DETAILED ACTION
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 .
Claim Status
The amendment of 12/23/2025 has been entered. Claims 16-33 are pending (claim set as filed on 12/23/2025). Claims 20-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 of Group I, drawn to a composition comprising Lactobacillus reuteri DS0384 or a culture broth thereof, and of the gene species OLFM4 and DEFA5 was made without traverse in the reply filed on 08/18/2025.
Claims 16-19 and 30-33 are currently under examination and were examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 12/22/2022 was considered.
Withdrawn Objections/Rejections
The rejection of claims 16 and 18 under 35 U.S.C. 102/103 set forth in the previous Office is withdrawn in light of the amendment filed on 12/23/2025. New rejections under 35 U.S.C. 103 have been presented, as discussed below.
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 16-19, 31 and 33 are rejected under 35 U.S.C. 101 because the claimed
invention is directed to a combination of judicial exceptions without significantly more. The statutory categories of invention under 35 U.S.C. 101 are processes, machines, manufactures, and compositions of matter. However, certain members of these categories constitute judicial exceptions, i.e., the courts have determined that these entities are not patentable subject matter. These judicial exceptions include abstract ideas, laws of nature, and natural phenomena. The Office released guidance on January 7, 2019 for the examination of claims reciting natural products under 35 U.S.C. 101 in light of the recent Supreme Court decisions in Association for Molecular Pathology v. Myriad Genetics, Inc. (569 U.S., 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013)) and Mayo Collaborative Services v. Prometheus Laboratories (566 U.S.,132 S. Ct. 1289, 101 USPQ2d 1961 (2012)). This guidance indicates that claims must pass an eligibility test to avoid rejection under 35 U.S.C. 101. Under this test, the product must (a) not be directed to a judicial exception or must (b) contain additional elements that
amount to significantly more than the judicial exception itself.
'Directed to a judicial exception' analysis:
Prong One: Does the claim recite an abstract idea, law of nature, or natural
phenomenon?
Base claims 16 and 18 recites “Lactobacillus reuteri DS0384 strain” which is considered a natural phenomenon since it is a natural isolate (“L. reuteri DS0384, isolated from neonatal feces”; see paragraph [113]), and further recite “cryoprotectant” which reads on trehalose and lactose (see paragraph [78]), which are natural phenomena. Base claim 16 recites “a culture broth thereof”, which is considered a natural phenomenon since it comprises the natural isolate L. reuteri DS0384 and/or its secreted metabolites (see paragraphs [32], [61]). Claims 17 and 19 recite the cryoprotectant alternatives trehalose, lactose, mannitol, glycerol, and honey which are natural phenomena. Claims 18 and 19 recite “fermentation starter” which is described as “a preparation comprising a microorganism involved in fermentation and other ingredients that provide essential ingredients for the growth of the microorganism” (see paragraph [49]), wherein the microorganism in the fermentation starter composition is Lactobacillus reuteri DS0384 strain (see claim 18 and paragraph [49]). Strain DS03841 is a natural phenomenon as discussed above. ‘Essential ingredients for the growth of the microorganism’ comprised in the fermentation starter composition reads on glucose and yeast extract (see paragraph [53]), which are natural phenomena. Claims 31 and 33 recite “Lactobacillus reuteri DS0384” which is a natural phenomenon. It is noted that the concentration of a bacterium does not change the function and characteristic of the bacterium, and thus, the recited bacteria are natural phenomenona independent from their concentration (see MPEP 2106.04(c) I.B).
The above listed microorganism, culture broth thereof, cryoprotectants trehalose, lactose, mannitol, glycerol, and honey, and essential ingredients for growth of the microorganism are all directed to natural products that do not interact to yield significantly more. It is noted that the Applicant merely claims cryprotectant but does not actually state it is cryopreserved. Thus one cannot ascertain there is an interaction (cryopreserving).
Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No additional elements are cited that would integrate the judicial exception into a practical application.
'Significantly more' analysis:
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because the claims do not include any additional elements other than the judicial exceptions.
Therefore, claims 16-19, 31 and 33 are directed to subject matter that is not patent-eligible and are rejected under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112(a)
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 16-19 and 30-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contain 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.
The microorganism Lactobacillus reuteri DS0384 is recited in the claims and, thus, is essential to the claimed invention. Because the microorganism is essential to the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the microorganism is not so obtainable or available, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials.
