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 .
Applicants Amendment
Applicant’s amendment filed 1/27/2026 has been received and entered. Claims 3 and 13 have been amended.
Claims 1-20 are pending.
Priority
This application filed 5/5/2022 is a 371 National stage filing of PCT/CN2021/096728 filed 5/28/2021 and claims benefit to foreign application CN20210447273.0 filed 4/25/2021 in China.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. See paper entered 1/27/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 3 and 13 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the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn.
The amendment to the claims to delete the limitation has addressed the basis of the rejection.
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.
Claims 1-20 stand rejected under 35 U.S.C. 103 as being unpatentable over Christy et al., Ziv et al. 1 and Ziv et al. 2.
Claims 3 and 13 have been amended to remove a Trademark limitation, otherwise the claims have not changed in scope.
Response to Applicants arguments
Applicants provide an overview of MPEP 2143.03 for evaluating every feature of the claims in evaluating obviousness. For the art, Applicants outline the method of Christy et al. and note that the resulting cDNA produced measure tertiary structure which appears different from the currently claimed invention. With respect to Ziv 1 & 2, Applicants note that they provide an enrichment step for both viral RNA and the crosslinked product which the instant claims do not require nor claim.
In response, with respect to Ziv and the steps of enrichment, it is acknowledged that the present claims do not specifically recite these enrichment steps however they are comprised within the breadth of the claims, and in part step 2 of claim 1 is effectively enriching when it is extracted. Further in Ziv et al (Dec 2020) the results clearly provide that the cross-linking was done in vivo (see 2nd column for discussion of samples analyzed) and do not require any first enrichment step as suggested in Applicants comments. The support of [0046] in the specification is acknowledged, however this guidance does not contrast or suggest that an enrichment step would be detrimental or presents a technical problem solved by the instant claims. With respect to Christy et al. it is acknowledged that the methodology is different from Ziv et al. but it is provided for the basis that a cDNA to create a library can be created with other known methodology beyond that of just Ziv et al., and further that the skilled artisan was interested in mapping the structure of higher order in RNA structures that might exist and that other forms cross-linking were also known. Applican’ts arguments have been fully considered, but not found persuasive.
Accordingly for the reasons above and of record the rejection is maintained.
Rejection of record
Independent claim 1 provides for a method of mixing an RNA virus with a cross linking agent, extracting the cross linked RNA, fragmenting it with RNase III, ligating the fragments and constructing a library of the ligated fragments. Dependent claims provide for the use of psoralen cross linking agents and specific concentrations, times and other conditions which each of the steps would be performed at. Independent claim 11 provides for the same steps with the additional step of 6) sequencing the library made through the method of claim 1 steps. As with claim 1 dependent claims provide for the use of psoralen cross linking agents and specific concentrations, times and other conditions which each of the steps would be performed at.
Both Ziv et al1 and Zive et al2 provide for short and long range mapping of RNA-RNA interactions for SARS RNA virus. The method is named COMRADES and requires adding a cross linking agent to a viruses, fragmenting and ligating the RNA from the virus, see for example illustration in Figure 1 of Ziv et al 2:
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The cross linker Ziv et al use is a psoralen derivative and perform the cross linking in vivo and provide for a product which is processed into a template and subsequently sequenced with high throughput sequencing (page 1068). Christy et al is provided as another method termed SHAPE JuMP, which provides for analyzing cross linked RNA and provide analysis of enzymes which can be used to create and sequence template formed from the steps. Christy et al. use light activated psoralen cross liners to investigate RNA structures by adding a cross linking agent to a RNA containing samples, fragmenting and ligating the RNA for further analysis by sequencing to a minimum read depth and analyzing the reads.
While each Christy et al., Ziv et al. 1 and Ziv et al. 2 provide for the specific optimized conditions relative to the samples they are analyzing, they do not provide an overview for the specific conditions required of the dependent claims as encompassed by the independent claims, however given the general characterization of enzyme activity and steps by Christy et al it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to substitute and provide conditions consistent with the sample and specific cross linking agents being used. One having ordinary skill in the art would have been motivated to provide known and appropriate buffers and reaction conditions for the broad range of different sample sources and possible psoralen cross linkers, enzyme fragmentation and ligation conditions encompassed by the claims. There would have been a reasonable expectation of success given the results of Christy et al., Ziv et al. 1 and Ziv et al. 2 to provide the necessary conditions which would result in cross linked RNA structures that could be sequenced and interpreted to give 2D and 3D structural information about RNA in viruses as analyzed in Ziv et al. 1 and Ziv et al. 2.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is 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 Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
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