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 .
Response to Arguments
Applicant’s arguments, see p. 5, filed 9/9/2026, with respect to rejection of claim 20 under 35 USC 112 have been fully considered and are persuasive. The 35 USC 112 rejection of 9/9/2026 has been withdrawn. Specifically, applicant argues that by amending claim 20 to replace "yeast strains" with "Saccharomyces cerevisiae strains.", withdrawal of the objection is respectfully requested. This is convincing and the rejection under 35 USC 112 has been withdrawn.
Applicant's arguments filed 9/9/2026 have been fully considered but they are not persuasive.
Regarding claims 18-22 rejection under 35 USC 101:
Applicant argues that claims 18 and 19 are amended to remove the clause "wherein, when at least Sra- 13, Str-2, Odr-10, Sra-17 and Str-130 are activated, said subject is determined to have cancer." and Claim 19 has similarly been amended to remove the clauses correlating the recited receptor activation and non-activation patterns with a determination that the subject has cancer, that the claims no longer recite the correlation or relationship between the response of the recited receptors and cancer alleged by the Office as judicial exception. This is not convincing because the preamble recites the "detecting cancer", so the correlation is considered an implied with the "detecting" to the "assessing" step.
Applicants argue that the claimed method may be performed by a human using mental steps or basic critical thinking does not apply because the pending claims do not recite mental processes. This is not convincing because as recited above, the "detecting cancer" in the preamble is implied that the "assessing" step includes the "detecting cancer" step.
Applicant argues that the particular assay for carrying out the assessment of receptor activation or non-activation using the Saccharomyces cerevisiae strains are concrete biological assay steps rather than a mental process. This is not convincing because the mental step is the method of detecting cancer step implied by the preamble.
Regarding rejections of Claims 18-19, 21-22 under 35 USC 103:
Applicant argues that Rejection of Claims 18-19 and 21-22 under 35 U.S.C. §103 over Hirotsu et al (US 20170016906) (hereinafter "Hirotsu") in view of Milanetti et al ("Investigation of the binding between olfactory receptors and odorant molecules in C. elegans organism" Biophysical Chemistry 255 (2019) 106264, pp. 1-8) (hereinafter "Milanetti) is traversed because neither Hirotsu nor Milanetti, alone or in combination, teaches or suggests assessing activation or non-activation of the particular combination of Sra-13, Str-2, Odr-10, Sra-17, and Str-130 in response to a biological fluid sample derived from a subject, as required by claim 18. The argument is made that the cited portions of Hirotsu do not teach assessing activation or non- activation of these receptors in response to a biological fluid sample derived from a subject, as required by claim 18 and that Hirotsu is generally directed to cancer detection using C. elegans, including exposure to subject-derived biological samples such as urine and assessment of the nematode's olfactory response. However, the cancer-detection experiments in Hirotsu are based primarily on the overall chemotactic or neuronal response of the nematode to the sample, rather than on assessing activation of a defined panel of individual GPCR receptors" This is not convincing because the recitation in claims is open ended using "comprising". The references combine the activation of various receptors that include the receptors claimed. The other references also include the additional receptors. Applicant argues that the various receptors are not correlated with the cancer detection. This is not convincing because the RNAi screening with C. Elegans to detect the volatile profiles mapped to RNAi are related to detecting cancer metabolites (Hirotsu: Claims 9-12, the expression of the receptor genes inhibited by RNAi are related to the smell of cancer types).
Regarding claims 18 and 19, Applicants argue that because "Milanetti acknowledges that the receptor-odorant relationships in C. elegans remain largely unknown and that the redundancy and combinatorial complexity of GPCR expression make it extremely difficult to associate specific receptors with specific sensory cues. The proposed computational protocol is presented as a tool that could guide the identification of candidate ligands and possible cancer metabolites activating the nematode's attractive behavior, rather than as experimental evidence identifying receptors involved in cancer detection. Accordingly, Milanetti's contribution is limited to proposing putative ligand-receptor interactions based on computational modeling. Milanetti does not establish that Sra-13 is responsive to a cancer-derived biological sample or provide a technical reason to select Sra-13, together with the other receptors recited in claim 18, for assessment in response to such a sample." This is not convincing because the candidate receptors in Milanetti of expressed as volatile are obvious targets to associate with the olfactory detection of cancer in C. Elegans as cancer metabolites (Milanetti p. 2 col. 2 para. 1).
Regarding claim 20-22 and New Claims 24-31, no further arguments have been put forward.
