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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3 and 25 Sep 2026 has been entered.
Claim Status
The amended claim set filed 3 Sep 2026 is acknowledged. Claims 1-20 are currently pending. Of those, claims 1, 11, and 19 are currently amended, and no claims are new. Claims 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12 Nov 2025. No claims are cancelled. Claims 1-7 and 10-20 will be examined on the merits herein.
Claim 15 is incorrectly listed as withdrawn, but it is part of the invention under examination.
Response to Arguments
The Applicants’ arguments filed 3 Sep 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Final Office Action mailed 3 June 2026 will be referred to as “FOA.”
When discussing support for an amendment in the specification as filed, such as at Remarks pg. 8-9, please cite to the specification as filed. For example, the text pointed to for Figure 1 is not present in the specification as filed. Using incorrect citations makes it harder for the examiner to assess arguments about support.
PNG
media_image1.png
202
632
media_image1.png
Greyscale
Excerpt from Remarks pg. 8.
PNG
media_image2.png
112
646
media_image2.png
Greyscale
PNG
media_image3.png
76
644
media_image3.png
Greyscale
Excerpt from specification filed 30 Jan 2023.
Priority
The priority objections for claims 1, 3-4, and 11 (FOA par. 5-11) are moot in view of the amended claims. Claim 19 was previously denied priority because the provisional did not support two or more F. prausnitzii strains (see NFOA par. 12), but this is withdrawn in view of applicant’s Arguments filed 17 Apr 2026 (pg. 9).
The instant application claims priority to provisional application 63/059,130 (filed 30 July 2020) and is a continuation-in-part of PCT/US21/43971 (filed 30 July 2021). The effective filing date used for searching the art is 30 July 2020.
Objection(s) and Rejection(s) Withdrawn
The objection to the drawings as being new matter is withdrawn in view of applicant’s arguments pointing out the support (Remarks pg. 8-9).
Objections relating to Figure 3B and 5A (FOA par. 16 b-c) are withdrawn in view of the new drawings.
The rejection of claims 1-5, 7, 10-14, and 16-20 under 35 U.S.C. 112(b) related to “and/or” (see FOA par. 62) is withdrawn in view of the claim amendments and arguments.
The rejection of claims 1-7 and 10-20 under 35 U.S.C. 112(b) related to GenBank accession numbers (see FOA par. 63-64) is withdrawn in view of the claim amendments and arguments.
The rejection of claims 1-7 and 10-20 under 35 U.S.C. 112(a) related to new matter (see FOA par. 65-68) is withdrawn in view of the claim amendments and arguments.
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 8 Sep 2026. In addition to the errors pointed out in this document, the examiner does not see a statement specifically directing the sequence listing’s entry, a statement that the sequence listing includes no new matter, and a statement that indicates support for the amendment in the application.
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.
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that the claims as amended 3 Sep 2026 and in the amended specification filed 3 Sep 2026 reference SEQ ID NOs: 1-37 but the sequence listing that would define these sequences is deficient. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 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
A statement that the substitute specification contains no new matter.
Drawings
The drawings filed 3 Sep 2026 are objected to because:
Figure 3, as amended, is smaller and has lower image quality. As a result, the text at the bottom is pixelated and hard to read, and the symbols in the line chart on the left cannot be differentiated from each other.
Figure 4A is smaller and has lower image quality than the original image. The text in the bar chart, especially the x-axis labels are small, pixelated, and difficult to read. Relevant sections of 37 C.F.R. 1.84 were cited in the FOA (par. 16 b).
PNG
media_image4.png
376
1135
media_image4.png
Greyscale
Comparison of Figure 3 as filed 3 Sep 2026 (left) and as filed 30 Jan 2023 (right).
PNG
media_image5.png
398
525
media_image5.png
Greyscale
Comparison of Figure 4A as filed 3 Sep 2026 (left) and as filed 30 Jan 2023 (right).
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.
