Antibodies to human complement factor C2B and methods of use
Provided are antibodies and antigen-binding fragments thereof that bind specifically to human complement factor C2 and are capable of inhibiting activation of the classical and lectin pathways of the complement system. The antibodies and antigen-binding fragment exhibit improved manufacturability, pharmacokinetics, and antigen sweeping. Also provided are pharmaceutical compositions comprising the antibodies and antigen-binding fragments, nucleic acids and vectors encoding the antibodies and antigen-binding fragments, host cells comprising the nucleic acids or vectors, and methods of making and using the antibodies and antigen-binding fragments. The antibodies and antigen-binding fragments can be used to inhibit the classical pathway of complement activation in a subject, e.g., a human. The antibodies and antigen-binding fragments can also be used to inhibit the lectin pathway of complement activation in a subject, e.g., a human.
1. A nucleic acid molecule or plurality of nucleic acid molecules encoding a monoclonal antibody or antigen-binding fragment thereof that specifically binds to human complement factor C2, wherein said monoclonal antibody or fragment thereof comprises:
a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and
a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 2.
2. A vector or plurality of vectors comprising the nucleic acid molecule or plurality of nucleic acid molecules of claim 1 .
3. A host cell comprising the nucleic acid molecule or plurality of nucleic acid molecules of claim 1 .
4. A host cell comprising the vector or plurality of vectors of claim 2 .
5. The host cell of claim 3 , wherein the host cell is a mammalian cell.
6. A method of making a monoclonal antibody or antigen-binding fragment thereof, comprising
culturing a population of host cells of claim 3 under conditions suitable for expression of the monoclonal antibody or antigen-binding fragment thereof; and
isolating the monoclonal antibody or antigen-binding fragment from the cells.
7. The nucleic acid molecule or plurality of nucleic acid molecules of claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises a full-length monoclonal antibody.
8. The nucleic acid molecule or plurality of nucleic acid molecules of claim 7 , wherein the monoclonal antibody comprises a human IgG heavy chain constant domain.
9. The nucleic acid molecule or plurality of nucleic acid molecules of claim 8 , wherein the heavy chain constant domain comprises a human IgG1 heavy chain constant domain.
10. The nucleic acid molecule or plurality of nucleic acid molecules of claim 9 , wherein the human IgG1 heavy chain constant domain comprises the amino acid sequence set forth in SEQ ID NO: 4.
11. The nucleic acid molecule or plurality of nucleic acid molecules of claim 8 , wherein the heavy chain constant domain comprises a human IgG4 heavy chain constant domain.
12. The nucleic acid molecule or plurality of nucleic acid molecules of claim 11 , wherein the human IgG4 heavy chain constant domain comprises the amino acid sequence set forth in SEQ ID NO: 5.
13. The nucleic acid molecule or plurality of nucleic acid molecules of claim 8 , wherein the monoclonal antibody comprises a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 6 and a light chain comprising the amino acid sequence set forth as SEQ ID NO: 7.
14. The nucleic acid molecule or plurality of nucleic acid molecules of claim 8 , wherein the monoclonal antibody comprises a heavy chain comprising the amino acid sequence set forth as SEQ ID NO: 8 and a light chain comprising the amino acid sequence set forth as SEQ ID NO: 7.