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 office action is a response to applicant’s communication submitted April 24, 2026, wherein claim 11 is amended and claim 13 is canceled. This application is a national stage application of PCT/US21/42890, filed July 23, 2021, which claims benefit of provisional application 63/055369, filed July 23, 2020.
Claims 11 and 14-20 are pending in this application.
Claims 11 and 14-20 as amended are examined on the merits herein.
The following rejections of record in the previous action are maintained:
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.
Claims 11, 14-18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US pre-grant publication 2016/0375045, cited in previous action) in view of Thomas-White et al. (Reference of record in previous action) in view of Atassi et al. (Reference of record in previous action)
Independent claim 11 claims a method for modulating a bladder microbiome in a subject comprising administering a composition comprising isomaltulose (also referred to in the art as palatinose) and a carrier to the urogenital region of the subject wherein the method is directed to treating overactive bladder, urinary urge incontinence, or urinary tract infections in a subject. Claim 11 as amended further specifies that administering the composition promotes the growth of Lactobacillus crispatus relative to Streptococcus anginosus. Based on Applicant’s disclosure, this effect on the relative abundance of bacterial species is an inherent result of administering the therapeutic agent isomaltulose, and will necessarily result from administering this compound to the urogenital region of a subject. For example table 6 in the present disclosure shows that isomaltulose selectively promotes growth of Lactobacillus crispatus in competition with Streptococcus anginosus. Therefore administering isomaltulose to the bladder of a subject is reasonably expected to meet this limitation. Dependent claim 13 specifies the magnitude of the therapeutic effect, and are similarly considered to be a necessary effect of administering the specific composition to the bladder of a subject.
Dependent claim 14 specifies that the composition is applied to the urethra or periurethral region. Dependent claims 15-17 specify the particular components that make up the composition and their amounts. Dependent claims 18-20 specify the physical form of the composition, which comprises a substrate such as a wipe, liquid, gel, cream, or spray.
Zeng et al. discloses a product for increasing the resistance of the vagina to pathogens and restoring the beneficial vaginal flora including L. crispatus. (p. 1 paragraph 10 – p. 2 paragraph 11) THE product preferably comprises isomaltulose at a concentration of 1.5-12%, which substantially overlaps the concentration recited in present claim 15. The composition promotes growth of Lactobacillus compared to pathogenic bacterial and fungi. (p. 2 paragraph 15) The composition can further be a water-soluble gel or cream. (p. 2 paragraph 18) In particular the composition promotes growth of protective bacteria such as L. crispatus. (p. 5 paragraph 47)
Zeng et al. does not disclose a method of treating urinary tract infection, urinary urge incontinence, or overactive bladder. However, Thomas-White et al. discloses that the microbiota of the bladder and vagina are interconnected, and that there exists a single urogenital microbiome. (p. 2 left column second and third paragraphs) In particular, both pathogenic bacteria such as S anginosus and health-promoting bacteria such as L crispatus are shown to be shared between the vaginal and bladder microbiota. (p. 5 left column second paragraph) Therefore it is reasonably expected that applying the prebiotic compositions described by Zeng et al. to the urogenital tract would affect the bacterial composition of the bladder microbiome, even if isomaltulose were not directly applied to the bladder.
Atassi et al. discloses that probiotic Lactobacillus based therapeutics are used to treat urinary tract infections. (p. 2 left column last paragraph, right column first paragraph) Atassi et al. further discloses a study of the inhibitory or killing effect of Lactobacilli including L. crispatus against uropathogenic bacterial strains. (pp. 3-4)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer the prebiotic isomaltulose compositions described by Zeng et al. to a subject suffering from a urinary tract infection. One of ordinary skill in the art would have found this to be obvious based on the disclosure by Atassi et al. of using Lactobacillus probiotics to treat UTIs, which would have suggested that any method such as that described by Zeng et al. which promotes L. crispatus would be expected to be useful for treating UTIs.
Therefore the invention taken as a whole is prima facie obvious.
Claims 11, 14-18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US pre-grant publication 2016/0375045, cited in previous action) in view of Thomas-White et al. (Reference of record in previous action) in view of Govender et al. (Reference of record in previous action)
Independent claim 11 claims a method for modulating a bladder microbiome in a subject comprising administering a composition comprising isomaltulose (also referred to in the art as palatinose) and a carrier to the urogenital region of the subject wherein the method is directed to treating overactive bladder, urinary urge incontinence, or urinary tract infections in a subject. Claim 11 as amended further specifies that administering the composition promotes the growth of Lactobacillus crispatus relative to Streptococcus anginosus. Based on Applicant’s disclosure, this effect on the relative abundance of bacterial species is an inherent result of administering the therapeutic agent isomaltulose, and will necessarily result from administering this compound to the urogenital region of a subject. For example table 6 in the present disclosure shows that isomaltulose selectively promotes growth of Lactobacillus crispatus in competition with Streptococcus anginosus. Therefore administering isomaltulose to the bladder of a subject is reasonably expected to meet this limitation. Dependent claim 13 specifies the magnitude of the therapeutic effect, and are similarly considered to be a necessary effect of administering the specific composition to the bladder of a subject.
