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 1-2, 4-5, 7-8, 10-13, 15-17, and 19 are pending.
Response to Amendment
Applicant canceled claims 3, 6, 9, 14, and 18. Applicant amended claims 1, 7 and 12 to add the limitation “at least 7 days” and limited the amount of the prebiotic to “1.5 weight % to 5 weight %”, amended claims 2, 8 and 13 to remove the parentheses, amended claim 4 to depend from claim 1 and claim 8 to depend from claim 7 and claim 15 to depend from claim 12.
The objection to claims 1, 7, and 12 is withdrawn in view of the amendment.
The rejection of claims 1-19 under 35 U.S.C. 112(a) is withdrawn in view of the statement filed on 07/29/2026.
The rejection of claims 1-6, 8, and 13 under 35 U.S.C. 112(b) is withdrawn in view of the amendment.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable.
Refer to document “Sequence Listing in Computer Readable Format is Defective” dated 07/29/2026.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3);
o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and
o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5).
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Maintained Rejection
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.
Claims 1-2, 4-5, 7-8, 10-13, 15-17, and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over Chen (Frontiers in microbiology 10 (2019): 789, of record in IDS) in view of He ( Advanced Materials Research 382 (2012): 450-453, of record in IDS), Nam (US-20200345798, published 11/05/2020, of record in IDS), Paek (US-20210023147, published 01/28/2021, of record in IDS), and Tajdozian (Journal of Microbiology and Biotechnology 31.10 (2021): 1383) and as evidenced by Tang (Journal of Microbiology, Immunology and Infection 52.2 (2019): 273-281) and Appendix A (Sequence alignment, 2026)
Regarding claims 1-2, 4-5, 7-8, 10-13, 15-17, and 19, Chen teaches Lactobacillus rhamnosus, Lactobacillus paracasei, and Lactobacillus plantarum exhibit good antibacterial activity against carbapenem resistant Enterobacteriaceae (CRE) (i.e., drug-resistant Enterobacteriaceae) and teaches this effect may have potential applications through the use of Lactobacillus strains as starter cultures in fermented foods or as food preservatives for controlling or preventing CRE infections and suggests animal studies (i.e., administering to a subject in need thereof) (Abstract, Conclusion, Discussion para.1). Chen teaches the Lactobacillus strains had antibacterial activity against carbapenem-resistant K. pneumoniae strains obtained from Tang et al. 2016b (page 2 “Bacterial Strains and Culture Conditions”). The latter reports that the carbapenem-resistant K. pneumoniae contain KPC-2 (Results first para.). Thus, it is understood that the CRE has KPC-2. Chen teaches growing the Lactobacillus in MRS (page 2 “Bacterial Strains and Culture Conditions”). Chen teaches the acidic pH is essential for the antibacterial activity observed and the effective inhibitory activity was generally observed at a pH of less than 4.2 (Discussion para 2.). Chen teaches using 105 to 108 CFU/ml of Lactobacillus isolates (i.e., ratio 1:1:1) Chen does not teach prebiotic isomaltooligosaccharide.
However, He teaches that isomaltooligosaccharide and lactulose are prebiotics (introduction) and teaches isomaltooligosaccharide promotes the growth of Lactobacillus strains and does not affect their pH or acidity and teaches that culture of Lactobacillus rhamnosus has a pH under 5 (Fig. 2). He teaches using 1.5 weight % of IMO (Fig. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Chen by adding Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus plantarum, and isomaltooligosaccharide and/or lactulose, as suggested by Chen and He. One of ordinary skill in the art would be motivated to do so in order to treat CRE infections and promote the growth of the bacteria without affecting their acidity. Since Chen teaches the acidic pH is pivotal for the antibacterial activity of the strains, there is a reasonable expectation of success. MPEP §2144.06(I) states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The claimed species of prebiotic isomaltooligosaccharide and lactulose would have been obvious to one of ordinary skill in the art since He teaches both are prebiotic that can be used to promote growth of probiotics. A person of ordinary skill in the art would be motivated to add one or more of the prebiotics taught by He while considering their effect on the growth of the strain and its acidity, as suggested by He. See MPEP 2144.08
Chen and He do not teach Lactobacillus rhamnosus JJ101 or Lactobacillus paracasei JJ102.
