Liquid purification or separation – Processes – Separating
Reexamination Certificate
2002-11-05
2004-01-27
Kim, John (Department: 1723)
Liquid purification or separation
Processes
Separating
C210S435000, C210S488000, C210S489000, C210S490000, C210S504000, C210S506000, C604S406000, C604S408000
Reexamination Certificate
active
06682656
ABSTRACT:
TECHNICAL FIELD
This invention relates to treating biological fluid, and particularly relates to removing at least one complement fragment from blood components, especially platelet concentrate or apheresis platelets, during storage.
BACKGROUND OF THE INVENTION
The complement system acts on its own and in cooperation with antibodies in defending vertebrates against infection. The complement system is composed of a series of plasma-borne blood proteins (proenzymes) that are sequentially activated in a series of reactions. The proteins are activated in cascade fashion, i.e., the output of one reaction is the input for the next. The cascade ultimately generates a terminal five-protein membrane attack complex (MAC, C5b-9), whose physiological function is protection of the host from invading microorganisms. The MAC causes lysis of the microorganisms.
While the complement system is generally beneficial in protecting the host, the presence of the various activated or activatable blood proteins (and fragments thereof) can be undesirable, particularly when these proteins and/or fragments are present in blood or blood components used for transfusion. For example, transfusing activated complement into a patient can cause adverse affects such as anaphylactoid reactions, platelet aggregation, and/or immune suppression. The problem can be magnified when transfusing stored blood or blood components, since the proteins can be activated while processing the blood components and/or while storing the components, e.g., due to contact between the plasma-borne proteins and the surfaces of the plastic blood bag and/or the blood bag tubing. Activation can lead to the administration of biologically active complement fragments such as C3a and its metabolite, C3a des Arg
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.
Accordingly, there is a need in the art for a device for use with blood and blood components that removes at least one complement fragment. Additionally, since activated complement can continue to accumulate during storage, there is an unaddressed need in the art for a device that removes at least one complement fragment from the desired blood component(s) during the storage period without requiring additional processing steps that could lead to further complement activation.
The present invention provides for ameliorating at least some of the disadvantages of the prior art. These and other advantages of the present invention will be apparent from the description as set forth below.
SUMMARY OF THE INVENTION
In accordance with the present invention, a biological fluid is placed in contact with a complement filter, wherein the filter depletes complement from the fluid. In a more preferred embodiment, the filter is capable of retaining complement without substantially retaining desirable components of the biological fluid.
Preferably, the present invention provides for collecting a biological fluid in a container including the complement filter, and storing the fluid in the container so that a significant amount of the complement produced during storage is captured or retained by the filter. Thus, the filter can provide a complement “sink.” In a more preferred embodiment, the movement of biological fluid in the bag, e.g., as the bag is handled during handling and/or storage protocols, exposes more of the fluid to the complement filter, thus continuing to remove or retain complement as it is produced.
Systems, methods and devices according to the present invention are compatible with a wide variety of biological fluid treatment protocols, and, in preferred embodiments, require little or no modification of existing biological fluid handling steps or procedures. Thus, another advantage of one embodiment of the present invention is that there is no need to re-train the technicians carrying out the biological fluid processing protocol.
The following definitions are used in accordance with the invention:
(A) Complement. As used herein, the term “complement” includes at least one of a complement protein, complement component (e.g., C1 through C9), complement fragment, biologically active fragment of a component (and metabolite of the fragment), complement factor (e.g., factor B and factor D), complement subcomponent, and complement complex (e.g., C{overscore (567)}1). Exemplary biologically active fragments and metabolites thereof include C3a, C3a des Arg
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, C4a, C4a des Arg, C5a, and C5a des Arg.
(B) Biological Fluid. A biological fluid includes any treated or untreated fluid (including a suspension) associated with living organisms, particularly blood, including whole blood, warm or cold blood, and stored or fresh blood; treated blood, such as blood diluted with at least one physiological solution, including but not limited to saline, nutrient, and/or anticoagulant solutions; blood components, such as platelet concentrate (PC), apheresed platelets, platelet-rich plasma (PRP), platelet-poor plasma (PPP), platelet-free plasma, plasma, serum, fresh frozen plasma (FFP), components obtained from plasma, packed red cells (PRC), buffy coat (BC); blood products derived from blood or a blood component or derived from bone marrow; red cells separated from plasma and resuspended in physiological fluid; and platelets separated from plasma and resuspended in physiological fluid. The biological fluid may have been treated to remove some of the leukocytes before being processed according to the invention. As used herein, blood product or biological fluid refers to the components described above, and to similar blood products or biological fluids obtained by other means and with similar properties.
A “unit” is the quantity of biological fluid from a donor or derived from one unit of whole blood. It may also refer to the quantity drawn during a single donation, e.g., during apheresis. Typically, the volume of a unit varies, the amount differing from patient to patient and from donation to donation. Multiple units of some blood components, particularly whole blood derived platelets and buffy coat, may be pooled or combined, typically by combining four or more units.
(C) Complement Filter. The complement filter separates complement from the biological fluid, e.g., it captures, binds, or retains complement (defined above). Thus, the complement filter can be used to provide a complement-depleted biological fluid. For example, the filter can remove or retain at least one complement fragment, e.g., biologically active complement fragments such as at least one of C3a and C5a. In a preferred embodiment, the complement filter removes C3a. In some embodiments, the complement filter can also suppress complement activation.
Preferably, the filter removes or retains complement, more preferably, C3a, without adversely affecting, or without significantly adversely affecting, the clinical effects of desirable biological fluid components such as plasma, platelets, and/or red blood cells. More preferably, the filter removes or retains C3a without significantly reducing the recovery of the desirable biological fluid component(s). In some embodiments, the complement filter also removes or retains undesirable material such as interleukin 8 (IL 8) and/or RANTES.
In an embodiment, the complement filter comprises at least one porous substrate of any suitable nature, e.g., a fibrous web, a membrane, combinations thereof, and the like. The porous substrate can have any suitable physical dimensions and typically will be in sheet form having two opposing sides (e.g., a first side and an opposing second side) with a central portion therebetween, wherein the pores in the porous substrate will generally enable fluid communication between the first and second sides of the porous substrate. Preferably, the complement filter comprises at least one membrane, more preferably a microporous membrane, through which at least a portion of the plasma component of a biological fluid (e.g., a portion of the plasma present in blood, or the plasma suspending other blood components such as red blood cells and/or platelets) passes. The membrane has two opposing sides (e.g., a first side and an opposi
DelGiacco Gerard R.
Garcez Randy
Gsell Thomas
Rothman Isaac
Salinaro Richard
Kim John
Leydig , Voit & Mayer, Ltd.
Pall Corporation
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