Dependent claim 14 specifies that the composition is applied to the urethra or periurethral region. Dependent claims 15-17 specify the particular components that make up the composition and their amounts. Dependent claims 18-20 specify the physical form of the composition, which comprises a substrate such as a wipe, liquid, gel, cream, or spray.
Zeng et al. discloses a product for increasing the resistance of the vagina to pathogens and restoring the beneficial vaginal flora including L. crispatus. (p. 1 paragraph 10 – p. 2 paragraph 11) THE product preferably comprises isomaltulose at a concentration of 1.5-12%, which substantially overlaps the concentration recited in present claim 15. The composition promotes growth of Lactobacillus compared to pathogenic bacterial and fungi. (p. 2 paragraph 15) The composition can further be a water-soluble gel or cream. (p. 2 paragraph 18) In particular the composition promotes growth of protective bacteria such as L. crispatus. (p. 5 paragraph 47)
Zeng et al. does not disclose a method of treating urinary tract infection, urinary urge incontinence, or overactive bladder. However, Thomas-White et al. discloses that the microbiota of the bladder and vagina are interconnected, and that there exists a single urogenital microbiome. (p. 2 left column second and third paragraphs) In particular, both pathogenic bacteria such as S anginosus and health-promoting bacteria such as L crispatus are shown to be shared between the vaginal and bladder microbiota. (p. 5 left column second paragraph) Therefore it is reasonably expected that applying the prebiotic compositions described by Zeng et al. to the urogenital tract would inherently affect the bacterial composition of the bladder microbiome, even if isomaltulose were not directly applied to the bladder.
Govender et al. discloses a review of the association of the female urinary microbiome with urinary incontinence. (p. 2 left column first paragraph) Lactobacillus including L. crispatus was reduced in both urinary urge incontinence (UUI) and overactive bladder, (OAB) suggesting a role of bacterial dysbiosis in these conditions. (p. 3 left column fifth paragraph – right column second paragraph) Govender et al. further suggests using vaginal probiotics to restore a healthy urobiome. (p. 7 right column first paragraph)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer the prebiotic isomaltulose compositions described by Zeng et al. to a subject suffering from UUI or OAB. One of ordinary skill in the art would have found this to be obvious based on the suggestion by Govender et al. of using vaginal probiotics to treat these conditions, which would have suggested that any method such as that described by Zeng et al. which promotes L. crispatus would be expected to be useful for treating UUI and OAB.
Therefore the invention taken as a whole is prima facie obvious.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US pre-grant publication 2016/0375045, cited in previous action) in view of Thomas-White et al. (Reference of record in previous action) in view of Atassi et al. (Reference of record in previous action) as applied to claims 11, 14-18, and 20 above, and further in view of Li et al. (US pre-grant publication 2018/0256615, of record in previous action)
The disclosures of Zeng et al., Thomas-White et al., and Atassi et al. are discussed above. Zeng et al. in view of Thomas-White et al. in view of Atassi et al. does not disclose an embodiment wherein the composition is applied to a wipe or adsorbent article. However, Li et al. discloses a similar vaginal composition for promoting dominance of Lactobacilli which contains a prebiotic that can be isomaltulose. (p. 1 paragraphs 5-8) Furthermore this composition can be administered using an applicator which can be a web such as a gauze or cotton swab, or a tissue web, which are reasonably considered to be a wipe or adsorbent article as described in claim 19. (p. 1 paragraph 9) It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the isomaltulose-containing prebiotic described by Zeng using one of the adsorbent articles described by Li et al. One of ordinary skill in the art would have found this to be obvious because Li clearly describes these modes of administration as being suitable for vaginally administering prebiotics.
Therefore the invention taken as a whole is prima facie obvious.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al. (US pre-grant publication 2016/0375045, cited in previous action) in view of Thomas-White et al. (Reference of record in previous action) in view of Govender et al. (Reference of record in previous action) as applied to claims 11, 14-18, and 20 above, and further in view of Li et al. (US pre-grant publication 2018/0256615, of record in previous action)
The disclosures of Zeng et al., Thomas-White et al., and Govender et al. are discussed above. Zeng et al. in view of Thomas-White et al. in view of Govender et al. does not disclose an embodiment wherein the composition is applied to a wipe or adsorbent article. However, Li et al. discloses a similar vaginal composition for promoting dominance of Lactobacilli which contains a prebiotic that can be isomaltulose. (p. 1 paragraphs 5-8) Furthermore this composition can be administered using an applicator which can be a web such as a gauze or cotton swab, or a tissue web, which are reasonably considered to be a wipe or adsorbent article as described in claim 19. (p. 1 paragraph 9) It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the isomaltulose-containing prebiotic described by Zeng using one of the adsorbent articles described by Li et al. One of ordinary skill in the art would have found this to be obvious because Li clearly describes these modes of administration as being suitable for vaginally administering prebiotics.
