Gut check: Microbiome patent update

June 26, 2017

Patent Alert

Author(s): Mark James FitzGerald, Ph.D., David S. Resnick

Despite challenges imposed by U.S. patent law regarding naturally occurring organisms and their products, patents relating to the microbiome and microbiome-based therapeutics are issuing from the U.S. Patent and Trademark Office. Issues encountered and the strategies used to overcome them are illustrated by the following selected examples of recently issued patent claims.

U.S. Patent 9,662,381

  • Issued: May 30, 2017
  • Titled: Composition for inducing proliferation or accumulation of regulatory T cells
  • Assignee: The University of Tokyo (Tokyo, Japan)

Claim of interest:

  1. A method of treating a human subject having an infectious disease, an autoimmune disease or an allergic disease, the method comprising administering to the subject a pharmaceutical composition comprising a spore-forming fraction of human fecal matter, wherein the composition induces proliferation and/or accumulation of regulatory T cells, and wherein the composition is formulated for oral administration.

This claim is noted for its broad recitation of indications, including infectious disease, autoimmune disease and allergic disease, as well as for the lack of reference to any specific fecal microbes, and the reliance on functional characteristics: spore-forming ability and the induction of Treg cells to define the microbes involved. The data provided in the Examples include those showing an increase in colonic Treg cells in germ-free mice, with and without administration of a chloroform-treated (spore-forming) fraction of human fecal matter.

The application leading to this patent was prosecuted under the Track One accelerated examination procedure.

U.S. Patent 9,655,839

  • Issued: May 23, 2017
  • Titled: “Probiotic arginolytic oral compositions and methods of making and using probiotic arginolytic oral compositions”
  • Assignee: The University of Florida Research Foundation (Gainesville, FL)

Claim of interest:

  1. A method for making a mixture of arginolytic bacterial strains for oral use, the method comprising: (a) obtaining a mixture of bacterial strains isolated from oral samples; (b) isolating and identifying arginolytic bacterial strains capable of producing ammonia via the arginine deiminase system (ADS); (c) conducting one or more separate assays to identify arginolytic bacterial strains capable of expressing ADS activity in at least one of the following assay conditions: in the absence of environmental arginine, in the presence of glucose, in a non-acidic pH, in aerobic conditions, and in the presence of at least one bacterial strain associated with dental caries; (d) selecting at least two different isolated arginolytic bacterial strains identified in step (c) to prepare a mixture of arginolytic bacteria; and (e) preparing a mixture of the at least two isolated arginolytic bacterial strains, wherein the mixture expresses ADS activity in at least two of the conditions, and wherein the mixture does not include any strains of Streptococcus mutans.

This method claim is of interest because, apart from requiring that the strains be isolated from oral samples and not include Streptococcus mutans strains, it defines the appropriate bacterial strains in functional terms only, based on their ability to produce ammonia via the ADS system under different specified conditions. The specification includes a description of the identification and characterization of more than 50 ADS-positive strains. Composition claims drawn to combinations of two or more arginolytic bacterial strains faced rejection for lack of patent-eligible subject matter and were cancelled to permit the method claims to issue.

U.S. Patent 9,642,881

  • Issued: May 9, 2017
  • Titled: “Human-derived bacteria that induce proliferation or accumulation of regulatory T cells”
  • Assignee: The University of Tokyo (Tokyo, Japan)

Claim of interest:

  1. A pharmaceutical composition comprising a purified bacterial mixture consisting of bacteria comprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42.

This composition claim is narrow in using “consisting of” language to specify the bacteria involved—each of the subject bacteria must be present to satisfy the claim—but remarkably broad in reciting the bacterial species only in terms of having 16S rDNA of at least 95% sequence homology—not identity—to the 16S rDNA sequences specified. The therapeutic indication is also very broad, encompassing any autoimmune disease. No patent-eligible subject matter issue was raised during prosecution.

A parallel application issued May 16 as U.S. Patent 9,642,881, with method claims broadly reciting “a method of treating an autoimmune disease” by administering a pharmaceutical composition defined exactly as in the composition claim above.

Both applications were prosecuted under the Track One prioritized examination procedure and had very few statements characterizing the invention on the part of the applicant or the Patent Office.

U.S. Patent 9,649,328

  • Issued: May 16, 2017
  • Titled: “Association of beta-glucans and arabinoxylans”
  • Assignee: General Biscuit (Clamart, FR)

Claim of interest:

  1. A method of improving the microbiota balance in human gut and digestive health in a subject, the method comprising administering to the subject an effective amount of a first cereal comprising high beta-glucan barley flour and a second cereal comprising wheat, wherein the ratio of beta-glucans in the first cereal to arabinoxylans in the second cereal is from 1:1 to 4:1.

This method claim is of interest, in part for the broadly stated indication of “improving the microbiota balance in human gut and digestive health,” but also for doing so by administering two prebiotic cereals with a specified ratio of beta-glucans in the first cereal to arabinoxylans in the second. An in vitro “Simulator of the Human Intestinal Microbial Ecosystem” was used to generate data regarding probiotic index for various compositions. Composition claims reciting a biscuit were under a prior art rejection at the time they were cancelled to permit the method claims to issue.

Among other things, these recently issued microbiome-related patents again demonstrate the benefits of using the Track One accelerated examination procedure to quickly secure patent coverage with a minimal prosecution record. Other aspects illustrated by these claims include:

  • Under certain circumstances, breadth can be secured through recitation of 16S rDNA sequence homology;
  • Functional, as opposed to structural limitations, are being accepted to define the microbes involved; and
  • Reasonable composition claims continue to issue, but allowance of several of the patents noted here resulted from the cancellation of rejected composition claims in favor of methods reciting the use of similar compositions.

The foregoing has been prepared for the general information of clients and friends of the firm. It is not meant to provide legal advice with respect to any specific matter and should not be acted upon without professional counsel. If you have any questions or require any further information regarding these or other related matters, please contact your regular Nixon Peabody LLP representative. This material may be considered advertising under certain rules of professional conduct.

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