Factor H potentiating antibodies and uses thereof

Inventors

Lauder, Scott • Purcell, Tom • Govindarajan, Sridhar • Kuijpers, Taco Willem • WOUTERS, Diana • BROUWER, Maria Clara • POUW, Richard Benjamin • RISPENS, Taede • Jongerius, Ilse • DEKKERS, Gillian

Assignees

Dna Twopointo Inc D/b/a Atum • Sanquin Ip BV • Disc Medicine Inc

Abstract

Provided herein are novel isolated, synthetic or recombinant antibodies and fragments thereof specific for factor H, or nucleic acids or vectors encoding such antibodies and fragments. Further provided herein is the use of such antibodies, fragments, nucleic acids or vectors for inhibiting complement activation and treatment of disorders associated with complement activation.

Core Innovation

The invention relates to an isolated, synthetic or recombinant antibody or an antigen binding fragment thereof that specifically binds complement control protein domain 18 (CCP18) of factor H (FH). The antibody is defined by particular light chain and heavy chain CDR sequences, with explicit sequence options provided using SEQ ID NOs for light chain CDR1, CDR2, and CDR3 and for heavy chain CDR1, CDR2, and CDR3.

The disclosure further potentiates anti-factor H antibodies or antigen-binding fragments that specifically bind FH CCP18, including variants built around enumerated light and heavy chain CDR sequence frameworks and SEQ ID numbers. The stated purpose is to enhance FH activity against alternative complement activation, with functional benchmarks tied to FH binding and complement-related readouts.

The reported functional performance includes increased FH binding to C3b with binding affinity improvements, including lower KD and/or increased affinity, and inhibition of C3b deposition on LPS with reduced hemolytic activity in human serum. The disclosure also includes competitive epitope binding to CCP18, described as competition with reference antibodies FH.07 and FHR-1.3B4.

Claims Coverage

The document includes one independent claim directed to an antibody or antigen-binding fragment with CCP18-specific binding defined by enumerated CDR sequence constraints. Dependent claims refine the independent claim by adding quantitative binding and functional thresholds, selecting particular fragment formats or Fc configurations, and narrowing binding-performance requirements tied to alternative complement activation readouts.

Overall claim coverage is centered on antibodies or antigen-binding fragments that specifically bind FH CCP18 using a constrained set of light- and heavy-chain CDR sequences. The dependent claim set further narrows this to quantitative binding and functional performance and to selected antibody fragment and human IgG4 Fc residue 297 variants.

Stated Advantages

Documented Applications