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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/260,323 on 08/17/2021.
All claims are given the priority date of 08/17/2021.
Application Status
Receipt is acknowledged of amendment, filed 01/16/2026. Claims 1-29 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group I, drawn to claims 1-21, 28 and 29, as well as SEQ ID NO: 49 for the specific Group II intron reverse transcriptase claimed in the reply filed on 01/16/2026 is acknowledged.
The previous election requirement for the specific Group II intron reverse transcriptase claimed has been withdrawn.
Claims 22-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/16/2026.
Claims 1-21, 28 and 29 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 01/13/2023 and 07/19/2024 have been received and all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. Specifically, Page 49 includes an embedded hyperlink. See MPEP § 608.01.
Claim Objections
Claim 2 contains periods within the claim. MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.” 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.
Claim 17 is 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 17 contains the trademark/trade name Deep Vent, Vent and KOD. 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 a DNA polymerase and, accordingly, the identification/description is indefinite.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 1-21, 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Armstrong et al (US 2018/0148717 A1) in view of Lambowitz et al (WO 2010/102085 A2).
Regarding claims 1 and 3-5, Armstrong teaches that for replicating the information stored in the nucleotide sequence of a circular RNA molecule by converting the RNA molecule into a circular DNA molecule wherein generating and amplifying circular DNA molecules from their circular RNA counterparts, rare or previously unknown circular RNAs are identified [0070-71]. Armstrong teaches a method of circRNA amplification by first combining an RNA template with one or more DNA primers and a mix of dNTPs for extending the primers for creating circular DNA [0082, 0093-0094 and 0104]. Armstrong teaches that after priming, a Protoscript II reverse transcriptase is added [0093-0094 and 0104] in order to produce concatemeric first strand cDNA molecules by rolling circle reverse transcription of the circRNA [0061-0068]. Armstrong teaches amplification of the circular DNA copy molecules by an isothermal polymerase (φ29) and a magnetic bead DNA cleanup step [0106]. Armstrong teaches the samples treated with the current method exhibited greater than 10-fold more circular RNA backsplice signals [0107].
Armstrong does not teach the Group II intron reverse transcriptase.
Lambowitz teaches the group II intron RT assists RNA splicing by stabilizing the
catalytically active RNA structure and then remains bound to the excised intron RNA in a
ribonucleoprotein (RNP) that promotes intron mobility by a process termed "retrohoming” wherein retrohoming occurs by a mechanism in which the excised intron RNA in the RNPs inserts directly into a DNA target site and is reverse transcribed by the RT and during retrohoming, in which the group II intron facilitates targeting of the intron to appropriate DNA sequences, the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary
structures; thus, group II intron RTs must have high processivity and fidelity in order to
carry out their biological function [0053]. Lambowitz teaches Group II intron-derived RTs also lack RNase H activity, which can be beneficial because RNase H specifically degrades the RNA of RNA:DNA hybrids, which allows any RNA to be copied only once and can lead to reduced yields of full-length cDNA [0053].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Armstrong to include the Group II intron reverse transcriptase as taught by Lambowitz because Armstrong teaches it is within the ordinary skill in the art to use a method for identifying circRNA in a sample by combining a sample comprising circRNA with a reverse transcriptase and dNTPs in a reaction mixture for producing, by rolling circle reverse transcription of the circRNA, a reaction product comprising concatemeric first cDNA strand molecule, and characterizing the concatemeric first strand cDNA to identify the circRNA and Lambowitz teaches Group II intron-derived RTs also lack RNase H activity leading to less degradation of RNA:DNA hybrids resulting in higher full-length cDNA yields as well as the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary structures.
One would have been motivated to make such a modification in order to receive the expected benefit of higher cDNA yields as well as more stable and compact secondary and tertiary structures of the cDNA as taught by Lambowitz.
Regarding claims 2 and 16-18, Armstrong teaches amplification of the circular DNA copy molecules by an isothermal polymerase (φ29) and a magnetic bead DNA cleanup step [0106]. Armstrong teaches the samples treated with the current method exhibited greater than 10-fold more circular RNA backsplice signals [0107].