Specification
The amendment filed 3 Sep 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: the sequences with SEQ ID NO: 1-37 in the sequence listing and the references to these sequences in para. [0049, 0111]. Applicant has not provided evidence that these sequences were in the specification at the time of filing and the support in the original specification is not apparent. Specifically, the specification as amended states that the GenBank sequences correspond to SEQ ID NOs: 1-37, but there is no evidence presented showing what sequences were found at those GenBank accession numbers at the time of filing.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Objections
Applicant is advised that should claim 6 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. (See also FOA par. 57) When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 6 recites: “The method of claim 1, wherein the composition comprises Faecalibacterium prausnitzii cells, cell components, and supernatant, wherein the Faecalibacterium prausnitzii cells, cell components, and supernatant have been dried”. Claim 15 recites: “The method of claim 1, wherein the composition comprises Faecalibacterium prausnitzii cells, cell components, and supernatant, and wherein the Faecalibacterium prausnitzii cells, cell components, and supernatant have been dried.” The claims differ only in that claim 15 has the extra word “and”, emphasized above, but the extra word does not change the claim scope because both claim constructions require both wherein clauses.
Rejection(s) Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
Claims 1-7 and 10-20 are each rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “live cells, killed cells, cell components, supernatant, a combination of cell components and supernatant, or extract from a Faecalibacterium prausnitzii culture,” is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The following groupings do not share a single structural similarity: (1) Products comprising whole bacterial cells (live cells, killed cells); (2) Products comprising macromolecules that can be identified as originating from F. prausnitzii (some cell components like proteins, some supernatants, and some extracts); (3) Products that cannot be identified as originating from F. prausnitzii (some cell components like amino acids, some supernatants like those that have been filtered, and some extracts). Each grouping is limited by comprising non-overlapping structures (cells, macromolecules, or neither), so they do not share a structural similarity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
Applicant argues (Remarks pg. 12-13) that “The Examiner's division of the claimed group into "whole cells," "macromolecules," and "non-identifiable products" is an artificial distinction. Unlike purely synthetic chemical compounds where structural similarity is defined by a shared chemical core, complex biological compositions are structurally unified by their genetic source and origin. Every single member of the claimed group is derived directly from a Faecalibacterium prausnitzii culture and is genetically defined by the same unique 16S rRNA gene sequences corresponding to SEQ ID NO: 1 through SEQ ID NO: 37. The "structure" of the cell components, the "structure" of the secretome found in the culture supernatant, and the "structure" of the whole cells are all structurally dictated by the expression of the same genome. They are biological manifestations of the same starting material.”
This argument has been carefully considered but is not found persuasive. Applicant is invited to amend and/or provide arguments in support of an alternate grouping based on alternate structural similarities if they feel the proposed grouping is “artificial” or incorrect.
“[T]he same unique 16S rRNA gene sequences corresponding to SEQ ID NO: 1 through SEQ ID NO: 37” is not a single structural similarity across the full breadth of compositions claimed because the claims do not require that 16S rRNA gene sequence be present in the composition. Arguments related to the bacterial genome are not persuasive because the bacterial genome is not claimed; the 16S rRNA gene sequences in the claims are only a single gene from the genome.
Applicant argues (Remarks pg. 13) that “Kawahara acknowledges that the bacteria or a processed product may be grouped together as therapeutic agents. See Kawahara at [0032] (describing that viable bacteria or a processed product of the bacteria may be used, and that a processed product may include culture supernatant of bacterial cells; bacterial cell components, such as protein complexes; or extracts thereof; and dead cells).
Because the prior art itself groups whole cells and their processed products (supernatants, cell components, extracts) together as therapeutic agents, and where the prior art's own teachings establish that these members are art-recognized counterparts sharing a common use, the claim language is proper.”
This argument has been carefully considered but is not found persuasive. This rejection is not related to using multiple different therapeutic agents in combination; Markush groupings are alternatives from which a selection is to be made. A common use is insufficient to make a Markush grouping; the products must also share a “single structural similarity” (see FOA par. 58, 60 and par. 21, 23 above).
