Antibody-peptide fusion proteins for treating amyloid disorders

An antibody-peptide fusion protein, comprising:

• an antibody that binds to amyloid fibrils comprising a first polypeptide and a second polypeptide each comprising a light chain of the antibody, and a third and a fourth polypeptide each comprising a heavy chain of the antibody, and
• an amyloid-reactive peptide that is linked to the N-terminus or the C-terminus of the light chain or the heavy chain, wherein
• a) the first polypeptide and second polypeptide comprise the amino acid set forth in SEQ ID NO:87, and the third and fourth polypeptide comprise the amino acid sequence set forth in SEQ ID NO:91;
• b) the first polypeptide and second polypeptide comprise the amino acid set forth in SEQ ID NO:88, and the third and fourth polypeptide comprise the amino acid sequence set forth in SEQ ID NO:92;
• c) the first polypeptide and second polypeptide comprise the amino acid set forth in SEQ ID NO:89, and the third and fourth polypeptide comprise the amino acid sequence set forth in SEQ ID NO:91;
• or
• d) the first polypeptide and second polypeptide comprise the amino acid set forth in SEQ ID NO:90, and the third and fourth polypeptide comprise the amino acid sequence set forth in SEQ ID NO:91.

A composition comprising

• an antibody-peptide fusion protein, comprising:
• i) an amyloid-reactive peptide;
• and
• ii) an antibody that is capable of inducing phagocytosis and serving as an opsonin, wherein the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a light chain comprising a light chain variable region (VL), wherein the amyloid-reactive peptide and antibody are linked at the N-terminal end or the C-terminal end of the heavy chain or the light chain, wherein the amyloid-reactive peptide is linked to the antibody via a spacer, or without a spacer;
• and
• wherein at least 90% of the antibody-peptide fusion protein is intact.

A method of producing an antibody-peptide fusion protein comprising

• a) culturing a host cell comprising a vector encoding an antibody-peptide fusion protein under perfusion cell culture conditions suitable for expression of the antibody-peptide fusion protein;
• and
• b) recovering the antibody-peptide fusion protein about every 12-36 hours;
• wherein the antibody-peptide fusion protein comprises
• i) an amyloid-reactive peptide;
• and
• ii) an antibody that is capable of inducing phagocytosis and serving as an opsonin, wherein the antibody comprises a heavy chain comprising a heavy chain variable region (VH) and a light chain comprising a light chain variable region (VL), wherein the amyloid-reactive peptide and antibody are linked at the C-terminal end of the light chain, wherein the amyloid-reactive peptide is linked to the antibody via a spacer, or without a spacer.