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 .
Status of the Application
2. Applicant’s response filed on September 18, 2025 has been entered.
Claims 1-11 and 13 pending. Claims 1-11 are under examination. Claims 13-20 remain withdrawn from consideration as being drawn to a nonelected invention.
Response to Arguments
3. Applicant’s arguments filed on September 18, 2025 have been fully considered.
Information Disclosure Statement (IDS)
Applicant argues that the IDS filed on September 18, 2025 addresses the issue raised previously concerning Cite No. #142 (Remarks, page 5).
This argument was not persuasive because the newly provided translation is also not legible. The document in question, which is Cite No. 8 on the IDS filed on September 18, 2025, has been lined through.
Claim Objections
Applicant argues that the objections to claims 1, 2, 7, 10, and 12 should be withdrawn in view of the amendments to claims 1, 2, 7, and 10 and the cancellation of claim 12 (Remarks, pages 6-7).
This argument was persuasive. The objections have been withdrawn.
Rejection of claims 1, 2, 4, 5, and 7-9 under 35 U.S.C. 102(a)(1) as being unpatentable over Lee
Applicant argues that the rejection should be withdrawn because independent claim 1 has been amended to incorporate the subject matter of claim 12, which was not included in the rejection (Remarks, page 8).
This argument was persuasive. The rejection has been withdrawn.
Rejection of claims 1, 2, and 4-9 under 35 U.S.C. 103 as being unpatentable over Wille in view of Vestheim
Applicant first argues that the rejection should be withdrawn because independent claim 1 has been amended to incorporate the subject matter of claim 12, which was not included in the rejection (Remarks, page 11).
This argument was persuasive. The rejection has been withdrawn.
Applicant also presents arguments on pages 11-16 concerning Behlke, which was used in combination with Wille and Vestheim to reject claim 12 under 35 U.S.C. 103. These arguments apply to the new rejection set forth below, in which claims 1, 2, and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Wille in view of Vestheim and also in view of Behlke. In particular, Applicant argues that Behlke in combination with Wille and Vestheim fails to render obvious amended claim 1 because each of Wille and Behlke teaches removing undesirable nucleic acids prior to amplification, whereas the instant claims require amplification in the presence of the blocking oligonucleotide (see, in particular, pages 13-15 of the Remarks, where Applicant points to paras. 16-17 and 66 of Behlke and paras. 18, 23, and 29 of Wille to support this argument).
These arguments were unpersuasive because the combined teachings of Wille, Vestheim, and Behlke do, in fact, suggest the method of amended claim 1. Applicant is correct that paras. 16-17 and 66 of Behlke and paras. 18, 23, and 29 of Wille discuss removing undesirable nucleic acid species prior to an amplification or reverse transcription step. The problem, though, is that the amended claims encompass such a removal step provided that a blocking oligonucleotide is present in the amplification reaction.
In this case, the ordinary artisan would have performed the post-reverse transcription amplification reaction in the presence of a blocking oligonucleotide since the cited portions of Vestheim and Wille each teach conducting amplification in the presence of a blocking oligonucleotide. In other words, the ordinary artisan would have recognized that, irrespective of the presence of a pre-amplification purification or removal step, a blocking oligonucleotide(s) should be present in the amplification step to ensure that any undesirable nucleic acids remaining after the pre-amplification purification/removal are not amplified.
Further, in performing the pre-amplification purification taught in Wille, the ordinary artisan would have been motivated to use any known method for removing undesirable nucleic acids from a mixture with a reasonable expectation of success, recognizing its suitability for the intended purpose. See MPEP 2144.07. In other words, the ordinary artisan would have recognized that undesirable nucleic acids could be removed using either a silica-based method as described in Wille or an affinity method as described in Behlke, and accordingly, would have been motivated to select either known method with a reasonable expectation of success, particularly since unexpected results have not been presented with respect to this aspect of the claimed methods.
Since Applicant’s arguments were not persuasive, claims 1, 2, and 4-9 are currently rejected under 35 U.S.C. 103 as being unpatentable over Wille in view of Vestheim and Behlke.
Rejections of claims 3, 10, and 11 under 35 U.S.C. 103 citing Wille and Vestheim as the primary combination of references
Applicant argues that the rejections should be withdrawn because the references cited in the rejections do not remedy the deficiency of the primary combination of references with respect to amended claim 1 (Remarks, pages 16-18).
