DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendments
2. The amendment filed Oct. 14, 2024 has been entered. Claims 1, 7, 11 and 13 have been amended. Claims 2-6, 12 and 14-16 are cancelled. Claim 17 was newly added. Claims 1, 7-11, 13 and 17 are under consideration in this Office Action.
Withdrawal of Claim Objections
3. The objection of claim 4 is withdrawn in view of Applicants cancellation of the claim.
Withdrawal of Claim Rejections - 35 USC § 112
4. The deposit rejection of claims 1-16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn because Applicants have complied with the written description requirement.
5. The scope of enablement rejection of claims 3 and 12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn because Applicants cancelled those claims.
6. The rejection of claims 1, 3-4 and 11-14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of Applicants cancelling of claims and claim amendments.
7. The rejection of claims 1-4, 7-14 and 16 under 35 U.S.C. 102(a)(1) as being anticipated by CN110964658 (published 2020-04-07; priority to 2018-09-30) is withdrawn in view of Applicants claim amendments and cancellation of claims.
Maintained Rejection
Double Patenting
8. 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.
9. Claims 1, 7-11, 13 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-12 of U.S. Patent No. 11,274,275. Although the claims at issue are not identical, they are not patentably distinct from each other because they are not patentably distinct from each other because both sets of claims are drawn to method of treating a subject comprising administering to a subject an composition comprising an effective amount of Lactobacillus paracasei, wherein the Lactobacillus paracasei strain has a deposit number of CGMCC 15077
The instant claims are drawn to a method of inhibiting adhesion by pathogenic bacteria to intestinal epithelial cells, comprising administering to a subject an composition comprising an effective amount of Lactobacillus paracasei, wherein the Lactobacillus paracasei strain has a deposit number of CGMCC 15077, wherein the pathogenic bacteria are Escherichia coli, the Escherichia coli are enterotoxigenic Escherichia coli strain ETEC H10407 and/or pathogenic Escherichia coli strain EPEC O119.
The patented claims recite a method for treating a subject, comprising administering an effective amount of Lactobacillus paracasei ET-22 strain to a subject in need thereof for 1) whitening teeth and/or inhibiting oral pathogens; 2) adjusting balance of flora in the subject; 3) promoting growth of bifidobacteria and/or lactic acid bacteria; and/or 4) enhancing immunity of the subject.
The patented claims and instant claims both administer the same Lactobacillus paracasei ET-22 strain deposited as CGMCC 15077. Both sets of claims affect the inhibition of pathogenic bacteria such as ETEC H10407 and EPEC O119. It is well known that ETEC H10407 and EPEC O119 are oral pathogen in the sense that they enter the body via the mouth (contaminated food/water/hands) and causes systemic issues. Both sets of claims administer the exact same bacteria, which inherently has the exact same abilities, i.e., to adjust the subject’s flora and promote growth of bifidobacteria and/or lactic acid bacteria all work to inhibit adhesion of pathogens like E. coli by direct competition and by enhancing the subject’s immune responses.
The claims are not patentably distinct, because both sets of claims treat to improve intestinal immunity by enhancing humoral immunity and/or cellular immunity of the subject, increasing the number of antibody-producing cells, increasing half hemolysis concentration HC50, and/or increasing activity of NK cells. Both sets of claims administered to the subject in an amount of equal to or more than 106 CFU. Both sets of claims recite the composition is a food composition, a pharmaceutical composition. There appears to be no patentable distinction.
This nonstatutory double patenting rejection is maintained.
