Originally posted on IPKat.
This type of invention will often struggle to overcome subject matter eligibility objections. One popular strategy is to define such products according to the process used to make them, so-called product-by-process claims. A recent decision from the U.S. Court of Appeals for the Federal Circuit confirmed that such claims are considered novel if the product per se is novel, regardless of whether the process steps are described in the prior art (Restem v. Jadi Cell). Whilst this decision is welcome to the regenerative cell therapy industry, questions of how easy such claims are to enforce remain.
Case background: Mesenchymal stem cell (MSC) therapy
The patent in this case, US9803176, related to a mesenchymal stem cell (MSC) therapy product, corresponding to the clinical-stage cell therapy, JadiCell. JadiCell is made of MSCs derived from umbilical cords. The therapy has been evaluated for the treatment of COVID-19acute respiratory distress syndrome (ARDS). The Defendant in this case, Restem LLC, is itself developing platforms leveraging umbilical cord lining modified progenitor cells to modulate immune responses and support tissue repair. Restem’s products include Restem-L for autoimmune diseases and Restem-X for orthopaedic conditions.
Claim 1 of the patent was a product-by-process claim. Specifically, the claims specified “an isolated cell prepared by a process” comprising culturing umbilical cord tissue. The claim defined specific cell surface markers that the isolated cell expressed, as well as specific cell surface markers that the isolated cell did not express.
Restem challenged the claims in an inter partes review before the Patent Trial and Appeal Board (PTAB). The key questions before the Federal Circuit were whether the cited prior art inherently anticipated the claimed cells.
Claim construction of “isolated cell”
The term “isolated cell” must be one of the most common claim terms in US cell therapy patents. Under US patent law, the patenting of naturally occurring phenomena, laws of nature, or abstract ideas is prohibited (35 U.S.C. § 101). The term isolated is used to distinguish, e.g. a cell therapy product, from a cell occurring naturally in the human body. The term isolated is meant to establish that the cell has been extracted from its natural environment through a non-natural process and is now in a controllable, usable state that nature did not provide on its own.
The question in this case was whether the term “isolated cell” could be construed to cover a cell population, as opposed to an individual cell. Restem argued that this definition was contrary to an express definition in the patent. In particular, the specification included the express definition: “As used herein, the term “isolated cell” refers to a cell that has been isolated from the subepithelial layer of a mammalian umbilical cord.” (Evolve insights).
The Federal Circuit was not convinced by Restem’s argument. Under established US patent law doctrine, claim terms are generally given their plain and ordinary meaning except where a) the patentee acts as their own lexicographer and clearly sets forth a definition of a claim term other than its plain and ordinary meaning and/or b) where the patentee disavows the full scope of a claim term either in the specification or during prosecution (file wrapper estoppel) (Evolve insights). In this case, the Federal Circuit found the prosecution history overcame the influence of the specification definition. The Federal Circuit noted that throughout prosecution, including the notice of allowance, the Examiner had referred to a “population of cells”. As such, the other features of the claims, particularly the cell surface markers, required there to be a cell population in which the markers could be measured. It was therefore clear to the Federal Circuit that the term isolated cell covered a population of cells. This practical approach to claim construction does make the whole G1/25 drama on description amendments seem rather ridiculous.
Inherent anticipation of product-by-process claims
The patent in this case claimed an isolated cell produced by a two-step process, namely “placing a subepithelial layer of a mammalian umbilical cord tissue in direct contact with a growth substrate; and culturing the subepithelial layer such that the isolated cell from the subepithelial layer is capable of self-renewal and culture expansion”.
Restem argued that the product would have necessarily been present had the process steps described in the prior art been followed. In other words, Restem argued that inherency is automatic for product-by-process claims (page 8).
However, for the Federal Circuit, when assessing the patentability of product-by-process claims, the focus should be on the product and not on the process of making it, because “an old product is not patentable even if it is made by a new process.” (Amgen v. Roche, Fed. Cir. 2009). The Federal Circuit was convinced by evidence that the processes described in the cited prior art would have resulted in different cell-to-cell interactions than cells produced from the subepithelial layer alone, and that this would have resulted in a different cell marker expression profile to that claimed by the patent. The Federal Circuit thus concluded that the prior art did not inherently anticipate the claimed invention.
Analysis
Defining your stem-cell invention with a product-by-process claim is sub-optimal from an enforcement perspective (Evolve insights). As the Federal Circuit themselves noted in this case, in determining infringement, “the focus is on the process of making the product as much as it is on the product itself”. In other words, for infringement of a product-by-process claim, the alleged infringement must be made according to the steps of the claimed process and not just have the claimed product features.
With respect to the patentability of a product claim, in this case the Federal Circuit also expressly confirmed that the product per se was novel, and if it hadn’t been, the product-by-process would also have been anticipated. The upheld claim was therefore only found novel because the product was. Indeed, in Europe, the patentee was able to obtain a patent for the product per se (EP2798058 B1). However, in the US, the patentee entered the national phase with product-by-process claims and did not attempt to claim the product.
So why did the patentee claim a product-by-process in the US? In the US, including process steps is a popular strategy to avoid subject-matter eligibility objections. Product patents for stem cell therapy products in the US are not without precedent. Indeed, one of the original foundational patents in the field claimed merely “An isolated, homogeneous population of human mesenchymal stem cells which can differentiate into cells of more than one connective tissue type.” However, more recent stem cell patents increasingly include product-by-process steps in response to the US’s more strict approach to subject-matter eligibility post-Myriad. In the US, patentees must therefore weigh up enforceability of process steps versus adding additional non-natural product features to a cell therapy product, such as claiming pharmaceutical compositions comprising pharmaceutical excipients, or by claiming the therapeutic use of such products.
Author: Rose Hughes
Rose is a biotech and pharmaceutical patent specialist with over a decade of experience in intellectual property. Rose is a patent attorney at Evolve, where she leverages our unique fractional in-house model to provide clients with deep patent law expertise combined with the strategic commercial oversight typically associated with senior in-house counsel.
With a PhD in Immunology from UCL, Rose applies her technical background to complex innovations in biologics, cell and gene therapies, and the rapidly emerging field of AI-assisted drug development. Previously, Rose held the role of Director. Patents at AstraZeneca, where she was responsible for global IP portfolios and IP strategy at every stage of the pharmaceutical pipeline, from platform development and on-market commercialization to SPCs and patent term extensions.
A recognized thought leader in the field, Rose has been a regular contributor to IPKat since 2018, offering practical insights into European patent law developments. She is also a frequent speaker on the epi podcast, a guest lecturer for the Brunel University IP law Postgrad Certificate, and a contributing author to published books A User’s Guide to Intellectual Property in Life Sciences (2021) and Developments and Directions in Intellectual Property Law (2023).