Claim Rejections - 35 USC § 102
Claims 1-5, 7, 12-13, 16, 18, and 20 remain rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kawahara et al. (WO-2018230695-A1, 2018; PTO-892 mailed 20 Jan 2026) with an English translation provided in the form of Kawahara et al. (US-20210145897-A1, a national stage application from the PCT application; hereafter Kawahara; PTO-892 mailed 20 Jan 2026). The rejection has been updated to reflect the claim amendments, and a response to arguments follows the rejection.
Regarding claim 1, Kawahara teaches “A method for preventing or treating a fat-associated disease and/or inflammation, the method comprising administering a Faecalibacterium bacterium or a processed product thereof to a human or a non-human animal” [0007 (8)], and teaches that “the fat-associated disease [can be] a metabolic syndrome-associated disease or non-alcoholic fatty liver disease (NAFLD)” [0007 (8-2)]. “The Faecalibacterium bacterium [can be] Faecalibacterium prausnitzii ATCC 27766, or Faecalibacterium prausnitzii TY-2 (Accession No. NITE ABP-02743)” [0007 (8-3)]. The bacteria processed product (“FPZ”) can be culture supernatants, or processed products that include sonicated bacterial cells, extracts from the cell such as products where cell walls are removed, protein complexes [0032].
The USPTO sequence databases cannot search a sequence without a correct sequence identifier. In the interest of compact prosecution, in this action, the claims are searched using any F. prausnitzii. (See also par. 75 below).
The claim has been amended to recite the process by which the composition is made (“wherein the Faecalibacterium prausnitzii used to make the composition has a 16S rRNA gene sequence comprising a nucleotide sequence selected from the group consisting of SEO ID NO: 1 through SEO ID NO: 37”). See MPEP 2113: “"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).” The claimed F. prausnitzii requires the presence of specific rRNA sequences, but these rRNA sequences are not proteins. So there is no evidence or reason to believe that the supernatant or protein complexes (i.e. cell components) of F. prausnitzii taught in Kawahara differs from the claimed F. prausnitzii in any way because these products do not comprise the cells’ genomes or rRNAs. Therefore, the method is the same as the claimed method because it administers the same product in the same way, even if the administered product was produced by a different method (purification from different bacteria).
Regarding claim 2, the Faecalibacterium product can be administered to a human or non-human animal [0007 (8)], which can include dogs and cats [0086].
Regarding claim 3, Kawahara did not find that there was a hypoglycemic effect on the mice when administered [0098, 0103-0104, 0112-0113].
Regarding claim 4, Kawahara teaches administering F. prausnitzii to “C57BL/6J mice at 8 weeks old [that] were given a high-fat high-fructose diet” [0110], and the instant specification provides evidence that C57BL/6J mice are pre-diabetic [0036] (i.e. have an elevated risk for developing diabetes) but have normal fasting blood glucose at 2 months (instant Figure 1A, [0037-0038]). Kawahara also teaches that the mice are at elevated risk for developing liver fibrosis [0112-0113].
Regarding claim 5, Kawahara teaches administering to subjects with metabolic syndrome [0007 (8-2), 0051, Example 3]. Also, Kawahara teaches administering F. prausnitzii to “C57BL/6J mice at 8 weeks old [that] were given a high-fat high-fructose diet” [0110], and the instant specification provides evidence that that C57BL/6J mice are pre-diabetic [0036].
Regarding claim 7, Kawahara teaches “the present invention can be used to prepare various types of formulations (compositions, pharmaceutical compositions, food compositions, or cosmetic compositions” [0064].
Regarding claim 12, Kawahara teaches the administration can be 1 time per day [0062, 0094].
Regarding claim 13, the administration was for 20 weeks in the example [0094].
