Compositions and methods for treating diseases of protein aggregation involving ic3b deposition
OwnerGuriqbal S. Basi, Robin Barbourinventors
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Abstract
The invention provides antibodies that preferentially bind to iC3b relative to C3b. These antibodies serve to reduce the toxicity of this fragment and find use in treatment and prophylaxis of a variety of diseases associated with deposits of the fragment.
Claims68
A chimeric, humanized, veneered or isolated human antibody that preferentially binds to iC3b relative to C3b.
The antibody of claim 1 that is a chimeric, humanized or veneered form of an antibody producible by the method of any of claims 37-42.
The antibody of any preceding claim that is an Fab fragment, single chain Fv, or single domain antibody.
The antibody of any preceding claim having at least one mutation in the constant region.
A pharmaceutical composition comprising an antibody of any preceding claim and a pharmaceutically acceptable excipient.
A method of treating or effecting prophylaxis of a disease characterized by abnormal levels or distribution of iC3b relative to healthy individuals comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having or at risk of a disease associated with iC3b aggregation and thereby treating or effecting prophylaxis of the disease.
A method of inhibiting formation of drusen comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having or at risk of a disease associated with drusen formation and thereby inhibiting drusen formation in the patient.
A method of inhibiting aggregation of iC3b comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having or at risk of a disease associated with iC3b aggregation and thereby inhibiting iC3b aggregation in the patient.
A method of stabilizing a non-toxic conformation of iC3b comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having or at risk of a disease associated with iC3b and thereby stabilizing a nontoxic conformation of iC3b.
A method of clearing drusen comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having drusen and thereby clearing drusen from the patient.
A method of clearing iC3b comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having an abnormally high level of iC3b and thereby clearing iC3b from the patient.
A method of treating or effecting prophylaxis of a disease associated with iC3b, comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having or at risk of the disease and thereby treating or effecting prophylaxis of the disease.
A method of treating or effecting prophylaxis of age related macular degeneration comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3 or an agent that induces such an antibody to a patient having or at risk of the disease and thereby treating or effecting prophylaxis of the disease.
A method of treating or effecting prophylaxis of Alzheimer's disease comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody, to a patient having or at risk of the disease and thereby treating or effecting prophylaxis of the disease;
- wherein the antibody stains plaques in immunohistochemical analysis of AD brain.
A method of reducing amyloid plaque in an Alzheimer's disease patient comprising administering an effective regime of an antibody that preferentially binds to iC3b relative to C3b or an agent that induces such an antibody to a patient having the disease and thereby treating or effecting prophylaxis of the disease;
- wherein the antibody stains plaques in immunohistochemical analysis of AD brain.
A method of producing a monoclonal antibody that preferentially binds to iC3b over C3b, comprising
- immunizing a mammal with substantially intact iC3b and isolating B-cells producing antibodies;
- forming immortalized cell lines from the isolated B-cells;
- and
- screening the cell lines to identify a cell line producing a monoclonal antibody that preferentially binds to iC3b over C3b;
- wherein the screening is performed by an immunoassay in which the iC3b is indirectly immobilized to a plate via an antibody.
A method of producing a monoclonal antibody that preferentially binds to iC3b over C3b, comprising
- immunizing a non-human animal with substantially intact iC3b and isolating B-cells producing antibodies;
- forming immortalized cell lines from the isolated B-cells;
- screening the cell lines to identify a cell line producing a monoclonal antibody that preferentially binds to iC3b over C3b;
- and
- producing a humanized, chimeric or veneered form of the antibody.
A method of producing a monoclonal antibody that preferentially binds to iC3b over C3b, comprising
- immunizing of a human or non-human animal with human immune system genes with substantially intact iC3b and isolating B-cells producing antibodies;
- forming immortalized cell lines from the isolated B-cells;
- and
- screening the cell lines to identify a cell line producing a monoclonal antibody that preferentially binds to iC3b over C3b.
A method of screening an agent for activity against a disease associated with iC3b, comprising administering the agent to a non-human animal disposed to develop deposits of iC3b, and determining whether the agent inhibits, reduces or delays deposits of iC3b or a consequential sign or symptom of a disease associated with such deposits, wherein the agent is
- (i) an antibody that preferentially binds to iC3b relative to C3b;
- or
- (ii) an agent that induces such an antibody.
A method of screening an agent for activity against Alzheimer's disease, comprising administering the agent to a transgenic non-human animal disposed to develop characteristic of Alzheimer's disease, and determining whether the agent affects the extent or rate of development of the characteristic relative to a control transgenic nonhuman animal, wherein the agent is
- (i) an antibody that preferentially binds to iC3b relative to C3b;
- or
- (ii) an agent that induces such an antibody.
A method of screening an agent for activity against Alzheimer's disease, comprising administering the agent to a non-human animal disposed to develop amyloid plaque, and determining whether the agent inhibits, reduces or delays deposits of amyloid plaque or a consequential sign or symptom of a disease associated with such amyloid plaque, wherein the agent is
- (i) an antibody that preferentially binds to iC3b relative to C3b;
- or
- (ii) an agent that induces such an antibody.
A method of determining a level of drusen deposits in a patient, comprising administering an antibody that preferentially binds to iC3b relative C3b;
- and detecting presence of bound antibody in the patient.
Dependencies are inferred from the claim text.