Introduction
In January 2024, the fifth Kolkata Transplant Colloquium was held in Thimphu, Bhutan which dealt with the issues and advances in the field of organ transplants.[1] While the number of people who need an organ transplant is quite high, it is surprising to note that the organ donation figures are still at an abysmal low. India especially stands at the lowest with a rate of 0.4[2] which means India has remained consistently below one donor per million population for a decade. This is tragic as 300,000 patients are still on the waitlist and 20 die awaiting the same.[3]
In stark contrast, India also has around 18000 successful organ transplant surgeries performed annually preceded by the US and China.[4] However, most of these surgeries are done by the private sector, therefore the fruits of the advancement in technology cannot be reaped by all and largely cater to the affluent section of the society. While more transplants are being performed, India still lacks on the equity and inclusivity front. Even the utilization of organs from deceased donors is suboptimal due to various factors like religious and cultural beliefs, healthcare system experiences, etc.[5] This becomes a critical issue as chronic diseases like diabetes and hypertension are on the rise leading to an increased demand for kidneys. While early detection and screening are often suggested as a solution, the state of India’s healthcare infrastructure and accessibility answer the same negative. However, with recent technological advancements, we now have the option to print organs. 3D bio-printed skins have been grafted on animals and the same are now being used by cosmetic companies for carrying out trials of their products.[6]
Advancements in Bioprinting: Creating Functional Blood Vessels with 3D Ice Printing
In today’s time, Bioprinting is a huge advancement in the field of personalized medicine which can solve the problem of organ transplants and the need for a matching donor. Bioprinting is a type of additive manufacturing wherein organs are printed in layers with the aid of bio-ink.[7] Bio ink can be composed of cultured cells and biocompatible materials. Lately, researchers at Nottingham Trent University (NTU) have developed realistic 3D-printed heart and lung models that can simulate the functions of real organs.[8] These models, designed for training purposes in organ transplants, can mimic bleeding, beating, and breathing, providing medical practitioners with a realistic training tool.
[Image Sources: Shutterstock]
However, one of the main hurdles in engineering artificial organs is creating functional blood vessels that accurately replicate the natural structure and function of biological ones. The earlier design struggled to achieve this. However, the work of Yang and his team, have created a solution which is 3D Ice Printing – an innovative method using 3D ice printing to create artificial blood vessels.[9] This technique involves depositing a stream of water onto a very cold surface and then maintaining a liquid phase on top of the water stream during printing, instead of letting it freeze entirely. This continuous, freeform process results in very smooth structures, avoiding the layering effects often seen in other 3D printing methods.
The research team used “heavy water (D₂O), which has hydrogen atoms replaced by deuterium, giving it a higher freezing point than regular water.”[10] This heavy water is streamed onto a cold surface, forming ice templates that stay partially liquid during the printing process. These ice templates are then used to mold vessel-like shapes in a gelatin-based material known as GelMA. The process involves embedding the ice templates into GelMA, which is then exposed to ultraviolet (UV) light. This UV exposure hardens the GelMA while the ice melts away, leaving behind intricate networks that resemble blood vessels. These artificial vessels are then seeded with endothelial cells, which are crucial for blood vessel formation.[11] The study found that these cells adhered well to the GelMA and remained viable for up to two weeks, suggesting that these artificial vessels could support cell viability and function.
While this new research is a breakthrough, certain legal implications like patentability crop up. This blog explores the existing legal framework and the challenges that bio-printed products would face in the Indian legal regime.
Patentability
In India, the Patent Act of 1970 outlines certain exclusions for patenting specific subjects. Section 3 of this act lists various exclusions, such as subject matter that could be harmful to public order and morality, naturally occurring living or non-living things, therapeutic efficacy, mere admixtures, methods for treating plants and animals to make them disease-free and enhance their economic value, and processes for producing and propagating plants and animals.
Legal Implications
In India, 3D bioprinting is a patentable technology. Patent claims can encompass pre-printing materials like bio-ink, the processes for preparing bio-ink compositions, and manufacturing bio printed products, as well as the bio-printed products themselves. Additionally, patents can be granted for bioprinters, related devices, systems, and 3D bioprinting software applications. However, there are certain complications, Section 3 of the Patents Act deals with what cannot be termed as Inventions. As per Section 3(c), inventions that originate from nature cannot be patented. The eligibility of bioprinting products, including bio-printed tissues and organs, as well as the materials used in the printing process, known as pre-printing materials to get patents hinges on the degree of human innovation involved and how much they differ from their natural counterparts.
This rule is based on the idea that just changing the biological structure isn’t enough for a patent if you’re merely using natural materials in a lab. If all the input materials come from natural sources, you might hit a roadblock for patenting. The Indian Patent Office has guidelines that specifically state that naturally occurring substances cannot be patented if they are just isolated directly from nature. Therefore, for printed components of the blood vessels or other organs to qualify for patents, they need to show some characteristics that aren’t naturally occurring.