Response to Arguments
10. Applicant's arguments filed Oct. 14, 2025 have been fully considered but they are not persuasive. Applicants argue that the new claim amendments overcome the double patenting rejection. However, both sets of claims administer the exact same bacteria. The patented claims adjust the subject’s flora and promote growth of bifidobacteria and/or lactic acid bacteria which inherently inhibit adhesion of pathogens like E. coli by direct competition and by enhancing the subject’s immune responses. Therefore the nonstatutory double patenting rejection is appropriate even though the conflicting claims are not identical. In this case, the patented claims and the instant claims are not patentably distinct one from the other. The broadest reasonable interpretation of the patented claim method inherently encompassed the instantly claimed method because administering the exact same Lactobacillus paracasei species will inhibit intestinal adhesion of pathogenic bacteria and inhibit oral pathogens; adjust the balance of subject’s flora; promote growth of bifidobacteria and/or lactic acid bacteria; and enhance immunity of the subject. Therefore the rejection is maintained.
Maintained Grounds of Rejection
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.
11. Claims 1, 7-11, 13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over CN110964658 (published 2020-04-07; priority to 2018-09-30) in view of Davoodabadi et al., (Jundishapur J Microbiol. 2015 Dec 26;8(12):e27852).
The instant claims are drawn to a method of inhibiting adhesion by pathogenic bacteria to intestinal epithelial cells, comprising administering to a subject an composition comprising an effective amount of Lactobacillus paracasei, wherein the Lactobacillus paracasei strain has a deposit number of CGMCC 15077, wherein the pathogenic bacteria are Escherichia coli, the Escherichia coli are enterotoxigenic Escherichia coli strain ETEC H10407 and/or pathogenic Escherichia coli strain EPEC O119.
CN110964658 Lactobacillus paracasei ET-22 with an immunoregulation function. The invention provides the use of a Lactobacillus paracasei ET-22 strain for enhancing the immunity of a subject. The present invention also provides a method for enhancing immunity in a subject, the method comprising administering to the subject a Lactobacillus paracasei ET-22 strain to enhance the immunity thereof [abstract]. The invention provides Lactobacillus paracasei ET-22 strain, which is deposited in China general microbiological culture Collection center (accession No. CGMCC No. 15077) [Disclosure of Invention]. Thus teaching claims 1 and 11.
The probiotics have multiple functions, such as regulating intestinal flora imbalance, enhancing intestinal immunity and inhibiting anaphylactic reaction [Existing problems]. ET-22 strain has superior immunomodulatory effects compared to a control strain. The ET-22 strain has the effect of increasing the humoral and/or cellular immunity of the subject as compared to a control strain [Disclosure of Invention]. Fig. 1 shows L. paracasei ET-22 simulates the tolerance of intestinal environment, gastric acid and bile salt environment. Example 2 shows L. paracasei ET-22 has strong adhesion to Caco-2 cells. ET-22 has a higher ability to activate NK cell activity than L. paracasei K56. It was found that L. paracasei ET-22 has positive humoral immunity; results in positive NK cell activity test and can be considered to have the effect of enhancing immunity [Example 3]. ET-22 are supplemented to regulate the balance of intestinal flora and inhibit the number of harmful bacteria and even pathogenic bacteria, thereby achieving the potential health effect [Variation in intestinal microbial diversity in mice]. Thus teaching claims 3-4 and `1.
At the level of pathopoiesia, vibrio desulfovis (Desulfovibrio) in the intestinal tracts of both the ET-22 low dose and medium dose groups of mice was significantly reduced compared to the control group; the number of Helicobacter pylori in the middle dose group and the high dose group is obviously reduced; the high Escherichia-Shigella was significantly reduced in both the low and medium dose groups. [Variation in intestinal microbial diversity in mice].
The single strain has the advantages of obviously enhancing humoral immunity and activating NK cell activity so as to solve the problems of low immunocompetence and the like caused by irregular diet and increased working pressure [Disclosure of Invention]. The strain is an active strain and the strain may be administered to the subject orally [Disclosure of Invention]. The Lactobacillus paracasei ET-22 strain may be formulated into suitable food compositions, including health foods, nutritional supplements, functional foods, and the like. In some embodiments, buffers, excipients, diluents, carriers, stabilizers, and/or preservatives, for example, may be included in the compositions. In some embodiments, the food product may include a beverage product such as a food product, oil, meat product, dairy product, seafood, can, sugar-containing food, cold food, wine, pet food, and the like. In some embodiments, the food product may include beverages such as dairy drinks, tea, coffee, chewing gum and dentrifice, jerky for pets, or combinations thereof. In some embodiments, the strain of the invention may be prepared as a food composition, e.g. a milk drink, tea, coffee, wherein the milk drink may comprise fermented milk, yoghurt, cheese or milk powder. In the composition, the strain may be present in an effective amount. Thus teaching claims 2, 9, and 10 [Disclosure of Invention].
