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
The instant application is a US national phase of PCT/EP2019/078011, filed October 15, 2019, and has a foreign priority application EP18200455.6, filed October 15, 2018.
The amendment filed January 28, 2026 is acknowledged. Claims 1-90 and 93-97 are canceled, claim 91 is amended, and claims 98-114 are newly added.
Claims 91-92 and 98-114 are pending and under examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 28, 2026 has been entered.
Claim Objections
Claims 99 and 101-102 are objected to because of the following informalities:
Claim 99, lines 1-13, needs to be changed to “wherein the consortium further comprises at least one bacterial strain from each of functional groups .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 99-100 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 99 recites “wherein the consortium comprises at least one bacterial strain from each of functional groups (A3), (A8), (A10), (A9), (A1) and (A2) or (A4)”. It is unclear which functional groups are required by the claim, such as (A1 AND A2) or (A4), or (A1 AND A2) or (A1 AND A4), therefore indefinite. Claim 100 is likewise rejected as being dependent on an indefinite claim.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 91-92, 98-103, 106, 110-111, and 113 are rejected under 35 U.S.C. 103 as being unpatentable over McKenzie et al. (AU 2014212004 82, cited in PTO-892 mailed 9/27/2024, hereinafter “McKenzie”), as evidenced by Rainey et al. ("Order I. Clostridiales Prévot 1953." Bergey’s Manual of Systematic Bacteriology, 3 (2009): 736, pgs. 1-1422, hereinafter “Rainey”).
Regarding claims 91, 98, 110-111, and 113, McKenzie teaches therapeutic compositions containing non-pathogenic, germination-competent bacterial spores, for the prevention, control, and treatment of gastrointestinal diseases, disorders and conditions and for general nutritional health (abstract). McKenzie teaches the bacterial compositions can be in the form of pharmaceutical compositions to be administered to humans (para [0243]). McKenzie teaches the bacteria are selected based on a ‘core network ecology’ as a designed consortium of microbes, typically non-pathogenic bacteria, that represents core features of a set of phylogenetically or functionally related network ecologies seen in many different subjects (para [0079]). McKenzie teaches the bacterial compositions are isolated from fecal samples of healthy patients, purified and ethanol treated, tested for viability and species identification, then administered to patients suffering from C. difficile infection (para [0382]-[0383]). McKenzie teaches in the culturing step, the strains in the composition can be cultivated alone or as an entire collection, and states the medium can be added during the culture, or may be continuously flowed through the culture, which meets the limitation in claim 91 (para [0184]). McKenzie teaches the compositions can have from 2 to no more than 20 or 10 types of bacteria, which meets the limitations recited in claims 91 and 113 (para [0128]).
McKenzie teaches the bacterial preparations contained 20% Bacteroides fragilis and 20% Phascolarctobacterium faecium which are members of functional group A8 and A10, respectively, in the claims (pg. 118, 119, Table GB). McKenzie teaches the bacterial preparations contained 50% Escherichia coli, 50% Clostridium mayombe, 20% Bacteroides fragilis, and 20% Phascolarctobacterium faecium, which are functional groups A3, A9, A10, and A8, respectively, which meets the limitations of the claims 91 and 98 (pg. 116, 118, 119, Table GB).
Regarding claim 99, McKenzie teaches the bacterial preparations contained 60% Ruminococcus bromii, 100% Faecalibacterium prausnitzii, 10% Bifidobacterium bifidum, 20% Bacteroides fragilis, 20% Phascolarctobacterium faecium, 50% Clostridium mayombei, 80% Eubacterium ramulus, 50% Escherichia coli, and 20% Coprococcus eutactus, which are members of the recited functional groups and genus in the claim (pgs. 115-119, Table GB).
