DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Receipt of Arguments/Remarks filed on 1/30/2026 is acknowledged. Claim 21 was amended. New claim 22 was added. Claims 2-8, 11-19, and 21-22 are pending. Claims 11-19 are withdrawn.
New and modified rejections necessitated by amendment
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 2-8 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Possemiers et al., US 2019/0015465 A1 in view of Yuille et al., WO 2019/211469 and as evidenced by Ungvarsky et al., “Enteral administration” EBSCO.
Regarding claim 21, the limitation “for an antibiotic inducing imbalance of gut microbiota in vivo” is an intended use of the claimed product that does not limit the product structurally, and any composition having this same structure is capable of performing the intended use. Further, Possemiers teaches probiotic compositions for treating antibiotic-induced gastrointestinal disorders in vivo by restoring the gut microbial community (Possemiers pp. 12-13 para. 123-124; p. 15 Ex. 3). The composition includes the bacteria Faecalibacterium prausnitzii, Roseburia hominis, and Anaerostipes caccae (Possemiers p. 2 para. 12 and p. 13 para. 124; p. 15 Ex. 3). Possemiers teaches that the composition further comprises a prebiotic (Possemiers p. 2 para. 18). Possemiers teaches that the composition can be formulated as a tablet, capsule or powder (Possemiers p. 8 para. 85).
Regarding claims 2-5, Possemiers teaches compositions comprising Eubacterium limosum, labeled as isolate 17 in the table on p. 10 of Possemiers reference, and present in compositions M4-B, M6-C, M7-C, M8-A, M8-C, and M9-A as shown in the table on p. 11 of Possemiers (Possemiers pp. 10-11 para. 106-108).
Regarding claim 6, Possemiers teaches that the composition further comprises Enterococcus faecium (Possemiers p. 15 para. 149).
Regarding claim 7, Possemiers teaches that the composition is used to treat an
antibiotic-induced gastrointestinal disorder (Possemiers pp. 12-13 para. 123-124).
Regarding claim 8, Possemiers teaches that the composition is a probiotic (Possemiers p. 8 para. 82-83).
Regarding claim 22, “enteral administration” refers to delivery of food or medicine directly to the GI system, for example via oral or rectal administration (see Ungvarsky para. 1). Possemiers teaches that the pharmaceutical composition is formulated either as a rectally administrated form or an orally ingestible form, i.e. for enteral administration (Possemiers p. 3 para. 22-23).
Possemiers does not teach that the composition comprises Roseburia faecis, Roseburia intestinalis, or Anaerostipes rhamnosivorans as recited in claim 21.
Regarding claim 21, Yuille teaches in vitro compositions for a simulated intestinal environment (Yuille p. 5 lines 14-15). Yuille teaches that the bacterial population of the composition may include Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, and Anaerostipes rhamnosivorans (Yuille p. 6 lines 10-24). Yuille teaches that the simulated intestinal composition comprising the bacteria is formulated in a liquid form, i.e. a liquid medium (Yuille p. 4 para. 9-13).
The limitation “for an antibiotic inducing imbalance of gut microbiota in vivo” is an intended use of the claimed product that does not limit the product structurally. However, it is additionally noted that Yuille teaches that accurate predictions of in vivo metabolic activity can be made in a simulated intestinal environment comprising far fewer species of organisms than were conventionally thought to be required for such assessments to be made (Yuille p. 4 lines 15-25).
Regarding claims 2-5, Yuille teaches that the composition additionally comprises Eubacterium limosum (Yuille p. 6 lines 10-24).
Regarding claim 6, Yuille teaches that the composition additionally comprises Lactobacillus salivarius (Yuille p. 6 lines 10-24).
It would have been obvious to a skilled artisan, before the effective filing date, to combine the teachings of these references, arriving at a composition comprising Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, and Anaerostipes rhamnosivorans; and a prebiotic. Possemiers teaches a composition comprising three of the strains, Faecalibacterium prausnitzii, Roseburia hominis, and Anaerostipes caccae, in addition to a prebiotic. While Possemiers does not teach all of the specific bacterial species, it is noted that Possemiers teaches bacteria from all of the genera recited in claim 21, i.e. Faecalibacterium, Roseburia, and Anaerostipes. Yuille teaches a composition comprising all the claimed bacterial species. It would have been obvious to a skilled artisan that a composition as taught by Possemiers could be modified with additional bacterial strains of the same genera, which are also associated with the human intestinal environment, to arrive at a composition comprising all of the strains recited in claim 21 and a prebiotic. As Yuille teaches all the species of claim 21 in a single composition, it would be obvious that all of these species could be combined in a formulation with a prebiotic as taught by Possemiers.
