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Preparation of pathogen inactivated solution of red blood cells having reduced immunogenicity

A technology for red blood cells and pathogens, which can be used in extracellular fluid diseases, organic active ingredients, antibacterial drugs, etc., and can solve problems such as formation and heterologous sensitization.

Inactive Publication Date: 2003-08-13
CERUS CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These methods have the disadvantage that neoantigens may be formed due to side reactions with cell membranes and plasma components
The risk is probably small, but repeated use of this pathogen-inactivated product could lead to heterologous sensitization

Method used

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  • Preparation of pathogen inactivated solution of red blood cells having reduced immunogenicity

Examples

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Embodiment 1

[0088] EXPERIMENTAL SECTION EXAMPLE 1: DETERMINATION OF THE INACTIVATION OF R17 BY THE COMPOUNDS AND METHODS OF THE INVENTION

[0089] This example describes a method for assaying the inactivation of bacteriophage R17 by compounds and methods of the invention. This method is used to determine the inactivation potency of compounds of the invention in different processing steps. Specifically, compounds and methods for inactivation and compounds and methods for masking erythrocyte immunogenicity are analyzed separately. All methods of producing less infectious and less immunogenic red blood cell compositions were also analyzed. Since R17 immunogenicity may be masked simultaneously with RBC immunogenicity, it is important to evaluate this separately. The purpose of this example was to determine whether the compounds and methods of the invention also inactivated R17.

[0090]The assay measures the ability of phages to infect bacteria and inhibit their gro...

Embodiment 2

[0091] To demonstrate the efficacy of compounds that mask immunogenicity of erythrocytes and the efficacy of the overall method of preparing the treated erythrocyte compositions, R17-Adsol solutions were treated appropriately and then plated as described above. Inactivation titers were assessed by adding appropriate solutions (without inactivating or antigen-masking compounds) to appropriate controls as described above. This assay can also be supplemented with other solutions instead of Adsol. Embodiment 2: Determination of the inactivation of the compounds and methods of the present invention to HIV

[0092] Cells infected with HIV in TC culture medium (Popovic et al., Science, 224:497 (1984): H9-IIIb cells were suspended in tissue culture medium to obtain a plaque-forming unit / mL assay titer Suspension. To a 2 mL aliquot of test medium in a 15 mL conical test tube was added sufficient pathogen-inactivating compound solution to obtain the desired concentration of active subs...

Embodiment 3

[0095] To demonstrate the efficacy of compounds that mask the immunogenicity of erythrocytes, as well as the efficacy of the overall method of preparing the treated erythrocyte compositions, HIV solutions were treated appropriately and then titrated as described above. Inactivation titers were assessed by adding appropriate solutions (without inactivating or antigen-masking compounds) to appropriate controls as described above. This assay can also be supplemented with other solutions instead of Adsol. Embodiment 3: Determination of the inactivation of compounds and methods of the present invention to Yersinia enterocolitica

[0096] Yersinia enterocolitica (California Department of Health Services, Laboratory of Microbial Diseases, Berkeley, CA) was grown overnight at 37°C in LB-broth on a shaker at 180 rpm. To determine the titer, measure the optical density diluted 1:100 in Adsol (10 8 OD at bacteria / mL 610 = 0.2). The bacterial stock was then diluted 1:100 into either s...

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PUM

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Abstract

Compounds and methods are provided for the preparation of a red blood cell composition which has significantly reduced antigenicity and in which any possible pathogen contaminants have been substantially inactivated. The red blood cell compositions are of particular use for introduction into an individual in cases where the potential for an immune reaction is high, for example in alloimmunized blood recipients or in trauma situations where the possibility of transfusion of a mismatched unit of blood is higher. The red blood cell compositions of this invention provide a much lower risk of transfusion associated disease transmission as well as a much lower risk of a transfusion associated immune reaction.

Description

[0001] Introduction to the application [0002] This application claims priority from US Provisional Patent Application 60 / 208962 (filed May 31, 2000), the disclosure of which is incorporated herein by reference. technical field [0003] The present invention relates to compositions and methods for reducing the risks associated with the inter-individual delivery of cellular components, in particular to reducing the risk of complications due to immune responses during blood transfusions, and to combinations that reduce the risk of infectious diseases during blood transfusions things and methods. The present invention is primarily concerned with reducing the risk of an immune response as well as the risk of disease transmission during the delivery of red blood cell components. Background of the invention [0004] Blood transfusions are necessary in the management of patients with anemia, trauma, surgical blo...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61K31/473A61K31/765A61K35/16A61K35/18A61P7/00A61P7/06A61P31/04A61P31/12A61P41/00C12N5/08
CPCA61K35/16A61K35/18A61P31/04A61P31/12A61P41/00A61P7/00A61P7/06
Inventor A·斯塔西诺普洛斯
Owner CERUS CORP
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