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 in the reply filed on 5/19/2026 is acknowledged.
Claims 1-2, 4, 6,8,11,18,21,37,39,41,44-46,50-51,57,117,153,176 are pending.
CLiams 117,153,176 are withdrawn as being drawn to a nonelected invention.
Claims 3,5,7,9-10,12-17,19-20,22-36,38,40,42,43,47-49,52-56,58-116,118-152,154-175 and 177-211 have been cancelled.
An action on the merits for Claims 1-2, 4, 6,8,11,18,21,37,39,41,44-46,50-51,57 is set forth below,
Claim Objections
Claim 18 is objected to because of the following informalities: The claims encompass brackets which are used in claims to indicate deletions. As such the claims should be amended to exclude the use of brackets so as it is not confusing which parts of claims are amended. 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 1-2, 4, 6,8,11,18,21,37,39,41,44-46,50-51,57 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 1-2, 4, 6,8,11,18,21,37,39,41,44-46,50-51,57 are indefinite over step ii of claim 1. Claim 1 recites the limitation "the ribosome" in step ii. There is insufficient antecedent basis for this limitation in the claim. The claims do not recite ribosome and therefore it is suggested to modify the method so that it is clear that it is “a ribosome”.
Claims 1-2, 4, 6,8,11,18,21,37,39,41,44-46,50-51,57 are indefinite over step of claim 1. In particular the step appears to require determinations of locations. However, the steps do not require any steps to provide determination of location including steps for spatial analysis. Further, Claim 57 is indefinite as the step requires that spatial information is not disrupted, however, the steps do not require any analysis towards spatial information.
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.
Claim(s) 1,2,4,8,11, 18,21,37,39,41,44,45,50,51,57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jarvius et al. (US 2016/0257991 September 8, 2016) in view of Frenz et al (US Patent Application Publication 2020/0277664 September 3, 2020).
With regard to claim 1, Jarvius et al. teaches profiling RNA by contacting cell with sets of probes, ligating a first probe together end to end to produce oligonucleotide, performing RCA and sequencing including the recited three probes (para 35 and 134-136). Jarvius et al teaches that the probe can comprise a barcode (para 35 and 134-136). Jarvis et al. teaches embedding on polymeric matrices (para 123-126). However, Jarvius does not teach that the third probe recognizes ribosome.
With regard to claim 18, and 21 Jarvis suggest that the first probe that comprise portions complementary to a second and third probe, RNA of interest and a barcode (tag) (para 36-40, figures 1-2).
With regard to claim 1, Frenz et al. teaches methods of sequencing and spatial analysis (abstract). Frenz et al. teaches RCA such that the probes can selectively hybridize to ribosome RNA (rRNA) (para 905 and 928-935).
With regard to claim 2, Frenz et al. teaches RCA such that the probes can selectively hybridize to ribosome RNA (rRNA) (para 905 and 928-935).
With regard to claims 4, and 8, Frenz et al. teaches detection of antibodies and 18srRNA (para 1096 and 448-458).
With regard to claim 11, Frenz et al. teaches a polymerization blocker (para 339, 357).
With regard to claim 37,39, Frenz et al. teaches multiple cells simultaneously of different cell types (para 1355).
With regard to claim 41, Frenz et al. teaches use of intact tissue (para 4).
With regard to claim 44-45, Frenz et al. teaches that up to 2000 optical barcodes can be used simultaneously (para 3-4).
With regard to claim 50-51, Frenz et al. teaches a method wherein there are amine modified nucleotides incorporated and reacting to the matrix (para 602). Frenz et al. teaches that these can be n-hydroxysuccinimide (para 602, 636).
With regard to claim 57, Frenz et al teaches not disrupting spatial information (para 1149).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Jarvius to use a known RNA (rRNA) in the RCA method of Jarvius. The ordinary artisan would be motivated as Frenz et al. teaches ribosomal RNA ca be detected using probes in an RCA method assay.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jarvius et al. (US 2016/0257991 September 8, 2016) and Frenz et al (US Patent Application Publication 2020/0277664 September 3, 2020) as applied to claims 1,2,4,8,11, 18,21,37,39,41,44,45,50,51,57 in view of Zhang et al. (2017/0175202 June 22, 2017).
Jarvius et al. teaches profiling RNA by contacting cell with sets of probes, ligating a first probe together end to end to produce oligonucleotide, performing RCA and sequencing including the recited three probes (para 35 and 134-136). Jarvius et al teaches that the probe can comprise a barcode (para 35 and 134-136). Jarvis et al. teaches embedding on polymeric matrices (para 123-126). Frenz et al. teaches methods of sequencing and spatial analysis (abstract). Frenz et al. teaches RCA such that the probes can selectively hybridize to ribosome RNA (rRNA) (para 905 and 928-935).
However, Jarvius and Frenz do not teach the recited antibody,.
With regard to claim 6, Zhang et al. teaches that in assays such as RCA (para 80) that antibodies included RPS3 can be used in the hybridization methods (para 123).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Jarvius et al. and Frenz et al to include the method of using particular antibodies including the RPS3 as taught by Zhang et al. The ordinary artisan would have a reasonable expectation of success as RPS3 is known in the prior art of Zhang et al and therefore a probe can be designed using the method of Jarvius and Frenz. As the claims only require sequencing to determine the identity and location of an RNA of interest in the cell, any portion of a known antibody can be used in the profiling method.
Claim(s) 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jarvius et al. (US 2016/0257991 September 8, 2016) and Frenz et al (US Patent Application Publication 2020/0277664 September 3, 2020) as applied to claims 1,2,4,8,11, 18,21,37,39,41,44,45,50,51,57 in view of Wang et al. (US Patent Application Publication 2021/0164039 publication date 4/4/2019).
Jarvius et al. teaches profiling RNA by contacting cell with sets of probes, ligating a first probe together end to end to produce oligonucleotide, performing RCA and sequencing including the recited three probes (para 35 and 134-136). Jarvius et al teaches that the probe can comprise a barcode (para 35 and 134-136). Jarvis et al. teaches embedding on polymeric matrices (para 123-126). Frenz et al. teaches methods of sequencing and spatial analysis (abstract). Frenz et al. teaches RCA such that the probes can selectively hybridize to ribosome RNA (rRNA) (para 905 and 928-935).
However, Jarvius and Frenz do not teach the recited SEDAL.
With regard to claim 46, Wang et al. teaches methods of using SEDAL with RCA in improved sequencing with error reduction (para 47-48).
Therefore it would be prima facie obvious to one of ordinary skill at the time of the effective filing date to modify the method of Jarvius and Frenz to further perform SEDAL. The ordinary artisan would be motivated to use such methodology with RCA to improve the sequencing by reducing errors (para 4748).
Conclusion
No claims are allowed.
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
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