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 .
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 amendments filed on 09/29/2025 and 10/31/2025 are acknowledged.
Claims 1, 3 and 5 are amended.
Claims 1-8 are pending (claim set filed 10/31/2025) and are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 10/31/2025 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The previous claims 1-8 rejections under 35 U.S.C. 112(b) have been withdrawn necessitated by amendment of claims.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 2, 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Nikniaz (Nikniaz et al. J. Human Lactation, 2013, 29, 591-596) 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 1, Nikniaz teaches effect of synbiotic supplementation on the level of IgA in breast milk (Abstract). Nikniaz describes that lactating mothers were treated with the following symbiotic supplement: “The synbiotic supplement consisted of freeze-dried Lactobacillus casei PXN 37, Lactobacillus rhamnosus PXN 54, Streptococcus thermophilus PXN 66, Bifidobacterium breve PXN 25, Lactobacillus acidophilus PXN 35, Bifidobacterium longum PXN 30, Lactobacillus bulgaricus PXN 39, and fructooligosaccharide” (p. 592, right column, 2nd paragraph). Nikniaz discloses that the breast milk IgA levels significantly increased in the group receiving supplement treatment (Abstract). Nikniaz mentions that the supplementation reduced diarrhea in infants of mothers receiving supplementation (Abstract). Nikniaz describes that breastfeeding provides immunologic protection when infant’s own immune system is immature. Nikniaz further discloses that immunological composition of breast milk can considerably differ between mothers depending on different conditions affecting the immunological composition such as allergy, infections, inflammation and stress (p. 591, Introduction).
Nikniaz does not teach bacterial strains of the genus Bacteroides or of the genus Prevotella with the recited 16S rRNA sequence identity. Nikniaz 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.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace Lactobacillus strains in the supplemental composition increasing IgA in breast milk of Nikniaz 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 Nikniaz and Yanagibashi teach effect of probiotic bacterial strains to induce IgA production.
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 Nikniaz 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.
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 Nikniaz , 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 Nikniaz teaches that immunological composition of breast milk can considerably differ between mothers and the breastfeeding is important to provide immunologic protection when infant’s own immune system is immature 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 Nikniaz describes how to measure IgA content in milk (p. 593, left column, 2nd 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, Nikniaz, Yanagibashi and Miyamoto teachings as evidenced by GenBank EU 136694.1 render claim 1 obvious.
Regarding claim 2, Yanagibashi teaches that Bacteroides acidifaciens induced PPs lymphocytes to produce IgA (p. 373, right column, 3rd paragraph and Figure 1) and induced PPs B cell differentiation to IgA+ B cells and subsequent terminal differentiation into IgA producing plasma cells, thus increasing the number of IgA producing plasma cells (p. 375, left column, 1st paragraph, Figure 2). Thus, Nikniaz, Yanagibashi and Miyamoto teachings as evidenced by GenBank EU 136694.1 render claim 2 obvious.
Regarding claims 4 and 6, Nikniaz describes oral administration of the supplement containing bacterial strains in the form of capsules (p. 592, right column, 1st paragraph) and therefore teaches oral inoculation of bacterial strains. Thus, Nikniaz, Yanagibashi and Miyamoto teachings as evidenced by GenBank EU 136694.1 render claims 4 and 6 obvious.
Claims 3, 5, 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Nikniaz (Nikniaz et al. J. Human Lactation, 2013, 29, 591-596) 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 claims 1 and 2 above, and further in view of Lee (Lee et al. Nature, 2013, 501, 426-431).
The teaching of Nikniaz, Yanagibashi and Miyamoto as evidenced by GenBank EU 136694.1 have been set forth above.
Nikniaz, Yanagibashi, Miyamoto and GenBank EU 136694.1 do not teach inoculation of bacterial strain when the ratio of the strain in intestinal bacterial flora is decreased.
Regarding claim 3 and 5, Lee teaches colonization of the gastrointestinal tract by Bacteroides. Lee mentions that Bacteroides is one of the most numerically prominent genera of human microbiome. (Abstract). Lee describes inoculation of Bacteroides to germ-free mice and monitoring the colonization. Lee discloses that animals were readily colonized by sequential addition of different Bacteroides species, however, animals were resistant to super-colonization with the same species. The data suggested that Bacteroides colonize the gut in the species-specific and saturable manner (p. 426, left column, last paragraph and 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 to follow Lee teaching and inoculate the Bacteroides strain to increase the content of IgA in the breast milk based on Nikniaz, Yanagibashi and Miyamoto teachings to mother with the decreased level of Bacteroides in the intestine. One would have been motivated to do so since Lee teaches that Bacteroides can readily colonize the gut with different Bacteroides species till the saturated level and Yanagibashi showed increase in IgA production by Bacteroides strain. A skilled artisan would have reasonably expected success in that because Nikniaz teaches increase in IgA content in the breast milk by inoculation of bacterial strains to mothers, Yanagibashi and Miyamoto provide bacterial strain to induce IgA production and Lee, Yanagibashi and Miyamoto describe Bacteroides strains. Thus, Nikniaz, Yanagibashi, Miyamoto and Lee teachings as evidenced by GenBank EU 136694.1 render claims 3 and 5 obvious.
Regarding claims 7 and 8, Nikniaz describes oral administration of the supplement containing bacterial strains in the form of capsules (p. 592, right column, 1st paragraph) and therefore teaches oral inoculation of bacterial strains. Thus, Nikniaz, Yanagibashi, Miyamoto and Lee teachings as evidenced by GenBank EU 136694.1 render claims 7 and 8 obvious.
