Methods of treating pruritic disease with IL-31 monoclonal antibodies
Inventors
Bondensgaard, Kent • Beckmann, Roland
Assignees
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Publication Number
US-11542327-B2
Publication Date
2023-01-03
Expiration Date
Abstract
The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.
Core Innovation
The document describes humanized mouse anti-human IL-31 antibodies and antibody fragments that specifically bind human IL-31 and act as IL-31 antagonists. The antibodies are configured so that neutralization targets IL-31 pro-inflammatory and pro-pruritic signaling, and the approach is directed to treating pruritic diseases, with atopic dermatitis and related skin disorders emphasized.
The invention specifies a humanized mouse antibody format with heavy chain variable domain and light chain variable domain comprising complementarity determining regions and framework regions. The complementarity determining regions are defined by particular amino acid sequences designated as SEQ ID NO:1 to SEQ ID NO:7, and the framework regions are defined by sequence identity thresholds of at least 90% with reference sequences designated as SEQ ID NO:8 to SEQ ID NO:21 and related sets.
The document further describes sequence-position effects within the humanized mouse variable domains, including specific framework positions associated with heavy chain and light chain regions. It also discusses constant-region options, including IgG4 and an IgG4 Ser to Pro mutation at position 241 (Kabat), and provides rationale related to measured binding and potency in biochemical and cell-based assays.
Claims Coverage
The partial content provides two independent claims: clm-00001 and clm-00014. Both claims cover a therapeutically effective administration of a monoclonal antibody that specifically binds human IL-31, with the antibody’s heavy and light chain variable domains defined by specified CDR sequences and framework regions having at least 90% sequence identity, and both limit the pruritic disease to a list of specified dermatologic indications.
Treating pruritic disease with IL-31 binding monoclonal antibody
A method of treating a pruritic disease in a human patient by administering a therapeutically effective amount of a monoclonal antibody that specifically binds to human IL-31, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain.
Defined heavy-chain CDR and framework identity
The heavy chain variable domain comprises complementarity determining region CDR1 having the amino acid sequence of SEQ ID NO:1, CDR2 having the amino acid sequence of SEQ ID NO:2, and CDR3 having the amino acid sequence of SEQ ID NO:3, and the heavy chain variable domain framework region comprises FR1 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:12, FR2 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:13, FR3 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:14, and FR4 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:15.
Defined light-chain CDR and framework identity
The light chain variable domain comprises complementarity determining region CDR1 having the amino acid sequence of SEQ ID NO:5, CDR2 having the amino acid sequence of SEQ ID NO:6, and CDR3 having the amino acid sequence of SEQ ID NO:7, and the light chain variable domain framework region comprises FR5 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:17, FR6 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:18, FR7 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:19, and FR8 having at least 90% sequence identity with amino acid sequence of SEQ ID NO:20.
Enumerated pruritic dermatologic disease indications
The pruritic disease is atopic dermatitis, contact dermatitis, dermatitis, prurigo nodularis, eczema, vitiligo, alopecia aerata, acne rosacea, acne vulgaris or bullous pemphigoid.
Pharmaceutical composition administration with IL-31 binding antibody
A method of treating a pruritic disease in a human patient comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds to human IL-31 and a pharmaceutically acceptable carrier, wherein the antibody comprises a heavy chain variable domain and a light chain variable domain with CDR and FR definitions as recited.
Optional restriction to human immunoglobulin constant domain class and sequence mutation
In dependent coverage, the method further includes that the monoclonal antibody comprises a human immunoglobulin constant domain, optionally narrowed to IgG1, IgG2, IgG3, or IgG4, and further constrained such that the human immunoglobulin constant domain is IgG4 and contains a serine-to-proline mutation at position 241, as determined by Kabat.
Further framework-region sequence specification by SEQ ID
Dependent coverage further specifies individual heavy-chain framework regions, including that the heavy chain variable domain FR1 comprises the amino acid sequence of SEQ ID NO:12 and that the heavy chain variable domain FR4 comprises the amino acid sequence of SEQ ID NO:15, and that the light chain variable domain FR5 contains the amino acid sequence of SEQ ID NO:17.
Across the independent claims, the core coverage is administration of a therapeutically effective amount of an IL-31-binding monoclonal antibody to treat enumerated pruritic dermatologic diseases, with antibody variable domains defined by SEQ ID-based CDR sequences and at-least-90% sequence identity framework regions. Dependent coverage further narrows the antibody’s human constant domain class, including IgG4, and optionally specifies an IgG4 Ser to Pro mutation at Kabat position 241 and additional framework-region SEQ ID assignments.
Stated Advantages
Documented Applications
No documented applications found
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