JPWO2021133723A5 - - Google Patents

Claims (19)

An isolated antibody that specifically binds to apolipoprotein L1 (APOL1), the antibody comprising :
A heavy chain variable region (VH) comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 113, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 114, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 115, and SEQ ID NO: 116. A light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 117, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 118 , and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 118. a VH that is at least 90%, at least 95%, at least 97% or at least 99% identical to the amino acid sequence of SEQ ID NO: 119 and/or at least 90%, at least 95%, at least 97% or at least the amino acid sequence of SEQ ID NO: 120; 2. The antibody of claim 1 further comprising a VL that is 99% identical. 3. The antibody of claim 1 or 2, further comprising a VH comprising the amino acid sequence of SEQ ID NO: 119. The antibody according to any one of claims 1-3, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 120. A heavy chain (HC) comprising an amino acid sequence that is at least 90%, at least 95%, at least 97% or at least 99% identical to SEQ ID NO: 121 and at least 90%, at least 95%, at least 97% or at least 99% identical to SEQ ID NO: 122. 5. An antibody according to any one of claims 1-4, further comprising a light chain (LC) comprising an amino acid sequence that is % identical . The antibody according to any one of claims 1 to 5, comprising a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 121 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 122. a) specifically binds to a region of APOL1 corresponding to amino acids 61-103 of APOL1 G0 (SEQ ID NO: 2); and/or
b) specifically binds to a region of APOL1 corresponding to amino acids 111-150 of APOL1 G0 (SEQ ID NO: 2);
The antibody according to any one of claims 1 to 6, which preferentially recognizes APOL1 expressed on podocytes over APOL1 found in serum . a) specifically binds to a region of APOL1 corresponding to amino acids 103-111 of APOL1 G0 (SEQ ID NO: 2); and/or
b) specifically binds to a region of APOL1 corresponding to amino acids 150-172 of APOL1 G0 (SEQ ID NO: 2);
7. The antibody according to any one of claims 1-6, which recognizes both APOL1 expressed on podocytes and APOL1 found in serum . An isolated antibody that specifically binds to apolipoprotein L1 (APOL1), the antibody preferentially binding to the G0 and G1 forms of APOL1 over the G2 form of APOL1 . Antibodies:
(i) is a humanized or chimeric antibody; or
(ii) is an IgG antibody such as IgG1, IgG2, IgG3 or IgG4; or
(iii) is an antibody fragment such as Fv, scFv, Fab, Fab' or (Fab') ₂ ;
An antibody according to any one of claims 1 to 4 or 7 to 9 . The antibody according to any one of claims 1 to 9, 10(i) or 10(ii), which is a full-length antibody . a bispecific or multispecific antibody or covalently or non-covalently conjugated to at least one other molecule, optionally covalently linked to at least one other molecule; 12. An antibody according to any one of claims 1 to 11, wherein the antibody is conjugated selectively or non-covalently and said at least one other molecule comprises a detection label and/or a pharmaceutical agent. 13. The antibody according to any one of claims 1 to 12, which specifically binds to a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 213 and/or SEQ ID NO: 214 . 14. An isolated nucleic acid encoding an antibody according to any one of claims 1 to 13 . 14. An isolated vector comprising one or more nucleic acids encoding the heavy and light chains of an antibody according to any one of claims 1 to 13 . An isolated host cell comprising an isolated nucleic acid according to claim 14 or an isolated vector according to claim 15 . 17. A method of producing an antibody that binds to APOL1, comprising culturing the isolated host cell of claim 16 under conditions suitable for expression of said antibody, optionally comprising A manufacturing method further comprising collecting the antibody . A method of distinguishing apolipoprotein L1 (APOL1) G0 and G1 types from APOL1 G2 types, the method comprising: providing a sample that can include at least one of G0, G1 and G2 types; contacting a sample with an anti-APOL1 antibody according to any one of claims 9 to 13, and detecting binding of the antibody to the sample, wherein the antibody is of a type greater than the G2 form of APOL1. A method that preferentially binds to the G0 and G1 forms of APOL1, optionally said sample comprising human kidney cells, human podocyte cells or human endothelial cells . 14. A method for specifically detecting podocyte cells expressing apolipoprotein L1 (APOL1), the method comprising: providing a sample containing podocyte cells; contacting an anti-APOL1 antibody according to any one of the preceding paragraphs and detecting binding of the antibody to the sample, wherein the antibody (a) preferentially binds to APOL1 found on (a) podocytes, (b) does not significantly bind to APOL2, and/or (c) does not significantly bind to APOL6; and/or (b) contacting said sample with a control antibody that recognizes APOL1 found both in the blood and serum and/or recognizes APOL1 found in the serum (e.g. in HDL particles), and/or (b) contacting the sample with an anti-APOL1 antibody capable of distinguishing type G1 from type G2 .