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3D Bio-printing: Addressing the Conundrum of Patent Eligibility.

Introduction:

One of the gravest upcoming challenges in the patent regime around the world and especially in India is the patentability of 3D bio-printed products. The technique of 3D printing builds a three-dimensional object using a computer-aided design (CAD) model, by consecutively adding ink of material layer by layer; accordingly, it is also known as additive manufacturing. From guns to bones, companies are rapidly moving towards manufacturing using 3D printing techniques. For instance, the majority of the hearing aids since 2013 are being manufactured using 3D printing[1]. A primary cause for such transformation is the fact that 3D printers have converted a huge labor-driven industry into an automated one.

When these 3D printing techniques are utilized to print cells, tissues, organs, or scaffolds it is termed as Bio-printing. With the help of bio-printing, scientists around the world have made several achievements in 3D printing bones, skin, artificial kidney, cardiac patch, etc. 3D bio-printing is a potential gamechanger which provides for biological materials including fully functional organs for transplantation. However, 3D bio-printing presents regulatory challenges in the protection of data, Intellectual property and privacy. Questions about ownership and patentability of devices and biological materials implanted in the patient’s bodies have created substantial confusion in the patent regime.

Patentability of 3D Printed Organs

For 3D bio-printing a standard computerized tomography (CT) or magnetic resonance imaging (MRI) scan is taken to get the exact dimensions of a tissue. Then a blueprint of the cell structure of the organ is designed. After this, stem cells are isolated (generally from the donor organs or the patient’s body itself) and segregated based on organ particularity. These cells are then embedded in the printer. The combination of living cells and a pertinent base (that provides cells with scaffolding to grow on and nutriment to survive on), like collagen, gelatin, etc. forms the bio-ink. The bio-ink is based on patient’s own cells and is function-specialized. In 3D bio-printing, bio inks or biomaterials are deposited layer by layer to create 3D tissues or organs. Thus, a new tissue or organ is built based on the patient’s own cells. The primary use of bio-printing includes, inter alia, organ transplantation, curbing the anathema of animal testing and in vivo skin repair. 3D printing of organs helps in resolving the issue of shortage of organs or rejection of mismatched organs for transplantation.

It is pertinent to note that the concept of printing 3D organs and tissues is not full of hot air. Many therapeutical achievements have already been made using 3D bio-printing techniques.

Some noteworthy instances include, Orgonovo, a company in San Diego that built human liver patches using bio-printing[1], axial3D 3D printed a kidney to successfully perform a transplant operation on a young mother in Belfast[2], Israeli Researchers from Tel Aviv University printed a small 3D heart using human cells[3], Professor Che Connon’s group of scientists from Newcastle University printed human cornea[4], Biolife4D successfully demonstrated its ability to 3D bio-print human cardiac tissue – specifically, a human cardiac patch[5], bio-engineers at Rice University and University of Washington figured out how to print the complex vasculature that can supply nutrients to densely populated tissues; the scientists made a model of an air sac that mimics human lung[6] and many hospitals are already equipped with 3D printed bones and skin[7] .Such anecdotes illustrate the potential game-changing power of 3D bio-printing and how scientists and bio-engineers around the globe are continuously endeavouring and are not very far away from 3D print fully functional human organs.

According to The European Parliamentary Research Service by Philip Boucher[8]– “3D bio-printing presents regulatory challenges in the protection of data, IP and privacy. For example, a decentralized network of 3D bio-printing services that deliver customized medical devices might have access to sensitive medical data and other personal information. Illegal file sharing amongst some communities – with blueprints for objects unlawfully traded in the same way as MP3 or video files – might present an additional threat to IP protection. Advances in 3D bio-printing may lead to questions about the ownership of devices and bio-materials implanted in patient’s bodies, and also about the patentability of novel biological materials which differ substantially from ‘natural’ bio-materials.”

