Polynucleotides encoding Toll-Like Receptor 3 antagonists
Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.
1. An isolated polynucleotide encoding an antibody heavy chain variable region (VH) comprising the heavy chain complemetarity determining regions (HCDR) 1, 2 and 3 (HCDR1, HCDR2 and HCDR3) amino acid sequences as shown in SEQ ID NOs: 82, 196 and 84, wherein the HCDR2 of SEQ ID NO: 196 is further defined as shown in Formula (V):
(V)
Xaa 24 -I-D-P-S-D-S-Y-T-N-Y-Xaa 25 -P-S-F-Q-G,
wherein
Xaa 24 may be Phe or Arg; and
Xaa 25 may be Ala or Ser.
2. The isolated polynucleotide of claim 1 , wherein the HCDR2 comprises the amino acid sequence as shown in SEQ ID NOs: 83, 86, 112, 114, 117 or 118.
3. The isolated polynucleotide of claim 1 , wherein the VH comprises the amino acid sequence as shown in SEQ ID NOs: 38, 40, 42, 124-129 or 216.
4. An isolated polynucleotide encoding an antibody light chain variable region (VL) comprising the light chain complementarity determining regions (LCDR) 1, 2 and 3 (LCDR1, LCDR2 and LCDR3) amino acid sequences as shown in SEQ ID NOs: 79, 80 and 195, wherein the LCDR3 of SEQ ID NO: 193 is further defined as shown in Formula (VI):
(VI)
Q-Q-Xaa 18 -Xaa 19 -Xaa 20 -Xaa 21 -Xaa 22 -Xaa 23 -T,
wherein
Xaa 18 may be Tyr, Gly or Ala;
Xaa 19 may be Gly, Glu or Asn;
Xaa 20 may be Ser or Thr;
Xaa 21 may be Val, Ile or Leu;
Xaa 22 may be Ser or Leu; and
Xaa 23 may be Ile, Ser, Pro or Tyr.
5. The isolated polynucleotide of claim 4 , wherein the LCDR3 comprises the amino acid sequence as shown in SEQ ID NOs: 81, 85, 87 or 113.
6. The isolated polynucleotide of claim 5 , wherein the VL comprises the amino acid sequence as shown in SEQ ID NOs: 37, 39, 41, 122 or 123.
7. A vector comprising the isolated polynucleotide as in any one of claims 1 - 6 .
8. An isolated host cell comprising the vector of claim 7 .
9. A method of making an antibody that binds toll-like receptor 3 (TLR3) comprising culturing the host cell of claim 8 and recovering the antibody produced by the host cell.