A tetrahedral antibody comprising a first, a second, a third, and a fourth domain, and optionally comprising one or more of a fifth, a sixth, a seventh, and an eighth domain, wherein:
- a) the first domain and the second domains are human IgG1 Fc domains,
- b) each of the first and the second domains comprise:
- i) a first polypeptide chain comprising a first N-terminus of the domain, and
- ii) a second polypeptide chain comprising a second N-terminus of the domain,
- c) the first N-terminus of the first domain and the first N-terminus of the second domain are joined to each other by a non-covalent linkage between
- i) a first angiotensin-converting enzyme 2 (ACE2) collectrin-like domain dimerizing polypeptide comprising the amino acids set forth in SEQ ID NO:
- 782 attached at its C-terminus by a peptide bond or via a peptide linker to the first N-terminus of the first domain, and
- ii) a second ACE2 collectrin-like domain dimerizing polypeptide comprising the amino acids set forth in SEQ ID NO:
- 782 attached at its C-terminus by a peptide bond or via a peptide linker to the first N-terminus of the second domain,
- d) the third domain is a Fab domain which comprises:
- 1) A first polypeptide chain which consists of a heavy chain variable region (VH) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a light chain variable region (VL), and a light chain constant region (CL), or
- 2) a first polypeptide chain which consists of light chain variable region (VL) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a heavy chain variable region (VH), and a light chain constant region (CL),
- wherein the first or second polypeptide chain of the third domain is attached at its C-terminus by a peptide bond or via a peptide linker to the N-terminus of the first ACE2 collectrin-like domain dimerizing polypeptide,
- e) the fourth domain is a Fab domain which comprises:
- 1) A first polypeptide chain which consists of a heavy chain variable region (VH) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a light chain variable region (VL), and a light chain constant region (CL), or
- 2) a first polypeptide chain which consists of light chain variable region (VL) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a heavy chain variable region (VH), and a light chain constant region (CL),
- wherein the first or second polypeptide chain of the fourth domain is attached at its C-terminus by a peptide bond or via a peptide linker to the N-terminus of the second ACE2 collectrin-like domain dimerizing polypeptide,
- f) the fifth domain, if present, is a Fab domain which comprises:
- 1) a first polypeptide chain which consists of a heavy chain variable region (VH) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a light chain variable region (VL), and a light chain constant region (CL), or
- 2) a first polypeptide chain which consists of light chain variable region (VL) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a heavy chain variable region (VH), and a light chain constant region (CL),
- wherein the first or second polypeptide chain of the fifth domain is attached at its C-terminus by a peptide bond or via a peptide linker to the second N-terminus of the first domain,
- g) the sixth domain, if present, is a Fab domain which comprises:
- 1) A first polypeptide chain which consists of a heavy chain variable region (VH) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a light chain variable region (VL), and a light chain constant region (CL), or
- 2) a first polypeptide chain which consists of light chain variable region (VL) and a heavy chain constant region 1 (CH1), and a second polypeptide chain which consists of a heavy chain variable region (VH), and a light chain constant region (CL),
- wherein the first or second polypeptide chain of the sixth domain is attached at its C-terminus by a peptide bond or via a peptide linker to the second N-terminus of the second domain,
- h) the seventh domain, if present, is attached at its N-terminus by a peptide bond or via a peptide linker to:
- i) the first C-terminus of the first domain, or
- ii) the second C-terminus of the first domain, and
- i) the eighth domain, if present, is attached at its N-terminus by a peptide bond or via a peptide linker to:
- i) the first C-terminus of the second domain, or
- ii) the second C-terminus of the second domain.