This argument was persuasive. The rejections have been withdrawn.
Rejection of claim 12 under 35 U.S.C. 103 citing Wille and Vestheim as the primary combination of references
Applicant argues that the rejection is moot since claim 12 was canceled in the response (Remarks, page 18).
This argument was persuasive. The rejection has been withdrawn.
Double Patenting
Applicant requests that the issue of double patenting with U.S. Patent No. 11,319,583 be held in abeyance until the instant application is otherwise in condition for allowance (Remarks, page 18).
In response, it is first noted that rejections cannot be held in abeyance. Therefore, Applicant’s response is not fully responsive as to the double patenting rejection. The rejection has been maintained with modifications necessitated by Applicant’s amendment since it remains applicable.
Information Disclosure Statements
4. The Information Disclosure Statement filed on September 18, 2025 has been considered.
Non-patent literature reference #8 has not been considered because the provided translation, which serves as the statement of relevance required by 37 CFR 1.98(a)(3), is not legible.
Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Applicant is also advised that a size fee assertion is required for any IDS submitted on or after January 19, 2025. See the response to Question 2 and also Example 3 in the Quick Reference Guide to the Information Disclosure Statement (IDS) Size Fee and Size Fee Assertion published on the USPTO website.
Claim Interpretation
5. As discussed in MPEP 2111, claims are to be given “their broadest reasonable interpretation consistent with the specification.” As well, MPEP 2111.01 II states that “This section of the MPEP also notes that “[I]t is improper to read a specific order of steps into method claims where, as a matter of logic or grammar, the language of the method claims did not impose a specific order on the performance of the method steps, and the specification did not directly or implicitly require a particular order.”
In this case, the broadest reasonable interpretation of claim 1 consistent with the specification encompasses performing the newly added “removing” step before, during, or after the concluding amplification step.
Claim Objections
6. Claim 1 is objected to because of the following minor informality. Amending lines 3-4 to recite “wherein the sample molecules also comprise extension products” or “wherein the sample molecules further comprise extension products” or wherein the sample molecules additionally comprise extension products” is suggested so that the provided sample molecules are more clearly described.
Claim Rejections - 35 USC § 112
7. 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 1-11 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.
Claim 1 is indefinite because the relationship between the “ribonucleic acids for hybridization” recited in lines 6-8 and the “sample molecules” in lines 2-3 is not entirely clear. The sample molecules include “nucleic acid target molecules and one or more undesirable nucleic acid species” (see lines 2-3). Based on the entirety of the claim, it seems that the “ribonucleic acids for hybridization” in lines 6-8 correspond to the “sample molecules” recited in lines 2-3, but this is not entirely clear from the claim language. Put another way, it is not clear that the extension products in lines 5-9 are generated using sample molecules as a template or if the ribonucleic acids for hybridization are unrelated to the nucleic acid target molecules recited in lines 2-3. As a result, claim 1 is indefinite.
Claims 2-11 are indefinite since they depend from claim 1 and do not correct its indefiniteness issues.
Claim Rejections - 35 USC § 103
8. 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.
9. 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.
10. Claims 1, 2, and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Wille et al. US 2006/0281092 A1) in view of Vestheim et al. (Methods in Molecular Biology 2011; 687: 265-274) and also in view of Behlke et al. (US 2015/0218620 A1).
The instant claims are drawn to a selective amplification method that comprises use of a blocking oligonucleotide.
Regarding claim 1, 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 target nucleic acid from a biological sample in the presence of at least one oligo(dT) primer to generate first-strand cDNA; (b) second-strand cDNA synthesis; and (c) amplification of the resulting double-stranded cDNA using one or more amplification primers.
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 requirement in the last clause in claim 1 for the blocking oligonucleotide to reduce amplification of undesirable nucleic acid species. Wille additionally teaches that the blocking oligonucleotide may be PNA or have a modification at its 3’ end to prevent it from acting as a primer capable of being extended by a polymerase (para. 59).
Further regarding amended claim 1, Wille teaches removing undesirable nucleic acids prior to downstream analysis and teaches various purification methods for this purpose (paras. 18 and 23-29). The reference does not teach removing a hybridized complex formed between the blocking oligonucleotide and an undesirable nucleic acid species via an affinity moiety on the blocking oligonucleotide as required by amended claim 1, however.
