DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 01 April 2026 in which claim 12 was amended to change the scope and breadth of the claims.
Claims 12-15, 17, 18 and 20 are pending in the current application and are examined on the merits herein.
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 .
Withdrawn Rejections
Applicant’s amendment, filed 01 April 2026, with respect to the rejection of claims 12-15, 17, 18 and 20 under 35 U.S.C. § 112, second paragraph, for indefiniteness, has been fully considered and is persuasive. The claim has been amended to delete “administered to the patient”. The rejection is hereby withdrawn.
Response to Arguments
Applicant's arguments filed 01 April 2026 have been fully considered but they are not persuasive.
Applicant contends one having ordinary skill in the art would not have had a reasonable expectation of success in administering 1-kestose to promote the growth of L. crispatus relative to E. coli, such that a therapeutic effect is greater than 30, because Paul found C. albicans consumes 46% of the DP3. Paul et al. found E. coli and C. albicans did not consume DP4-DP7. And concluded the use of a DP equal to 4 favors the growth of beneficial vaginal microflora. Since DP3 caused C. albicans to grow, Applicant argues one of ordinary skill in the art could not have a reasonable expectation of growing L. crispatus relative to E. coli.
The above arguments are not found persuasive, because the claims are not concerned with C. albicans. With respect to the claimed L. crispatus and claimed E. coli, Paul et al. found 76% of 1-kestose was consumed by L. crispatus after 48 h incubation, while only 21% of 1-kestose was consumed by E. coli after 48 h incubation (i.e. a very low rate, per Rousseau et al. at page 152 and Table 6). Paul et al. found of the three oligosaccharides present in FOS Actilight®, 1-kestose (DP3) was the only one consumed by L. crispatus (see e.g. claim 11, 4, 6, 10, 15, 17, 18 translation). Paul et al. conclude FOS Actilight® (DP3) has remarkable prebiotic potential with respect to the beneficial vaginal flora, because it constitutes a growth substrate for this flora that is both very effective and very specific (p.19 translation).
Furthermore, Rousseau et al. found two oligosaccharide series (FOS Actilight® DP3 and all α-1,6/α-1,4 GOS DP≥4) were consumed only by the lactobacilli strains, while the pathogenic microorganisms were unable to metabolize them (abstract; tables 5, 6).
Paul et al. found lactobacillus growth observed for the FOS Actilight®/GOS α-1,6/lactic acid mixture reached the same levels as with each oligosaccharide used alone (para [0268] of Espacenet translation; comparing tables 5 and 11). Thus, Paul et al. provide motivation to use FOS Actilight® without GOS α-1,6. Second, both references disclose G-F2 (DP3) itself is active, and is alone responsible for the activity observed from FOS Actilight ®. Since both references found G-F2 (DP3) itself is active, one of ordinary skill in the art would have been motivated to administer a composition comprising only G-F2 (DP3), or 1-kestose, with a reasonable expectation of success in maintaining a healthy microflora balance in the urogenital area of a patient in need thereof.
Furthermore, the recitation “wherein the composition promotes the growth of L. crispatus relative to E. coli in the colony such that a therapeutic effect is greater than 30, the therapeutic effect being a ratio of L. crispatus to E. coli calculated by the Therapeutic Effect Protocol” will necessarily occur upon performing the positively recited steps.
The rejection is hereby maintained.
Maintained Rejections
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.
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.
Claim(s) 12-15, 17-18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Paul et al. (WO2006/030100, cited in previous Office Action; Espacenet English translation cited in previous Office Action) in view of Rousseau et al. (Clinical Microbiology, 2005, vol. 11, pp. 145-153, cited in previous Office Action), as evidenced by Campbell et al. (J. Agric. Food Chem, 1997, vol. 45, pp. 3076-3082, cited in previous Office Action).
Paul et al. teach a pharmaceutical composition comprising prebiotic oligosaccharides for vaginal use, including to promote the growth of beneficial endogenous vaginal bacterial strains (abstract). The composition comprises 1 to 5% by weight of the oligosaccharide (claim 5). The composition has a pH of about 4.5 to 6 (claim 7). The composition preferably comprises an acid buffer, including lactic acid (e.g. Example 2; p.5 of translation). The oligosaccharides can be incorporated into any type of composition suitable for topical application to the vagina, including a liquid soap, vaginal gel, intravaginal cannula or ovum, or any suitable medical device (p.5, translation).
