Arginine-lowering enzymes against cancer: a technocommercial analysis through patent landscape

ABSTRACT

Introduction: Rise in incidence of various cancers and growing adoption of biological therapy to avoid side effects of conventional cancer therapies is driving the growth of the cancer biotherapy market globally. One such therapy available for the treatment of certain tumors employs arginine-lowering enzymes (ALEs). Several patents have been filed in this technology domain, and many Phase I/II clinical trials of the ALEs especially arginine deiminase (ADI) are underway.

Areas covered: Patents and clinical trials in the domain of ALEs for the treatment of cancer were studied with an objective to understand technology trends, targeted areas, key players, and inventors involved.

Expert opinion: Amongst the various ALEs, ADI is the most promising enzyme for cancer therapy. ADI-based cancer therapy holds potential in treating liver, skin, lung, gastrointestinal, and blood cancer. ADI-PEG20 has proved to be very effective when used as a component of combination therapy in a first-line treatment. Polaris Group holds the worldwide rights for ADI-PEG20 and is the leading player in developing ADI as a therapeutic agent. Many clinical studies, especially in a combinatorial approach, are underway whose success will pave the way for ADI-PEG to the multimillion cancer market.

KEYWORDS:

• Arginine-lowering enzymes
• PEGylation
• ADI-PEG20
• cancer
• Polaris Group

Article highlights

• Cancer biotherapy using ALEs is currently under clinical investigation and is emerging as a promising therapy for the treatment of various types of cancers especially liver, skin, and lung cancer.

• ADI has been identified as the most promising ALE for its use in cancer therapy.

• The native enzyme having antitumor activity has serious limitations such as short half-life, strong antigenicity, high K_m, poor thermostability, and nonphysiological optimum pH.

• Cayman Island-based Polaris Group is the leading player in cancer biotherapy using ADI and it holds the worldwide rights for ADI-PEG20 molecule.

• ADI-PEG20 shows promising results when used as a component of combination therapy in a first-line treatment.

A higher and sustained dosage of ADI-PEG20 is required to promote effective arginine depletion through repeated doses via the intramuscular or intravenous route.

This box summarizes key points contained in the article.

Acknowledgments

The authors sincerely thank the Department of Science and Technology- Science and Engineering Research Board (DST-SERB) for providing financial assistance (Grant No. SB/YS/LS-145/2014). The authors also thank DST-SERB for providing research fellowship to Ms. Rakhi Dhankhar. Authors also acknowledge the infrastructural support from Department of Science and Technology, Govt. of India through FIST grant (Grant No. 1196 SR/FST/LS-I/2017/4).

Declaration of interest

RD received a research fellowship from Department of Science and Technology, Govt. of India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.