Regarding claims 101 and 103, McKenzie teaches the bacterial preparations contained 60% Ruminococcus bromii, 100% Faecalibacterium prausnitzii, 10% Bifidobacterium bifidum, 20% Bacteroides fragilis, 20% Phascolarctobacterium faecium, 50% Clostridium mayombei, 80% Eubacterium ramulus, and 50% Escherichia coli, which are members of the recited functional groups and species in the claims (pgs. 115-119, Table GB).
Regarding claim 102, McKenzie teaches the bacterial preparations contained 60% Ruminococcus bromii, 100% Faecalibacterium prausnitzii, 10% Bifidobacterium bifidum, 20% Bacteroides fragilis, 20% Phascolarctobacterium faecium, 50% Clostridium mayombei, 30% Eubacterium eligens, 20% Coprococcus eutactus, and 50% Escherichia coli, which are members of the recited functional groups and genus in the claim (pgs. 115-119, Table GB).
Regarding claim 106, McKenzie teaches The bacterial compositions can also be administered in gel or liquid form by the oral route or through a nasogastric tube, or by the rectal route in a gel or liquid form, by enema or instillation through a colonoscope or by a suppository (para 208).
Regarding claim 92, McKenzie teaches the therapeutic composition comprising a purified population of germination-competent bacterial spores, in an amount effective to treat or prevent or reducing the severity of at least one symptom of a dysbiosis, associated with Clostridium difficile, including recurrent C. difficile infection, or ulcerative colitis (para 9d).
Regarding claims 91-92, 98-99, 101-103, 106, 110-111, and 113, although McKenzie is silent of the particular functional characteristic of each strain in the composition, except for referring to operational taxonomic units, members of the same clade, due to their evolutionary relatedness, play similar functional roles in microbial ecology such as the ecological functions found in the human gut, and therefore compositions substituting one species with another from the same clade are likely to have conserved ecological function (para 428). Thus, the compositions taught by McKenzie inherently possess the functional characteristics of the bacteria recited in the instant claims, and thus are obvious of the compositions recited in the instant method. “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Therefore, in view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ product they exemplify. As such, the claimed compositions taught by McKenzie are within the scope of the compositions recited in the method claims, and thus McKenzie’s compositions render the invention prima facie obvious. The rationale to support this conclusion of obviousness is that McKenzie provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed compositions exhibits any unexpected results compared to the prior art.
Regarding claim 100, McKenzie does not teach the bacterial compositions administered comprise Clostridium celatum, a member of functional group A5. However, McKenzie teaches C. celatum is identified as part of clade_253, which also includes the species Clostridium disporicum that is present in 40% of the bacterial compositions administered (pgs. 115, Table GB; pg. 147, Table 1). McKenzie teaches OTU’s, wherein members of the same clade, due to their evolutionary relatedness, play similar functional roles in a microbial ecology such as that found in the human gut, and compositions substituting one species with another from the same clade are likely to have conserved ecological function (para 428). Thus, 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 use the bacterial compositions in a method for the treatment of intestinal dysbiosis taught by McKenzie and substitute a similar strain, such as C. celatum, that has similar functional characteristics as the C. disporicum strain taught in McKenzie’s bacterial compositions with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to substitute strains that are functionally equivalent which inherently possess the desired function of consuming lactate or proteins, and producing propionate and acetate. As evidenced by Rainey, Clostridium celatum differs from Clostridium disporicum in that it produces acetic and formic acids and ethanol while the latter only produces acetate and lactate, therefore C. disporicum would be a member of functional group A5, as recited in the claims, as ‘producing acetate’ (pg. 784, col. 2, para 2). Furthermore, Figure 128 on page 741 of Rainey discloses C. disporicum and C. celatum’s close phylogenetic relatedness, thus would be obvious to substitute.
Claims 104-105 and 107-108 are rejected under 35 U.S.C. 103 as being unpatentable over McKenzie as applied to claims 91-92, 98-103, 106, 110-111, and 113 above, and further in view of Chatila et al. (WO 2017 /079450 A1, previously cited in PTO-892 mailed 9/27/2024, hereinafter “Chatila”).
