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US 12,643,945 B2Granted
Apolipoprotein L1-specific antibodies and methods of use
AssigneeGenentech, Inc.
InventorsSuzanna Jane Scales, Nidhi Gupta, Andrew Scott Peterson
Life of this patent
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Abstract
This disclosure provides anti-apolipoprotein L1 (APOL1) antibodies, including anti-APOL1 antibodies that distinguish the G0 and G1 forms from the G2 form of APOL1, distinguish APOL1 found on podocytes from that found on HDL particles in serum, and distinguish APOL1 from apolipoproteins L2, L3, L4 and L6 (APOL2, APOL3, APOL4 and APOL6), and methods of using the same.
Claims20
An isolated antibody that specifically binds to apolipoprotein L1 (APOL1), wherein the antibody comprises:
- (a) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 3, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 4, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 5;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 6, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 7, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 8;
- (b) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 13, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 14, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 15;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 16, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 17, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 18;
- (c) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 23, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 24, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 25;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 26, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 27, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 28;
- (d) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 33, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 34, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 35;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 36, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 37, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 38;
- (e) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 43, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 44, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 45;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 46, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 47, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 48;
- (f) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 53, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 54, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 55;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 56, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 57, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 58;
- (g) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 63, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 64, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 65;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 66, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 67, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 68;
- (h) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 73, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 74, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 75;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 76, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 77, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 78;
- (i) heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 85;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 86, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 87, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 88;
- (j) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 93, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 94, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 95;
- and a light chain variable region (VL) comprising a CDR-LI comprising the amino acid sequence of SEQ ID NO:
- 96, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 97, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 98;
- (k) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 103, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 104, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 105;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 106, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 107, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 108;
- (l) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 113, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 114, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 115;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 116, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 117, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 118;
- (m) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 123, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 124, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 125;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 126, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 127, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 128;
- (n) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 133, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 134, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 135;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 136, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 137, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 138;
- (o) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 143, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 144, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 145;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 146, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 147, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 148;
- (p) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 153, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 154, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 155;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 156, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 157, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 158;
- (q) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 163, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 164, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 165;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 166, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 167, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 168;
- (r) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 173, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 174, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 175;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 176, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 177, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 178;
- (s) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 183, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 184, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 185;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 186, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 187, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 188;
- (t) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 193, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 194, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 195;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 196, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 197, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 198;
- or
- (u) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 203, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 204, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 205;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 206, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 207, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 208.
166 more elements
An isolated antibody that specifically binds to apolipoprotein L1 (APOL1), wherein the antibody:
- 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);
- wherein the antibody preferentially recognizes APOL1 expressed on podocytes over APOL1 found in serum;
- and further
- wherein the antibody comprises:
- (a) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 173, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 174, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 175;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 176, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 177, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 178;
- or
- (b) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 183, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 184, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 185;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 186, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 187, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 188.
22 more elements
An isolated antibody that specifically binds to apolipoprotein L1 (APOL1), wherein the antibody:
- a) specifically binds to a region of APOL1 corresponding to amino acids 103-111 of APOL1 G0 (SEQ ID NO:
- 2);
- b) specifically binds to a region of APOL1 corresponding to amino acids 150-172 of APOL1 G0 (SEQ ID NO:
- 2);
- c) specifically binds to a region of APOL1 corresponding to amino acids 314-333 of APOL1 G0 (SEQ ID NO:
- 2);
- and/or
- d) specifically binds to a region of APOL1 corresponding to amino acids 376-398 of APOL1 G0 (SEQ ID NO:
- 2);
- wherein the antibody recognizes both APOL1 expressed on podocytes and APOL1 found in serum;
- and further
- wherein the antibody comprises:
- (a) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 3, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 4, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 5;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 6, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 7, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 8;
- (b) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 53, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 54, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 55;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 56, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 57, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 58;
- (c) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 63, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 64, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 65;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 66, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 67, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 68;
- (d) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 85;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 86, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 87, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 88;
- (e) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 73, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 74, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 75;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 76, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 77, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 78;
- (f) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 133, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 134, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 135;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 136, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 137, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 138;
- (g) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 143, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 144, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 145;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 146, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 147, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 148;
- or
- (h) a heavy chain variable region (VH) comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 123, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 124, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 125;
- and a light chain variable region (VL) comprising a CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 126, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 127, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 128.
74 more elements
Dependencies are inferred from the claim text.