Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This application is a US national phase of PCT/EP2022/056284 filed March 11,
2022, with foreign priority application EP21162403.6, filed March 12, 2021. Applicant's
amendment filed April 15, 2026 is acknowledged.
The claim amendment dated 04/15/2026 does not comply with 37 C.F.R. 1.121(c) (4) When claim text shall not be presented; canceling a claim.
No claim text shall be presented for any claim in the claim listing with the status of "canceled" or "not entered."
Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as "canceled" will constitute an instruction to cancel the claim.
Claims 9 and 14-15 are canceled and present full claim text.
Claims 16-18 are newly added. Claims 1-8, 10-13, and 16-18 are pending.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on April 15, 2026 is acknowledged. Newly added claims 16-18 fall within the scope of Group II.
Claims 1-7 and 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 15, 2026.
Claims 8, 10, and 16-18 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The drawings are objected to because the drawings are labeled “Figure” instead of “FIG.”. See MPEP 608.02 V. DRAWING STANDARDS (u):
(u) Numbering of views.
(1) The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.
(2) Numbers and letters identifying the views must be simple and clear and must not be used in association with brackets, circles, or inverted commas. The view numbers must be larger than the numbers used for reference characters.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 8 and 17-18 are objected to because of the following informalities:
Claim 17, line 2, delete “(L. acidophilus)”, as this is unnecessary to the claim.
Claim 18, line 2, delete “obtained” as this is convoluted claim language. 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 8, 10, and 16-18 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus."
The specification does not sufficiently describe a Lactobacillus strain that is not Lactobacillus reuteri, comprising a LacS transporter sequence having a sequence identity of at least 70% to SEQ ID NO: 1 (claim 8), and/or comprising a GH42 β-galactosidase sequence having a sequence identity to at least 70% to SEQ ID NO: 2 (claim 16).
The claims require a Lactobacillus strain that is not L. reuteri, with at least 70% sequence identity to the aforementioned SEQ ID’s. However, the specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to the activity. For example, SEQ ID: 1 is 1923 base pairs long. A sequence sharing only 70% identity relative to SEQ ID: 1 could have anywhere from 1 to 575 substitutions, deletions or additions in any combination along any length of SEQ ID: 1. Thus, an enormous genus (4574 = 3.8 x 10345) comprising literally more than trillions of sequences is encompassed by the tremendously broad scope of the claims.
However, while the claims are drawn to a genus that comprises literally trillions of sequences, the specification has only adequately described and successfully reduced to practice the full-length of SEQ ID NO: 1 (from L. reuteri), and a 640 bp sequence of LacS with 70.038% identity to SEQ ID 1 from L. acidophilus NCC12 strain (pg. 36, Table 1). This is not representative of the extremely large genus of sequences claimed, since only one other variant of SEQ ID NO: 1 is demonstrated to be from a non-L. reuteri strain. At best, the specification contemplates the use of NBLAST and Gapped BLAST to identify desired alignment homologs based on sequence homology. When reviewing the prior art for 70% homology based on local similarity, a Lactobacillus johnsonii NCC 533 strain has 70.9% homology with a 98% query cover, wherein the sequence is annotated as a lactose permease (Pridmore et al. (NCBI Accession # AE017198.1, Proc. Natl. Acad. Sci. U.S.A. 101 (8), 2512-2517 (2004), See attached sequence comparison). However, local homology alone and/or query cover of the sequence is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, Friedberg (Brief. Bioinformatics (2006) 7: 225-242) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling of domains can lead to errors in annotation (page 227, second column, page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thorton et al. (Nature structural biology, structural genomics supplement, November 2000, pgs. 991-994) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thorton et al. further describe examples of little correlation between specific enzyme function and overall protein structure (see page 992, right column, at lines 2-10).
Thus, when taken with the teachings of Friedberg and Thorton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that are derived from non-L. reuteri strains, particularly when identifying the gene as encoding a ‘LacS transporter’ or ‘GH42 B-gal’.
In the absence of a representative number of examples and any art-recognized structure-function relationship, the specification must at least describe the structural features that are required for the claimed function, in this case a Lactobacillus strain containing a constituted LacS transporter sequence and/or GH42 B-gal sequence, that is not a L. reuteri strain. However, as discussed above, the specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to the non-L. reuteri strain comprising these sequence variants. Instead, Applicant merely offers a statement that any strain comprising the sequence having the specified homology will work.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing. Claims 10 and 17-18 are likewise rejected since they fail to ameliorate the written description requirement of the base claims above upon which they depend.
