Co-author: Dr James Burnley, Senior Associate
By harnessing the body’s own protein disposal machinery, protein degraders can selectively remove disease-causing proteins, opening the door to treatments for previously ‘undruggable’ targets.
Recent clinical milestones, such as Phase III readouts for vepdegestrant (Arvinas/Pfizer), are bringing this approach closer to market. As these technologies progress from academic labs into late-stage pipelines, the intellectual property landscape is becoming increasingly crowded and complex. The stakes are high: robust patent protection is essential to secure investment, safeguard exclusivity, and enable long-term commercial success.
Many of the same IP considerations apply to other ‘linked’ or bifunctional therapeutic platforms, such as antibody-drug conjugates (ADCs).
Understanding the Patent Process for Protein Degraders
Obtaining patent protection for a protein degrader follows the same procedural steps as any other small molecule, from provisional or priority filing, through international (PCT) stages, to national phase entry and eventual grant. However, the modular architecture of these molecules brings specific challenges around novelty, inventive step, and freedom-to-operate.
Establishing Novelty
A typical PROTAC contains three modular parts: the E3 ligase ligand, the linker, and the target protein ligand. Each of those parts could be claimed separately, in sub-combinations, or as part of a complete construct.
For PROTACs, novelty can be a particular hurdle because their individual components may already be well-known:
- E3 ligase ligands (such as cereblon binders) have been disclosed for over twenty years.
- Target-binding ligands are often derived from previously published structures.
- Linker strategies frequently draw on established chemical motifs.
Establishing novelty often comes down to demonstrating that the specific combination and structural arrangement is clearly and unmistakably different from prior art- sometimes relying on subtle chemical modifications or entirely new assemblies.
Inventive Step: Going beyond the predictable
Inventive step it is often assessed through the lens of a ‘problem/solution’ approach, which considers whether the claimed invention provides a non-obvious solution to a known problem.
In this field, structural changes that might appear ‘routine’ can be argued to be inventive if they result in a demonstrable technical benefit, such as:
- Improved degradation efficiency or selectivity.
- Enhanced pharmacokinetic–pharmacodynamic (PK–PD) profiles.
- Better safety, stability, or delivery characteristics.
Importantly, supporting data, sometimes even if obtained after filing, can strengthen arguments for inventive step during examination or opposition. Established case law highlights that even minor modifications can be patentable if they deliver unexpected results.
Freedom to Operate and the Patchwork Problem
FTO is particularly complex for protein degraders because each component may be covered by separate patent rights owned by different parties. For example:
- The E3 ligase ligand may be subject to composition or use patents.
- The target ligand may be protected as part of earlier inhibitor programs.
- Linker technologies may themselves be proprietary.
This ‘patent thicket’ means companies must carefully map and navigate overlapping rights before advancing a degrader program to market.
In Australia, experimental use exemptions and specific ‘regulatory approval’ defences offer some protection for pre-commercial research and development, even if the ultimate goal is commercialisation. In addition, importation of a PROTAC manufactured overseas may still constitute an infringement of process claims even if the compound itself is not covered by an enforceable patent in Australia. Therefore, the defence provisions can be helpful, but they are not a substitute for a thorough FTO strategy.
Strategic Claim Drafting in a Crowded Field
Given the rapid expansion of prior art in this space, claim strategy needs to be both creative and commercially focused. Potential approaches include:
- New Compounds: Covering novel ligands, linkers, or their combinations.
- Selections: Narrowing broad prior disclosures to specific, advantageous compounds.
- Solid-State Forms: Including crystalline and polymorphic variants.
- Compositions and Combinations: Such as synergistic therapies with other drugs.
- Manufacturing Processes: Protecting proprietary synthetic or purification methods.
- Medical Uses: First and subsequent therapeutic indications.
- Delivery Systems: For example, nanoparticle carriers or depot formulations.
Early and targeted prior art searching is essential to identify opportunities and avoid wasted drafting effort in over-crowded claim space.
Conclusion
The patenting of protein degraders is a high-stakes, high-complexity endeavour. With key E3 ligase and linker technologies already well-explored, the race is on to define and secure novel structural space and therapeutic uses. Success will depend on early strategic planning, deep prior art awareness, and claim drafting that anticipates not just today’s competitors, but tomorrow’s.
In this rapidly evolving area, the window for obtaining commercially meaningful patents is narrowing. Those who navigate the IP landscape with foresight and precision will be best positioned to reap the rewards as protein degrader therapeutics move firmly into the clinical mainstream.
For further insights on patent strategies for PROTACs and other protein degraders, please contact Dr James Burnley and Dr Annabella Newton.
