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 .
DETAILED ACTION
Claims 30, 32, 34-35, 38-44 and 46 are pending.
Response to Amendment
Applicant added in claim 30 new limitation “wherein the pre-adapting comprises incubating the at least 3 bacterial species together; and subsequent to the pre-adapting, storing the functional microbial network, wherein the storing comprises freezing the at least 3 bacterial species”.
Applicant canceled claim 45 and added new claim 46.
The rejection of claim 32, 34 and 44-45 under 35 U.S.C. 112(b) is withdrawn in view of the amendment.
The rejection of claims 30, 32, 34-35, 38-45 are rejected under 35 U.S.C. 103 is withdrawn in view of the amendment.
The rejection of claims 30, 32, 34-35, 39, 41-42, and 44-45 on the ground of nonstatutory double patenting is withdrawn in view of the amendment.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/02/2026 is acknowledged and has been considered.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 30, 32, 34-35, 38, 44, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Duncan (WO 2004085628, of record in Office Correspondence mailed on 01/29/2024, hereinafter “Duncan”) in view of Murphy (Archives of microbiology 138 (1984): 49-53, of record in Office Correspondence mailed on 09/19/2024) and Guerin (Microbial Ecology in Health and Disease 11.3 (1999): 180-182).
Regarding claims 30 and 46, Applicant discloses that pre-adapted microorganism is also called collaborome strategy or alternative collaborome strategy ([0066]) and discloses in Example 1.3 that the strains were mixed and inoculated in growth medium in SHIME setup to create a collaborome ([0114]) or mixed and inoculated in growth medium in a fermenter ([0116]). Thus, the limitation “pre-adapting” will be interpreted as mixing and inoculating the bacteria in growth medium in fermenter.
Duncan teaches a composition comprising live bacterial strain of Anaerostipes caccae in combination with live lactic acid producing bacteria Lactobacillus spp. and Bifidobacterium spp. (claim 6, claims 19-20) (i.e., providing at least 3 bacterial species). Duncan teaches that in vitro co-fermentation of Anaerostipes caccae (L1-92) and at least one lactic acid producing bacteria (L2-32) increases butyrate production compared to fermenting each strain separately (i.e., incubation of bacterial species together) (Fig. 2, Table 3a). Duncan teaches that the strains were co-fermented for 24 hours (i.e., for at least one day) (page 23 lines 9-10, Table 3a). Duncan teaches that combination of lactate-utilizing strain Anaerostipes caccae with lactic acid producing bacteria such as Lactobacillus spp. enhances production of butyrate (i.e., incubating the species together) (page 8 lines 8-17). Duncan teaches F. prausnitzii is capable of utilizing lactate and acetate to produce formate and butyrate (Table 1 page 15 row 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add F. prausnitzii to the composition comprising live bacterial strain of Anaerostipes caccae, as suggested by Duncan. One of ordinary skill in the art would be motivated to do so in order to further increase the production of butyrate. Since Duncan teaches both strains, Anaerostipes caccae and F. prausnitzii, are butyrate producers, there is a reasonable expectation of success.
Duncan does not teach the species Lactobacillus plantarum.
However, Murphy teaches Lactobacillus plantarum produces lactate and acetate (page 49, Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by adding Lactobacillus plantarum, as suggested by Murphy. One of ordinary skill in the art would be motivated to do so in order to produce higher amounts of butyrate. MPEP §2144.06(I) states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” Since Duncan teaches a desire to increase butyrate production by co-fermenting lactate-utilizing bacteria with lactate producing bacteria and since Murphy teaches Lactobacillus plantarum is a lactate producing bacteria, there is a reasonable expectation of success.
Duncan teaches using bacteria from stock collection (page 13 line 12). Duncan and Murphy do not teach subsequent to the pre-adapting, storing the functional microbial network, wherein the storing comprises freezing the at least 3 bacterial species.
However, Guerin teaches that freezing a group of bacteria including lactobacilli, anaerobes or facultative anaerobes in glycerol at -80oC is a way to conserve and store the bacteria for subsequent usage and teaches that with this technique the relative equilibrium between the bacterial populations is preserved (Abstract, Introduction, Result and Discussion).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by freezing the bacteria at -80oC, as suggested by Guerin. One of ordinary skill in the art would be motivated to do so in order to preserve and store the bacterial mix for later usage and additional subsequent growth. Since Duncan teaches bacteria from stocks can be used and since Guerin teaches freezing is a successful way to store a mix of bacteria, there is a reasonable expectation of success.
Regarding claim 32, Duncan teaches the strains are purified (page 12 lines 15-16) and teaches isolating single colonies and growing the culture in broth (i.e., bacterial species are isolated before the co-culturing) (page 12 lines 11-14).
Regarding claim 34, Duncan teaches the strains were co-cultured for 24 hours (i.e., culturing for 1 to 10 days) (page 23 lines 9-10, Table 3a).
