IS THE SKY REALLY FALLING?: MYRIAD AND ITS IMPACT ON THERAPEUTIC DEVELOPMENT.

• Author: Beardall, Taylor

INTRODUCTION 312 I. MYRIAD'S LIMITS ON PATENTING PRODUCTS OF NATURE 315 A. Recent Judicial Limits on Patent Eligibility 315 B. The Myriad Decision 318 C. Reactions to Myriad 320 II. MYRIAD'S IMPACT ON THERAPEUTIC DEVELOPMENT 323 A. But First, the Patent System's Ambiguous Impact on Innovation 323 B. Applying Myriad to Therapeutics Derived from Natural Products in the Lower Courts and at the USPTO's Patent Trial and Appeal Board 325 C. Unpursued Therapeutic Innovation 329 1. Stories Submitted to the USPTO 329 2. The Story of Mambalgin-1 332 III. WHAT NOW?: A MYRIAD OF OPTIONS 336 A. Increase Regulatory Exclusivity Periods for Natural Therapeutics that Treat Chronic Illness 338 B. Sufficiently Fund Grants and Direct Funding Opportunities at the National Center for Complimentary and Integrated Health 339 C. Create Federal Tax Credits for Clinical Trials of Natural Therapeutics That Treat Chronic Illness 341 CONCLUSION 342 INTRODUCTION

For those affected by chronic illnesses, such as cancer or multiple sclerosis, prolonged pain management is critical. (1) Unfortunately, however, there are not great options to control serious and long-term discomfort. Given the widespread addiction epidemic that plagues our country (2) and the many uncomfortable side effects associated with narcotic painkillers, (3) doctors are hesitant to prescribe opioid medications for longer than brief periods of time. (4) This leaves non-narcotic pain medications, such as acetaminophen, ibuprofen, and aspirin, for long-term pain control. (5) Yet these drugs are not as powerful as their narcotic counterparts, such as hydrocodone or oxycodone, that can treat moderate to severe pain. (6)

Researchers estimate that about twenty percent of all U.S. adults experience chronic pain every day, leading to a loss of productivity estimated at about $300 billion per year. (7) Thus, the healthcare community and government have a vested interest in developing a non-narcotic pain therapy that does not lead to uncomfortable side effects and can attack moderate to severe pain. Subsequently, innovation is necessary to meet the need for a non-addictive pain management option that will simultaneously address our country's chronic illness and opioid epidemics. (8) This example highlighting the need for a non-narcotic pain medication elucidates the importance of medical innovation, but represents just one of many areas where society would benefit from pharmaceutical advancement.

One potential avenue to search for these advances is in repurposing natural products for therapeutic use. Many therapeutic drugs are already derived from nature, (9) and researchers emphasize that natural products remain a promising area for future research, particularly in the field of pain management. (10) But in 2013, the Supreme Court sharply limited the patentability of natural products in Association for Molecular Pathology v. Myriad Genetics, (11) leading some to worry that natural product innovation would subside--particularly with regard to therapeutics, where patents have played an important role in development. (12) Patents are so crucial to the development of pharmaceutical therapeutics because of the need to conduct rigorous and expensive clinical trials before even applying for drug approval from the FDA. Because of this historic relationship between patents and pharmaceutical therapies, academics and researchers alike have proclaimed that post-Myriad, "the sky is falling" on the development of future therapeutics derived from natural products. (13)

Because of fears that Myriad and other recent patentable subject matter eligibility cases will lead to less innovation as patents become harder to come by, there has been a great deal of recent focus on reforming the patent eligibility statute to abrogate the Court's recent case law. (14) In 2019, Senate hearings were held to assess the impact of Myriad and related cases, and in 2021, the Department of Commerce, Patent and Trademark Office (USPTO) requested public comments to assess the impact of current patent eligibility jurisprudence on innovation. (15) But there is still little rigorous evidence of how Myriad and its family of cases have affected innovation in general, and of promising therapeutics derived from products of nature in particular.

This Note seeks to fill this gap by contributing new evidence to the debate. It does not, however, make broad conclusions, such as recommending that Myriad be reversed. Instead, it simply aims to add facts to the conversation about Myriad's actual impact and show that post-2013, there has been at least some negative impact on therapeutic innovation. While a review of lower court decisions may suggest that Myriad's impact has been negligible, the case has made a greater impact during initial patent examination. A review of post-2013 cases before the USPTO's Patent and Trial Appeal Board (PTAB) shows that there are patent applications being rejected under a Myriad standard.

