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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/16/2026 has been entered.
Priority
This application is a 371 of PCT/JP2021/030571 filed 08/20/2021. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) based on JP 2020-146884 filed 09/01/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of the Claims
Applicant’s amendment filed on 03/23/2026 is acknowledged.
Claim 1 is amended. Claims 9-13 are new.
Claims 1-13 are pending (claim set filed 03/23/2026) and are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 03/23/2026 are acknowledged. All of the amendment and arguments have been thoroughly reviewed and considered.
For the purposes of clarity of the record, the reasons for the Examiner's withdrawal and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner's response to arguments section.
The previous claims 1-8 rejections under 35 U.S.C. 103 have been withdrawn necessitated by amendment of claims. Upon further consideration new 35 U.S.C. 103 rejection is applied.
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 2, 3, 5-8, 10 and 12 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 2 recites the limitation “the bacterial strain” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 from which claim 2 depends recites one or more bacterial strains of the genus Prevotella. It is not clear if claim 2 is directed to any strain of the genus Prevotella or a specific strain. The scope and boundaries of claim 2 are not certain making claim 2 indefinite.
Claim 3 recites the limitation “the bacterial strain” in line 1 and has the same issue as discussed above for claim 2. There is insufficient antecedent basis for this limitation in the claim. It is not clear if claim 2 is directed to any strain of the genus Prevotella or a specific strain since claim 1 from which claim 2 depends recites one or more bacterial strains of the genus Prevotella. Besides, claim 3 recites the limitation "a ratio of the bacterial strain of the genus Bacteroides" in line 2. There is insufficient antecedent basis for these limitation in the claim. The amended claim 1 from which claim 3 depends recites one or more bacterial strains of the genus Prevotella and does not recite a bacterial strain of the genus Bacteroides. It is not clear to what bacterial strain of the genus Bacteroides Applicant is referring to. The scope and boundaries of claim 3 are not certain making claim 3 indefinite.
Claim 5 has the same issue as claim 3. Claim 5 recites the limitation "a ratio of the bacterial strain of the genus Bacteroides" in line 2. There is insufficient antecedent basis for these limitation in the claim. The amended claim 1 from which claim 3 depends recites one or more bacterial strains of the genus Prevotella and does not recite a bacterial strain of the genus Bacteroides. It is not clear to what bacterial strain of the genus Bacteroides Applicant is referring to. The scope and boundaries of claim 5 are not certain making claim 5 indefinite.
Claim 6, dependent on claim 2, claim 7, dependent on claim 3, and claim 8, dependent on claim 5, do not resolve the issues mentioned above and are rejected.
Claim 10 recites the limitation “the bacterial strain” in line 1. There is insufficient antecedent basis for this limitation in the claim. It is not clear if claim 10 is directed to any strain of the genus Bacteroides or to a specific strain since claim 9 from which claim 10 depends recites one or more bacterial strains of the genus Bacteroides. Besides, claim 10 recites the limitation "a ratio of the bacterial strain of the genus Prevotella" in line 5. There is insufficient antecedent basis for this limitation in the claim. Claim 9 from which claim 10 depends recites one or more bacterial strains of the genus Bacteroides and does not recite a bacterial strain of the genus Prevotella. It is not clear to what bacterial strain of the genus Prevotella Applicant is referring to. The scope and boundaries of claim 10 are not certain making claim 10 indefinite.
Claim 12 recites the limitation "a ratio of the bacterial strain of the genus Prevotella" in line 8. There is insufficient antecedent basis for these limitation in the claim. Claim 12 is directed to inoculation of one or more bacterial strains of the genus Bacteroides and does not recite inoculation of a bacterial strain of the genus Prevotella. It is not clear to what bacterial strain of the genus Prevotella Applicant is referring to. The scope and boundaries of claim 12 are not certain making claim 12 indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Takahashi (Takahashi et al. J. Dent. Res., 1992, 71, 1509-1515 on record in IDS) and Shah (Shah and Collins Int. J. Syst. Bacteriol., 1990, 40, 205-208) as evidenced by GenBank L16476.1 (GenBank L16476.1, Prevotella buccalis ATCC 35310 16S rRNA gene, 2013 [retrieved on 09/21/2026]. Retrieved from the Internet: <Prevotella buccalis ATCC 35310 16S ribosomal RNA gene, partial sequence - Nucleotide - NCBI>).
