DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is the national stage of PCT/EP2021/069952, filed 07/16/2021, claiming foreign priority benefit to EP20186398.2, filed 07/17/2020. The International Search Report and Written Opinion issued in the PCT application have been received and reviewed.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-13) in the reply filed on 23 December 2025 is acknowledged. It is noted that all claims directed to non-elected Groups II-III (claims 14-16) have been canceled.
Applicant’s election of the species of “(i) determining the level; (ii) first biomarker: METTL3; (iii) second biomarker: combination of CTU1, CTU2, MOCS3, and URM1; and (iv) disease: cancer (and if necessary….breast cancer)” in the reply filed on 23 December 2025 is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-13 are therefore under consideration herein as directed to the elected species identified above. It is noted that:
The alternative of “determining the level” appears in each of independent claims 1 and 8;
METTL3 is recited as a “preferable” first biomarker in dependent claims 2 and 9;
CTU1, CTU2, MOCS3, and URM1 are recited as alternative second biomarkers in dependent claims 2 and 9, with the elected combination/“panel” of genes being required by dependent claim 10;
Cancer is recited as an alternative in dependent claim 3, which also recites breast cancer as a “preferable” cancer embraced by the claims.
It is noted that the prior art was not found to apply against the elected “second biomarker” combination of CTU1, CTU2, MOCS3, and URM1 (resulting in claim 10 having been found to be free of the prior art, although the claim is rejected on other grounds). Accordingly, search and examination has been extended to “at least one” of CTU1, CTU2, MOCS3, and URM1 (as is encompassed by all claims other than claim 10, and dependent claims 2 and 9 in particular).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see in particular multiple entries in Table 1 at pages 39-40, and citation 2 on page 45). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 10 is objected to because of the following informalities: the claim recites two alternatives for “said at least one biomarker”, both of which are identified as “(ii)”. As there is no recitation in a prior claim of (i), this appears to be a typographical error in specifying two possible “panels” having different boundaries. Appropriate correction is required (and specifically, the objection could be overcome by simply amending the claim to identify the first alternative as “(i)”).
Claim Interpretation
Regarding claim 8 and claims dependent therefrom, it is noted that the reference to “the biological sample from said patient” in line 3 is considered clear and definite in view of the subsequent recitation (following the reference of “as a first step, identifying…and as a second step, deciding…”) of the method employed to “identify” the differential level, etc., which method employs a “biological sample of said patient” (see (a) of claim 8).
Claim Rejections - 35 USC § 112(b)/second paragraph
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 1-13 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.
Rejections of claim 1 and claims dependent therefrom (claims 2-7, 10, and 13):
Claim 1, 3-7, 10, and 13 are indefinite over the recitation in independent claim 1 of the limitations “biomarker indicative and/or selective for the status and/or activity of the pathway regulating N6-methyladenosine (m6A) mRNA modification” and “biomarker indicative and/or selective for the status and/or activity of the pathway regulating 5-methoxycarbonlmethyl-2-thiouridine (mcm5s2U)-tRNA modification”. While it is noted that the specification, claims, and prior art (see, e.g., Delaunay et al [Nature Cell Biology 21:552 [May 2019]; cited in IDS) provide many examples of biomarkers that constitute members of/participants in each of the recited pathways, the language “indicative and/or selective for the status and/or activity of the pathway” is not defined in the specification, does not have a recognized meaning in the art, and does not provide clear boundaries for what is being claimed. Accordingly, further clarification is required. (It is noted that claim 2, dependent from claim 1, was deliberately excluded from this rejection in view of the recitation in that claim of clearly defined biomarkers/categories of biomarkers.)
Claims 1-7, 10, and 13 are indefinite over the recitation in independent claim 1 of the limitations “said first and said second biomarker in steps (b) and (c)” (see lines 11-12) and “said first and/or second biomarker” (see claim 1 at lines 13 and 17). The claim previously refers to “at least one” first biomarker and “at least one” second biomarker, such that clear antecedent basis is lacking for the identified limitations in lines 11-12, 13 and 17, and it is unclear what is being further limited (and specifically whether the recited further limitations apply to any individual biomarker, a particular biomarker, all of “at least one” of the groups of biomarkers, etc.). Clarification is therefore required.