Regarding claim 18, Kawahara teaches that “HOMA-IR, which is an indicator of insulin resistance, was significant improved by administration of F. prausnitzii ATCC 27768 (FIG. 5)” [0098].
Regarding claim 20, Kawahara teaches the composition can be formulated with food or drinks [0076], or can be mixed with a pharmaceutically acceptable carrier [0068].
Regarding claims 3-4, 16, and 18, these claims only describe effects on the subject that occur after the method’s step of administering an effective amount of a composition comprising materials derived from one or more F. prausnitzii cultures to a subject in need. Kawahara teaches the same composition, as described above, and also teaches the same method of administering the composition to a subject in need. MPEP 2112.01.I states: when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. As the claim and Kawahara teach the same product administered in the same way to the same subject population, the functional limitations of claims 3-4, 16, and 18 are presumed to be inherently present, absent evidence to the contrary.
Response to Arguments
Applicant argues (Remarks pg. 10) that “Kawahara does not disclose or suggest F. prausnitzii strains having 16S rRNA gene sequences corresponding to SEQ ID NO: 1 through SEQ ID NO: 37. Rather, Kawahara teaches only F. prausnitzii (now reclassified to F. moorei) ATCC 27768, ATCC 27766, and TY-2 (Accession No. NITE ABP-02743). See Kawahara, paragraphs [0027], [0029]. Importantly, these are different strains from those recited in claim 1. Because Kawahara does not teach the specific F. prausnitzii strains required by claim 1, Kawahara cannot anticipate claim 1 or any of its dependent claims.”
This argument has been carefully considered but is not found persuasive. For clarity of the record, only Faecalibacterium prausnitzii ATCC 27768 was reclassified as F. moorei; the other Kawahara strains are still classified as F. prausnitzii to the examiner’s knowledge. This argument was also addressed in the FOA par. 35-36.
Applicant’s argument that “these are different strains from those recited in claim 1” is not persuasive because it is not supported by evidence that the claimed sequences are not present in the Kawahara strains. MPEP 2145.I states: “Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”
Further, the claims are not limited to compositions comprising the cells, except for claims 6, 15, and 19 that are not rejected. The argument does not address how the supernatant, extracts, and non-nucleic acid cell components would differ based on the presence of the 16S rRNA sequence(s) in the bacteria. See MPEP 2113 for applicant’s burden in products-by-process: “"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).”
Applicant argues (Remarks pg. 10-11) that “Examiner's reliance on MPEP § 2113 (which governs "Product-by-Process" claims) is misplaced. Claim 1 is a method of treatment claim, not a product claim defined by its process of manufacture. The patentability of a method claim is determined by the active steps of the method-here, the administration of a specific composition derived from a genetically defined bacterial strain to treat specific conditions. Because the active step requires administering a composition derived from Faecalibacterium prausnitzii having the specific 16S rRNA gene sequences corresponding to SEQ ID NO: 1 through SEQ ID NO: 37, a prior art reference must disclose this complete administration step to anticipate. Kawahara completely fails to do so.”
This argument has been carefully considered but is not found persuasive. Product-by-process analysis is not prohibited for method claims. See MPEP 2113: “See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims.");”
Product-by-process analysis is appropriate here because both examiner and applicant agree that the composition is defined by its source-- being “derived from a genetically defined bacterial strain” (Remarks quoted above). So, the broadest reasonable interpretation of method’s active step requires administering the same product that is claimed, but that may or may not be produced by the method described in the claims.
Applicant argues (Remarks pg. 11) that “A person of skill would understand that different strains, even within the same bacterial species, possess distinct genomic profiles. These genomic differences directly dictate their metabolic pathways, secretome, and cell-wall compositions. Consequently, the culture supernatant (which contains secreted proteins, enzymes, and metabolites) and cell components (lipids, proteins, peptidoglycans) derived from the claimed strains (corresponding to SEQ ID NO: 1 through SEQ ID NO: 37) are chemically and functionally distinct from those of Kawahara's strains. The Examiner has provided no scientific evidence to show that the supernatants or cell components of Kawahara's strains are identical to those of the claimed strains, and thus no "sound basis" for believing the claimed and prior art products are the same. See MPEP § 2112.01.”
