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
This application is a US national phase of PCT/US2022/081195, filed December 8, 2022, with foreign priority application IE2021/0210, filed December 8, 2021.
Applicant’s amendment filed July 20, 2026 is acknowledged. Claims 1-12 and 14-18 are canceled, claims 19-24 are newly added, and claim 13 is amended.
Currently claims 13 and 19-24 are pending and under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 13 and 19-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating gastrointestinal infections in a human subject by administering Bacillus coagulans comprising SEQ ID NO’s 1-3, does not reasonably provide enablement for a method for treating skin and urinary tract infections or protection against oxidative stress in a human subject by administering the claimed strain. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of the claims:
Claims 13 and 19-24 are drawn to a method for treating a broad range of unrelated conditions by administering a Bacillus coagulans strain comprising a nucleotide sequence SEQ ID NO’s: 1-3, including skin infections, urinary tract infections, gastrointestinal infections, and protection against oxidative stress, in a human subject. Thus, the claims are broad in that they include treatment of a large number of conditions which would not be expected to be treated in the same manner with the same agents.
The nature of the invention:
The nature of the invention relies upon administering a B. coagulans strain comprising nucleotide sequences SEQ ID NO’s: 1-3 to a human subject with any of the recited conditions, and administering said strain will treat or improve those conditions.
The state of the prior art:
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
A thorough review of the patent and non-patent literature indicates that the state of the art demonstrating administering a B. coagulans strain comprising nucleotide sequence SEQ ID NO’s: 1-3 to a human subject for treating and/or improving any of the recited conditions is variable. Maity et al. (Journal of Dietary Supplements, 2021, 18(6), 577–596, cited in PTO-892 mailed 4/20/2026) discloses treatment with a closely related B. coagulans LBSC strain (having a 16S rRNA sequence that is 99% identical to instant SEQ ID NO: 2) reversed gut microbiome ‘dysbiosis’ due to enhanced microbial diversity and improved pathophysiological symptoms of IBS strain (abstract). Another study by Xing et al. (Environmental Pollution 255 (2019) 113139, pgs. 1-10, cited in PTO-892 mailed 4/20/2026) showed treatment with another closely related B. coagulans R11 strain (which has 100% sequence identity with instant SEQ ID NO: 2) also maintained intestinal health and decreased intestinal injury in lead-exposed mice by regulating the gut microflora (title). Zhang et al. (Medicine (2020) 99:45, pgs. 1-7) discloses the effectiveness of administering B. coagulans in humans with active Helicobacter pylori infections (abstract).
Cao et al. (Journal of Functional Foods 64 (2020) 103643, pgs. 1-11, cited in PTO-892 mailed 4/20/2026) reviews B. coagulans probiotic’s success in treating gastrointestinal diseases, strengthening immunity function, and reforming the microbiome profile of the gut (Tables 2-3), and suggests B. coagulans could probably be an excellent therapy agent for several metabolic diseases (pg. 5, sec. 4.2). However Cao discloses there are multiple B. coagulans strains with different host origins, and many of the probiotic functions of B. coagulans are strain-dependent, thus may be advantageous to combine different strains of B. coagulans to maximize their beneficial effects in the future (pg. 8, col. 2, para 1).
Thus a review of the prior art does not reasonably support or find a strong correlation between administering specific probiotic B. coagulans strains for treating or improving the full scope of the recited conditions, except for gastrointestinal diseases.
The level of one of ordinary skill and predictability in the art:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention. Because the state of the prior art does not provide evidence of the degree of predictability that methods for treating skin, gastrointestinal, and urinary tract infections, or protection against oxidative stress, by administering the B. coagulans probiotic strain, one of ordinary skill in the art would look for guidance or direction in the instant specification.
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03). In the instant case, the various conditions that fall within the claimed scope would require different treatment methods. For instance, treating skin infections or protecting against oxidative stress would not necessarily be treated with the same agent or by the same mechanism.
The amount of direction provided by the inventor and existence of working examples:
The instant application describes administering the B. coagulans CGI314 strain that comprises SEQ ID NO’s: 1-3 to healthy human subjects to evaluate safety, tolerance, and gastrointestinal health for its use as a probiotic (pg. 41, Example 3). The CGI314 strain was administered daily for 45 days at a dose of 1 x 109 CFU, as well as a probiotic cocktail containing CGI314, Bacillus subtilis DE111, Bacillus megaterium MIT411, and Bacillus clausii CSI08 (pg. 41, Example 3). Only the probiotic cocktail significantly decreased incidence of loose stools throughout the entire study, however recorded respiratory, urinary and gastrointestinal symptoms were not influenced (pg. 53, lines 24-29). In Example 3, a borderline significant result was observed for clinically relevant gastrointestinal infection [0251]. In Example 1, CGI314 was demonstrated to have antimicrobial activity against E. coli, S. enteriditis, S. aureus, and P. aeruginosa in an in-vitro study [0128, 131].
