With so many companies developing products related to the microbiome that include live microbes, we were curious about how companies are protecting their intellectual property. Since some of the companies are developing products with bacteria derived from human stool or from other bacteria found in nature, we thought it would be useful to see what strategies they were using in patent applications.

To learn more, we spoke with Bryan Zerhusen at Cantor Colburn LLP. Bryan is an experienced patent attorney working in the life sciences arena. His clients include: solo inventors, academic institutions, foreign law firms, venture firms, as well as companies ranging from start-ups to global corporations in the medical biotechnology, agricultural biotechnology, diagnostic, chemical, pharmaceutical, medical device and healthcare sectors.

Prior to entering into a career as a patent attorney, Bryan worked as a post-doctoral fellow at Case Western Reserve University where he studied the molecular mechanisms underlying cystic fibrosis.  Bryan also worked for a number of years as a research scientist for a genomics company in Connecticut. Bryan earned a J.D. from Quinnipiac University School of Law and a Ph.D. in Cell Physiology and Biophysics at Case Western Reserve University School of Medicine; his undergraduate degree is in zoology from Miami University.

CP:There has been a lot of activity in the area of the human biome. Have you seen a big increase in activity in patent filings and actions around microbiome treatments particularly related to live microbes?

Bryan: I would say over the past couple of years there has been an uptick in this area. It has been around for a while with probiotics and the nutraceutical space. But I think in terms of more rigorous scientific scrutiny leading to potentially patentable inventions it seems to have been on a rise in the last couple of years – particularly in the agricultural, skin and gut areas.

Additionally I have seen more writing in industry blogs, email updates, etc about interest in the microbiome and companies developing novel therapeutics based on microbials.

CP: A number of companies targeting the microbiome are developing products that include live bacteria. If those bacteria are derived from nature or the human gut for example, how can they protect the IP or patent a product that is based on existing bacteria that has not been bioengineered or genetically altered in some way?

Bryan: That's a great question. The typical route would be that the bacteria would be modified genetically in some way. But I have seen patents and we have prosecuted patents that were directed to strains where we have made arguments that the processes for developing the strain results in a markedly different microbe from the naturally occurring bacteria. The standard the patent office generally applies to these things is that if they are markedly different from the natural product, if the answer to that question is yes, then the patentability question is over right there. So when there is a basis for arguing that the product is markedly different from the naturally occurring bacteria then we are seeing some success with those types of claims.

The other avenue that I've seen used successfully relates to claims to microbial formulations. This might include the accompanying reagents included in the formulation. This might also include what has been done to the bacteria to adapt them to the formulation. This might be another possibility for getting claims allowed in view of the 101 issues (this refers to 35 USC 101).

CP: If the patent was based on the first pathway you mentioned, would that provide broad protection against another company developing a product based on the same bacterial strain or strains, or would it simply provide protection against another company using the same process for developing a product based on the same strain.

Bryan: That's another good question. So the product is different from the method. I think generally methods of growing or culturing bacteria fair better than pure composition-of-matter claims. In terms of a therapeutic, the important claims are going to be how you manufacture the therapeutic product and the therapeutic itself. So having claims drawn to as many aspects as possiblegives you the best overall protection. And in terms of scope of any particular claim, you are probably, based on the current climate with 101, going to get broader protection around method types of claims than composition.

Regarding method steps, there have been a couple of Federal Circuit cases that have made it a little more difficult on examiners to dismiss those methods out of hand as being well understood and conventional types of activity. It is now required that examiners view those steps more inclusively as whole – looking at the entire process. And whether or not those steps were applied in this context. And in order to raise those types of rejections, the patent office and the Fed Circuit now requires that the examiners provide some evidence in the record. So there is some recent case law has been more favorable to applicants.

CP: So the cases were in the Federal Circuit?

Bryan: Yes, the Federal Circuit Court of Appeals is the key appellate court for patent cases. They have exclusive jurisdiction over patent appeals. The US Supreme Court frequently weighs in also, but when the Fed Circuit weighs in on these types of matters, particularly when they apply to patent prosecution at the level of the USPTO (US Patent and Trademark Office), it is binding authority for the examiners.

The name of one case in particular is Berkheimer V. HP. It was earlier in 2018. This  case clarified the evidentiary standard for a challenge on the basis of patent eligibility. And subsequently a guidance document went out to the examining core clarifying and raising the evidentiary requirement for supporting a rejection based on what is considered, quote, well understood routine and conventional activity. Examiners cannot merely rely on their own experience or nebulous knowledge of skill in the art. So raising the evidentiary bar makes it a little more difficult for examiners to raise rejections and is more helpful in the end to applicants because now the examiner has to provide evidence in the record.

CP: That actually addressed one question I had - what are some of the recent landmark cases that might affect patents around these types of products.

Bryan: Berkeimer is definitely one to take a look at. There is another case from 2016, Rapid Litigation Management Ltd. v. CellzDirect, which was also a Fed Circuit case. As I mentioned when the Fed Circuit weighs in, particularly on subject matter eligibility, which had been in flux since the Mayo and Alice cases, everyone pays close attention. There has been a lot of inconsistent application of the law at the level of the patent office. So when the Fed Circuit weighs in and tries to clarify some of these issues it has generally been very helpful.

