Methods of treating complement mediated diseases with fusion protein constructs comprising anti-C3d antibody and a complement modulator
Inventors
CURTIS, MICHAEL STEVEN • Storek, Michael • VIOLETTE, SHELIA MARIE • Kalled, Susan L. • FAHNOE, KELLY C. • HUANG, CHENG RAN • STARK, ELLEN GARBER • TAYLOR, FREDERICK ROBBINS • Caravella, Justin Andrew • Holers, Vernon Michael
Assignees
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Publication Number
US-11879008-B2
Publication Date
2024-01-23
Expiration Date
Abstract
Provided herein are fusion protein constructs that can bind a complement-associated antigen, comprising a targeting moiety and a complement modulator protein, or a fragment thereof or a variant thereof. The targeting moiety is an antibody or an antigen binding fragment thereof, in some examples. Further provided are methods of using the fusion protein constructs, for example, in treating complement mediation conditions.
Core Innovation
The invention relates to methods of treating a complement mediated disease characterized by an increased deposition of C3d by administering a fusion protein construct. The fusion protein construct includes an antibody or an antigen-binding fragment thereof that specifically binds complement protein 3d (C3d), with defined heavy chain and light chain complementarity determining regions (CDR-H1, CDR-H2, CDR-H3; CDR-L1, CDR-L2, CDR-L3) indicated by SEQ ID NOs.
The fusion protein construct further comprises a complement modulator polypeptide selected from CR1, DAF, MCP, Crry, MAp44, MAp19, CD59, factor H, and biologically active fragments thereof. The fusion architecture combines the C3d-binding antibody component with the selected complement modulator component, and includes antibody and Fc-fusion formats, linker and cleavage-related elements, and Fc structural region configuration information.
The described approach is directed to complement-associated kidney disease contexts involving increased C3d deposition. The document further describes extensive amino-acid sequence listings for exemplary anti-C3d antibody/fusion protein constructs, including heavy and light chain arrangements.
Claims Coverage
Two independent claim themes are present: a method of treating a complement mediated disease characterized by increased C3d deposition by administering a C3d-binding antibody–complement modulator fusion protein, and a fusion protein construct with specified CDR amino acid sequences and a defined complement modulator selection set.
Treating complement mediated disease with increased C3d deposition using a C3d-binding fusion protein
A method of treating a complement mediated disease characterized by an increased deposition of C3d by administering to a subject a fusion protein construct comprising an antibody or an antigen-binding fragment thereof that specifically binds to complement protein 3d (C3d), and a complement modulator polypeptide selected from CR1, DAF, MCP, Crry, MAp44, MAp19, CD59, factor H, and biologically active fragments thereof.
Defined C3d-binding antibody CDR sequences
The antibody or antigen-binding fragment thereof comprises a heavy chain with CDR-H1, CDR-H2, and CDR-H3 sequences defined by SEQ ID NO: 29, SEQ ID NO: 260, and SEQ ID NO: 31, and a light chain with CDR-L1, CDR-L2, and CDR-L3 sequences defined by SEQ ID NO: 32, SEQ ID NO: 33, and SEQ ID NO: 34.
Complement modulator polypeptide selection set
The complement modulator polypeptide comprises a complement protein selected from the group consisting of CR1, DAF, MCP, Crry, MAp44, MAp19, CD59, factor H, and a biologically active fragment thereof.
Defined linker connection between antibody and complement modulator polypeptide
The fusion protein construct further contains a linker connecting the antibody or antigen-binding fragment to a complement modulator polypeptide, with linker sequence options defined by SEQ ID NO: 138, 161 to 183, and 241.
Overall, the claim coverage centers on a C3d-binding antibody or antigen-binding fragment with specified CDR sequences fused to a complement modulator polypeptide selected from a defined set, for treating complement mediated disease characterized by increased C3d deposition.
Stated Advantages
Provides a method for treating a complement mediated disease characterized by an increased deposition of C3d.
Documented Applications
Treatment of a complement mediated disease characterized by an increased deposition of C3d.
Complement mediated kidney disease.
Treatment of complement-mediated disease more generally.
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