Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 1-5, 7, 10, 12, and 13 are cancelled. Claims 19-21 are newly added. Claims 6, 8, 9, 11, and 14-21 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submissions filed on 7/9/2025 and 10/03/2025 have been entered.
Response to Arguments
With regard to the rejection of claims 6, 8, 9, 11, 16, and 17 under 35 USC 103, Applicant argues that claim limitation of a residual glucose concentration of 0.05% to 0.3% is not met. Applicant points to Exhibit 1, filed as an Appendix on 11/13/2024, which discloses that glucose is the preferred carbon source of B. longum, and argues that the B. longum of Bogicevic would utilize the glucose of the culture medium before the GOS or galactose. However, Applicant provides no evidence that glucose at a concentration of 0.24%, as taught by Bogicevic, would be completely depleted.
Moreover, as stated, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” The instant disclosure provides no evidence suggesting that a residual glucose concentration of 0.05% to 0.3% is critical for increasing serpin levels. In fact, Applicant admits on p. 3 of the Remarks that glucose needs to be depleted in order to induce serpin production. Figure 2 of the instant specification also discloses that serpin production is highest with a galactose concentration of 1% and a glucose concentration of 0%. Therefore, even if the glucose of Bogicevic was entirely depleted, increased serpin production would be an inherent result as there is no evidence that a residual glucose concentration is critical for producing serpin.
Applicant also argues that the starting glucose concentration in Bogicevic would result in too much residual glucose to induce serpin production because the BMOS percentage is too high. However, Bogicevic provides a breakdown of the component concentrations of the BMOS in Table 3. There is no evidence provided in the instant disclosure demonstrating that the BMOS of Bogicevic contains the same concentrations of ingredients as the BMOS used in the instant application. Moreover, as stated, the starting glucose concentration of Bogicevic is 0.24%. Figure 2 of the instant specification discloses that a starting glucose concentration of 0.33% still results in increased serpin production. 0.33% is a higher starting concentration than that of Bogicevic. Therefore, Applicant has presented no evidence to prove that the method of Bogicevic would not induce serpin production.
Applicant argues that one would not be motivated to use the compositions of Bogicevic to treat celiac disease, non-celiac gluten sensitivity, gluten ataxia, dermatitis herpetiformis, or wheat allergy as taught by McCarville. However, as stated, Bogicevic teaches that the composition may be used to treat or reduce infections, inflammation, or prevent allergic reactions in a subject (Claims 14, 15). The disorders of McCarville fall under the umbrella of inflammation and allergic reactions as taught by Bogicevic.
Therefore, Applicant’s arguments are not persuasive.
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 6, 8, 9, 11, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Bogicevic et al. (WO 2019/025637 A1), previously cited.
Regarding claim 6, Bogicevic teaches a method of fermenting probiotic bacteria on growth medium comprising a source of GOS (Paragraph spanning pages 12 and 13), which are galactooligosaccharides comprising galactose units (Page 10, line 5). Bogicevic teaches that, preferably the GOS source is the sole source of carbohydrates (Paragraph spanning pages 12 and 13). Bogicevic teaches that Bifidobacterium longum subsp. longum was selected as the one of the probiotic strains (Table 1). Although Bogicevic does not mention increasing serpin protein levels, the instant claims recite that fermentation of B. longum on media comprising GOS or galactose results in increased serpin production, then an increased serpin production would be an expected outcome of the method taught by Bogicevic.
Bogicevic does not mention the concentration of residual glucose in the culture medium. However, Bogicevic teaches that BMOS was used as a GOS source (Page 29, Section 2.2). Bogicevic teaches that BMOS contains 8 g of glucose per 100 mg of dry matter (Table 3). Example 1 of Bogicevic teaches that 30 g of BMOS was added to 1 L of culture medium. 30 g of BMOS would contain 2.4 g of glucose, i.e., the culture medium would contain 0.24 wt% glucose. Although the residual glucose concentration may differ from the glucose concentration of the instant claim, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”
Regarding claim 8, Bogicevic teaches the use of B. longum subsp. longum strains ATCC 15707 and ATCC BAA-999 (Page 26, Table 1; Claim 6).
