Immunoadsorption
AssigneeuniQure IP B.V.
InventorValerie Ferreira
Life of this patent
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Abstract
Upon administration of rAAV vectors the humoral immune response (neutralizing antibodies) is the first barrier that needs to be overcome. Surprisingly it was found that by using immunoadsorption for depletion of immunoglobulins from the blood (plasma), subjects can be highly efficiently treated with rAAV vectors, i.e. obtain highly efficient transduction after rAAV vector administration, in spite of the presence of high levels of nAb.
Claims25
A method of administering a recombinant adeno-associated virus (rAAV) to a subject, comprising:
- (a) selectively depleting a subject's circulating anti-AAV immunoglobulins by contacting the subject's blood with an extracorporeal device for immunoadsorption, the device comprising a binding moiety attached to a matrix, wherein the binding moiety selectively binds anti-AAV immunoglobulins, and
- (b) subsequently administering an rAAV to the subject.
A method of decreasing a humoral immune response to a recombinant adeno-associated virus (rAAV) gene therapy in a subject comprising:
- (a) contacting the subject's blood with an extracorporeal device comprising a binding moiety that selectively binds anti-AAV immunoglobulins, wherein the binding moiety is attached to a matrix, thereby decreasing the humoral immune response to the rAAV gene therapy;
- and
- (b) subsequently administering rAAV gene therapy to the subject.
A method for reducing an anti-rAAV immunoglobulin concentration in the blood of a subject, comprising:
- a) obtaining blood from the subject, wherein the subject's blood comprises neutralizing antibodies that bind to a capsid of the rAAV as a result of previously receiving a treatment comprising a rAAV vector;
- b) separating the blood into plasma components and cellular components;
- c) contacting the plasma components with an extracorporeal immunoadsorption device, the device comprising a binding moiety attached to a matrix, wherein the binding moiety comprises an AAV epitope that is known to generate anti-AAV antibodies to selectively bind anti-rAAV immunoglobulins;
- d) reconstituting the blood by combining the cellular components with the plasma components that were subjected to immunoadsorption;
- and
- e) administering the reconstituted blood to the subject, thereby reducing the anti-rAAV immunoglobulin concentration in the subject's blood.
Dependencies are inferred from the claim text.