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’s amendment filed 11/17/2025 is acknowledged. Claims 1-16 and 19 have been canceled. Claims 17, 20-21, 30-32 and 36 have been amended. Claims 17-18 and 20-36 are pending. All of the amendment and arguments have been thoroughly reviewed and considered.
Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims.
This action is made Final.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/17/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Previous Rejection
The prior art rejection directed to claims 17-36 as being unpatentable over Shum et al in view of Willie et al is withdrawn in view of the new grounds of rejections necessitated by applicant’s amendment of the claims.
New Ground(s) of Rejections
The new ground(s) of rejections were necessitated by Applicant’s amendment of the claims.
Claim Rejections - 35 USC § 103
Note** The following are new grounds of rejections necessitated by Applicant's amendments. Although the claims were previously rejected as being anticipated and/or unpatentable over the same reference(s), Applicant's amendments have necessitated the inclusion of new grounds of rejections in this Office action. It is noted that, to the extent that they apply to the present rejection; Applicant's arguments are addressed following the rejection.
4. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
5. Claim(s) 17-18 and 20-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shum et al [Shum, used interchangeably herein] (US 20180216174, publication date August 2, 2018, effective filing date February 1, 2017) in view of Willie et al {Willie, used interchangeably herein, December 2006).
Regarding claims 17 and 18, Shum teaches kit for selective amplification of nucleic acid molecules in a sample, comprising: a plurality of oligonucleotide probes, wherein each of the plurality of oligonucleotide probes comprises a molecular label sequence and a target binding region comprising a poly-dT sequence; and a plurality of blocking oligonucleotides that specifically binds to a plurality of undesirable mRNA species in the sample, wherein the plurality of blocking oligonucleotides binds to region(s) of the plurality of undesirable mRNA species, and wherein each blocking oligonucleotide probe is unable to function as a primer for a reverse transcriptase or a polymerase (paragraphs [0012] - [0018], [0049], [0055], [0057], [0061], [0078] –[0084]). Shum further teaches wherein one of the plurality of blocking oligonucleotides comprises (i) a sequence that specifically binds to at least one of the plurality of undesirable nucleic acid species, and, and/or (iii) a sequence that does not hybridize to the at least one of the plurality of undesirable nucleic acid species ([0013] – [0018], [0049], [0057], [0061], [0078] – [0084].
Regarding 20, Shum teaches the kit of claim 17, wherein the blocking oligonucleotide comprises a 3' non-annealing region configured to not anneal to the one or more undesirable nucleic acid species ([0009] – [0010], [0016] [0043], [0045], [0055], [0079])
Regarding claims 21, Shum teaches the kit of claim 20, wherein the non-complementarity between the 3' non-annealing region and the region of the undesirable nucleic acid species 5' adjacent to the sequence specifically bound by the blocking oligonucleotide is at least 50%, is at least 60%, is at least 70%, is at least 80%, is at least 90%, is at least 95%, or is about 100%. ([0008] – [0009], [0016], [0043], [0055], [0079])
Regarding claim 22, Shum teaches the kit of claim 17, wherein the blocking oligonucleotide is a locked nucleic acid (LNA), a peptide nucleic acid (PNA), a DNA, an LNA/PNA chimera, an LNA/DNA chimera, or a PNA/DNA chimera ([0005], [0014], [0045], [0052], [0055], [0081], [0083] and [0084]).
Regarding claim 23, the kit of claim 17, wherein the plurality of oligonucleotide probes is immobilized on a particle [ [0012], [0017], [0035], [0108], [0110] – [0114], [0122] – [0124]).
Regarding claim 24, the kit of claim 17, wherein each blocking oligonucleotide probe has a Tm of at least 60 0C ([0018], [0080])
Regarding claim 25, Shum teaches the kit of claim 17, wherein the blocking oligonucleotide does not comprise non-natural nucleotides ([0052], [0081]).
Regarding claim 26, Shum teaches the kit of claim 19, wherein the poly-dT sequence of the oligonucleotide probe is longer than the poly-dT sequence of the blocking oligonucleotide ([0053], [0082]).
