Complement factor d antagonist antibodies and conjugates thereof
AssigneeKodiak Sciences Inc.
InventorsD. Victor Perlroth, Wah Yuen To, Hong Liang, Rachel Marie DeVay Jacobson, Fernando Corrêa
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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.
Claims93
An isolated antagonist antibody that specifically binds to complement factor D (CFD) and directly inhibits a proteolytic activity of CFD.
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.
An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody does not bind a human CFD mutant comprising mutations R157A and R207A.
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An isolated antagonist antibody comprising:
- a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3 of the VH having an amino acid sequence selected group the group consisting of SEQ ID NO:
- 541, SEQ ID NO:
- 542;
- and SEQ ID NO:
- 543;
- and
- a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL having an amino acid sequence selected from the group consisting of SEQ ID NO:
- 544;
- SEQ ID NO:
- 545;
- and SEQ ID NO:
- 546.
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An isolated antagonist antibody that specifically binds to CFD comprising:
- a heavy chain variable region (VH);
- and
- a light chain variable region (VL), wherein the antibody comprises the following mutations:
- L234A, L235A, and G237A.
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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.
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 NOs:
- 520 or 525.
An isolated antagonistic antibody that binds to CFD, the antibody 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;
- a CDRL1 that is the CDRL1 in SEQ ID NO:
- 525;
- a CDRL2 that is the CDRL2 in SEQ ID NO:
- 525;
- 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.
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An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody is configured to provide a reduced complement reaction, wherein the antibody specifically binds to complement factor D (CFD), and wherein the antibody at least inhibits a proteolytic activity of CFD or inhibits CFD binding to C3bB complex.
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A conjugate comprising:
- (a) an isolated antagonist antibody that specifically binds to complement factor D (CFD);
- and
- (b) a phosphorylcholine containing polymer, wherein the polymer is covalently bonded to the antibody.
A conjugate comprising:
- (a) an isolated antagonist antibody that specifically binds to complement factor D (CFD);
- and
- (b) a polymer comprising a zwitterionic monomer, wherein the zwitterionic monomer is selected from the group consisting of HEMA-phosphorylcholine, PEG, biocompatible fatty acids and derivatives thereof, Hydroxy Alkyl Starch (HAS), Hydroxy Ethyl Starch (HES), Poly Ethylene Glycol (PEG), Poly (Glyx-Sery) (HAP), Hyaluronic acid (HA), Heparosan polymers (HEP), Fleximers, Dextran, Poly-sialic acids (PSA), Fe domains, Transferrin, 25 Albumin, Elastin like (ELP) peptides, XTEN polymers, PAS polymers, PA polymers, Albumin binding peptides, CTP peptides, and FcRn binding peptides.
A conjugate comprising an anti-CFD antibody and a polymer that is capable of blocking at least 80% of an interaction between CFD and C3bB.
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An isolated antagonist antibody, wherein the antibody binds an epitope on human CFD that is the same as or overlaps with the epitope recognized by an antibody comprising the amino acid sequences shown in SEQ ID NO:
- 520 and SEQ ID NO:
- 525.
An isolated antagonist antibody that binds to CFD, wherein the antibody does not increase an enzymatic activity of CFD when bound thereto.
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An isolated antagonist antibody that binds to CFD, wherein the antibody does not maintain an enzymatic activity of CFD when bound thereto.
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An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody binds to one or more of residues 156 or 209 of SEQ ID NO:
- 1 of CFD.
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An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody, when bound to CFD, is not within 6 angstroms of at least one of 117, 118, and 156 of SEQ ID NO:
- 1.
An isolated antagonist antibody that specifically binds to complement factor D (CFD), wherein the antibody binds to CFD as described in Tables:
- 1.1, 0.1A, 0.1B, 0.1D, and/or 11.3.
A crystallized CFD-antibody complex, wherein the antibody comprises any one or more of the CDRs within SEQ ID NO:s 183 and 184.
An isolated antagonist antibody that binds an epitope on human CFD that is the same as or overlaps with the epitope recognized by an antibody comprising the amino acid sequences shown in SEQ ID NO:
- 45 and SEQ ID NO:
- 46.
Dependencies are inferred from the claim text.