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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/10/2025 has been entered.
Priority
This application is a 371 of PCT/CA2020/050531 filed 04/22/2020 which claims benefit of provisional application 62/857,479 filed 06/05/2019 and claims benefit of provisional application 62/867,369 filed 06/27/2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Status of the Claims
Claim 30 was amended. Claims 30-41, 43-46, 50 and 51 are pending. Claims 36 and 40 were withdrawn.
Claims 30-35, 37-39, 41, 43-46, 50 and 51 (claim set filed 06/10/2025) and are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 06/10/20245 are acknowledged. All of the amendment and arguments have been thoroughly reviewed an considered.
For the purposes of clarity of the record, the reasons for the Examiner's withdrawal and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner's response to arguments section.
New Rejection
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 30-35, 37-39, 41, 43, 44, 50 and 51 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim 30 recites a method comprising detecting Parasutterella levels in a first microbiome sample taken prior to the treatment and administering the microbiome modulating treatment when a relative abundance of Parasutterella is at least 0.1% in the individual’s gut microbiome. The method includes the mental process of correlating the collected data in microbiome sample with the value of 0.1% and making a decision to start the treatment when Parasutterella abundance is at least 0.1% in the individua’s gut microbiome.
This judicial exception is not integrated into a practical application because in addition to the mental steps of correlating and deciding, the claim recites steps of collecting the data, i.e. taking a sample from the individual and detecting the Parasutterella levels, and administering to the individual a gut microbiome modulating treatment on a dosage regimen for a suitable period of time from 1 week to 6 months. Steps are recited at high level of generality, for instance, the treatment period is very broad, i.e. from 1 week to 6 month and dosage is not specified. These steps add insignificant extra solution activity to the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because steps of detecting bacterial levels in the microbiome sample and microbiome modulating treatment are well-understood, routine and conventional as evidenced by Li (Li et al. Food Func., 2019, 10, 2560-2572 on record in IDS). Li teaches microbiome modulating treatment of high fat diet-fed rats administering polysaccharides from edible mushroom Grifola frondose (Abstract). Treatment is performed on a dosage regimen for 8 week (p. 2562, left column, 1st paragraph) after which serum biochemical analysis and a gut microbial analysis are performed (p. 2562, left column, 3rd and 6th paragraphs).
Based on the above claim 30 is rejected as ineligible.
Dependent claim 32 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 32 is directed to detecting the Parasutterella levels in the second sample, comparing the levels in the first and second sample and deciding to continue treatment when the levels are higher in the second sample compared to the first one. Claim is drawn to a mental process of comparing data and making a decision.
This judicial exception is not integrated into a practical application because in addition to the mental steps of comparing and deciding, the claim recites step of obtaining a sample from the individual and detecting the Parasutterella levels, and continuing the dosage treatment. Steps are recited at high level of generality and add insignificant extra solution activity to the judicial exception. Steps are not sufficient to amount to significantly more than the judicial exception, because these steps are routine and conventional as described above for claim 30. Therefore, claim 32 is rejected as ineligible.
Claims 31, 33, 34 and 41, dependent on claim 30, are directed to measurement of dyslipidemia related parameters, determination of necessity of treatment based on the measured parameter or evaluation of the risks such as genetic predisposition, family history, heredity or lifestyle. Evaluation of the risks and determination of the necessity of treatment based on analysis of parameters or risks are the mental processes. Measurement of dyslipidemia related parameters is recited at high level of generality and is not sufficient to amount to significantly more than the judicial exception, because that step is well-understood, routine and conventional as evidenced Li teaching determination of dyslipidemia related parameters, such as the level of cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) (p. 2562, left column, 3rd paragraph and p. 2563, Figure 1). Therefore, claims 31, 33, 34 and 41 are rejected as ineligible.
Dependent claims 35, 37-39 and 44 are directed to resistant potato starch (elected species) treatment and resistant starch being RS1, RS2, RS3, RS4 or RS5. Claims are recited at high level of generality and do not amount to significantly more than the judicial exception since they do not make contribution over prior art of McLaren (WO 2018010013) teaching the use of resistant potato starch for modulation of microbiome (Abstract) and RS2 type starch (p. 7, lines 22-23). Claims 35, 37-39 and 44 do not alter the judicial exception or make it markedly different. Therefore, claims 35, 37-39 and 44 are rejected as ineligible.
Dependent claims 43, 50 and 51 recite the methods of measurement of Parasutterella levels including RT-PCR, qPCR, FISH, antibody-based and cell-based methods. These methods are routine and conventional and do not add significantly more to alter judicial exception or make it markedly different. Therefore, claims 43, 50 and 51 are rejected as ineligible.
