What icotrokinra is and how it works at the receptor level

Icotrokinra is an orally active cyclic peptide inhibitor that binds directly to the IL-23 receptor (IL-23R), blocking the downstream signalling cascade that drives inflammatory skin conditions including moderate to severe plaque psoriasis. Unlike injectable monoclonal antibodies, which intercept the IL-23 cytokine before it reaches the receptor, icotrokinra occupies the receptor binding site itself — a mechanistic distinction with significant implications for selectivity and oral bioavailability.

Protagonist Therapeutics has published crystal structures of the IL-23 receptor both alone and in complex with icotrokinra (designated PN-235 in early research filings). These structural data, disclosed in US patent applications assigned to Protagonist Therapeutics, provide direct evidence for the receptor-binding mechanism and are also used in methods for identifying additional molecules that can bind IL-23R — a strategy that underpins the company’s broader platform. According to WIPO, structural characterisation of a drug-receptor complex is a foundational step in establishing freedom-to-operate and enabling derivative patent claims.

The co-development agreement between Protagonist Therapeutics and Janssen Research & Development, a subsidiary of Johnson & Johnson, is reflected directly in the patent record. Multiple PCT filings published in 2023 and 2024 — including WO2023212427, WO2023212432, WO2024026471, and WO2024026472 — are jointly assigned to both entities and describe icotrokinra formulated specifically as an oral formulation for treating inflammatory conditions. The choice to file PCT applications jointly signals that both companies intend to pursue protection across major markets simultaneously.

The patent landscape: Protagonist, Janssen, and the oral formulation race

The patent estate around icotrokinra is built on two parallel tracks: Protagonist Therapeutics’ foundational cyclic peptide composition-of-matter claims, and Janssen Pharmaceutica’s method-of-use and formulation filings that extend those claims into specific therapeutic applications and oral delivery strategies.

Protagonist Therapeutics has filed multiple independent US and WO patent families covering cyclic peptides that bind the IL-23 receptor, with publications spanning from 2021 (US11180535B2, granted) through to 2024 (US20240279278A1, US20240117001A1). The granted US patent US11180535B2 — published November 2021 — establishes an early priority date for the core cyclic peptide scaffold, which is strategically important for blocking competitor design-arounds. The company also holds a separate US patent application (US20220002372A1) and a continuation (US20230056947A1) specifically disclosing crystal structures of IL-23R bound to icotrokinra, which can be used to identify and claim structurally related molecules.

Janssen Pharmaceutica’s independent US patent applications — US20220315636A1, US20230054416A1, and US20240091320A1 — cover IL-23R peptide inhibitors and their use in inflammatory bowel disease, psoriasis, and other inflammatory conditions, with the most recent publication dated March 2024. These filings are distinct from the jointly assigned oral formulation patents, suggesting that Janssen is building a layered IP portfolio that covers both the formulation and the method-of-use dimensions independently of Protagonist’s composition-of-matter estate.

Who else is targeting the IL-23 receptor orally?

Icotrokinra is not the only oral IL-23 receptor inhibitor in the patent record, and the competitive landscape is more crowded than the clinical trial registries alone would suggest. At least four distinct organisations have filed patent claims on molecules that bind or inhibit the IL-23 receptor through non-antibody mechanisms.

Boehringer Ingelheim International has filed two US patent publications — US11530239B2 (granted December 2022) and US20230416329A1 (published December 2023) — covering small-molecule inhibitors of the IL-23 receptor for autoimmune and inflammatory diseases including psoriasis, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis, and rheumatoid arthritis. The granted status of US11530239B2 means Boehringer Ingelheim already holds enforceable claims in the US on at least one structural class of small-molecule IL-23R inhibitor — a potential freedom-to-operate consideration for any company developing in this space.

“At least four distinct organisations — Protagonist Therapeutics, Boehringer Ingelheim, Bicycle Therapeutics, and Glenmark Pharmaceuticals — have filed patent claims on non-antibody molecules that bind or inhibit the IL-23 receptor, creating a multi-front competitive landscape around oral and topical alternatives to injectable biologics.”

Bicycle Therapeutics has taken a structurally different approach, filing US patents on bicyclic peptide ligands specific for IL-23 itself (rather than the receptor) — including US11952408B2, granted April 2024, and the earlier published application US20230159594A1. Bicyclic peptides are constrained by two covalent bridges, conferring conformational rigidity that can improve target selectivity and metabolic stability compared with monocyclic peptides. According to research published by Nature, constrained peptide scaffolds represent a growing strategy for accessing historically undruggable protein-protein interaction surfaces.