However, Nam teaches that a Lactobacillus rhamnosus strain and a Lactobacillus paracasei strain have health benefits such as antimicrobial activity against Gardnerella vaginalis and Candida albicans, excellent acid resistance, bile resistance, autoaggregation ability and epithelial cell adhesion ability and are suitable for probiotics (Abstract, claim 1), and teaches that the strains may be used in combination with each other for better antimicrobial activity ([0075]). Nam teaches that SEQ ID NO: 1 and 2 are the 16S rDNA of the Lactobacillus paracasei and Lactobacillus rhamnosus strains, respectively ([0093]). Applicant discloses that the 16S rDNA of Lactobacillus rhamnosus JJ101 is SEQ ID NO:3 and Lactobacillus paracasei JJ102 is SEQ ID NO:4 ([0047] of the specification). Alignment of the instant sequences and Nam’s sequences show 100% identity (See Appendix A pages 1-4). Thus, it is understood that the strains are the same. He teaches the composition comprises corn starch (i.e. a binder and stabilizer) and is formulated in powder form ([0131]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Chen by substituting Lactobacillus rhamnosus strain and Lactobacillus paracasei strain as suggested by Nam for Chen’s strain. One of ordinary skill in the art would be motivated to do so in order to treat CRE infections. MPEP 2144.06 II states it is obvious to substitute equivalents know for the same purpose. Since Nam teaches that the strains are safe for consumption and have excellent acid resistance, bile resistance, autoaggregation ability and epithelial cell adhesion ability, there is a reasonable expectation of success.
Chen, He, and Nam do not teach Lactobacillus plantarum JJ103.
However, Paek teaches a composition comprising Lactobacillus plantarum (claim 1). Paek teaches that SEQ ID NO: 1 is the 16S rRNA of the bacterium. Applicant discloses that 16S rDNA of Lactobacillus plantarum JJ103 is SEQ ID NO:5 ([0047] of the specification). Alignment of both sequences shows 100% identity (See Appendix A pages 5-6). Thus, it is understood that these strains are the same. Paek teaches that the strain has health benefits such as blood glucose lowering activity and antioxidant activity, and has excellent acid tolerance, bile tolerance, auto-aggregation, and adhesion to epithelial cells, and thus is suitable for probiotics (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Chen by substituting Lactobacillus plantarum strain as suggested by Paek for Chen’s strain. One of ordinary skill in the art would be motivated to do so in order to treat CRE infections. MPEP 2144.06 II states it is obvious to substitute equivalents know for the same purpose. Since Paek teaches the strains are safe for consumption and have excellent acid resistance, bile resistance, auto-aggregation ability and epithelial cell adhesion ability, there is a reasonable expectation of success.
The limitation “compared to culture solutions obtained by culturing the Lactobacillus rhamnosus JJ101, the Lactobacillus paracasei JJ102, and the Lactobacillus plantarum JJ103 with MRS, respectively, co-culture solutions obtained by subjecting the Lactobacillus rhamnosus JJ101, the Lactobacillus paracasei JJ102, and the Lactobacillus plantarum JJ103 to a co-culture step with the MRS having the prebiotic, respectively, have a lower pH that is less than 5” does not require active method steps. Claim scope is not limited by claim language that suggest or makes optional but does not require steps to be performed. See MPEP 2111.04.
Chen, He, Nam, and Paek do not teach composition is administered to the subject with an effective dose for at least 7 days to less than 14 days.
