Use of IL-31 monoclonal antibodies for reducing pruritus
Inventors
Siadak, Anthony W. • Rene, Shirley A. • Bilsborough, Janine M.
Assignees
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Publication Number
US-10273297-B2
Publication Date
2019-04-30
Expiration Date
Abstract
The present invention relates to methods of treating pruritic diseases, including but not limited to Contact dermatitis, Atopic Dermatitis, Drug induced delayed type cutaneous allergic reactions, Toxic epidermal necrolysis, Cutaneous T cell Lymphoma, Bullous pemphigoid, Alopecia wereata, Vitiligo, Acne Rosacea, Prurigo nodularis, Scleroderma, Herpes simplex virus, or combination thereof by administering IL-31 monoclonal antibodies. The invention provides the hybridomas that generate the monoclonal antibodies and the amino acid sequences of the variable regions of the monoclonal antibodies and chimeric antibodies comprising the amino acid sequences of the light and heavy chain variable regions.
Core Innovation
The invention relates to monoclonal antibody antagonists of IL-31 that bind to a polypeptide consisting of amino acid residues 27 to 164 of SEQ ID NO:2 and neutralize IL-31/IL-31RA signaling. By blocking IL-31 activity directed to IL-31RA, the antibodies reduce pro-inflammatory activity associated with pruritus and skin/epidermal conditions.
The problem addressed is pruritus and inflammatory skin diseases, with the approach framed as reducing scratching and dermatitis by antagonizing IL-31 signaling through specific binding to the defined IL-31 polypeptide region. The therapeutic use is described for administration to a mammal, including subcutaneous administration, with pruritus reduced after administration.
The core antibody concept includes monoclonal antibodies with defined heavy chain variable-region and light chain variable-region complementarity determining region sequences. The document further describes pharmaceutical compositions comprising a therapeutically effective amount of the monoclonal antibody and a pharmaceutically acceptable carrier.
Claims Coverage
Two independent claims are provided, covering administration of a monoclonal antibody and administration of a pharmaceutical composition containing that monoclonal antibody. Each independent claim specifies the same IL-31-binding target polypeptide and the same CDR-defined heavy- and light-chain variable regions, with subcutaneous administration and pruritus reduction as the functional outcome.
Administering an IL-31-binding monoclonal antibody to reduce pruritus
A method of reducing pruritus in a mammal with a skin or epidermal condition comprising administering to the mammal a therapeutically effective amount of a monoclonal antibody that specifically binds to a polypeptide consisting of amino acid residues 27 to 164 of SEQ ID NO:2, wherein the monoclonal antibody comprises a heavy chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO:51, CDR2 having the amino acid sequence of SEQ ID NO:52, and CDR3 having the amino acid sequence of SEQ ID NO:53; and a light chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO:54, CDR2 having the amino acid sequence of SEQ ID NO:55, and CDR3 having the amino acid sequence of SEQ ID NO:56; wherein the monoclonal antibody is administered subcutaneously to the mammal; and wherein after administration of the antibody the pruritus is reduced.
Administering an IL-31-binding monoclonal antibody pharmaceutical composition to reduce pruritus
A method of reducing pruritus in a mammal with a skin or epidermal condition comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds to a polypeptide consisting of amino acid residues 27 to 164 of SEQ ID NO:2 and a pharmaceutically acceptable carrier, wherein the monoclonal antibody comprises a heavy chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO:51, CDR2 having the amino acid sequence of SEQ ID NO:52, and CDR3 having the amino acid sequence of SEQ ID NO:53; and a light chain variable region comprising CDR1 having the amino acid sequence of SEQ ID NO:54, CDR2 having the amino acid sequence of SEQ ID NO:55, and CDR3 having the amino acid sequence of SEQ ID NO:56; wherein the composition is administered subcutaneously to the mammal; and wherein after administration of the composition the pruritus is reduced.
Across both independent claims, the inventive coverage centers on subcutaneous administration of an IL-31-antagonizing monoclonal antibody that specifically binds amino acid residues 27 to 164 of SEQ ID NO:2, with pruritus reduction observed after administration. The antibodies are further characterized by specified heavy-chain and light-chain variable-region CDR amino acid sequences (SEQ ID NOs: 51-53 and 54-56).
Stated Advantages
Reduces pruritus after administration in a mammal with a skin or epidermal condition.
Neutralizes IL-31/IL-31RA signaling to reduce pro-inflammatory activity associated with pruritus and inflammatory skin diseases.
Reduces scratching and dermatitis in pruritic and inflammatory skin diseases.
Documented Applications
Therapeutic reduction of pruritus in a mammal with a skin or epidermal condition, including pruritic and inflammatory skin diseases such as atopic dermatitis, contact dermatitis, prurigo nodularis, bullous pemphigoid, and drug-induced delayed type cutaneous allergic reactions.
Therapeutic targeting of additional conditions explicitly listed as IL-31-associated diseases, including toxic epidermal necrolysis, cutaneous T cell lymphoma, alopecia areata, vitiligo, acne rosacea, acne vulgaris, and viral-associated pruritis.
Assessment of itch/dermatitis outcomes in an NC/Nga mouse model and measurement of biomarker effects including TARC/MDC.
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