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/CA2021/050765, filed 06/03/2021, which claims priority to US provisional application 63/035,081, filed 06/05/2020. 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 in the reply filed on 07 January 2026 is acknowledged.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07 January 2026.
Applicant’s election of the species of a) measurement of transcription products and b) epigenetic therapy (with an elected subspecies of DNMTi/DNMT as epigenetic target), in the reply filed on 07 January 2026 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)). The examiner concurs that claims 1-6 and 11-14 read on the elected species.
Claims 7-10 and 15-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07 January 2026.
Claim Objections
Claims 13-14 are objected to because of the following informalities: in claim 13 (from which claim 14 depends) Applicant employs abbreviations without first reciting the complete terminology. Appropriate correction is required; for example, with regard to the elected species of DNA methyltransferases, the claim should recite “DNA methyltransferases (DNMTs)”.
Claim Interpretation
With regard to the recitation in claim 1 of the limitation “measuring or estimating the expression levels of inverted repeats (IR) Alus in the cells”, it is noted that this claim language is interpreted as encompassing any manner of measuring or estimated levels of any number/type of IR Alu expression products (i.e., the reference to “the expression levels” does not render the claims indefinite when used in this manner).
With regard to claim 1 and claims dependent therefrom (claims 2-6 and 11-14), it is noted that the language “determining that the subject would be responsive to cancer therapy if the subject cells exhibit higher expression levels of inverted repeats (IR) Alus with reference to expression levels in control samples” is clearly a conditional/contingent limitation (given the use of the language “determining….if” followed by the statement of a condition that may or may not result from the performance of the recited active method steps). Regarding such limitations, MPEP 2111.04(II) states:
“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, the BRI of claim 1 requires only the recited “providing” and “measuring” set forth in the claim.
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 2-5 and 11-14 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.
Claim 2 is indefinite over the recitation of the limitation “measuring the transcription product of IR Alus”, because there is insufficient antecedent basis in the claims for any particular “transcription product”, and because it is unclear whether the claim is referring to a single particular “transcription product”, or potentially to a “transcription product” corresponding to each IR Alu, etc. Further clarification is therefore required to ensure that the boundaries of the claim are clear.
Claims 3-5 are each indefinite over the recitation in the claims of the limitation “IR Alus shown in Table B”, as well as the limitations “a majority of the IR Alus shown in Table B” (claim 3), “at least 60%....of the IR Alus shown in Table B” (claim 4), and “all or substantially all of the IR Alus shown in Table B” (claim 5). First, Applicant is reminded that:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). (MPEP 2173.05(s)).
In the instant case, the reliance on a Table creates confusion as to what elements of the table are/are not required to meet the claims, and further the subject matter being claimed could simply be recited in the claim itself. Further, as the nature of what elements of the Table are required is not clear, the further requirements for “a majority”, “at least 60%”, etc., of items identified by reference to the table are also unclear (as such limitations require knowledge of what is encompassed by the reference to “Table B”). Finally, regarding claim 5, the specification does not define what is meant by “substantially all”, and this terminology does not have a standard meaning in the art +that would allow one of ordinary skill in the art to identify the boundaries of what is claimed (i.e., it is not clear what would/would not be considered as “substantially all” of “the IR alus shown in Table B”). Accordingly, clarification is required.
Claims 11-14 are indefinite over the recitation in claim 11 (from which claims 12-14 depend) of the limitation “the treating the patient with the cancer therapy”. There is insufficient antecedent basis for this limitation in the claims, as claim 1 (from which claim 11 depends) never recites/references a “patient” or a “treating the patient”. Further, to the extent that the claim may be intended to require some type of active “treating”, it is not clear how this action relates to the method of claim 1 (it appears that the claim contains a typographical error and/or may be incomplete, given the present wording). Accordingly, clarification is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6 and 11-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al (Artificial Cells, Nanomedicine, and Biotechnology 47(1):1349-1356 [April 2019]; cited herein).
Sun et al disclose measuring expression levels of the circular RNA (circRNA) circCDYL in bladder cancer tissues (see entire reference). As Sun et al teach that circCDYL is a circular IR Alu-containing RNA (“Results” on page 1351 bridging to page 1352, left column, including Figure 1), disclose provision of both bladder cancer tissue samples (which inherently contain “cancer cells”) and paired normal bladder samples (page 1350, left column, “Human tissue specimens”), and disclose measuring expression levels of nuclear and cytoplasmic circCDYL RNA in such samples (page 1350, left column “RNA extraction and real-time PCR assays”; page 1351, right column bridging to 1352, left column), Sun et al anticipate claim 1. More particularly, Sun et al clearly disclose a “providing” and “measuring” meeting the requirements of the claims, and (as discussed above) the “determining” of the claim is a contingent/conditional (rather than required step; it is also noted that even to the extent that the “determining” may be a required element, such a “determining” constitutes an instructional limitation added to a method known in the art, 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]). Additionally, regarding the preamble recitation “of assessing a subject’s responsiveness to cancer therapy”, it is noted that this constitutes a statement of an intended use that does not result in a manipulative difference between the claimed invention and the prior art teachings of Sun et al, and thus is not limiting of what is claimed (particularly as the “determining” of the claim as written need not have a positive outcome; see MPEP 2111.02, and see again the Claim Interpretation above).
