Nucleic acid molecules encoding humanized IL-31 monoclonal antibodies

Inventors

Bondensgaard, Kent • Beckmann, Roland

Assignees

Merck Serono SA • Zymogenetics Inc

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Publication Number

US-10640559-B2

Patent

Publication Date

2020-05-05

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 invention relates to isolated nucleic acid molecules encoding humanized monoclonal antibodies that specifically bind to human IL-31. The encoded humanized monoclonal antibodies comprise a heavy chain and a light chain, with the heavy chain amino acid sequence defined as SEQ ID NO:47 and the light chain amino acid sequence defined as SEQ ID NO:46.

The invention further describes humanized monoclonal antibodies and antigen-binding molecules targeting IL-31 signaling through IL-31RA/OSMRbeta. It includes specific humanized heavy and light variable domain compositions, and an optional constant region is described, including a human IgG4 constant domain with Ser241Pro and alternative constant domain isotypes.

The document also describes nucleic acids encoding the humanized monoclonal antibodies, recombinant expression constructs, and recombinant expression host cells for producing the antibodies. Functional characterization is described using binding affinity and inhibitory potency assessments, including Biacore and cell-based assays together with in vivo disease model descriptions.

Claims Coverage

The claim set contains one independent claim. The independent claim is directed to an isolated nucleic acid molecule encoding a specific humanized monoclonal antibody, with the antibody defined by a heavy chain sequence and a light chain sequence, yielding two key inventive features.

Isolated nucleic acid encoding a human IL-31-binding humanized monoclonal antibody

An isolated nucleic acid molecule encoding a humanized monoclonal antibody that specifically binds to human IL-31.

Defined heavy chain and light chain sequences for the humanized monoclonal antibody

The encoded monoclonal antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:47 and a light chain comprising the amino acid sequence of SEQ ID NO:46.

Across the independent claim, the inventive scope is grounded in the encoding of a humanized monoclonal antibody that specifically binds human IL-31, with the antibody uniquely defined by the heavy-chain amino acid sequence SEQ ID NO:47 and the light-chain amino acid sequence SEQ ID NO:46.

Stated Advantages

Specifically binds human IL-31.

Provides inhibitory potency for IL-31 signaling through IL-31RA/OSMRbeta as assessed in described assays.

Supports treatment of IL-31-mediated inflammatory and pruritic skin diseases and other inflammatory conditions.

Documented Applications

Treating IL-31-mediated inflammatory and pruritic skin diseases.

Treating other inflammatory conditions.

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