PATENT INFRINGEMENT IN PERSONALIZED MEDICINE: LIMITATIONS OF THE EXISTING EXEMPTION MECHANISMS.

• Author: Kim, Jiyeon

INTRODUCTION

Mr. X suffers from recurrent glioblastoma, a type of deadly brain cancer. One of his physicians reads a study reporting a novel immunotherapy, which uses the chimeric antigen receptor T cell (CAR-T) technology, leading to regression of glioblastoma in a small number of patients. (1) Although the therapy has recently been approved by the U.S. Food and Drug Administration (FDA) and is now offered by two major pharmaceutical companies, (2) it is only approved for certain hematological cancers. (3) In addition, Mr. X's cancer does not express the biomarker that is necessary for the CAR-T therapy used in the published glioblastoma trial. (4) Fortunately, the physicians are aware of a research laboratory at the university associated with the medical center that has expertise on the technologies associated with the CAR-T immunotherapy as well as certain biomarkers associated with Mr. X's cancer. (5) In collaboration with the laboratory's researchers, Mr. X's physicians conduct a small clinical trial administering an experimental CAR-T therapy to Mr. X and other glioblastoma patients, for whom this clinical trial was their only remaining hope. Later, one of the pharmaceutical companies holding multiple CAR-T patents sues the physicians, researchers, and academic institution for patent infringement.

This hypothetical scenario involving the first FDA-approved gene therapy, CAR-T therapy, (6) illustrates a potential patent infringement lawsuit that might occur more frequently as we enter the new era of personalized and precision medicine. (7) The beauty and power of personalized medicine is that it is inherently experimental and innovative. Naturally, therapies in personalized medicine are built upon many patented technologies. Thus, underlying these novel therapies is the potential for alleged patent infringement by the physicians and researchers who experiment with and personalize the therapy in order to cure patients and save their lives.

This Note uses the CAR-T therapy as a case study to examine the unique challenges that patent law faces in the dawn of the personalized medicine era, particularly regarding patent infringement. Specifically, this Note inquires whether a use of patented medical therapy (8) related to a clinical experiment or trial by physicians, researchers, and academic institutions for the purpose of patient treatment renders them liable for patent infringement. Patent law confers exclusive rights to inventors and allows them to enforce those rights associated with a specific patent by bringing a patent infringement claim against the alleged infringer. (9) At the same time, however, patent law also permits certain unauthorized uses of patented inventions to be exempted from infringement challenges or infringement liability. (10) There are two key defenses under which an alleged infringer can be exempted: one provides exemption largely based on the status (11) of the alleged infringer ("medical procedure exemption"12) and the other based on the nature or purpose of the alleged infringing use ("experimental use exemption"). (13) This Note analyzes whether the two exemptions indeed provide effective immunity from patent infringement or infringement liability for physicians, researchers, and academic institutions involved in the use of experimental therapies in the personalized medicine era.

Analysis of the statutory text, legislative history, and case law of the medical procedure exemption reveals that the "biotechnology patents" exception renders the provision ineffective for infringement lawsuits involving CAR-T therapy. (14) Therefore, this Note argues that the medical procedure exemption is incompatible with the personalized medicine era. (15)

Meanwhile, the experimental use exemption bifurcates into a narrow common law doctrine (16) and a statutory provision that is interpreted relatively broadly when related to FDA submission. (17) However, it is ambiguous whether a clinical trial would be considered as an "experimental use" under the narrow common law experimental use doctrine and whether the statutory experimental use exemption would permit uses that might not have any realistic potential for FDA submission. (18) While many scholars have argued for a broad experimental use doctrine, the discussions have remained largely in the context of basic science. (19) This Note presents a novel argument for a broad experimental use doctrine in the context of personalized medicine and suggests that the new era of personalized medicine calls for an additional factor in the experimental use analysis--clinical trials and experiments that cure and save patients' lives. (20)

Part I provides an overview of the CAR-T immunotherapy as a model therapy representing personalized medicine and presents the issue of patent infringement. Part II examines the medical procedure exemption and analyzes its effectiveness as a defense to patent infringement liability involving CAR-T patents. Then, Part III turns to the experimental use exemption, examines its effectiveness for providing immunity from CART patent infringement, and concludes by arguing for a broader experimental use doctrine for the personalized medicine era.

