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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a method for analyzing a multivalent RNA composition, in the reply filed on 27 April 2026 is acknowledged.
Claims 37, 39, 43, 46, 47, 51, 55, 56, 58, 62, and 63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 27 April 2026.
Claim Objections
Claim 8 is objected to because of the following informalities: the claims recites LC-MS and LC-UV without first identifying what the abbreviation stands for. Appropriate correction is required.
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 11 and 16 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 11 and 16 are indefinite because it is not clear from the claim if the RNase H guide oligonucleotides are binding to both 5’ UTR (3’) regions of the different target sequences or only the first or only the second.
Claim Rejections - 35 USC § 102
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 4, and 22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Koodathingal and Zhang (WO 2019/030718 A1).
Regarding claim 1, Koodathingal and Zhang teach a method of detecting the presence of a first subject nucleic acid (claim 1) and a second subject nucleic acid (claim 10). The nucleic acid can be RNA or DNA. (Page 4, lines 17-29). The method comprises contacting a sample with a distinct query nucleic acid. (claim 1 and 10). The query nucleic acid is equivalent to an RNase H guide oligonucleotide because it guides a nuclease to the subject nucleic acid. (Page 4 line 30- page 5 line 16). The method further comprises adding a nuclease specific to the hybrid of the query nucleic acid and the subject nucleic acid under conditions to facilitate cleavage. (claims 1 and 10). The nuclease is RNase H. (claims 1 and 10). Finally, the method fractions the sample by size to determine the presence of the cleaved subject nucleic acids.
Regarding claim 2, Koodathingal and Zhang teach that each subject nucleic acid has a unique portion that differs from the other different subject nucleic acid. (Line 6, lines 24-30).
Regarding claim 4, one of the choices is that the first identifying sequence and the second identifying sequence are not isomers. Applicant has defined isomer to mean
a "sequence isomer" refers to a nucleic acid sequence that comprises the same number of each base as a reference sequence, wherein the order of bases in a sequence isomer differs from that of the reference sequence. For example, each of the RNA sequences AGUU, GUUA, and UUGA is a sequence isomer of the reference sequence UGUA.
Specification, page 50, lines 29-33. Based on this definition, a sequence that is a different length will not be an isomer. Koodathingal and Zhang teach that the first and second identifying sequences can differ by one base. (Page 6, lines 26-29). A one base difference therefore satisfies the limitations of the claim based on applicant’s definition.
Regarding claim 22, Koodathingal and Zhang teach that the subject nucleic acids differ from each other by at least one nucleotide which is the unique portion. Therefore, the subject nucleic acid can be identical except for the identifying sequence. (Page 6, lines 24-31).
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.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Koodathingal and Zhang (WO 2019/030718 A1) in view of Beverly et al. (Analytical and Bioanalytical Chemistry, 2016).
Regarding claim 1, Koodathingal and Zhang teach a method of detecting the presence of a first subject nucleic acid (claim 1) and a second subject nucleic acid (claim 10). The nucleic acid can be RNA or DNA. (Page 4, lines 17-29). The method comprises contacting a sample with a distinct query nucleic acid. (claim 1 and 10). The query nucleic acid is equivalent to an RNase H guide oligonucleotide because it guides a nuclease to the subject nucleic acid. (Page 4 line 30- page 5 line 16). The method further comprises adding a nuclease specific to the hybrid of the query nucleic acid and the subject nucleic acid under conditions to facilitate cleavage. (claims 1 and 10). The nuclease is RNase H. (claims 1 and 10). Finally, the method fractions the sample by size to determine the presence of the cleaved subject nucleic acids.
Regarding claim 2, Koodathingal and Zhang teach that each subject nucleic acid has a unique portion that differs from the other different subject nucleic acid. (Line 6, lines 24-30).
Regarding claim 8, Koodathingal and Zhang teach using chromatography to eliminate proteins and free nucleotides. Koodathingal and Zhang are interested in a method for detecting the presence of nucleic acids, and use agarose gels to determine the difference between samples. Beverly et al. teach a method of detecting different RNA species using LC-MS. Beverly et al. teach that the method allows for detection by differences in mass an retention time and does not need a radiolabel. (Page 5022). This allows for detection based on an intrinsic property that has a high resolution. (Page 5022). Therefore, one of ordinary skill in the art would use LC-MS with the method taught by Koodathingal and Zhang to identify the different cleaved RNAs without the need for a label while detecting the different RNAs with high resolution.
Regarding claim 10, Beverly et al. teach determining the specific amounts of each RNA species detected. (Table 3). One of ordinary skill in the art would understand how to create a ratio from that data.
Claims 11, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Koodathingal and Zhang (WO 2019/030718 A1) in view of Von der Mülbe et al. (WO 2016/180430 A1).
Regarding claim 1, Koodathingal and Zhang teach a method of detecting the presence of a first subject nucleic acid (claim 1) and a second subject nucleic acid (claim 10). The nucleic acid can be RNA or DNA. (Page 4, lines 17-29). The method comprises contacting a sample with a distinct query nucleic acid. (claim 1 and 10). The query nucleic acid is equivalent to an RNase H guide oligonucleotide because it guides a nuclease to the subject nucleic acid. (Page 4 line 30- page 5 line 16). The method further comprises adding a nuclease specific to the hybrid of the query nucleic acid and the subject nucleic acid under conditions to facilitate cleavage. (claims 1 and 10). The nuclease is RNase H. (claims 1 and 10). Finally, the method fractions the sample by size to determine the presence of the cleaved subject nucleic acids.
Regarding claim 2, Koodathingal and Zhang teach that each subject nucleic acid has a unique portion that differs from the other different subject nucleic acid. (Line 6, lines 24-30).
Regarding claims 11, 16, and 19, Koodathingal and Zhang teach that the query nucleic acid can be designed to be complementary to the target. Koodathingal and Zhang do not specifically teach that it is capable of hybridizing to a 5’ or 3’ UTR. Von der Mülbe et al. teach a method of producing RNAs and also teach an RNAse H assay to remove poly(A) tails from mRNAs or RNA mapping. (Page 68 lines 18-32 and section B.2.5). Von der Mülbe et al. discuss the 5’ UTR and 3’ UTR and what comprises them. (Pages 13-14). Von der Mülbe et al. discuss conserved sequences in both regions such as the Kozak sequence in the 5’ UTR. (Page 20). It would have been obvious to one of ordinary skill in the art to utilize a conserved sequence in the 5’ or 3’ UTR in the method taught by Koodathingal and Zhang because that conserved region would be cleaved RNase H, leaving the translation region of the RNA for further analysis.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MINDY G BROWN whose telephone number is (571)270-5605. The examiner can normally be reached Monday -Friday, 9:00 am - 5:00 pm EST.
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/MINDY G BROWN/Patent Examiner, Art Unit 1683
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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