IPSCs: An Analysis of Changing Landscape of Stem-Cell Research and the Need for the Legal Field to Catch Up

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Written By: John Tully

Articles Editor, American Journal of Trial Advocacy

Stem-cell research has long been a hotly debated and highly regulated area of the medical and science fields. Legislators have attempted to embrace the potential for great medical and scientific advance while balancing the moral and ethical cost of this research.^[i] As we look to the future of stem-cell research and its patentability, it is important to first take a look back at its history.

There are two primary characteristics that highlight the usefulness of stem-cells: “(1) they are able to differentiate into different types of cells, and (2) they are able to self-renew, or multiply into more stem cells.^[ii] Currently, stem-cell research is conducted on three types of cells: adult stem cells (ASCs), human embryonic stem cells, and induced pluripotent stem cells.^[iii] The first research was performed on ASCs beginning in the 1950’s.^[iv] ASCs are considered to be multipotent, meaning that they can be differentiated into a limited number of types of cells, which greatly limits their usefulness as it relates to research and therapeutic purposes.^[v] For example, neural stem cells harvested in the brain can “replace neurons in the nervous system, but neural stem cells are unable to become heart, liver, or lung cells.”^[vi] There is little controversy regarding ASC research because they are harvested from consenting adult humans and do not involve the destruction of a human embryo.^[vii]

Human embryonic stem cells (hESCs) can be found in “the embryonic layer of week-old human embryos” and, unlike ASCs, hESCs are pluripotent—meaning that “they can divide into nearly any type of cell in the human body, but do not have the capacity to develop into an independent, fully functional organism.”^[viii] The potential benefits of harvesting these pluripotent hESCs are weighed down by the fact that “in order to extract the stem cell, the human embryo must be destroyed.”^[ix] In most cases, “hESCs are harvested . . . [from] surplus preimplantation embryos from in vitro fertilization procedures—which have been donated for research purposes with the informed consent of both parents.”^[x] While there is potential for medical advance using these hESCs, the destruction of human embryos, even those created via in vitro fertilization, has been condemned by many. This condemnation led to the Dickey-Wicker Amendment to the Balanced Budget Downpayment Act of 1996, which stated, in pertinent part, that “none of the funds made available in this Act may be used for . . . the creation of a human embryo . . . [or for] research in which a human embryo or embryos are destroyed.”^[xi] The concerns about hESC research that culminated with the enactment of the Dickey-Wicker Amendment may no longer be an issue because of the introduction of the third type of stem-cells, induced pluripotent stem cells.

Induced pluripotent stem cells (iPSCs) are formed as a result of “genetically reprogramming ASCs to behave like hESCs,” changing them from multipotent cells to pluripotent.^[xii] The first successfully generated iPSCs were created in 2006, when “Doctors Shinya Yamanaka and Kazutoshi Takahashi artificially produced a stem cell that mirrored an embryonic stem cell.”^[xiii] This discovery was groundbreaking as it offered an opportunity for stem-cell research to circumvent the moral and ethical objections that had hindered it for so long.^[xiv] Because there is an abundance of ASCs that do not involve the destruction of a human embryo, iPSCs create almost limitless possibilities when it comes to pluripotency.^[xv]

As the research and development of the uses of iPSCs has progressed, a number of problems have arisen in the legal landscape of stem-cell research that need to be addressed. One such issue is the patentability of iPSCs. In his article on refining tests for patentable subject matter, Tyler Laudick notes the “uncertainty and tension [that] exists between the innovation of biotechnology and the preservation of intellectual property rights through patents.”^[xvi] Laudick further highlights the “financial incentive for researchers and developers to create new products that benefit the public and [] build upon scientific knowledge.”^[xvii] The United States Supreme Court has decided several notable cases relating to the patentability of biotechnology and come to the conclusion that there are “three judicial exclusions from patentable subject matter: abstract ideas, laws of nature, and natural phenomena.”^[xviii] In Diamond v. Chakrabarty, the Supreme Court found that in order for a genetically engineered bacterium to be patent eligible, it must differ from anything found in nature.^[xix]