With further regard to dependent claim 2 and dependent claim 6 (dependent from claim 2), Sun et al disclose measuring expression levels of nuclear and cytoplasmic RNA products via RT-PCR, which meets the requirements of both claims (see page 1350, left column, “RNA extraction and real-time PCR assays”; page 1351, right column bridging to page 1352, left column).
Regarding dependent claims 3-5, it is reiterated that these claims are not clearly further limiting of what is claimed, such that the teachings of Sun et al are sufficient to anticipate what is presently required by the claim language.
Regarding claims 11-14, again, these claims are not clearly further limiting, as there is not prior reference to a “patient”, a “treating”, etc., such that the claims are anticipated for the same reasons that apply to claim 1 (although it is also noted that Sun et al disclose that their tested patients had undergone radical cystectomy, which is a type of bladder cancer treatment/therapy; see page 1350, left column). With further regard to claims 12-14, it is also noted that the “cancer therapy” of claim 1 is an element of the claim preamble and the “determining” of the claim (i.e., elements of the claims that are not limiting of claim scope based on the present wording of the claims, as discussed above); nothing recited in the present claims indicates a requirement for any kind of active/manipulative step in which therapies of the types recited in claims 12-14 are employed.
Accordingly, Sun et al anticipate claims 1-6 and 11-14.
Claim Rejections - 35 USC § 103
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) 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al (Artificial Cells, Nanomedicine, and Biotechnology 47(1):1349-1356 [April 2019]; cited herein) in view of Chovanec et al (Targeted Oncology 13:49-60 [2017]; cited herein).
It is reiterated that claims 11-14 are rejected under 35 USC 102(a)(1) for the reasons given above; this rejection applies to the claims to the extent that they may require subjects/patients treated with a DNA methyltransferase inhibitor (DNMTi), which appears to be a potential embodiment also embraced by these claims.
Sun et al disclose measuring expression levels of the circular RNA (circRNA) circCDYL in bladder cancer tissues (see entire reference), teaching that a purpose of their study was to gain a better understanding of the role, function, and mechanism of circCDYL – which is already known as “a prognostic biomarker for patients diagnosed with early-stage bladder cancer” – in bladder cancer (see page 1349, right column). As Sun et al teach that circCDYL is a circular IR Alu-containing RNA (“Results” on page 1351 bridging to page 1352, left column, including Figure 1), disclose provision of both bladder cancer tissue samples (which inherently contain “cancer cells”) and paired normal bladder samples (page 1350, left column, “Human tissue specimens”), and disclose measuring expression levels of nuclear and cytoplasmic circCDYL RNA in such samples (page 1350, left column “RNA extraction and real-time PCR assays”; page 1351, right column bridging to 1352, left column), Sun et al teach methods meeting all of the requirements of claim 1, from which claims 11-14 depend. More particularly, Sun et al clearly disclose a “providing” and “measuring” meeting the requirements of the claims, and (as discussed above) the “determining” of the claim is a contingent/ conditional (rather than required step; it is also noted that even to the extent that the “determining” may be a required element, such a “determining” constitutes an instructional limitation added to a method known in the art, 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]). Additionally, regarding the preamble recitation “of assessing a subject’s responsiveness to cancer therapy”, it is noted that this constitutes a statement of an intended use that does not result in a manipulative difference between the claimed invention and the prior art teachings of Sun et al, and thus is not limiting of what is claimed (particularly as the “determining” of the claim as written need not have a positive outcome; see MPEP 2111.02, and see again the Claim Interpretation above).
With particular regard to claims 11-14, while Sun et al teach that their tested samples were obtained from subjects/patients treated by radical cystectomy (page 1350, left column) and state that their disclosed testing is pertinent to whether circCDYL “might be used as a new target for bladder cancer therapy” (Abstract) - and the claims as written encompass performing a “treating” at any point in time relative to other method steps (given the “further comprising” language of claim 11) - Sun et al do not teach subjects/patients treated with a DNMTi, i.e., the elected species of therapy type.
Chovanec et al teach that DNMTis are in use in the treatment of genitourinary malignancies (including bladder cancer), stating that “the efficacy of these agents in genitourinary malignancies was reported in a number of studies and suggests a role of induced DNA hypomethylation in overcoming resistance to conventional cytotoxic treatments” (see entire reference, particularly the Abstract). Chovanec et al disclose several clinical trials of different DNMTis that are underway, including with respect to bladder cancer (see Table 2 and section 6.2 “Bladder Cancer” on pages 53-55).