Regarding claim 9, as stated above, Bogicevic teaches a method of fermenting probiotic bacteria such as Bifidobacterium longum subsp. longum (Table 1) on growth medium comprising a source of GOS (Paragraph spanning pages 12 and 13), which are galatooligosaccharides comprising galactose (Page 12, line 5). Example 1 of Bogicevic teaches a 1L culture medium supplemented with 30 g of BMOS (30 g of BMOS contains 2.4 g of glucose), therefore the culture medium would have a starting glucose concentration of 0.24 wt%, which would result in a residual glucose concentration of 0.24 wt% or less.
Regarding claim 11, Bogicevic teaches growth of B. longum strains ATCC 15707 and ATCC BAA-999 (Page 26, Table 1; Claim 6).
Regarding claims 16 and 17, Bogicevic teaches a harvesting step in which the bacterial cells are separated (i.e., isolated) from the growth medium (Page 15, line 21).
Claims 14, 15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Bogicevic et al. (WO 2019/025637 A1) in view of McCarville et al., 2017 (A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor), previously cited.
Regarding claims 14 and 18, Bogicevic teaches a method of treating or reducing infections, inflammation, or preventing allergic reactions in a subject (Claims 14, 15, and 22) by administering a probiotic composition comprising Bifidobacterium longum subsp. longum and at least 0.2% GOS (Table 1; Claims 1-7). Bogicevic teaches that GOS refers to oligosaccharides comprising galactose units (Page 10, line 5). As stated above, Bogicevic teaches a culture medium comprising approximately 0.24 wt% residual glucose (Example 1).
Regarding claim 15, as stated above, Bogicevic teaches that the composition may comprise B. longum strains ATCC 15707 or ATCC BAA-999 (Claim 6).
Bogicevic does not teach that the composition may be used to treat Celiac disease, non-celiac gluten sensitivity, gluten ataxia, dermatitis herpetiformis, or wheat allergy.
However, McCarville teaches that administration of Bifidobacterium longum NTCC2705 attenuates gliadin-induced immunopathology in gluten-sensitive mice (Abstract; Page 2, Paragraphs 2-3) and that administration of Bifidobacterium has been used as a therapy for Celiac disease (Page 1, Paragraph 1).
Therefore, it would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to administer a probiotic composition comprising Bifidobacterium longum, as taught by Bogicevic, to treat gluten sensitivity or Celiac disease, as suggested by McCarville. One of ordinary skill in the art would have been motivated to do so because McCarville teaches that administration of Bifidobacterium has been used as a therapy for Celiac disease (Page 1, Paragraph 1). One of ordinary skill in the art would have had a reasonable expectation of success because Bogicevic and McCarville are in the same field of endeavor of probiotic therapy development.
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Bogicevic et al. (WO 2019/025637 A1) as applied to claims 6 and 9 above, and further in view of Hsu et al., (Production of beta-galactosidase by Bifidobacteria as influenced by various culture conditions. Int J Food Microbiol. 2005 Oct 15;104(2)).
See discussion of Bogicevic above, which is incorporated into this rejection as well.
Regarding claims 20 and 21, Hsu teaches fermenting Bifidobacterium longum in a culture medium comprising galactose is the sole carbohydrate source (p. 200, col. 2, para. 2; Figure 1). Replacing the GOS carbon source with galactose would result in a residual glucose concentration of 0%, as the starting medium would have 0% glucose.
Although this concentration differs from the glucose concentration of independent claims 6 and 9, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to ferment the Bifidobacterium longum strain of Bogicevic with galactose instead of GOS, as taught by Hsu. One of ordinary skill in the art would have been motivated to do so because Hsu teaches that fermenting B. longum in medium containing galactose as the sole carbon source results in greater β-galactosidase production than when B. longum is fermented with glucose (Figure 1.). One of ordinary skill in the art would have had a reasonable expectation of success because Bogicevic and Hsu are in the same field of endeavor of B. longum fermentation methods.
Allowable Subject Matter
Claim 19 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
There are no prior art references that teach the administration of a composition comprising Bifidobacterium longum fermented with galactose without beta-galactooligosaccharides (GOS), and the Examiner is unaware of any prior art disclosure that suggests that B. longum in combination with galactose may treat celiac disease, gluten-sensitivity, gluten ataxia, dermatitis herpetiformis, or wheat allergy.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657