Regarding claim 28, Shum teaches the kit of claim 17, wherein none of the plurality of oligonucleotide probes comprises the blocking oligonucleotide ([0064], [0088].
Regarding claim 30, Shum teaches the kit of claim 17, wherein the plurality of blocking oligonucleotides specifically binds to two or more undesirable nucleic acid species ([0049]).
Regarding claim 31, Shum teaches the kit of claim 17, wherein the blocking oligonucleotide is 8 nt to 100 nt long ([0007], [0015]).
Regarding claim 32, Shum teaches the kit of claim 17, wherein the plurality of undesirable mRNA species comprises ribosome mRNA, mitochondrial mRNA, or a combination thereof ([0042] and [0047]).
Regarding claim 33, Shum teaches the kit of claim 17, wherein the blocking oligonucleotides specifically bind to within 100 nt of the 3' end of the undesirable nucleic acid species. [0016]).
Regarding claim 34, Shum teaches the kit of claim 17, wherein the plurality of oligonucleotide probes is immobilized on a substrate, and wherein the substrate is a particle ([0009], [0016]. [0035]).
Regarding claim 35, Shum teaches the kit of claim 17, further comprising an enzyme selected from the group consisting of a reverse transcriptase, a polymerase, a ligase, a nuclease, and a combination thereof ([0006], [0013], [0018] and [0039]).
Regarding claim 36, Shum teaches the kit of claim 17, wherein the plurality of blocking oligonucleotides specifically binds to at least 50 undesirable nucleic acid species ([0005], [0014]).
While Shum teaches multiple embodiments and components of the blocking oligonucleotide and oligonucleotide probes, Shum does not expressly disclose wherein the blocking oligonucleotide comprise of a poly-dT sequence, wherein the poly-dT sequence of the poly-dT sequence of the blocking oligonucleotide and the poly-dT of the oligonucleotide probe have an identical length and wherein the 3' non-annealing region is 1 nt to 100 nt long, is 1 nt to 50 nt long, is 1 nt to 21 nt long, is 1 nt to 10 nt long, or is about 5 nt long.
Regarding claims 17-18 and 20-36, in a similar endeavor, Wille discloses a method that comprises selective amplification and/or reverse transcription of a desired group of nucleic acids present in a complex biological sample (paras. 1, 12, and 13). The method can include the following steps (see para. 18): (a) reverse transcription of an RNA from a biological sample in the presence of at least one oligo(dT) primer to generate first-strand cDNA (i.e., extension of an oligonucleotide probe hybridized to a target RNA to produce an extension product); (b) second-strand cDNA synthesis; and (c) amplification of the resulting double-stranded cDNA using one or more amplification primers. Wille teaches that the plurality of amplicons may comprise a cDNA library (see, e.g., paras. 15, 18, and 20, where reverse transcription of mRNA isolated from a complex biological sample using an oligo(dT) primer will generate a cDNA library. See also para. 70 and Examples 4-6 on pp. 8-10).
Wille further teaches that the method may include adding “a molecular species….to suppress an RT and/or amplification reaction of the unwanted mRNA transcripts” (para. 49). The “molecular species” in Wille, which corresponds to the “blocking oligonucleotide” recited in the instant claims, may be present during any or all of steps (a)-(c) above (para. 50) and binds to undesirable nucleic acid species (e.g., the globin mRNA transcripts discussed in para. 49), thereby preventing them from participating in the reverse transcription and/or subsequent amplification reaction (paras. 49-51). In other words, this embodiment of Wille meets the embodiments of the claims for the blocking oligonucleotide to reduce amplification of undesirable nucleic acid species and also extension of oligonucleotides hybridized to undesirable nucleic acid species Wille teaches that the method may comprise providing blocking oligonucleotides that specifically bind to two or more undesirable nucleic acid species in the sample (para. 58).