This argument has been carefully considered but is not found persuasive. The examiner provided a sound basis for believing the claimed and prior art products are the same: “The claimed F. prausnitzii requires the presence of specific rRNA sequences, but these rRNA sequences are not proteins. So there is no evidence or reason to believe that the supernatant or protein complexes (i.e. cell components) of F. prausnitzii taught in Kawahara differs from the claimed F. prausnitzii in any way because these products do not comprise the cells’ genomes or rRNAs.”
The argument that the examiner must provide evidence to demonstrate the product is identical is incorrect. See MPEP 2113: “As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith." In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).” “"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983)”
The argument about what one of ordinary skill in the art would know is not persuasive because it is only the applicant’s opinion and is not supported by evidence. MPEP 2145.I states: “Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”. The argument also does not appear commensurate in scope with what is claimed because it describes strains with different “metabolic pathways, secretome, and cell-wall compositions” (Remarks cited above), but the claims only require the presence of a 16S rRNA gene, which is not part of any of those processes.
Claim Rejections - 35 USC § 103
Claims 1-5, 7, 10-14, 16-18 and 20 remain rejected under 35 U.S.C. 103 as being unpatentable over Kawahara et al. (US-20210145897-A1, filed 2018, published 20 May 2021; hereafter Kawahara; PTO-892 mailed 20 Jan 2026) in view of Bianchi et al. (2007; hereafter Bianchi; PTO-892 mailed 20 Jan 2026). The rejection has been updated to reflect the claim amendments, and a response to arguments follows the rejection.
Claims 1-5, 7, 12-13, 16, 18, and 20 are anticipated by Kawahara, as laid out above.
Kawahara teaches that their method is “for preventing or treating a fat-associated disease and/or inflammation” [Abstract], and specifically teaches use with “a metabolic syndrome-associated disease or non-alcoholic fatty liver disease (NAFLD).” [0007 (8-2)]. Kawahara teaches “ Metabolic syndrome, also called “visceral fat syndrome”, is associated with various diseases and abnormalities, including lipid metabolic abnormalities and carbohydrate metabolic abnormalities. Those with metabolic syndrome are highly likely to develop symptoms and diseases, such as arteriosclerosis, fatty liver, hyperlipemia, obesity, hypertension and diabetes mellitus.” [0002] “Metabolic syndrome is a condition that includes a cluster of diseases and abnormalities. Examples of the diseases and abnormalities include obesity (for example, lipid metabolic abnormalities, fatty liver, etc.), carbohydrate metabolic abnormalities, abnormal insulin resistance, heart diseases such as angina pectoris and myocardial infarction, arteriosclerotic diseases (for example, cerebral infarction, arteriosclerosis obliterans, etc.), etc.” [0051].
Kawahara teaches effects that are relevant to this subject population including reduction in weight gain, liver weight, and fat around the epididymis [0098], improvement in an indicator of insulin resistance and reduced insulin levels [0098], reduced cholesterol levels [0103], reduced fatty liver and liver fibrosis [0104, 0113], and reductions in serum inflammatory cytokines [0107].
Kawahara does not teach that the subject is also receiving one or more anti-diabetic drugs, wherein the antidiabetic drug is chosen from the group consisting of: metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors, as in claim 10. Kawahara does not teach that the subject is a human with a excess body fat around the waist, and wherein the subject has an Hb A1C level of 5.7 percent or higher, as in claim 11. Kawahara does not teach the subject is also receiving insulin or an insulin analog, as in claim 14. Kawahara does not teach the subject is also receiving one or more of blood thinners, blood pressure medications, and statins, as in claim 17.