Regarding claim 1, Prescott teaches effect of the maternal probiotic supplementation on immune markers in breast milk (Abstract). Prescott describes treatment of women with daily supplements of Lactobacillus rhamnosus or Bifidobacterium lactis beginning 2-5 weeks before delivery and continuing for 6 months in lactating women (Abstract). Prescott discloses that mothers who had been on a probiotic had higher level of IgA compared to placebo group especially for early breast milk samples (p. 1609, left column, last paragraph, Figure 3).
Prescott does not teach bacterial strains of the genus Prevotella with the recited 16S rRNA sequence identity. Prescott does not explicitly teach inoculation of bacterial strains to a mammalian mother in need of increasing the IgA antibody content in milk.
Takahashi teaches that immunization of pregnant cows with single strains of oral bacteria or pools of strains leads to increase in immunoglobulins IgG1, IgG2, IgM and IgA (Abstract). Takahashi describes Prevotella intermedia strains ATCC 25611 and ATCC 25261 used for immunization (p. 1509, right column, 3rd ‘paragraph).
Shah teaches Prevotella genus, reclassification of several Bacteroides species to Prevotella (Abstract) and provides description of different Prevotella species (p. 206, right column, p. 207, left column). Among these species is Prevotella intermedia ATCC 25611 strain used by Takahashi. Shah discloses information on various strains of Prevotella genus including prior art for strains’ description. One of these strains is Prevotella buccalis ATCC 35310 strain. The sequence of 16S rRNA of the Prevotella buccalis ATCC 35310 has 98.8% identity to instant SEQ ID NO:2 as evidenced by GenBank L16476.1.
First, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add or replace the Lactobacillus rhamnosus or Bifidobacterium lactis in the supplemental composition increasing IgA in breast milk of Prescott teaching with Prevotella strain based on Takahashi teaching. One would have been motivated to do so since Takahashi showed increase of IgA in the milk of cow immunized with Prevotella strains. A skilled artisan would have reasonably expected success in the combination because Prescott and Takahashi teach effect of probiotic bacterial strains on induction of IgA production.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to try using Prevotella strains described by Shah one of which is Prevotella buccalis ATCC 35310 (the sequence of the 16S rRNA of which is 98.8% identical to SEQ ID NO:2 as evidenced by GenBank L16476.1) for supplemental composition increasing IgA in breast milk based on Prescott and Takahashi teachings. One would have been motivated to do so with the reasonably expected success since Takahashi teaches Prevotella strain from Shah teaching to increase IgA content in cow’s milk and Shah provides description of various Prevotella strains including ATCC 356310 strain the 16S rRNA sequence of which is provided by GenBank L16476.1.
Last, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the supplemental composition increasing the content of IgA in the breast milk based on Prescott, Takahashi and Shah teachings to mother in need to increase the IgA content in the milk. One would have been motivated to do so since Prescott teaches that breast milk has an immunomodulatory effect (p. 1607, left column, 2nd paragraph) and therefore it would be beneficial to increase the level of IgA in the breast milk in case of its deficiency. A skilled artisan would have reasonably expected success in that because Prescott describes how to measure IgA content in milk (p. 1608, left column, 4th paragraph) and teaches increase in IgA content in the breast milk by inoculation of bacterial strains to mothers and Takahashi and Shah provide bacterial strain to induce IgA production. Thus, Prescott, Takahashi and Shah teachings as evidenced by GenBank L16476.1 render claim 1 obvious.
Regarding claim 4, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Takahashi and Shah teachings as evidenced by GenBank L16476.1 render claim 4 obvious.