A person of ordinary skill in the art would have been motivated to modify the composition of Possemiers and include the additional species taught by Yuille, because Roseburia faecis,
Roseburia intestinalis, and Anaerostipes rhamnosivorans are known to be butyrate producing bacteria (Yuille p. 12 lines 10-26). Short-chain fatty acids (SCFA) such as butyrate are the end products of dietary fiber fermentation by the intestinal microbiota and are known to exert several beneficial effects on host health (Possemiers p. 10 para. 104). Possemiers teaches that it is beneficial to obtain microbial compositions with maximal SCFA production for treating gut dysbiosis issues (Possemiers p. 10 para. 105). Thus, a skilled artisan would have been motivated to include additional butyrate producing strains, which are known to be beneficial in the human gut, in a composition for treating antibiotic-induced gastrointestinal disorders which additionally comprises a prebiotic.
A skilled artisan would have a reasonable expectation of success in creating a composition comprising all of the bacteria recited in claim 21 and a prebiotic based on the teachings of Yuille directed to a composition comprising all of these bacteria in a single composition. Further, Possemiers teaches many of the same probiotic bacteria in a composition for use in treating gut microbiota imbalances, so a skilled artisan could reasonably expect success in creating a composition comprising all of these bacteria used for this same purpose.
Response to Arguments
Applicant's arguments filed 1/30/2026 have been fully considered but they are not persuasive.
Applicant argues that Possemiers in combination with Yuille fails to teach or suggest the
microbiota recovery composition of claim 21. Applicant argues that Possemiers does not teach Roseburia faecis, Roseburia intestinalis, and/or Anaerostipes rhanmnosivorans, and Yuille does not make up for the deficiencies of Possemiers. Applicant argues that Yuille does not teach or suggest a specific composition that includes Roseburia faecis, Roseburia intestinalis, and Anaerostipes rhamnosivorans, let alone in in combination with Faecalibacterium prausnitzii, Roseburia hominis, and Anaerostipes caccae, for use in a composition for an antibiotic inducing imbalance of gut microbiota in vivo, as recited in claim 21, and Yuille fails to teach any bacterial species or combinations thereof for use in a composition for use in vivo.
In response to this argument, it is first noted that the limitation “for an antibiotic
inducing imbalance of gut microbiota in vivo” is an intended use of the claimed composition. Any composition having the same structure as that of claim 21 is capable of performing this intended use. Possemiers teaches Faecalibacterium prausnitzii, Roseburia hominis, and Anaerostipes caccae in a composition with a prebiotic. Yuille teaches Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, and Anaerostipes rhamnosivorans in a composition. Thus, the composition of Yuille comprises all of the recited strains in claim 21. Possemiers does not teach all of these species, but teaches bacteria of the same genera in a composition with a prebiotic. All of these strains are known probiotics, as taught by Possemiers and/or Yuille. Thus, it would have been obvious to a skilled artisan to modify the composition of Possemiers to include additional strains in the genus Roseburia or Anaerostipes, with a reasonable expectation of success given the teachings of Yuille directed to a composition with each of these species.
It is further noted that while Yuille teaches bacterial compositions in an in vitro simulated intestinal environment, Yuille specifically teaches that accurate predictions of in vivo metabolic activity can be made in a simulated intestinal environment comprising far fewer species of organisms than were conventionally thought to be required for such assessments to be made (Yuille p. 4 lines 15-25). Possemiers teaches a composition comprising Faecalibacterium, Roseburia, and Anaerostipes used in vivo. A skilled artisan would have found it obvious to utilize strains as taught by Yuille in a composition of Possemiers because Yuille specifically teaches that the simulated intestinal environment can be used to accurately predict in vivo metabolic activity, and therefore would have had a reasonable expectation of success in utilizing the strains of Yuille, of the same genera as those taught by Possemiers, in vivo.
Applicant argues that the instant application discloses identifying for the first time new SCFA-producing species that were not previously described for use as a component of probiotics before (see applicant arguments p. 9).
In response to this argument, it is noted that several of the strains listed on p. 9 of applicant arguments have been previously described as a component of probiotics. For example, Possemiers teaches Faecalibacterium prausnitzii, Roseburia hominis, Akkermansia muciniphila, Anaerostipes caccae, Eubacterium limosum, and Enterococcus faecium in probiotic compositions.
