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 .
Applicant cancels claims 4 and 8. Applicant newly adds claims 12-17. Claims 1-3, 5-7, 9-17 are currently pending and under examination.
Any objection or rejection of record in the previous Office Action, which is not addressed
in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This
action is Final.
Information Disclosure Statement
The Information Disclosure Statements filed April 02, 2026 has been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5-7 and 9-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre- AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection, necessitated by Applicants’ amendments.
The instant specification, as originally filed does not provide support for the invention as now claimed in independent claim 1: “…wherein no more than 0.9% of the total cDNA is reverse transcribed from ribosomal RNA (rRNA) of the cell”. The specification does not provide sufficient blaze marks, or direction for the instant methods encompassing the above-mentioned limitations, as currently recited.
Specifically, the specification does not disclose “no more than 0.9% of the total cDNA is reverse transcribed from ribosomal RNA (rRNA) of the cell”. While the specification does disclose rRNA UMI percentage of 0.9%, the specification does not disclose that no more than 0.9% of the total cDNA is reverse transcribed from ribosomal RNA (rRNA) of the cell. It is noted that the claims, as presently written, encompass no more than 0.9% of the total cDNA is reverse transcribed from ribosomal RNA (rRNA) of the cell.
Thus, the instant claims now recite limitations which were not disclosed in the specification as-filed, and now change the scope of the instant disclosure as-filed. Such limitations recited in the present claims, which did not appear in either the instant specification, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. § 112.
Claims 2-3, 5-7 and 9-17 depend on claim 1 and are therefore included in this rejection.
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 3 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. This is a new rejection as necessitated by amendments.
Claim 3 recites the limitation "the 3’ end" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-7, and 9-17 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Bibillo et al. (U.S. Patent Application Publication US 2019/0071711 A1, published March 07, 2019). This is a new rejection as necessitated by amendments.
Regarding claim 1, Bibillo teaches Whole cell transcriptome analysis (Page 1, [0007], Page 25, [0202], Page 76, [0439]). Bibillo teaches methods and systems for amplifying and analyzing nucleic acids including non-coding RNAs and cDNA reverse transcribed from rRNA as well as lncRNA (Pages 1-2, [0007]-[0014]). Bibillo teaches adding a tag sequence on the 3’ end of a rRNA of cell to provide a tagged RNA (Page 68, [0356], Page 41, [0221]-[0222], Page 55, [0293]-[0294], Page 53, [0286]-[0288], Example 17 and Table 16). Bibillo teaches capturing the tagged RNA with a primer that recognizes the tag sequence (Page 1, [0009], Pages 1-2, [0014], Page 2, [0021], Page 6, [0090], Pages 6-7, [0093], Page 8, [0112], Page 14, [0150], Page 19, [0169], Page 41, [0221]-[0222], Page 50, [0267]-[0268] and Page 81, [0536]-[0537]). Bibillo teaches the primer comprises a unique molecular index (UMI) sequence for quantifying different RNA molecules of the cell (Page 1,[0007]-[0009], Pages 1-2, [0014], Page 2, [0021], Page 6, [0090], Pages 6-7, [0093], Page 8, [0112], Page 14, [0150], Page 19, [0169], Page 25, [0202] Page 41, [0221]-[0222], Page 50, [0265]-[0268], Page 58, [0321] and Page 81, [0536]-[0537]). Bibillo teaches reverse transcribing the tagged RNA to provide a complementary deoxyribonucleic acid (cDNA) (Page 4, [0053]-[0054], Page 8, [0106], Page 9, [0117], Page 19, [0168]). Bibillo teaches that it is often desirable to separate mRNA from rRNA because rRNA can adversely affect the quantitative analysis of mRNA (Page 12, [0144]). Bibillo teaches a complete depletion comprises decreasing all of the rRNA in the sample (i.e., less than 0.9% of the starting sample is rRNA, therefore less than 0.9% of the total cDNA can be reverse transcribed from rRNA; Page 12, [0144]). Bibillo teaches analyzing the cDNA at single cell level (Page 1, [0007], Page 4, [0053]-[0054], Page 23, [0187] and Page 25, [0202]).
Regarding claim 2, Bibillo teaches the RNA is non-coding RNA (Page 1, [0014], Page 6, [0086], Page 7, [0098], Page 12, [0143] and Page 57, [0307]).
Regarding claim 3, Bibillo teaches the primer sequence comprises a sequence that acts as cell barcode that identifies the cell (Page 1,[0007]-[0009], Pages 1-2, [0014], Page 2, [0021], Page 6, [0090], Pages 6-7, [0093], Page 8, [0112], Page 14, [0150]-[0151], Page 19, [0169], Page 25, [0202] Page 41, [0221]-[0222], Page 50, [0265]-[0268], Page 58, [0321] and Page 81, [0536]-[0537]). Bibillo teaches a specific sequence that can be used to prime the reverse transcription of the tagged RNA (Page 1,[0007]-[0009], Pages 1-2, [0014], Page 2, [0021], Page 6, [0090], Pages 6-7, [0093], Page 8, [0112], Page 14, [0150]-[0152], Page 15, [0155], Page 19, [0168]-[0169], Page 25, [0202] Page 41, [0221]-[0222], Page 50, [0265]-[0268], Page 58, [0321] and Page 81, [0536]-[0537]).
