DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 3, 2026 has been entered.
Claims 1-5 are pending and under examination.
Applicant’s response, in which claims 1 and 2 were amended, has overcome all of the previously made rejections. They have been withdrawn accordingly.
Applicant’s arguments filed on February 3, 2026 have been considered, but they are moot in view of the new grounds of rejection set forth below.
Claim Rejections - 35 USC § 103
3. 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.
4. 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.
5. Claims 1, 2, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Wickersheim & Blumenstiel (BioTechniques 2013; 55: 269-272) in view of Chen et al. (Analytical and Bioanalytical Chemistry 2014; 406: 2477-2487) and also in view of Wittwer et al. (US 2005/0233335 A1; newly cited) and further in view of Godfrey et al. (US 2006/0068433 A1).
The instant claims are drawn to a kit comprising a 3’ adapter, a 5’ adapter, and a single-stranded nucleic acid blocker that is complementary to an undesired RNA species.
Regarding claim 1, Wickersheim & Blumenstiel disclose a method that uses the following components: (i) a 3’ adapter, (ii) a 5’ adapter, and (iii) a single-stranded blocker nucleic acid that hybridizes to an undesired RNA species (i.e., 2S rRNA). See Figure 1 on page 270. Also, as can be seen in Figure 1, the blocker of Wickersheim & Blumenstiel does not form a unimolecular duplex under conditions suitable for hybridization of the blocker to the undesired RNA. Further regarding amended claim 1, the 3’ adapter of Wickersheim & Blumenstiel is blocked at the 3’ end with C3 spacer (Fig. 1).
Regarding claim 2, the 3’ adapter used by Wickersheim & Blumenstiel contains an rAPP at its 5’ end and also a 3’ blocking group (C3 spacer) (Fig. 1).
Regarding claim 5, the blocker used by Wickersheim & Blumenstiel contains a plurality of deoxyribonucleotides (Fig. 1).
Wickersheim & Blumenstiel do not teach providing the components of the method disclosed in Figure 1 in a kit as required by all of the instant claims. As well, Wickersheim & Blumenstiel do not teach or suggest that the blocker contains locked nucleic acid (LNA) as required by claim 1, from which claims 2-5 depend. Further, the 3’ adapter in Wickersheim & Blumenstiel contains a 3’ C3 spacer as the blocking group rather than the 3’ dideoxynucleotide required by amended claim 1.
Prior to the effective filing date of the invention, though, it would have been prima facie obvious for the ordinary artisan to modify the blocker of Wickersheim & Blumenstiel to contain at least one LNA (i.e., to form a blocker containing deoxyribonucleotides and at least one LNA as encompassed by claims 1 and 5). Chen provides motivation to do so by teaching that LNA offers the following benefits when provided in a blocker oligonucleotide designed to hybridize to an undesired nucleic acid present in a sample (see page 2484): (i) much greater binding affinity compared to DNA; (ii) better ability to discriminate between closely related target and nontarget sequences; (iii) ability to be designed to contain a modified 3’ phosphate, which prevents polymerase-mediated extension. The ordinary artisan would have recognized that these advantages of LNA would also to apply to the blocker of Wickersheim & Blumenstiel, and accordingly, would have been motivated to incorporate LNA into the Wickersheim & Blumenstiel to obtain the same benefits. The ordinary artisan also would have been motivated to not incorporate LNA at every position in the blocker of Wickersheim & Blumenstiel since Chen taught that an LNA/DNA chimera (e.g., as encompassed by the instant claim 5) can be used to “[t]o reduce costs…without decreasing sensitivity and specificity” (page 2484, col. 2). The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided by Chen concerning LNA/DNA chimeras (pages 2478-2479).
