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 .
DETAILED ACTION
1. The applicant’s response to the office action filed on March 03, 2026 is acknowledged.
Status of the Application
2. Claims 19-24, 26, 30-31 are pending under examination. Claims 33-43 were previously withdrawn from further consideration as being drawn to non-elected group. Claims 1-8, 25, 27-29 and 32 were canceled. The Applicant’s arguments were fully considered and found unpersuasive for the following reasons.
Objection to the Specification-Maintained
3. The disclosure is objected to because of the following informalities:
The use of the term (Alexa fluor 647; Alexa fluor 405, Alexa fluor 488, CY5, CY7, Iowa black, dabsyl, FITC, DAPI in para 0183-0184), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. In the specification trademarks are not followed by generic names. Appropriate correction is required.
Response to Arguments:
The objection to the specification has been maintained because the paragraphs 183-184 recite trademarks that are not followed by generic names or chemical name. The arguments were found unpersuasive because fluorophores or fluorescent label do not represent generic names for the disclosed labels in para 0183-0184.
Claim Rejections - 35 USC § 112-Maintained
4. 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 31 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 31 recites ‘(or amplified cDNA sequences)’ and ‘(or further amplified cDNA product)’. The limitations enclosed in parenthesis are unclear and indefinite because it is unclear whether the
limitation(s) in the parenthesis are part of the claimed invention or indicate as an example.
Response to Arguments:
With reference to the rejection of claim 31 under 35 USC 112(b), the Applicant’s arguments and the amendment have been fully considered and found persuasive in-part. The rejection has been maintained because the amendment did not address the limitations in the parentheses (or further amplified cDNA product).
Claim Rejections - 35 USC § 103-Maintained
5. 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.
A. Claims 19-23, 26 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al. (WO 2019/133874) in view of Goldfless et al. (WO 2018/218222).
Bennett et al. teach a method of claim 19, providing one or more barcoded cDNA sequences from a biological cell, comprising: providing the biological cell within a chamber (a well or an enclosure of a microfluidic device or sequestration pen located within an enclosure of a microfluidic device) (para 0005-0011, 0111-0116) ; providing a capture object in the chamber, the capture object comprising a label, a plurality of first oligonucleotides, and a plurality of second oligonucleotides, wherein each first
oligonucleotide of the plurality comprises a barcode sequence, wherein each second oligonucleotide of the plurality comprises a capture sequence (para 0005-0011, 0111-0116, 00199, 0134-0135, 00151-0165, 00369, 00372-00375, 00401-00407, 0412-00419, 0536: indicating first capture and second capture object comprising oligonucleotide sequences, a first set of capture oligonucleotides comprise barcode and capture sequence and a second set of capture oligonucleotides comprise capture sequences), lysing the biological cell and allowing RNA released therefrom the lysed biological cell to be captured by the capture sequences of the plurality of second oligonucleotides, thereby forming captured RNA (para 0011, 0111-0116, 00480-0482, 00369, 00372-00375, 00401-00407, 00412-00419, 0536); and reverse transcribing the captured RNA, thereby producing one or more barcoded cDNA sequences, each
comprising an oligonucleotide sequence complementary to a corresponding one of the captured RNA and covalently linked to the reverse complement of the barcode sequence of the first oligonucleotide (para 0005-0011, 0111-0116).
With reference to claim 20, Bennett et al. teach that the chamber comprises a microwell or a sequestration pen of a microfluidic device (para 0005-0012, 0111).
With reference to claim 21, Bennett et al. teach that a single capture object is provided in the chamber (para 0196-0197).
With reference to claim 22, Bennett et al. teach that the capture sequence binds to, and thereby, captures RNA and primes transcription from the captured RNA (para00154, 00162, 00368).
With reference to claim 23, 26, Bennett et al. teach that the method further comprising identifying the barcode sequence of the plurality of first oligonucleotides while the capture object is located within the chamber and the ratio of the second oligonucleotide to the first oligonucleotide on the capture object ranges from 1:10 to 10:1 (para 0058, 00115, 00199-0206, 0130, 0405).
With reference to claim 30, Bennett et al. teach that the method further comprising exporting the capture object from the chamber (para 0022, 00369, 0408-0409, 0480-0482).
With reference to claim 31, Bennett et al. teach that providing one or more barcoded cDNA sequences comprises providing a plurality of barcoded cDNA sequences, each barcoded cDNA sequence of the plurality encoding a protein of interest, corresponding to any one of a plurality of different proteins, linked to a corresponding reverse complement barcode sequence; and the method further comprising: selectively amplifying the plurality of barcoded cDNA sequences using a barcode-specific forward primer and a reverse primer specific to the protein of interest to produce an amplified cDNA product encoding the protein of interest or a fragment thereof; annealing a 5’ end of the amplified cDNA product to a 5’ corresponding end of a DNA fragment for transcriptionally-active PCR (TAP) to produce an annealed TAP product; and amplifying the annealed TAP product using a TAP adapter primer (para 00456, 00461).
However, Bennett et al. did not teach barcode capture oligonucleotide comprising three consecutive guanines at 3’ end of the first oligonucleotide.