Regarding claim 6, Armstrong teaches a method of circRNA amplification by first combining an RNA template with one or more DNA primers and a mix of dNTPs for extending the primers for creating circular DNA [0082, 0093-0094 and 0104].
Regarding claims 7-10 and 12, Armstrong teaches rolling circle replication of the circularized first strand cDNA molecules results in long DNA strands containing tandem repeats of the cDNA sequence, thus amplifying multiple cassette copies of the original circular RNA sequence [0060]. Armstrong teaches that the rolling circle cDNA replication of circular GFP RNA control wherein the first strand cDNA concatemer is 3x length of the original circRNA (~812 nt in length) with ~2400 nt in length which would comprise 3 complementary copies of the circRNA (Page 15, Fig. 9; [0027]). Armstrong teaches the long-read sequences of the cDNA sequencing and amplification purposes since fewer reads need to be generated for the same level of sensitivity of circular RNA detection when assaying withnext-generation sequencing machines (ex. Illumin, Pacific Biosciences) [0051]. Armstrong teaches size separating the concatemeric first strand cDNA from non-concatemeric cDNA [0118-0120].
Regarding claim 11, Armstrong teaches the use of RNase R (a 3’ to 5’ RNase) and RNase H (a 5’ to 3’ RNase) for enriching the circRNA in the total RNA by degrading linear RNA [0076 and 0094].
Regarding claim 13, Armstrong does not teach wherein the sample contains circRNA and (a) does not include RNA depletion with an RNase.
Lambowitz teaches Group II intron-derived RTs also lack RNase H activity,
which can be beneficial because RNase H specifically degrades the RNA of RNA: DNA
hybrids, which allows any RNA to be copied only once and can lead to reduced yields of full
length cDNA [0053].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Armstrong to include the sample contains circRNA and does not include RNA depletion with an RNase as taught by Lambowitz because Armstrong teaches it is within the ordinary skill in the art to use a method for identifying circRNA in a sample by combining a sample comprising circRNA with a reverse transcriptase and dNTPs in a reaction mixture for producing, by rolling circle reverse transcription of the circRNA, a reaction product comprising concatemeric first cDNA strand molecule, and characterizing the concatemeric first strand cDNA to identify the circRNA and Lambowitz teaches Group II intron-derived RTs also lack RNase H activity leading to less degradation of RNA:DNA hybrids resulting in higher full-length cDNA yields as well as the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary structures.
One would have been motivated to make such a modification in order to receive the expected benefit of higher cDNA yields as well as more stable and compact secondary and tertiary structures of the cDNA as taught by Lambowitz.
Regarding claims 14 and 15, Armstrong teaches the circRNA, DNA primers and reverse transcriptase were incubated for 10 min at 25° C., followed by 50 minutes at 42° C [0104].
Regarding claim 19, Armstrong teaches in order to digest and remove single-stranded linear cDNA (leaving only cccDNA), tl1e ligation products can be treated with an exonuclease that digests linear DNA, such as Exonuclease I or T5 Exonuclease [0087].
Regarding claim 20, Armstrong teaches rolling circle replication of the circularized first strand cDNA molecules results in long DNA strands containing tandem repeats of the cDNA sequence, thus amplifying multiple cassette copies of the original circular RNA sequence [0060]. Armstrong teaches amplification of a covalently closed circular DNA template with φ29 polymerase is expected to yield high molecular weight DNA products comprised of concatemers containing tandem repeats representing the original circular GFP control RNA template [0118].
Regarding claim 21, Armstrong does not teach wherein the amount of cDNA copies of the circRNA in a concatemer provides at least 2-fold higher concentration of copies of the circRNA than can be obtained using a retroviral reverse transcriptase.
