Across Canada

STEM CELL PATENTS

Securing Intellectual Property for Regenerative Medicine

Stem cells are at the centre of research into regenerative medicine. They are also a valuable tool for drug discovery and development. The transition to successful clinical treatments using stem cells has been slow and difficult.

However, there is still commercial optimism as the use of stem cells becomes more established and therapeutic applications of stem cells start to enter the market. For example, Hemacord™, a cord blood hematopoietic progenitor cell therapy, was recently the first stem cell product approved by the FDA. Also, Prochymal™, a formulation of adult cultured mesenchymal stem cells, recently received regulatory approval in Canada for the treatment of acute graft versus host disease in children.

Since the discovery of stem cells in Toronto by Drs. Ernest McCulloch and James Till in the 1960s, Canadian scientists have been at the forefront of stem cells and regenerative medicine research. More recently, specialized institutions like the Centre for Commercialization of Regenerative Medicine and the Ontario Stem Cell Initiative have been formed to encourage collaboration and commercial ventures for moving innovations forward towards patient care. Obtaining effective patent protection for inventions related to stem cells is vital as the practical commercial and clinical applications of stem cells start to come of age.

Criteria for Patentability

Any invention must meet certain key criteria for patentability in the U.S., Europe and Canada. It must be “patentable subject matter,” meaning that it must be a type of invention that is eligible for patenting. For example, abstract ideas or scientific principles are not patentable. Methods of surgery are patentable in the U.S., but not in Europe and Canada. The boundaries of what is considered patentable subject matter differ in each patent office.

An eligible invention must also be new, useful and inventive compared to previously known information (called “prior art’). For stem cells, there can be difficult issues in drafting patent claims, since they are a complex living system, unlike pharmaceuticals, proteins or nucleic acid molecules that have a readily describable chemical structure.

Proving to patent offices that an isolated stem cell is new and inventive compared to previously known cells, and therefore patentable, can be a challenge. The new stem cell may produce different cell lineages with variable expression patterns of biological markers depending on the culture conditions. Prior art stem cells are also dynamic and even the same cell type will have some inherent differences if taken from a genetically different tissue source. It can be difficult to compare and reconcile each researcher’s limited data set and make direct comparisons to show that a new cell is a patentably unique stem cell. Inventors should be prepared to provide detailed evidence to patent offices.

Another important criteria for patentability is that the patent application must disclose the invention in sufficient detail to show a skilled person how to make and use the invention (called “enablement” or “support”). In brief, it is usually readily satisfied for methods of isolating stem cells or using cells for drug screening. Enablement becomes a challenge for patent claims on medical applications of stem cells because stem cells are highly unpredictable and difficult to use successfully in treatment. Patents are also normally filed well in advance of any experimental use in humans. However, the necessary level of data to support a patent claim is generally significantly less than what may be required for regulatory approval for clinical treatment. Demonstrating a particular effect in vitro or in a model organism that

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In Canada, isolated biological material such as cells, nucleic acid molecules or proteins is patentable subject matter. Claims to “higher” life forms including plants or transgenic mice are not considered patentable subject matter.

provides a correlation to effects in humans can be sufficient to enable claims to therapeutic uses in humans.

Embryonic Stem Cells

Embryonic Stem (ES) cells are derived from the inner cell mass of a developing embryo and are characterized by their ability to differentiate into every cell type (i.e. pluripotency). While a number of human ES cell lines are now available, their creation traditionally required the destruction of a human embryo which has generated substantial controversy.

United States

In the U.S., ES cells are considered patentable subject matter, as are methods for isolating or producing ES cells, even if the invention requires that a human embryo be destroyed.

A well-known, early stem cell patent portfolio belongs to the Wisconsin Alumni Research Foundation (WARF) that was granted three related U.S. patents based on pioneering work by Dr. James Thomson. For example, WARF patent no. 5,843,780 claims a purified preparation of pluripotent primate embryonic stem cells by reference to functional properties of the cells, rather than chemical markers, in order to establish novelty and inventiveness. Subsequently, WARF patented methods of isolating a pluripotent human embryonic stem cell line (see U.S. patent no. 6,200,806) and a replicating in vitro culture of human embryonic stem cells (US patent no. 7,029,913). Protecting the isolated cells, methods of production and methods of use is a common strategy for building an effective patent portfolio.

The claims in the WARF patents have come under third-party scrutiny, resulting in requests for re-examination of the patents at the U.S. Patent Office. WARF’s first two patents 5,843,780 (1998) and 6,200,806 (2001) were upheld on re-examination with amendments, however the Board of Patent Appeals and Interferences eventually invalidated WARF’s patent no. 7,029,913 on stem cell cultures as being obvious in light of prior art.

More recently, U.S. patent no. 7,968,337 “Neural precursor cells, method for the production and use thereof in neural defect therapy” was issued to Brüstle on June 28, 2011 with claims directed to methods for the generation of an isolated, non-tumourigenic cell composition that involve culturing mouse or human embryonic stem cells to produce neural precursor cells. This process is considered patentable even though it could result in the destruction of a human embryo. A different result occurred in Europe where the case was eventually heard by the Court of Justice for the European Union (CJEU) and has received considerable attention.