Therefore the invention taken as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 11 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 11-16 and 18-20 of copending Application No. 18/997917 (US pre-grant publication 2026/0000694, cited in PTO-892, herein referred to as ‘917) in view of Thomas-White et al. (Reference of record in previous action) in view of Atassi et al. (Reference of record in previous action)
Claim 11 of ‘917 claims a method of modulating growth of urogenital microorganisms in a subject comprising administering to a subject a prebiotic compositions comprising isomaltulose. Dependent claims 13-16 further define the composition as affecting the same two bacterial species recited in the present claims. Claims 1, 4, and 5 claim a prebiotic formulation wherein the prebiotic agents comprise between 0.01-20% of the prebiotic formulation, and additionally a carrier. This range substantially overlaps the range recited in present claim 16, and furthermore if the remainder of the composition is a carrier substantially overlaps the carrier range in present claim 16. Regarding present claims 17 and 20, claim 12 of ‘917 specifies that the composition can be a liquid, spray, or gel, for example, all of which would imply the present of water as a carrier. Claims 18-20 of ‘917 further describe the composition being applied by an adsorbent article, as recited in present claims 18 and 19.
The claims of ‘917 do not claim a method of treating urinary tract infection, urinary urge incontinence, or overactive bladder, or specifically modulating the bladder microbiome. However, Thomas-White et al. discloses that the microbiota of the bladder and vagina are interconnected, and that there exists a single urogenital microbiome. (p. 2 left column second and third paragraphs) In particular, both pathogenic bacteria such as S anginose and health-promoting bacteria such as L crispatus are shown to be shared between the vaginal and bladder microbiota. (p. 5 left column second paragraph) Therefore it is reasonably expected that applying the prebiotic compositions described by the claims of ‘917 to the urogenital tract would inherently affect the bacterial composition of the bladder microbiome, even if isomaltulose were not directly applied to the bladder.
Atassi et al. discloses that probiotic Lactobacillus based therapeutics are used to treat urinary tract infections. (p. 2 left column last paragraph, right column first paragraph) Atassi et al. further discloses a study of the inhibitory or killing effect of Lactobacilli including L. crispatus against uropathogenic bacterial strains. (pp. 3-4)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer the prebiotic compositions claimed by ‘917 to a subject suffering from a urinary tract infection. One of ordinary skill in the art would have found this to be obvious based on the disclosure by Atassi et al. of using Lactobacillus probiotics to treat UTIs, which would have suggested that any method such as that claimed by ‘917 which promotes L. crispatus would be expected to be useful for treating UTIs.
Therefore the invention taken as a whole is prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 11 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 11-16 and 18-20 of copending Application No. 18/997917 (US pre-grant publication 2026/0000694, cited in PTO-892, herein referred to as ‘917) in view of Thomas-White et al. (Reference of record in previous action) in view of Govender et al. (Reference of record in previous action)
Claim 11 of ‘917 claims a method of modulating growth of urogenital microorganisms in a subject comprising administering to a subject a prebiotic compositions comprising isomaltulose. Dependent claims 13-16 further define the composition as affecting the same two bacterial species recited in the present claims. Claims 1, 4, and 5 claim a prebiotic formulation wherein the prebiotic agents comprise between 0.01-20% of the prebiotic formulation, and additionally a carrier. This range substantially overlaps the range recited in present claim 16, and furthermore if the remainder of the composition is a carrier substantially overlaps the carrier range in present claim 16. Regarding present claims 17 and 20, claim 12 of ‘917 specifies that the composition can be a liquid, spray, or gel, for example, all of which would imply the present of water as a carrier. Claims 18-20 of ‘917 further describe the composition being applied by an adsorbent article, as recited in present claims 18 and 19.
The claims of ‘917 do not claim a method of treating urinary tract infection, urinary urge incontinence, or overactive bladder, or specifically modulating the bladder microbiome. However, Thomas-White et al. discloses that the microbiota of the bladder and vagina are interconnected, and that there exists a single urogenital microbiome. (p. 2 left column second and third paragraphs) In particular, both pathogenic bacteria such as S anginose and health-promoting bacteria such as L crispatus are shown to be shared between the vaginal and bladder microbiota. (p. 5 left column second paragraph) Therefore it is reasonably expected that applying the prebiotic compositions described by the claims of ‘917 to the urogenital tract would inherently affect the bacterial composition of the bladder microbiome, even if isomaltulose were not directly applied to the bladder.