However, Tajdozian teaches administering to mouse Lactobacillus strain at a dose of 1.6x109 CFU/mice to treat carbapenem-resistant Klebsiella. Applicant discloses that 1.0x1011 CFU/kg bw/day is equivalent to 2.0x109 CFU/mouse ([0039]). Tajdozian teaches that after 8 days of treatment, the illness severity score dropped to zero (Fig. 2A and 2C).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Chen by administering to a mouse a dose of 1.6x109 CFU/mice for 8 days, as suggested by Tajdozian. One of ordinary skill in the art would be motivated to do so in order to safely and effectively treat the mouse. Since Chen and Tajdozian teach a desire to treat carbapenem resistant bacterial infections using Lactobacillus, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 07/29/2026 have been fully considered but they are not persuasive.
Applicant argues that He teaches away from the present claim 1 regarding to the amount of the prebiotics and that He teaches that the growth of Lactobacillus rhamnosus by adding IMO was inhibited and obviously in the high concentration (i.e., more than 1 %, w/v).
In response to the argument, He does not teach away from the present claim because He teaches IMO is a prebiotic that significantly increases lactobacilli and bifidobacteria populations in the gut and teaches high concentrations of IMO affect the growth of the L. rhamnosus in a specific environment which is the goat milk (Abstract). He teaches at concentrations of 2 % of IMO, the enumeration of L. rhamnosus decreased from 1.73×109 cfu/mL to 0.65×109 cfu/mL in a composition of goat milk (Introduction). Furthermore, at concentrations of 1.5 % of IMO, the decrease in L. rhamnosus was from about 1.7×109 cfu/mL to about 1.3×109 cfu/mL. One of ordinary skill in the art would be motivated to use a concentration of 1.5% of IMO in order to maintain a sufficient concentration of the bacterium while keeping the pH under 5, as suggested by He.
Applicant argues that Tajdozian teaches that the CPE amount can only be reduced by 2 log units by 8 days of the administration of Lactobacillus plantarum merely (i.e., without Lactobacillus rhamnosus, Lactobacillus paracasei, and probiotics) whereas the present invention shows that the CPE amount can be reduced by 3 log units after 7 days.
In response to the argument, the claims do not limit the amount of reduction of CPE. Tajdozian teaches administering Lactobacillus plantarum for at least 7 days in order to treat the infection. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues He, Nam, Tajdozian, and Paek do not teach, suggest and motivate the mixed LAB (i.e., Lactobacillus rhamnosus JJ101, Lactobacillus paracasei JJ102, and Lactobacillus plantarum JJ103), the specific probiotics (i.e. isomaltooligosaccharide) and its amount used (i.e., 1.5 weight% to 5.0 weight %) as well as how to achieve the effect (i.e., reduces the CPE amount by 3 log units after at least 7 days of administration) of the synbiotic composition recited in present claim 1.
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, Chen teaches that Lactobacillus rhamnosus, Lactobacillus paracasei, and Lactobacillus plantarum have antibacterial activity against carbapenem resistant Enterobacteriaceae and teaches that the acidic pH (is essential for the antibacterial activity. He teaches IMO and lactulose are prebiotic for Lactobacillus strains and keep the pH of the culture under 5. Nam and Park teach isolated strains of Lactobacillus rhamnosus, Lactobacillus paracasei, and Lactobacillus plantarum that have health benefits and safe to be administered. Tajdozian teaches administering to mouse Lactobacillus strain to treat carbapenem-resistant Klebsiella and teaches that after 8 days of treatment, the illness severity score dropped to zero. One of ordinary skill in the art would be motivated to combine the teachings of Chen, He, Nam, Park and Tajdozian in order to treat carbapenem-resistant Enterobacteriaceae.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY A CRUM whose telephone number is (571)272-1661. The examiner can normally be reached M-F 8:00-5:00 CT with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY A CRUM/ Examiner, Art Unit 1657
/THANE UNDERDAHL/ Primary Examiner, Art Unit 1699
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