Dependent claims 45 and 46 recite the dosage regimen parameters for treatment with resistant potato starch and hence integrate the judicial exception into practical application and are eligible.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims are 30-34, 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al. Food Func., 2019, 10, 2560-2572 on record in IDS) in view of Everard (Everard et al. Diabetes, 2011, 60, 2775-2786) and Apte (WO 2016065075 A1).
Regarding claims 30 and 32, Li teaches microbiome modulating treatment of high fat diet-fed rats administering polysaccharides from edible mushroom Grifola frondose (GFP) (Abstract). Treatment is performed on a dosage regimen for 8 week (p. 2562, left column, 1st paragraph) after which serum biochemical analysis and a gut microbial analysis are performed (p. 2562, left column, 3rd and 6th paragraphs). Li discloses that treatment resulted in significant promotion of the relative abundance of certain microbial phylotypes: “GFP supplementation significantly increased the proportions of Helicobater, Intestinimonas, Barnesiella, Defluviitalea, Ruminococcus, Flavonifractor and Paraprevotella” (p. 2569, left column, 2nd paragraph). Barnesiella and Paraprevotella were shown to be at a lower level in high fat diet group compared to control (p. 2567, left column, 1st paragraph) and their abundance increased with the treatment. Besides, microbiome modulating treatment resulted in reduction of LDL cholesterol that correlated with increase in levels for Barnesiella and Paraprevotella (p. 2569, left column 2nd paragraph).
Li does not teach detection of Parasutterella levels and performing treatment based on determination of Parasutterella levels.
Everard teaches response of gut microbiota to prebiotics in genetic or diet-induced obese mice (Abstract). Everard discloses the relative amount of Parasutterella of 0.17% in obese mice and increase to 0.6% after prebiotic treatment (p. 2778, Table 1). The limitation “at least 0.1%” is interpreted as Parasutterella relative abundance of 0.1% or more, and hence Everard teaching meets this limitation. Everard mentions that prebiotics improved lipid metabolism in obese mice: “Interestingly, plasma triglycerides (Fig. 3D) and muscle lipid (total, triglycerides, and phospholipids) content were dramatically reduced in the prebiotic-treated mice” (p. 2780, left column 1st paragraph).
Apte teaches a method for diagnosing and treating an immune microbial disfunction by modulating microbiome (Abstract). The method includes collection of biological sample from the subjects to characterize the microbiome prior to treatment (p. 2, paragraph 0001). The model generated based on microbiome characterization provides therapeutic measures to modulate the subject’s microbiome towards the desired equilibrium state (p. 3, paragraph 0002). Apte discloses that additional samples are taken from a subject during therapy to monitor and adjust therapies: “… can further facilitate monitoring and/or adjusting of therapies provided to a subject, for instance, through reception, processing, and analysis of additional samples from a subject throughout the course of therapy.” (p. 3, paragraph 0002). Apte teaches the personalized treatment when based on the biological samples received throughout therapy a therapy-effectiveness model is generated (p. 34, paragraph 0070). Among parameters measured from biological samples Apte mentions cholesterol levels and lipid levels (p. 6, paragraph 0009). Apte mentions Parasutterella as one of the microorganism used for diagnostic of different immune disfunctions (p. 24, paragraphs 0045 and p. 25, paragraph 0048). Apte teaches different therapies including probiotic therapies, small-molecule-based therapies and diet related therapies (p. 27, paragraph 0052). Thus, Apte teaches method to determine efficacy of a microbiome modulating treatment by detecting the baseline level of microbiome bacteria, administering treatment, measuring level of microbiome bacteria several times during treatment to determine efficiency and continue in case of improvement.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Everard teaching and add detection of Parasutterella levels to Li teaching of modulation of microbiome and consider Parasutterella levels of 0.17% as the level to start microbiome modulating treatment. One would have been motivated to do so since Everard showed that Parasutterella levels can be increased from the initial level of 0.17% by prebiotic treatment and hence the subject can respond to treatment and indicated strong effect of prebiotic treatment on lipid metabolism and Li showed that increase in the level of certain bacteria which was lower with the high fat diet correlated with reduction in LDL levels. A skilled artisan would have reasonably expected success in the combination because Li and Everard teach modulation of the gut microbiome with the diet and detection of the level of different bacteria.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add Apte method of monitoring modulation of microbiome by detection of level of microbiome bacteria before treatment and throughout the treatment to teachings of Li and Everard on reduction of LDL cholesterol by modulating levels of certain bacteria including Parasutterella. One would have been motivated to do so since Apte describes that monitoring of microbiome level throughout treatment allows to adjust treatment for individual subjects. A skilled artisan would have reasonably expected success in the combination because Li, Everard and Apte teach modulation of microbiome with diet-related therapy and describe detection of lipid levels and Everard and Apte are detecting Parasutterella.
Thus, Li, Everard and Apte teachings render claims 30 and 32 obvious.
