Chakrabarty and Bioprinting
Although, at first glance, bioprinted organs appear to be no more than an assembly of naturally occurring cells in a 3D structure, but under the Chakrabarty two-prong test it becomes clear that such manufactures constitute patent-eligible subject matter. The first prong of the Chakrabarty test asks whether or not a bioprinted organ is a naturally occurring manufacture. The Supreme Court has defined the term “manufacture” as “the production of articles for use from raw or prepared materials by giving to these materials new forms, qualities, properties, or combinations, whether by hand-labor or by machinery.”9 Based on this definition, a bioprinted organ is a “manufacture,” but is it also naturally occurring? Given the current state of bioprinting of organs and tissues, the answer to this question is a resounding “yes”.
The current state of the art in the field of regenerative medicine is directed to (1) the 3D printing of biocompatible cell-free solid scaffolds (e.g., cellulose) in the shape of an organ (e.g., an ear) that can act as a support for human cells (e.g., cartilage or skin cells) to then adhere to and naturally grow on them; (2) the 3D printing of cellularized scaffolds that allows for fabrication of structures with two or more cell types located at precise locations (e.g., a joint structure with bone and cartilage portions);10 (3) the 3D bioprinting of tissue and organs without the need for solid supports.11
In general, 3D bioprinting of tissues and organs without solid scaffolds involves sequential depositing of layers of a soft biocompatible matrix (e.g., elastin, collagen) into which stem cells are printed in a nonrandom predetermined pattern. The printed cells of each layer are subsequently differentiated into a specialized cell type (e.g., muscle cells, umbrella cells, urotheliel cells of bladder) and allowed to fuse to cells of the adjacent layers to form a multilayer structure resembling a human tissue or organ (e.g., human bladder). A recently issued patent to bioprinted organs includes the following claim: a three-dimensional layered structure comprising at least one layer of a matrix; and a plurality of cell aggregates, each cell aggregate comprising a plurality of living cells, wherein the cell aggregates are embedded in at least one layer of matrix in a nonrandom predetermined pattern, the cell aggregates having predetermined positions in the pattern.12 Alternatively, some groups have claimed the bioprinted organs as engineered, living, three-dimensional connective tissue constructs comprising connective tissue cells cohered to one another to provide a living, three-dimensional connective tissue construct, wherein the construct is substantially free of preformed scaffold at the time of use.13
The Supreme Court has recognized that “[g]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry, [nor does] extensive effort alone.”14 Although an extensive research effort is required to isolate and propagate the naturally occurring stem cells for using them in an iterative process of printing, growing, differentiating, etc., the research efforts play no role in a section 101 patent eligibility inquiry. However, given the current state of the art, bioprinted tissues and organs appear to be significantly different from their current human counterparts. The structural differences between a bioprinted organ and a parent organ clearly are significant. For example, state of the art of bioprinting technology cannot generate innervated organs. Currently, the printed organs do not contain vasculature and are composed primarily homogeneous cells or at best, layers of different cell types. These structural differences from their human counterparts are significant. Although the individual cells of a bioprinted organ are naturally occurring, their assembly into a functional organ is not.
The second prong of the Chakrabarty test asks whether the bioprinted organ or tissue is a product of human ingenuity, which is subject to some of the same considerations associated with the first prong of the Chakrabarty test. In Chakrabarty, the genetic alteration that rendered the bacteria functionally different from any other naturally occurring bacteria (i.e., the ability to biodegrade oil) convinced the Court that the engineered bacteria were a product of human ingenuity. In Myriad, a DNA fragment that lacked any genetic alterations but was isolated from a larger, naturally occurring DNA stretch was found not to be a product of human ingenuity. Unlike DNA, a bioprinted organ is distinct from the naturally occurring product and is certainly a product of human ingenuity. Without human intervention, stem cells cannot self-assemble into a uniform structure in vitro, let alone function as an organ. Thus, a bioprinted organ would most likely satisfy the second prong of the Chakrabarty test.
In summary, although a bioprinted organ may contain cells that are genetically identical to a naturally occurring counterpart, the organ itself is patent-eligible subject matter because of its novel functional and structural properties. The Supreme Court in Myriad cautioned that “[t]he rule against patents on naturally occurring things is not without limits, however, for all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas,” and “too broad an interpretation of this exclusionary principle could eviscerate patent law.”15 Thus, a court should find that the structural and/or functional differences between bioprinted organs and naturally occurring cells or organs are sufficient enough to satisfy the requirement of 35 U.S.C. § 101. However, just having patent-eligible subject matter does not automatically make a claim to a bioprinted organ patentable. Other requirements such as novelty, obviousness, written description, and enablement must still be satisfied before the claim is found patentable.
Want more on bioprinting? Be sure to check out "Bioprinting: From Patches to Parts" from our May 15 issue.