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 8, 10, and 16-18 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 8 recites “…at least one Lactobacillus strain comprising… and/or comprising a GH42 B-gal sequence,”. It is unclear whether ‘B-gal sequence’ is referring to a DNA sequence or an amino acid sequence. The specification discloses preferably the GH42 B-gal sequence has at least 70% identity to SEQ ID NO: 2, which is a nucleic acid sequence. Thus, one of ordinary skill in the art would not be apprised of what B-gal sequence is required in the Lactobacillus strain, therefore indefinite. Claim 8 further recites wherein the probiotic Lactobacillus strain is provided from at least one lactobacillus strain comprising a LacS transporter and/or comprising a GH42 B-gal. The term “provided from” is indefinite. It is uncertain whether the Lactobacillus strain recited in part (i), or another Lactobacillus strain to be added in the composition, is required to comprise a LacS transporter and/or GH42 B-gal. Claims 10 and 16-18 are rejected as being dependent on claim 8.
Regarding claim 10, the phrase "such as" in line 4 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 8, 10, and 16-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring organism without significantly more.
The Supreme Court has required analysis based on a 3-part test for subject
matter eligibility.
- Step 1: Is the claim to a process, machine, manufacture, or composition of
matter?
- Step 2A (The Judicial Exceptions): Prong 1: Is the claim directed to a law of nature, a natural phenomenon (product of nature), or an abstract idea?
-Step 2A (The Judicial Exceptions): Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?
- Step 2B: Does the claim recite additional elements that amount to significantly
more than the judicial exception?
Claims 8, 10, and 16-18 recite a composition comprising an effective amount of a pre-conditioned probiotic Lactobacillus strain and an effective amount of a galacto-oligosaccharide (GOS), wherein the Lactobacillus comprises a LacS transporter sequence with at least 70% identity to SEQ ID NO: 1, and/or a GH42 B-gal sequence, wherein the Lactobacillus strain is not Lactobacillus reuteri, which is a statutory category of invention (Step 1: Yes).
Claims 8, 10, and 17-18 are drawn to a composition comprising a pre-conditioned Lactobacillus strain with a naturally occurring GH42 B-gal sequence, that is not L. reuteri, and a naturally occurring GOS. Claim 17 is drawn to the composition requiring a B-gal sequence that is at least 70% identical to SEQ ID NO: 2. As evidenced by Moon (Direct Submission, (19-AUG-2018) Bioprocess Engineering, Research Laboratories, Ildong Pharmaceutical, Samsung 1-ro, Hwaseong 18449, Korea), a Lactobacillus johnsonii strain IDCC9203 isolated from infant feces has a B-gal sequence that is 72.79% identical to instant SEQ ID NO: 2. Thus, the scope of the claims encompass naturally occurring Lactobacillus strains. The claims recite the Lactobacillus strain is ‘preconditioned’, and the specification discloses ‘preconditioned’ to mean the bacteria are grown in nutrient media with the GOS. The specification also indicates that the ‘preconditioning’ of the Lactobacillus strains enhanced growth/abundance in the presence of GOS. However, the evidence appears consistent with metabolic adaptation resulting from prior exposure to GOS rather than a markedly different characteristic sufficient to distinguish the claimed strain from its naturally occurring counterpart. Thus the claims recite a judicial exception in the form of a product of nature (Step 2A, Prong 1: Yes).
Claim 8 recites the composition is an administrable form, selected from the group consisting of nutritional composition, pharmaceutical formulations, dietary supplements, inter alia, and claim 18 recites the Lactobacillus strain is present in the composition in an amount between 103 cfu to 1012 cfu per daily dose. As evidenced by Bogicevic et al. (WO 2019/025637 A1, cited in IDS filed 9/8/2023), it is common in the art to combine Lactobacillus species with GOS in nutritional compositions such as infant formula (pg. 9, lines 6-9), and common in the art to formulate compositions in the recited concentrations (pg. 17, lines 5-8). Thus the claims do not recite integration into a practical application, nor do they recite additional elements that amount to significantly more than the judicial exception (Step 2A, Prong 2: No) (Step 2B: No).