Regarding claim 31 and 41, Li teaches determining a dyslipidemia related parameters, such as the level of cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) (p. 2562, left column, 3rd paragraph and p. 2563, Figure 1). Everard describes measurement of triglycerides in plasma and muscle (p. 2780, left column, 1st paragraph). Thus, Li and Everard teachings in combination with Apte teaching render claims 31 and 41 obvious.
Regarding claim 33 and 34, Li teaches treatment of subjects with dyslipidemia developed as a result of high fat diet (Abstract). Li mentions different factors leading to development of dyslipidemia, including lipid accumulation in liver and high cholesterol: “Hepatic TC plays a substantial role in the development of hyperlipidaemia mellitus; thus improving hepatic TC may be a therapeutic approach for the treatment of hyperlipidaemia.” (p. 2568, right column, last paragraph). Thus, Li teaching in combination with Everard and Apte teachings renders claims 33 and 34 obvious.
Regarding claim 43, Li teaches measurement of gut microbiota levels by high-throughput sequencing (p. 2562, left column, last paragraph and right column, 1st paragraph). Thus, Li teaching in combination with Everard and Apte teachings renders claim 43 obvious.
Claims 35, 37-39 and 44-46 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al. Food Func., 2019, 10, 2560-2572 on record in IDS) in view of Everard (Everard et al. Diabetes, 2011, 60, 2775- 2786) and Apte (WO 2016065075 A1) and as applied to claim 30 above, and further in view of McLaren (WO 2018010013).
The teachings of Li, Everard and Apte have been set forth above.
Li, Everard and Apte do not teach the microbiome modulating compound to be resistant potato starch wherein the resistant starch is RS1, RS2, RS3, RS4 or RS5 and do not teach the dosage regimen for resistant potato starch.
Regarding claims 35, 38, 39 and 44, McLaren teaches the use of resistant potato starch for modulation of microbiome (Abstract). McLaren discloses that treatment with resistant potato starch provides increase in levels of beneficial Bifidobacteria: “ method of increasing beneficial Bifidobacteria content in the gut microbiota of an individual in need of such treatment comprising administering to said individual an effective amount of a suitable resistant potato starch on a dosage regimen.” (p. 5, lines 16-19). McLaren discloses that Bifidobacterium provides different beneficial effects including reduction of cholesterol (p. 18, line 30). McLaren mentions that resistant starch is: “effective dietary prebiotic supplement to modulate intestinal function and improve systemic health in both animals and humans.” (p. 1, lines 16-17) and has potential application in improvement of blood lipids (p. 1, lines 18- 19).
Regarding claim 37, McLaren teaches resistant potato starch from MSP Starch Products to be an unmodified RS2 type starch (p. 7, lines 22-23).
Regarding claims 45 and 46, McLaren teaches the dosage regimen for resistant potato starch: “the dosage regimen may be an effective amount comprising 0.25-40 g of an unmodified RS type 2 potato starch administered to an individual as defined herein on a dosage regimen of daily for at least 12 weeks.” (p. 15, lines 27-29) that reads on instant limitations in claims 45 and 46.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute polysaccharides from Grifola frondose in Li teaching on reduction of LDL cholesterol by modulating microbiome with resistant potato starch of RS2 type from McLaren teaching and apply the dosage regimen from McLaren teaching and measure its effect on Parasutterella levels as described in Everard teaching before treatment and throughout the treatment as described by Apte. One would have been motivated to do so since McLaren teaches that resistant potato starch has potential in improvement of blood lipids and increases level of beneficial Bifidobacterium which provides effect of cholesterol reduction similar to certain bacteria in Li teaching which can be replaced with Parasutterella from Everard teaching as described above and hence resistant potato starch has potential to increase Parasutterella levels. A skilled artisan would have reasonably expected success in the combination because McLaren, Li, Everard and Apte teach diet-based treatment for modulation of microbiome that is related to reduction of cholesterol and lipid levels. Thus, McLaren, Li, Everard and Apte teachings render claims 35, 37-39 and 44-46 obvious.
Claims 50 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al. Food Func., 2019, 10, 2560-2572 on record in IDS) in view of Everard (Everard et al. Diabetes, 2011, 60, 2775-2786) and Apte (WO 2016065075 A1) as applied to claim 30 above, and further in view of Gopinath (Gopinath et al. Biosensors and Bioelectronics, 2014, 60, 332-342).
The teachings of Li, Everard and Apte have been set forth above.
Li, Everard and Apte do not teach the antibody-based methods and the cell binding-based methods to determine Parasutterella levels.