Regarding claims 1-7, 10, and 13, the term “reduced” in claim 1 (line 15) is a relative term which renders the claim indefinite. The relative term “reduced” 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. Particularly, the claim does not provide a point of comparison/reference with respect to which/what time of PFS/OS would be considered as “reduced”, such that it is not clear what conclusion is to be drawn in instances when a “differential level” is present (although it is noted that the claim as written does not actually require a “differential level” as an outcome).
Regarding claim 2, the recitation of the term "preferably" (line 3) and “more preferably” (line 13) render the claim indefinite because it is unclear whether the limitation(s) following “preferably”/“more preferably” are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 3, the recitation of the terms "preferably" (see line 5) renders the claim indefinite because it is unclear whether the limitation(s) following “preferably” are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 4, the recitation of the phrases/terms "such as" (see line 2) and “preferably” (line 5) render the claim indefinite because it is unclear whether the limitation(s) following these phrases/terms are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 5, the recitation of the phrases/terms “preferably” (see lines 5 and 13), "such as" (see line 6) and “for example” (line 7) render the claim indefinite because it is unclear whether the limitation(s) following these phrases/terms are part of the claimed invention. See MPEP § 2173.05(d).
Claim 5 recites the limitation “said method” in line 5. As the term “method” appears multiple times, and in reference to different things, prior to the recitation of “said method”, further clarification is required. In particular, the claim refers to the method of claim 1, to a “detection method”, and to a “method for determining” a SNP prior to reciting “said method”.
Claim 5 also contains several references to products as alternative “methods”, which is confusing. In particular, the claim states “wherein said method is” followed by alternatives of a polymorphic array, a GeneChip, “antibody-based protein chips”, a bead array, and a polymorphic array; all of these alternatives are products potentially usable in various methods, and the claim language fails to actual indicate a use/method involving the recited products that would reasonably constitute a possible further limitation of “said method”. Further clarification is therefore required.
Claim 5 contains the trademarks/trade names Affymetrix, GeneChip, nanoString, nCounter, MSIA, and SISCAPA. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe reagents/materials for medical/biotechnological/diagnostic use, and, accordingly, the identification/ description is indefinite.
Claim 6 is indefinite over the recitation of the term “reduced” in line 4, as this is again a relative term which renders the claim indefinite. While it is noted that the claim sets forth a further limitation on what is indicated by a “reduced time” and sets forth a more particular type of reference sample or value (i.e., is a further limitation of “wherein” language pertaining to a hypothetical patient set forth in claim 1), as was the case with the language in claim 1, the relative term “reduced” 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. Particularly, the claim does not provide a point of comparison/reference with respect to which/what time of PFS/OS would be considered as “reduced”.
Claim 6 is also indefinite over the language of the entire final “wherein” clause set forth at lines 6-10 of the claim. First, the claim references “the level, mutation status, and/or activity of said at least one first biomarker and/or said at least one second biomarker in the reference sample or reference value…”, but the claim does not previously refer to these particular limitations in reference to “the reference sample or reference value” (such that clear antecedent basis is lacking). Second, the claim concludes with the statement “is indicative for an increased time of” PFS and/or OS, which language: a) includes the relative terminology “increased” without defining this relative term or providing a point of comparison therefore (such that this claim language is unclear for the same general reasons that apply to the use of “reduced” as set forth above); and b) it is not clear who or what the “increased time” applies to based on the present wording of the claim (as while the claimed method in general relates to prognosis/diagnosis/monitoring of a subject, the manner of wording of the claim appears to indicate a conclusion regarding the reference sample or value relative to the biological sample. Accordingly, several aspects of claim 6 require further clarification.
Claim 7 is indefinite over the recitation of the limitation “the determined differential level, mutation status, and/or activity of said first and/or second biomarker in the biological sample…” because while claim 1 (from which claim 7 depends) does requiring determining levels of the recited biomarkers, it does not recite or require a “determined differential level” (rather, claim 1 states what is indicated by a “differential level, mutation status, and/or activity”). Accordingly, clear antecedent basis is lacking for this limitation, and it is also unclear how the claim is further limiting of claim 1.
