3D Bioprinting and Biologics: A Look at Patent and FDA Market Exclusivity Strategies

Co-Authored by: Jeff Vockrodt  and Paul Gadiock 

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The industrialization of 3D printing opens the possibility of making products efficiently with complex structure previously thought impossible or impractical using the tools of the first industrial revolution. Early industrial applications of 3D printed metal parts lowered the weight and reduced the number of components for highly engineered components, such as jet aircraft engine parts. As innovators seek to increase applications, much effort has been underway to expand available materials to include biopolymers and even tissue or cells. 

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3D bioprinting employs 3D printing and similar techniques to combine cells, growth factors, and biocompatible materials to fabricate products that mimic natural materials such as printed bone, skin, arteries, and even whole organs. The promise of 3D bioprinting is to leverage the computer-controlled, layer-by-layer additive process of 3D printing to selectively deposit cells to build complex living tissues that can be used in patients. Because the cells can come from the patient, there would be no need for organ donors, and lessened risk of transplant rejection.    

Bringing these 3D bioprinted products to market will require significant investment in order to gain marketing approval from the Food & Drug Administration (FDA). The question immediately arises as to whether innovators in 3D bioprinting will be able to leverage enough patent and FDA marketing exclusivity to make their investment worthwhile. Both (1) the type of patents available and (2) the regulatory pathway chosen will determine the amount of exclusivity available for first movers. 

Patents for 3D Bioprinting

Patents generally provide their owner with a right to exclude others for a limited time period from making, using, offering to sell, or selling the patented invention. 

The scope of what the patent covers is determined by (1) the category of the patent claim being made (e.g., product, the method of using, or method of making), and (2) the breadth of the claim language. To obtain a patent an invention must be new, non-obvious, and directed to the patent-eligible subject matter. 

Printing organs will require new printing techniques and materials. The initial patents found in 3D bioprinting will likely focus on these technologies. One of the main challenges for these kinds of pioneering patents is that they will likely be at or near expiry by the time 3D bioprinted products become available. This happened with other 3D printing technologies and commonly occurs with pioneering patents particularly where a patent term of 20 years is linked to the filing date. A repeat of the early 3D printing patent wars is less likely in the bioprinting space where the safe harbor provisions of 35 U.S.C. 271(e) may shield those practicing the technologies in order to gain FDA approval of 3D bioprinted products.

As the time for regulatory submission and approval approach, 3D bioprinters will likely file more patents directed to the products for which approval is sought. In general, product claims offer the patent owner a broader scope of protection relative to method claims. This is because a product claim can only be avoided by changing the product itself, whereas method claims can often be avoided by using the product differently or making it differently. The complexity of 3D bioprinted products will likely provide many avenues for patenting. 

The patent portfolios of companies who bring these products to market will likely be large, similar to those found for currently approved biologic products. For example, Abbvie has amassed over 100 patents covering its Humira product. The portfolios would likely include claims to the 3D bioprinted products themselves. These product claims would need to include features that distinguish the claimed subject matter from the prior art, which may present a challenge. Another hurdle for product claims is that they are often filed at an earlier stage of technological development, and may expire before products make it to market.  

Aside from patent claims to the products, 3D bioprinting patents will likely also be granted on intermediate products, processes of making (harvesting cells, using cells in bioprinting, constructing organs and tissue from the cells), growth factors and other products used in the manufacturing process. Because 3D printing and bioprinting fundamentally relate to new methods of making, patents directed to various aspects of the process itself may be the most straight forward to obtain. These patents related to the process of 3D bioprinting will likely make up the bulk of patent portfolios covering 3D bioprinted products.  

Regulatory Pathway and Exclusivity for 3D Bioprinting

The FDA has already acknowledged that bioprinting is on the horizon and that a policy framework is needed to help ensure regulatory consistency and predictability. There are generally three categories of medical products that are regulated by FDA―devices, drugs, and biologics―each with their own range of pathways to market. How a medical product is categorized will dictate the group within the FDA that governs the bioprinted product under its authority: 

Pathway Responsibility within the FDA
Medical Device Center for Devices and Radiological Health
Drug Center for Drug Evaluation & Research
Biologic Center for Biologics Evaluation & Research

Further, bioprinted medical products that share a device, drug, and biologic attributes, so-called “combination products,” can blur the lines between FDA regulatory categories. In these scenarios, the FDA’s Office of Combination Products determines the product’s “primary mode of action” and, in turn, the FDA Center that will have primary jurisdiction over the bioprinted medical product. The determination of the primary mode of action typically has a significant impact because each category of medical products is afforded its own regulatory paradigm, some of which are far more demanding than others. 

There has been some debate about whether a 3D bioprinted product would be a medical device, a drug, or a biologic product. Because a 3D bioprinted organ would be implanted into a patient during use, it has led some to believe that it could be regulated as a medical device, similar to a pacemaker. In fact, the FDA has been promoting the development of an artificial pancreas device system; however, the agency has been keen to point out it does not consider products that involve biomaterial, synthetic or artificial tissue or organs to meet this definition. Seeing as how the definition of a medical device requires that it “does not achieve its primary intended purpose through chemical action within or on the body of a man . . . .,” some have argued a device classification for bioprinted products as being unlikely. 