Herein, by interpreting a couple of cases we seek to conclude as to whether 3D printed organs are patentable or not?

In Bilski v. Kappos, 2010[9]it was stated that an invention based on human ingenuity is protected under the Patent Law but it should not be based on something already existing in nature. The public domain of nature is not the patentable subject matter in the U.S. patent law because it is for all of humanity to share.

In Parke-Davis & Co. v. H.K. Mulford Co., 1911[10], patent on purified adrenaline created by structural differences from the natural form derived from animal glands was upheld. The Judge reasoned that because the adrenaline was isolated and purified from its natural surroundings, it was not a product of nature and was a new product both commercially and therapeutically. Parke-Davis was the foundation of the product-of-nature question in patent law, demonstrating the lack of a clear line between the natural and non-natural in patent law.

In American Fruit Growers, Inc. v. Brogdex Co., 1931[11], an orange dipped in a solution of borax to render the skin mold-resistant was held not to be a manufactured article and non-patentable. The decision considered whether the addition of a chemical to a product of nature was a new use or property. The Supreme Court held that the addition of borax to a rind of fruit only protects the natural article and does not produce a new article with a “distinctive form, quality, or property.”

In re Ewald, 1942[12], a cored pear, was held to be not manufactured because it did not possess a new name, character, or use.

In re Merz, 1938[13], It was held that a purified substance that differed from that found in nature is the patentable subject matter.

In the case of Funk Brothers Seed Co. v. Kalo Innoculant Co., 1948[14], a specific combination of different kinds of bacteria was not patent eligible because the invention covered the aggregation of bacteria, which did not “create a state of inhibition or of non-inhibition in the bacteria” and which was a quality that was “free to all men”.

These early cases manifested that a product of nature that undergoes a change from its state in nature, be it in encountering a structural difference or being purified, would be patentable subject matter. However, no case accurately construed what represented a change from nature, or whether purification was required to be a certain degree, amount or kind. Patents of altered products of nature for biotechnology applications continued to be obtained in the 1950s and 1960s and without much contention for decades after. Patents with a claim element of “gene” and for “DNA” were issued in the 1970s.

Anyhow, it was broadly accepted that nonliving substances that were not changed from their natural state were not patentable subject matter until the landmark Diamond v. Chakrabarty decision.

Diamond v. Chakrabarty, 1980 [15]

In this case, the inventor of a genetically modified bacterium that was capable of breaking down crude oil made three kinds of claims:

First, a process claim for the method of generating the bacterium; second, claims for an inoculum composed of a carrier material floating on water; and third, claims to the bacterium itself.

The patent claim directed at the oil-eating bacterium was rejected by the United States Patent and Trademark Office (USPTO) as not constituting patentable subject matter because bacterium was considered a: 1) product of nature and 2) living thing; and, living things  were generally understood to not be a patentable subject matter under Section 101 of Title 35 United States Code.  However, the Supreme Court rejected these two grounds and found the bacterium to be patentable subject matter because the bacterium was “a non-naturally occurring manufacture or composition of matter.” The Supreme Court declared that “anything under the sun that is made by man” was eligible for patent protection. The Supreme Court upheld the patent because, contrary to the bacterium in Funk Brothers, the bacterium was of modified nature. The Supreme Court broadly construed the terms “manufacture” and “composition” of matter in inferring that the patent claim directed to the bacterium was “a product of human ingenuity with a distinctive name, character, and use.” The Supreme Court stated: “Here, the patentee has produced a new bacterium with markedly different characteristics from any found in nature and one having the potential for significant utility. His discovery is not nature’s handiwork, but his own; accordingly, it is patentable subject matter under §101.”

