A core objective of the medical industry is to identify ‘biomarkers’: indicators of whether a patient is susceptible to, or has, a particular disease or will respond to a particular drug or treatment. Improvements in diagnostic testing are essential to bring about the long-heralded promise of personalised medicine. But as patenting related inventions becomes increasingly important, uncertainty remains around the world as to exactly what is patentable.
Patenting opportunities for diagnostics
Diagnostics may present the following opportunities for patenting:
- assay to test the level of the biomarker;
- method of diagnosis of a disease based on the level of the biomarker;
- method to test an individual for predisposition to a disease;
- method to evaluate a patient’s suitability for treatment;
- method to adjust the level of the biomarker by administering medication;
- method to treat a disease by adjusting the level of the biomarker;
- kit for conducting the assay; and
- apparatus for conducting the assay.
These opportunities may be reflected by patent claims of products (biomarker, kit and apparatus) and methods (method of diagnosis or treatment).
With respect to product claims, while in the United States questions remain about patent eligibility of patents directed towards purified genomic DNA molecules and possible non-genomic DNA biological products, these products are patent eligible in China and Europe, as well as in many other countries. With respect to method claims, the practice varies. This article focuses on diagnostic methods and explains the practice in China and how it compares to that elsewhere.
Uncertainty in United States; establishment in Europe
The US Supreme Court decision in Mayo Collaborative Services v Prometheus Laboratories, Inc 132 S Ct 1289 (2012) shifted the interpretation of patent eligibility under 35 USC §101 and significantly chilled the fledgling diagnostics industry. In Prometheus, the court invalidated a claim that was directed to a method of optimising thiopurine dosage by determining the level of the thiopurine metabolite in the blood and adjusting the dosage accordingly. In reaching this conclusion, the court set up a two-step framework inquiry:
- to determine whether claims are directed to a patent-ineligible concept (ie, laws of nature, natural phenomena or abstract ideas); and
- if so, to search for the “inventive concept” by determining whether additional elements “transform the nature of the claim” into a patent-eligible application.
For diagnostic method claims or claims involving diagnostic steps, patent eligibility likely comes from the conclusion of the second step analysis. Moreover, current US Patent and Trademark Office guidance suggests that although claims involving diagnostic methods may still be allowable, the scope of such claims is likely to be greatly reduced compared to that pre-Prometheus.
In Europe, the European Patent Convention (EPC) excludes discoveries, scientific theories and mathematical methods from patent protection. However, unlike the US judicial exceptions, the EPC exclusions are applied more narrowly. The Enlarged Board provided guidance in G01/04, holding that a diagnostic method is excluded from patentability under the following relatively narrow circumstances:
in order that the subject-matter of a claim relating to a diagnostic method practised on the human or animal body falls under the prohibition [ ], the claim is to include the features relating to:
(i) the diagnosis for curative purposes [ ] representing the deductive medical or veterinary decision phase as a purely intellectual exercise,
(ii) the preceding steps which are constitutive for making that diagnosis, and
(iii) the specific interactions with the human or animal body which occur when carrying those out among these preceding steps which are of a technical nature.
Thus, a method is excluded only if all technical steps are practised on the human or animal body. In vitro diagnostic tests performed on blood removed from the body do not constitute a diagnostic method step practised on the human or animal body and are therefore patent eligible.
China’s statutory exclusion
Article 25.1(3) of China’s Patent Law specifically excludes diagnostic methods from patentability. However, instruments or apparatus for implementing diagnostic methods or treatment, or substances or materials used in such methods, do constitute patentable subject matter (Section 4.3, Chapter 1, Part II of the Guidelines for Patent Examination).
The Guidelines for Patent Examination provide that a diagnostic method which meets the following criteria is not patentable:
- It is practised on a living human or animal body; and
- Its immediate purpose is to obtain the diagnostic result of a disease or health condition.
The guidelines further elaborate as follows: “If an invention, as viewed from its description, is practiced on samples in vitro, but its immediate purpose is to diagnose a disease or health condition for the same subject, it shall not be granted a patent right. If a claimed method in a patent application includes diagnostic steps, or includes testing steps if no diagnostic steps, and the diagnostic result of a disease or health condition can be reached immediately based on the diagnostic or test information thus obtained according to the medical knowledge in the prior art and the disclosure of the application, then the method can be regarded as unpatentable.”
Accordingly, a method is not patentable in China if it involves the diagnosis of a disease or health condition.
Examination of diagnostic method patent applications
(Article 22: novelty and inventive step requirement; Article 33: no new matter requirement; Article 26.3: sufficiency requirement; Article 26.4: support requirement; Article 31: unity requirement; Article 25: eligibility requirement)
A search of the Patent Re-examination Board (PRB) database reveals 174 re-examination decisions issued in 2015 for invention patent applications with International Patent Classification (IPC) C12Q which had claims directed to diagnostic methods. Of these decisions, only 19 (11%) addressed the issue of eligibility under Article 25.1(3) of the Patent Law. However, nearly half (49%) of the decisions dealt with the issue of novelty and inventiveness (see Figure 1).
During re-examination, many applicants have chosen to amend claims to overcome a rejection for lack of eligibility under Article 25.1(3). Such amendments may include:
- deleting claims directed to diagnostic methods;
- rewriting method claims to use claims such as “use of a compound in the preparation of a kit for diagnosing diseases”;
- rewriting method claims to kit claims such as “a kit for diagnosing diseases”; and
- narrowing the claim scope to exclude the diagnostic method, such as “a diagnostics method not for diagnosing diseases, comprising”.