Lambowitz teaches unlike retroviral RTs, group II intron RTs lack an RNase H domain which can be beneficial because RNase H specifically degrades the RNA of RNA: DNA
hybrids, which allows any RNA to be copied only once and can lead to reduced yields of full
length cDNA [0052-0053]. Lambowitz teaches comparing the Group II intron RT (Tel4c RT) versus the MMLV RT (Superscript RT) such as, the 188-257 amplicon primer/probe set, 972,815 copies were detected with the MalE-RF-4c Tel4c RT versus 64,456 copies with Superscript RT at 6cPC (~15-fold difference) [0096].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Armstrong to include the Group II intron reverse transcriptase with a higher concentration as compared to concentration produced from retroviral reverse transcriptase as taught by Lambowitz because Armstrong teaches it is within the ordinary skill in the art to use a method for identifying circRNA in a sample by combining a sample comprising circRNA with a reverse transcriptase (Protoscript II reverse transcriptase) and dNTPs in a reaction mixture for producing, by rolling circle reverse transcription of the circRNA, a reaction product comprising concatemeric first cDNA strand molecule, and characterizing the concatemeric first strand cDNA to identify the circRNA and Lambowitz teaches Group II intron-derived RTs also lack RNase H activity leading to less degradation of RNA:DNA hybrids resulting in higher full-length cDNA yields as well as the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary structures.
One would have been motivated to make such a modification in order to receive the expected benefit of higher cDNA yields as well as more stable and compact secondary and tertiary structures of the cDNA as taught by Lambowitz.
Regarding claims 28 and 29, Armstrong teaches that for replicating the information stored in the nucleotide sequence of a circular RNA molecule by converting the RNA molecule into a circular DNA molecule wherein generating and amplifying circular DNA molecules from their circular RNA counterparts, rare or previously unknown circular RNAs are identified [0070-71]. Armstrong teaches a method of circRNA amplification by first combining an RNA template with one or more DNA primers and a mix of dNTPs for extending the primers for creating circular DNA [0082, 0093-0094 and 0104]. Armstrong teaches that after priming, a Protoscript II reverse transcriptase is added [0093-0094 and 0104] in order to produce concatemeric first strand cDNA molecules by rolling circle reverse transcription of the circRNA [0061-0068]. Armstrong teaches amplification of the circular DNA copy molecules by an isothermal polymerase (φ29) and a magnetic bead DNA cleanup step [0106]. Armstrong teaches the samples treated with the current method exhibited greater than 10-fold more circular RNA backsplice signals [0107].
Armstrong does not teach the Group II intron reverse transcriptase.
Lambowitz teaches the group II intron RT assists RNA splicing by stabilizing the
catalytically active RNA structure and then remains bound to the excised intron RNA in a
ribonucleoprotein (RNP) that promotes intron mobility by a process termed "retrohoming” wherein retrohoming occurs by a mechanism in which the excised intron RNA in the RNPs inserts directly into a DNA target site and is reverse transcribed by the RT and during retrohoming, in which the group II intron facilitates targeting of the intron to appropriate DNA sequences, the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary
structures; thus, group II intron RTs must have high processivity and fidelity in order to
carry out their biological function [0053]. Lambowitz teaches Group II intron-derived RTs also lack RNase H activity, which can be beneficial because RNase H specifically degrades the RNA of RNA:DNA hybrids, which allows any RNA to be copied only once and can lead to reduced yields of full-length cDNA [0053].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Armstrong to include the Group II intron reverse transcriptase as taught by Lambowitz because Armstrong teaches it is within the ordinary skill in the art to use a method for identifying circRNA in a sample by combining a sample comprising circRNA with a reverse transcriptase and dNTPs in a reaction mixture for producing, by rolling circle reverse transcription of the circRNA, a reaction product comprising concatemeric first cDNA strand molecule, and characterizing the concatemeric first strand cDNA to identify the circRNA and Lambowitz teaches Group II intron-derived RTs also lack RNase H activity leading to less degradation of RNA:DNA hybrids resulting in higher full-length cDNA yields as well as the group II intron RT must produce an accurate cDNA copy of the intron RNA, which is typically 2-2.5 kb long and folds into highly stable and compact secondary and tertiary structures.
One would have been motivated to make such a modification in order to receive the expected benefit of higher cDNA yields as well as more stable and compact secondary and tertiary structures of the cDNA as taught by Lambowitz.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637