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 1-14 and 19 are pending.
Priority
Acknowledgment is made of Applicant’s claim for priority to the filing date of SG10202010833R filed 30 October 2020 and PCT/SG2021/050662 30 October 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Therefore, the effective filing date is 30 October 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 28 April 2023 and 27 March 2025 are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-7, 14, and 19 in the reply filed on 04 September 2025 is acknowledged.
Claims 8-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04 September 2025.
Therefore, claims 1-7, 14, and 19 are under examination.
Public Availability of the Biological Materials
Biological materials Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917 are all well-known and readily available strains of microorganisms.
Streptococcus thermophilus B of R is commercially available from ATCC under accession number ATCC 19258, as evidenced by ATCC (S. thermophilus) (Streptococcus thermophilus Orla-Jensen, https://www.atcc.org/products/19258, accessed on 29 September 2025).
Lactobacillus plantarum WCSF1 is commercially available from ATCC under accession number BAA-793, as evidenced by ATCC (L. plantarum) (Lactoplantibacillus plantarum (Orla-Jensen) Zheng et al., https://www.atcc.org/products/baa-793, accessed on 29 September 2025).
Escherichia coli Nissle 1917 is commercially available from DSMZ under accession number DSM No. 115365, as evidenced by DSMZ (E. coli) (Escherichia coli Product number: DSM 115365, https://webshop.dsmz.de/en/bacteria/Escherichia-coli-oxid-488.html, accessed 29 September 2025).
However, while Lactobacillus reuteri MM2-3 is a well-known strain that has been deposited at the ATCC under accession number PTA 4659, as evidenced by pg. 2 right col. Materials and Methods para. 1 of Sendelius et al. (Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659, Journal of Industrial Microbiology and Biotechnology, 2023, 50, kuad041), there is no evidence that the strain is readily available to the public.
Claim Objections
Claims 1-2 and 7 are objected to because of the following informalities:
Claim 1 needs a comma added after the term “B of R” on line 2 of the claim.
Claim 2 needs a comma added after the term “B of R” on line 2 of the claim.
Claim 7 needs a comma added after the term “beverage” on line 2 of the claim. Additionally, the term “gel cap” is extraneous because it is a colloquial name for the term “gelatin capsule” recited prior in the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7, 14, and 19 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is apparent that Lactobacillus reuteri MM2-3 is required to practice the claimed invention. As such the biological material must be known and readily available or obtainable by a repeatable method set forth in the specification, or otherwise known and readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the Lactobacillus reuteri MM2-3.
The process disclosed in the specification does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the Lactobacillus reuteri MM2-3 that is considered necessary to make and use the invention is both known and readily available to the public.
Therefore, a deposit at a recognized depository may be made to obviate this rejection.
If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, that all restrictions imposed by the depositor on the availability to the public on the deposited material will be irrevocably removed upon granting of the patent, would satisfy the deposit requirement made herein.
If the deposit is a non-Budapest Treaty deposit, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, a statement, affidavit or declaration by Applicant or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit would satisfy the requirements herein by stating and providing that:
(a) During the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) All restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) The deposit will be maintained in a public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) Provide evidence of the test of the viability of the biological material at the time of deposit (see 37 CFR 1.807).
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7, 14, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a composition comprising or consisting of two or more of Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917, formulated to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject. It is unclear if the term “formulated” is a structural requirement for the composition, such that some structure is necessary for the composition to be considered formulated to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject, or if the term “formulated” merely links the use of the claimed composition for the intended purpose of preventing or treating intestinal barrier dysfunction and/or heat stress in a subject. It is unclear to one of ordinary skill in the art what constitutes a “formulated” composition in the context of the claim.
Claims 2-7, 14, and 19 are dependent on claim 1, and so are indefinite for the same reason.
Claim 4 further recites the composition of claim 1 is formulated to prevent or treat heat stress-induced gut permeability in said subject. It is unclear if the term “formulated” is a structural requirement for the composition, or if it merely links the use of the claimed composition for the intended purpose of preventing or treating heat stress-induced gut permeability in a subject. It is unclear to one of ordinary skill in the art what constitutes a “formulated” composition in the context of the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7, 14, and 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a product of nature without significantly more.
Claims 1-7, 14, and 19 are drawn to the statutory category of a composition of matter (Step 1: Yes).
Claim 1 recites a composition comprising or consisting of two or more of Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917, formulated to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject.