The working embodiments do not describe any method treatments for treating skin or urinary tract infections, or protection against oxidative stress, and how administering the claimed B. coagulans strain would effectively treat those conditions, only describing a safety efficacy study of the strain, wherein a borderline significant result was observed for gastrointestinal infections and an in-vitro study demonstrating the strain’s antimicrobial activity. While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role that a B. coagulans strain comprising nucleic acid sequences SEQ ID NO’s 1-3 for treating skin or urinary tract infections, or for protection against oxidative stress, and given the broad scope of the claims and the different conditions encompassed, it is unpredictable if administering said strain would reasonably treat all of the aforementioned unrelated conditions as claimed.
The specification does not provide sufficient guidance on administering the B. coagulans strain in the treatment of the full scope of the recited conditions. Rather the specification merely describes a safety evaluation of the probiotic. The prior art also does not provide additional guidance to enable treating the full scope of the claims.
Therefore due to the unpredictability in the art with respect to treating the scope of the conditions recited in the claims, one would have to engage in experimentation that is not reasonable in order to determine the effective methods of treatment by administering the B. coagulans strain for the various conditions.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial-and-error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
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 13 and 19-24 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 13 recite “a Bacillus coagulans strain comprising a purified microbial population that comprises a bacterium”. The claim recites a narrower limitation (i.e. B. coagulans strain) comprising a broader limitation (i.e. a purified microbial population) in the same claim. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Similarly it is unclear whether the strain comprises separate bacteriums comprising the different SEQ ID NO’s, since SEQ ID NO: 3 already comprises SEQ ID NO’s: 1 & 2.
Claim 13 also recites “wherein bacterial levels are decreased by inhibition of growth in skin, urinary tract, or gastrointestinal tract, and wherein antioxidant capacity is increased in the human subject.”, which fails to identify what ‘bacterial levels’ are decreased by inhibition of growth in skin, urinary tract, or gastrointestinal tract, as this limitation could be referring to B. coagulans growth or some other unidentified bacteria. and what exactly is inhibited in the recited tissues, or if the limitation is satisfied by inhibition of any bacteria in any of the tissues, regardless of the treatment method employed. The limitation ‘bacteria levels are decreased’ is also relative, and not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The term “antioxidant capacity is increased” in claim 13 is a relative term which renders the claim indefinite. The term “antioxidant capacity is increased” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 13 also recites the method is for ‘treating skin infections, urinary tract infections, gastrointestinal infections or protection against oxidative stress’, but at the end of the claim requires both “bacterial levels are decreased by inhibition of growth in skin, urinary tract, or gastrointestinal tract, and wherein antioxidant capacity is increased in the human subject”, thus ambiguity arises as to if both results recited in the wherein clause are required regardless of the method of treating or protection employed.
Claim 23 recites “The method of claim 13, wherein the antioxidant capacity of the Bacillus coagulans strain has a Trolox equivalent concentration of greater than about 3000 Trolox equivalents in nmol/mL.”, which is indefinite because the recitation of ‘the antioxidant capacity of the Bacillus coagulans strain’ renders the scope unclear, since claim 13 recites that ‘the antioxidant capacity is increased in the human subject’, whereas claim 23 recites the antioxidant capacity as being a property of the B. coagulans strain. The term ‘about 3000 Trolox equivalents’ is also a relative term that lacks objective boundaries and is not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 19-22 and 24 are likewise rejected as being dependent on an indefinite claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 22-23 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 recites “wherein the bacterial levels of bacteria selected from the group consisting of E. coli, S. enteriditis, S. aureus, and P. aeruginosa are reduced compared to control.”, which does not further limit the claimed method recited in claim 13 from which it depends. The ‘wherein’ clause is an intended result, therefore does not modify or narrow the method in any way. Similarly claim 23 recites “wherein the antioxidant capacity of the Bacillus coagulans strain has a Trolox equivalent concentration of greater than about 3000 Trolox equivalents in nmol/mL.”, which does not further limit the claims. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 13 and 19-22 are rejected under 35 U.S.C. 103 as being obvious over Deaton (US20210145899 A1, IDS 09/19/2024) in view of Zhang et al. (Medicine (2020) 99:45, pgs. 1-7, hereinafter “Zhang”) and Wu et al. (Int. J. Mol. Sci. 2018, 19, 2084, pgs. 1-17, hereinafter “Wu”), as evidenced by Zhou et al. (Animals 2020, 10, 454, pgs. 1-9, hereinafter “Zhou”).