Claim 7 also recites several relative terms, including “lower” (lines 3 and 6), “higher” (lines 4 and 6), “reduced” (line 5), and “enhanced” (line 8), none of which terms is defined by the claim; further, the specification does not provide a standard for ascertaining the requisite degree, no point of comparison for the relative terms is provided, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Accordingly, further clarification is needed.
Regarding claim 13, the recitation of the term "preferably" (line 2) renders the claim indefinite because it is unclear whether the limitation(s) following “preferably” are part of the claimed invention. See MPEP § 2173.05(d).
Rejections of claim 8 and claims dependent therefrom (claims 9, 11, and 12):
Claim 8, 11, and 12 are indefinite over the recitation in independent claim 8 of the limitations “biomarker indicative and selective for the status and/or activity of the pathway regulating N6-methyladenosine (m6A) mRNA modification” and “biomarker indicative and selective for the status and/or activity of the pathway regulating 5-methoxycarbonlmethyl-2-thiouridine (mcm5s2U)-tRNA modification”. While it is noted that the specification, claims, and prior art (see, e.g., Delaunay et al [Nature Cell Biology 21:552 [May 2019]; cited in IDS) provide many examples of biomarkers that constitute members of/participants in each of the recited pathways, the language “indicative and selective for the status and/or activity of the pathway” is not defined in the specification, does not have a recognized meaning in the art, and does not provide clear boundaries for what is being claimed. Accordingly, further clarification is required. (It is noted that claim 9, dependent from claim 8, was deliberately excluded from this rejection in view of the recitation in that claim of clearly defined biomarkers/categories of biomarkers.)
Claims 8-9 and 11-12 are indefinite over the recitation in independent claim 8 of the limitation “said first and second biomarker in steps (b) and (c)”, because: i) there is insufficient antecedent basis for this limitation; and ii) as the claim previously references “at least one” first and “at least one” second biomarker, it is unclear whether the claim is then referencing a particular first/second biomarker, any single/individual first and second biomarker, or the previously referenced “at least one” first and second biomarker. Further clarification is therefore needed.
Regarding claim 9, the recitation of the terms "preferably" (see line 3) renders the claim indefinite because it is unclear whether the limitation(s) following “preferably” are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 11, the recitation of the terms "preferably" (see line 3) renders the claim indefinite because it is unclear whether the limitation(s) following “preferably” are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 12, the recitation of the terms "preferably" (see line 2) renders the claim indefinite because it is unclear whether the limitation(s) following “preferably” are part of the claimed invention. See MPEP § 2173.05(d).
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.
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) 1-9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al (BMC Cancer 19:326 [April 2019]; cited in IDS) in view of Delaunay et al (Nature Cell Biology 21:552-559 [May 2019]; cited in IDS).
Wu et al teach methods in which expression levels of m6A methylases, including the elected biomarker METTL3, were determined in 36 pairs of breast cancer tissues and adjacent non-cancerous tissue (see entire reference, particularly the Abstract; page 2, “Patients”; page 3, right column, “Quantitative RT-PCR (qRT-PCR)”; Results at pages 4-6, particularly page 5, right column bridging to page 6, left column; and Fig. 5). With more particular regard to the methods steps of independent claims 1 and 8, Wu et al teach providing biological samples from subjects/patients by collecting “samples of fresh BC cancerous tissues and paired normal tissues” (see again page 2, “Patients), and teach determining and comparing expression levels of METTL3 and other m6A biomarkers in both the cancerous and normal tissues (see again page 3, right column); Wu et al thus teach methods including a “providing” meeting the requirements of a) of the claims, a “determining” meeting the requirements of b) of the claims, and a “comparing” meeting the requirements of d) of the claims with respect to a “first” biomarker.
