Crystal Form of Imidazolinone Derivative Stable Crystal Structures for a Next-Generation DNA-PK Inhibitor

This patent covers six distinct crystal forms of an imidazolinone compound designed to inhibit DNA-dependent protein kinase (DNA-PK), a key enzyme that cancer cells use to repair the DNA damage inflicted by radiotherapy and chemotherapy.

The Problem

One of oncology’s most persistent challenges is that tumours resist DNA-damaging treatments by rapidly repairing the breaks that radiation and chemotherapy create. DNA-dependent protein kinase (DNA-PK) sits at the centre of this repair machinery. It is a serine/threonine kinase that, in combination with the Ku70/Ku80 heterodimer, detects and ligates DNA double-strand breaks. In cancer cells, which are already under high replication stress and often lack backup repair pathways, inhibiting DNA-PK forces those breaks to persist and drives cell death. This makes DNA-PK inhibitors an attractive partner for radiotherapy, platinum-based chemotherapy, and other DNA-damaging regimens. The challenge then shifts to the chemistry: a drug candidate with strong DNA-PK inhibitory activity in the laboratory still needs to be manufacturable, stable on the shelf, and bioavailable when taken orally. Amorphous forms of active pharmaceutical ingredients routinely fail on one or more of these counts, which is why identifying the right crystal polymorph is a critical and patentable step in drug development.

What This Invention Does

Kangbaida Biotechnology has characterised six crystalline forms (Forms I through VI) of Compound A, a substituted imidazolinone with the chemical name 4-((7-ethyl-8-oxo-9-(tetrahydro-2H-pyran-4-yl)-8,9-dihydro-7H-purin-2-yl)amino)-2-fluoro-5-methylbenzamide. The compound originated in PCT/CN2021/087912 and shows good inhibitory activity against DNA-PK. The parent Australian application AU 2022350562 covers the compound itself; this divisional application claims the crystal forms, each characterised by its unique X-ray powder diffraction (XRPD) pattern. The patent also covers pharmaceutical compositions incorporating the crystalline forms, and preparation methods for producing Form I via controlled heating and crystallisation from alcohol-based solvents.

Key Features

• Six distinct polymorphs characterised. Each of the six crystal forms (I through VI) is defined by its XRPD diffraction peaks, with Form I additionally characterised at multiple levels of specificity from a handful of key peaks down to a comprehensive fingerprint pattern. This layered claim structure is designed to provide broad coverage against minor formulation variations.
• Form I as the lead candidate. Crystalline Form I is anhydrous and is disclosed with the most preparation detail. Two synthesis methods are described: reflux-and-cool crystallisation, and a controlled two-stage cooling protocol from 75-85 degrees Celsius to 55-65 degrees Celsius then to 15-25 degrees Celsius, both using alcohol-based solvents or alcohol/water mixtures.
• Pharmaceutical advantages over the amorphous form. The patent asserts that the crystalline forms offer improved chemical and physical stability, better oral bioavailability, longer storage life, and easier manufacture into solid dosage forms compared with amorphous Compound A.
• Anti-cancer utility. Pharmaceutical compositions comprising the crystalline forms are claimed for use in preparing DNA-PK inhibitor medicaments for the treatment and prevention of cancer, intended to be used in combination with existing DNA-damaging therapies.
• Scalable API loading. Claims cover the crystalline form as a proportion of the active pharmaceutical ingredient from approximately 5% to effectively 100% by weight, accommodating a wide range of formulation approaches.

Who Is Behind It?

The applicant is Kangbaida (Sichuan) Biotechnology Co., Ltd., a Chinese biopharmaceutical company based in Sichuan province focused on oncology drug development. The named inventors are Xuezhen Xu, Feiquan Lei, Lvxue He, Yonggang Wei, and Yi Sun. This Australian application is a divisional of AU 2022350562. The Australian patent attorney is Davies Collison Cave in Melbourne.

Why It Matters

DNA-PK inhibitors are an active area of oncology drug development, with several candidates in clinical trials globally as radiosensitisers and chemosensitisers. Securing crystal-form patents alongside composition-of-matter patents is standard practice in pharmaceutical IP strategy: it extends the effective protection period and creates barriers to generic entry by competitors who might otherwise reformulate the same compound. The Australian application positions Kangbaida’s polymorph portfolio in a market where combination cancer therapies incorporating DNA-repair inhibitors are of growing clinical and commercial interest. For radiotherapy centres and oncology practices in Australia, this class of compound is relevant to treatment protocols for a wide range of solid tumours.

Related Concepts

This application sits within the broader field of DNA repair inhibition as a cancer treatment strategy. By blocking the non-homologous end joining pathway that DNA-PK controls, the aim is to force persistent double-strand breaks in tumour cells that are already under replication stress, amplifying the damage caused by radiotherapy or platinum-based chemotherapy.

The layered claim structure covering six polymorphs characterised by their X-ray powder diffraction patterns is a well-established pharmaceutical IP strategy. It provides broad protection against reformulation attempts and extends effective commercial exclusivity beyond the underlying compound patent, which is a central concern for any developer seeking to commercialise a novel oncology drug.

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AU 2026201824 was published in the Australian Official Journal of Patents on 2 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.