Response to Arguments
Applicant's arguments filed 10/31/2025 have been fully considered but they are not persuasive.
Applicant argues (addressing p. 6 of the Remarks) that Nikniaz does not teach bacterial strains of Bacteroides or Prevotella and that “a skilled person would consider that the four Lactobacillus strains in the supplement are active ingredients and would not consider intentionally replacing them with other bacterial strains”. Applicant further argues that Nikniaz teaches symbiotic supplement by combining bacterial strains and oligosaccharide and “it would be unusual to consider the combinations by changing individual bacterial strains contained in the specific synbiotic supplement”. These arguments are not persuasive because:
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, although Nikniaz does not teach Bacteroides or Prevotella strains, Yanagibashi teaches that Bacteroides induced PPs lymphocytes to produce higher levels of IgA than Lactobacillus (p. 373, right column, 3rd paragraph and Figure 1) providing motivation to use Bacteroides strains in supplement taught by Nikniaz. Regarding prebiotic component in Nikniaz supplement, fructooligosaccharide (FOS), please note that claim 1 does not exclude inoculation of additional components due to transitional phrase “comprising”. Additionally, FOS are known to be prebiotic not only to Lactobacillus, but to different probiotics including Bacteroides as evidenced by Singh (Singh et al. Food Bioscience, 2025, 63, 105726, 1-13). Singh teaches that: “FOS holds considerable potential as prebiotics because of their ability to withstand digestion in the GIT & specifically foster the proliferation of healthy bacteria” (p. 10, right column, 2nd paragraph). Singh provides examples of combination of FOS with Bacteroides in treatment of different disease conditions (Table 2, p. 8). Therefore, combination of FOS with Bacteroides can provide beneficial effect on increase in the IgA content of breast milk based on Nikniaz and Yanagibashi teachings.
Applicant argues that Yanagibashi teaches in vitro secretion of IgA and “it cannot be foreseen that orally inoculating a breast-feeding mammalian mother with a bacterial strain of the genus Bacteroides would increase the IgA antibody content in milk of the mammalian mother”. Applicant further argues a superior effect: “By contrast, the Examples of the present specification show in an in vivo system that orally inoculating mother mice with Bacteroides acidifaciens or Prevotella buccalis increased the ratio and number of lgA-producing plasma cells in the mammary gland and a milk-derived IgA antibody concentration in the mother mice without employing a combination with a plurality of bacterial strains or a combination with fructooligosaccharide as in the synbiotic supplement of Nikniaz (see paragraph [0062], Fig. 21). Applicant believes that such a superior effect cannot be foreseen by a skilled person based on the prior art references of Nikniaz, Yanagibashi, Miyamoto, and GenBank EU 136694.1.”. These arguments are not persuasive because:
First, Nikniaz teaches significant increase in the concentration of IgA in breast milk of lactating mothers receiving supplement comprising Lactobacillus strains (Abstract). Since Yanagibashi teaches higher production of IgA by lymphocytes co-cultured with Bacteroides compared to Lactobacillus, it is predicted that Nikniaz supplement with Lactobacillus replaced with Bacteroides and more specifically with Bacteroides acidifaciens strain JCM10556 taught by Yanagibashi, Miyamoto, and GenBank EU 136694.1 will provide higher level of IgA in breast milk. Yanagibashi describes that intestinal microorganisms increase the number of IgA-secreting plasma cells by activating Peyer’s patches (PP) (p. 372, right column) and discloses that Bacteroides more strongly induce Peyer’s patches 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 is known that IgA-committed B cells emerging from Peyer’s patches in the small intestine, migrate to other mucosal sites, including lactating mammary gland as evidenced by Goldblum (Goldblum and Goldman Hand book of Mucosal Immunology, 1994, chapter 51, 643-652; p. 646, left column, 1st paragraph). Therefore, it is expected that the combination of prior art of Nikniaz, Yanagibashi, Miyamoto, and GenBank EU 136694 will provide higher number of lgA-producing plasma cells in the mammary gland.
Second, the advantage of increased ratio and number of lgA-producing plasma cells in the mammary gland and a milk-derived IgA antibody concentration in the mother mice by orally inoculating mother mice with Bacteroides acidifaciens or Prevotella buccalis recognized by the Applicant does not make the combination of prior art nonobvious because the prior art does not need to point out all advantages if there is a motivation to combine for other reasons, then it is still obvious. MPEP 2145: The fact that appellant 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." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).” In instant case, the prior art of Nikniaz, Yanagibashi, Miyamoto, and GenBank EU 136694.1 is obvious to combine as described above. Although Yanagibashi does not teach in vivo increase in the secretion of IgA and increase in the number of IgA-producing plasma cells in mammary gland, Nikniaz teaches increase in IgA in human milk of mothers treated with probiotic supplement and Yanagibashi shows increase in B cell differentiation into IgA producing plasma cells which migrate to mammary gland as evidenced by Goldblum. Therefore, it is expected that modification of Nikniaz supplement based on prior art of Yanagibashi, Miyamoto, and GenBank EU 136694.1 will increase ratio and number of lgA-producing plasma cells in the mammary gland and concentration of milk-derived IgA antibody in the mother mice.
Last, assuming arguendo applicant has shown superior effect, claims are not commensurate in scope with the superior effect. In instant case, example depicted on FIG. 21 is based on results obtained in mouse mothers and in specific strains of mice that are not present in claim 1 directed to broad genus of mammalian mother and hence the claims are not commensurate in scope with the superior effect.
Therefore, the 35 U.S.C. 35 103 rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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