Regarding claims 2 and 4, the target nucleic acid in Wille is a double-stranded cDNA, and the undesirable nucleic acid species is double-stranded cDNA from an unwanted mRNA molecule(s) (paras. 49-50 and 56). Since the unwanted mRNA molecule may be a high-abundance sequence (paras. 49 and 54), the resulting cDNA may also be considered a high-abundance sequence.
Regarding claim 6, Wille teaches that the method may comprise providing blocking oligonucleotides that specifically bind to two or more undesirable nucleic acid species in the sample (paras. 50, 51, 56, and 58).
Regarding claim 8, Wille teaches that the blocking oligonucleotides may have a length within the claimed range (paras. 55 and 57).
Wille does not teach all of the elements of the claims. As to claim 1, as noted above, the reference fails to teach all of the requirements of the newly added “removing step.” Further as to claim 1 and also as to claim 7, Wille fails to teach or suggest that the blocking oligonucleotide binds to an undesirable nucleic acid species within 100 nt or within 50 nucleotides of the 5’ end of the undesirable nucleic acid species. As to claim 5, Wille does not teach that the unwanted cDNA in the sample is present at an amount within one of the recited ranges. As to claim 9, Wille does not disclose a blocking oligonucleotide with the required melting temperature.
Vestheim, though, describes a method for inhibiting amplification of “dominant or unwanted DNA templates” present in a sample that also contains a target nucleic acid(s). The method comprises conducting the amplification in the presence of a blocking oligonucleotide that binds to the unwanted DNA templates and inhibits their amplification (abstract and pp. 265-266). The blocking oligonucleotide is not extendable by a polymerase and targets a sequence in the unwanted DNA template that would be bound by one of the amplification primers (sections 2.1 and 3.1; see also Fig. 2a, where the “annealing inhibiting blocking oligo” is taught). Vestheim teaches that the “annealing inhibiting blocking oligos” are more efficient compared to blocking oligonucleotides that bind between the regions targeted by amplification primers (p. 267).
Behlke discloses a selective amplification method that comprises the following steps (see paras. 16-17 as well as para. 66): (a) providing a sample that comprises a plurality of target nucleic acid molecules and one or more undesirable nucleic acid species; (b) providing one or more blocking oligonucleotides (i.e., the “baits” in Behlke) that specifically bind to at least one of the undesirable nucleic acid species; (c) removing hybridization complexes formed between the blocking oligonucleotides and the undesirable nucleic acid species by immobilizing said hybridization complexes on a solid support comprising a binding partner (streptavidin) of the affinity moiety (biotin) contained on the blocking oligonucleotides; (d) subjecting the remaining nucleic acids (i.e., the target nucleic acids) to a primer extension reaction to generate a cDNA library; and (e) sequencing the cDNA library. The cDNA library generation process may comprise primer extension followed by PCR and sequencing the resulting amplicons (see, e.g., paras. 86-90 and 101-106). Behlke also teaches that the blocking oligonucleotides may contain streptavidin or digoxigenin as the affinity tag (para. 34).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for the ordinary artisan to practice the method of Wille using an “annealing inhibiting blocking oligo” designed to inhibit amplification of double-stranded cDNA generated from unwanted mRNA(s). As discussed above, Wille teaches using a blocking oligonucleotide(s) to inhibit amplification from unwanted mRNA or cDNA present in a sample. Wille does not teach that a blocking oligonucleotide binds within 100 nt or within 50 nt of the 5’ end of an unwanted cDNA, but the ordinary artisan would have recognized from the teachings of Vestheim cited above that a blocking oligonucleotide binding site could overlap with the binding site of a forward or reverse primer. Then, when the undesirable nucleic acid species is double-stranded cDNA, the blocking oligonucleotide should target either the region targeted by the forward or reverse amplification primer to obtain the more efficient blocking described in Vestheim. And, when the blocking oligonucleotide targets the region targeted by the forward primer, the blocking oligonucleotide binds within 50 or 100 nt of the 5’ end of the unwanted double-stranded cDNA. The ordinary artisan would have had a reasonable expectation of success in view of the guidance provided in Wille and Vestheim concerning blocking oligonucleotide design and also since both references are directed to the goal of selective amplification.
