Isolated antigen binding protein binding to a complement protein C5 and a method of detecting thereof
An isolated antigen binding protein, which includes at least one CDR of a heavy chain variable region and at least one CDR of a light chain variable region and a method to encode an isolated nucleic acid molecule. A vector with the nucleic acid molecule. A cell with the nucleic acid molecule. A pharmaceutical composition with the isolated antigen binding protein. A method for preventing, alleviating or treating a C5-related disease or disorder. A method for detecting C5 in a sample.
1 . An isolated antigen binding protein, which is capable of binding to a complement factor 5 (C5) protein, comprising three complementary determining regions of a heavy chain variable region (VH): HCDR1, HCDR2, and HCDR3, and three complementary determining regions a light chain variable region (VL): LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 18, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 19, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 20, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 16, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:17.
2 . The isolated antigen binding protein according to claim 1 , wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 2.
3 . The isolated antigen binding protein according to claim 1 , wherein the antigen binding protein is an antibody or an antigen binding fragment thereof.
4 . The isolated antigen binding protein according to claim 1 , wherein the VL comprises framework regions L-FR1, L-FR2, L-FR3, and L-FR4, and the VH comprises H-FR1, H-FR2, H-FR3 and H-FR4, wherein the L-FR1 comprises the amino acid sequence of any one of SEQ ID NOs: 21-23, the L-FR2 comprises the amino acid sequence of any one of SEQ ID NOs: 24-25, the L-FR3 comprises the amino acid sequence of any one of SEQ ID NOs: 26-28, the L-FR4 comprises the amino acid sequence of any one of SEQ ID NOs: 29-30, the H-FR1 comprises the amino acid sequence of any one of SEQ ID NOs: 31-33, the H-FR2 comprises the amino acid sequence of any one of SEQ ID NOs: 34-35, the H-FR3 comprises the amino acid sequence of any one of SEQ ID NOs: 36-38, and the H-FR4 comprises the amino acid sequence of any one of SEQ ID NOs: 39-40.
5 . The isolated antigen binding protein according to claim 1 , comprising the VL and the VH, wherein
(a) the VL comprises the amino acid sequence of SEQ ID NO:41 and the VH comprises the amino acid sequence of SEQ ID NO:44;
(b) the VL comprises the amino acid sequence of SEQ ID NO:42 and the VH comprises the amino acid sequence of SEQ ID NO:45; or
(c) the VL comprises the amino acid sequence of SEQ ID NO:43 and the VH comprises the amino acid sequence of SEQ ID NO:46.
6 . The isolated antigen binding protein according to claim 1 , comprising an antibody light chain constant region, and wherein the antibody light chain constant region comprises a human Kappa light chain constant region.
7 . The isolated antigen binding protein according to claim 6 , wherein the antibody light chain constant region comprises the amino acid sequence of SEQ ID NO: 47.
8 . The isolated antigen binding protein according to claim 1 , comprising an antibody heavy chain constant region, and the antibody heavy chain constant region is derived from a human IgG heavy chain constant region.
9 . The isolated antigen binding protein according to claim 1 , comprising an antibody light chain (LC) and an antibody heavy chain (HC), and wherein comprise
(a) the LC comprises the amino acid sequence of SEQ ID NOs:49 and the HC comprises the amino acid sequence of SEQ ID NO:50;
(b) the LC comprises the amino acid sequence of SEQ ID NO:51 and the HC comprises the amino acid sequence of SEQ ID NO:52; or
(c) the LC comprises the amino acid sequence of SEQ ID NO: 53 and the HC comprises the amino acid sequence of SEQ ID NO:54.
10 . An immunoconjugate comprising the isolated antigen binding protein of claim 1 .
11 . A pharmaceutical composition comprising the isolated antigen binding protein of claim 1 .
12 . An isolated nucleic acid molecule encoding the isolated antigen binding protein according to claim 1 .
13 . A vector comprising the nucleic acid molecule according to claim 12 .
14 . An isolated cell comprising the nucleic acid molecule according to claim 12 .
15 . A method for detecting C5 in a sample, comprising: contacting the sample isolated from a subject with the isolated antigen binding protein of claim 1 , wherein the antigen binding protein of claim 1 is labeled with a detectable label or a reporter molecule; and
detecting presence of an immunocomplex of the C5 protein and the antigen binding protein with the detectable label or reporter molecule in the sample by an immunoassay;
wherein the detectable label or reporter molecule is selected from the group consisting of a radioisotope, a fluorescent or chemiluminescent moiety, an enzyme and a biotin/avidin.