It also would have been prima facie obvious to substitute the 3’ C3 spacer in the 3’ adapter of Wickersheim & Blumenstiel with a 3’ dideoxynucleotide. As discussed in MPEP 2144.06 and 2144.07, respectively, in the absence of unexpected results, it is prima facie obvious to substitute art-recognized equivalents known to be useful for the same purpose or to select a known material based on its suitability for the intended purpose. In this case, no evidence of unexpected results has been presented with respect to the use of a 3’ dideoxynucleotide on the 3’ adapter, and the teachings of Wittwer indicate that a 3’ dideoxynucleotide and a 3’ C3 spacer were each known to be useful for preventing unwanted polymerase-mediated extension of an oligonucleotide (see, e.g., para. 258). In other words, the teachings of Wittwer establish that a 3’ C3 spacer and 3’ dideoxynucleotide were art-recognized equivalents known to be useful for the same purpose of blocking unwanted polymerase-mediated extension of an oligonucleotide. The teachings of Wittwer, in combination with the lack of evidence of unexpected results concerning the presence of a 3’ dideoxynucleotide in the 3’ adapter, is sufficient to establish a prima facie case of obviousness per MPEP 2144.06 and 2144.07.
Lastly, it would have been prima facie obvious to provide the blocker suggested by Wickersheim & Blumenstiel in view of Chen as well as the other reagents used by Wickersheim & Blumenstiel in view of Wittwer in a kit. Since Godfrey taught that kits can be “particularly useful” for commercializing nucleic acid detection methods that make use of reagents that include oligonucleotides and DNA polymerases (para. [0112]), the ordinary artisan would have recognized that the library preparation method disclosed in Figure 1 of Wickersheim & Blumenstiel, which comprises adapter ligation, reverse transcription, and amplification (i.e., the use of oligonucleotides and polymerases) could also be commercialized by providing the reagents used to practice the methods (i.e., the blocker nucleic acid suggested by Wickersheim & Blumenstiel in view of Chen, the 5’ adapter, and the 3’ adapter in view of Wittwer) in a kit. Accordingly, the ordinary artisan would have been motivated to provide such a kit to obtain the ability to commercialize the suggested library preparation method. The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided by Godfrey in paras. [0112]-[0115].
Thus, the kits of claims 1, 2, and 5 are prima facie obvious.
6. Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Wickersheim & Blumenstiel (BioTechniques 2013; 55: 269-272) in view of Chen et al. (Analytical and Bioanalytical Chemistry 2014; 406: 2477-2487) and also in view of Wittwer et al. (US 2005/0233335 A1; newly cited) and further in view of Godfrey et al. (US 2006/0068433 A1) and further in view of Vigneault et al. (Current Protocols in Human Genetics 2012; Chapter 11: pp. 11.12.1 – 11.12.10).
As discussed above, the teachings of Wickersheim & Blumenstiel in view of Chen and Wittwer and further in view of Godfrey render obvious the kits of claims 1, 2, and 5.
Regarding claims 3 and 4, the method disclosed in Figure 1 of Wickersheim & Blumenstiel comprises ligation, but the reference, including the supplemental information, fails to specify that a ligase was used. Godfrey, Chen, and Wittwer do not remedy this deficiency.
Wickersheim & Blumenstiel do teach, though, at pages 269-270 that the method disclosed in Figure 1 is based on the protocol disclosed in the Vigneault reference cited above. The Vigneault reference teaches the use of truncated T4 RNA ligase 2 for ligation of a 3’ adapter that contains a 5’ rAPP and the use of T4 RNA ligase 1 for ligation of a 5’ adapter. See pages 11.12.3 and 11.12.5 of Vigneault.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for the ordinary artisan to further include the two ligases disclosed in Vigneault in the kit suggested by the teachings of Wickersheim & Blumenstiel in view of Chen and also in view of Wittwer and further in view of Godfrey. As noted above, the method disclosed in Wickersheim & Blumenstiel includes ligation of a 5’ and 3’ adapter, but the reagent(s) used for the ligation reactions are not disclosed. The protocol from which the method of Wickersheim & Blumenstiel was adapted, though, uses truncated T4 RNA ligase 2 and T4 RNA ligase 1 for adapter ligation (pages 11.12.3 and 11.12.5). Therefore, when seeking to commercialize the method disclosed in Wickersheim & Blumenstiel by providing reagents for performing the method in a kit, the ordinary artisan would have been motivated to further include ligases suitable for use in the method, recognizing that doing so would result in a more useful kit. Thus, the kits of claims 3 and 4 are prima facie obvious.
Conclusion
7. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681