Lactobacillus reuteri MM2-3 is a naturally occurring bacteria isolated from human breast milk, as evidenced by pg. 2 right col. Materials and Methods para. 1 of Sendelius et al. (Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659, Journal of Industrial Microbiology and Biotechnology, 2023, 50, kuad041). Lactobacillus plantarum WCSF1 is a naturally occurring bacteria isolated from human saliva in 2002, as evidenced by ATCC (L. plantarum) (Lactoplantibacillus plantarum (Orla-Jensen) Zheng et al., https://www.atcc.org/products/baa-793, accessed on 29 September 2025). Streptococcus thermophilus B of R is a naturally occurring bacteria isolated from pasteurized milk, as evidenced by ATCC (S. thermophilus) (Streptococcus thermophilus Orla-Jensen, https://www.atcc.org/products/19258, accessed on 29 September 2025). Escherichia coli Nissle 1917 is also a naturally occurring bacteria isolated from the feces of a human military officer, as evidenced by pg. 1012 right col. para. 1 of Schultz et al. (Clinical Use of E. coli Nissle 1917 in Inflammatory Bowel Disease, Inflamm Bowel Dis, Volume 14, Number 7, July 2008). The phrase “formulated to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject” is interpreted as being a desired use of claim 1’s composition, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition of claim 1.
Claim 2 limits claim 1 to comprise or consist of all four strains of Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917. As described above, these bacterial strains are naturally occurring.
Claim 3 recites the heat stress that the composition of claim 1 is formulated to prevent or treat is at least in part due to physical exertion by the subject, which limits the desired use of claim 1’s composition, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition.
Claim 4 recites that the composition of claim 1 is formulated to prevent or treat heat stress-induced gut permeability in said subject, which is interpreted as being a desired use of claim 1’s composition, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition.
Claim 5 recites that the composition of claim 4 comprises a dose of about 108 colony-forming units (CFU) of each strain, which limits the amount of each bacterial strain in the composition, but does not add any non-natural elements to the composition.
Claim 6 recites that the subject for which the composition of claim 1 is formulated to prevent or treat intestinal barrier dysfunction and/or heat stress is a human, which is interpreted as limiting the subject of the desired use of claim 1’s composition to prevent or treat intestinal barrier dysfunction and/or heat stress, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition.
Claim 7 recites that the composition of claim 1 is in the form of a gelatin capsule, pressed tablet, gel cap, liquid beverage, or sachet. The specification lacks definitions for the terms “gelatin capsule” and “gel cap”. Since “gel cap” is a colloquial form of “gelatin capsule”, the two terms are interpreted to be the same thing. Gelatin is a naturally occurring polymer, as evidenced by pg. 240 sec. 1 sent. 1 of Alipal et al. (A review of gelatin: Properties, sources, process, applications, and commercialization, Materials Today: Proceedings 42 (2021) 240–250), as such this form of the instant composition comprises all naturally occurring components, and there is no evidence that the encapsulation of the instant composition affords any markedly different characteristics as compared to the components as found in nature. The BRI of the term “liquid beverage” includes beverages such as water, which is a naturally occurring liquid beverage.
It is noted that the compositional forms a pressed tablet and sachet are non-natural forms of the instant composition. Applicant may amend the claims to limit the instant composition to be in these forms to obviate the 101 rejection.
Claim 14 recites the composition of claim 1 for use in a method of treating or ameliorating conditions associated with intestinal barrier dysfunction and/or heat stress in a subject, which is interpreted as being a desired use of claim 1’s composition, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition.
Claim 19 recites the composition of claim 2, for use in a method of treating or ameliorating conditions associated with intestinal barrier dysfunction and/or heat stress in a subject, which is interpreted as being a desired use of claim 2’s composition, but it does not add any new structural limitations to the composition, so does not add any non-natural elements to the composition.
Therefore the instant invention recites a judicial exception of a product of nature (Step 2A Prong One: Yes).
This judicial exception is not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are drawn to a nature-based composition, and not to any method or application of the composition for a specific use. Although the claims recite the intended use of the composition to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject, the claims do not recite any active step which applies the composition for this purpose.
Therefore, the instant invention does not include any additional elements that amount to significantly more than the recited judicial exception of a product of nature, and so the instant invention is not patent eligible subject matter under 35 USC §101 (Step 2A Prong Two and Step 2B: No).
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 1-4, 6, 14, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ahl et al. (Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice, Acta Physiol 2016, 217, 300–310) in view of Foligne et al. (Recommendations for Improved Use of the Murine TNBS-Induced Colitis Model in Evaluating Anti-inflammatory Properties of Lactic Acid Bacteria: Technical and Microbiological Aspects, Digestive Diseases and Sciences, Vol. 51, No. 2 (February 2006), pp. 390–400), Ou et al. (Antioxidative Effects of Intracellular Extracts of Yogurt Bacteria on Lipid Peroxidation and Intestine 407 Cells, Journal of Food and Drug Analysis, Vol. 14, No. 3, 2006, Pages 304-310), and Schultz et al. (Clinical Use of E. coli Nissle 1917 in Inflammatory Bowel Disease, Inflamm Bowel Dis, Volume 14, Number 7, July 2008), and as evidenced by Sendelius et al. (Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659, Journal of Industrial Microbiology and Biotechnology, 2023, 50, kuad041), ATCC (L. plantarum) (Lactoplantibacillus plantarum (Orla-Jensen) Zheng et al., https://www.atcc.org/products/baa-793, accessed on 29 September 2025), and ATCC (S. thermophilus) (Streptococcus thermophilus Orla-Jensen, https://www.atcc.org/products/19258, accessed on 29 September 2025).