Regarding claim 35, Duncan teaches the composition comprises 3 bacteria, which falls within the limitation of the instant claim of up to 14 bacterial species (claims 19-20).
Regarding claim 38, Duncan teaches Anaerostipes caccae is DSMZ accession no: 14662 (page 6 line 10)
Regarding claim 44, the limitation “wherein after the pre-adapting step, the at least 3 bacterial species are present in an effective amount for increasing butyrate when measured by gas chromatography after 48 hours of in vitro growth in a culture compared to measurement of butyrate generated by an equivalent amount of any one bacterial species alone” is the result of the co-culturing step and does not require additional steps to be performed, and therefore, do not limit the method claimed. “Whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited”. See MPEP 2111.04
Claims 39 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Duncan, Murphy and Guerin as applied to claim 30 above, and as evidenced by NCBI (NCBI Taxonomy Browser, Roseburia hominis A2-183, 2020, hereinafter “NCBI”).
Regarding claims 39 and 40, Duncan teaches that strain Roseburia sp. A2-183 degrades acetate and produces butyrate (Table 1). Evidentiary reference NCBI shows Roseburia sp. A2-183 is Roseburia hominis A2-183 with DSM 16839 (page 1 Table “External Information Resources” row 5). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by adding Roseburia hominis A2-183 DSM 16839. One of ordinary skill in the art would be motivated to do so in order to further increase the butyrate production in the composition.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Duncan, Murphy, and Guerin as applied to claim 30 above, and further in view of De Vuyst (Journal of applied microbiology 116.3 (2014): 477-491, of record in Office Correspondence mailed on 08/19/2024)
Regarding claim 41, Duncan, Murphy, and Guerin do not teach the bacterial species further comprising Butyricicoccus pullicaecorum, Roseburia inulinivorans and Akkermansia muciniphila.
However, De Vuyst teaches that bacteria with health-promoting assignments due to their potential to produce butyrate or propionate are getting increased attention, and teaches that the important butyrate producers include Roseburia spp., Butyricicoccus pullicaecorum and Faecalibacterium prausnitzii (page 478 right column). De Vuyst teaches that Roseburia inulinivorans is a butyrate producer that is able to degrade oligofructose and long chain inulin (page 482 right column last line through page 483 first line). De Vuyst teaches that Akkermansia muciniphila is an important propionate producer (page 478 right column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by adding butyrate producing bacteria such as Butyricicoccus pullicaecorum and Roseburia inulinivorans, and propionate producing bacteria such as Akkermansia muciniphila, as suggested by De Vuyst. One of ordinary skill in the art would be motivated to do so in order to increase production of butyrate and propionate. Since Duncan and De Vuyst teach a desire to form a composition with high amount of butyrate, there is a reasonable expectation of success.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Duncan, Murphy, Guerin, and De Vuyst, as applied to claim 41 above, and as evidenced by NCBI.
Regarding claim 42, Duncan teaches strain Roseburia sp. A2-183 that produces butyrate and degrades acetate (Table 1). Evidentiary reference NCBI shows Roseburia sp. A2-183 is Roseburia hominis A2-183 with DSM 16839 (page 1 Table “External Information Resources” row 5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by adding other butyrate producing bacteria such as Roseburia hominis as suggested by Duncan. One of ordinary skill in the art would be motivated to do so in order to increase the production of butyrate.
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Duncan, Murphy, Guerin, and De Vuyst, as applied to claim 41 above, and further in view of Li (Genome Announcements, March/April 2013, volume 1, Issue 2; of record in IDS filed on 12/02/2022), Geirnaert (Anaerobe 30 (2014): 70-74, of record in IDS filed on 08/02/2021) and DSM-22959 (DSM-22959, Akkermansia muciniphila, DSMZ German collection of microorganisms and cell cultures, 2004, of record in IDS filed on 12/02/2022).
Duncan teaches Anaerostipes caccae DSMZ accession no: 14662. De Vuyst teaches F. prausnitzii DSM 17677 (page 483 left column first para.) and Roseburia inulinivorans DSM 16841 (page 482 right column last para.). Duncan, Murphy, Guerin, and De Vuyst do not teach Lactobacillus plantarum is strain ZJ316, Butyricicoccus pullicaecorum is strain LMG 24109 and Akkermansia muciniphila is DSMZ accession no: 22959.
However, Li teaches Lactobacillus plantarum stain ZJ316 has many probiotic properties and antimicrobial activity against various pathogens (page 1 left column first para.).
Geirnaert teaches that Butyricicoccus pullicaecorum LMG 24109 is a butyrate producer with probiotic potential and is intrinsically tolerant to stomach and small intestine conditions (title, para. 2.1).
DSM-22959 teaches an isolated and commercially available Akkermansia muciniphila 22959 (whole document).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Duncan by adding Lactobacillus plantarum stain ZJ316, Butyricicoccus pullicaecorum with deposit number LMG24109 and Akkermansia muciniphila 22959, as suggested by Li, Geirnaert and DSM-22959. One of ordinary skill in the art would be motivated to do so in order to use pure and isolated bacterial strains with probiotic potential.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 30, 32, 34-35, 39, 41-42, 44 and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 14-15, 19, 22-23, and 25 of U.S. Patent No. 12,458,672 in view of Guerin.
