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 .
This action is in response to papers filed 9/05/2025.
Applicant’s election of Group I in the reply filed on 3/14/2025 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)).
Claims 1-3,5,7,9-11,14,17,21-23,25-26,28-30,33-34,36,39-40,44, 54-55 are pending. Claims 4,6,8,12-13,15-16,18-20,24,27,31-32,35,37-38,41-43,45-53 have been cancelled.
The following rejections are maintained or newly applied for newly presented Claims 54-55. Response to arguetmsn follows.
This action is FINAL.
Claim Objections
Claims 54-55 are objected to because of the following informalities: The term in claim 54 of “nt” should be spelled out to “nucleotides” for clarity. Claim 55 depends from this rejected claim. 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 54-55 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 54-55 are indefinite over the spectral identifier sequences. The claims appear to require multiple microbeads and spectral identifier sequences, however, claim 1 is drawn to a microbead and a spectral identifier sequence.
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) 1-3,5,7,9-11,14,17,21-23,25-26,28-30,33-34,36,39-40,44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shalek et al. (WO2017/161325 September 21, 2017).
With regard to claim 1, Shalek et al. teaches a method of generating an array of a plurality of single cells and microbeads (para 309, 312). Shalek et al. teaches a method of binding a capture tag to lanthanide (para 21-22). Shalek et al. teaches that another capture nucleic acid sequence binds to the target in a cell (para 309-312). However, Shalek does not teaches the lanthanide spectral signal is distinguishable from other signatures based upon the combination with the capture oligonucleotide. Shalek et al teaches that lanthanide can be attached to a oligonucleotides and used as a barcoded tag (para 21). As such differences in this tag signature would allow for a difference in the signals and allows for differential detection. Shalek et al. teaches imaging to determine spatial positions (para 132-134). Shalek et al. teaches analyzing to determine specific spatial locations (para 134). Shalek et al. teaches further amplifying and performing single cell sequencing (para 25).
With regard to claim 2, Shalek et al teaches assembling the single cell components prior to computational analysis (para 25).
With regard to claim 3, Shalek et al. teaches performing an image based assay (para 345).
With regard to claim 5, Shalek et al. teaches a method of measuring spatial and spectral at the same time (para 193-194).
With regard to claim 7, Shalek et al taches fluorescent signals (para 22).
With regard to claim 9, Shalek et al. taches single emulsion compartments that have reagents (para 309-310).
With regard to claims 10-11, Shalek et al. teaches that the beads can include other reagents such as antibodies, enzyme or other proteins (para 328).
With regard to claim 14, Shalek et al. teaches analysis of morphology (para 133).
With regard to claim 17, Shalek et al. teaches a method of lysing the single cell (para 309).
With regard to claims 21-22, Shalek et al. teaches methods wherein the target polynucleotides is mRNA (para 309).
With regard to claim 23, Shalek et al. teaches capture oligonucleotides with unique spatial barcodes (para 103 and 126).
With regard to claim 25, Shalek et al. teaches a method of creating a single cell sequencing library and therefore teaches collecting microbeads (para 312).
With regard to claim 26, Shalek et al. teaches using a step of RNA-Seq analysis (para 199).
With regard to claim 28, Shalek et al. teaches methods of further performing genotyping or methylation profiling (para 357 and 366).
With regard to claim 29, Shalek et al. teaches a method of generating an array of a plurality of single cells and microbeads (para 309, 312). Shalek et al. teaches a method of binding a capture tag to lanthanide (para 21-22). Shalek et al. teaches that another capture nucleic acid sequence binds to the target in a cell (para 309-312). However, Shalek does not teaches the lanthanide spectral signal is distinguishable from other signatures based upon the combination with the capture oligonucleotide. Shalek et al teaches that lanthanide can be attached to a oligonucleotides and used as a barcoded tag (para 21). As such differences in this tag signature would allow for a difference in the signals and allows for differential detection. Shalek et al. teaches imaging to determine spatial positions (para 132-134). Shalek et al. teaches analyzing to determine specific spatial locations (para 134). Shalek et al. teaches further amplifying and performing single cell sequencing (para 25). Shalek et al. teaches using a step of RNA-Seq analysis (para 199).