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 therefore, subject to the conditions and requirements of this title.
Subject Matter Eligibility - Step 1:
Claims 18-22, 24-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural process without significantly more. The claim recites a series of steps or acts, including method of detecting cancer. Thus, the claim is directed to a process, which is one of the statutory categories of invention.
Subject Matter Eligibility - Step 2A, Prong 1:
Regarding claims 18, the step of " assessing activation or non-activation of at least Sra-13, Str-2, Odr-10, Sra-17 and Str-130,wherein” and claim 24 “wherein the subject has cancer and at least Sra-13, Str-2, Odr-10, Sra-17 and Str-130 are activated” is a step describing a correlation or relationship between the presence of response of a gene and cancer. It is noted that claim 18 recites “detecting cancer” and thus the preamble provides an implied correlation with the “detecting” and “assessing” steps. This limitation sets forth a judicial exception, because this type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo). The step could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception, which may be termed a law of nature, an abstract idea, or both. Note that although the claim recites several nature-based product limitations (e.g., the sample and biomarker), the claim as a whole is focused on a process of detecting whether the biomarker is present in a sample, and is not focused on the products per se.
Regarding claims 19, 26, 28, 30, the correlation is not resolved, because the limitations include two additional genes.
Regarding claim 20, the correlation is not resolved as it further modifies the detection method.
Regarding claim 21-22, 25, 27, 29, and 31 the correlation is not resolved as it limits the type of cancer and the type of sample.
Subject Matter Eligibility - Step 2A, Prong 2:
This judicial exception is not integrated into a practical application because the step of claims 18-19: "assessing activation or non-activation…” with the implied correlation to “detecting cancer” and claims 24-30 “said subject has cancer" “cancer is breast cancer” is merely linking the abstract idea to the field of endeavor and would not be considered a particular practical application (MPEP 2106.05(h)). The claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Besides the law of nature, the claim recites additional steps of "subjecting C. elegans to odorant stimuli with a biological fluid sample derived from a subject". Introducing a sample in order to perform tests is well-understood, routine and conventional activity for those in the field of diagnostics. Further, the step is recited at a high level of generality such that it amounts to insignificant presolution activity, e.g., a mere data gathering step necessary to use the correlation. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well- understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting an activation of a gene. Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)). Therefore the limitation is not considered a particular practical application (MPEP 2106.05(h))
Regarding claims 19, 24, 26, 28, 30, there is not significantly more than the exception because the limitation merely adds genes to be observed.
Regarding claim 20, there is not significantly more than the exception because modifies the detection method that is well known and routine activity for diagnostics.
Regarding claim 21-22, 25, 27, 29, and 31, there is not significantly more than the exception because it further limits the type of cancer and the type of sample.
Subject Matter Eligibility - Step 2B:
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the introducing and capturing biomarker steps are the other elements. Subjecting, and assessing gene activation of C. Elegans are well understood and conventional as evidenced by Hirotsu et al (US 20170016906, see rejection below for details). The claim is therefore not patent eligible.
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.
Claim(s) 18-19, 21-22, 24-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hirotsu et al (US 20170016906) in view of Milanetti et al, "Investigation of the binding between olfactory receptors and odorant molecules in C. elegans organism" Biophysical Chemistry 255 (2019) 106264, pp. 1-8.
Regarding claim 18 and 24-25, Hirotsu et al teach a method for detecting cancer comprising: subjecting C. elegans AWA and AWC GPCR receptors to odorant stimuli with a biological fluid sample derived from a subject (Para. 0259; Claim 7: urine), and assessing activation or non-activation of sra-17 (Table 5), str-2 (Table 4), odr-10 (Par. 0184), str-130 (Table 4) and wherein sra-17 (Table 5), str-2 (Table 4), odr-10 (Par. 0184), str-130 (Table 4) are activated (Para. 0184: detection of the expression of odr-10), said subject is determined to have cancer (Para. 0075: detect breast cancer). Hirotsu is silent to sra-13.