With further regard to the preamble and “wherein” clauses of claim 1, it is also noted that:
a) the method of Wu et al constitutes at least a type of “monitoring” of breast cancer, such that the intended use of the preamble of claim 1 is achieved by Wu et al;
b) the “wherein” clauses recited at the end of claim 1 state what is indicated by possible – but not required - outcomes of the claimed methods that pertain to levels of “said first and/or second biomarker”, such that claim scope is not limited by this claim language (see MPEP 2111.04). However, while not required to meet the claims, it is noted that Wu et al do in fact teach that “expression of m6A members including METTL3” was tightly associated with cancer progression and poor survival” (see the Abstract; see also page 5, right column-page 6, left column; Fig. 5) (such that Wu et al do teach a “differential level” of a “first biomarker” that is associated with “reduced” survival, although this teaching is not required to meet the claim).
With further regard to independent claim 8, the teachings of Wu et al set forth above also meet the requirements of the “identifying a differential level” recited in independent claim 8 at lines 2-3 (which only requires “at least one first and/or at least one second biomarker”). Additionally, with regard to the intended use of “stratifying a patient for treatment” and the recitation of “deciding in favor of or against said treatment based on said differential level…”, the claim never sets forth any active steps of treating/treatment/administering or equivalent actions, but rather recites “stratifying” and “deciding in favor of or against” a treatment; such limitations constitutes instructional limitations, i.e., nonfunctional descriptive material that need not be given patentable weight when comparing a claimed invention to the prior art (see MPEP 2111.05). Furthermore, the claims set forth no particular requirements with regard to what “identifying a differential level” requires; rather, the claim states that such an “identifying” is achieved by performing the “providing”, “determining”, and “comparing” of (a)-(d) of claim 8, for which no particular outcome is specified. Thus, performance of steps of (a)-(d) of claim 8 is all that is required to meet the claims (with the “comparing” of d) also being an instructional step requiring nothing more than thinking about the results of prior steps, although it is reiterated that Wu et al do disclose such a “comparing” with regard to m6A biomarkers inclusive of METTL3).
Wu et al do not teach determining levels of “at least one second biomarker” of the mcm5s2U-tRNA pathway (including any of the preferred second biomarkers CTU1, CTU2, MOCS2, and URM1), and thus do not teach methods meeting all requirements of the claims.
Delauney et al teach that “altered RNA modification patterns are widely linked to developmental diseases”, and that RNA modifications are also contributors to cancer (see entire reference, particularly the Abstract). Delauney et al provide an overview of how different types of RNA modifications contribute to cancer, describing the role of both the m6A pathway (which is taught as requiring METTL3) and the mcm5s2U pathway; see entire reference including Figures 1 and 2; page 552, right column, second paragraph; page 553, right column, first full paragraph; and the entirety of page 554-556, noting that both pathways are disclosed as being implicated in breast cancer (see, e.g., page 556, left column, 4th full paragraph regarding upregulation of mcm5s2U genes in breast cancer), and that all of METTL3, CTU1, and CTU2 are disclosed/depicted in, e.g., Figures 1-2. With further regard to claim 8 and claims dependent therefrom, while it is reiterated that the elements of the claims related to “treatment” constitute non-functional descriptive material, Delauney et al also teach that “recent studies have demonstrated a link between RNA modifications and tumour cell survival in response to chemotherapy, and state that “modulation or inhibition of RNA modification pathways offers therapeutic strategies to target specific tumor populations” (page 556, right column), providing motivation to analyze and consider both m6A and mcm5s2U pathway members in relation to drug resistance (including chemotherapy resistance) and treatment selection.
In view of the teachings of Delauney et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of Wu et al so as to have included therein additional steps of determining levels of one or more biomarkers of the mcm5s2U pathway (including specific biomarkers such as CTU1 and CTU2). As Delauney et al teach that both the m6A and mcm5s2U pathways have been implicated in cancer, including breast cancer, an ordinary artisan would have been motivated to have made such a modification simply for the benefit of determining additional relevant biomarkers exhibiting altered expression in association with breast cancer, achieving a more comprehensive “monitoring” of the cancer as compared to Wu et al alone. Additionally, as Wu et al state that their goal in performing their analysis of m6A methylases and demethylases was to aid in “understand the pathogenic molecular mechanisms of m6A and for diagnosis” (page 2, left column, last full paragraph), an ordinary artisan would also have been motivated to have performed analogous measurements/determinations regarding mcm5s2U markers for these same benefits (and it is reiterated that the claims as presently written do not require a particular outcome of the “determining” and “comparing” steps of the claims, such that only performance of the recited steps is required to meet the claims). Furthermore, given Delauney et al’s teachings of the relevance of both the m6A and mcm5s2U pathways to drug resistance (including chemotherapy resistance in cancer), an ordinary artisan also would have been motivated to have made such a modification for the benefit of identifying any altered expression levels in either pathway that could aid in better selection of treatment/therapy for a patient. Finally, given the guidance provided by Wu et al and Delauney et al, and particularly the identification by Delauney et al of specific markers that are suitable targets for such analysis, an ordinary artisan would have had a reasonable expectation of success in performing such methods.