Therefore, claims 8, 10, and 16-18 are not patent eligible subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8, 10, 16, and 18 are rejected under 35 U.S.C. 102(a)(1)(a)(2) as being anticipated by Bogicevic et al. (WO 2019/025637 A1, cited in IDS filed 9/8/2023, hereinafter “Bogicevic”) as evidenced by Pridmore et al. (NCBI Accession # AE017198.1, Proc. Natl. Acad. Sci. U.S.A. 101 (8), 2512-2517 (2004), hereinafter “Pridmore”).
Regarding claim 8, Bogicevic teaches probiotic bacteria preconditioned in a GOS-containing medium, wherein the effect is boosting the symbiotic effect of the probiotic bacteria with the GOS (title, abstract). Bogicevic teaches compositions comprising an effective amount, preferably a therapeutically effective amount, of GOS and a preconditioned probiotic bacteria (pg. 16, lines 18-20). Bogicevic teaches Lactobacillus johnsonii NCC533 was preconditioned with concentrations of 0.6-2.04% GOS displayed a shorter lag time and faster growth than the strain grown without GOS (pg. 45, lines 16-23). Bogicevic teaches the probiotic bacteria in the composition of the invention possesses the galCDEGR(A) operon, such genes have been identified previously as being essential for probiotic bacteria to grow on GOS, wherein L. johnsonii NCC533 has been selected in this experiment as it comprises the full galCOEGR(A) operon, excluding galA (pg. 11, lines 14-16; pg. 45, lines 5-6). As evidenced by Pridmore, L. johnsonii NCC533 strain contains a lactose permease sequence having 70.90% identity to instant SEQ ID NO: 1 (See attached sequence comparison). Thus Bogicevic anticipates the claimed composition.
Regarding claim 10, Bogicevic teaches the composition can be formulated into a nutritional composition, such as infant formula, infant cereal, inter alia (pg. 17, lines 16-22), thus anticipates the claim.
Regarding claim 16, Bogicevic teaches The galCDEGR(A) operon is a gene cluster comprising the genes galC, galD, galE, galG and galR and optionally comprising the gene galA, wherein the genes galC, galD and galE encode an ABC transport system which is specifically internalizing GOS with low degree of polymerization (DP), and these are then hydrolyzed by intracellular β-galactosidases, one of them being encoded by galG (pg. 11, lines 20-24). As evidenced by Pridmore, L. johnsonii NCC533 strain contains a β-galactosidase sequence having 72% identity to instant SEQ ID NO: 2 (See attached sequence comparison), thus Bogicevic anticipates the claimed composition.
Regarding claim 18, Bogicevic teaches the probiotic bacteria are present in an amount of at least 5 x 105 cfu/g, which falls within the range recited, thus anticipates the claim (claim 8).
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.
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.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Bogicevic as evidenced by Pridmore as applied to claims 8, 10, 16, and 18 above, and further in view of Andersen et al. (PNAS, 2011, vol. 108, no. 43, 17785-90, cited in PTO-892 mailed 2/20/2026, hereinafter “Andersen”).
As discussed above, claims 8, 10, 16, and 18 are anticipated by Bogicevic as evidenced by Pridmore. Bogicevic does not teach the probiotic strain is a Lactobacillus acidophilus strain.
However, Andersen teaches Lactobacillus acidophilus mechanisms for GOS transport and catabolism, and identified a B-galactosidase GH42 that indicates GOS transport and catabolism before entering the Leloir and glycolysis pathways (abstract, pg. 17787, col. 2, para 2). Andersen teaches lacS, a galactoside-pentose-hexuronide permease-encoding gene, was up-regulated 5.1-fold in the presence of GOS, and two β-galactosidases, LacA and LacLM, and enzymes in the Leloir pathway were also encoded by genes within this locus and up-regulated by GOS stimulation (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill before the effective filing date of the claimed invention to add a L. acidophilus strain as taught by Andersen in the composition comprising an effective amount of GOS and a Lactobacillus strain as taught by Bogicevic. One of ordinary skill in the art would have been motivated to add an L. acidophilus strain for preconditioning with GOS with a reasonable expectation of success, since this strain is known to contain LacS and LacA, which are crucial for GOS catabolism as taught by Andersen, thus would effectively be preconditioned in the methods and compositions taught by Bogicevic.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA EDWARDS whose telephone number is (571)270-0938. The examiner can normally be reached M-F 8am-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise 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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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
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