Regarding claims 104-105, McKenzie teaches the bacterial composition is substantially free of residual habitat products (i.e., biological matter associated with the microbial environment) (para 72). McKenzie does not specifically teach the bacterial compositions are free of other viable live bacteria or free of succinate, formate, and lactate.
However, Chatila teaches compositions of microbial consortia that can prevent or cure food allergy (abstract). Chatila teaches the composition is a microbial consortium consisting of essentially four to eleven strains of viable gut bacteria which meets the limitation of claim 85 (pg. 79, claim 1). Chatila does not specifically teach the composition is essentially free of succinate, formate, and lactate, however Chatila teaches the composition involves concentration, removal of undesirable medium components, and/or introduction into a chemical milieu that preserves the bacterial composition and renders it acceptable for administration via the chosen route (pg. 52, para 327). Thus, the composition of the synergistic microbial consortium and the method of harvesting the consortium of essentially the bacterial components inherently meets the limitations of claims 104-105, since ‘the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established’. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112 for further explanation of anticipation by inherency. Therefore, 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 formulate the compositions taught by McKenzie, wherein the compositions are essentially free of other viable live bacteria and succinate, formate, and lactate, as taught by Chatila with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to remove any other bacteria as well as extraneous compounds, to formulate a composition acceptable for administration via the chosen route as taught by Chatila.
Regarding claims 107-108, McKenzie teaches the bacterial compositions are characterized by 16S rRNA analysis and administered as a single oral dose in the range of 104 – 1015 CFUs (para [0121]). McKenzie does not teach the composition has each bacterial strain present in amounts of 105-1014 16S rRNA gene copies per mL, nor the recited method of obtaining the consortium recited in claim 108.
However, Chatila teaches the component members of the composition are grown anaerobically in liquid media to ensure maximal culture density, concentrated by centrifugation, and assessed by 16S rRNA gene phylotyping with cultured qPCR-based methods to arrive at final concentrations of ~5 x 108 CFU/mL which meets the limitation of claim 107 (pg. 69, para 395, pg. 67, para 384). After the strains are co-cultivated in a single culture medium, the bacterial strains are harvested and preserved for banking or storage which meets the limitations of claim 108 (pg. 51, para 326).
Therefore, 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 grow and harvest the bacterial strains, then quantify by qPCR the 16S rRNA gene copies to arrive at desired concentration of 105-1014 16S rRNA gene copies per mL, taught by Chatila, to be included and administered in the bacterial compositions taught by McKenzie with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to use routine and conventional laboratory methods to grow, isolate, and quantify the bacterial strains to advantageously arrive at the microbial consortiums taught by McKenzie.
Claims 105 and 109 are rejected under 35 U.S.C. 103 as being unpatentable over McKenzie and Chatila as applied to claims 104-105 and 107-108 above, and further in view of Henson, et al. (Processes 2017, 5, 13, pgs. 1-23, previously cited in PTO-892 mailed 9/27/2024, hereinafter “Henson”).
As discussed above, Chatila teaches each bacterial strain is grown to a concentration of ~5 x 108 CFU/mL using 16S rRNA gene phylotyping with cultured qPCR-based methods to arrive at final concentrations which meets this limitation in the claim (pg. 69, para 395, pg. 67, para 384).
McKenzie and Chatila do not teach measuring the stable metabolic profile of each bacterial strain as being below the concentration of, or free of, one or more metabolites selected from formate, lactate, and succinate in the medium below 15mM.