More likely, 3D bioprinted products will be deemed either drugs or biologics and regulated as such. FDA regulations define the term “drug,” in part, by reference to its intended use, as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.” Notably, the definition of a drug is very similar to the definition of a device, less the qualifier that it does not achieve its primary intended purpose through chemical action within or on the body. 

By implication, drugs can be expected to achieve their primary intended purpose through chemical action. The FDA interprets that a product exhibits “chemical action” if it interacts at the molecular level with bodily components (e.g., cells or tissues) to mediate (including promoting or inhibiting) a bodily response. Under this interpretation, it is apparent that FDA can expect drugs to operate at a molecular level. Contrast that characteristic with cells and tissues that are regulated by FDA as biologics.

Human cells or tissues intended for implantation, transplantation, infusion, or transfer into a human recipient are regulated by FDA as biologics. Examples of these types of products include bone, skin, corneas, ligaments, tendons, dura mater, heart valves. Based on the definition and examples, it is evident that these products are on a different physical scale than the drugs previously described. However, though finished bioprinted products would seem more akin to tissues, the scale on which the product is actually bioprinted may ultimately decide the category in which the medical product will fall. Suffice it to say that FDA’s current regulatory paradigm does not specifically contemplate bioprinted medical products. Legislation may be required to resolve whether the technology would be a drug or biologic, and the consequent patent implications that flow from that decision.

The Intersection of Regulatory and Patents for 3D Bioprinting

The Hatch-Waxman Act governs the process for FDA approval of generics for products regulated as drugs. One aspect of Hatch-Waxman is that it links FDA approval of a generic to product and method of therapeutic use patents, which are listed in the orange book for each approved product. The existence of orange book patents for a new chemical entity drug can nearly guarantee an additional 2.5 years of market exclusivity on top of the 5 years granted for a new chemical entity, for 7.5 years total. That period may be further extended based on a patent term extension for up to an additional five years for one of the orange book patents. 

Hatch-Waxman’s patent linkage leads to a clear preference for product and method of therapeutic use patent for drugs. This allows the patent owner of a drug product bring an infringement lawsuit while lessening the prospect that the generic competitor would launch its generic product “at risk,” meaning while the patent dispute has not been resolved. Because the bulk of a patent portfolio for 3D bioprinting will likely relate to aspects of the bioprinting process itself as discussed above, many of those patents would not be in the orange book. This could make regulation of 3D bioprinted products as drugs less desirable from a patent owner’s perspective.  

No such patent linkage exists for biologics and biosimilars, which are regulated under the Biologics Price Competition and Innovation Act (BPCIA) enacted in 2010. Instead of tying the exclusivity to particular patents and extending marketing exclusivity based on the listed patent, approved biologics receive 12 years of market exclusivity regardless of the patent situation. There is no equivalent of the orange book for biologics. Instead, patent owners and biosimilar applicants can engage in a “patent dance” to narrow down the number of patents involved in pre-launch litigation. Unlike Hatch-Waxman litigation for drugs which are limited to product and therapeutic use patents, biosimilars litigation under the BPCIA often involves all kinds of patents, including a method of making patents. This could make the biosimilar regulatory pathway more desirable than the drug pathway for 3D bioprinting patent owners. 

While there is some uncertainty as to how the FDA will regulate 3D bioprinting, the character of these products suggests that assuming no new category of regulation is created, they are likely to be regulated as biologics. The lessons learned from BPCIA litigation is likely relevant for 3D bioprinting. While BPCIA litigation is relatively new, we know that obtaining a large patent portfolio surrounding important products has been important for branded biologics manufacturers. This suggests 3D bioprinters should actively seek to patent all aspects of their 3D bioprinting processes. 

 

About the Authors:

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Jeff Vockrodt advises companies on patent matters involving chemical and life science technologies, including pharmaceutical, medical device, and biotechnology inventions. Jeff has overseen the preparation and prosecution of hundreds of patent applications involving a wide range of technologies, including additive manufacturing and biopharmaceutical patents. Jeff has served as lead counsel in inter partes review (IPR) proceedings before the Patent Trial and Appeal Board (PTAB). Jeff is a registered patent attorney with a chemical engineering background. He served for four years as patent examiner before the United States Patent and Trademark Office and a law clerk in the US International Trade Commission before entering private practice. He is currently a partner at Arent Fox LLP and adjunct professor teaching IP, Regulation & Compliance for Biotechnology at Katz Business School, Yeshiva University.  

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Paul Gadiock is a is a Senior Attorney in Arent Fox’s Life Sciences group where he provides premarket and postmarket regulatory solutions on a variety of subject matters for medical product clients. Paul regularly counsels on conventional medical products as well as transformative technologies including digital health, 3D printed products, and regenerative therapies. As a former policy director at FDA and business development leader at a national biotechnology company, he brings unique first-hand experience with the development and application of regulatory programs to benefit clients at all stages of the medical product life cycle. Paul speaks frequently at industry conferences and writes articles and legal alerts on cutting-edge topics concerning the life sciences sector. 

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