Regarding instant claims 30, 32, 34-35, 39, 41-42, 44 and 46, patent claims 1, 14 and 22 recite a composition wherein the composition comprises: at least 10^5 colony-forming units in total of bacterial isolates, wherein the bacterial isolates in the composition have been co-cultured in a dynamic simulator of the gastro-intestinal tract in vitro together for at least one day to form a functional microbial network, wherein the functional microbial network produces a higher amount of butyrate when measured by gas chromatography after 48 hours of in vitro growth compared to an amount of butyrate generated by an equivalent amount of bacterial isolates that have not been co-cultured, and wherein the functional microbial network comprises: at least one lactate or acetate producing bacterial species selected from a species of: Lactobacilli or Enterococci, or at least one fiber degrading bacterial species selected from a species of: Bifidobacteria or Bacteroides, or at least one mucin degrading bacterial species comprising Akkermansia muciniphila; and at least one butyrate or propionate producing bacterial species selected from: Anaerostipes caccae, Butyricicoccus pullicaecorum, Faecalibacterium prausnitzii, Roseburia hominis, Roseburia inulinivorans, Clostridium butyricum, Bacteroides thetaiotaomicron, Bacteroides vulgatus, and Akkermansia muciniphila. Patent claims 6, 19, and 25 recite wherein the composition comprises at least two of the butyrate or propionate producing bacterial species. Patent claims 2, 15, and 23 recite wherein the bacterial species comprise up to 14 bacterial species.
Patent claims 1-2, 6, 14-15, 19, 22-23, and 25 do not recite subsequent to the pre-adapting, storing the functional microbial network, wherein the storing comprises freezing the at least 3 bacterial species.
However, Guerin teaches that freezing a group of bacteria including lactobacilli, anaerobes or facultative anaerobes in glycerol at -80oC is a way to conserve and store the bacteria for subsequent usage and teaches that with this technique the relative equilibrium between the bacterial populations is preserved (Abstract, Introduction, Result and Discussion).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited in patent claims 1-2, 6, 14-15, 19, 22-23, and 25 by adding more than one of the recited bacterial species and by freezing the bacteria at -80oC, as suggested by Guerin. One of ordinary skill in the art would be motivated to do so in order to further increase the butyrate production and to preserve and store the bacterial mix for later usage and additional subsequent growth.
Response to Arguments
Applicant's arguments filed 04/02/2026 have been fully considered but they are not persuasive.
Applicant argues the cited references do not teach the limitation wherein the storing comprises freezing the at least 3 bacterial species. Applicant argues Duncan describes measuring butyrate production after mixing bacterial strains together and culturing for 24 hours, similar to the "Assembly" method, which produces less butyrate than the collaborome method as shown in Fig 4. Applicant argues the claimed method has unexpected results.
In response to the argument, newly cited reference Guerin teaches bacteria can be stored by freezing at -80oC. One of ordinary skill in the art would be motivated to store the bacterial mix by freezing it at -80oC in order to preserve it and reuse it subsequently.
Regarding the “assembly method” argument, the claim requires the steps of 1) providing at least 3 bacterial species, 2) pre-adapting the 3 bacterial species, and 3) storing the functional microbial network. The limitation “wherein when a culture is inoculated with the stored functional microbial network, the culture produces a higher amount of butyrate when measured by gas chromatography compared to a culture inoculated with an equivalent amount of the at least 3 bacterial species without pre-adapting for at least one day” does not require a step to be performed. This limitation expresses the result of the recited steps. Duncan teaches providing bacterial species and co-fermenting them for 24 hours and teaches an increase in butyrate production compared to when each species is cultured alone. The claim does not require inoculating another culture with the stored functional microbial network or with the pre-adapted bacterial species.
Regarding the unexpected result, any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. An unexpected property or result must actually be unexpected and of statistical and practical significance. The burden is on the applicant to establish the results are in fact unexpected, unobvious and of statistical and practical significance. See MPEP 716.02. While FIG. 4 shows a difference in butyrate production between assembly and collaborome methods, it is not clear if this difference is unexpected and of statistical and practical significance. The figure does not show any error bars or statistical analysis.
Applicant requests that the double patenting rejection over co-pending application 17/502,454 (now published as US 12,458,672) be held in abeyance (Remarks p. 9). A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see 37 CFR 1.111(b) and MPEP §714.02). Thus, the double patenting rejections of record have been maintained as no response to these rejections has been filled by applicant at this time.
Conclusion
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 MARY A CRUM whose telephone number is (571)272-1661. The examiner can normally be reached M-F 8:00-5:00 CT with alternate Fridays off.
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/MARY A CRUM/Examiner, Art Unit 1657
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
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