The applied reference has a common inventor with the instant application. Although the assignee names appear similar, the record does not establish that the reference and the present application were commonly owned. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Deaton teaches Bacillus coagulans CGI314 strain was grown in LB and TSB [0082], which as evidenced by GenBank Accession number JABBFU000000000.1 and disclosed in the instant specification [0068, 0084-0086] comprises the gyrB sequence that is 100% identical to instant SEQ ID NO: 1, the 16S rRNA sequence that shares 100% identity to instant SEQ ID NO: 2, and the whole genome sequence that is instant SEQ ID NO: 3. Deaton teaches CGI314 had strong antimicrobial properties against E. coli, Salmonella enteriditis, and Staphylococcus aureus, as well as preventing E. coli and Pseudomonas aeruginosa adherence in in-vitro studies [3392, 3422, 3433], which meets the limitation of ‘inhibiting growth’ of the recited bacteria in claims 13 and 22. Deaton also teaches a method of inhibiting growth or activity of bacteria, yeast, and/or fungi on skin or a mucous membrane in a mammal by administering a Bacillus subtilis DE111 strain (claims 12-13).
Deaton does not teach a method for treating gastrointestinal diseases by administering the CGI314 strain to a human subject, thereby decreasing bacterial levels in the gastrointestinal tract and wherein the antioxidant capacity is increased in the human subject.
However, Zhang teaches the efficacy and safety of Bacillus coagulans in Helicobacter pylori treatment (title). Zhang teaches administration of B. coagulans tablets (350 mg x 3 tablets TID) to patients diagnosed with active H. pylori infections, and found B. coagulans 20% eradication rate, which was statistically significant (abstract, pg. 2, sec. 2.4), which meets the limitation of ‘comestibly acceptable carrier’ recited in claim 19. Zhang teaches B. coagulans may effectively inhibit H pylori to some extent, with rare adverse events, and thus may reduce the burden of antibiotic resistance (abstract). Neither Deaton nor Zhang teach the method increases antioxidant capacity in the human subject.
However, Wu teaches the beneficial impact and molecular mechanism of B. coagulans on piglets’ intestines (title). Wu teaches a method of administering to piglets in the B6 group (basal diet + 2 x 106 CFU/g B. coagulans) and the B7 group (basal diet + 2 x 107 CFU/g B. coagulans) which falls within the range of the unit dose recited in claims 20-21, and found the B6 and B7 groups had a significantly decreased diarrhea rate and diamine oxidase (DAO) activity in plasma (p < 0.05), increased villus height in ileum and decreased crypt depth in the jejunum (p < 0.05); increased activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the content of malondialdehyde (MDA) and H2O2 in the intestine (p < 0.05) (abstract). Wu teaches the data suggested that supplementing B. coagulans had beneficial impacts on promoting nutrients’ metabolism, maintaining intestinal integrity, and alleviating oxidative stress and diarrhea (abstract). Wu teaches the results of the redox status showed that supplementing B. coagulans alleviated oxidative stress and enhanced the antioxidative capacity of the intestine, which meets this limitation in claim 13 (pg. 5, para 2). Although Wu teaches the antioxidative capacity in piglets, B. coagulans is known to alleviate oxidative stress by binding heavy metals that induce production of ROS in other animal models, as evidenced by Zhou (pg. 5 para 1-2).
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 utilize the B. coagulans CGI314 strain that has antimicrobial properties as taught by Deaton, in a method for treating gastrointestinal infection as taught by Zhang, with a reasonable expectation of decreasing bacterial levels by inhibition of growth in the gastrointestinal tract as taught by Deaton and Zhang, as well as expect the antioxidant capacity would be increased in the human subject as taught by Wu. One of ordinary skill in the art would have been motivated to administer the CGI314 probiotic in a method for treating gastrointestinal infections, since this strain has been proven effective in inhibiting common gut pathogens such as E. coli, S. enteriditis, and S. aureus growth as taught by Deaton.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Response to Arguments
Applicant's arguments filed July 20, 2026 have been fully considered but they are not persuasive. Regarding remarks directed to the 35 U.S.C. 112(a) scope of enablement rejection of claims 13 and 19-24, Applicant argues certain claimed methods of use are enabled; however, in the present application amended independent claim 13 is not directed to the gastrointestinal diseases, or improving immune health subject matter, but instead claim 13 is directed to a method of treating skin infections, urinary tract infections, gastrointestinal infections, or protection against oxidative stress in a human subject. However, as explained in the modified/maintained 112(a) rejection, the currently claimed methods are not enabled for the full scope of the claimed methods, thus the rejection stands.
Applicant’s arguments with respect to claim 13 rejected under 35 USC § 102 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
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.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
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