Section 3(d) of the Indian Patents Act further complicates things by preventing patents on mere discoveries of new forms of known substances unless they significantly improve their known efficacy. It also excludes new properties or uses of known substances or the mere use of known processes, machines, or apparatuses unless they result in a new product or involve at least one new reactant. This means you need to demonstrate an inventive step however, 3D bioprinting uses the same technology to produce new outputs, leading to objections under Section 3(d). If the output is just a combination of different input materials without fundamentally changing their identities, objections under Section 3(e) could arise, as it might be seen as a mere mixture with only the aggregated properties of its components. This opposition can be raised against bioink which is made up of biological components like collagen, gelatin, alginate, fibrin, and hyaluronic acid.
Thus, various subsections of Section 3 pose a challenge to the patentability of bio-printed organs and blood vessels. Therefore, it is time that the distinction between discoveries and natural products needs to be reconsidered. Natural materials can be part of patent-eligible inventions, and the presence of these components in a claimed invention should not hinder its patentability. Instead, the focus should be on the innovative way these components are combined. As Judge Markey aptly noted in the debate over the patentability of combinations, “Only God creates from nothing. Man must work with existing elements.”[12]
In the Indian context, our country has made significant strides in 3D bioprinting. This is illustrated by the launch of a dedicated facility for artificial organs at the Andhra Pradesh MedTech Zone (AMTZ) in Visakhapatnam, Andhra Pradesh. AMTZ.[13] It is the country’s first medical device park, providing common manufacturing and scientific facilities, including laboratories, warehousing, and testing centers. Another significant step was taken by the Indian Institute of Science which has developed bioprinted silk fibroin (SF) scaffolds for bone tissue regeneration, using silk fibroin from silkworms. The Indian Institute of Technology Bombay and the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Thiruvananthapuram, Kerala, are also at the forefront of 3D bioprinting efforts.[14]
Conclusion
Law must progress alongside technological advancement to ensure that society reaps its benefits to the fullest. This is also the main objective behind the Patents Act, which provides a monopoly in exchange for details of the invention, ultimately benefiting society. This crucial balance between granting a monopoly to incentivize inventions and ensuring public interest must be maintained with changing times. While technology has advanced at a great pace, offering creative and viable solutions to the problem of organ transplants, the law must grant it the necessary support to ensure that the solutions materialize. To ensure this, Section 3 of the Patents Act which excludes inventions involving natural components must be looked at and what exactly should be considered as naturally occurring should be addressed. Additionally, terms like “contrary to public order or morality” or “which causes serious prejudice” need to be clarified as inventions such as bioprinting, which uses stem cells or other biological components, would be deterred due to such vague terminology.
Author : Deshna Jain, a Student at Maharashtra National Law University, Nagpur, in case of any queries please contact/write back to us via email to chhavi@khuranaandkhurana.com or at IIPRD
[1] Organ transplantation in India: needs a bigger push, Lancet Reg Health Southeast Asia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866917/.
[2] https://www.thehindu.com/sci-tech/health/indias-poor-organ-donation-record-continues-to-cost-lives/article67161978.ece#:~:text=According%20to%20the%20Health%20Ministry’s,to%20about%2016%2C041%20in%202022.&text=Vivek%20Kute%2C%20secretary%2C%20Indian%20Society,population%20for%20a%20decade%20now.
[3] Ibid.
[4] Supra n.1.
[5] Ibid.
[6] L’Oréal 3D Prints Human Skin in Partnership With University of Oregon, https://www.3dnatives.com/en/loreal-prints-human-skin-with-university-of-oregon-190320246/#:~:text=To%20effectively%20mimic%20the%20intricate,closely%20resembled%20the%20extracellular%20matrix.
[7] Kačarević, Željka P et al., “An Introduction to 3D Bioprinting: Possibilities, Challenges and Future Aspects,” Materials (Basel, Switzerland), Vol. 11, 2018.
[8] Alex Tyrer-Jones, “Researchers 3d Print New Ultra-Realistic Heart And Lung Models That Can Bleed, Beat, And Breath”, https://3dprintingindustry.com/news/researchers-3d-print-new-ultra-realistic-heart-and-lung-models-that-can-bleed-beat-and-breath-229447/.
[9] Beatrice Bowlby, Icy veins: a new 3D printing method for building artificial blood vessels, https://www.biotechniques.com/news/icy-veins-a-new-3d-printing-method-for-building-artificial-blood vessels/#:~:text=Researchers%20are%20using%20ice%20as,blood%2Dvessel%2Dlike%20structures.
[10] Ibid.
[11] Ibid.
[12] W. P. Pessers, The evolution of the inventiveness requirement. [Thesis, fully internal, Universiteit van Amsterdam], (2015).
[13] 3D Bioprinting patentability challenges in India, https://asiaiplaw.com/section/in-depth/3-d-bioprinting-patentability-challenges-in-india.
[14] Ibid.
