Humanized anti-IL-20 antibody and uses thereof

Inventors

Chang, Ming-ShiTsurushita, NaoyaKumar, Shankar

Assignees

Lbl Biotechnology IncJN Biosciences LLC

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Publication Number

US-9683036-B2

Patent

Publication Date

2017-06-20

Expiration Date


Abstract

Humanized antibodies specific to human interleukin 20 (IL-20) and uses thereof in treating diseases associated with the IL-20 signaling pathway, e.g., osteoporosis, inflammatory disease (e.g., rheumatoid arthritis), cancer, stroke, and renal failure.

Core Innovation

The patent discloses humanized anti-interleukin 20 (IL-20) antibodies and associated nucleic acids that bind human IL-20. The humanized antibodies include heavy chain variable region (VH) and light chain variable region (VL) design criteria using SEQ ID sequences, with VH containing the same heavy chain complementary determining regions (CDRs) as those in SEQ ID NO:1 and being at least 90% identical to SEQ ID NO:1 or SEQ ID NO:3, and VL containing the same light chain CDRs as those in SEQ ID NO:5 and being at least 90% or 95% identical to SEQ ID NO:5 or SEQ ID NO:7, with an additional sequence option SEQ ID NO:15 described in the disclosure.

The disclosure further covers isolated nucleic acids encoding VH and VL, vectors including expression vectors with promoter-linked operable linkage, host cells containing such vectors, and therapeutic use via pharmaceutical compositions. Sequence referencing for CDR mapping and signal peptide arrangement is described, and the patent identifies antibody format coverage including IgG, Fab, F(ab’)2, Fv, and single-chain antibody, and mentions the possibility of bi-specific antibodies.

Example binding and biological efficacy data are reported for the parent antibody and humanized antibodies HL1 and HL2, including BIOCORE binding affinity measurements and an osteoclast differentiation/TRAP assay in which HL2 inhibits osteoclast differentiation comparably to the parent antibody. A reported unexpectedly high IL-20 affinity is stated for the disclosed antibodies.

Claims Coverage

The consolidated content includes three independent claims directed to isolated nucleic acids encoding humanized anti-IL-20 heavy-chain variable region, isolated nucleic acids encoding humanized anti-IL-20 light-chain variable region, and a method for producing a humanized antibody by culturing host cells and isolating the antibody. Across these claims, the core inventive features are preserved CDRs from SEQ ID reference sequences and sequence-identity constraints applied to VH and VL, with production features tied to host-cell expression and antibody isolation.

Heavy chain variable region encoding with preserved CDRs and identity constraint

An isolated nucleic acid encoding a heavy chain variable region (VH) of a humanized antibody that binds human IL-20, wherein the VH contains the same heavy chain CDRs as those in SEQ ID NO:1 and is at least 90% identical to SEQ ID NO:1 or SEQ ID NO:3.

Light chain variable region encoding with preserved CDRs and identity constraint

An isolated nucleic acid encoding a light chain variable region (VL) of a humanized antibody that binds human IL-20, wherein the VL contains the same light chain CDRs as those in SEQ ID NO:5 and is at least 95% identical to SEQ ID NO:5 or SEQ ID NO:7.

Producing a humanized antibody by culturing vector-bearing host cells and isolating the antibody

A method for producing a humanized antibody binding to human IL-20, comprising culturing host cells comprising expression vectors encoding a humanized antibody under conditions allowing for expression of the humanized antibody, wherein the humanized antibody comprises a VH containing the same heavy chain CDRs as those in SEQ ID NO:1 and at least 90% identical to SEQ ID NO:1 or SEQ ID NO:3, and a VL containing the same light chain CDRs as those in SEQ ID NO:5 and at least 90% identical to SEQ ID NO:5 or SEQ ID NO:7; and isolating the humanized antibody thus produced.

Overall, the claim coverage centers on humanized anti-IL-20 antibody variable regions defined by specific preserved CDRs (SEQ ID NO:1 for VH and SEQ ID NO:5 for VL) and identity thresholds, together with production by culturing expression-vector-bearing host cells followed by isolating the produced humanized antibody.

Stated Advantages

High or unexpectedly high IL-20 affinity is stated for the disclosed antibodies.

HL2 inhibits osteoclast differentiation comparably to the parent antibody in the osteoclast differentiation/TRAP assay.

Therapeutic use for IL-20-mediated diseases including osteoporosis, inflammatory diseases such as rheumatoid arthritis, cancer, stroke, and renal failure is stated.

Supports therapeutic use for bone loss/osteoporosis and related inflammatory/cancer conditions.

Documented Applications

Therapeutic use for IL-20-mediated diseases, including osteoporosis, rheumatoid arthritis, cancer, stroke, and renal failure.

Osteoporosis therapy using the humanized anti-IL-20 antibody constructs.

Inflammatory disease use including rheumatoid arthritis.

Cancer treatment use.

Stroke treatment use.

Renal failure treatment use.

Therapeutic use for bone loss/osteoporosis.

Related inflammatory/cancer conditions.

Inhibition of osteoclast differentiation as a biological example.

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