For example, in a food composition or a pharmaceutical composition, the number of lactic acid bacteria strains is 106CFU or more, e.g. 107CFU above, 108CFU above, 109CFU above, 1010Above CFU; preferably, the number of lactic acid bacteria strains is 1010Above CFU [Disclosure of Invention].
Therefore, CN110964658 teach a method of inhibiting adhesion by pathogenic bacteria to intestinal epithelial cells, comprising administering to a subject an composition comprising an effective amount of Lactobacillus paracasei, wherein the Lactobacillus paracasei strain has a deposit number of CGMCC 15077, but does not explicitly state the pathogenic bacteria are enterotoxigenic Escherichia coli strain ETEC H10407 and/or pathogenic Escherichia coli strain EPEC O119.
Davoodabadi et al., teach among the enteric pathogens, diarrheagenic Escherichia coli are important causes of diarrhea in children in both developing and industrialized countries. Some Lactobacillus species are commonly used as probiotics, with effects especially against acute diarrhea in childhood [Background]. Lactobacillus strains were isolated from infants against five diarrheagenic E. coli pathotypes such as enteroaggregative E. coli (EAEC), enterohaemorrhagic E. coli (EHEC) enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) [Objective]. The antimicrobial activity was tested against references strains, including EAEC 042, ETEC H10407, EHEC O157:H7 EDL933, EPEC E2348/69 and EIEC 4608-58 [Antimicrobial Activity]. Table 1 shows the antimicrobial activity of cell free culture supernatants of the Lactobacillus paracasei isolates against diarrheagenic Escherichia coli where Lactobacillus isolates with no additional treatment inhibited the growth of both ETEC H10407 and EHEC O157:H7 [Antimicrobial Activity]. The L. paracasei in these studies, in accordance with our study had antimicrobial activity against EAEC and ETEC [Discussion]. The inhibition of diarrheagenic E. coli growth appeared to be due to the production of organic acids or hydrogen peroxide produced by the Lactobacillus strains [Discussion]. Our findings show that Lactobacillus strains with human origin had an inhibitory activity against the diarrheagenic E. coli, and these strains may be useful as probiotic candidates in prevention of intestinal infections caused by diarrheagenic E. coli [Conclusion].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Davoodabadi et al’s teaching that L. paracasei treats intestinal infections caused by diarrheagenic E. coli to CN110964658 method for improving intestinal immunity, comprising administering an effective amount of Lactobacillus paracasei having deposit number of CGMCC 15077 (ET-22) in order improve intestinal immunity and inherently, inhibition of E coli to intestinal cells. It is well known that the inhibition of diarrheagenic E. coli growth appears to be due to the production of organic acids or hydrogen peroxide produced by the Lactobacillus strains. One of ordinary skill in the art would have a reasonable expectation of success in administering L. paracasei because it is known to have antimicrobial activity against EAEC and ETEC H10407.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of improving intestinal immunity, comprising administering to the subject a therapeutically effective amount of L. paracasei, wherein the pathogenic bacteria is E coli and there is no change in the respective function of the L. paracasei, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
12. Applicant's arguments filed Oct. 14, 2025 have been fully considered but they are not persuasive. Applicants argue that the new claim amendments overcome the double rejection. Applicants argue that Table 1 of Davoodabadi, when the CFCS of Lactobacillus paracasei S14 was adjusted to a pH of 6.5, there was no inhibitory effect on all E. coli strains. Thus because the intestinal pH is about 6-7.5, the L. paracasei would not be effective at inhibiting E.coli strains. However, this argument is misplaced because Table 1. Antimicrobial Activity of Cell Free Culture Supernatants(CFCS) of the Lactobacillus Isolates Against Diarrheagenic Escherichia coli. The supernatant is cell free, therefore Table 1 does not describe the activity of L. paracasei. Therefore Applicants argument that cell free supernatant would be ineffective at pH 6 has no bearing on the efficacy of L. paracasei being administered to a subject. The comparisons are not equivalent and the argument is not persuasive.