Claim 1 recites the phrase “formulated to prevent or treat intestinal barrier dysfunction and/or heat stress in a subject”, which is an intended use that does not add any new structural limitations to the composition. Claims 3, 4, 6, 14 and 19 recite intended uses that do not further limit the claimed composition. Therefore, if a composition in the prior art teaches all of the structural limitations of the claimed composition, claims 1, 3-4, 6, 14, and 19 will be considered to be rendered obvious.
Ahl teaches probiotic strain Lactobacillus reuteri ATCC PTA 4659, and that the strain significantly reduced inflammatory markers and increased mucus thickness when administered to DSS-induced colitis mice, thus is able to ameliorate colitis (Ahl title and abstract). Lactobacillus reuteri ATCC PTA 4659 is also known as Lactobacillus reuteri MM2-3 (as evidenced by Sendelius et al. pg. 2 right col. Materials and Methods para. 1).
Ahl does not teach probiotic strains Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, or Escherichia coli Nissle 1917.
Foligne teaches that Lactobacillus plantarum NCIMB 8826 was able to protect and attenuate colitis and intestinal inflammation in TNBS-induced colitis mice (Foligne abstract). Lactobacillus plantarum NCIMB 8826 is also known as Lactobacillus plantarum WCSF1, as evidenced by ATCC (L. plantarum).
Foligne does not teach probiotic strains Streptococcus thermophilus B of R and Escherichia coli Nissle 1917.
Ou teaches Streptococcus thermophilus ATCC 19258 was highly antioxidative, reduced the genotoxicity of H2O2, and demonstrated high inhibition of the cytotoxicity of H2O2 (Ou abstract). Ou also teaches that oxidative stress is closely related to gastrointestinal diseases, including intestinal ischemia, radiation enteritis, inflammatory bowel diseases, and promotion of gastric and colorectal cancers (Ou pg. 304 right col. sent. 3). Streptococcus thermophilus ATCC 19258 is also known as Streptococcus thermophilus B of R, as evidenced by ATCC (S. thermophilus).
Ou does not teach probiotic strain Escherichia coli Nissle 1917.
Schultz teaches the probiotic microorganism Escherichia coli Nissle 1917 and that it is a safe and effective candidate for treating chronic inflammatory bowel diseases (Schultz abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to have combined probiotic strains Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917 into a composition in order to treat intestinal inflammation, inflammatory bowel disease, and colitis in a subject in need thereof.
MPEP §2144.06(I) states "[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.... [T]he idea of combining them flows logically from their having been individually taught in the prior art."
Each of the strains were known to be effective treatments of inflammatory bowel disease, colitis, intestinal inflammation, and/or symptoms thereof, so each of the strains shared a common purpose and beneficial effects. Thus, combining probiotic strains Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917 together into a single composition would have been predictably expected by one of ordinary skill in the art to be suitable to treat intestinal inflammation, inflammatory bowel disease, and colitis in a subject in need thereof.
Claims 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Ahl in view of Foligne, Ou, and Schultz as applied to claims 1-4, 6, 14, and 19 above, and further in view of Prioult et al. (US 20120141443 A1, published 07 June 2012).
Ahl, Foligne, Ou, and Schultz do not teach about 108 colony-forming units (CFU) of each strain, nor that the composition is in the form of a gelatin capsule, pressed tablet, gel cap, liquid beverage or sachet.
Regarding claim 5, Prioult teaches a composition comprising probiotic microorganisms Lactobacillus reuteri, Lactobacillus plantarum, Streptococcus thermophilus, and Escherichia coli, and that their composition treats colitis and IBD (Prioult claim 16 and [0118]-[0119]). Prioult teaches that the microorganisms are present in the composition in an amount ranging from 104 to 109 CFU (commensurate in scope with instant claim 5) (Prioult [0077]).
Regarding claim 7, Prioult teaches that the composition may be in the form of tablets, capsules, sachets, and liquids (Prioult [0082]).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to have included 104 to 109 CFU of the probiotic strains Lactobacillus reuteri MM2-3, Lactobacillus plantarum WCSF1, Streptococcus thermophilus B of R, and Escherichia coli Nissle 1917 in the composition of Ahl, Foligne, Ou, and Schultz, and to have made the composition into tablets, capsules, sachets, and liquids. One of ordinary skill in the art would have been motivated to do so, and have reasonable expectations of success, because Prioult teaches a similar composition comprising the same species of bacteria Lactobacillus reuteri, Lactobacillus plantarum, Streptococcus thermophilus, and Escherichia coli in an amount between 104 to 109 CFU, and that their composition is capable of treating colitis and IBD, just as the composition of Ahl, Foligne, Ou, and Schultz is able to do. Prioult also taught that the composition may be in the form of tablets, capsules, sachets, and liquids, which one of ordinary skill in the art would consider to be convenient and administrable forms of the obvious composition of Ahl, Foligne, Ou, and Schultz.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER M DURYEE whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/Alexander M Duryee/Examiner, Art Unit 1657