The Supreme Court then doubled down on this ruling in Association for Molecular Pathology v. Myriad Genetics, Inc. when it held that an isolated gene itself was not patentable because it was naturally occurring.^[xx] In the same case, the Court determined that complementary DNA was patentable because it was synthetically created and different from DNA, making it not a product of nature.^[xxi] While this ruling makes sense in the context of a biotechnology engineered to be different than a product of nature, biotechnological advances still face ambiguity when it comes to advances such as iPSCs, which are engineered to identically reflect hESCs.^[xxii] An argument can be made that iPSCs meet the Chakrabarty standard of being “genetically engineered and transformed into something different,” but there is still a crying need for clarity as biotechnology continues to advance.^[xxiii] Laudick proposes a four-part test to become the standard for United States Patent and Trademark Office examiners, as well as inventors seeking certainty of the patentability of their inventions, to use:

“[Determine] whether the claim is meant to reflect a product of nature;”^[xxiv]
“whether the claim adds an inventive or transformative characteristic;”^[xxv]
“the degree of the invention’s functionality before and after the method or process;”^[xxvi] and
“the potential and likelihood that, if granted, the invention would provide significant contribution to the industry.”^[xxvii]

Laudick then goes on to apply how an iPSC’s patentability would be assessed under this standard.^[xxviii] The first factor presents the biggest barrier to patentability, given that scientists developing iPSCs specifically “intend to mirror the naturally-occurring cell as closely as possible because it maximizes efficiency;” however, so long as the inventors can show that the iPSCs are a “sufficiently inventive application, [have] an increase or change in functionality, or [provide] a significant public benefit,” they have a greater chance of gaining a patent.^[xxix] iPSCs clearly have a transformative characteristic, given that ASCs are taken and transformed to behave like hESCs.^[xxx] Similarly, iPSCs change greatly in their functionality when they are converted from ASCs to iPSCs because they change from multipotent to pluripotent.^[xxxi] Lastly, a USPTO examiner would analyze the public benefit of iPSCs.^[xxxii] Biotechnologies such as iPSCs have massive public policy implications given their potential to radically change the medical field as we know it.^[xxxiii] Scientists’ ability to replicate hESCs in the form of iPSCs and subsequently perform research should be incentivized in the form of allowing patents to be claimed, not discouraged because iPSCs are too similar to hESCs. Laudick notes that “not granting a patent solely because the subject matter represents a product of nature would actually incentivize inventors to reduce efficacy of iPSC technologies and risk harmful side effects to make research economically viable.”^[xxxiv]The creation of iPSCs has created an avenue to circumvent the ethical issues surrounding stem-cell research, and now the legal obstacles surrounding the research need to change to incentivize further research and advancement. Technology, specifically biotechnology, has advanced at an exponential rate in recent years, and the field of law is woefully behind. Scientific advances have been made that were never contemplated by the law, including the introduction of iPSCs as a means of performing stem-cell research in a more morally and ethically acceptable way. Scientists and researchers are stuck in a cloud of ambiguity when it comes to the potential patentability, and subsequent financial viability, of their research of iPSCs. The legal field needs to provide clarity and allow for these advancements to

^[i] See Nicholas J. Diamond, The Flaws of Stem Cell Legislation: Sherley, Brüstle, and Future Policy Challenges Posed by Induced Pluripotent Stem Cells, 14 MNJLST 259, 268-77 (2013).

^[ii] Tyler R. Laudick, Patently Confusing: Refining a test for Patentable Subject Matter and Its Implication Toward Biotechnology, 60 WBNLJ 131, 134 (2020).

^[iii] See Layla Cummings, Sherley v. Sebelius: A Call to Congress to Explicitly Support Medical Research on Human Embryonic Stem Cells, 12 N.C. J.L. & Tech. 77, 79 (2010).

^[iv] See id. at 80.

^[v] See id.

^[vi] Diamond, supra n. 1, at 266.

^[vii] See Cummings, supra n. 4.

^[viii] Diamond, supra note 1, at 266; see also Cummings, supra note 2 at 79, 80.

^[ix] R. Alta Charo, Esq., et al., Stem Cell Research, 20110126 AHLA Seminar Papers 75.

^[x] Diamond, supra note 1, at 266.

^[xi] Id. at 276-77.

^[xii] Id. at 266-67.

^[xiii] Laudick, supra n. 2, at 131.

^[xiv] See id. at 135-36.

^[xv] See Diamond, supra note 1, at 267.