Bispecific antibody

A bispecific antibody comprising:

• a first antigen-binding polypeptide that binds to amyloid beta (Aβ);
• and
• a second antigen-binding polypeptide that binds to human transferrin receptor (TfR),
• wherein:
• (i) the first antigen-binding polypeptide comprises a first heavy chain, a second heavy chain, and two light chains,
• wherein the first heavy chain and the second heavy chain each comprise a heavy chain variable region (VH) consisting of the amino acid sequence set forth in SEQ ID NO:
• 238,
• wherein the first heavy chain and the second heavy chain each comprise a constant region,
• wherein the two light chains each comprise a light chain variable region (VL) consisting of the amino acid sequence set forth in SEQ ID NO:
• 239;
• (ii) the second antigen-binding polypeptide comprises a heavy chain variable region comprising a heavy chain CDR1 (HCDR1) consisting of the amino acid sequence set forth in SEQ ID NO:
• 2, a heavy chain CDR2 (HCDR2) consisting of the amino acid sequence set forth in SEQ ID NO:
• 8 or SEQ ID NO:
• 13, and a heavy chain CDR3 (HCDR3) consisting of the amino acid sequence set forth in SEQ ID NO:
• 3, and a light chain variable region comprising a light chain CDR1 (LCDR1) consisting of the amino acid sequence set forth in SEQ ID NO:
• 4, a light chain CDR2 (LCDR2) consisting of the amino acid sequence set forth in SEQ ID NO:
• 5, and a light chain CDR3 (LCDR3) consisting of the amino acid sequence set forth in SEQ ID NO:
• 6;
• and
• (iii) the second antigen-binding polypeptide is connected to a C-terminus of the constant region of the second heavy chain of the first antigen-binding polypeptide via a peptide linker.

A bispecific antibody that binds to amyloid beta (Aβ) and human transferrin receptor (TfR), wherein

• the bispecific antibody comprises a first polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 189, a second polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 269, and a third polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 197.

A bispecific antibody that binds to amyloid beta (Aβ) and human transferrin receptor (TfR), wherein

• the bispecific antibody comprises a first polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 189, a second polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 277, and a third polypeptide consisting of the amino acid sequence set forth in SEQ ID NO:
• 197.