Patenting Diagnostic Methods: potential challenges for biotech innovators

Written by: YANG Zhuoyan of the IPSA Core Team
Edited by: Denise THIA of the IPSA Core Team

In the past few months, tremendous biotechnology breakthroughs in the treatment of COVID-19 have arrived in the forms of the Pfizer-BioNTech and Moderna vaccines, among several others. Not to be belittled, researchers from Singapore have also developed their own medical innovations. One, in particular, is a portable diagnostic system made for carrying out swab tests created by NUS researchers led by Prof Lim Chwee Teck (the “Epidax”). The system is reportedly in the midst of its patent application, providing an avenue for a timely discussion on the more prominent legal obstacles to patenting diagnostic methods.

Image Source: NUS News

Pursuant to Singapore’s Patents Act (Cap 221) (“the Act”), Section 13(1) sets out three main requirements for an invention to be considered patentable: the invention must (a) be new; (b) involve an inventive step; and (c) be capable of industrial application.

The traditional swab test for COVID-19 is a polymerase chain reaction (PCR) test, a type of molecular test where the collected DNA sample undergoes a series of reactions at the laboratory. The sample is processed to isolate and collect the patient’s RNA. The RNA is then mixed with other ingredients, e.g enzymes, DNA building blocks, cofactors, probes and primers that recognize and bind to SARS-CoV-2. The viral RNA is then converted to a DNA copy, which is then converted into millions of copies using PCR which can be easily detected. If SARS-CoV-2 complementary DNA is present in the sample, the primers can copy the targeted regions and signal its existence. (Source: Discovery’s Edge).

Meanwhile, the Epidax bypasses the intermediate step of RNA extraction through use of a microfluidic chip. Using a reagent which enables both RNA extraction and amplification on the chip, the PCR test can be performed right after a nasal swab sample is collected. The main improvement made to the current PCR test is that sample handling is minimized and waiting time is drastically shortened  (Source: NUS News). 

On a surface level, three discrete points of law may be raised:

(1) “Invention”

Since patents protect inventions, a mere discovery naturally falls outside of s 13(1) of the Act. The Examination Guidelines for Patent Applications at IPOS (last revised Apr 2019) (“IPOS Guidelines”) state that discoveries of a natural process that occurs in nature are not inventions (IPOS Guidelines at para 8.12-8.16; see also Merck & Co Inc v Pharmaforte Singapore Pte Ltd [2000] SGCA 39).

Recent Federal decisions in the US have applied the two-step Alice/Mayo test to differentiate mere applications of natural law from inventions. In Step One, the court considers whether the claims are directed to ineligible subject matter such as a law of nature. In Step Two, the court examines the elements of the claims to determine whether they contain an inventive concept sufficient to transform the claimed naturally occurring phenomena into a patent-eligible application (Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (2019); Cleveland Clinic Found. v. True Health Diagnostics LLC, 859 F.3d 1352 (2017)). 

While the above two-step test had not been adopted locally, its direction is not dissimilar from the IPOS Guidelines. It stands to reason that if followed in Singapore, the Epidax may face a hard time given that many Federal decisions have declined to grant patents for PCR diagnostic methods which merely instruct on what to make of naturally occurring reactions between DNA sequences and a particular substance (see Roche Molecular Systems, Inc. v. CEPHEID, 905 F.3d 1363 (2018); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (2015)). The Epidax’s reagent, if included as a product claim, may not be an “invention” if it comprises, without more, a naturally occurring enzyme; a process claim which uses observations of natural reactions as diagnostic indicators may also fail (Roche v CEPHEID).

(2) Diagnostic method exclusion

As regards to sub-section 13(1)(c), there is an enumerated exception found in s 16(2) of the Act, which states that “An invention of a method of … diagnosis practised on the human or animal body shall not be taken to be capable of industrial application.”

The rationale for this exception was laid down by the Singapore Court of Appeal in the recent case of Warner-Lambert Company LLC v Novartis (Singapore) Pte Ltd [2017] 2 SLR 707 (at [31], citations omitted):

“… the [s 16(2)] limitation rests on a legal fiction that methods of treatment and diagnosis are not capable of industrial application. … the fear of adverse impact on the health system lies at the heart of the exclusion of methods of medical treatment. The real reason is that it is not in the interest of the public to have methods of treatment and diagnosis controlled by a few …”

However, a PCR test, either conventional ones or in Epidax, may not be excluded because s 16(2) contemplates diagnosis “practised on the human or animal body”. For instance, in vitro diagnostic methods performed on blood or tissue samples obtained from a patient’s body are prima facie capable of industrial application. In T 0666/05 (Mutation/UNIVERSITY OF UTAH) (European Patent Office), claims defining methods for diagnosing a predisposition for breast cancer by detecting a mutation in the BRCA1 gene in a tissue sample from the subject was allowable since the technical steps of the claimed methods are not performed directly on the subject (IPOS Guidelines at para 8.15; 8.105).

(3) Inventive Step

s 13(1)(b) of the Act stipulates that an invention must  involve an inventive step, with s 15 setting out the test for the same. This requirement essentially involves the consideration of whether the invention, when compared to the state of the art at the priority date of the patent application, would have been obvious to the hypothetical skilled addressee.

It is once again helpful to look at US decisions given the dearth of local case law in the diagnosis context. In Arioso Diagnostics, Inc. v. Sequenom, Inc. 788 F.3d 1371 (2015), a process claim for detecting paternally inherited cffDNA by instructing doctors to apply PCR to amplify and detect cffDNA was held to be not sufficiently new and useful because PCR itself was a “well-understood, routine, and conventional activity”. Likewise, there was a lack of inventive step in Genetic Technologies Ltd. v. Merial L.L.C., 818 F.3d 1369 (2016) with respect to a claim for detecting a coding region of a person’s genome because the physical steps claimed were no different from established PCR techniques.  

However, perhaps the Epidax may be distinguished – while the diagnosis still revolves around testing for a PCR, its incorporation of microfluidic chips appears to set it apart from its predecessors. As our courts have emphasized repeatedly, the four step approach from Windsurfing International v Tabur Marine [1985] RPC 59 adopts the perspective of a skilled but unimaginative addressee when considering obviousness. A close reading of the prior art is still key in this step (see Element Six Technologies Ltd v ILA Technologies Pte Ltd [2020] SGHC 26).

Conclusion

The policy consideration thrust to the forefront is certainly the need to balance incentivizing innovation against the public interest in securing access to affordable healthcare. Thankfully, in Singapore, even if the patent was granted, ss 56-62 of the Act empowers the Government to initiate compulsory licensing at least for the duration of the pandemic so the potential harm to public interest is far reduced.

The above discussion is hypothetical; without a close reading of the claims made by the NUS team, it is difficult to say for sure what the outcome may be. Where the Epidax is distinguishable, the patent office may rightly conclude that neither of the above-mentioned problems surface. It will be interesting to see if novel biotechnology patent issues would be brought up in the imminent patent prosecution.

IPSA is a student-led interest group and the above article is a reflection of the author’s opinions, and not professional legal advice for any matter. All errors are the author’s own.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s