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US 11,584,790 B2Granted
Complement factor D antagonist antibodies and conjugates thereof
AssigneeKodiak Sciences Inc.
InventorsDaniel Victor Perlroth, Wah Yuen To, Hong Liang, Rachel Marie DeVay Jacobson, Fernando Corrêa
Life of this patent
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Abstract
The present invention provides antagonizing antibodies that bind to complement factor D (CFD), conjugates thereof, and methods of using same. The anti-CFD antibodies can be used therapeutically alone or in combination with other therapeutics to treat age related macular degeneration and other diseases.
Claims45
An isolated antagonist antibody that specifically binds to complement factor D (CFD) and directly inhibits a proteolytic activity of CFD, wherein the antibody comprises:
- a heavy chain variable region (VH) comprising:
- a VH complementarity determining region 1 (CDRH1) that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- and
- a light chain variable region (VL) comprising:
- a VL complementarity determining region 1 (CDRL1) comprising H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);
- a CDRL2 comprising L51 or H51, 153 or V53, and K55 (EU numbering);
- and
- a CDRL3 comprising F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering).
10 more elements
An isolated antagonist antibody that specifically binds to complement factor D (CFD), inhibits a proteolytic activity of CFD, and inhibits CFD binding to C3bB complex, wherein the antibody comprises:
- a heavy chain variable region (VH) comprising:
- a VH complementarity determining region 1 (CDRH1) that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- and
- a light chain variable region (VL) comprising:
- a VL complementarity determining region 1 (CDRL1) comprising H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);
- a CDRL2 comprising L51 or H51, 153 or V53, and K55 (EU numbering);
- and
- a CDRL3 comprising F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering).
10 more elements
An isolated antagonist antibody that specifically binds to human complement factor D (CFD), wherein the antibody does not bind a human CFD mutant comprising mutations R157A and R207A, and wherein the antibody comprises:
- a heavy chain variable region (VH) comprising an amino acid sequence at least 85% identical to SEQ ID NO:
- 520;
- and
- a light chain variable region (VL) comprising an amino acid sequence at least 85% identical to SEQ ID NO:
- 525.
2 more elements
An isolated antagonist antibody comprising:
- a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3, wherein:
- the VH CDR1 comprises the amino acid sequence consisting of SEQ ID NO:
- 541;
- the VH CDR2 comprises the amino acid sequence consisting of SEQ ID NO:
- 542;
- and
- the VH CDR3 comprises the amino acid sequence consisting of SEQ ID NO:
- 543;
- and
- a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3, wherein:
- the VL CDR1 comprises H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);
- the VL CDR2 comprises L51 or H51, 153 or V53, and K55 (EU numbering);
- and
- the VL CDR3 comprises F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering).
11 more elements
An isolated antagonist antibody that binds to CFD, wherein the antibody comprises:
- a heavy chain comprising the amino acid sequence shown in SEQ ID NO:
- 183, with or without the C-terminal lysine;
- and
- a light chain comprising the amino acid sequence shown in SEQ ID NO:
- 184.
2 more elements
An isolated antagonist antibody that binds to CFD, wherein the antibody comprises:
- a VH comprising the amino acid sequence shown in SEQ ID NO:
- 520, or a sequence that is at least 90% identical thereto, having amino acid substitutions in residues that are not within a CDR of SEQ ID NO:
- 520;
- and
- a VL comprising:
- a VL complementarity determining region 1 (CDRL1) comprising H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);
- a CDRL2 comprising L51 or H51, 153 or V53, and K55 (EU numbering);
- and
- a CDRL3 comprising F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering).
6 more elements
An isolated antagonistic antibody that binds to CFD, the antibody comprising:
- a VH comprising:
- a CDRH1 that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- and
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- a VL comprising:
- a CDRL1 that is the CDRL1 in SEQ ID NO:
- 525;
- a CDRL2 that is the CDRL2 in SEQ ID NO:
- 525;
- and
- a CDRL3 that is the CDRL3 in SEQ ID NO:
- 525;
- at least one of the following mutations (EU numbering):
- L234A, L235A, and G237A;
- and
- at least one of the following mutations (EU numbering):
- Q347C or L443C.
18 more elements
An isolated antagonist antibody that specifically binds to complement factor D (CFD), comprising:
- a heavy chain variable region (VH) comprising:
- a VH complementarity determining region 1 (CDRH1) that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- a VL complementarity determining region 1 (CDRL1) comprising H31, N33, G34 or E34 or F34 or S34, D35 or E35, T36 or S36 or V36, Y37, L38 or I38, and E39 (EU numbering);
- a CDRL2 comprising L51 or H51, 153 or V53, and K55 (EU numbering);
- and
- a CDRL3 comprising F94 or L94, Q95, G96, S97, V99 or N99 or Q99 or W99, P100, and P101 or V101 (EU numbering),
- wherein the antibody comprises an Fc region comprising one or more amino acid substitutions to reduce effector function, and wherein the antibody inhibits a proteolytic activity of CFD or inhibits CFD binding to C3bB complex.