Claims 2 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Takahashi (Takahashi et al. J. Dent. Res., 1992, 71, 1509-1515 on record in IDS) and Shah (Shah and Collins Int. J. Syst. Bacteriol., 1990, 40, 205-208) as evidenced by GenBank L16476.1 (GenBank L16476.1, Prevotella buccalis ATCC 35310 16S rRNA gene, 2013 [retrieved on 09/21/2026]. Retrieved from the Internet: <Prevotella buccalis ATCC 35310 16S ribosomal RNA gene, partial sequence - Nucleotide - NCBI>) as applied to claim 1 above, and further in view of Yanagibashi (Yanagibashi et al. Biosci. Biotechnol. Biochem., 2009, 73, 372-377 on record in IDS).
The teachings of Prescott, Takahashi and Shah have been set forth above.
Prescott, Takahashi and Shah do not teach bacterial strains to activate immune function in Peyer’s patches and increase the number of IgA producing plasma cells.
Regarding claim 2, Yanagibashi teaches production of IgA by the gut mucosal immune system. Yanagibashi describes that intestinal microorganisms increase the number of IgA-secreting plasma cells by activating Peyer’s patches (PP) (p. 372, right column). Yanagibashi showed the immunomodulatory effect of Bacteroides and Lactobacillus on IgA production by Peyer’s patches (PP) lymphocytes (Abstract). Yanagibashi discloses that Bacteroides induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus (p. 373, right column, 3rd paragraph and Figure 1) and Bacteroides more strongly induced PPs B cell differentiation to IgA+ B cells and subsequent terminal differentiation into IgA producing plasma cells (p. 375, left column, 1st paragraph, Figure 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to suggest that Prevotella strains taught by Takahashi and Shah will increase IgA in the maternal milk based on Prescott and Takahashi teachings by activating immune function in Peyer’s patches and increasing the number of IgA producing plasma cells as taught by Yanagibashi for Bacteroides and Lactobacillus strains. One would have been motivated to do so with reasonably expected success because Prescott teaches increase in production of IgA in breast milk after Lactobacillus and Bifidobacterium supplementation, Takahashi describes Prevotella strains to increase IgA content in maternal milk and Yanagibashi discloses the mechanism of IgA increase in maternal milk by Lactobacillus and Bacteroides activation of immune function in Peyer’s patches. Thus, Prescott, Takahashi, Shah and Yanagibashi teachings as evidenced by GenBank L16476.1 render claim 2 obvious.
Regarding claim 6, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Takahashi, Shah and Yanagibashi teachings as evidenced by GenBank L16476.1 render claim 6 obvious.
Claims 3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Takahashi (Takahashi et al. J. Dent. Res., 1992, 71, 1509-1515 on record in IDS) and Shah (Shah and Collins Int. J. Syst. Bacteriol., 1990, 40, 205-208) as evidenced by GenBank L16476.1 (GenBank L16476.1, Prevotella buccalis ATCC 35310 16S rRNA gene, 2013 [retrieved on 09/21/2026]. Retrieved from the Internet: <Prevotella buccalis ATCC 35310 16S ribosomal RNA gene, partial sequence - Nucleotide - NCBI>) as applied to claim 1 above, and further in view of Sun (Sun et al. Frontiers in Cell. Infec. Microbiol., 2019, 9, 99, 1-13).
The teachings Prescott, Takahashi and Shah have been set forth above.
Prescott, Takahashi and Shah do not teach inoculation of the bacterial strain to a mammalian mother with the decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora before inoculation.