Thus, based on the framework outlined in Chakrabarty, which applies to all biotechnology-akin subject matters, to evade the “product of nature” exclusion, a manufacture or a composition of matter must be (1) non-naturally occurring (“with markedly different characteristics from any found in nature”)and (2) it must be a product of human ingenuity

These two tests have been applied in the following 2 recent cases-

  1. Association for Molecular Pathology v. Myriad Genetics, 2011[16]

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. The Supreme Court held that naturally occurring DNA segments were products of nature and not patentable subject matter simply by being isolated, whereas cDNA (complementary DNA) was patentable subject matter because it was not naturally occurring. The Supreme Court reasoned that genes contained in the form of cDNA would be patentable subject matter because cDNA is a synthetic creation by scientists. Even though cDNA was made up of naturally occurring nucleotides the resultant product was held to be patentable.

However, in a matter, a patent was not granted to coffee prepared from dates because firstly, dates were a product available in nature and secondly, coffee was not a novel creation with markedly different characteristics.

On the other hand, in Myriad cDNA, although retained the naturally occurring nucleotides but it is distinct from the DNA from which it was derived in that “the non-coding regions have been removed.” the nucleotide sequence of cDNA is dictated by nature, not by the lab technician but the lab technician unquestionably creates something new when cDNA is made.

The bottom line is that an invention may be based on something already existing in nature but the final product to be patentable must be inter alia, novel or non-naturally occurring (markedly different from its natural counterpart). This means that a 3d printed organ can be patent-eligible, even though it is based on the naturally occurring cells of the patient’s body if it has novel or distinct structural or functional properties from its human counterpart

2. In re Roslin Institute (Edinburgh), 2014 [17]

A cloned sheep was found to be unpatentable because they were identical copies of naturally occurring parent sheep. A cloned animal “is an exact genetic replica of another [animal] and does not possess ‘markedly different characteristics’ from any farm animals found in nature.” Dolly the Sheep had nucleic genetic material that was a copy of the adult from which she was cloned, and the word “clone” in the patent claims demonstrated an undifferentiated genetic identity.  Despite the patentee’s arguments that the sheep did have phenotypic or mitochondrial differences, the Federal Circuit held that such differences were not claimed in the patent claims, which were drafted in terms of genetic identity.

However, better patent claims drafting could have highlighted the differences from nature and, therefore, may have enabled patent eligibility in view of the features that may have been markedly different from nature.

Dolly the Sheep had shorter telomeres than other animals of the same age. Therefore, Dolly would not be considered an exact replica of her donor and, hence, would have the necessary markedly different characteristics to be considered patentable subject matter. This subtle difference of shorter telomeres, which resulted in Dolly the Sheep’s early death was overlooked by the court and. Such a biological example is a type of difference that would have yielded markedly different characteristics.

A well-drafted plea would endeavor to highlight such fundamental biological diversities in a patent claim. Similarly, any such biological differences promoted by 3D bio-printing technology would yield markedly different characteristics to result in the patentable subject matter. 3D bio-printing technology itself has technological limitations that inherently would yield-related biological variations. Moreover, 3D bio-printing technology permits precision design to create engineered differences in biology, and such a design choice can lead to markedly different characteristics than what is found in nature.[18]

DO 3D PRINTED ORGANS SATISFY THE TWO CHAKRABARTY TESTS?

The markedly different characteristics standard concentrates on the extent of physical differences between modified items and their naturally occurring counterparts.

Given the present scenario, bio-printed tissues and organs appear to be substantially distinct from their human counterparts. The structural differences between a bio-printed organ and a parent organ clearly are significant. For example, state of the art of bio-printing technology cannot generate innervated organs (organs that supply with nerves). As of now, the printed organs do not contain vasculature and are composed primarily of homogeneous cells or at best, layers of different cell types. Creating a working vascular system is deemed to be such a monumental accomplishment that NASA is granting a prize of $500,000 for the first research team that can do it. The Vascular Tissue Challenge will award the prize for a 1cm thick piece of human tissue with a fully working blood system that can survive for 30 days in vitro. Bio engineers at Rice University and the University of Washington have presented their exploration with a striking model of a breathing lung that passes oxygen into surrounding blood vessels. It marks a significant quantum leap because hitherto, although it has been somewhat easy to grow living cells in a lab, the intricate part has been keeping them alive. To encounter this, the team generated a new open-source technology for bio-printing called the stereolithography apparatus for tissue engineering (SLATE). This required printing a liquid, pre-hydrogel solution contrived of living cells, and curing each layer by exposing it to a blue light. So as to attain the intricacies crucial to recreate the vascular system, the team added food dyes that assisted in absorbing the blue light and focus the solidification onto very thin layers. ‘One of the biggest roadblocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues,’ explained Jordan miller, lead researcher on the study.[19]

