Methods and compositions for treating inflammatory and autoimmune conditions with ECM-affinity peptides linked to anti-inflammatory agents
Inventors
Hubbell, Jeffrey A. • Katsumata, Kiyomitsu • ISHIHARA, Ako • Ishihara, Jun • MANSUROV, ASLAN
Assignees
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Publication Number
US-12465640-B2
Publication Date
2025-11-11
Expiration Date
Abstract
The disclosure relates to the engineering of collagen-binding modification of anti-inflammatory agents using collagen-binding peptide (CBP) and vWF A3 to achieve targeted therapy for inflammatory diseases. Accordingly, embodiments of the disclosure relate to a composition comprising an anti-inflammatory agent operatively linked to an extracellular matrix (ECM)-affinity peptide. Also disclosed are cytokines and anti-inflammatory agents, such as CD200, linked to a serum protein and/or an ECM-affinity peptide. Further aspects of the disclosure relate to a method for treating an autoimmune or inflammatory condition in a subject comprising administering a composition of the disclosure to the subject.
Core Innovation
The invention relates to reducing inflammation in a subject by administering a composition comprising IL-10 linked to a peptide having at least 95% sequence identity to one of SEQ ID NOs: 3, 4, 5, 47, or 52. The linked peptide is an ECM-affinity component, including a collagen-binding peptide or a vWF A3 domain, and the disclosure also allows serum protein linkage, notably albumin, to improve pharmacokinetics and influence biodistribution.
The disclosure describes collagen-binding peptide/domain fusions and albumin-fused IL-10 variants, including recombinant constructs such as SA-IL-10 and CBD-SA-IL-10. It further states that exposed collagen in inflamed and affected tissues provides a rationale for localization of IL-10-linked anti-inflammatory activity, with binding and utility contexts involving ECM-affinity and FcRn binding.
The disclosure reports that engineered collagen-/albumin-affinity cytokine and antibody constructs exhibit improved binding and localization to inflammatory sites or lymphoid organs. It also states that such constructs provide enhanced anti-inflammatory therapeutic effects across arthritis, IBD, IPF, EAE, and T1D models, with translational advantages including human protein domains reducing immunogenicity.
Claims Coverage
The independent claim covers a method of reducing inflammation by administering IL-10 linked to a peptide with at least 95% sequence identity to specified SEQ ID NOs. The claim set includes inventive features that narrow the inflammation condition, refine the peptide identity or sequence correspondence, optionally add a serum protein, and define intravenous administration.
IL-10 linked to a peptide with at least 95% sequence identity to specified SEQ ID NOs
Administering an effective amount of a composition comprising IL-10 linked to a peptide having at least 95% sequence identity to one of SEQ ID NOs: 3, 4, 5, 47, or 52.
Inflammation condition selected from specified inflammatory diseases and inflammation types
Administering the method of the IL-10-linked composition to reduce inflammation in an inflammation condition selected from specified inflammatory diseases and inflammation types.
Peptide amino acid sequence corresponding to specified SEQ ID NOs
Linking IL-10 to a peptide such that the amino acid sequence corresponds to SEQ ID NOs: 3, 4, 5, 47, or 52.
Serum protein linked to the peptide or to IL-10
Further linking a serum protein to a peptide having 95% sequence identity or to IL-10.
Intravenous injection administration
Administering the composition via intravenous injection.
Overall, the claim coverage centers on IL-10 linked to an ECM-affinity peptide with at least 95% sequence identity to specified SEQ ID NOs, with dependent coverage that narrows the targeted inflammation conditions, tightens the peptide sequence specification, optionally adds a serum protein component, and defines an intravenous administration context.
Stated Advantages
Reduces inflammation in a subject.
Improved binding and localization to inflammatory sites or lymphoid organs.
Enhanced anti-inflammatory therapeutic effects across arthritis, IBD, IPF, EAE, and T1D models.
Enhanced comparative efficacy versus unmodified cytokines and antibodies.
Translational advantages, including human protein domains reducing immunogenicity.
Documented Applications
Inflammatory bowel disease, including Crohn's disease.
Idiopathic pulmonary fibrosis.
Multiple sclerosis (EAE model).
Type 1 diabetes.
Arthritis, including collagen antibody-induced arthritis (CAIA).
Treating inflammatory diseases and inflammation types including inflammatory bowel disease, idiopathic pulmonary fibrosis, multiple sclerosis, type 1 diabetes, Crohn's disease, psoriasis, acute inflammation, chronic inflammation, neuroinflammation, and rheumatoid arthritis.
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