However, Henson teaches a byproduct cross-feeding and community stability in an in-silico biofilm model of the gut microbiome (title). Henson teaches the development of a biofilm metabolic model of a gut microbiome community consisting of a representative Bacteroidetes (Bacteroides thetaiotaomicron), firmicute (Faecalibacterium prausnitzii) and proteobacterium (Escherichia coli) to investigate the putative role of metabolic byproduct cross feeding between species on community stability, robustness and flexibility (abstract). Henson teaches each bacterial strain is mono-cultured and grown until a steady-state spatial profile is reached, wherein B. thetaiotaomicron achieves a state of virtually no lactate is detected in the media, E. coli has virtually no lactate or succinate detected in the media, and F. prausnitzii has virtually no succinate detected in the media (pg. 4, Figure 2). Henson teaches when all three bacteria are cultured in a biofilm, virtually no lactate is detected in the media after ~20 hours and less than 1mmol/L of succinate is detected throughout the experiment (pg. 6, Figure 3A).
Therefore, 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 formulate a pharmaceutical composition in a method for the treatment of intestinal dysbiosis comprising the bacterial strains taught by McKenzie that are cultured and harvested according to the teachings of Chatila, and co-culture these bacterial strains until the consortium reaches a stable metabolic profile, wherein the intermediate metabolites such as formate, lactate, and succinate are virtually absent as taught by Henson with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to culture the bacterial strains to a stable metabolic profile wherein the absence of these particular metabolites are evidence of efficient utilization of these substrates and advantageously create a steady-state growth environment of each species which would be formulated into the compositions taught by Chatila and McKenzie. By culturing to a steady-state spatial profile of each single species biofilm, one of ordinary skill in the art would have been able to predict cross-feeding patterns based on substrate availability with a reasonable expectation of success as taught by Henson (pg. 4, para 2).
Claims 112 and 114 are rejected under 35 U.S.C. 103 as being unpatentable over McKenzie as applied to claims 91-92, 98-103, 106, 110-111, and 113 above, and further in view of Wargo (WO 2018/064165 A2, previously cited in PTO-892 mailed 9/27/2024, hereinafter “Wargo”), as evidenced by Ibrahim (Lactic Acid Bacteria: Lactobacillus spp.: Other Species, Reference Module in Food Science, Elsevier, 2016, ISBN 9780081005965, cited in PTO-892 mailed 10/29/2025).
McKenzie teaches the pharmaceutical compositions are useful in treating or preventing dysbiosis associated with Clostridium difficile (para 9a). McKenzie teaches compositions comprising Phascolarctobacterium faecium and Bacteroides fragilis. McKenzie teaches lists of species assigned to OTU assigned to specific clades, wherein members of the same clade, due to their evolutionary relatedness, play similar functional roles in a microbial ecology such as that found in the human gut, thus compositions substituting one species with another from the same clade are likely to have conserved ecological function [0428]. McKenzie teaches Blautia hydrogenotrophica is assigned to clade 368 and Lactobacillus rhamnosus is assigned to clade 373 in Table 1 (pgs. 149, 165). McKenzie teaches in Table GB the spore treated preparation contained 10% Lactobacillus perolens, which is also a member of the same clade as L. rhamnosus (pg. 116). McKenzie teaches bacterial compositions comprise at least one and preferably more than one of the following: Bacteroides fragilis, Bacteroides ovatus, inter alia [0141].
McKenzie does not teach compositions comprising Bacteroides xylanisolvens, however, McKenzie teaches B. xylanisolvens is a part of the same OTU clade as B. ovatus (pg. 165, Table 1). McKenzie also does not teach compositions comprising B. hydrogenotrophica or species from clade 368.
However, Wargo teaches pharmaceutical compositions for the treatment of cancer by modulating the microbiome to enhance efficacy of immune checkpoint blockade by administering butyrate-producing bacteria (abstract, para 116). Wargo teaches loss of diversity (dysbiosis) is associated with chronic health conditions and cancer, and is also associated with poor outcomes to certain forms of cancer therapy (para 182). As evidenced by McKenzie, the presence of Fusobacterium indicates a profoundly dysbiotic gut microbiota, which the particular species Fusobacterium nucleatum is termed an emerging gut pathogen based on its association with colorectal cancer in humans, demonstrating a causative in the development of colorectal cancer in animal models (para 369). Wargo teaches the pharmaceutical compositions comprise at least one or two isolated purified bacteria belong to the species P. faecium and B. xylanisolvens (para 11), as well as B. hydrogenotrophica and Lactobacillus casei (claim 19). As evidenced by Ibrahim, L. rhamnosus was previously known as L. casei subsp rhamnosus, and is included with other highly related species in the Lb. casei group, thus functionally equivalent (pg. 1).
