[authors Nicholas Vincent* and Anthony D. Sabatelli**]
As we have discussed in previous installments of "The Emergent Microbiome," we have seen a distinct growth in the interest of the microbial communities found in our environment beyond the confines of the human body. Earlier articles in this series have focused on the microbiology of the built environment (see "Part VII, The Microbiology of the Built Environment") and the microbial communities of plants that have been characterized and manipulated to maximize their growth and crop yield (see "Part XI: Agriculture and the Microbiome"). In both circumstances, we noted robust intellectual property activity. Likewise, we have also observed an increased interest in the microbial communities found in livestock animals, and how manipulations of these communities could result in more effective, productive, and sustainable means of food production. Although this area is less well developed than other areas of microbiome research, including that of plant agriculture, we see it as a promising area of development in terms of both the science and the innovation that will inevitably flow from it.
Antibiotics and Livestock Microbiomes
Antibiotics have played a central role in the treatment of bacterial infections and disease and the reduction of associated deaths, yet, according to the United States Food and Drug Administration (FDA), use in humans constitutes a mere 20% of total usage. The remaining 80% is devoted to increasing the productivity of livestock: animals fed antibiotics grow faster and larger than their counterparts that are not fed antibiotics. Importantly, antibiotics have been shown to elicit changes in the bacterial communities that live within the confines of the digestive tracts of both humans and livestock animals. In fact, it is even possible that these changes in microbial communities are what cause the larger growth seen in antibiotic-fed animals. In addition to these changes, however, there are serious concerns over the effects that such antibiotic usage can have, including unintended ingestion by humans and the risk for increased bacterial resistance to antibiotics, and, as a result, resistant strains that can no longer be combatted with any known antibiotics.
Antibiotics are not the only agent responsible for changes in livestock microbiomes; changes in dietary content have also been shown to affect the microbiome population distribution of livestock animals. Taken together, these areas have seen increased research and increased intellectual property activity, which, we believe, will continue to expand in the coming years. In particular, we have observed an interest in modulating the dietary intake of livestock animals with the aims of subsequently modifying their microbiomes (Appendix A).
Intellectual Property Challenges
As we have discussed more extensively in earlier installments of this series (see "Part XI: Agriculture and the Microbiome"), there have historically been challenges related to the patenting of naturally occurring bacterial communities and inoculants. The basis for these challenges is rooted in 35 U.S.C. § 101, which states three judicial exceptions that are not patent-eligible: laws of nature, natural phenomena, and abstract ideas. In the landmark case Funk Brothers Seed Co. v. Kalo Inoculant Co., (1948), the Supreme Court held that the use of naturally occurring bacterial species, or combinations of these species, could not be patented since the inoculant amounted to a naturally occurring product, and was therefore considered a judicial exception under 35 U.S.C. § 101. In the area of livestock and the microbiome, we have noticed an interest in attempts to modulate the diets of livestock animals with the end goal of modifying their microbiome, either to prevent disease or to improve growth, without the use of antibiotics. As a result, we do believe that there is a path to patent-eligible advancements in this space, particularly if the patent claims are carefully crafted to distinguish themselves from Funk Bros. and those of more recent cases on subject matter eligibility.
Recent Developments and Future Paths
The desire to manipulate livestock microbiomes is strong with clear benefits to food production. Although livestock microbiome research and business efforts are not as developed as those in the agriculture sector, it does not mean that corresponding growth will not occur in this space. In fact, we expect that researchers and innovators in this space will look towards the advancements made in the area of plant agriculture, as well as human microbiome research, as guidance to the further development of advancements.
Some recent examples of patents and applications in this space are provided in Appendix A. In particular, WO 2017/083520 A1 (Animal therapeutic and feed compositions and methods of use) concentrates on modulating the host microbiome through the use of oligosaccharide compounds added to feed. Additionally, US 2017/0072002 A1 (Combination, composition, and method of administering the combination or composition to animals) seeks to use plant extracts to modulate the microbiome in livestock hosts with the aim of treating disease or increasing overall productivity and production. As previously discussed, these efforts are focusing on attempts to modulate the microbiome through feedstock changes, not through the addition of bacterial strains or inoculants.
There have, however, been attempts to modify livestock microbiomes through the introduction of live bacteria. One new startup company of note, Bactana, is seeking to modulate the microbiome of livestock animals through the introduction of Faecalibacterium prausnitzii, which is a naturally occurring bacterium that has been found preferentially in the digestive tracts of healthy calves (see Appendix A: US9700586B2, Probiotic compositions and methods). Trials have revealed a 13% increase in weight gain in animals that have been colonized with F. prausnitzii, suggesting a promising, antibiotic-free method of weight gain for livestock.
In order to progress, livestock microbiomes will need to be characterized further, thereby establishing an understanding of how microbiomes are established and persist in these animals. While basic microbiome communities have been investigated in cattle, chicken, and swine, there has yet to be a synthesizing effort similar to the Human Microbiome Project. In particular, it will also be important to see precisely how different antibiotic cocktails modulate the microbiomes of these animals and how those changes may be directly linked to the weight gain that many meat producers focus on so heavily. Some work has already been done in this area, but it has lagged behind that of human microbiome research.
A Path Forward
Modulating the microbiome of livestock is a very exciting area that we expect will expand rapidly in the coming years. As research into the human microbiome and microbial communities around us expands, we expect to see a corresponding increase in both the basic science surrounding livestock microbiome research as well as the desire to innovate novel methods of modulating microbial communities in these animals with the specific aim of increasing production without relying on antibiotics.
* Nicholas Vincent is a Technology Specialist at Dilworth IP
** Dr. Sabatelli is a Partner with Dilworth IP
