Bacteriophage Gene 3 Protein Compositions and Use as Amyloid Binding Agents

A fusion protein, comprising a first domain that binds amyloid, wherein the first domain comprises at least one g3p or amyloid binding fragment thereof;

• and a second domain for use in reducing amyloid, inhibiting amyloid formation, inhibiting amyloid aggregation, or removing and/or preventing the formation of toxic oligomers in a patient in need thereof.

A pharmaceutical composition comprising an isolated filamentous phage that expresses a mutant or variant g3p for use in reducing amyloid, inhibiting amyloid formation, inhibiting amyloid aggregation, or removing and/or preventing the formation of toxic oligomers in a patient in need thereof.

A pharmaceutical composition comprising an isolated filamentous phage that expresses 5 or more copies of g3p, or 5 or more copies of a mutant or variant g3p for use in reducing amyloid, inhibiting amyloid formation, inhibiting amyloid aggregation, or removing and/or preventing the formation of toxic oligomers in a patient in need thereof.

The pharmaceutical composition of claim 32, wherein the use comprises treating Alzheimer's disease.

A composition comprising a polypeptide that binds amyloid, wherein the polypeptide comprises a detectable label and a gene 3 protein (g3p), an amyloid binding fragment of g3p, or a mutant or variant thereof, wherein the amyloid binding fragment comprises the entire N2 domain of g3p and wherein the polypeptide does not comprise a bacteriophage.

A composition comprising a polypeptide that binds amyloid, wherein the polypeptide comprises a gene 3 protein (g3p), an amyloid binding fragment of g3p, or a mutant or variant thereof for use to detect or image an amyloid aggregate.

A method of detecting amyloid in a patient, comprising the steps of:

• a) administering to the patient a pharmaceutical composition comprising a polypeptide that binds amyloid, wherein the polypeptide comprises a gene 3 protein (g3p), an amyloid binding fragment of g3p, or a mutant or variant thereof, and a detectable label;
• and
• b) detecting the label.

A composition comprising a g3p polypeptide, an amyloid binding fragment that comprises the entire N2 domain of g3p, or a mutant or variant thereof, fused to at least one protein with which it is not normally associated.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a polypeptide that binds amyloid, wherein the polypeptide comprises a g3p protein, an amyloid binding fragment that comprises the entire N2 domain of g3p, or a mutant or variant thereof;

• and wherein the polypeptide does not comprise a bacteriophage.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a polypeptide that binds amyloid, wherein the polypeptide comprises a g3p protein or an amyloid binding fragment thereof, wherein the polypeptide comprises a N1 and a N2 domain of g3p, wherein the hinge region of N2 is mutated such that the hinge Tm is lower than the hinge Tm of a wild type M13 phage, and wherein the polypeptide binds amyloid with higher affinity than M13.

A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a fusion protein, comprising a first domain that binds amyloid, wherein the first domain comprises at least one Op or amyloid binding fragment thereof and wherein the second domain is an immunoglobulin Fc fragment.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a fusion protein, comprising a first domain that binds amyloid, wherein the first domain comprises at least one g3p or amyloid binding fragment thereof that comprises an entire N2 domain;

• and a second domain.