Regarding claim 3, Sun teaches disruption of gut microbiota by different antibiotics (Abstract). Sun describes that mice were treated with the broad-spectrum antibiotic enrofloxacin, gram-positive bactericidal antibiotic vancomycin, and gram-negative bactericidal antibiotic polymixin B sulfate. These antibiotics lead to different effect on mice (p. 7, right column, last paragraph). The most significant changes of gut microbiota were with vancomycin treatment (p. 11, left column, last paragraph). Sun discloses changes at the taxonomical family level for various bacterial families that include increase in the abundance of some families, such as Enterobacteriaceae, and significant decrease in Prevotellaceae and Bacteroidaceae families (p. 4, right column, last paragraph). Sun mentions that gut microbiome plays an essential role in modulating host immune responses (Abstract) and indicates that antibiotic treatment with vancomycin can impact the immune cells. Sun provides example of mice with dysbiosis induced by ampicillin treatment that have decreased amount of secretory IgA in the colon (p. 7, right column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that method of increasing IgA in mammalian mothers by inoculation of recited Prevotella strain based on Prescott, Takahashi and Shah teachings can be applied to subjects that have decreased ratio of the recited Prevotella and Bacteroides to the whole intestinal bacterial flora. One would have been motivated to do so since Sun showed significant reduction in the abundance of both Bacteroides and Prevotella after antibiotic vancomycin treatment and mentions that vancomycin treatment impacts immune cells and that dysbiosis decreases amount of secretory IgA in the colon. A skilled artisan would have reasonably expected success in that because combination of Prescott, Takahashi and Shah teachings suggests inoculation of instant Prevotella strain to increase IgA in the breast milk and Sun describes conditions in which such inoculation is necessary to restore/increase Prevotella level leading to increase of IgA in the milk.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that vancomycin treatment taught by Sun will decrease the ratio of instant strains of Bacteroides and Prevotella. One would have been motivated to expect that since Sun teaches reduction in the abundance of taxonomical families of Prevotellaceae and Bacteroidaceae that include instant strains.
Thus, Prescott, Takahashi, Shah and Sun teachings as evidenced by GenBank L16476.1 render claim 3 obvious.
Regarding claim 7, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Takahashi, Shah and Sun teachings as evidenced by GenBank L16476.1 render claim 7 obvious.
Claims 5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Takahashi (Takahashi et al. J. Dent. Res., 1992, 71, 1509-1515 on record in IDS), Shah (Shah and Collins Int. J. Syst. Bacteriol., 1990, 40, 205-208) and Yanagibashi (Yanagibashi et al. Biosci. Biotechnol. Biochem., 2009, 73, 372-377 on record in IDS) as evidenced by GenBank L16476.1 (GenBank L16476.1, Prevotella buccalis ATCC 35310 16S rRNA gene, 2013 [retrieved on 09/21/2026]. Retrieved from the Internet: <Prevotella buccalis ATCC 35310 16S ribosomal RNA gene, partial sequence - Nucleotide - NCBI>) and as applied to claims 1 and 2 above, and further in view of Sun (Sun et al. Frontiers in Cell. Infec. Microbiol., 2019, 9, 99, 1-13).
The teachings Prescott, Takahashi, Shah and Yanagibashi have been set forth above.
Prescott, Takahashi, Shah and Yanagibashi do not teach inoculation of the bacterial strain to a mammalian mother with the decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora before inoculation.
Regarding claim 5, Sun teaches disruption of gut microbiota by different antibiotics (Abstract). Sun describes that mice were treated with the broad-spectrum antibiotic enrofloxacin, gram-positive bactericidal antibiotic vancomycin, and gram-negative bactericidal antibiotic polymixin B sulfate. These antibiotics lead to different effect on mice (p. 7, right column, last paragraph). The most significant changes of gut microbiota were with vancomycin treatment (p. 11, left column, last paragraph). Sun discloses changes at the taxonomical family level for various bacterial families that include increase in the abundance of some families, such as Enterobacteriacea,e and significant decrease in Prevotellaceae and Bacteroidaceae families (p. 4, right column, last paragraph). Sun mentions that gut microbiome plays an essential role in modulating host immune responses (Abstract) and indicates that antibiotic treatment with vancomycin can impact the immune cells. Sun provides example of mice with dysbiosis induced by ampicillin treatment that have decreased amount of secretory IgA in the colon (p. 7, right column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that method of increasing IgA in mammalian mothers by inoculation of recited Prevotella strain based on Prescott, Takahashi and Shah teachings can be applied to subjects that have decreased ratio of the recited Prevotella and Bacteroides to the whole intestinal bacterial flora. One would have been motivated to do so since Sun showed significant reduction in the abundance of both Bacteroides and Prevotella after antibiotic vancomycin treatment and mentions that vancomycin treatment impacts immune cells and that dysbiosis decreases amount of secretory IgA in the colon. A skilled artisan would have reasonably expected success in that because combination of Prescott, Takahashi and Shah teachings suggests inoculation of instant Prevotella strain to increase IgA in the breast milk and Sun describes conditions in which such inoculation is necessary to restore/increase Prevotella level leading to increase of IgA in the milk.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that vancomycin treatment taught by Sun will decrease the ratio of instant strains of Bacteroides and Prevotella. One would have been motivated to expect that since Sun teaches reduction in the abundance of taxonomical families of Prevotellaceae and Bacteroidaceae that include instant strains.