Additionally, through investigative research, this Note presents the case of Mambalgin-1, a novel contribution that answers the call by intellectual property academics for more evidence of discontinued projects due to patent eligibility concerns. A peptide found in Black Mamba venom that possesses painkilling qualities and little-to-no patient side effects, Mambalgin-1 was not pursued as a commercial therapeutic because of Myriad-related concerns. (16) Therefore, while the sky has not fallen en mass, this new case study shows that at least a few chunks have left the atmosphere. Or put differently, there is specific evidence that Myriad has negatively impacted at least some innovation and development. How significant these impacts are, and whether these negative impacts outweigh Myriad's benefits, remain questions for future research.

This Note proceeds in three parts. Part I describes recent judicial limits placed on patentable subject matter and unpacks the Myriad decision and reactions to its holding. Part II evaluates Myriad's actual impact in three ways. Part II.A addresses current views on the patent system's general impact on research and development. Part II.B contributes the first review of Myriad's impact in lower courts and at the PTAB, with a specific focus on therapeutics derived from natural products. Part II.C highlights new comments submitted to the USPTO from concerned members of the biotech community with regard to Myriad's impact on therapeutic development. It also offers the story of Mambalgin-1, an unpursued natural therapeutic with the potential to alter chronic pain management. While the novel case study presented is but one instance of Myriad deterrence, it is concrete evidence that Myriad has had an impact on therapeutic development and that patents do impact innovation. Part III provides non-patent options, such as longer periods of regulatory exclusivity, increased grants and direct funding, and tax credits, that can be used to spur natural therapeutic innovation under the shadow of Myriad.

1. MYRIAD'S LIMITS ON PATENTING PRODUCTS OF NATURE

   While Myriad is the focus of this Note, it is but one string in the web of patentable subject matter restraints. Part I delineates the current statutory and judicial limits placed on patent eligibility and describes where Myriad falls in this legal environment. It also describes the Myriad holding in detail and the reactions that followed this decision.

   1. Recent Judicial Limits on Patent Eligibility

      In exchange for the right to exclude others from their invention, the U.S. Patent Act imposes a number of requirements for obtaining a patent. (17) In particular, four statutory provisions outline the core legal requirements for patentability. (18) Section 102 requires that the claimed invention is novel. (19) Section 103 establishes a non-obviousness condition, demanding that the claim in question does not cover trivial alterations to previously known inventions. (20) And Section 112 necessitates a clear disclosure of the invention, including information that will allow a person having ordinary skill in the art (PHOSITA) to make and use the claimed invention without undue experimentation. (21) But it is Section 101 that is of primary relevance to this Note's inquiry: the requirement of subject matter eligibility. (22)

      Even if an invention is new, non-obvious, and adequately disclosed, a patent will be denied if the claimed invention does not fall within one of four broad statutory categories, as a "process, machine, manufacture, or composition of matter." (23) The broad statutory language of Section 101 may appear all-embracing, but since the Patent Act's ratification, a number of implicit judicial limits have been attached to restrict the apparent breadth of the four patentable subject matter categories.

      The Supreme Court has long struggled to clarify what is patentable subject matter and what is not; in so doing, they created unclear boundaries of subject matter limits. (24) In an attempt to provide a modern and coherent framework for delineating the extremities of patentable subject matter, the Court specifically addressed Section 101 in 1981 when it excluded "[l]aws of nature, natural phenomena, and abstract ideas" from the safe harbor of patentability, regardless of whether claimed inventions fall under one of the four Section 101 categories. (25) The Court has justified this Section 101 carve out as necessary to avoid the "monopolization of [the basic tools of scientific and technological work that]... might tend to impede innovation more than it would tend to promote it." (26) While the Court intended to protect the "progress of science," (27) their attempt to promote ingenuity led to an unclear understanding of what "laws of nature, natural phenomena, and abstract ideas" include.

      Beginning in 2010 and ending in 2014, the Court attempted to further clarify when "laws of nature, natural phenomena, and abstract ideas" are sufficiently...