United States – Limits on Patentability and the Mayo Decision

No U.S. patent may give rights in a human being or organ, which are considered nonpatentable subject matter. Certain living matter, such as transgenic animals, that is the result of human intervention can be patentable subject matter. Isolated naturally occurring biological material, such as isolated genes, proteins or stem cells, is also considered patentable.

The recent US Supreme Court decision in Mayo v. Prometheus has rekindled the debate regarding whether certain types of inventions are patent eligible. Exceptions to patent eligibility include claims that are considered to be effectively directed to a “law of nature,” a “natural phenomenon,” or an “abstract idea.” The decision in Mayo concerned the patentability of method claims directed towards assessing a suitable drug dosage for autoimmune disease therapy by measuring levels of the drug’s metabolites in patient blood. The U.S. Supreme Court considered this to be unpatentable, and is going to be considering patentability issues again shortly in a case involving Myriad Genetics. These cases could have future implications for stem cell patentability.

Canada

In Canada, isolated biological material such as cells, nucleic acid molecules or proteins is patentable subject matter. Claims to “higher” life forms including plants or transgenic mice are not considered patentable subject matter. This is more restrictive than the U.S. and Europe. Embryonic, multipotent and pluripotent stem cells which do not have the potential to develop into an entire animal are patentable subject matter. Processes or methods that involve embryonic stem cells or the harm or death of an embryo are not excluded from patentability.

Canadian patent no. 2,190,528 is in the same family as WARF’s U.S. patent no. 5,843,780 and was granted in Canada on April 4, 2010. The Canadian patent issued with claims to primate ES cells very similar to those found in the corresponding U.S. patent, reflecting a similarity of practices in the U.S. and Canadian Patent Offices with respect to patentable subject matter for ES cells.

Brüstle’s Canadian patent application no. 2,315,538 directed to methods for turning ES cells into neurons was issued on July 24, 2012.

Adult Stem Cells and Induced Pluripotent Stem Cells

Adult stem cells are found in most tissues and are characterized by their ability for self-renewal and for differentiating into specialized cell types. Patents directed towards adult stem cells have been less controversial than ES cells and accordingly have been greeted with less resistance. Recent advances in the molecular biology surrounding cellular programming have led to the development of induced pluripotent stem cells (iPSCs). iPSCs are technically not adult stem cells, but rather cells that

have been reprogrammed, typically using transcription factors, to generate pluripotent cells. Cancer stem cells are cancer cells with the ability to give rise to all cell types found in a particular cancer sample through the processes of self-renewal and differentiation. Cancer stem cells have emerged as a promising research tool and target for the development of cancer therapeutics and screening assays.

Adult stem cells, cancer stem cells and iPSCs are patentable subject matter in the U.S., Europe and Canada. Any claims to compositions or methods that involve adult stem cells, cancer stem cells or iPSCs must still meet the usual criteria for patentability such as novelty and inventiveness. Notably, distinguishing iPSCs from previously known adult stem cells that they may claim to emulate is a challenge that may block some claims from being patented. Such patent applications will have to focus on the methods of making the iPSCs, rather than the cells themselves.

Consistent strategies can be applied in the U.S., Europe and Canada to patent inventions involving adult stem cells and iPSCs. Patents can cover the cells per se as well as OBIO Ad (Final):Layout 1 12-05-14 5:13 PM Page 1

their uses and methods of production. In the next few years, the law should continue to evolve and further clarify the boundaries of patentability. The availability of strong patent protection will remain a key driver of investment into stem cell technology and the development of regenerative medicine.

References

1. Methods of medical treatment, generally, are excluded from patentability in

Europe under Article 53(c) of the EPC and in Canada following the Supreme

Court decision in Tennessee Eastman v.

Commissioner of Patents [(1972), 8 C.P.R. (2nd), 202 (S.C.C.)). “Medical use” claims are permitted and can often indirectly provide suitable protection. 2. U.S. BPAI decision dated April 28, 2010.

Control No. 95/000,154 3 Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. ___ (2012). 4. Association for Molecular Pathology et al v. Myriad Genetics Inc et al, 94 USPQ2d 1683 (S.D.N.Y. March 29, 2010); reversed in part by the Court of Appeals for the

Federal Circuit 2010-1406 (July 29, 2011). Petition granted by the U.S. Supreme

Court, No. 12-398 (Nov. 30, 2012). 5. Harvard College v. Canada (Commissioner of Patents) 2002 SCC 76

Laurence MacPhie and Noel Courage are patent lawyers at Bereskin & Parr LLP, a leading Canadian intellectual property firm. They can be reached at lmacphie@bereskinparr.com and ncourage@bereskinparr.com, respectively. This paper is based on a journal article by the authors originally published as “Differentiating stem cell patents” Pharm. Patent Analyst, (2012) 1(4) 407-413.

To see this story online visit http://biotechnologyfocus. ca/stem-cell-patents-securingintellectual-property-for-

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