Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Animal cell – per se – expressing immunoglobulin – antibody – or...
Reexamination Certificate
2000-07-14
2004-09-14
Smith, Lynette R. F. (Department: 1645)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Animal cell, per se, expressing immunoglobulin, antibody, or...
C424S001490, C424S009200, C424S009340, C424S093100, C424S093480, C424S137100, C424S150100, C424S163100, C424S164100, C424S165100, C424S169100, C424S178100, C424S184100, C424S278100, C435S002000, C435S007100, C435S007320, C435S007370, C435S007920, C435S007930, C435S007940, C435S007950, C435S069600, C435S174000, C435S176000, C435S177000, C435S325000, C436S020000, C436S021000
Reexamination Certificate
active
06790661
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the screening of blood or a blood product (including whole blood, hematopoietic stem cells, leukocytes, plasma, serum, red blood cells, and platelets) or a donor tissue for the presence of a clinically relevant amount of bacteria More particularly, the invention relates to the screening for the presence of a clinically relevant amount of contaminating bacteria in blood and blood products or donor tissue that will be used for transfusion or transplantation.
2. Summary of the Related Art
Transfusion of blood and blood products is a therapeutically important aspect of patient care. Transplantation of donor tissues and organs is likewise therapeutically important. The absence of clinically relevant levels of contaminating bacteria in donor blood, donor blood product, or a donor tissue or organ is a requirement necessary for the safe, therapeutic use of these donated fluids and tissues for transfusion or transplantation. For example, bacteremia (the invasion of bacteria into the blood) can be transient, continuous, or intermittent. Wagner et al. (Clin. Microbiol. Rev. 7: 290-302 (1994)) and Goldman et al. (Trans. Med. Revs. 5: 73-83 (1991)) teach that a large number of different species of bacteria have been identified in contaminated blood transfused to patients who, following transfusion, developed septicimia. Tadler et al. (J. Clin. Laboratory Analysis 2: 21-25 (1989)) teaches that although transient bacteremia is generally of little consequence, continuous or intermittent bacteremia can present life-threatening situations for several patient populations, particularly immunocompromised, neonatal, and geriatric patients. Thus, if blood contaminated with a clinically relevant amount of bacteria were to be transfused to a recipient patient, the recipient patient might suffer complications, particularly since transfusions of blood and/or blood products are often performed when the patient is undergoing major surgery, or is otherwise vulnerable.
Similarly, donor tissues and organs are preferably microbe-free to retard and, preferably, prevent rejection by the recipient.
Despite the need for a safe, microbe-free supply of blood or a blood product, no rapid, efficient method exists for detecting the presence of contaminating bacteria in blood or a blood product. Although there are methods for determining whether or not blood is infected with bacteria, most current bacterial testing is done on patients suspected of having infected blood, with the prime intent of identifying the exact micro-organism that is causing the infection, so that the appropriate antibiotic therapy can begin. In these methods, to identify the infecting bacteria, a sample of patient blood is grown in a culture media that favors the growth of the bacteria for a relatively long period of time. Eventually, the number of micro-organisms present is amplified to the point that a reasonable quantity exists and can be detected.
Although these culture-based blood testing techniques are useful for determining the particular type of bacteria that is infecting a patient's blood, the length of the time required to perform these techniques makes them impractical to use to test donor blood and blood products or donor organs. This is because donor blood, blood products, and organs are often needed for use as transfusions or transplantations on relatively short notice. Thus, there may be no time to test the donated blood (or blood product) or organ with a culture-based technique before the donated blood or organ is needed for use.
In addition, donated organs and blood or blood products have a relatively short shelf-life due not only to a loss of function of the donated material, but also to an increase in amount of any contaminating bacteria present. Since bacteria have a rapid propagation rate, even a small amount of contaminating bacteria present in the donated blood or blood product will quickly amplify with time. For example, while donated platelets are functionally viable only 7 days post-donation, they are rarely used more than 5 days post-donation for fear of bacterial contamination that, when donated, may not have been significant but, over time, may have increased to a level that is clinically relevant. Moreover, these culture-based blood testing techniques take too long to routinely screen platelets, which have a short shelf-life (approximately 5 days post-donation), for transfusion use.
Brecher et al. (Transfusion 34(9): 750-755 (1994)) teaches another technique for detecting a particular contaminating bacteria in blood using labelled nucleic acid probes to hybridize to the genetic material of potential contaminants The probes used in these studies, however, are very limited in the number of micro-organisms that can be detected and, unfortunately, no commercially viable test has emerged from this technology. Given their complexity, these techniques are too labor-intensive and too time-costly to be routinely used to screen blood or blood products for bacterial contamination.
There is, therefore, a need for a technique for rapidly detecting the presence of a clinically relevant amount of any contaminating bacteria in donor blood or a blood product, or in a donor tissue. Ideally, antigen binding techniques could be rapidly and effectively employed. Unfortunately, Wagner, S. J. (Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. 283(3):253-257 (1996)) teaches that no common antigenic source exists for broad based bacterial detection. Thus, there is a need for antigen binding-based techniques for detecting clinically relevant amounts of contaminating bacteria in donor blood or blood products or in donor tissues.
BRIEF SUMMARY OF THE INVENTION
The invention provides rapid antigen binding-based methods for detecting clinically relevant amounts of contaminating bacteria in blood or blood products or in donor tissue, particularly donor blood or blood products or donor tissue to be transferred from one individual to another.
Accordingly, in a first aspect, the invention provides a method for screening for the presence of a clinically relevant amount of bacteria in donor blood or a donor blood product from a donor mammal for transfer to a recipient mammal comprising contacting a sample of blood or a blood product with a set of binding agents, wherein the set of binding agents comprises binding agents that specifically bind to a Gram-negative bacterial antigen and binding agents that specifically bind to a Gram-positive bacterial antigen, and determining binding of the set of binding agents to the sample, wherein binding indicates the presence of a clinically relevant amount of bacteria in the donor blood or blood product and no binding indicates the absence of a clinically relevant amount of bacteria in the donor blood or blood product.
In certain embodiments of the first aspect of the invention, the sample is treated prior to or concomitantly with contacting the sample with the set of binding agents. Preferably, the treatment exposes a binding site of the binding agent on the Gram-negative bacterial antigen or on the Gram-positive bacterial antigen. In certain embodiments of the first aspect of the invention, the donor blood or blood product determined to have an absence of a clinically relevant amount of bacteria is administered to a recipient mammal. Preferably, the donor mammal and the recipient mammal are of the same species. In certain preferred embodiments, the binding agents that specifically bind to a Gram-negative bacterial antigen comprise antibodies or antibody derivatives that specifically bind to a Gram-negative bacterial antigen. In certain preferred embodiments, the binding agents that specifically bind to a Gram-negative bacterial antigen thereof comprise a molecule selected from the group consisting of a Limulus anti-lipopolysaccharide factor (LALF), a lipopolysaccharide binding protein (LBP), a bactericidal/permeability-increasing protein (BPI), and an antibiotic, such as polymixin or bacitracin. Preferably, the binding agent
Hines J.
Ropes & Gray LLP
Smith Lynette R. F.
Verax Biomedical, Inc.
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