Bianchi teaches that “metabolic syndrome (MS) [is] a cluster of metabolic abnormalities with insulin resistance as its central component, … and is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus (T2DM)” (Abstract). Bianchi teaches that subjects with metabolic syndrome are treated with metformin (claim 10) or insulin (claim 14) if hyperglycemia is a risk factor (Figure 2). Bianchi teaches that subjects with metabolic syndrome are treated with statins if atherogenic dyslipidemia is a risk factor, and are treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blockers and other drugs to reduce blood pressure if hypertension is a risk factor (claim 17, Figure 2). Kawahara teaches that subjects with metabolic syndrome can have obesity (Figure 2) and Bianchi teaches that the obesity criteria is defined as a high waist circumference (Table 1, see claim 11). Kawahara teaches that subjects with metabolic syndrome can have diabetes, and that the goal is for the Hb A1c level to be below 6.5% (Figure 2, i.e. greater than 5.7%, see claim 11).
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to modify the Kasahara method of administering a F. prausnitzii composition to specifically humans with metabolic syndrome receiving insulin or metformin or with Hb A1c levels of 5.7% or higher, as is taught to be a standard of care in Bianchi, rather than the broader genus of humans with metabolic syndrome, thereby arriving at the invention of claims 10-11 and 14, because Kawahara specifically points out that the subject population of those with metabolic syndrome can have carbohydrate metabolic abnormalities and diabetes, and because Kawahara teaches that the F. prausnitzii composition would be beneficial in this population due to the observed improvement in an indicator of insulin resistance and reduced insulin levels. Therefore the combination would be desirable to improve the symptoms specifically in this subset of humans with metabolic syndrome. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.”
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to modify the Kasahara method of administering a F. prausnitzii composition to specifically humans with metabolic syndrome and obesity with high waist circumference, as is taught as a diagnostic criteria in Bianchi, rather than the broader genus of humans with metabolic syndrome, thereby arriving at the invention of claim 11, because Kawahara specifically points out that the subject population of those with metabolic syndrome can have obesity and because Kawahara teaches that the F. prausnitzii composition would be beneficial in this population due to the observed prevention of weight gain. Therefore the combination would be desirable to improve the symptoms specifically in this subset of humans with metabolic syndrome. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.”
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to modify the Kasahara method of administering a F. prausnitzii composition to specifically humans with metabolic syndrome receiving statins or blood pressure medications as is taught to be a standard of care in Bianchi, rather than the broader genus of humans with metabolic syndrome, thereby arriving at the invention of claim 17, because Kawahara specifically points out that the subject population of those with metabolic syndrome can have arteriosclerosis and hypertension, and because Kawahara teaches that the F. prausnitzii composition would be beneficial in this population due to the observed improvement in cholesterol levels. Therefore the combination would be desirable to improve the symptoms specifically in this subset of humans with metabolic syndrome. See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.”
Additionally, for all of the above, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art (Kawahara) teaches a method that only differs from the claimed invention by the substitution of a single component (i.e. substitution of the specific subject population within metabolic syndrome for the generic, broader subject metabolic syndrome population used); the substituted element (i.e. the specific sub-populations) were already known and already shown to function as a population where the method would be useful, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting a narrower subject population for the broader population with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
Applicant argues (Remarks pg. 12-13) that Kawahara does not teach or suggest F. prausnitzii strains having 16S rRNA gene sequences corresponding to SEQ ID NOs: 1-37, and Bianchi does not teach any specific F. prausnitzii strains so it does not cure the deficiency of Kawahara.
The argument has been carefully considered but is not found persuasive. Applicant’s argument that “these are different strains from those recited in claim 1” is not persuasive because it is not supported by evidence that the claimed sequences are not present in the Kawahara strains. MPEP 2145.I states: “Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”
Further, the claims are not limited to compositions comprising the cells, except for claims 6, 15, and 19 that are not rejected. The argument does not address how the supernatant, extracts, and non-nucleic acid cell components would differ based on the presence of the 16S rRNA sequence(s) in the bacteria. See MPEP 2113 for applicant’s burden in products-by-process: “"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).”
