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 .
The prior restriction requirement based on lack of unity has been withdrawn.
Restriction/Unity of Invention
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 2, 4, 5 ,8, and 12-13, drawn to a method of treating gut dysbiosis.
Group II, claims 2, 3, 5, 9, and 10, drawn to drawn to a method of treating cardiovascular diseases.
Group III, claims 14, 17-18, 20-25, 29, and 30, drawn to a method for determining whether a subject is likely to respond to treatment with a composition comprising an extract obtained from Aronia melanocarpa.
Group IV, claim 31, drawn to a composition for use in treating and/or preventing cardiovascular diseases and/or gut dysbiosis.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-IV lack unity of invention because even though the inventions of these groups require the technical feature of an extract obtained from Aronia melanocarpa, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Mele and Rinninella (WO 2021/074913 A1), abbreviated “Mele”. Mele recites an Aronia melanocarpa fruit extract as a component of their invention, a composition in particular for use in the treatment of a cardiovascular disease having an inflammatory component or origin (Abstract). Mele recites polyphenols as a family of natural antioxidants (page 1, line 23) and lists a fruit extract of Aronia melanocarpa as a source of polyphenols and a biologically active component (page 5, lines 9-30).
The shared technical feature is taught by the reference, or in the alternative, would have at least been obvious to one of ordinary skill in the art to modify the invention as taught by Mele to make an extract obtained from Aronia melanocarpa. Therefore, the technical feature linking the inventions of groups I-IV does not constitute a special technical feature as defined by PCT Rule 13.2, as it does not define a contribution over the prior art. Accordingly, groups I-IV are not so linked by the same or a corresponding special technical feature as to form a single general inventive concept.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Election/Restrictions
Applicant's election with traverse of Group I (claims 2, 4, 5, 8, and 12-13) in the reply filed on April 28th, 2026 is acknowledged. The traversal is on the grounds that the prior art reference Le Sayec et al. Clinical nutrition 2022, 41 (11), 2549-2561, cited in the previous restriction requirement (March 10th, 2026) to demonstrate a lack of unity of invention, is not available as a prior art reference under 35 U.S.C. 102(A)(1) or (A)(2) as a journal article having been published after the effective filing date of the claimed invention. While the argument was persuasive, the groups of claims recite. Claims 3, 9, 10, 14, 17-18, 20-25, and 29-3 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
The applicant’s election without traverse of Faecalibacterium prausnitzii (Species I, claim 4), a faecal microbiome gene count of less than 400,000 (Species II, claims 8 and 9), and greater than or equal to 100 mg/day of polyphenols by weight of the composition (Species IV, claim 12) in the reply filed on April 28th, 2026 is acknowledged. Alternative ranges for Species II and IV are withdrawn as being drawn to non-elected species. The species election for Species I (claim 4) is withdrawn for the purpose of compact prosecution. The election of Species III is not applicable to the elected invention, instead relating to withdrawn claims 14, 22, and 23.
Claims 2, 4, 5, 8, 12, and 13 are pending and were examined on the merits.
Information Disclosure Statement
The information disclosure statement filed April 26th, 2024 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because a reference has an incorrect identifier. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
DE 102009009030 A is listed as DE 2009009030 A in the IDS. The examiner has provided the correct citation identification on the PTO-892 form and the reference is attached.
Drawings
The drawings were received on April 26th, 2024. These drawings are acceptable.
Specification
The use of the terms OMRON, SphygmoCor, Smart Medical (note the registered names "Smart Medical Devices Inc., and Smart Medical Technology Inc.), OmniGene, DNA Genotek, CosmosID, Qubit, Thermofisher Scientific (registered as "Thermo Fisher Scientific"), Nextera, Illumina, AMpure, Beckman Coulter, QIAGEN, HiSeqX, each of which is a trade name or a mark used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore, each term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 2 is objected to because of the following informalities: the species name "Aronia melanocarpa" should be italicized. Appropriate correction is suggested.
Claim objected to because of the following informalities: the phrase "and/or" in claim 4 line 6 is italicized and should not be italicized. Appropriate correction is suggested.
Claim 8 is objected to because of the following informalities: the phrase "oroprtionally" should be corrected to "or optionally". Appropriate correction is required.
Claim 12 is objected to because of the following informalities: the phrase "300 mg/day,200" should be corrected to "300 mg/day, 200" . Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 12 is 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.
The term “about” in claim 12 is a relative term which renders the claim indefinite. The term “about” 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. the dosage of polyphenols in mg/day, is rendered indefinite by the use of the term "about".
Regarding claim 4, the phrase "such as" 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 13 recites the limitation "the bacteria". There is insufficient antecedent basis for this limitation in the claim. Claim 2, from which claim 13 depends, does not recite antecedent basis for this limitation. Furthermore, it is unclear how the abundance of the bacteria (claim 13) is related to the gut dysbiosis (claim 2).
Claim Rejections - 35 USC § 103
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 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.
Claims 2, 4, 5, 8, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kong et al. (Journal of Agricultural and Food Chemistry 2021, 69 (11), 3312-3325), abbreviated "Kong".
