims 1 to 12, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process. 16. The method of claim 15, wherein subjecting the pooled platelet preparation to a pathogen inactivation process comprises treating the pooled platelet preparation with a pathogen inactivating compound. 17. The method according to claim 14 or 16, where the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin and merocyanine 540; optionally, wherein the pathogen inactivating compound is psoralen; optionally, wherein the pathogen inactivating compound is amotosalen. 18. The method of any one of claims 1 to 17, wherein each unit of platelets contains at least about 2.0 x 1011 platelets. 19. The method of claim 5, wherein tailoring the platelet collection includes one or more of determining optimal platelet collection, providing input to the apheresis system, and providing a collection volume to the apheresis system. 20. A method for collecting a portion of platelets by apheresis from a donor, including: a) maintaining a repository log of platelet preparations collected by apheresis, the repository log containing for each platelet preparation a unique identifier, the donor's blood type, the date of donation and the number of platelets in the preparation; b) identification of a suitable donor for apheresis platelet donation; c) selecting from the storage log one or more platelet preparations suitable for combination with a new platelet portion collected by apheresis from a donor, where one or more selected platelet preparations are from a donor other than the donor specified in b); d) determining a target volume of the new platelet supply, wherein the target volume optimizes the number of platelet units that can be obtained from the combination containing the new platelet supply and one or more selected platelet preparations; e) collecting the target volume of a new portion of platelets by apheresis from the donor; f) combining one or more of the selected platelet preparation and a new portion of platelets to obtain a pooled platelet preparation; and g) dividing the pooled platelet preparation into a plurality of platelet units, each in a separate container, wherein each of the platelet units in the plurality of platelet units contains a therapeutic dose suitable for infusion into a human subject. 21. The method of claim 20, wherein the plurality of platelet units comprises a greater number of platelet units than the total number of platelet units that can be obtained from one or more selected platelet preparations from the stock of platelet preparations obtained by apheresis and a new supply of platelets from a donor without combining one or more selected platelet preparations and a new supply of platelets. 22. The method according to any one of claims 20, 21, wherein the one or more selected platelet preparation contains more platelets than the number required to obtain one unit of platelets, but less than the number of platelets necessary to obtain two units of platelets. 23. The method of claim 22, wherein collecting a new supply of platelets from a donor includes collecting enough platelets to obtain three units of platelets from the pooled preparation. 24. The method according to any one of claims 20, 21, wherein the one or more selected platelet preparation contains more platelets than the number required to obtain two units of platelets, but less than the number of platelets necessary to obtain three units of platelets. 25. The method of claim 24, wherein collecting a new supply of platelets from a donor includes collecting enough platelets to obtain five units of platelets from the pooled preparation. 26. The method according to any one of claims 20-25, further comprising subjecting the pooled platelet preparation to a pathogen inactivation process. -