In view of the teachings of Sun et al and Chovanec 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 Sun et al so as to have performed those methods on samples from bladder cancer patients participating in clinical trials as taught by Chovanec et al, and thereby to have performed methods including both a “treating” with a DNMTi and all testing steps taught by Sun et al (i.e., methods meeting all requirements of the present claims). An ordinary artisan would have been motivated to have made such a modification by the teaching of Sun et al that their methods may serve to better characterize how circCDYL plays a role in bladder cancer (such that the modification would provide a benefit in expanding the testing of Sun et al to additional bladder cancer patients, including patients undergoing DNMTi therapy), as well as by the teaching of Sun et al suggesting a relationship between circCDYL and the targeting of bladder cancer therapy (providing the advantage of assessing any relationship between DNMTi therapy and circCDYL expression levels). Further, given the detailed guidance of Sun et al, an ordinary artisan would have had a reasonable expectation of success in expanding the testing of Sun et al to other types of samples as well as other bladder cancer patients.
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 1-6 and 11-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 1 (from which all claims depend) recites “assessing a subject’s responsiveness to cancer therapy” and “determining that the subject would be responsive to cancer therapy if the subject cells exhibit higher expression levels of inverted repeats (IR) Alus with reference to expression levels in control samples”. These activities of “assessing” and “determining” may be accomplished entirely in the human mind (by forming an “assessment” regarding responsiveness, and mentally “determining” responsiveness based on a possible outcome of expression level measurement, respectively), such that the claims are directed to abstract ideas, i.e., a judicial exception (JE). (Additionally, while “measuring” transcription products of IR Alus is the elected species, in the interest of compact prosecution it is noted that the claims also embrace “estimating” expression levels, which may also encompass activities performed entirely in the human mind, such as mentally estimating levels based on the results of physical testing steps).
These judicial exceptions are not integrated into a practical application because the activities of “providing a sample…comprising cancer cells or suspected cancer cells” and “measuring….the expression levels of inverted repeats (IR) Alus in the cells”, whether considered individually or in combination, are data gathering steps that do not add a meaningful limitation to the method as they are insignificant extra-solution activity”; nothing corresponding to an application/implementation of a JE is recited in the claims. 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 sample comprising (suspected) cancer cells and measuring expression levels of IR Alus therein also corresponds to well-understood, routine, and conventional activity as of Applicant’s effective filing date (see, e.g., Sun et al, cited above; and see also Okholm et al (npj Genomic Medicine 2:36 [2017]; cited herein)). Additionally, the types of activities set forth in the claims – “providing” a sample and “measuring… expression levels” – whether considered individually or in combination, are recited at a high level of generality, and correspond to laboratory techniques recognized by the courts as constituting well-understood, routine, and conventional activities in the life science arts when recited at a high level of generality (as they are in the present claims) (see MPEP 2106.04(d)(II). It is also noted that the association of altered expression levels of IR Alus in cancer cells with responsiveness to therapy is a natural phenomenon (rather than something “more” than a JE), and 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)).
With further regard to dependent claims 2 and 6, the measurement of transcription products of IR Alus, including comprising “use of RNA sequencing or PCR/digital PCR”, are clearly data gathering steps, corresponding to insignificant extrasolution activity (for the same reasons noted above regarding claim 1). Such activities also corresponds to generic/general recitations of a well-known techniques/methods in the life science arts, such that nothing “significantly more” than a JE is added. Regarding claims 3-5, which provide an indefinite/unclear description of IR Alus “to be measured”, this again clearly corresponds to data-gathering/insignificant extrasolution activity, and embraces any manner of “measuring the expression levels”, i.e., a general recitation embracing any of a variety of well-known techniques of expression level measurement, such that nothing significantly more than a JE is added.
Regarding dependent claims 11-14, it is reiterated that it is unclear how these claims further limit claim 1, as there is no patient or “treating” recited in claim 1 that might correspond to “the treating the patient”. Thus, as these claims are not clearly further limiting of claim 1, they are patent ineligible for the same reasons claim 1 is patent ineligible. Further, even to the extent that the claims may embrace embodiments in which “treating” of the type recited is performed with regard to the “subject” of claim 1, there is no indication that such a “treating” would correspond to an implementation/application of the JEs of claim 1 (as such a treating could be performed at any point in time during the practice of the claimed method). Additionally, the types of “treating” recited correspond to well-understood, routine, and conventional activities as of Applicant’s effective filing date; see, e.g., Chovanec et al (Targeted Oncology 13:49-60 [2017]; cited herein), teaching the administering of DNMTis to cancer patients.
Accordingly, none of claims 1-6 and 11-14 is directed to patent eligible subject matter.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Orsini et al (Diagnostic Pathology 13:98 [2018]; cited herein) disclose the use of droplet digital PCR in quantifying Alu repeat methylation status.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682