The specification does not disclose a repeatable process to obtain the microorganism, and it is not apparent if the biological material is readily available to the public. It is noted that applicant has deposited the microorganism (see, for example, claim 16 and specification, paragraph [38]), but there is no indication in the specification as to public availability.
If the deposit is made under the Budapest Treaty, then an affidavit or declaration by applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the specific strain has been deposited under the Budapest Treaty and that the specific strain will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 C.F.R. §§ 1.801-1.809, applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that:
(a) during the pendency of this 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 effective life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit will be made (see 37 C.F.R. §1.807); and
(e) the deposit will be replaced if it should ever become inviable.
Applicant’s attention is directed to M.P.E.P. § 2400 in general, and specifically to § 2411.05, as well as to 37 C.F.R. § 1.809(d), wherein it is set forth that “the specification shall contain the accession number for the deposit, the date of the deposit, the name and address of the depository, and a description of the deposited material sufficient to specifically identify it and to permit examination.” It is noted that the instant specification fails to provide any information about whether the deposit was made under the Budapest Treaty or whether the deposited organism is available to the public; the specification should be amended to include this information.
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.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-19 and 30-33 are newly rejected as necessitated by amendment under 35 U.S.C. 103 as being unpatentable over Wang et al. (“Lactobacillus reuteri Promotes Intestinal Development and Regulates Mucosal Immune Function in Newborn Piglets”, published on 02/07/2020, Frontiers in Veterinary Science, Vol. 7, Article 42, pages 1-8), hereinafter ‘Wang’, in view of Hao et al. (WO2019161631A1, published on 08/29/2019), hereinafter ‘Hao’, as evidenced by Remel (“MRS Agar”, published on 03/23/2011, IFU 454051, downloaded from https://documents.thermofisher.com/TFS-Assets/LSG/manuals/IFU454051.pdf, one page), hereinafter ‘Remel’,
Wang’s general disclosure relates to treatment of 3-day-old newborn piglets with Lactobacillus reuteri (L. reuteri) D8 and its beneficial effects on piglets (see entire document, including abstract).
Regarding claims 16 and 18, pertaining to a bacterial composition comprising isolated Lactobacillus reuteri DS0384 strain or a culture broth thereof, Wang teaches compositions comprising isolated Lactobacillus reuteri and a culture broth thereof (“L. reuteri D8 was isolated”, “L. reuteri D8 (109 CFU) suspended in 2 mL PBS”, “L. reuteri D8 were grown in MRS ag[a]r medium”; page 2, left column, paragraph 3; the Examiner notes that L. reuteri grown in MRS-agar medium inherently indicates a composition comprising L. reuteri). Please note the ‘culture broth’ in the instant specification is merely defined as “culture broth itself obtained by culturing a strain, or the culture supernatant obtained by removing the strain therefrom, and a filtrate, concentrate or dry matter product thereof, and may be used interchangeably with "culture supernatant," "conditioned culture broth," or "conditioned medium." (specification, paragraph [32]).
Regarding claim 18, pertaining to the fermentation starter composition, the claim recites the phrase ‘fermentation starter’ in the preamble which the instant specification describes as “a preparation comprising a microorganism involved in fermentation and other ingredients that provide essential ingredients for the growth of the microorganism” (see paragraph [49]), and wherein “[t]he fermentation starter composition may not comprise bacteria other than the Lactobacillus reuteri DS0384 strain” (see specification, paragraph [54]).
Pertaining to the fermentation starter composition, Wang teaches “L. reuteri D8 were grown in MRS ag[a]r medium” (page 2, left column, paragraph 3), which inherently indicates a composition comprising the microorganism L. reuteri and other ingredients that provide essential ingredients for the growth of the microorganism L. reuteri, wherein the ingredients are provided by the MRS agar medium, as evidenced by Remel (“Gelatine peptone and beef extract provide essential nutrients and amino acids necessary for bacterial growth”; page 1, paragraph 3).