Thus, Prescott, Takahashi, Shah, Yanagibashi and Sun teachings as evidenced by GenBank L16476.1 render claim 5 obvious.
Regarding claim 8, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Takahashi, Shah, Yanagibashi and Sun teachings as evidenced by GenBank L16476.1 render claim 8 obvious.
Claims 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Yanagibashi (Yanagibashi et al. Biosci. Biotechnol. Biochem., 2009, 73, 372-377 on record in IDS) and Miyamoto (Miyamoto and Itoh, Int. J. Syst. Evol. Microbiol., 2000, 50, 145-148) as evidenced by GenBank EU 136694.1 (GenBank EU 136694.1, Bacteroides acidifaciens strain JCM 10556 16S rRNA gene, 2008, p. 1 on record in IDS).
Regarding claim 9, Prescott teaches effect of the maternal probiotic supplementation on immune markers in breast milk (Abstract). Prescott describes treatment of women with daily supplements of Lactobacillus rhamnosus or Bifidobacterium lactis beginning 2-5 weeks before delivery and continuing for 6 months in lactating women (Abstract). Prescott discloses that mothers who had been on a probiotic had higher level of IgA compared to placebo group especially for early breast milk samples (p. 1609, left column, last paragraph, Figure 3). Prescott teaches treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and does not teach inoculating the mammalian mother with sugar.
Prescott does not teach bacterial strains of the genus Bacteroides with the recited 16S rRNA sequence identity. Prescott does not explicitly teach inoculation of bacterial strains to a mammalian mother in need of increasing the IgA antibody content in milk.
Yanagibashi teaches production of IgA by the gut mucosal immune system. Yanagibashi describes that intestinal microorganisms increase the number of IgA-secreting plasma cells by activating Peyer’s patches (PP) (p. 372, right column). Yanagibashi compared the immunomodulatory effect of Bacteroides and Lactobacillus on IgA production by Peyer’s patches (PP) lymphocytes (Abstract). Yanagibashi discloses that Bacteroides induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus (p. 373, right column, 3rd paragraph and Figure 1) and Bacteroides more strongly induced PPs B cell differentiation to IgA+ B cells and subsequent terminal differentiation into IgA producing plasma cells (p. 375, left column, 1st paragraph, Figure 2).
Yanagibashi describes using three strains of Bacteroides, two of which were not identified and the third strain was Bacteroides acidifaciens type A43 from the prior art of Miyamoto (p. 373, left column, 3rd paragraph).
Miyamoto describes isolation of several strains that were characterized as Bacteroides acidifaciens (Abstract). The 16S rRNA analysis of strains (including A43 strain used by Yanagibashi) allowed to divide strains into two groups with very high homology between them of 98.2% (p. 147, right column, 3rd paragraph). The type strain A40 was deposited in the Japan Collection of Microorganism as JCM10556 (p. 148, left column, 5th paragraph). The sequence of 16S rRNA of the Bacteroides acidifaciens strain JCM10556 is 100% identical to instant SEQ ID NO:1 as evidenced by GenBank EU 136694.1.
First, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the Lactobacillus rhamnosus or Bifidobacterium lactis in the supplemental composition increasing IgA in breast milk of Prescott teaching with Bacteroides strain from Yanagibashi teaching. One would have been motivated to do so since Yanagibashi showed that Bacteroides strains induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus strains and more strongly induced PPs B cell differentiation into IgA producing plasma cells. A skilled artisan would have reasonably expected success in the combination because Prescott and Yanagibashi teach effect of probiotic bacterial strains to induce IgA production.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Bacteroides acidifaciens strain JCM10556 (the sequence of the 16S rRNA of which is 100% identical to SEQ ID NO:1 as evidenced by GenBank EU 136694.1) from Miyamoto teaching for supplemental composition increasing IgA in breast milk based on Prescott and Yanagibashi teachings. One would have been motivated to do so with the reasonably expected success since Yanagibashi teaches strain from Miyamoto teaching to increase IgA production by PP and differentiation of B cells into IgA secreting plasma cells and Miyamoto characterized isolated strains as having 98.2% 16S rRNA identity with each other and deposited the type strain JCM10556 the 16S rRNA sequence of which is provided by GenBank 136694.1.