Four oligosaccharide compositions were tested, including FOS Actilight® (Table 1, p.11). FOS Actilight® consists of three molecules: G-F2 (DP3), G-F3 (DP4) and G-F4 (DP5), wherein G-F2 contains a glucose molecule and two molecules of fructose. FOS Actilight® is defined as: [β-D-Fruf-(2->1)]n-β-D-Fruf-(2<->1)-α-D-Glcp. While Paul et al. describe the compound’s name as “1-cetose”, “G-F2” (DP3) having this structural formula is also known as 1-kestose as evidenced by Campbell et al.: see Figure 1, also see p.3076-3077, bridging paragraph wherein 1-kestose is referred to as GF2 of Campbell et al.
L. crispatus is naturally present in the urogenital tract. According to Paul, 76% of 1-kestose was consumed by L. crispatus after 48 h incubation. While only 21% of 1-kestose was consumed by E. coli after 48 h incubation (i.e. a very low rate, per Rousseau et al. at page 152 and Table 6). Paul et al. found of the three oligosaccharides present in FOS Actilight®, 1-kestose (DP3) was the only one consumed by L. crispatus (see e.g. claim 11, 4, 6, 10, 15, 17, 18 translation). Paul et al. conclude FOS Actilight® (DP3) has remarkable prebiotic potential with respect to the beneficial vaginal flora, because it constitutes a growth substrate for this flora that is both very effective and very specific (p.19 translation).
Paul et al. do not expressly disclose administering a composition “comprising only a single therapeutic agent” (present claim 12).
Rousseau et al. is a co-author of the above Paul et al. reference, and similarly discuss the results of testing FOS Actilight® on select vaginal lactobacilli and pathogenic microorganisms (title and abstract). The test was based on the ability of oligosaccharides to promote the growth of three beneficial strains of Lactobacilli selected but not the pathogenic microorganisms often encountered in urogenital infections such as Candida albicans, E. coli and G. vaginalis. Rousseau et al. found two oligosaccharide series (FOS Actilight® DP3 and all α-1,6/α-1,4 GOS DP≥4) were consumed only by the lactobacilli strains, while the pathogenic microorganisms were unable to metabolize them (abstract; tables 5, 6). Rousseau et al. teach “to enhance the prebiotic effect, it would be interesting to test FOS Actilight® DP3 alone…” (p.152, penultimate para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer 1-kestose as the sole source of carbon for bacterium because Paul et al. found 1-kestose (G-F2, DP3) was the only oligosaccharide of the three different oligosaccharides within FOS Actilight® (DP3), with the desired prebiotic effect. Within the vaginal flora, 1-kestose promoted the growth of beneficial bacteria. More specifically, 1-kestose (G-F2, DP3) was a great carbon source for lactobacilli, including L. crispatus, but not a carbon source for pathogenic bacteria like Candida albicans, E. coli and G. vaginalis.
First, Paul et al. found lactobacillus growth observed for the FOS Actilight®/GOS α-1,6/lactic acid mixture reached the same levels as with each oligosaccharide used alone (para [0268] of Espacenet translation; comparing tables 5 and 11). Thus, Paul et al. provide motivation to use FOS Actilight® without GOS α-1,6. Second, both references disclose G-F2 (DP3) itself is active, and is alone responsible for the activity observed from FOS Actilight ®. Since both references found G-F2 (DP3) itself is active, one of ordinary skill in the art would have been motivated to administer a composition comprising only G-F2 (DP3), or 1-kestose. To further support this finding of obviousness, it is now noted Rousseau et al. expressly teach “to enhance the prebiotic effect, it would be interesting to test FOS Actilight® DP3 alone…” (p.152, penultimate para). Thus, the ordinary artisan would expressly have been motivated to administer a composition comprising only 1-kestose to maintain a healthy microflora balance in the urogenital area of a patient.
From Paul et al. and Rousseau et al., the ordinary artisan would have also known 1-kestose promotes the growth of L. crispatus to a greater degree than E. coli. According to Paul, 76% of 1-kestose was consumed by L. crispatus after 48 h incubation. Conversely, 21% of 1-kestose was consumed by E. coli after 48 h incubation. Thus, the ordinary artisan would have known 1-kestose promotes the growth of L. crispatus at least 3 times higher than it does E. coli. While the references do not expressly describe this using the “Therapeutic Effect Protocol”, this is necessarily a property of the compound, and performing the positively recited step, which is obvious for the reasons discussed above.
The ordinary artisan would have been motivated to administer 1 to 5% by weight of the oligosaccharide, which overlaps with the amount recited in present claim 13. And the ordinary artisan would have been motivated to optimize the pH of the composition, wherein the pH of 4.5 to 6 disclosed by Paul et al. encompasses the range presently claimed. The ordinary artisan would have been motivated to optimize both the concentration and pH of the composition to provide a composition that best promotes the growth of lactobacilli, including L. Crispatus. See MPEP 2144.05, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
THIS ACTION IS MADE FINAL. 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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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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