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 .
Priority
Filing date is 02/16/2023. No priority claimed.
Information Disclosure
Examiner again notes that an IDS was not filed in this application. Applicant is reminded of the duty of disclosure as per 37 CFR 1.56 and detailed in MPEP § 2000.
Status
Claims 1-23 are pending.
Rejections not reiterated are withdrawn.
New Claim Rejections - 35 USC § 103
Claims 1-23 are rejected under 35 U.S.C. 103 as being unpatentable over Galley et al. (US20090036420) in view of Romero et al. (Food Chemistry: X 13 (2022) 100195, 11 pages) and Roager et al. (Nat Commun, 9, 3294 (2018), 10 pages).
Galley teaches compounds, including “N-(3-ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide” (claim 5), as affecting TAAR1 ([0025], [0211], [0217]-[0218]) with therapeutic use for “metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation” ([0004]).
Galley does not teach determining a marker from a fecal sample for assessing a metabolic disorder.
Romero teaches the analysis of metabolites, including phenylethylamine and tryptamine, produced by gut microbiota, including Ruminococcus gnavus, and correlated with metabolic disease, including studies of feces (Abstract, Fig. 4, p. 5-6). Romero teaches the conditions correlated with metabolites includes insulin resistance (p. 6). Romero teaches “Mechanisms of action of polyamines on host physiology are via enterochromaffin cells, where tryptamine induces the release of 5-Hydroxytryptamine (5-HT, serotonin) and stimulates gastrointestinal motility by acting on enteric nervous system neurons (Roager & Licht, 2018)” (p. 6, citing Roager et al. (Nat Commun, 9, 3294 (2018), 10 pages)).
Roager reviews gut microbiota tryptophan catabolites in health and disease (title, abstract) and that tryptamine is a tryptophan catabolite produced by Ruminoccocus gnavus that incluences gut health via stimulating gastrointestinal motility (Table 1; p. 6). Roager teaches that the catabolites are detected in fecal samples (p. 2).
One of ordinary skill in the art following the teaching of Galley would have considered using known techniques to diagnose a patient, including from a fecal sample to identify biomarkers known to correlate with the need for treatment as taught by Romero and Roager, including R. gnavus-derived tryptamine. One of ordinary skill in the art would have used the known correlation of markers with disease and compared the sample with that known to indicate disease as is routinely done in the art. One of ordinary skill in the art would have had a reasonable expectation of success because both are in the same field of endeavor and relate to identification and treatment of disease via TAAR1. Thus, one of ordinary skill in the art would have arrived at the claimed invention of claims.
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that Galley only mentions therapeutic uses in a background section without any experiments or data to demonstrate or prove such therapeutic use. Applicant appears to question an enabling disclosure based on limited tests of TAAR1 inhibitors.
This argument is not persuasive because Galley includes substantial data supporting the compounds therein, including diverse chemical space, as being effective in assays with Ki of nanomolar concentrations, i.e. Table 1 ([0215]-[0218]). In contrast, the instant application claims a method of treating a metabolic disorder in a subject by administering “a trace amine-associated receptor 1 (TAAR1) inhibitor to the subject.” However, the instant specification only describes experimental results for a single compound, thus Applicant’s argument is unclear as to how the prior art methods of treatment are not supported, while allegedly the instant application is. Clarification is requested. As per MPEP 2121.01: “Even if a reference discloses an inoperative device, it is prior art for all that it teaches.” Beckman Instrumentsv.LKB Produkter AB, 892 F.2d 1547, 1551, 13 USPQ2d 1301, 1304 (Fed. Cir. 1989). Therefore, “a non-enabling reference may qualify as prior art for the purpose of determining obviousness under 35 U.S.C. 103.” Symbol Techs. Inc. v. Opticon Inc., 935 F.2d 1569, 1578, 19 USPQ2d 1241, 1247 (Fed. Cir. 1991). However, in this case it appears that the prior art is in fact operative as it suggested with “Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds are useful for the treatment of … metabolic disorders” ([0025]) and supported by the assay results of Table 1 ([0215]-[0218]) which one of ordinary skill in the art would have considered in view of the mechanism involved in various disease ([0002]-[0004]) as a sufficient demonstration to give a reasonable expectation of success that the compounds would be effective in metabolic disorders.
Applicant argues Romero: does not teach determining the amount of one or more markers in the fecal sample, does not provide any teaching about the amount of metabolites in feces or correlation between such metabolites with metabolic disease, and only teaches tryptamine is related to intestine-brain axis in CNS disorders.
This argument is not persuasive because Romero teaches “Microbioal protein metabolites can regulate immune, metabolic and neuronal responses in different target organs. Metabolic pathways of these compounds and their mechanisms of action on different pathologies can lead to the discovery of new diagnostic techniques, drugs and the potential use as functional ingredients in food.” (Abstract). Furthermore, Romero and Roager teach that tryptamine is a tryptophan catabolite produced by Ruminoccocus gnavus that incluences gut health via stimulating gastrointestinal motility which are detected in fecal samples.
Applicant argues Romero’s teaching regarding metabolic disorders such as type II diabetes mellitus or insulin resistance, phenethylamine, tryptamine, or Ruminococcus gnavus are not taught to be relevant and that “Romero teaches that the current studies on the effect of protein metabolites conflict and inconclusive”.
This argument is not persuasive because one of ordinary skill in the art following the combined teaching of the cited art, including Romero, would have considered that tryptamine produced by R. gnavus stimulates gastrointestinal motility and would be relevant to metabolic disorders.
Applicant argues that Romero does not teach any correlation with insulin resistance and one of ordinary skill in the art would not expect R. gnavus to be relevant to insulin resistance.
This argument is not persuasive because one of ordinary skill in the art following the combined teaching of the cited art, including Romero and Roager (p. 6: “Tryptamine, a tryptophan catabolite produced by … Ruminococcus gnavus”, “tryptamine may act as a signaling molecule that affects intestinal transit time, which is strongly associated with the gut microbial composition, diversity and metabolism in humans”), would have considered that tryptamine produced by R. gnavus stimulates gastrointestinal motility and would be relevant to metabolic disorders, including insulin resistance.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626