Akin structural differences are symbolic. Albeit the individual cells of a bio-printed organ are naturally occurring, their aggregation into a functional organ is not.

Unlike DNA, a bio-printed organ is different from the naturally occurring organ and is definitely a product of human ingenuity. Without human intervention, stem cells cannot self-assemble into a uniform structure in vitro (in a test tube/culture dish), let alone function as an organ. Thus, a bio-printed organ would most likely satisfy the second prong of the Chakrabarty test. 

The bottom line is that because of its novel functional and structural properties, a bio-printed organ in itself can be patent-eligible subject matter, even though it may contain cells that are genetically identical to its naturally occurring counterpart.

Prima facie, it can appear that 3D bio-printed living tissues (whether for organ transplants, in vivo skin repair, or wearable microbiomes) are merely an assembly of cells organized in a 3D structure. However, 3D bio-printed tissues are manufactured by natural growth through intrinsic self-assembly principles found in nature. In such cases, where nature is emulated inside of a 3D bio-printer, the resulting product would arguably not have markedly different characteristics because nature is directing the creation. However, human ingenuity is plausibly the cause for the accuracy, ejection and automation of the bio-ink particles inside of a 3D bio-printer that produce 3D bio-printed materials. In other cases, the assembly of 3D bio-printing cells could be combined with artificial materials, such that a mixed living and nonliving 3D bio-printed material would be achieved. The result is an easy case of markedly different characteristics because the infusion of artificial materials would structurally and visibly be considered markedly different.

As a conceptual example, artificial materials, such as Kevlar, could be introduced into a product of natural materials to be 3D bio-printed for in vivo skin repair, or as discussed above the addition of food dyes that assisted in absorbing the blue light that in turn helped the engineers at Rice University re-creating the vascular system can be termed as an addition of artificial materials. A more difficult case is 3D bio-printed materials lacking any addition of artificial materials.

Inventors can thus avoid the patentable subject matter challenges with producing exact replicas by slightly modifying the 3D bio-printed object from what appears in nature. Any change in structure, function, or properties produced by the 3D bio-printing process specified in the patent specification would deem the material patentable subject matter. The markedly different standard does not distinguish well between slightly modified and wholly modified 3D bio-printed materials

CORE LIMITATIONS PERTAINING TO THE PATENTABILITY OF 3D PRINTED ORGANS IN INDIA:

For an invention to be patentable under The Patents Act, 1970, it must fulfill the requirements stated in Sec. 2(j) i.e. it must be novel, have an inventive step and must be capable of industrial application. In addition, it must also fulfill the stipulations mentioned in Sec. 3 i.e. it must not be a part of the exceptions in Sec. 3 of the Patents Act. With regard to 3D bio-printing this could lead to notable perplexity. For e.g. Bio-printed organs may not be patentable as such organs may be seen as “naturally occurring” (S. 3(c)). However, in line with the Myriad decision, it could be assumed that 3D printed organs could be patented, whereas the naturally occurring material could not be. Nonetheless, in the Indian framework the decision could be different. Sec 3(j) of the 1970 Act forbids patents in “plants and animals in part thereof”. To create 3D printed organ of an animal, biomaterial of that animal would necessarily have to be used, and would straightaway come within the brackets of ‘any part thereof’ within the expression as under Sec. 3(j). A 3D patented organ of an animal therefore, may not be patentable, granting that it is non-naturally occurring and involves a considerable degree of human ingenuity.