Last, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the supplemental composition increasing the content of IgA in the breast milk based on Prescott , Yanagibashi and Miyamoto teachings to mother in need to increase the IgA content in the milk. One would have been motivated to do so since Prescott teaches that breast milk has an immunomodulatory effect (p. 1607, left column, 2nd paragraph) and therefore it would be beneficial to increase the level of IgA in the breast milk in case of its deficiency. A skilled artisan would have reasonably expected success in that because Prescott describes how to measure IgA content in milk (p. 1608, left column, 4th paragraph) and teaches increase in IgA content in the breast milk by inoculation of bacterial strains to mothers and Yanagibashi and Miyamoto provide bacterial strain to induce IgA production. Thus, Prescott, Yanagibashi and Miyamoto teachings as evidenced by GenBank EU 136694.1 render claim 9 obvious.
Regarding claim 11, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Yanagibashi and Miyamoto teachings as evidenced by GenBank EU 136694.1 render claim 11 obvious.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Yanagibashi (Yanagibashi et al. Biosci. Biotechnol. Biochem., 2009, 73, 372-377 on record in IDS) and Miyamoto (Miyamoto and Itoh, Int. J. Syst. Evol. Microbiol., 2000, 50, 145-148) as evidenced by GenBank EU 136694.1 (GenBank EU 136694.1, Bacteroides acidifaciens strain JCM 10556 16S rRNA gene, 2008, p. 1 on record in IDS) as applied to claim 9 above, and further in view of Sun (Sun et al. Frontiers in Cell. Infec. Microbiol., 2019, 9, 99, 1-13).
The teaching of Prescott, Yanagibashi and Miyamoto have been set forth above.
Prescott, Yanagibashi and Miyamoto do not teach inoculation of the bacterial strain to a mammalian mother with the decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora before inoculation.
Regarding claim 10, Sun teaches disruption of gut microbiota by different antibiotics (Abstract). Sun describes that mice were treated with the broad-spectrum antibiotic enrofloxacin, gram-positive bactericidal antibiotic vancomycin, and gram-negative bactericidal antibiotic polymixin B sulfate. These antibiotics lead to different effect on mice (p. 7, right column, last paragraph). The most significant changes of gut microbiota were with vancomycin treatment (p. 11, left column, last paragraph). Sun discloses changes at the taxonomical family level for various bacterial families that include increase in the abundance of some families, such as Enterobacteriaceae and significant decrease in Prevotellaceae and Bacteroidaceae families (p. 4, right column, last paragraph). Sun mentions that gut microbiome plays an essential role in modulating host immune responses (Abstract) and indicates that antibiotic treatment with vancomycin can impact the immune cells. Sun provides example of mice with dysbiosis induced by ampicillin treatment that have decreased amount of secretory IgA in the colon (p. 7, right column, 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that method of increasing IgA in mammalian mothers by inoculation of recited Bacteroides strain based on Prescott, Yanagibashi and Miyamoto teachings can be applied to subjects that have decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora. One would have been motivated to do so since Sun showed significant reduction in the abundance of both Bacteroides and Prevotella after antibiotic vancomycin treatment and mentions that vancomycin treatment impacts immune cells and that dysbiosis decreases amount of secretory IgA in the colon. A skilled artisan would have reasonably expected success in that because combination of Prescott, Yanagibashi and Miyamoto teachings suggests inoculation of instant Bacteroides strain to increase IgA in the breast milk and Sun describes conditions in which such inoculation is necessary to restore/increase Bacteroides level leading to increase of IgA in the milk.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that vancomycin treatment taught by Sun will decrease the ratio of instant strains of Bacteroides and Prevotella. One would have been motivated to expect that since Sun teaches reduction in the abundance of taxonomical families of Prevotellaceae and Bacteroidaceae that include instant strains.