Govender et al. discloses a review of the association of the female urinary microbiome with urinary incontinence. (p. 2 left column first paragraph) Lactobacillus including L. crispatus was reduced in both urinary urge incontinence (UUI) and overactive bladder, (OAB) suggesting a role of bacterial dysbiosis in these conditions. (p. 3 left column fifth paragraph – right column second paragraph) Govender et al. further suggests using vaginal probiotics to restore a healthy urobiome. (p. 7 right column first paragraph)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer the prebiotic isomaltulose compositions claimed by ‘917 to a subject suffering from UUI or OAB. One of ordinary skill in the art would have found this to be obvious based on the suggestion by Govender et al. of using vaginal probiotics to treat these conditions, which would have suggested that any method such as that claimed by ‘917 which promotes L. crispatus would be expected to be useful for treating UUI and OAB.
Therefore the invention taken as a whole is prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments, submitted April 24, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejections.
Applicant argues that there is no prima facie case of obviousness because there is no reasonable expectation of success for using isomaltulose to modulate a bladder microbiome by promoting growth of L. crispatus relative to S. anginosus having a therapeutic effect of at least 100. However, as discussed in MPEP 2145(II), mere recognition of latent properties does not render nonobvious an otherwise known invention. While it is true that the cited references do not specifically describe the relative effects on the particular bacterial species L. crispatus and S. anginosus, Zeng does specifically describe topical administration of isomaltulose to the vagina to beneficially affect the vaginal microbiome, including by increasing the population of L. crispatus. The disclosure of Thomas-White et al. further provides evidence that this would further affect the urinary microbiome. It is reasonably expected that performing the same treatment on the same subject population (i.e. topically administering isomaltulose to the urogenital area of a subject suffering from urinary tract infection or bladder dysfunction associated with dysbiosis as suggested by Atassi or Govender. The fact that this is not literally spelled out in the prior art does not negate the finding of prima facie obviousness.
Applicant further argues that the present disclosure includes evidence of unexpected results commensurate in scope with the claims. Specifically, Applicant argues that the effect of prebiotics on bacteria from different environments is unpredictable and that the Office’s arguments fail to account for the unexpected finding that isomaltulose, among a variety of known prebiotic substances tested, supported growth of L. crispatus from the bladder microbiome and inhibited growth of S. anginosus and E. faecalis.
Firstly, the examiner observes that all of the results provided in the present specification (e.g. table 3) describe the results of in vitro growth in assay plates, not the modulation of a living subject’s microbiome in vivo. While they can demonstrate certain results, for example that isomaltulose achieves better selectivity between commensal and pathogenic bacterial species than most other prebiotics tested, they do not address other elements of the claimed invention, for example the effect of vaginal administration of these prebiotics on the bladder of a living subject. Applicant’s arguments appear to stem from the fact that certain species tested (e.g. LC-2, LC-3, and SA-2) were isolated from the bladder and allegedly represent different organisms from others (e.g. LC-1, LC-4, and AS-1) obtained from a culture collection or from a vaginal microbiome. In order to support such a finding of unexpected results, the data provided would need to demonstrate that the therapeutic effect was unexpectedly better when applied to bacteria from the bladder microbiome, as opposed to the same species from different sources. It is further observed that table 6 on pp. 12-13, while it serves to compare the effects of various different prebiotics, only tests them against the strains SA-2 and LC-3, which are bladder-derived strains, and does not compare the results to equivalent strains taken from other sources. Tables 4-5 on p. 10 further disclose comparative testing between bladder and vaginal derived strains of E. coli, but finds no difference between the observed effects on the different strains. Tables 2-3 on pp. 6-8 do compare bladder-derived bacterial strains to several strains from other sources (Ef-1, Lc-1, Lc-4. And Sa-1) However, the prebiotic isomaltulose (referred to as palatinose in table 3) was not tested against any of the culture collection derived strains. Furthermore of the three strains of L. crispatus that is was tested against, it supported growth of one of the two bladder derived strains as well as the one vaginal-derived strain. More broadly, of the 29 different prebiotics tested, there was no consistent trend of bladder-derived strains responding differently than non-bladder-derived strains, as would be necessary for a finding of unexpected results.
Still further, the fact that isomaltulose was shown to unexpectedly produce selectivity for L. crispatus over S. anginosus is not evidence of unexpected results, since the closest prior art (Zeng) already describes isomaltulose as the preferred prebiotic.
For these reasons the rejections are deemed proper and maintained.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 5/20/2026
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