CD1a antibodies and uses thereof
Inventors
WINAU, Florian • KOVALENKO, Oleg V. • Chang, Chew Shun • Wu, Di • MARZE, Nicholas Andrew • Chiang, Shian-Huey
Assignees
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Publication Number
US-12528868-B2
Publication Date
2026-01-20
Expiration Date
Abstract
Antibodies, and antigen-binding fragments thereof, that specifically bind to Cluster of Differentiation 1a (CD1a) are provided. Embodiments include uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.
Core Innovation
The invention provides anti-CD1a antibody embodiments for inhibiting CD1a-dependent T cell activation in a subject in need thereof. The antibody specifically binds human CD1a and is defined by particular CDR-H1, CDR-H2, CDR-H3, and CDR-L1, CDR-L2, and CDR-L3 amino acid sequences. The approach is presented in terms of antibody structural definition through selected CDR sequences and corresponding antibody characteristics and constraints.
The disclosure further describes humanization and germline framework selection for the anti-CD1a antibodies, including selection of human VH/VL frameworks and percent identity/substitution ranges as well as conservative and non-conservative variants. The invention characterizes antibody/epitope properties by naming antibodies and CD1a binding residues and by reporting binding affinity ranges obtained using methods such as surface plasmon resonance and bio-layer interferometry. Cross-reactivity limits with CD1b/c/d are addressed together with functional inhibition metrics.
Functional and immunological effects are presented by reporting inhibition of CD69 expression, IL-2 production, and serum IgE levels, and by including gene-expression improvement in atopic dermatitis models. The document also identifies rat anti-human CD1a hybridomas and reports binding specificity excluding CD1b/c/d, together with structural and epitope definition, including X-ray co-crystal structure data and mapping of the Ab138/CD1a interface residues.
Claims Coverage
The provided claim coverage centers on one independent method claim. It specifies inhibition of CD1a-dependent T cell activation by administering a therapeutically effective amount of a human CD1a-specific antibody or antigen-binding fragment defined by six CDR sequences.
Method of inhibiting CD1a-dependent T cell activation
Administering to the subject a therapeutically effective amount of an antibody, or antigen binding fragment thereof, that specifically binds to human CD1a, wherein the antibody comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27, thereby inhibiting CD1a-dependent T cell activation.
The claim coverage is centered on therapeutic administration of a human CD1a-specific antibody defined by the specified CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 sequences to inhibit CD1a-dependent T cell activation.
Stated Advantages
Inhibits CD1a-dependent T cell activation.
Inhibits CD69 expression.
Inhibits IL-2 production.
Inhibits serum IgE levels.
Prevents CD1a from binding a T cell receptor.
Inhibits expression of genes including TSLP, FLG, IL-33, CCL-26, IL-23p40, CXCL-1, and CCL-20.
Documented Applications
Treatment/modulation of atopic dermatitis, including atopic dermatitis gene signature suppression and related clinical metrics.
Treatment/modulation of inflammatory bowel disease.
Inhibition of CD1a-mediated disease conditions across inflammatory, allergic, respiratory, gastrointestinal, fibrotic, metabolic, autoimmune, infectious, and neurodegenerative diseases or conditions, including Crohn's disease, ulcerative colitis, and multiple sclerosis.
Diagnostic use context described alongside treatment and composition context.
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