Written by Daniel K. Yarbrough, Ph.D. and Jing Liu, Ph.D.
Once considered parasites, free riders, or “opportunistic pathogens,” in recent years the roughly 100 trillion symbiotic bacteria that inhabit the various tissues of the human body have been increasingly recognized for their importance in maintaining human health. While development of probiotics to enhance oral and gastrointestinal health provided initial steps into the world of microbiome-focused medicine, the field has continued to grow, as researchers and inventors are moving microbiome-focused therapies forward to explore a vastly larger number of indications. For example, the past year alone has seen patents issued in the U.S. claiming probiotic approaches to treat allergy, heart diseases, skin disorders, and neurological disorders, as well as animal health applications. Synthetic probiotics are also being developed, utilizing engineered microorganisms in the hope that they will be able to insinuate themselves into the normal flora and deliver useful molecules ranging from necessary metabolites to sunscreens. As well, efforts to utilize our understanding of the fungal microbiome are emerging alongside our growing ability to manipulate our cohabiting bacteria. Finally, as our knowledge of the relationships between the microbiome and disease states grows, microbiome-focused diagnostic devices and methods are beginning to rise. Here, we will mention a few intellectual property issues that are particularly relevant to innovation in the probiotic space. The following are three things that inventors may wish to keep in mind as they seek to leverage the power of our internal ecosystems.
As exciting as the prospects for development in this field are, the IP landscape surrounding probiotics hold a number of traps for the unwary. For example, inventors seeking patent protection on inventions involving probiotic microorganisms need to be careful of two areas: the requirements for written description and enablement under 35 U.S.C. §112, and the changing world of patentable subject matter under 35 U.S.C. §101. Section 112 requires, among other things, that the patent specification must describe the invention in such detail that ordinary practitioners in the field would not only recognize that the inventors had created the organism or composition, but that those same practitioners, having read the patent, would also be capable of making or using the invention themselves. Inventions drawn to microorganisms, such as probiotic strains and compositions, can face a more challenging analysis under section 112 than non-living inventions. This is based on the difficulty of adequately describing replicable ways in which a unique strain can be obtained. In cases involving microorganisms, the requirements of section 112 can most easily be met by depositing a sample of the organism with a suitable repository, such as the American Type Culture Collection (ATCC). (1) Such deposits can be avoided, however, if the strains are described in such a way that they could be isolated by one of ordinary skill without undue experimentation. (2) In the demanding case of microorganisms, these descriptions should include any features by which a skilled artisan would be able to uniquely identify or obtain the organism-- possibly including such items as, gene sequences, metabolic idiosyncrasies, methods of isolation, and/or the presence of synthetic plasmids, among others. Because deposit is not always required (or desirable), each individual invention encompassing a probiotic organism should be carefully evaluated in order to determine the best path forward.
Whether or not an invention drawn to a probiotic even constitutes patentable subject matter provides another concern, requiring careful analysis and skillful claim drafting. 35 U.S.C. §101 states that patents can be obtained for, “any new and useful process, machine, manufacture, or composition of matter,” but the Supreme Court has found a number of exceptions over the years, barring patenting of “abstract ideas,” “laws of nature,” and “products of nature.” Notably (especially within the microbiome space), one of the most significant cases finding an invention to be unpatentable under the so-called “product of nature” exception directly involved a combination of bacterial strains (the Supreme Court determined that a combination of bacterial strains was unpatentable because the combination did nothing more than each of the strains could do individually). (3) Recently, the Supreme Court has held that inventions that are identical to naturally occurring products are similarly unpatentable. (4) However, these rulings are not a blanket ban on patenting bacterial strains, combinations, and their uses. In the case of probiotic strains, the possibility of using an isolated strain in a new way, incorporating the strain into a novel method, demonstrating a novel activity, or incorporating novel genes or prebiotic compounds each has some potential as a means of rendering a probiotic-related invention patentable. Certainly the existence of numerous recently-issued patents (5) drawn to probiotics suggests that the hurdles presented by the patent statute and the courts are not insurmountable, but innovators in this space should certainly be aware of these potential issues.
Finally, probiotics also present some unique difficulties in patent enforcement. The Supreme Court has ruled that growing and reproducing a patented organism can constitute infringement of the underlying patent, (6) but identifying infringement in this space can be difficult, especially given relative ease with which a competitor might culture the underlying organism. Assiduous monitoring of competitors and market entrants is a must. Additionally, careful crafting of licenses, possibly including end-user license agreements, can provide additional avenues for enforcement. Beyond the patent sphere, some success has also been found in pursuing trademark protection for the names of specific strains, (7) an approach which offers leverage to develop a brand strategy to attract consumers and deter competitors. For those probiotics that are intended to treat specific diseases or conditions and will thus be subject to the FDA regulatory process, the possibility of data exclusivity remains, though it is not yet clear how, or even whether, this exclusivity would apply to a live biotherapeutic product.
Protecting IP rights in probiotics and microbiome-focused technologies has unique features that provide a twist on standard pharmaceutical and biotechnology patent practice. However, IP law has tools that can be used to craft protection strategies for this burgeoning field of discovery. Inventors working closely with creative patent counsel should be well positioned to take advantage of these tools to help realize the substantial promise of these technologies.
(1) See In re Argoudelis, 434 f .2d 1390, 1392 (CCPA 1970), See also Manual of Patent Examining Procedure §2164.06(a)(II) (Examples of enablement issues- Microorganisms) and §2400 (Deposit rules).
(2) See 37 C.F.R. §1.802(b) (“Biological material need not be deposited, inter alia, if it is known and readily available to the public or can be made or isolated without undue experimentation.”)
(3) Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948)
(4) See Association for Molecular Pathology v. Myriad Genetics, Inc.133 S.Ct. 2107 (2013)
(5) See, for example, U.S. Pat. No. 9,492,487 (“Microbial product containing multiple microorganisms”); U.S. 9,480,276, “Dry food product containing live probiotic”); or U.S. 9,314,489 (“Bacterium for use as a probiotic for nutritional and medical applications “)
(6) See Bowman v. Monsanto Co., 133 S.Ct. 1761 (2013), holding that planting of patented soybeans was an unauthorized “making” that infringed Monsanto’s patent rights.
(7) For example, “Bifidus regularis” is a trademarked name owned by Compagnie Gervais Danone, S.A.F. (U.S. Trademark Reg. No. 3641245) for Bifidobacterium animalis strain DN 173 010.