Polynucleotides encoding anti-C1s antibodies
The present disclosure provides humanized anti-C1s antibodies. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the humanized anti-C1s antibodies; and host cells comprising the nucleic acids. The present disclosure provides compositions comprising the humanized anti-C1s antibodies. The present disclosure provides methods of use of the humanized anti-C1s antibodies.
1. One or more nucleic acids encoding a humanized antibody that specifically binds complement component C1s, wherein the antibody comprises a VH region comprising the amino acid sequence of SEQ ID NO: 26 and a VL region comprising the amino acid sequence of SEQ ID NO: 27.
2. The one or more nucleic acids of claim 1 , wherein the antibody is selected from the group consisting of:
a) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:14 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:22;
b) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:10 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:20;
c) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:10 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:22;
d) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:10 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:24;
e) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:12 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:20;
f) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:12 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:22;
g) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:12 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:24;
h) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:14 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:20;
i) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:14 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:24;
j) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:16 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:20;
k) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:16 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:22;
l) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:16 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:24;
m) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:18 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:20;
n) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:18 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:22; and
o) an antibody comprising a VH region comprising the amino acid sequence set forth in SEQ ID NO:18 and a VL region comprising the amino acid sequence set forth in SEQ ID NO:24.
3. The one or more nucleic acids of claim 1 , wherein the humanized antibody is a Fab fragment, a F(ab′)2 fragment a F(ab′)2 fragment, a scFv, or a Fv.
4. The one or more nucleic acids of claim 1 , wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.
5. The one or more nucleic acids of claim 1 , wherein the nucleic acids comprise:
a) the nucleotide sequence of SEQ ID NO: 15 and the nucleotide sequence of SEQ ID NO: 23;
b) the nucleotide sequence of SEQ ID NO: 11 and the nucleotide sequence of SEQ ID NO: 21;
c) the nucleotide sequence of SEQ ID NO: 11 and the nucleotide sequence of SEQ ID NO: 23;
d) the nucleotide sequence of SEQ ID NO: 11 and the nucleotide sequence of SEQ ID NO: 25;
e) the nucleotide sequence of SEQ ID NO: 13 and the nucleotide sequence of SEQ ID NO: 21;
f) the nucleotide sequence of SEQ ID NO: 13 and the nucleotide sequence of SEQ ID NO: 23;
g) the nucleotide sequence of SEQ ID NO: 13 and the nucleotide sequence of SEQ ID NO: 25;
h) the nucleotide sequence of SEQ ID NO: 15 and the nucleotide sequence of SEQ ID NO: 21;
i) the nucleotide sequence of SEQ ID NO: 15 and the nucleotide sequence of SEQ ID NO: 25;
j) the nucleotide sequence of SEQ ID NO: 17 and the nucleotide sequence of SEQ ID NO: 21;
k) the nucleotide sequence of SEQ ID NO: 17 and the nucleotide sequence of SEQ ID NO: 23;
l) the nucleotide sequence of SEQ ID NO: 17 and the nucleotide sequence of SEQ ID NO: 25;
m) the nucleotide sequence of SEQ ID NO: 19 and the nucleotide sequence of SEQ ID NO: 21;
n) the nucleotide sequence of SEQ ID NO: 19 and the nucleotide sequence of SEQ ID NO: 23; or
o) the nucleotide sequence of SEQ ID NO: 19 and the nucleotide sequence of SEQ ID NO: 25.
6. A vector comprising the one or more nucleic acids of claim 1 .
7. An isolated host cell comprising the isolated vector of claim 6 .
8. The isolated host cell of claim 7 , wherein the cell is a mammalian cell, an insect host cell, a yeast cell, or a prokaryotic cell.
9. The isolated host cell of claim 8 , wherein the cell is a mammalian cell selected from HeLa cells, CHO cells, 293 cells, Vero cells, NIH 3T3 cells, Huh-7 cells, BHK cells, PC12 cells, COS cells, COS-7 cells, RAT1 cells, mouse L cells, HEK cells, and HLHepG2 cells.
10. A method of producing a humanized antibody that specifically binds complement component C1s, comprising culturing the host cell of claim 7 , so that the antibody is produced.
11. The method of claim 10 , further comprising recovering the antibody.