Wang does not teach wherein the bacterial composition and the fermentation starter composition further comprise an effective amount of cryoprotectant (instant claims 16 and 18), wherein the cryoprotectant is one or more selected from the group consisting of skim milk powder, maltodextrin, dextrin, trehalose, maltose, lactose, mannitol, cyclodextrin, glycerol, and honey (instant claims 17 and 19). Wang does not teach wherein the isolated Lactobacillus reuteri DS0384 strain is in a lyophilized form and remains viable (instant claims 30 and 32), and wherein the isolated Lactobacillus reuteri DS0384 strain is comprised in the bacterial composition and in the fermentation starter composition at a concentration of 109 to 1012 CFU/g (instant claims 31 and 33).
Hao’s general disclosure relates to Lactobacillus reuteri SS23-52, preparation of dry powder starter thereof, and application thereof in purebred probiotic yogurt (see entire document, including abstract).
Regarding claims 16 and 18, pertaining to the composition comprising a cryoprotectant, Hao teaches a composition comprising Lactobacillus reuteri and a cryoprotectant (paragraph [0013]).
Regarding claims 17 and 19, pertaining to cryoprotectant, Hao teaches wherein the cryoprotectant is maltodextrin and skim milk powder (paragraphs [0017]-[0018], [0174]).
Regarding claims 30 and 32, pertaining to the Lactobacillus reuteri, Hao teaches wherein the Lactobacillus reuteri is in lyophilized form and viable (paragraph [0013], [0015]- [0016], [0175]).
Regarding claims 31 and 33, pertaining to the viable cell count of L. reuteri, Hao teaches wherein the Lactobacillus reuteri strain is comprised in a composition at concentration of 4.4×1010 CFU/g (paragraphs [0015]-[0016], [0175]).
While Wang does not teach wherein the bacterial composition and the fermentation starter composition further comprise an effective amount of cryoprotectant (instant claims 16 and 18), wherein the cryoprotectant is one or more of selected from the group consisting of skim milk powder, maltodextrin, dextrin, trehalose, maltose, lactose, mannitol, cyclodextrin, glycerol, and honey (instant claims 17 and 19), wherein the isolated Lactobacillus reuteri DS0384 strain is in a lyophilized form and remains viable (instant claims 30 and 32), and wherein the isolated Lactobacillus reuteri DS0384 strain is comprised in the bacterial composition and in the fermentation starter composition at a concentration of 109 to 1012 CFU/g (instant claims 31 and 33), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Wang’s Lactobacillus reuteri compositions with Hao’s teachings on freeze dried Lactobacillus reuteri, in order to create a bacterial composition comprising Wang’s isolated Lactobacillus reuteri or a culture broth thereof, and a fermentation starter composition, wherein the compositions comprise Wang’s isolated Lactobacillus reuteri and the cryoprotectants maltodextrin and skim milk powder, wherein the isolated Lactobacillus reuteri strain is in a lyophilized form and remains viable, and wherein the isolated Lactobacillus reuteri strain is comprised in the bacterial composition and in the fermentation starter composition at a concentration of 4.4x1010 CFU/g. One would have been motivated to do so to create lyophilized compositions comprising Wang’s isolated Lactobacillus reuteri strain with high viability (Hao, paragraphs [0169], [0175]) that can be further used for developing probiotic applications that promote the development of intestine mucosal system and maintain intestinal mucosal barrier (Hao, paragraph [0074]; Wang, abstract and page 2, left column, paragraph 2). A skilled artisan would have reasonably expected success in combining Wang’s and Hao’s teachings, since both are directed to Lactobacillus reuteri.
Wang does not teach wherein Lactobacillus reuteri is Lactobacillus reuteri DS0384 strain deposited under Accession No. KCTC 14164BP, or a culture broth thereof. However, the instant specification describes the claimed Lactobacillus reuteri strain DS0384 as having the ability to promote intestinal development (“when mice are orally gavaged with the Lactobacillus reuteri DS0384 strain of the present invention and its culture broth, intestinal development is promoted, such as the length and area of the villus and the depth of the crypt in the small intestine increase and the mucosa/submucosa ratio of the large intestine increases,”; see instant specification, paragraph [19]). Wang teaches wherein Lactobacillus reuteri strain D8 promotes intestinal development (“piglets were treated with … L. reuteri D8 (109 CFU) suspended in 2mL PBS”, “we treated 3-day-old newborn piglets with Lactobacillus reuteri (L. reuteri) D8 and observed its beneficial effect on piglets. The body weights, villus height, and crypt depth of jejunum were all significantly increased after L. reuteri treatment in piglets.”, “L. reuteri D8 treatment … promoted growth of intestinal epithelium to maintain the intestinal mucosal barrier; page 2, left column, paragraph 3; page 3, right column, paragraph 1; see abstract). The culture broth would be considered anticipated by Wang since the prior art strain and instant strain, even if there was a slight variation, both would produce the same metabolites in the broth. The broth is merely defined as the culture broth of culturing a strain (specification, paragraph [32]). Based on Wang’s teachings, it is highly likely that Wang’s strain and Applicant’s strain are the same strain since both strains are Lactobacillus reuteri strains and share the ability to promote intestinal development.