Glenmark Pharmaceuticals has taken yet another route, disclosing in US20230313006A1 a pharmaceutical composition for topical or transdermal delivery of an IL-23 receptor antagonist for treating psoriasis, psoriatic arthritis, and atopic dermatitis. While this approach would not compete directly with an oral systemic therapy, it illustrates the breadth of delivery modality innovation occurring around the IL-23R target.

Oral peptide vs. injectable biologic: what the patent record reveals

The strategic tension between icotrokinra and the existing injectable IL-23 biologic franchise is visible not just in clinical development timelines, but in the parallel patent strategies that J&J’s subsidiaries are pursuing simultaneously. Janssen Biotech — a separate J&J entity from Janssen Pharmaceutica and Janssen Research & Development — holds three recently granted or published US patents (US11866477B2, US11891429B2, US12006349B2) covering methods of treating moderate to severe plaque psoriasis using antibodies that specifically bind the p19 subunit of IL-23, administered subcutaneously at fixed doses at 4-week or 8-week intervals.

This p19-targeting antibody approach is the mechanism of guselkumab (Tremfya), J&J’s approved injectable IL-23 biologic for psoriasis. The fact that Janssen Biotech is actively filing and obtaining new use patents on these methods — with the most recent grant dated June 2024 (US12006349B2) — signals that J&J intends to maintain a robust injectable biologic IP position even as the oral icotrokinra programme advances. For IP strategists, this dual-track approach is a textbook example of portfolio lifecycle management: protect the existing revenue stream while building the next-generation asset.

The structural difference between the two approaches matters for patent scope. Injectable anti-IL-23 antibodies target the cytokine (specifically the p19 subunit of IL-23) before it reaches the receptor. Icotrokinra targets the receptor itself. These are non-overlapping mechanisms, meaning that composition-of-matter patents on one do not directly block the other — but method-of-use patents for the same indication (moderate to severe plaque psoriasis) can create overlapping claim territory that requires careful freedom-to-operate analysis. Standards bodies such as ISO and regulatory authorities including the EMA treat these as distinct therapeutic modalities for regulatory purposes, but the commercial and IP competition is direct.

Indication breadth as a competitive moat

Both the injectable biologic patents and the oral peptide filings claim psoriasis as a primary indication, but the oral IL-23R inhibitor filings extend substantially further. The jointly assigned PCT applications and Janssen Pharmaceutica’s independent filings cover psoriatic arthritis, inflammatory bowel disease (both Crohn’s disease and ulcerative colitis), ankylosing spondylitis, and hidradenitis suppurativa. This breadth of claimed indications — if supported by clinical data — could allow icotrokinra to address a larger patient population than the injectable biologic alone, providing a commercial rationale for the oral programme that goes beyond simply replacing an injection with a pill.

Strategic implications for IP professionals and R&D leaders

The icotrokinra patent landscape offers several concrete lessons for IP and R&D professionals tracking the oral immunology space. First, the co-development and co-assignment structure between Protagonist Therapeutics and Janssen Research & Development creates a shared IP position that neither party can license or enforce independently — a structural feature that affects both freedom-to-operate assessments and any future licensing negotiations with third parties.

Second, the layered filing strategy — composition-of-matter (Protagonist, granted), crystal structure and receptor-binding method (Protagonist), oral formulation (joint PCT), and method-of-use for specific indications (Janssen Pharmaceutica independent) — represents a multi-layer protection architecture that is increasingly common in peptide drug development. According to patent data tracked through PatSnap’s IP intelligence platform, peptide therapeutics with oral bioavailability represent one of the fastest-growing patent filing categories in immunology, reflecting the industry’s recognition that oral delivery is a key differentiator for chronic disease markets.

Third, the presence of Boehringer Ingelheim’s granted small-molecule IL-23R inhibitor patent (US11530239B2) and Bicycle Therapeutics’ granted bicyclic peptide patent (US11952408B2) in the same design space means that freedom-to-operate clearance for any new IL-23R-targeting molecule requires analysis across at least four distinct structural modalities: monocyclic peptides, bicyclic peptides, small molecules, and antibodies. This is a broader FTO landscape than the clinical trial registry alone would suggest.

For R&D leaders, the indication expansion strategy visible in the icotrokinra filings — from psoriasis to IBD, psoriatic arthritis, and hidradenitis suppurativa — mirrors the playbook used successfully by injectable IL-23 biologics over the past decade. The difference is that oral administration, if proven efficacious in Phase III, removes the principal patient and physician barrier to first-line use: the requirement for subcutaneous injection. The PatSnap Insights blog has tracked similar oral-versus-injectable competitive dynamics in the JAK inhibitor and S1P receptor modulator spaces, where oral formulations ultimately captured significant market share from established injectable therapies.