Claim 2 recites “A method for treating gut dysbiosis and/or cardiovascular disease in a subject, wherein the method comprises administering a composition comprising an extract obtained from Aronia melanocarpa to a subject in need thereof”. Claim 4 recites “The method as defined in claim 2, wherein treating gut dysbiosis comprises at least one of: (a) Increasing microbiome diversity as measured by faecal microbiome gene count; or (b) Increasing levels of beneficial bacterial, such as Faecalibacterium prausnitzii 2, Lawsonibacter asaccharolyticus, Intestinimonas butyriciproducens, Faecalibacterium, Roseburia intestinalis and/or Eggerthella lenta”. Claim 5 recites “The method according to claim 2, wherein the extract obtained from Aronia melanocarpa is an aqueous or hydroalcoholic extract, optionally, wherein the composition comprises at least 10%, or at least 20%, or at least 30%, or at least 40%, or at least 50% w/w polyphenols by weight of the composition”. Claim 8 recites “The method according to claim 2, wherein the treating gut dysbiosis is in a mammal having a faecal microbiome gene count of less than 400,000, optionally less than 375,000, oroptionally less than 350,000, or optionally less than 300,000, or optionally less than 275,000, or optionally less than 250,000, or optionally less than 225,000, or optionally less than 200,000, or optionally less than 175,000, or optionally less than 150,000”. Claim 12 recites: “The method according to claim 2, wherein the dosage for treating gut dysbiosis provides: a) from about 100mg/day to about 500mg/day of polyphenols by weight of the composition, optionally from about 200 to 400 mg/day, optionally about 300 mg/day of polyphenols by weight of the composition; b) less than or equal to 500 mg/day of polyphenols by weight of the composition, optionally less than 400 mg/day, 300 mg/day,200 mg/day, or less than or equal to 100 mg/day of polyphenols by weight of the composition; and/or c) greater than or equal to 100 mg/day, optionally greater than or equal to 200 mg/day, 300 mg/day, 400 mg/day, or greater than or equal to 500 mg/day of polyphenols by weight of the composition”.
Kong recites modulating gut microbiota composition in rats using an Aronia melanocarpa polyphenols extract, promoting intestinal barrier function: “Aronia melanocarpa polyphenols (AMPs) can alleviate the degree of liver diseases in rats. However, the mechanism by which this is achieved through gut microbiota modulation remains unclear. Here, a rich-polyphenol extract of A. melanocarpa (AMPs) was used to treat lipopolysaccharide (LPS)-induced liver diseases in rats. … After AMPs treatment, the gut microbiota composition was modulated, promoting the intestinal barrier function by increasing the expression of intestinal epithelial cell tight junction proteins to reduce the LPS content in serum. The expression levels of inflammatory factors interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and related mRNAs were reduced. These results showed that AMPs, as a bioactive substance, could enhance the intestinal barrier function and modulate the gut microbiota of LPS-induced liver diseases” (Kong, Abstract; instant claim 2). Although Kong does not explicitly recite treating gut dysbiosis, the modulation of gut microbiota composition, promoting intestinal barrier function is treating gut dysbiosis under a broadest reasonable interpretation of the term “dysbiosis” (instant claim 2).
Kong further recites polyphenols can gut microbiota because they can improve dysbiosis: “Studies have shown that polyphenols can regulate gut microbiota disorders because they can improve dysbiosis, thus increasing the ratio of beneficial bacteria and harmful bacteria such as Lactobacillus and Proteobacteria” (Introduction, paragraph 2). Kong further recites “A. melanocarpa is also a rich source of polyphenols, such as anthocyanins, flavonols, and hydroxycinnamates” (Introduction, paragraph 3); therefore, one of skill in the art would have had a reasonable expectation of success at treating gut dysbiosis by administering an Aronia melanocarpa extract to a subject in need thereof (instant claim 2). Therefore, it would have been obvious to one of skill in the art, at the time of the claimed invention to treat gut dysbiosis by administering an extract from Aronia melanocarpa to a subject in need thereof (instant claim 2).
Kong recites obtaining the extract from Aronia melanocarpa through a hydroethanolic extraction: “Briefly, polyphenols of A. melanocarpa (10 g) were extracted in an ethanol/water solution (55:45%, v/v), the solid/liquid ratio was 1:44, and ultrasonic assistance was used for 90 min at 40 °C” (Kong, Materials and Methods, Preparation of A. melanocarpa Polyphenols (AMPs); instant claim 5). It would also be within the knowledge of one of skill in the that amphiphilic organic compounds such as polyphenols dissolve in amphiphilic solvents such as water-alcohol mixtures. Therefore, it would be obvious to one of skill in the art to make a hydroalcoholic extract of Aronia melanocarpa, a polyphenol extract thereof having utility for treating gut dysbiosis, as of record above (instant claim 5).