Applicants argue that inhibiting the growth of E coli is not the same as inhibiting the adhesion of E coli to intestinal cells. Applicants are reminded that CN110964658 provides Lactobacillus paracasei ET-22 strain, which is deposited in China general microbiological culture Collection center (accession No. CGMCC No. 15077). CN110964658 teaches the administration of CGMCC No. 15077, which is exactly the same as the instantly claimed strain. It is the position of the Office that something which is old (CGMCC No. 15077) does not become patentable upon the discovery of a new property. [T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Id.
Additionally, the inherent feature (i.e., inhibition of adhesion) need not be recognized at the relevant time. See MPEP 2112. Finally, if the composition is physically the same, then it must have the same properties. “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. In this case, CN110964658 provides Lactobacillus paracasei ET-22 strain, which is deposited in China general microbiological culture Collection center (accession No. CGMCC No. 15077) which is exactly the as the instant claims. There is no difference in the composition preparation or the composition comprising CGMCC 15077 being administered. All are facts which Applicant does not dispute.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Davoodabadi et al’s teaching that L. paracasei treats intestinal infections caused by diarrheagenic E. coli to CN110964658 method by improving intestinal immunity, comprising administering an effective amount of Lactobacillus paracasei having deposit number of CGMCC 15077 (ET-22) in order improve intestinal immunity and inherently inhibit adhesion by pathogenic E coli to intestinal epithelial cells. Therefore none of Applicants arguments are persuasive and the rejection is maintained.
Pertinent Art
13. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
CN110893195 (published 2020-03-20; priority to 2019-09-30) The Lactobacillus paracasei ET-22 strain can obviously inhibit inflammatory factors IL-6 and TNF-alpha and improve the generation of the inflammatory factors IL-10, and has the effect of relieving intestinal inflammation.
CN110960559 (published 2020-04-07; priority to 2018-09-30) ) The ET-22 strain, which is preserved in China general microbiological culture Collection center with the preservation number of CGMCC No. 15077. The ET-22 strain for inhibits oral pathogens which may include Streptococcus mutans and Fusobacterium nucleatum.
WO2020063531 published 2020-04-02; priority to 2018-09-30) A method for treating a subject, comprising administering an effective amount of Lactobacillus paracasei ET-22 strain to a subject in need thereof for 1) whitening teeth and/or inhibiting oral pathogens; 2) adjusting balance of flora in the subject; 3) promoting growth of bifidobacteria and/or lactic acid bacteria; and/or 4) enhancing immunity of the subject. See also EP3822338
WO2023236452 published 2023-12-14; priority to 2022-11-21) The Lactobacillus paracasei culture comprises Lactobacillus paracasei ET-22 cells and/or extracellular metabolites thereof. Lactobacillus paracasei ET-22 is a strain with accession number CGMCC No. 15077.
WO2000053200A1 teach Lactobacillus strains preventing diarrhea pathogenic bacteria.
Pazhoohan et al., (Microbial Pathogenesis. Vol 148, Nov 2020, 104271) teach the features and antagonistic action of Lactobacillus strains, against the growth and adhesion of Enterotoxigenic Escherichia coli (ETEC) and Enteroaggregative Escherichia coli (EAEC) strains creating diarrhea in children.
Conclusion
14. No claims allowed.
15. 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.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Vanessa Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645