Milanetti et al teach genes encoding for GPCRs expression on AWC neurons including sra-13, str-2, str-130, srsx-5, and str-199 as well as odr-10 on the AWA neuron (p. 3 para. 2.1 Datasets). It is desirable to provide GPCRs genes in AWA and AWC that due to volatile compounds which express in the presence of cancer metabolites are indicative of cancer in patients (p. 2 col. 2 para 1). In re Boesch (205 USPQ 215) teaches the optimization of an effective variable is ordinarily within the skill of the art. A result effective variable is one that has well known and predictable results. The choice of a GPCRs gene expression that is linked to cancer is a result effective variable that gives the well-known and expected results of detecting cancer. In the absence of a showing of unexpected results, the Office maintains the sra-13 of Milanetti et al would have been within the skill of the art as optimization of a results effective variable to include in the method of Hirotsu.
Regarding claim 19, 26, Hirotsu/Milanetti teach srsx-11 and str-199 (Hirotsu: Table 4), Hirotsu is silent to srsx-5. Milanetti et al teach genes encoding for GPCRs expression on AWC neurons including sra-13, str-2, str-130, srsx-5, and str-199 as well as odr-10 on the AWA neuron (p. 3 para. 2.1 Datasets). It is desirable to provide GPCRs genes in AWA and AWC that due to volatile compounds which express in the presence of cancer metabolites are indicative of cancer in patients (p. 2 col. 2 para 1). In re Boesch (205 USPQ 215) teaches the optimization of a result effective variable is ordinarily within the skill of the art. A result effective variable is one that has well known and predictable results. The choice of a GPCRs gene expression activation or not activated that is linked to cancer is a result effective variable that gives the well-known and expected results of detecting cancer. In the absence of a showing of unexpected results, the Office maintains the srsx-5 of Milanetti et al would have been within the skill of the art as optimization of a results effective variable to include in the method of Hirotsu to determine if the subject is determined to have cancer.
Regarding claims 21, 25, 27, 29, 31, Hirotsu/Milanetti teach the cancer is breast cancer. (Para. 0073: breast cancer)
Regarding claim 22, Hirotsu/Milanetti teach the body fluid is urine. (Para. 0071: bodily fluid is urine)
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hirotsu/Milanetti in view of Tehseen et al, "Functional Coupling of a Nematode Chemoreceptor to the Yeast Pheromone Response Pathway", PLoS One. 2014 Nov 21;9(11), pp. 1-21.
Regarding claim 20, Hirotsu teaches the fluorescent imaging of yellow cameleon gene to detect the activation neurons. (Para. 0184). Hirotsu is silent to said assessment is carried out by putting in contact with said biological fluid sample distinct Saccharomyces cerevisiae strains comprising each, a DNA coding for one of said AWC and/or AWA GPCR receptors, coupled to Saccharomyces cerevisiae Ga subunit so to express a GPCR- Ga chimera, each of said yeast strains also comprising a pheromone-responsive fluorescent transcriptional reporter gene, said GPCR receptors being at least Sra-13, Str-2, Odr-10, Sra-17 and Str-130;and when emission of fluorescence is observed in at least in Saccharomyces cerevisiae strains expressing Sra-13-Ga; Saccharomyces cerevisiae strains expressing Str-2-Ga;Saccharomyces cerevisiae strains expressing Odr-10-Ga; Saccharomyces cerevisiae strains expressing Sra-17-Ga and Saccharomyces cerevisiae strains expressing Str-130-Ga, Sra-13, Str- 2, Odr-10, Sra-17 and Str-130 GPCR receptors are assessed as activated.
Tehseen et al teach putting in contact with said biological fluid sample distinct Saccharomyces cerevisiae strains comprising each, a DNA coding for one of said AWC and/or AWA GPCR receptors, coupled to Saccharomyces cerevisiae Ga subunit so to express a GPCR- Ga chimera, each of said yeast strains also comprising a pheromone-responsive fluorescent transcriptional reporter gene, said GPCR receptors being Odr-10; and when emission of fluorescence is observed in at least in Saccharomyces cerevisiae strains expressing Odr-10-Ga GPCR receptors are assessed as activated (Abstract; p. 13: fluorescent reporter lacZ; Fig. 5). It is desirable to provide a robust assay for analysis of C. elegans GPCR function to enable de-orphaning of C. elegans chemoreceptors GPCR (p. 17, para. 1-2). Simple substitution of one known element for another to obtain predictable results is held to be obvious. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the assay of Hirotsu/Milanetti for the Saccharomyces cerevisiae Ga subunit assay of Tehseen et al to provide the above advantage of enabling de-orphaning of C. elegans chemoreceptors GPCR.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS MICHAEL WHITE whose telephone number is (571)270-3747. The examiner can normally be reached M-F 8:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris R. Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Dennis White/Primary Examiner, Art Unit 1758
