The Hidden Patent Threat Undermining IntoCell’s Nexatecan PlatformA forensic patent analysis following ABL Bio’s sudden technology withdrawal
1. Context: Technology Retraction with Strategic Shockwaves
On July 9th, 2025, ABL Bio publicly disclosed its decision to return the ADC payload platform ‘Nexatecan’, originally introduced from IntoCell in October 2024. The abrupt termination was triggered by the late-stage emergence of a structurally similar patent publicly disclosed in China—identified by ABL Bio as a “submarine patent” [1].
This event follows a growing trend in the biotech sector where undisclosed filings in jurisdictions like China resurface post-contract, exposing licensees to unforeseen IP liabilities.
2. IntoCell’s Platform: Nexatecan and its Mechanistic Promise
IntoCell’s Nexatecan platform is anchored on exatecan derivatives functionalized to improve systemic stability and intratumoral release. The system employs a phenolic linker designed for enzymatic activation (e.g., Val-Cit-PABC) and is compatible with IntoCell’s proprietary Opas linker system. The technology is disclosed under US20220047717A1 [2].
The application outlines:
Modified exatecan cores functionalized at C10/C20
Phenol-based self-immolative linkers
Conjugation strategies for monoclonal antibody payload delivery
3. The Submarine Patent: WO2023088235A1
In May 2023, WIPO published WO2023088235A1, derived from Chinese PCT filing PCT/CN2022/131904, filed November 16, 2021 [3]. The assignee is not publicly linked to IntoCell, and the patent presents:
Exatecan derivatives conjugated via carbamate or carbonate linkers
Triggered release by enzymatic or pH-sensitive cleavage
Explicit ADC application language
A key risk is the scope of claims, which are written broadly enough to overlap with multiple exatecan payload configurations—including ones previously believed to be novel under IntoCell’s Nexatecan program.
4. Structural Similarity Analysis
FeatureIntoCell (US20220047717A1)WO2023088235A1Core ScaffoldExatecan (topoisomerase I inhibitor)ExatecanLinker ChemistryPhenol–PABCCarbamate/Carbonate–PABCRelease MechanismEnzymatic (Val-Cit)Enzymatic or pH-cleavableADC ConjugationMonoclonal antibodiesMonoclonal antibodiesJurisdictionUS, KR, PCTCN, WO, PCT
While the specific chemical bonds differ, both patents converge on:
The use of exatecan
Cleavable linker design
Application in ADCs for cancer therapy
Thus, functional overlap is significant enough to challenge Freedom to Operate (FTO), particularly in Chinese and PCT-bound jurisdictions.
5. Strategic Implications and FTO Exposure
ABL Bio's decision reflects a strategic emphasis on preemptive IP risk management. Even in the absence of legal proceedings, the perception of encroachment on a submarine patent can:
Compromise enforceability of internal patents
Disrupt partnerships with firms like Samsung Bioepis (which uses Nexatecan)
Jeopardize preclinical development under uncertainty
Furthermore, FTO threats in China—now the fastest-growing region for ADC clinical trials—are no longer peripheral but central to biopharma strategic calculus.
6. Closing Remarks: A Wake-Up Call for ADC Developers
This episode underscores a pivotal reality for platform biotech firms: in high-convergence therapeutic classes like ADCs, structural novelty is no longer enough. Clear territorial FTO and real-time international patent monitoring are now baseline requirements for de-risked licensing and cross-border development.
📚 References
[ABL Bio press release regarding Nexatecan return – July 9, 2025]
(Disclosure via KRX/DART system – translated source)[US20220047717A1 – “Phenol-linked exatecan derivatives for ADC applications”, IntoCell Co., Ltd.]
https://patents.google.com/patent/US20220047717A1/en[WO2023088235A1 – “Exatecan derivatives, linker-payloads, and conjugates thereof” (PCT/CN2022/131904)]
https://patents.google.com/patent/WO2023088235A1/en[CNIPA Chinese Patent Database – CN115990269B]
https://patents.cnipa.gov.cn[WIPO – Timeline and rules for international publication of PCT applications]
https://www.wipo.int/pct/en/texts/time_limits.html
