Chimeric inhibitor molecules of complement activation
Inventors
Garred, Peter • Glue, Tina Hummelshoj • Skjodt, Mikkel-Ole
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11945848-B2
Publication Date
2024-04-02
Expiration Date
Abstract
The present invention relates to novel chimeric molecules of ficolin-associated polypeptides, such as fusion polypeptides for the use in the treatment of conditions associated with inflammation, apoptosis, autoimmunity, coagulation, thrombotic or coagulopathic related diseases. The present invention further relates to nucleic acid molecules encoding such fusion polypeptides, vectors and host cells used in the production of the fusion polypeptides.
Core Innovation
The invention relates to chimeric ficolin-associated polypeptides that comprise a human ficolin-associated polypeptide and an inhibitor of complement activation. The human ficolin-associated polypeptide includes the amino acid sequence set forth in SEQ ID NO:1 or a variant thereof having at least 80% sequence identity to SEQ ID NO:1.
The disclosed chimeric molecules are based on ficolin-associated polypeptide (FAP/MAP-1) and lectin pathway recognition in the complement system. The invention is positioned to inhibit complement activation associated with the lectin complement pathway.
The inhibitor of complement activation is selected from Factor H, GAS6, Protein S, C1-inhibitor, complement component 4 binding protein, Factor I, CR1, DAF(CD55), CD59, CR2, or a fragment thereof that inhibits complement activation, or an immunoglobulin molecule or part thereof that is an inhibitor of complement activation. The disclosed scope includes homodimer forms and directly fused fusion protein formats, and the chimeric molecule inhibits complement activation in a subject suffering from an autoimmune disorder.
Claims Coverage
The claim coverage identifies one independent treating method. It recites administering a composition containing a chimeric ficolin-associated polypeptide comprising a human ficolin-associated polypeptide and an inhibitor of complement activation, with the chimeric molecule inhibiting complement activation; dependent claims add sequence, structural, and inhibitor-selection refinements.
Chimeric ficolin-associated polypeptide for autoimmune disorder treatment
A method of treating a subject suffering from an autoimmune disorder comprising administering a composition comprising a chimeric molecule of a ficolin-associated polypeptide, where the molecule comprises a human ficolin-associated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:1 or a variant thereof having at least 80% sequence identity to SEQ ID NO:1; and an inhibitor of complement activation selected from Factor H, GAS6, Protein S, C1-inhibitor, complement component 4 binding protein, Factor I, CR1, DAF(CD55), CD59, CR2, or a fragment thereof that inhibits complement activation, or an immunoglobulin molecule or part thereof that is an inhibitor of complement activation; wherein the chimeric molecule inhibits complement activation in a subject suffering from an autoimmune disorder.
Treatment of a defined autoimmune disorder list
The autoimmune disorder is selected from Addison's disease, autoimmune hemolytic anemia, autoimmune thyroiditis, Crohn's disease, Graves' disease, Guillain-Barre syndrome, systemic lupus erythematosus, lupus nephritis, multiple sclerosis, myasthenia gravis, psoriasis, primary biliary cirrhosis, rheumatoid arthritis, uveitis, asthma, atherosclerosis, type I diabetes, and allergies.
Homodimer form of the ficolin-associated polypeptide
The ficolin-associated polypeptide is provided in a homodimer form.
Direct fusion protein construction
A ficolin-associated polypeptide and an inhibitor of complement activation are directly fused together as a fusion protein.
Factor H selection with defined SCR-domain fragment constraint
The complement activation inhibitor is Factor H, or an inhibiting fragment containing at least the first four SCR domains of Factor H.
Fc component constraint for immunoglobulin-based complement inhibition
The immunoglobulin molecule or a portion of it comprises the Fc component of human IgG1–IgG4.
The claims center on treating defined autoimmune disorders by administering a composition containing a chimeric molecule of a ficolin-associated polypeptide defined by SEQ ID NO:1 or an at-least-80% identity variant and a selected inhibitor of complement activation, with dependent claims refining homodimer and direct fusion formats and limiting certain inhibitor options.
Stated Advantages
Inhibits complement activation in a subject suffering from an autoimmune disorder.
Provides a treating method for autoimmune disorders selected from a listed group.
Documented Applications
Treating a subject suffering from an autoimmune disorder, where the autoimmune disorder is selected from Addison's disease, autoimmune hemolytic anemia, autoimmune thyroiditis, Crohn's disease, Graves' disease, Guillain-Barre syndrome, systemic lupus erythematosus, lupus nephritis, multiple sclerosis, myasthenia gravis, psoriasis, primary biliary cirrhosis, rheumatoid arthritis, uveitis, asthma, atherosclerosis, type I diabetes, and allergies.
Interested in licensing this patent?