The compositions taught by McKenzie as modified by Wargo would inherently possess the functional characteristics of the bacteria recited in the instant claims. “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Therefore, 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 formulate a pharmaceutical composition in a method for the treatment of intestinal dysbiosis based on their functional taxonomic groups comprising at least one P. faecium and a functionally equivalent L. rhamnosus species (i.e. L. perolens) as taught by McKenzie, and by replacing B. ovatus taught by McKenzie with two functional equivalents, B. xylanisolvens and B. hydrogenotrophica, as taught by Wargo. It would also have been prima facie obvious to substitute various functionally equivalent species in the compositions taught by McKenzie and Wargo to effectively modulate the human gut microbiome for health benefits.
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 91-92, 98-101, 103-111, 113 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,219,649 (cited in PTO-892 mailed 9/27/2024) in view of McKenzie.
Regarding claims 91-92, 98-101, 103, 110-111, 113, claims 1, 3, 10, and 14 of ‘649 recite a pharmaceutical composition comprising live bacteria strains that comprise functional groups A1-A9. The genus and strains recited in ‘649 encompass the genus and strains comprised in the compositions recited in the instant methods (i.e., Eubacterium, Roseburia, Lactobacillus, Bifidobacterium, Clostridium, Phascolarctobacterium, Blautia, inter alia). The functional groups listed in ‘649 are functionally the same as the instant. The instant claims do not recite the species of functional group A7 being C. aerofaciens, C. intestinalis, C. stercoris, however it has been held that the generic invention (is “anticipated” by a “species” (‘649 species of A7) which is within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Claim 7 of ‘649 recites the composition is used for a prophylaxis, treatment, prevention, or delay of progression of a disease associated with microbiota dysbiosis. Claim 8 of 649 recites the composition is used for diseases such as Clostridium difficile infection, inter alia.
Although ‘649 claims do not recite a method for treating the recited diseases, administering the ‘649 composition to perform the disclosed therapeutic use would have been an obvious variation of the claimed invention and therefore the instant claims are not patentably distinct.
Claims of ‘649 do not recite functional group A10 of the instant invention, nor that the genus of A10 is Bacteroides (B. xylanisolvens or B. fragilis). ‘649 claims also do not recite the composition comprises no more than 20 or 10 different bacterial strains.
However, McKenzie teaches therapeutic compositions containing non-pathogenic, germination-competent bacterial spores, for the prevention, control, and treatment of gastrointestinal diseases, disorders and conditions and for general nutritional health (abstract). McKenzie teaches the bacterial compositions can be in the form of pharmaceutical compositions to be administered to humans (para 243). McKenzie teaches the bacteria are selected based on a ‘core network ecology’ as a designed consortium of microbes, typically non-pathogenic bacteria, that represents core features of a set of phylogenetically or functionally related network ecologies seen in many different subjects (para 79). McKenzie teaches the bacterial compositions are isolated from fecal samples of healthy patients, purified and ethanol treated, tested for viability and species identification, then administered to patients suffering from C. difficile infection (para 382-383). McKenzie teaches the compositions can have from 2 to no more than 20 or 10 types of bacteria, which meets the limitations recited in claims 91 and 113 (para 128). McKenzie teaches the bacterial preparations contained 20% Bacteroides fragilis and 20% Phascolarctobacterium faecium (pg. 118, 119, Table GB), therefore meets the limitation in claim 110.