Applicant argues that the Office Action has failed to provide a reasonable rationale to modify the teachings of Possemiers with the bacterial strains of Yuille to prepare a composition
comprising the particular bacteria Faecalibacterium prausnitzii, Roseburia faecis, Roseburia hominis, Roseburia intestinalis, Anaerostipes caccae, and Anaerostipes rhamnosivorans and a prebiotic. Even though Yuille teaches a composition comprising all the claimed bacterial
species, neither the Office Action nor the cited references provide a reasonable rationale
or scientific reasoning for adding a prebiotic to such a composition. Applicant argues that there is no teaching, suggestion, or rationale grounded in the cited art that would have led a person of ordinary skill in the art to specifically select these species from Yuille's broad and non-preferential laundry list of bacterial species for inclusion in the composition of Possemiers.
In response to this argument, it is first noted that the instant claims are not exclusive of additional unrecited elements, based on the use of “comprising” language. Yuille teaches a composition which comprises all of the claimed bacteria, in addition to other bacteria. Further, Possemiers teaches a composition comprising bacteria from the genera Roseburia and Anaerostipes with a prebiotic. Thus, a skilled artisan would have found it obvious that other species from the same genus which are also gut bacteria, and in a composition together as taught by Yuille, could be successfully used in a composition that also comprises a prebiotic.
Applicant argues that Yuille provides no disclosure, preference, or comparative data indicating that these species would produce maximal SCFA levels, nor any teaching that they would be capable of producing maximum butyrate-particularly when combined with Faecalibacterium prausnitzii, Roseburia hominis, Anaerostipes caccae, and a prebiotic. Applicant argues that the gut microbiome is highly complex and inherently unpredictable, and neither Yuille nor Possemiers provides any teaching or suggestion of synergistic interactions among these species that would support a reasonable expectation of success, and the Examiner's position represents an unsupported selection from a genus without guidance or expectation of success and relies on impermissible hindsight reconstruction of Applicants' claimed invention.
In response to this argument, it is noted that the teaching of Possemiers regarding maximal SCFA production is relied upon to provide motivation to use bacterial strains that are known to produce butyrate in a composition for treating antibiotic-induced GI disorders, because SCFAs such as butyrate are known to be beneficial to host health. The position of the examiner is not that the strains of Yuille will each individually produce maximum butyrate, but rather that if maximal SCFA production is desirable (as Possemiers teaches is the case), there would be motivation to use strains that have the capacity for butyrate production to help achieve increased SCFA production. Given the known function of these bacteria in producing SCFAs as taught by Yuille, there would be a reasonable expectation of success in using these strains for such a purpose in a composition as taught by Possemiers. Additionally, while it is true that the microbiome is complex, the claims do no require that there is a synergistic interaction between these species. Given the known characteristics of these bacteria and the teachings of Yuille that the simulated intestinal environment can provide accurate predictions of in vivo activity, and especially given the fact that Yuille teaches compositions comprising all of the claimed strains together, it is not considered to require hindsight reconstruction to arrive at a composition with the claimed bacterial strains and a prebiotic.
Applicant argues that at the time of the invention, there was no reasonable basis
to predict whether the addition of Roseburia faecis, Roseburia intestinalis, and/or Anaerostipes rhamnosivorans would beneficially affect butyrate production, as the added species could potentially outcompete one or more of the proficient butyrate-producing species of the Possemiers composition in the gut, thereby diminishing overall butyrate production in vivo depending on the relative contribution of each species.
In response to this argument, while it is true that there is some level of unpredictability in combining various probiotic species for in vivo use, it is the position of the examiner that there is sufficient information provided in the references to give a skilled artisan a reasonable expectation of success in creating a composition with all of these bacteria with beneficial effects on butyrate production. Yuille teaches that Roseburia faecis, Roseburia intestinalis, and/or Anaerostipes rhamnosivorans are all butyrate producing bacteria, and further teaches that the process of the invention, simulated intestinal environment, allows a reliable prediction of the in vivo metabolic properties of an organism of interest in a gut microbial community (Yuille p. 25 lines 1-9). Thus, a skilled artisan could have reasonably expected that the butyrate-producing microbial compositions of Yuille in vitro would have similar metabolic properties in vivo. Further, it is again noted that increased butyrate production or synergistic interactions of the bacteria are not required claim elements. However, the butyrate production capacity of the strains would provide sufficient motivation and reason for a skilled artisan to create a composition comprising all of these strains, as increased butyrate/SCFA production could reasonably be expected and would be beneficial based on the known properties of these bacteria.
Conclusion
Claims 2-8 and 21-22 are rejected. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
Prosecution Insights