The CellzDirect case clarified what the standard is for assessing method steps in a process. It really goes to emphasizing that all of the method steps have to be viewed as a whole in considering what the objective of the claim concept is. This is in contrast to myopically looking at each limitation and saying “it was known to freeze cells and thaw cells”. You have to look at it from a higher elevation to see exactly what the invention is and whether it is truly something that is routine or if it is something that is new and worthy of patent protection.

CP: Are there any guidelines or specifics that a layman might want to keep in mind or look for when assessing the value of a patent?

Bryan: In particular, when assessing the value of 101 and eligibility, it is important to have an understanding of and take into due consideration whether the claim is drawn to natural phenomena or naturally occurring product, and what sorts of other limitations are included in the claim, if any, that help better define those concepts in order to assess the strength of the patents.

For a layman that might not be an easy task because it does require an understanding of the legal principles involved in claim construction. It's not something that I would necessarily recommend that a layman take on. But form a high level you could look at the claims and ask is this something that could preempt a natural law or a naturally occurring product just as a course filter to help assess if a patent might have issues. The best course would always be to retain the services of a professional. This is especially true if we are talking about an assessment for purposes of investment.

CP: With reference to a couple of recently issued patents, 9,962,413 and 10,022,406 – looking them over as a layman, they seem overly broad, but this might simply be because I don't have the experience or knowledge to make a reasonable assessment.

Bryan: Without delving into the filing history, what jumps out at me are a couple of potential rationales for why these claims were allowed. In one instance it looked like a formulation. What was probably going on there is that the applicant was likely presenting a case to the examiner that what is being claimed is markedly different from the naturally occurring bacteria because it's been filtered or refined or formulated with other reagents. That is one possible argument that could have been made. The claim adds significantly more so it is not preempting the material that exists in nature. We have successfully made these sorts of arguments for probiotics.

The other case is a method claim - this is in reference to the '413 patent. The method claims some specific steps that I think they were successful in arguing that this was significantly more than just the conventional, routine and well-understood activity. Cases like CellzDirect and Berkheimer clarify how examiners have to view method steps in the context of the entire claim. And they impose more stringent evidentiary requirements when raising rejections.

CP:  In reference to the '413 patent the first claim says “A method comprising: receiving a stool sample from a healthy donor at a central location, wherein the donor has been prescreened for infectious agents; placing the stool sample within a stool collection device; mixing the stool sample with a liquid to form a mixture, wherein the liquid comprises a buffer and a cryoprotectant; homogenizing and filtering the mixture to separate fiber from bacteria and produce a filtrate comprising a substantially entire microbiota of the stool sample. “

To a layman that does not necessarily sound like a unique process. Would this patent mean that other companies will no longer be allowed to develop products using that process.

Bryan: If there is an example in the art of someone actually using this method prior to the filing date then these claims would have validity issues. And if there exists somewhere in the universe a publication describing that or even makes it obvious, then this claim could be vulnerable on that basis. Subject matter eligibility is just one of the hurdles that a patent applicant has to overcome. Looming in the background is always the prior art issue of anticipation. If technically novel, that is novel per se, it could still be obvious in view of one or a combination of references or information including what would be known to a person of ordinary skill in the art.

So just because these claims got through examination and were granted doesn't necessarily mean that they are valid. That would have to be tested through enforcement or other avenues. This might include inter partes review at the level of the USPTO. This can allow one to stress test a patent's claims to see if they pass muster. The USPTO does a pretty good job of prior art searching during examination but they don't necessarily catch everything.

When a patent is granted, it is true that you now have an enforceable right to exclude others from practicing that method or a method that is not substantially different but that exclusive right is always subject to the potential challenge that might occur during litigation. The bottom line being that if someone felt like they had been practicing this method for years and they had evidence of that then it would difficult to enforce this patent. Or if it were enforced then it would be invalidated on that basis.

CP: So as an example, suppose someone discussed in a study that they received stool from a donor, added a buffer with a cryoprotectant and filtered it. Would that invalidate the entire patent or would you go down the list of 31 claims and the applicant would continue to have protection for the more specific claims?

Bryan: The validity would be on a claim-by-claim basis. So maybe the initial claim might be invalid based on prior art but going down the list if there is a claim that adds additional elements that could survive a challenge and still support a claim of infringement that could still cause problems for an alleged infringer.

In some cases it is not uncommon that a patent owner might sue on some claims but not others – realizing that some claims might be more vulnerable than others. And perhaps only suing on as many claims as they need to cover what a potential infringer is doing without risking broad claims. The caveat to broad claims is that they are always more vulnerable to a challenge than narrow claims.

CP: That covers the questions that we have. Is there anything you would like to add that might help a layman in evaluating these types of patents, particularly those that involve live microbes?

Bryan: I think the best advice for a layman is to not try to evaluate patents on your own. There are a lot of factors to consider. These include recent changes in case law and changes in procedure at the US patent office aside from the enforcement issues. So even for the person that understands the science, it is difficult to understand all of the legal pitfalls. I think you can still do your coarse filter evaluation of the technology, but before you jump in, make sure you have a legal professional review the patent and provide their opinion.