Wang does not teach wherein the Lactobacillus reuteri strain is Lactobacillus reuteri DS0384 strain deposited under Accession No. KCTC 14164BP. If there should be a slight variation between Wang’s strain and the instantly recited strain, and between their respective culture broths comprising cells, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have substituted the instant strain or culture broth thereof with Wang’s strain or culture both thereof, respectively, since Wang’s strain and the instant strain are both Lactobacillus reuteri strains and share the same properties, i.e. ability to promote intestinal development.
Response to Arguments
Applicant has traversed the previous rejections of claims 16-19 under 35 U.S.C. 101, under 35 U.S.C. 112(a), under 35 U.S.C. 102/103, and under 35 U.S.C. 103 (remarks, pages 7-13)in the reply filed on 12/23/2025. As discussed above, the previous rejection under 35 U.S.C. 102/103 has been withdrawn, and new rejections have been presented under 35 U.S.C. 103 in light of Applicant’s amendment of 12/23/2025. Li is no longer relied upon in the above rejection, therefore Applicant’s arguments regarding Li are moot. Wang is still relied upon in the above rejections. Applicant's arguments have been fully considered but they are not persuasive.
In Applicant’s reply, Applicant states that “even if individual components are natural products, a composition in which such components are artificially combined should not be
regarded as a natural phenomenon” (remarks, page 8).
The Examiner responds that, as discussed above, Lactobacillus reuteri, culture broth thereof, cryoprotectant, cryoprotectants trehalose, lactose, mannitol, glycerol, and honey, and essential ingredients for growth of the microorganism, are all directed to natural products that do not interact to yield significantly more. It is noted that the specification does not provide any evidence to support otherwise.
Applicant describes that “as evidenced by the Reference Material 5, the DS0384 strain has been deposited under the Budapest Treaty, thereby meeting the "national patentability
disclosure requirements" (remarks, page 9). While the Receipt in the Case of an Original Deposit was considered, an affidavit or declaration by Applicant, or a statement by an Attorney of record over his or her signature and registration number, stating that the specific strain has been deposited under the Budapest Treaty and that the specific strain will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, is required to satisfy the deposit requirement made by the Office, as discussed above.
Applicant states that “ DS0384 strain of the present invention is a novel strain and is different from the D8 strain of Wang as evidenced by the superior effects exhibited by the DS0384 strain” (remarks, page 10), and compares the instant experimental results with Wang’s experimental results regarding LYZ gene expression and jejunum morphology (remarks, pages 11-12).
The Examiner responds that a comparison of the instant experimental results and of Wang’s results on a quantitative level is not possible due to major differences between the instant experimental conditions and Wang’s experimental conditions. Regarding Difference 1 (LYZ gene Expression; remarks, page 11), it is noted that Applicant determined gene expression in intestinal organoids treated with L. reuteri culture broth (specification, paragraphs [113], [118], [122], [124]-[125]), while Wang examined gene expression in jejunum tissue from piglets gavaged with L. reuteri (Wang, page 2, left column, paragraph 3, page 2, right column, paragraph 5 -page 6, left column, paragraph 1; see Figure 3C). Regarding Difference 2 (Effects on Villus Length and Crypt Depth; remarks page 12), it is noted that Applicant determined jejunum morphology in mice gavaged with L. reuteri culture broth for seven days (paragraphs [144]-[145], [147], [150]) while Wang studied jejunum morphology in piglets gavaged with L. reuteri for five days (page 2, left column, paragraph 3; see Fig. 1E).
Conclusion
No claims are allowed.
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.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA ZINGARELLI whose telephone number is (703)756-1799. The examiner can normally be reached M-F 9-5.
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/SANDRA ZINGARELLI/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653