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 .
DETAILED ACTION
This action is in response to papers filed 1/14/2026.
Applicant’s election of has-miR-889 in the reply filed on 7/15/2025 is 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)).
3. Claims 58-71, 76, 86-88 are pending. Claims 1-57, 72-75, 77-85 have been cancelled.
4. Claims 59-61 are withdrawn as being drawn to a non-elected species.
5. The following rejections for claims 58,62-71,76,86-88 are maintained (35 USC 112d) or newly applied (35 USC 112b, 35 USC 103). Response to arguments follows the 35 USC 112d.
6. This action is FINAL.
Withdrawn Rejections
The 35 USC 112b, 35 USC 112a, 35 USC 101 and 35 USC 103(a) rejections made in the previous office action is withdrawn based upon amendments to the claims.
Maintained Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claims 58,62-71,76,86-88 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of miR markers listed is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different miR position. Each miR that could be detected is itself located in a separate region of the genome and has its own structure. The nature of miR is that they are differences within a population. The only structural similarity present is that all detected positions are part of miR molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with colorectal cancer. For example, the polymorphism at position mir889 has a distinct chemical structure as compared to, for example, miR223 since the miR can only be understood within the context of the surrounding nucleotides, which are structurally dissimilar. Accordingly, while the different markers are asserted to have the property of being indicative of bladder cancer, they do not share a single structural similarity. Nor is the functionality is clear from the very nature of the miR markers.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the miRNA panel now have been amended to require comprising language (p. 10-11). This arguetmsn has been reviewed but have not been found persuasive. After review of the claims on record it is noted that although the claims are drawn to a “panel of miRNAs”, the use of “or” at the end of the comprising would encompass just one of the miRNAs listed . As such the claims can be interpreted as a panel of miRNAs that comprise any of the has-mirs (singularly or in combination) as such there issues with regard to the structure set forth above is maintained. It is noted for advanced prosecution that if the panel comprises all of the listed miRs (e.g. no “or” statement) the Markush rejection would no longer apply.
Newly Applied Claim Rejections - 35 USC § 112
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 58,62-71,76,86-88 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.
Claims 58,62-71,76,86-88 are indefinite over “a panel of miRNAs comprising has….or has-mir 656”. This phrase is unclear as the term “panel of miRNAs” appear to indicate multiple miRNAs, whereas, the “or” statement appears to indicate only one miRNA. As such it is not clear the structures that are intending to be encompassed by the language of f in claim 58.
Newly Applied Claim Rejections - 35 USC § 103
12. 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.
13. 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.
14. 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.
15. Claim(s) 58,62-68,76,86-88 is/are rejected under 35 U.S.C. 103 as being unpatentable over Haj-Ahmad et al. (US Patent Application Publication 2017/0268040 September 21, 2017) in view of Ajit et al. (US Patent Application Publication 2016/0076098 March 17, 2016).
With regard to claim 58, Haj-Ahmad et al. taches a method of isolating cell free RNA molecules from the cell free biological sample (para 99). Haj-Ahmad et al. teaches a method of reverse transcribing to cDNA (para 203). Haj-Ahmad et al. teaches a method of ligating adapters to the cDNA after transcribing (para 203). Haj-Ahmad et al. teaches amplifying and determining the sequences (para 203, 219). Haj-Ahmad et al. teaches a method of aligning and sequencing (para 218-219).
With regard to claim 62, Haj-Ahmad et al. teaches a method of enriching cDNA (para 219).
With regard to claim 63, Haj-Ahmad et al. teaches a method of preparing miRNA library before the amplifying (para 32-33).
With regard to claim 64-65, Haj-Ahmad et al. teaches ligating the RNA adapters prior to transcribing and then ligating after transcribing (para 203, 219).
With regard to claim 66, Haj-Ahmad et al. teaches a method of using a barcode indexing sequence which would be considered a specific barcode (p. 219).
With regard to claim 67, Haj-Ahmad et al. teaches a method of adapter blocking (para 203).
With regard to claim 68, Haj-Ahmad et al. teaches a method of 3’ and 5’ adapter ligation (para 203).
With regard to Claim 76, Haj-Ahmad et al. teaches a method wherein the sample is plasma (para 109).
However, Haj-Ahmad et al. does not teach aligning to a reference human transcriptome or the elected has-mir-889.
With regard to claim 58 and 87, Ajit et al. teaches a method of miRNA detection (abstract). Ajit et al. teaches methods of aligning to a human transcriptome (para 226-239) to detect has-miR-889 (see table 10).
With regard to claim 86, Ajit et al. teaches that the miRNA comprise mature miRNAs and hairpins (para 98 and 240).
With regard to claim 88, Ajit et al. teaches that the reference includes both the mature and the hairpin precursors (para 98, 239-240).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date. The ordinary artisan would be motivated to modify the method of Haj-Ahamad to detect any known miRNA region including miR889 of Ajit et al with a reasonable expectation of success of detection. As Ajit et al. teaches detection in blood samples of mRNA (para 155-201) it would be obvious to screen these markers in the method of Haj-Ahmad et al. to detect markers in cell free samples as taught by Haj-Ahmad.
15. Claim(s) 69-71 is/are rejected under 35 U.S.C. 103 as being unpatentable over Haj-Ahmad et al. (US Patent Application Publication 2017/0268040 September 21, 2017) and Ajit et al. (US Patent Application Publication 2016/0076098 March 17, 2016) as applied to claims 58,62-68,76,86-88 and in view of Mortimer et al. (US Patent Application 2019/0085406 March 21, 2019).
Haj-Ahmad et al. taches a method of isolating cell free RNA molecules from the cell free biological sample (para 99). Haj-Ahmad et al. teaches a method of reverse transcribing to cDNA (para 203). Haj-Ahmad et al. teaches a method of ligating adapters to the cDNA after transcribing (para 203). Haj-Ahmad et al. teaches amplifying and determining the sequences (para 203, 219). Haj-Ahmad et al. teaches a method of aligning and sequencing (para 218-219). Ajit et al. teaches a method of miRNA detection (abstract). Ajit et al. teaches methods of aligning to a human transcriptome (para 226-239) to detect has-miR-889 (see table 10).
However, Haj-Ahmad and Ajit et al. teaches does teach measuring cfRNA using ddPCR.
With regard to claim 69, Mortimer et al. teaches methods of measuring miRNA from cfRNA samples (para 115 and 126). Mortimer et al. teaches performing A tailing for ddPCRR and comparison to read counts (para 232-270 and 306).
With regard to claim 70, Mortimer et al. teaches a method of generating a counts table (para 243 and 270).
With regard to claims 71, Mortimer et al. teaches a method wherein the counts are based on determining abundant miRNA (para 243-272).
Therefore it would be prima facie obvious to the ordinary artisan at the time of the effective filing date to modify the method of Haj-Ahmad and Ajit et al. to measure the cfRNA of Haj-Ahmad using the ddPCR methodology of Mortimer et al.. The ordinary artisan would be motivated to use one of the finite types of PCR including ddPCR of Mortimer with a reasonable expectation of detection miRNA in cfRNA samples. These assays such as ddPCR are known assays that can be used for detection of target regions.
Conclusion
16. No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682