Regarding claim 5, Bibillo teaches the tag sequence is added using an enzyme (Page 6, [0086], Page 68, [0356] and Table 16).
Regarding claim 6, Bibillo teaches the tag sequence is added chemically (Page 6, [0086], Page 68, [0356] and Table 16).
Regarding claim 7, Bibillo teaches the enzyme is a Poly(A) Polymerase (Page 6, [0086], Page 68, [0356] and Table 16).
Regarding claim 9, Bibillo teaches the enzyme is a ligase (Page 13, [0149] and Page 71, [0368]).
Regarding claim 10, Bibillo teaches the analyzing is sequencing (Page 1, [0016], Page 3, [0029] and Page 54, [0288]-[0289]).
Regarding claim 11, Bibillo teaches a product or kit comprising reagents for performing the process as described in Claim 1 (see Claim 1 above; Page 8, [0106], Page 11, [0138], Page 24, [0194]-[0195], Page 46, [0246] and Page 52, [0280]—Page 53, [0285]).
Regarding claim 12, Bibillo teaches at least 3.6% of total UMIs detected in (d) corresponds to long non-coding RNA (lncRNA) of the cell (Page 53, [0286]—Page 54, [0291]).
Regarding claim 13, Bibillo teaches the tag sequence comprises a poly-A tag (Pages 6-7, [0093], Page 53, [0286] and Example 17).
Regarding claim 14, Bibillo teaches amplifying the cDNA to obtain amplified cDNAs (Page 1, [0024] and Page 5, [0081]).
Regarding claim 15, Bibillo teaches analyzing the amplified cDNA (Abstract, Page 1, [0007] and Page 4, [0052]-[0054]).
Regarding claim 16, Bibillo teaches the primer comprises a sequence for amplification of the cDNA (Page 1, [0007]-[0009], Page 4, [0052]-[0054] and Page 13, [0148]-[0149]).
Regarding claim 17, Bibillo teaches the primer comprises an oligo-dT sequence (Page 1, [0005] and Page 42, [0225])
Bibillo teaches each and every limitation of claims 1-3, 5-7, and 9-17, therefore Bibillo anticipates claims 1-3, 5-7, and 9-17.
Response to Arguments
Applicant’s arguments and amendments, filed April 02, 2026 with respect to the rejection under 35 U.S.C. § 112(b) and 112(d) have been fully considered and are persuasive, therefore these rejections have been withdrawn.
Applicant’s arguments and amendments, filed April 02, 2026 with respect to the rejection under 35 U.S.C. § 112(a) have been fully considered and are rendered moot due to the cancellation of claim 8, therefore these rejections have been withdrawn.
Applicant’s arguments, filed February 20, 2024 with respect to the rejection under 35 U.S.C. § 102 have been fully considered and are persuasive in part, therefore these rejections have been withdrawn.
It is acknowledged that Van Oudenaarden does not explicitly disclose “no more than 0.9% of the total cDNA is reverse transcribed from rRNA”. However, applicant asserts that “Potemkin et al. (Sci Rep. 2022 Jan 12;12(1):621, [cited] in an Information Disclosure Statement), published on January 12, 2022, summarizes and reports that "previously published methods ... range anywhere from 1 to 20% rRNA content"…. Accordingly, even if Van Oudenaarden were practiced as disclosed, there is no evidence that the claimed "no more than 0.9%" element would be achieved. At most, the methods of Van Oudenaarden would have been consistent with the Potemkin description of rRNA content in the 1 to 20% range, which does not meet claim 1”. Potemkin does disclose a range of 1-20% rRNA content, but also discloses an rRNA content 0.5 to 20% of final rRNA-depleted sequencing libraries on Page 2, Second Paragraph, which is at or below the amount of 0.9% rRNA content”.
Additionally, new rejections under 35 U.S.C. § 102 are made in view of applicant’s amendments.
As discussed above, newly cited Bibillo discloses whole cell transcriptome analysis as well as methods and systems for amplifying and analyzing nucleic acids including non-coding RNAs and cDNA reverse transcribed from rRNA as well as lncRNA. Bibillo disclose that it is often desirable to separate mRNA from rRNA because rRNA can adversely affect the quantitative analysis of mRNA. Bibillo discloses a complete depletion comprises decreasing all of the rRNA in the sample (i.e., less than 0.9% of the starting sample is rRNA, therefore less than 0.9% of the total cDNA can be reverse transcribed from rRNA).
Therefore, all these reasons and those listed above Bibillo is deemed to render the instant invention anticipated.
Conclusion
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 JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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