9 more elements
An isolated antagonist antibody, wherein the antibody binds an epitope on human CFD that is the same as the epitope recognized by an antibody comprising the amino acid sequences shown in SEQ ID NO:
- 520 and SEQ ID NO:
- 525, wherein the antibody directly inhibits a proteolytic activity of human CFD, wherein the antibody interacts with human CFD at one or more of the amino acids at position 157, 158, 159, 161, 206, 207, 208, 209, 116, 119, 150, 151, 152, 153, 155, 156, 162, 163, 164, 165, or 166 of SEQ ID NO:
- 1, when bound thereto.
An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody comprises:
- a heavy chain variable region (VH) comprising the amino acid sequence of any one of SEQ ID NOs:
- 515, 517-521;
- and
- a light chain variable region (VL) comprising the amino acid sequence of any one of SEQ ID NOs:
- 524-526.
2 more elements
A crystalized CFD-antibody complex, wherein the antibody comprises any one or more of the CDRs within SEQ ID NOs:
- 183 and 184.
An isolated antagonist antibody that binds an epitope on human CFD that is the same as the epitope recognized by an antibody comprising the amino acid sequences shown in SEQ ID NO:
- 45 and SEQ ID NO:
- 46,
- wherein the antibody comprises:
- a heavy chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 19;
- and a light chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 20;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 17;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 18;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 49;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 50;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 45;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 46;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 5;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 6;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 47;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 48;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 51;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 52;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 43;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 44;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 53;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 54;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 7;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 8;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 15;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 16.
54 more elements
An isolated antibody that binds to CFD, the antibody comprising:
- a VH comprising:
- a CDRH1 that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- and
- a VL comprising:
- a CDRL1 that is the CDRL1 in SEQ ID NO:
- 525;
- a CDRL2 that is the CDRL2 in SEQ ID NO:
- 525;
- and
- a CDRL3 that is the CDRL3 in SEQ ID NO:
- 525.
13 more elements
An antibody comprising six complementarity determining regions (CDRs) comprising:
- a VH comprising:
- a complementarity determining region 1 (CDRH1) that is the CDRH1 in SEQ ID NO:
- 520;
- a CDRH2 that is the CDRH2 in SEQ ID NO:
- 520;
- a CDRH3 that is the CDRH3 in SEQ ID NO:
- 520;
- a VL comprising:
- a CDRL1 that is the CDRL1 in SEQ ID NO:
- 525;
- a CDRL2 that is the CDRL2 in SEQ ID NO:
- 525;
- and
- a CDRL3 that is the CDRL3 in SEQ ID NO:
- 525.
12 more elements
An antibody comprising:
- a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 183, with or without the C-terminal lysine;
- and
- a light chain comprising the amino acid sequence of SEQ ID NO:
- 184.
2 more elements
An The isolated antagonist antibody that binds to CFD, wherein the antibody comprises:
- a heavy chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 339;
- and a light chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 340;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 343;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 344;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 435;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 436;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 437;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 438;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 441;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 442;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 443;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 444;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 445;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 446;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 447;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 448;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 351;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 352;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 373;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 374;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 387;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 388;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 385;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 386;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 389;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 390;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 391;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 392;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 509;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 510;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 485;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 486;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 495;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 496;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 471;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 472;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 337;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 338;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 423;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 424;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 439;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 440;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 459;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 460;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 477;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 478;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 461;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 462;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 493;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 494.
121 more elements
An isolated antagonist antibody that binds to CFD, wherein the antibody comprises:
- a heavy chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 339;
- and a light chain variable region (VH) comprising 3 CDRs of the CDRs in SEQ ID NO:
- 340;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 343;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 344;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 435;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 436;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 437;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 438;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 441;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 442;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 443;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 444;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 445;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 446;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 447;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 448;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 393;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 394;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 417;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 418;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 387;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 388;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 385;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 386;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 389;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 390;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 391;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 392;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 509;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 510;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 485;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 486;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 495;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 496;
- or
- a VH comprising 3 CDRs of the CDRs in SEQ ID NO:
- 471;
- and a VL comprising 3 CDRs of the CDRs in SEQ ID NO:
- 472.
86 more elements
An antibody or antigen binding fragment thereof, comprising:
- a heavy chain variable region (VH) comprising an amino acid sequence at least 90% identical to SEQ ID NO:
- 520;
- and
- a light chain variable region (VL) comprising an amino acid sequence at least 90% identical to SEQ ID NO:
- 525.
2 more elements
Dependencies are inferred from the claim text.