Wille teaches that the blocking oligonucleotides preferably specifically binds near the 3’ end of the undesirable nucleic acid species (para. 56). The reference also teaches examples of blocking oligonucleotides that bind within 100 nucleotides of the 3’ end of a particular undesirable nucleic acid species (beta-globin) (see, e.g., page 5, where the blocking oligonucleotides disclosed in paras. 63 and 65 are disclosed).
Wille teaches that the blocking oligonucleotide may be PNA wherein the blocking oligonucleotide may comprise of a poly-dT and wherein the oligonucleotide probe may comprise of an oligo-dT wherein they oligonucleotide and probe may have identical length or may of a different length and further wherein the 3’ non annealing region of the blocking oligonucleotide may comprise of at least 1 nt in long (pages 4-5 and examples).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have been motivated to have combined the teachings of Shum with the teachings of Willie since they are of similar scope and such combinations would not negatively alter or modify the results of performing selective amplification. Willie expressly teaches that combining one or more DNA oligonucleotides, PNAs and/or LNA as molecular species are useful for selectively suppressing or blocking reverse transcription or amplification of unwanted mRNA [0061]. The combination of the cited prior art is prima facie obvious in the absence of secondary consideration.
Response to Arguments
Applicant’s rebuttal
6. Applicant traverses the rejections on the following grounds: Applicant summarizes the rejections and teachings of the prior art of Shum et al in view of Willie et al and states the following:
(a) Shum’s teaching that the location at which a Shum blocking oligonucleotide hybridizes can vary in no way (expressly nor inherently) teaches a separate non-hybridizing element of the blocking oligonucleotide.
(b) Applicant states regardless of whether the Shum blocking oligonucleotide binds the 5’ or 3’ portions of an undesirable species, or whether the Shum blocking oligonucleotide binds all or a portion of an undesirable species, it does not logically follow that this teaches a separate non-hybridizing element of the blocking oligonucleotide and Willie fails to remedy the deficiencies of Shum.
(c) Applicant states no of the above disclosures in Shum or Willie teaches or suggests blocking oligonucleotides comprising a sequence that specifically binds to at least of the plurality of undesirable mRNA species; a poly-DT sequence and a sequence that does not hybri8dize to the at least one of the plurality of undesirable mRNA species. Applicant states that the compositions comprising blocking oligonucleotides with a tripartite structure provides a non-obvious means of selective amplification. Applicant cites the specification at Figure 6D as support and states that the combination of the cited prior art does not teach directly or indirectly the claimed limitations of the claims 17 and further claims 18 and 20-36. Applicant request the obviousness rejection be withdrawn.
Examiner’s Response
7. All of the amendment and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons that follow:
The examiner acknowledges applicant’s arguments but respectfully disagree.
(a) In response to Applicant’s arguments concerning Shum not teaching a separate non hybridizing element of the blocking oligonucleotide, it is noted that the feature(s) upon which applicant relies (i.e., a separate non-hybridizing element of the blocking oligonucleotide) is not recited in the rejected claim(s). In fact, the specification does not expressly recite a “non-hybridizing element of the blocking oligonucleotide” but rather the claims and specification recite a sequence that does not hybridize to the at least one of the plurality of undesirable mRNA species. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
(b) Regarding Applicant’s arguments that the cited prior art of Shum in view of Willie does not teach a composition comprising blocking oligonucleotide with a tripartite structure, this argument is not found persuasive because the claims do not recite a composition requiring a tripartite structure. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant’s arguments are not commensurate in scope with the claims because the features upon which applicant relines are within the scope of the teachings of the cited prior art of Shum and Willie. Applicant is reminded that the Court commented "[r]esponding to concerns about uncertainty in the prior art influencing the purported success of the claimed combination, this court [in O'Farrell] stated: '[o]bviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success."' Kubin, 561 F.3d at 1360 (citing In re O'Farrell, 853 F.2d at 903-904). Thus, the examiner maintains that the combination of the cited prior art meets the limitations of the claims as currently amended.
Conclusion
8. No claims are 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.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY BENZION can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681