While these formalistic amendments may render previously ineligible subject matter eligible, in many cases they may not pass the substantive novelty and inventiveness assessment, because a correlation between a biomarker and a particular disease stage or diagnostic method steps may not be construed as a technical limitation to these products or use claims. Consequently, many applications – as indicated by 49% of the PRB decisions above – would founder on a determination of novelty and inventiveness, rather than of patentable subject matter.
Chinese practice versus US and European practice: example
The PRB affirmed the rejection on the ground of ineligibility of Chinese Application 200780034610.0 for methods for quantitation of collagen in tissue. The application, assigned to KCI Licensing, Inc on its face, stated that measurements of collagen in the granulating wound bed may be predictive of successful healing and provide an accurate, specific and reliable method over existing methods to quantify collagen from tissue. The claims examined before the PRB were directed to methods for quantifying collagen. The main issue was whether the claimed methods fell within the statutory exclusion for diagnosis of diseases.
Representative claim 1 read as follows:
1. A method of quantitation of total collagen in tissue comprising:
(a) obtaining a tissue sample from a wound site on a subject’s tissue wherein the tissue is a skin, and processing the sample by the steps of:
(i) removing fat from the sample;
(ii) dehydrating the sample;
(iii) hydrolyzing the sample to amino acids; and
(iv) derivatizating the sample;
(b) separating glycine, proline, and hydroxyproline in the processed sample by high-pressure liquid chromatography to obtain analyte peaks areas;
(c) determining concentrations of the glycine, proline, and hydroxyproline in the sample;
(d) correlating the concentrations of the glycine, proline, and hydroxyproline in the sample with an amount of total collagen in the sample.
The applicant argued that the claims were patent eligible because:
- they were directed to a method of quantitation of total collagen, but not to a method of determining a wound healing stage, let alone the diagnosis of a disease;
- the method of the invention was performed in vitro and the purpose was not to diagnose a disease or health condition; and
- the invention was an improvement to existing methods for collagen measurement.
However, the PRB disagreed, reasoning as follows:
- The ultimate goal of the claimed methods was to assess healing progress by comparing the amount of collagen at the wound site to the amount of collagen in non-wounded tissue;
- The specification provided that the amount of collagen reflected the healing progress and was thus directed to a health condition (see Section 188.8.131.52, Chapter 1, Part II of the guidelines); and
- Although the method was an improvement to existing methods, it was nevertheless a method practised on a living human body with the purpose of obtaining the diagnostic result of a health condition.
Accordingly, the PRB reaffirmed the rejection for ineligibility.
The Chinese application that was deemed patent ineligible has granted US and European counterparts (US Patents 7,491,541 and 7,713,743, and European Patent 2061898B1, respectively). The granted claims are similar to those examined in the Chinese re-examination procedure. For example, US Patents 7,491,541 and EP 2061898B1 both have a similar claim 1 which meets the threshold for patent eligibility in the United States and Europe:
1. A method of assessing wound healing progress comprising: (a) processing a tissue sample obtained from a wound site of a subject; wherein processing includes the following steps: (i) fat removal from the tissue sample; (ii) dehydration of the tissue sample; (iii) hydrolyzing the sample to amino acids; and (iv) derivatization of the sample; (b) separating glycine, proline, and hydroxyproline in the processed tissue sample by high-pressure liquid chromatography to obtain analyte peaks areas; (c) determining concentrations of the glycine, proline, and hydroxyproline in the tissue;(d) correlating the concentrations of the glycine, proline, and hydroxyproline in the tissue with an amount of total collagen in the tissue; and (e) comparing the amount of total collagen in the tissue at the wound site with the amount of collagen in non-wounded tissue to assess wound healing progress.
Chinese practice has been settled for a number of years and clearly excludes methods for diagnosing diseases or health conditions – regardless of whether they are performed in vivo on a subject or on samples in vitro – where the immediate purpose is to diagnose a disease or health condition of the subject.
The current restrictions and uncertainty in the United States should not shape people’s perception of diagnostic patents elsewhere. The current situation both in China and in Europe is rather more settled, and the global market remains important for diagnostic companies.
Diagnostic companies are recommended to focus on the limitations they should include in their patent claims to make claims patent eligible in the United States, while providing a thorough patent specification for broad diagnostic claims in their patent applications for the purpose of securing protection worldwide.
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Qinghong Xu is a partner at Lung Tin focusing on all IP matters, from patent application preparation and prosecution to invalidation and litigation, technology transfers, licences, strategic alliances, R&D and commercialisation collaborations. She also advises clients on regulatory matters, especially before the Chinese State Food and Drug Administration.
Prior to joining Lung Tin in 2009, Dr Xu was a patent attorney with a New York general practice firm and a patent agent with an IP boutique since 2000.
Dr Xu obtained her PhD in chemistry from University of Minnesota and JD from New York Law School.
Xiaoying Wu is a partner and patent attorney at Lung Tin focusing on patent matters – primarily on patent application preparation and prosecution in the fields of pharmacy, chemistry, biotechnology, food, chemical engineering and materials science. She also provides patent opinions and strategic patent counselling, as well as assistance with patent re-examination, invalidation and litigation. Ms Wu is honoured as an expert in the National IP Experts Database and has been designated as a national high-level talent in patent drafting by the State IP Office.
Prior to joining Lung Tin in 2002, Ms Wu was engaged in R&D in medicinal chemistry and pharmacology.
Ms Wu obtained her BS in pharmacy science from Inner Mongolia Medical University and her MS in medicinal chemistry from Beijing Union Medical College.