Therefore, 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 combine the compositions recited in ‘649 with the compositions including B. fragilis and formulate compositions comprising no more than 20 or 10 different bacterial strains as taught by McKenzie that are both used in the treatment for intestinal dysbiosis or C. difficile infection to arrive at the claimed method. One of ordinary skill in the art would have been motivated to include B. fragilis with the microbial consortia composition of ‘649, since this is a common intestinal microorganism frequently used in therapeutic compositions to treat intestinal dysbiosis as taught by McKenzie (para 362).
Regarding claims 104-109, claim 11 of ‘649 recites the pharmaceutical composition is free of, or essentially free of, other viable, live bacteria; and/or free of, or essentially free of, succinate, formate and lactate which meets these limitations in instant claims 104-105. Claim 13 of ‘649 recites the pharmaceutical composition is adapted to rectal administration, or oral administration which meets the limitations in instant claim 106. Claims 1 and 2 of ‘649 recite each bacterial strain is present in the amount of 105 – 1014 16SrRNA gene copies/mL which meets these limitations in instant claims 107 and 109. Claims 4-6 and 12 of ‘649 recite the composition is grown in co-cultivating medium and/or cryo-protecting medium which meets the limitation of a preservation treatment in instant claim 108. Claim 1 of ‘649 recites succinate, formate, and lactate are present in amounts less than 5mM which meets the limitation of the stable metabolic profile of instant claim 108-109.
Thus, claims 91-92, 98-101, 103-111, 113 are obvious over claims 1-14 of U.S. Patent No. 11219649 in view of McKenzie.
Response to Arguments
Applicant's arguments filed January 28, 2026 have been fully considered but they are not persuasive.
Regarding response directed to the 103 rejections, Applicant argues the bacterial strains of Table GB, according to McKenzie, were generated from ten different ethanol treated spore preparations made from 6 different donors and the percentages cited at pages 7-8 of the Office Action are disclosed by McKenzie to be frequencies of detection of OTUs in the 10 ethanol treated spore preparations (McKenzie, paragraph 382 referring to Table GB). Thus, Table GB does not disclose "a preparation" comprising the OTUs as alleged by the Office Action. Instead, Table GB discloses combined OTU data from 10 different spore preparations, and based on Table GB, a person of ordinary skill in the art would not know whether the bacterial strain of the genus Phascolarctobacterium detected in 2 out of 10 spore preparations was present in a spore preparation together with other select bacterial strains from the genus Bacteroides; at least one bacterial strain selected from the genus Lactobacillus, Streptococcus, Escherichia, Lactococcus and Enterococcus; at least one bacterial strain selected from the genus Acetobacterium, Blautia, Clostridium, Moorella, Sporomusa and Eubacterium as required by the claims. In response, Examiner agrees that McKenzie does not teach a single administered composition of the exact same bacteria of the claimed invention; however, this is an obviousness rejection, wherein McKenzie teaches specific combinations of bacterial mixtures based on OTUs, and the elements of the present invention were taught in McKenzie’s compositions.
Applicant also argues McKenzie does not teach or suggest a method that such separate spore preparations were combined into a consortium in order to administer bacterial strains of the select functional groups to a subject as required by the claims. Moreover, McKenzie teaches that for an OTU in Table GB to be considered a member of a spore preparation, that OTU must engraft in a patient because non-engrafting OTUs may include non-viable spores or contaminating sequences (McKenzie, paragraph 384). And, Phascolarctobacterium faecium cited in the Office Action as being present in McKenzie's bacterial preparations, is disclosed in Table GB as 0% engraftment, which, according to McKenzie, means that Phascolarctobacterium faecium is either a non-viable spore or a contaminating sequence. The Examiner agrees McKenzie does not identify each functional group as claimed in the instant, but does teach compositions comprising species that belong to each functional group as claimed, thus does teach these elements. Furthermore, P. faecium is present in the compositions taught by McKenzie, and whether or not the spores could be proven as viable or not does not detract from the obviousness analysis, since one of ordinary skill in the art would be able to verify the viability of the particular species in the compositions taught by McKenzie.