Thus, Prescott, Takahashi, Shah, Yanagibashi and Sun teachings as evidenced by GenBank L16476.1 render claim 10 obvious.
Claims 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Prescott (Prescott et al. Clin. Exper. Allergy, 2008, 38, 1606-1614) in view of Yanagibashi (Yanagibashi et al. Biosci. Biotechnol. Biochem., 2009, 73, 372-377 on record in IDS), Miyamoto (Miyamoto and Itoh, Int. J. Syst. Evol. Microbiol., 2000, 50, 145-148) and Sun (Sun et al. Frontiers in Cell. Infec. Microbiol., 2019, 9, 99, 1-13) as evidenced by GenBank EU 136694.1 (GenBank EU 136694.1, Bacteroides acidifaciens strain JCM 10556 16S rRNA gene, 2008, p. 1 on record in IDS).
Regarding claim 12, Prescott teaches effect of the maternal probiotic supplementation on immune markers in breast milk (Abstract). Prescott describes treatment of women with daily supplements of Lactobacillus rhamnosus or Bifidobacterium lactis beginning 2-5 weeks before delivery and continuing for 6 months in lactating women (Abstract). Prescott discloses that mothers who had been on a probiotic had higher level of IgA compared to placebo group especially for early breast milk samples (p. 1609, left column, last paragraph, Figure 3).
Prescott does not teach bacterial strains of the genus Bacteroides with the recited 16S rRNA sequence identity, does not explicitly teach inoculation of bacterial strains to a mammalian mother in need of increasing the IgA antibody content in milk and does not teach inoculation of the bacterial strain to a mammalian mother with the decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora before inoculation
Yanagibashi teaches production of IgA by the gut mucosal immune system. Yanagibashi describes that intestinal microorganisms increase the number of IgA-secreting plasma cells by activating Peyer’s patches (PP) (p. 372, right column). Yanagibashi compared the immunomodulatory effect of Bacteroides and Lactobacillus on IgA production by Peyer’s patches (PP) lymphocytes (Abstract). Yanagibashi discloses that Bacteroides induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus (p. 373, right column, 3rd paragraph and Figure 1) and Bacteroides more strongly induced PPs B cell differentiation to IgA+ B cells and subsequent terminal differentiation into IgA producing plasma cells (p. 375, left column, 1st paragraph, Figure 2).
Yanagibashi describes using three strains of Bacteroides, two of which were not identified and the third strain was Bacteroides acidifaciens type A43 from the prior art of Miyamoto (p. 373, left column, 3rd paragraph).
Miyamoto describes isolation of several strains that were characterized as Bacteroides acidifaciens (Abstract). The 16S rRNA analysis of strains (including A43 strain used by Yanagibashi) allowed to divide strains into two groups with very high homology between them of 98.2% (p. 147, right column, 3rd paragraph). The type strain A40 was deposited in the Japan Collection of Microorganism as JCM10556 (p. 148, left column, 5th paragraph). The sequence of 16S rRNA of the Bacteroides acidifaciens strain JCM10556 is 100% identical to instant SEQ ID NO:1 as evidenced by GenBank EU 136694.1.
Sun teaches disruption of gut microbiota by different antibiotics (Abstract). Sun describes that mice were treated with the broad-spectrum antibiotic enrofloxacin, gram-positive bactericidal antibiotic vancomycin, and gram-negative bactericidal antibiotic polymixin B sulfate. These antibiotics lead to different effect on mice (p. 7, right column, last paragraph). The most significant changes of gut microbiota were with vancomycin treatment (p. 11, left column, last paragraph). Sun discloses changes at the taxonomical family level for various bacterial families that include increase in the abundance of some families, such as Enterobacteriaceae and significant decrease in Prevotellaceae and Bacteroidaceae families (p. 4, right column, last paragraph). Sun mentions that gut microbiome plays an essential role in modulating host immune responses (Abstract) and indicates that antibiotic treatment with vancomycin can impact the immune cells. Sun provides example of mice with dysbiosis induced by ampicillin treatment that have decreased amount of secretory IgA in the colon (p. 7, right column, 1st paragraph).
First, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the Lactobacillus rhamnosus or Bifidobacterium lactis in the supplemental composition increasing IgA in breast milk of Prescott teaching with Bacteroides strain from Yanagibashi teaching. One would have been motivated to do so since Yanagibashi showed that Bacteroides strains induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus strains and more strongly induced PPs B cell differentiation into IgA producing plasma cells. A skilled artisan would have reasonably expected success in the combination because Prescott and Yanagibashi teach effect of probiotic bacterial strains to induce IgA production.
Second, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use Bacteroides acidifaciens strain JCM10556 (the sequence of the 16S rRNA of which is 100% identical to SEQ ID NO:1 as evidenced by GenBank EU 136694.1) from Miyamoto teaching for supplemental composition increasing IgA in breast milk based on Prescott and Yanagibashi teachings. One would have been motivated to do so with the reasonably expected success since Yanagibashi teaches strain from Miyamoto teaching to increase IgA production by PP and differentiation of B cells into IgA secreting plasma cells and Miyamoto characterized isolated strains as having 98.2% 16S rRNA identity with each other and deposited the type strain JCM10556 the 16S rRNA sequence of which is provided by GenBank 136694.1.
Third, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the supplemental composition increasing the content of IgA in the breast milk based on Prescott , Yanagibashi and Miyamoto teachings to mother in need to increase the IgA content in the milk. One would have been motivated to do so since Prescott teaches that breast milk has an immunomodulatory effect (p. 1607, left column, 2nd paragraph and therefore it would be beneficial to increase the level of IgA in the breast milk in case of its deficiency. A skilled artisan would have reasonably expected success in that because Prescott describes how to measure IgA content in milk (p. 1608, left column, 4th paragraph) and teaches increase in IgA content in the breast milk by inoculation of bacterial strains to mothers and Yanagibashi and Miyamoto provide bacterial strain to induce IgA production.
Forth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that method of increasing IgA in mammalian mothers by inoculation of recited Bacteroides strain based on Prescott, Yanagibashi and Miyamoto teachings can be applied to subjects that have decreased ratio of the recited Bacteroides and Prevotella to the whole intestinal bacterial flora. One would have been motivated to do so since Sun showed significant reduction in the abundance of both Bacteroides and Prevotella after antibiotic vancomycin treatment and mentions that vancomycin treatment impacts immune cells and that dysbiosis decreases amount of secretory IgA in the colon. A skilled artisan would have reasonably expected success in that because combination of Prescott, Yanagibashi and Miyamoto teachings suggests inoculation of instant Bacteroides strain to increase IgA in the breast milk and Sun describes conditions in which such inoculation is necessary to restore/increase Bacteroides level leading to increase of IgA in the milk.
Last, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that vancomycin treatment taught by Sun will decrease the ratio of instant strains of Bacteroides and Prevotella. One would have been motivated to expect that since Sun teaches reduction in the abundance of taxonomical families of Prevotellaceae and Bacteroidaceae that include instant strains.
Thus, Prescott, Yanagibashi, Miyamoto and Sun teachings as evidenced by GenBank EU 136694.1 render claim 12 obvious.
Regarding claim 13, Prescott describes treatment via daily supplements containing bacterial powder in a capsule (p. 1607, right column, 2nd paragraph) and hence teaches oral inoculation of bacterial strains. Thus, Prescott, Yanagibashi, Miyamoto and Sun teachings as evidenced by GenBank EU 136694.1 render claim 13 obvious.
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive.
Applicant’s arguments have been considered but are moot because the new ground of rejections does not rely on Nikniaz reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The previous 35 U.S.C. 103 rejections have been withdrawn necessitated by amendment of claims and new 35 U.S.C. 103 rejection was applied. Current rejection is based on combinations of prior art of Prescott, Takahashi, Shah, Yanagibashi, Miyamoto and Sun as described above.
Conclusion
No claims are allowed.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