With regard to claims 30, Shalek et al. teaches that the beads can include other reagents such as antibodies, enzyme or other proteins (para 328).
With regard to claim 33, Shalek et al. teaches analyzing cell morphology (para 133).
With regard to claim 34, Shalek et al. suggests that the parameter can encompass responses to differential drug treatment (para 36)).
With regard to claim 36, Shalek et al. teaches capture oligonucleotides with unique spatial barcodes (para 103 and 126).
With regard to claim 39-40, Shalek et al. teaches an array of microwells that has a clamping slide (para 210, 301 and 303).
With regard to claim 44, Shalek et al. teaches an array generated by droplets deposited in wells of a microwell (para 307-308).
Response to Arguments
The reply traverses the rejection. A summary of the arguetmsn is provided below with response to arguments following. The reply asserts that Shalek does not teach that the barcode are described as being selected on the basis of a lanthanide spectral signature (p. 11). The reply asserts that the reference does not teach an arrangement in which a capture oligonucleotide contains a sequence that is specifically associated with the lanthanide spectral signature, rather, Shalek discusses identifying spatial locations and therefore the microbead is not tied to lanthanide spectral signature (p. 11). The reply asserts that the capture oligonucleotide and the spectral signature are not unambiguously paired (p 12). The reply asserts that the claims require a configuration to provide unambiguous assignment of both phenotypic data and sequencing date (p. 13).
These arguments have been reviewed but have not been found persuasive.
Shalek does not teaches the lanthanide spectral signal is distinguishable from other signatures based upon the combination with the capture oligonucleotide. Shalek et al teaches that lanthanide can be attached to a oligonucleotides and used as a barcoded tag (para 21). As such differences in this tag signature would allow for a difference in the signals and allows for differential detection. Shalek et al. teaches imaging to determine spatial positions (para 132-134). Shalek et al. teaches analyzing to determine specific spatial locations (para 134). Shalek et al. teaches further amplifying and performing single cell sequencing (para 25). Shalek et al. teaches using a step of RNA-Seq analysis (para 199).
With regard to the wherein clause in step b of claim 1, this is not a positive active step, but rather the intended result of having a microbead having a lanthamide spectral signature. Furhtermore, the claims only require one microbead and therefore this wherein clause of multiple microbeads does not limit the signal microbead step claimed.
Claim(s) 54-55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shalek et al. (WO2017/161325 September 21, 2017) as applied to Claims 1-3,5,7,9-11,14,17,21-23,25-26,28-30,33-34,36,39-40,44 and in view of Shum et al. (US Patent Application Publication 2017/0342465 Nov 30, 2017).
Shalek et al. teaches a method of generating an array of a plurality of single cells and microbeads (para 309, 312). Shalek et al. teaches a method of binding a capture tag to lanthanide (para 21-22). Shalek et al. teaches that another capture nucleic acid sequence binds to the target in a cell (para 309-312). However, Shalek does not teaches the lanthanide spectral signal is distinguishable from other signatures based upon the combination with the capture oligonucleotide. Shalek et al teaches that lanthanide can be attached to a oligonucleotides and used as a barcoded tag (para 21). As such differences in this tag signature would allow for a difference in the signals and allows for differential detection. Shalek et al. teaches imaging to determine spatial positions (para 132-134). Shalek et al. teaches analyzing to determine specific spatial locations (para 134). Shalek et al. teaches further amplifying and performing single cell sequencing (para 25).
Shalek et al. does not teach spectral identifier sequences with hamming distance or that it is pairing with one of at least 1000 different lanthanide spectral signatures of the microbeads.
Shum et al. teaches detection targets with error corrections. With regard to claim 54, Shum et al wherein using multiple barcodes that the Hamming distance should be at least 4 (para 23 and 33).
With regard to claim 55, Shum et al. teaches that the sue of stochastic barcodes (e.g. spectral identifier sequence) can be pairted with at least 1000 different cell labesl (para 130-136).
Therefore it would be prima facie obvious to the ordinary artisan at the time of the effective filing date to modify the method of Shalek et al. to use multiple microbeads in combination. The ordinary artisan would be motivated in order to screening a number of target positions. In order to perform the analysis, Shum et al. would be used in order to have multiple microbeads without having interference between the labels.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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