Applicant argues McKenzie does neither expressly nor inherently disclose the claimed pharmaceutical compositions and method. Applicant submits that the allegation that, due to the evolutionary relatedness of members of the same clade, compositions substituting one species with another from the same clade "are likely to have conserved ecological function (para 428)" (emphasis added) is an improper basis for the finding that the claimed invention is obvious. In response, McKenzie teaches OTUs are frequently defined by comparing sequences between organisms, generally, sequences with less than 95% sequence identity are not considered to form part of the same OTU [071]. McKenzie also teaches clades are constructed to ensure that all OTUs in a given clade are: (i) within a specified number of bootstrap supported nodes from one another (generally, 1-5 bootstraps), and (ii) within a 5% genetic similarity, and states that the power of clade based analysis is that members of the same clade, due to their evolutionary relatedness, play similar functional roles in a microbial ecology such as that found in the human gut [0366].
Applicant argues McKenzie's disclosure of culturing conditions are "for banking" and specifically for banking conditions that use a culturing step, not for continuously co-cultivated isolated selected live viable bacterial strains for administration as claimed. Applicant further argues McKenzie’s compositions teach spore formulations, not a consortium of co-cultivated live viable bacterial strains as claimed. In response, the Examiner would like to point out that a ‘spore’ is considered a live, viable organism, just in a vegetative state, and the instant Specification states the compositions can be lyophilized for administration, which causes spores to form, as disclosed by McKenzie [059]. Thus, McKenzie teaches the core-network ecology blueprint of the compositions recited in the claimed method, and their use as an effective treatment in intestinal dysbiosis, the only limitations not taught by McKenzie are the labeling of the specific functional groups recited in the claims, instead they are indicated as phylogenetic clades that are disclosed to have a functional niche in the intestinal biome which when combined have synergistic properties to improve the health of the subject, thus the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding responses directed to the 103 rejections of McKenzie in view of Chatila, Henson, and Wargo, Applicant states claim 86 is canceled thereby rendering the rejection moot, however this is incorrect. Applicant also states regarding the obviousness type double patenting over US Patent No. 11219649 that the rejection is moot because claim 77-82, 84, 90, 93-94 are canceled, which is also incorrect. Applicant argued that there would be no motivation to include Bacteroides as taught by McKenzie to a composition comprising Phascolarctobacterium as recited in ‘649. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as stated above, McKenzie teaches the bacteria are selected based on a ‘core network ecology’ as a designed consortium of microbes, typically non-pathogenic bacteria, that represents core features of a set of phylogenetically or functionally related network ecologies seen in many different subjects (para 79). McKenzie teaches the bacterial preparations contained 20% Bacteroides fragilis and 20% Phascolarctobacterium faecium (pg. 118, 119, Table GB), and the secondary references Chatila, Henson, Wargo, and evidentiary reference Ibrahim disclose the limitations not taught in McKenzie, thus would be obvious to combine and arrive at the claimed method.
Regarding the obviousness double patenting rejection of US Patent 11,219,649, Applicant argues it would not be obvious to include Phascolarctobacterium with Bacteroides because McKenzie would not motivate a person skilled in the art to modify a composition lacking Phascolarctobacterium (McKenzie’s) with a composition comprising Phascolarctobacterium but lacking Bacteroides (‘649 claims). As discussed above, McKenzie does teach compositions comprising Phascolarctobacterium and Bacteroides, thus would motivate a person to modify the compositions recited in ‘649 by adding Bacteroides species for therapeutic use, as taught by McKenzie, thus the double patenting rejection is maintained.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA EDWARDS whose telephone number is (571)270-0938. The examiner can normally be reached M-F 8am-5pm EST.
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, Louise Humphrey can be reached at (571) 272-5543. 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.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
Prosecution Insights