With further regard to dependent claims 2 and 9, the teachings of the references in relation to the elected biomarkers (specifically METTL3 and CTU1 and/or CTU2) are set forth above.
Regarding claim 3, Wu et al in view of Delauney et al teach at least the preferred embodiments of cancer, including breast cancer (although it is noted that neither of these is clearly required by the present claim language).
Regarding claim 4, Wu et al teach tissue samples (including breast cancer tissues and paired normal tissues), as discussed above (see again page 2, “Patients”).
Regarding claim 5, Wu et al teach qRT-PCR (see page 3, right column, first full paragraph).
Claim 6-7 each recite what is indicated by possible outcomes of the performance of the active method steps of the claims, without actually requiring the stated outcomes.
“The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (MPEP 2111.04(II)). Thus, claims 6-7 are suggested by Wu et al in view of Delauney et al for the same reasons given above regarding claim 1 (although it is reiterated that Wu et al do teach a differential expression of a “first biomarker” in association with reduced breast cancer survival/poor breast cancer prognosis).
Claim 11 recites “deciding in favor of” a treatment “based on” a “differential level” that is not required by the claims. Again, the BRI of such a claim requires only those steps that must be performed. Further, the act of “deciding” is an instructional limitation, i.e., nonfunctional descriptive material that need not be given patentable weight when comparing a claimed invention to the prior art (see MPEP 2111.05).
Finally, dependent claim 12 requires that “the method is a non-invasive method, preferably an ex vivo method or an in vitro method”, and the testing of tissue samples disclosed by Wu et al is performed ex vivo (which meets the requirements of the claim).
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 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon/law of nature without significantly more.
Independent claim 1 (from which claims 2-7, 10, and 13 depend) is drawn to a method “for the prognosis, diagnosis, and/or monitoring of a disease, condition or disorder in a subject”, and recites “comparing the determined level, mutation status, and/or activity” of said first and said second biomarkers in steps (b) and (c) with a reference sample or a reference value, wherein a differential level, mutation status, and/or activity” of said first or second biomarker in the sample as compared to said reference sample or value “is indicative for” either a “reduced time” of survival (progression free survival [PFS] and/or overall survival [OS}) or “for the presence of” the disease, condition or disorder. Such a “comparing” requires nothing more that reviewing and mentally comparing the results of the prior steps of “determining” with a reference sample or value (i.e., another type of information), which is an activity that may be performed entirely in the human mind, i.e., an abstract idea.
Independent claim 8 (from which claims 9 and 11-12 depend) is drawn to a method “of stratifying a patient for a treatment”, and recites “comparing the determined level, mutation status, and/or activity” of said first and said second biomarker in steps (b) and (c) with a reference sample or a reference value (which levels were determined in a provided “biological sample”), as well as “identifying a differential level, mutation status, and/or activity of at least one first and/or at least one second biomarker in the biological sample…compared to a reference sample or reference value, and…deciding in favor of or against said treatment based on said differential level, mutation status, and/or activity”. Each of the activities of “comparing” and “deciding”, as well as aspects of the “identifying” that correspond to the “comparing” of (d) of the claim, are also activities that may be performed in the human mind, i.e., abstract ideas.
It is also noted with regard to all claims that while the “determining the level, mutation status, and/or activity” of biomarkers “in a biological sample that is provided as an initial step of the claimed methods requires the performance of active method steps to achieve such “determining”, the properties of biomarker levels, mutation status, and activity of the recited markers in a biological sample are natural phenomena/laws of nature, i.e., another type of judicial exception (JE).