Applicant argues (Remarks pg. 12-13) that there is no teaching, suggestion, or motivation in the cited references that would lead to selecting the specific F. prausnitzii strains having 16S rRNA gene sequences corresponding to SEQ ID NOs: 1-37 because the strains were isolated from calves and piglets and are not known in the art to have any utility in treating glucose metabolism disorders prior to the instant disclosure. KSR and Kerkhoven do not apply because the strains in claim 1 as amended were not previously known or suggested for this use.
The argument has been carefully considered but is not found persuasive. The argument about Kerkhoven is moot because it is not cited in the maintained rejection. The argument about KSR is not persuasive because using the supernatant and cell components from F. prausnitzii to treat glucose metabolism disorders is part of the anticipation rejection. The argument does not address the modifications to the subject population that are made based on Bianchi to choose subjects with certain medication histories and body properties from within the broader patient population disclosed in Kawahara.
The arguments also do not correspond with the claimed method’s scope because the claim is not limited to compositions comprising the claimed F. prausnitzii cells.
New Rejection(s)
Claim Rejections - 35 USC § 112(b)
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 and 10-20 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.
Regarding claim 1, the claim has been amended to read “live cells, killed cells, supernatant, a combination of cell components and supernatant, or extract from a Faecalibacterium prausnitzii culture”. One of ordinary skill in the art would not be able to clearly determine claim scope because the claim language does not make clear whether “from a Faecalibacterium prausnitzii culture” applies to all options listed or only to the extract. Therefore, it is unclear whether administration of any live cells, killed cells, supernatant, and combination of cell components and supernatant are claimed, or only those from a Faecalibacterium prausnitzii culture, wherein the F. prausnitzii have specified 16S rRNA gene sequences. Dependent claims 2-7 and 10-20 are also rejected because they depend from claim 1 and do not obviate this grounds of rejection. In the interest of compact prosecution, in this action, the claims are interpreted as being limited to components from a Faecalibacterium prausnitzii culture due to the case history and arguments.
Regarding claims 1 and 19, the term “a nucleotide sequence selected from the group consisting of SEO ID NO: 1 through SEO ID NO: 37” lacks antecedent basis because there is not a correct sequence listing that defines the sequence identifiers. Therefore, one of ordinary skill in the art cannot determine which sequences are claimed. Dependent claims 2-7 and 10-20 are also rejected because they depend from claim 1 and do not obviate this grounds of rejection. The USPTO sequence databases cannot search a sequence without a correct sequence identifier. In the interest of compact prosecution, in this action, the claims are searched using the F. prausnitzii strains with GenBank accession numbers from the previous claim set.
Regarding claim 11, the term “excess body fat” in claim 11 is a relative term which renders the claim indefinite. The term “excess” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As a result, one of ordinary skill in the art would not be able to determine which subjects fall within the claim scope as having “excess” body fat.
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 1-7 and 10-20 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.
Claims 1 and 19 each have been amended to recite the term “a nucleotide sequence selected from the group consisting of SEO ID NO: 1 through SEO ID NO: 37”. Dependent claims 2-7 and 10-20 also recite this term by depending from claim 1, directly or indirectly.
Applicant has not pointed out where the amended claim is supported, nor does there appear to be a written description of the claim limitations SEQ ID NOs: 1-37 in the application as filed. Instead, applicant only stated “No new matter has been added.” (Remarks pg. 7). It is not apparent that these sequences were present in the application as filed, so they are new matter. Specifically, the specification as amended states that the GenBank sequences correspond to SEQ ID NOs: 1-37, but there is no evidence presented showing what sequences were found at those GenBank accession numbers at the time of filing.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA N DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-F 8:30-4:30 (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
AMELIA N DICKENS
Examiner
Art Unit 1645
/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