Kong recites an increase in the abundance of beneficial bacteria belonging to the genus Lactobacillus upon treatment with Aronia melanocarpa polyphenols (AMPs): “After treatment with AMPs, … the abundance of Lactobacillus significantly increased. Lactobacillus is a probiotic that regulates the structure of the gut microbiota, promoting body health and reducing the LPS content” (instant claim 4).
The instant claims are distinguished from Kong in that Kong does not explicitly recite treating gut dysbiosis in a mammal having a faecal microbiome gene count of less than 400,000 (instant claim 8). Kong recites administering an Aronia melanocarpa extract to a mammal (rats), modulating intestinal health gut microbiota composition, promoting the intestinal barrier function, as of record above. Administering an Aronia melanocarpa extract to a mammal having a faecal microbiome gene count of less than 400,000 is obvious to one of skill in the art over routine optimization. One of skill in the art could measure faecal microbiome gene count through DNA sequencing of faecal organisms. One of skill in the art could observe the effects of administering an Aronia melanocarpa extract to different mammalian subjects having different faecal microbiome gene counts. One of skill in the art could analyze the faecal microbiome before and after the treatment, to measure changes in microbiome composition (Kong, Gut Microbiota Analysis by 16S rRNA Gene Sequencing), and identify changes in harmful and beneficial bacteria composition (Kong, Discussion, paragraphs 6-9). Subjects that demonstrated an increase in beneficial faecal bacteria and/or a decrease in harmful faecal bacteria could be used to establish a range of faecal microbiome gene counts of organisms that show a decrease in gut dysbiosis in response to Aronia melanocarpa extract administration (instant claim 8). Therefore, it is obvious to one of sill in the art, over routine optimization, to treat gut dysbiosis in a mammal having a faecal microbiome gene count of less than 400,000 (instant claim 8).
Although Kong does not explicitly recite a dosage of greater than or equal to 100 mg/day of polyphenols by weight of the composition (instant claim 12), this dosage is obvious to one of skill in the art over routine optimization, and the utility of an Aronia melanocarpa polyphenol extract for treating gut dysbiosis is of record above. One of skill in the art could administer different dosages of polyphenols to different subject organisms and measure the effect of each dosage on the gut microbiome through 16S rRNA Gene Sequencing (Kong, Materials and Methods, Gut Microbiota Analysis by 16S rRNA Gene Sequencing). One of skill in the art could identify changes in harmful and beneficial faecal bacteria composition (Kong, Discussion, paragraphs 6-9). One of skill in the art could additionally perform a histological assessment of intestinal tissue to observe intestinal tissue damage in the subject organisms administered different dosages of the polyphenols (Kong, Materials and Methods, Histological Assessment). Therefore, it would be obvious to one of skill in the art over routine optimization to treat gut dysbiosis by administering an Aronia melanocarpa extract in a dosage of a dosage of greater than or equal to 100 mg/day of polyphenols by weight of the composition (instant claim 12).
Kong is relied upon for the reasons discussed above. If not expressly taught thereby, based upon the overall beneficial teachings provided by the references with respect to providing the method of treating gut dysbiosis by administering an Aronia melanocarpa extract, the adjustments of particular conventional working conditions (e.g., the selection from among known components and determining one or more suitable ranges (amounts, proportions, ratios thereof) in which to provide the method of treating gut dysbiosis), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
From the teachings of Kong, the invention as a whole, drawn to a method of treating gut dysbiosis as described in Claims 2, 4, 5, 8, and 12, would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, and one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ methods with the methods (including compositions thereof) of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed methods and the methods of the prior art (and compositions thereof). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “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).
Claims 2, 4, 5, 8, 12, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Kong (Journal of Agricultural and Food Chemistry 2021, 69 (11), 3312-3325) as applied to claims 2, 4, 5, 8, and 12 above, and further in view of Kong (Journal of Agricultural and Food Chemistry 2021, 69 (11), 3312-3325) and Zymo Research (16S Sequencing vs Shotgun Metagenomic Sequencing).
Claim 13 recites: “The method according to claim 2, wherein determining the abundance of the bacteria in a sample of faeces obtained from the subject is performed using shotgun sequencing”.
The instant claims are distinguished from Kong in that Kong does not explicitly recite determining the abundance of the bacteria in a sample of faeces obtained from the subject using shotgun sequencing (instant claim 13). Kong recites 16S rRNA gene sequencing for gut microbiota analysis (Kong, Material and Methods). Both 16S rRNA gene sequencing and shotgun sequencing are known in the art as microbiome sequencing methods (Zymo Research, paragraph 1). One of skill in the art could have substituted the 16S rRNA gene sequencing method recited by Kong with shotgun sequencing of gut microbiota with the predictable results of improved taxonomic resolution, but a higher risk of false positives (Zymo Research, Table 1). Therefore, it would have been obvious to one of skill in the art to determine the abundance of bacteria in a sample of faeces obtained from the subject using shotgun sequencing (instant claim 13).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert F Spaine whose telephone number is (571)272-9099. The examiner can normally be reached 8:00 AM - 4:00 PM United States Eastern Time, Monday-Friday.
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/R.F.S./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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