Proclara Biosciences, Inc.

Amyl Therapeutics Srl

Amyl Therapeutics

Richard Fisher

Rajaraman Krishnan

Eva Asp

Ming Proschitsky

Francis Joseph Carr

Timothy David Jones

Robert G E Holgate

Timothy Gareth Jones

Robert George Edward Holgate

Robert GE Holgate

The present invention relates to variants of the general amyloid interaction motif (GAIM) of bacteriophage gene 3 protein (g3p) and fusion proteins thereof. The GAIM variants and fusion proteins of the invention are partially or fully deimmunized and demonstrate superior binding and specificity to a diverse array of amyloid proteins, and exhibit enhanced amyloid remodeling and inhibition of amyloid aggregation. The present invention further relates to nucleic acids, vectors, host cells, and methods of making the GAIM variants and fusion proteins thereof. The present invention also relates to pharmaceutical compositions and methods of increasing bacteriophage infectivity, methods of detecting amyloid aggregates, and methods of diagnosing and/or treating a disease associated with misfolded and/or aggregated amyloid protein.

General amyloid interaction motif (GAIM)

The invention relates to polypeptides that comprise a portion of filamentous bacteriophage gene 3 protein (g3p) sufficient to bind to and/or disaggregate amyloid, e.g., the N1-N2 portion of g3p and mutants and fragments thereof, wherein that g3p amino acid sequence has been modified through amino acid deletion, insertion or substitution to remove a putative glycosylation signal. The invention further relates to such polypeptides that are also modified through additional amino acid substitution to be substantially less immunogenic than the corresponding wild-type g3p amino acid sequence when used in vivo. The polypeptides of the invention retain their ability to bind and/or disaggregate amyloid. The invention further relates to the use of these g3p-modified polypeptides in the treatment and/or prevention of diseases associated with misfolding or aggregation of amyloid.

Polypeptides comprising a modified bacteriophage G3P amino acid sequence lacking a glycosylation signal

The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of an proteins. The compositions may also be used to detect amyloid.

Fusion proteins comprising P3 of bacteriophage

The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Bacteriophage gene 3 protein compositions and use as amyloid binding agents

The invention relates to polypeptides that comprise a portion of filamentous bacteriophage gene 3 protein (g3p) sufficient to bind to and/or disaggregate amyloid, e.g., the N1-N2 portion of g3p and mutants and fragments thereof, wherein that g3p amino acid sequence has been modified through amino acid substitution to be substantially less immunogenic than the corresponding wild-type g3p amino acid sequence when used in vivo. The polypeptides of the invention retain their ability bind to and/or disaggregate amyloid. The invention relates furthermore to the use of these variant g3p-polypeptides in the treatment and/or prevention of diseases associated with misfolding or aggregation of amyloid.

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Cambridge, MA, United States of America

Richard Fisher