These judicial exceptions (JEs) are not integrated into a practical application because the active method steps set forth in the claims of providing a biological sample and determining levels/mutation status/activity of biomarkers therein are data gathering steps that do not add a meaningful limitation to the method as they are insignificant extrasolution activity, rather than any type of application/implementation of a JE. With particular regard to claim 8 and claims dependent therefrom, it is noted that while the claims recite “stratifying a patient for a treatment”, the activity in the claim related to treatment is “deciding in favor of or against said treatment”, which (as already noted) is a JE, rather than an application of a JE. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the activities of providing a biological sample and “determining” levels/mutation status/activity of biomarkers therein, whether considered individually or in combination, clearly constituted well-understood, routine, and conventional activity as of Applicant’s effective filing date; see again, e.g., Wu et al (BMC Cancer 19:326 [April 2019]; cited in IDS) and Delaunay et al (Nature Cell Biology 21:552-559 [May 2019]; cited in IDS).
Further, even to the extent that the claims may require, e.g., determining levels/status of a particular biomarker or biomarker combination that is not disclosed in the prior art (as is the case with respect to, e.g., the combination of claim 10), the levels/mutation status/activity of such biomarkers is (as noted above) another type of JE, rather than something “more” than a JE. An inventive concept cannot be furnished by a judicial exception (i.e., a law of nature/natural phenomenon/abstract idea) itself (see MPEP 2106.05(I)). Thus, Applicant’s claims are not directed to patent eligible subject matter.
With further regard to dependent claims 2, 9, and 10, while these claims recite “determining” more particular biomarkers/biomarker combinations, this constitutes a further limitation on the type of data gathered, rather that setting forth any type of practical application/implementation of a JE; further, the active steps required to achieve such “determining” (e.g., to measure biomarker expression levels in a biological sample) was well-known as of Applicant’s effective filing date, and the outcome of such testing with regard to various markers – e.g., elevated or reduced expression in association with a disease such as cancer – is (as already noted) another type of JE, rather than something “more” than a JE. Dependent claim 3 is further limiting of JEs of the claims (specifically, of the type of conclusions drawn regarding a sample), and does not add anything constituting an application of a JE, or add anything “significantly more” than a JE. Claim 4 recite broad categories of types of biological samples that may be employed in the claimed methods, setting forth a limitation on where data is to be gathered from, rather than adding an application/implementation of a JE; further, such sample types (“a tissue sample or a body liquid sample”, etc.) were clearly well-known types of biological samples for expression/mutation/activity testing, in routine and conventional use, as of Applicant’s effective filing date. Claim 5 sets forth broad categories of well-known methods/techniques for testing biological samples with respect to expression levels, etc.; again, the claim is further limiting of data gathering, and does not set forth any type of application of a JE, or add anything “significantly more”. Claim 6-7 each recite what is indicated by possible outcomes of the performance of the active method steps of the claims; nothing corresponding to an application/implementation of a JE, or something “significantly more” than a JE, is added. Claim 11 recites further decisions that are made based on possible outcomes of the active steps of claim 8; the claims sets forth a more particular abstract idea rather than any type of application of JE, and does not recite anything constituting “more” than a JE. Claim 12 similarly is further limiting of a JE (reciting a more particular type of treatment with regard to which “deciding” occurs); nothing constituting an application of a JE or something more than a JE is added. Finally, dependent claim 12 requires that “the method is a non-invasive method, preferably an ex vivo method or an in vitro method”; this claim is further limiting of the type of data gathering performed, but adds nothing that might constitute an application of a JE, and “non-invasive” diagnostic methods involving the measurement of expression levels, etc., were clearly well-understood, routine, and conventional as of Applicant’s effective filing date.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Fry et al (Oncotarget 9(58):31231-32243 [2018]; cited in IDS) teach altered expression of METTL3 in a model of breast cancer development/progression (see entire reference). Goodarzi et al (Cell 165:1416-1427 [June 2016]; cited in IDS) teach a tRNA profiling method and its application in measuring upregulation of specific tRNAs in metastatic breast cancer (see entire reference).
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682