1. PERSONALIZED MEDICINE AND PATENT INFRINGEMENT

   1. CAR-T Therapy: The First FDA-Approved Gene Therapy Heralding the Personalized Medicine Era

      The new era of personalized medicine and health care is marked by the Precision Medicine Initiative (21) and the 21st Century Cures Act of 2016, (22) aiming to incorporate innovative diagnostics and therapies tailored to individual patients into the health care practice. Under this movement, cancer immunotherapy has advanced exponentially as a prototype embodying the idea of personalized medicine. (23) At the forefront is a therapy that utilizes a cancer patient's own immune cells, genetically modifies them to recognize cancer cells, and places those modified cells back into the patient's body to attack the cancer--chimeric antigen receptor T cell (CART) therapy. (24) This novel therapy has successfully treated (25) previously incurable cancers such as advanced chronic lymphoid leukemia (CLL) (26) and acute lymphoid leukemia (ALL). (27)

      In addition to being in the media spotlight for its efficacy in treating cancer, the CAR-T therapy has also been at the center of patent battles between pharmaceutical companies and academic institutions. (28) The number of patents involving the CAR-T technology is already staggering and continues to grow. (29) And, on August 30, 2017, CAR-T surprised the world again when the FDA approved Novartis's CAR-T therapy--Kymriah--for the treatment of ALL in pediatric and young adult patients, (30) making it the first FDA-approved gene therapy. (31) Subsequently, the FDA approved a second CAR-T therapy--Yescarta--to Kite Pharma, Inc. (32) for the treatment of large B-cell lymphoma in adult patients. (33) Heralding the era of personalized medicine, FDA approval of CAR-T therapy provides promise for the field of genetic engineering and gene therapy.

      However, this unconventional drug raises novel questions. Compared to a traditional drug with a fixed chemical composition, CAR-T therapy utilizes a patient's own immune cells, and, thus, there is a wide range of efficacy and toxicity. (34) Many detailed aspects of the CAR-T therapy remain unknown, requiring more clinical trials and experimentations. Also, while the therapy thus far has been successful mostly in hematological cancers, there is excitement for the application of CAR-T therapy in other solid cancers. (35) These aspects, potential for new discovery and application, can in fact be considered as characteristics of therapies in personalized medicine that are tailored to individual patients and are often based on cutting-edge biotechnology with ample possibilities for future applications. These therapies are inherently experimental and, thus, potently innovative. All this therapeutic potential, in turn, harbors potential for patent infringement: a physician, a researcher, or an academic institution using and experimenting with the CAR-T therapy to treat more patients and cure more diseases could become liable for patent infringement.

   2. Patent Infringement and Exemption from Infringement

      United States patent laws confer an exclusive right to make, use, or sell an invention for twenty years (36) to achieve the constitutional prerogative "[t]o promote the Progress of Science and useful Arts." (37) The patentee has "the right to exclude others from making, using, offering for sale, or selling the invention," (38) regardless of the alleged infringer's intention or access to the invention. (39) Despite the seemingly unqualified rights of the patentee, patent statutes allow certain unauthorized uses of a patented invention by providing exemption from patent infringement or liability. (40) Conceptually, these statutes can be categorized as providing an exemption based on either the alleged infringer's special status or the special nature or purpose of the infringing act. Indeed, for physicians, researchers, and academic institutions that become liable for patent infringement from using a patented medical therapy, such as CAR-T, patent law provides two sources of potential exemptions: (41) exemption from infringement liability for a medical practitioner's medical activity (42) and exemption from infringement for experimental use of the invention. (43)

2. 35 U.S.C. [SECTION] 287(C): MEDICAL PROCEDURE EXEMPTION FROM PATENT INFRINGEMENT LIABILITY

   This Part provides a brief legislative history of 35 U.S.C. [section] 287(c), (44) the so-called "medical procedure exemption" provision, and reviews the case law interpreting the statute. It proceeds to an analysis of whether a physician, researcher, or academic institution using the CAR-T therapy will qualify under [section] 287(c) for immunity from infringement liability and concludes by arguing that the provision is...