Liquid purification or separation – Processes – Separating
Reexamination Certificate
1999-03-08
2002-01-08
Kim, John (Department: 1723)
Liquid purification or separation
Processes
Separating
C210S435000, C210S446000, C210S483000, C210S488000, C210S490000, C210S491000, C210S503000, C210S504000, C210S505000, C210S508000, C428S323000, C428S327000
Reexamination Certificate
active
06337026
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the filtration of a blood products and more specifically, to a filtration media for the removal of leukocytes from blood products.
BACKGROUND OF THE INVENTION
The technology of human blood transfusion has improved significantly in recent years. Unlike early transfusion practices that involved the transfusion of units of whole blood, a recipient will now typically only receive that fraction of whole blood that is needed under the particular circumstances. For example, a patient in need of red blood cells can receive a transfusion of packed red cells (pRBC) or concentrated red cells (cRBC) and a patient in need of platelets can receive a transfusion of platelet concentrate, while a patient in need of increased blood volume can receive a transfusion of plasma or a plasma product. For transfusion purposes, a donated whole blood supply is typically separated into the aforementioned three components by centrifugation. In addition to these basic components, whole blood also contains various types of white blood cells, collectively known as leukocytes, which are present in substantial levels in both RBC and platelet suspensions.
Leukocytes, which include for example, granulocytes, macrocytes and lymphocytes, function to provide protection against a wide range of bacterial and viral infections. As such, the transfusion of a leukocyte-containing product might be expected to be beneficial in the therapy of immunosuppressive diseases. To the contrary however, research has shown that patients who received granulocyte transfusions will quickly develop such adverse effects as rigor, nausea, headache, and high fever, and shortly thereafter, will reject the transfused cells. In addition, it is known that certain viruses are resident in leukocytes and as a result, transfusion of infected cells to an immunosuppressed patient has the potential of inducing a life-threatening viral disease. Graft versus Host disease, as well as certain viruses, such as HIV, HTLV1 and CMV, among others, are now believed to be transmitted by the transfusion of infected leukocytes. Although a unified world-wide standard for acceptable leukocyte levels in donated blood products has yet to emerge, it is generally accepted that a majority of severe adverse effects may be reduced or prevented if the leukocyte content is reduced to, for example, less than one to five million leukocytes per unit of red cells transferred. Accordingly, it is therefore quite desirable to provide a clinically effective means for significantly and efficiently reducing the leukocyte content of donated biological fluids, namely, whole blood and blood component products.
A typical unit of pRBC averaging about 350 mL in volume contains between about 1×10
9
and 5×10
9
leukocytes. Differences in the leukocyte content are largely attributable to differences in the donor. According to internationally accepted standards, a unit of RBC must contain no more than 10
6
leukocytes for it to qualify as being leukocyte depleted. The corresponding leukocyte depletion rate required is thus on the order of 99.9% and 99.99%. Commercially viable filters should routinely deliver the higher level of leukocyte depletion to accommodate for normal variations in the source, filtration conditions, and age of the blood being filtered.
Various methods for removing leukocytes from biological fluids are known in the art and include for example, repeated centrifugation, saline washing, filtration and agglutinant incorporation/sedimentation. Of these methods, filtration has been accepted as the removal technique of choice. A typical leukocyte filtration process involves passing a leukocyte-rich blood product through a filter comprised of a material that adsorbs leukocytes and/or entraps them within the filter and obtaining a leukocyte-depleted filtered product without altering the physical and therapeutic characteristics of other blood components present in the product.
Leukocyte filtration of blood products may rely primarily on two mechanisms: sieving and adhesion. Sieving is typically caused by the mechanical entrapment of leukocytes within a filter material, while adhesion typically results from interactions between the leukocyte cell surface and the filter material itself. Conventional leukocyte reduction devices may involve a depth filtration medium that is comprised of various diameter fibers entwined into a web-like matrix, which provides for tortuous flow paths that offer different resistance to cells of different sizes and shapes, as well as substantial internal surface areas for preferential leukocyte adhesion. To accomplish acceptable selectivity between leukocytes and red blood cells, media of this type typically exhibit relatively small average pore sizes; thus resulting in modest flow rates through the filtration device.
U.S. Pat. No. 5,454,946 (the “'946 patent”) describes a leukocyte filter material that is comprised of a matrix of interlocked fibers having spaces between adjacent interstices wherein fibrillated particles of polymeric material are disposed within the spaces and a thermoplastic binder is disposed at least at cross-over sections of the matrix fibers. This patent states that the weight ratio of the fibrillated particles to the matrix fibers must be between about 1:99 and 40:60, and especially between about 5:95 and 40:60, and preferably less than about 20:80. If that ratio is less than about 3:97, the additional surface area supplied by the fibrillated particles is marginal for desired leukocyte filtration, and at below about 1:99, the surface area is simply not sufficient to achieve a minimum desired depletion of leukocytes, i.e., at least a 70% depletion. This patent further teaches that with increasing ratios of fibrillated particles to matrix fibers, the depletion of leukocytes from blood will be correspondingly increased, such that at a ratio of about 5:95, the depletion percentage will be close to about 90%, and at about 10:90, the depletion may be as high as about 99%, for some modes of blood filtration.
Thus, the '946 patent teaches that the filter media described therein achieves minimum desired leukocyte depletion if the weight ratio of fibrillated fibers to matrix fibers is within a specifically defined range, about 1:99 to 40:60. Moreover, leukocyte depletion rates increase with increasing weight ratios with optimal performance occurring at a weight ratio of 10:90. Conversely, leukocyte depletion rates decrease with decreasing weight ratio and that insufficient leukocyte reduction occurs at a weight ratio of fibrillated fibers to matrix fibers of less than about 1:99. According to the '946 patent, the desired minimum leukocyte reduction rate is 70%. In reality, however, leukocyte depletion devices, in order to meet commercial and medical requirements, typically should achieve leukocyte reduction rates of 99.9% or higher. Therefore, the '946 patent does not describe a leukocyte depletion device which achieves commercially and medically acceptable leukocyte filtration rates with a weight ratio of fibrillated fibers to matrix fibers of less than about 1:99.
The '946 patent also describes the use of fibrillated particles having a surface area of 30 or 50 or 70 square meters per gram in a filtration media and suggests that the use of surface area particles up to 100 square meters per gram may be used in a way where the particles are still retained in the matrix. However, the '946 patent does not teach or contemplate how one may achieve acceptable and/or superior leukocyte reduction using fibrillated particles of a higher surface area such as 100 m
2
/g, or even how to obtain fibrillated particles of such a high surface area.
SUMMARY OF THE INVENTION
We have discovered a way to achieve leukocyte reduction rates of substantially greater than 70% even when using a weight ratio of fibrillated fibers or particles to matrix fibers of less than or equal to about 1:100. We have also discovered that leukocyte reduction rates of 99.99% and higher may be achie
Lee Eric K.
Vernucci Paul J.
Williams Samuel C.
Clement, Esq. Candice J.
Heslin Rothenberg Farley & & Mesiti P.C.
Kim John
Whatman Hemasure, Inc.
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