Gopinath teaches multiple methods of bacterial detection including methods of detection based on the binding to different bacterial surface proteins (p. 336, right column, 2nd paragraph). Gopinath teaches that antibodies have advantage of high affinity and specificity to their target (p. 336, right column, last paragraph). Gopinath discloses that antibodies can recognize the whole bacterial cell or proteins on its surface and provides examples of detection of specific bacteria with antibodies (p. 337, left column, 1st paragraph). Since antibodies can bind to the bacterial cell, antibody-based methods are also the cell binding-based methods. Besides detection of bacteria with antibodies Gopinath describes other cell-binding methods, such as aptamer (nucleic acid ligands) specific to certain bacteria (p. 337, Aptamers) or different probes immobilized on the surface and used in biosensors (p. 338, Biosensors).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Gopinath guidance and add detection of Parasutterella levels by antibody-based and cell binding-based methods to Li, Everard and Apte teachings of modulation of microbiome including Parasutterella levels to reduce LDL cholesterol level. One would have been motivated to do so since Gopinath provided description and examples of various antibody-based and cell binding-based techniques for detection of bacteria with high specificity. A skilled artisan would have reasonably expected success in the combination because Li, Everard, Apte and Gopinath teach detection of the level of different bacteria. Thus, Li, Everard and Apte and Gopinath teachings render claims 50 and 51 obvious.
Response to Arguments
Applicant's arguments filed 06/10/2025 have been fully considered but they are not persuasive.
The arguments related to the prior art of Zhang are moot since the current rejection does not involve prior art of Zhang.
Applicant’s argues (addressing pages 7-9 of the Remarks) that: “ … Parasutterella was not one of the "phylotypes" tested by Li. …Apte provides a framework for how testing could be done but provides a very large set of bacteria to be analyzed for possible useful features for characterizing immune-related diseases.” Applicant states that: “As such, Li teaches that some bacteria levels are correlated with lipid metabolism disorder related parameters. Parasutterella was not one of the bacteria tested. … Everard also teaches that Parasutterella levels can be increased. Apte teaches that if examining celiac disease or ulcerative colitis, Parasutterella is one of several "taxa" that could be used to "derive" a "set of features" for characterizing these diseases.”, these arguments are not persuasive because:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In instant case, the current rejection of claim 1 is based on combination of prior art of Li, Everard and Apte. Li provides treatment method to modulate gut microbiome and describes correlation between the increase in the levels of certain bacteria (which are lower in the high fat diet-fed rats) with reduction in LDL levels (p. 2569, left column 2nd paragraph). Everard teaching provides motivation to include detection of Parasutterella levels since Everard showed that Parasutterella responds to treatment by increasing the abundance (p. 2778, Table 1) and indicated dramatic reduction in lipid content for prebiotic treated subjects (p. 2780, left column 1st paragraph). Apte discloses method to monitor and adjust a microbiome modulating treatment by detecting the baseline level of microbiome bacteria and measuring level of microbiome bacteria several times during the treatment (p. 2, paragraph 0001; p. 3, paragraph 0002) and mentions Parasutterella as one of the detected microorganisms (p. 24, paragraphs 0045 and p. 25, paragraph 0048). Therefore, combination of prior art of Li, Everard and Apte makes claim 1 obvious as described in the rejection above.
Applicant describes development of a “Responders” and “Non-Responders” model (addressing pages 9-11 of the Remarks) according to which: “individuals with adequate levels of Parasutterella, that is, effective amounts of Parasutterella (Parasutterella levels correspond to a relative abundance of at least 0.1 % Parasutterella in the individual's gut microbiome, as recited in claim 30), in their gut microbiome at the start of treatment (Responders) showed a decrease in LDL levels whereas individuals with an insufficient amount of Parasutterella (less than 0.1 % Parasutterella in the individual's gut microbiome) or Non-Responders, did not.” Applicant argues that: “ … the fact that this critical threshold level of Parasutterella (0.1 % relative abundance) is necessary in order for an increase in the relative levels of Parasutterella as a result of treatment to cause LDL-cholesterol levels to decrease over time is not taught or suggested by the prior art”, these arguments are not persuasive because:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the critical threshold of Parasutterella level and the “Responders” and “Non-Responders” model) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In instant case, although the prior art does not teach the different response depending on the Parasutterella levels, however, the prior art of Everard showed increase in the level of Parasutterella from 0.17% to 0.6% with prebiotic treatment that corresponds to instant “Responders”.
Additionally, the recitation “decreasing LDL-cholesterol” can be interpreted as intended use. The intended use is given weight to the extent that it imparts a structural limitation and the prior art needs to be capable of performing the intended use. See MPEP 2111.02, section II. In instant case, the prior art renders the instantly claimed method steps of detection of Parasutterella and administration of gut microbiome modulating treatment obvious, prior art of Everard teaches increase of Parasutterella level and reduction in lipid content (not explicitly mentioning LDL-cholesterol) and the prior art of Li showed correlation between the increase in the levels of certain bacteria with reduction in LDL levels. Therefore, the method described in the combination of prior art of Li, Everard and Apte is capable of achieving the same goal of decreasing LDL-cholesterol.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653