Goldfless et al. teach a method for transcriptome analysis of a nucleic acid sample comprising producing a polynucleotide library from a cell or cells using of barcode oligonucleotides comprising three or more non-templated nucleotides which include three consecutive guanines at 3’ end of the oligonucleotide which acts as a template switch oligo in reverse transcription (para 0035-0039) or one or more ribonucleotides which include uridine (para 0274) and overlap extension PCR with barcode primer and an oligo dT or target-specific primer to form full-length products (para 441, 0445).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the invention to combine the method of Bennett et al. with the barcode oligonucleotide comprising three consecutive guanines at 3’-end as taught by Goldfless et al. to develop an improved method for producing barcoded cDNAs. The ordinary person skilled in the art would have motivated to combine the method as taught by Bennett et al. with the barcode oligonucleotides comprising three consecutive guanines at 3’-end as taught by Goldfless et al. and have a reasonable expectation of success that the combination would result in improved method for producing barcoded cDNAs because Goldfless et al. explicitly taught barcode oligonucleotide comprises a barcode sequence and three consecutive guanines at 3’ end of the oligonucleotide which acts as a template switch oligo in reverse transcription (para 0036-0039) and such a modification of the method is considered obvious over the prior art. Further, it would be obvious to further modify the method with one or more ribonucleotides and overlap extension PCR to produce full-length amplification products (para 0274, 0441, 0445) and such a modification of the method is considered obvious over the cited prior art.
B. Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Bennett et al. (WO 2019/133874) in view of Goldfless et al. (WO 2018/218222) as applied to claims above, and further in view of Belgrader et al. (US 2018/0179591).
Bennett et al. and Goldfless et al. teach a method for producing barcoded cDNA as discussed above in section 6A. However, Bennett et al. and Goldfless et al. did not teach an oligonucleotide comprises one or more uridine nucleotides 5’ to the barcode sequence and an enzyme that cleaves a sequence containing one or more uridine nucleotides.
Belgrader et al. teach barcoding nucleic acids using oligonucleotides comprising barcodes with one or more uridines and reverse transcribing captured RNA in the presence of an enzyme that cleaves a sequence comprising one or more uridine nucleotides (para 0149, 0188, 0214-0216).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the invention to combine the method of Bennett et al. and Goldfless et al. with the barcode oligonucleotide comprising one or more uridines and an enzyme that cleaves a sequence comprising uridine nucleotide as taught by Belgrader et al. to develop an improved method for producing barcoded cDNAs. The ordinary person skilled in the art would have motivated to combine the method as taught by Bennett et al. and Goldfless et al. with the barcode oligonucleotides comprising one or more uridine nucleotides as taught by Belgrader et al. and have a reasonable expectation of success that the combination would result in improved method for producing barcoded cDNAs because explicitly taught barcode oligonucleotide comprising one or more uridine nucleotides and an enzyme that cleaves the sequence comprising uridine nucleotide during reverse transcription that generates single strand breaks for downstream processing (para 0149) and such a modification of the method is
considered obvious over the prior art.
Response to Arguments:
A. With reference to the rejection of claims under 35 USC 103 as being obvious over Bennett et al. in view of Goldfless et al., the Applicant’s arguments directed to some portions of the disclosure of Bennett et al. were fully considered and found unpersuasive. With reference to no teaching of first and second oligonucleotides, wherein each first oligonucleotide of the plurality comprises a barcode and the second oligonucleotide of the plurality comprises a capture sequence, the Applicant’s arguments were found unpersuasive because the examiner cited portions clearly teach capture object comprise plurality of first and second capture oligonucleotides, wherein, each capture oligonucleotide comprises a barcode sequence and priming sequence and a capture sequence for capturing RNA (para 0009, 00132-00135, 00151). With reference to the Applicant’s arguments drawn to a portion of the Bennett et al. disclosure (fig.9) in comparison to a Fig. 7 of the instant specification, the arguments were fully considered and the arguments do not commensurate with the scope of the claims, which require a capture object comprising plurality of a first oligonucleotides and a plurality of and a second oligonucleotides, wherein a first oligonucleotide of the plurality comprises a barcode and a second oligonucleotide of the plurality comprises a capture sequence. As discussed in the rejection, it would be obvious to modify the method of Bennett et al. with a barcode oligonucleotide comprising three consecutive guanines as taught by Goldfless et al. to improve the method in analyzing a biological cell. For all the above, the rejection has been maintained.
B. With reference to the rejection of claim 24 under 35 USC 103 as being obvious over Bennett et al. in view of Goldfless et al. and further in view of Belgrader et al., the Applicant’s arguments were found unpersuasive. As discussed above, Bennett et al. in view of Goldfless teach the method of claim 19 and as discussed in the rejection it would be obvious to further modify the method one or more uridines as taught by Belgrader et al. to improve the method. For all the above the rejection has been maintained.
Conclusion
No claims are allowable.
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 SURYAPRABHA CHUNDURU whose telephone number is (571)272-0783. The examiner can normally be reached 8.00am-4.30pm.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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