The need of the hour, in conclusion, is that with the emergence of 3D bio-printing, India’s patent regulations must be accordingly amended to do away with retrogression.


[1]Hasan Chowdhury,  Liver success holds promise of 3D organ printing, FINANICIAL TIMES, (Mar 5, 2018), https://www.ft.com/content/67e3ab88-f56f-11e7-a4c9-bbdefa4f210b

[2] Sam Davies, axial3D printed kidney model provides solution to complex procedure, TCT MAGAZINE (Jan 25, 2018, 10:33), https://www.tctmagazine.com/3d-printing-news/axial3d-printed-kidney-model-complex-procedure/

[3]David Freeman, Israeli scientists create world’s first 3D-printed heart using human cells,  NBC NEWS MACH, (Apr 19, 2019, 9:41 PM), https://www.nbcnews.com/mach/science/israeli-scientists-create-world-s-first-3d-printed-heart-using-ncna996031

[4] First 3D printed human corneas, NEWCASTLE UNIVERSITY, (May 30, 2018), https://www.ncl.ac.uk/press/articles/archive/2018/05/first3dprintingofcorneas/

[5] BIOLIFE4D Successfully Demonstrates Ability to 3D Bioprint Human Cardiac Tissue, BIOLIFE4D, (Jun 25, 2018), https://biolife4d.com/biolife4d-successfully-3dbioprints-cardiac-patch/

[6] Jade boyd, Organ bioprinting gets a breath of fresh air, RICE NEWS, (May 2, 2019), https://news.rice.edu/2019/05/02/organ-bioprinting-gets-a-breath-of-fresh-air-2/

[7] Sarah Saunders, Custom 3D Printed CT-Bone Graft Implants Coming to Japan and Europe, 3DPRINT.COM, (Jul 7, 2018), https://3dprint.com/220737/3d-printed-ct-bone-grafts/

[8] Philip Boucher, 3D Bio-Printing For Medical And Enhancement Purposes, EUROPEAN PARLIAMENTARY RESEARCH SERVICE, (July 2018), http://www.europarl.europa.eu/RegData/etudes/IDAN/2018/614571/EPRS_IDA(2018)614571_EN.pdf

[9] Bilski v. Kappos, 561 U.S. 593

[10] Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95 (C.C.S.D.N.Y. 1911)

[11] Fruit Growers, Inc. v. Brogdex Co., 283 U.S. 1 (1931)

[12] In re Ewald, 129 F. 2d 340

[13] In Re Merz, 97 F.2d 599 (C.C.P.A. 1938)

[14] Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127

[15] Diamond v. Chakrabarty, 447 U. S. 303, 308–309 (1980)

[16] Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576

[17] In re Roslin Institute (Edinburgh), 750 F.3d 1333

[18]Tabrez Y. Ebrahim , 3D Bioprinting Patentable Subject Matter Boundaries,  41:1, SULR, (2017), https://digitalcommons.law.seattleu.edu/cgi/viewcontent.cgi?article=2443&context=sulr

[19] Ibid 7.


Cite this article (The Bluebook 20th ed.)-

Riya Agarwal and Priya Agarwal, 3D Bio-printing: Addressing the Conundrum of Patent Eligibility., Ex Gratia Law Journal, (December 1, 2020), https://exgratialawjournal.in/journal/volume-1/vol1-issue3-dec2020/3d-bio-printing-addressing-the-conundrum-of-patent-eligibility-by-riya-agarwal-and-priya-agarwal/.

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Author

Riya Agarwal
Student - Vivekananda Institute of Professional Studies (VIPS)
Priya Agarwal
Student - Dr. Ram Manohar Lohiya National Law University