It also would have been prima facie obvious for the ordinary artisan to use an affinity method to remove complexes formed between the undesirable nucleic acid species and blocking oligonucleotides before the amplification step when practicing the method suggested by Wille in view of Vestheim. As noted above, Wille teaches removing undesirable nucleic acids prior to cDNA amplification, and the instant claims encompass removal before the amplification step, so long as a blocking oligonucleotide(s) is provided during the amplification step. As discussed above, Wille and Vestheim suggest providing a blocking oligonucleotide(s) during amplification. In conducting the pre-amplification removal step, the ordinary artisan would have recognized that affinity methods (e.g., biotin-streptavidin capture of hybridized complexes containing an undesirable nucleic acid as described in Behlke) would be suitable for this purpose, and no evidence of unexpected results related to the removal step has been presented. This is sufficient to establish a prima facie case of obviousness per MPEP 2144.07. As well, the ordinary artisan would have had a reasonable expectation of success since Behlke provides detailed guidance concerning the disclosed affinity purification method.
Thus, the methods of claims 1, 2, 4, and 6-8 are prima facie obvious.
Further regarding claim 5, Wille does not specify the amount of double-stranded cDNA that may result from uninhibited reverse transcription and second strand synthesis from a high-abundance mRNA sequence. However, the reference teaches in Examples 6 and 8 that “It was possible to lower the signal intensities for the globin mRNA transcripts by 40-60% using the PNAs” (paras. 143 and 160). Wille also discloses in Example 5 reductions in amplification of 95% and 99% for an undesirable nucleic acid species (paras. 136-137). These teachings indicate that Wille contemplates using blocking oligonucleotides with samples that contain large amounts of the undesirable nucleic acid species. Similarly, Vestheim teaches that blocking oligonucleotides may be used to produce “a 70% reduction in amplification efficiency of non-target templates” (p. 266). Therefore, the ordinary artisan would have had a motivation and reasonable expectation of success in practicing the methods suggested by Wille in view of Vestheim and Behlke using samples containing large amounts of the undesirable nucleic acid species. Thus, the method of claim 5 is also prima facie obvious.
Further regarding claim 9, it also would have been prima facie obvious to design the blocking oligonucleotide to have a temperature of at least 60 ⁰C. The ordinary artisan would have recognized that the melting temperature of the blocking oligonucleotide is a results-effective variable and would have been motivated to conduct routine experimentation to determine the optimal value(s). As discussed in MPEP 2144.05 II, such experimentation is prima facie obvious in the absence of unexpected results, which have not been presented in this case. As well, Vestheim and Wille suggest the use of blocking oligonucleotides with a melting temperature within the claimed range in view of the following: (1) Vestheim teaches that the blocking oligonucleotide should have a melting temperature “slightly higher than that of the primers it is intended to outcompete” (p. 268), and (2) Wille teaches that a suitable annealing temperature for blocking oligonucleotides is 70 ⁰C (pp. 9-10). Thus, the method of claim 9 is also prima facie obvious.
11. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Wille et al. US 2006/0281092 A1; IDS reference) in view of Vestheim et al. (Methods in Molecular Biology 2011; 687: 265-274; IDS reference) and also in view of Behlke et al. (US 2015/0218620 A1) and further in view of Jiang et al. (Cellular and Molecular Life Sciences 2015; 72: 3425-3439).
As discussed above, the teachings of Wille in view of Vestheim and Behlke render obvious the methods of claims 1, 2, and 4-9.
Regarding claim 3, it is not clear that the sample molecules in the method of Wille comprise whole transcriptome amplification (WTA) products.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious to practice the method suggested by Wille in view of Vestheim and Behlke using a sample comprising WTA products. Jiang provides motivation to do so by teaching that WTA, which analyzes both coding and non-coding RNA, “plays an essential role in deciphering genome structure and function, identifying genetic networks underlying cellular, physiological, biochemical and biological systems and establishing molecular biomarkers that respond to diseases, pathogens and environmental challenges” (abstract) (see also p. 3425). The ordinary artisan would have recognized from these teachings of Jiang that WTA products would provide more information compared to the analysis of Wille, which is limited to coding RNA, and accordingly, would have been motivated to substitute WTA products to obtain the ability to more fully analyze genome structure and function as described in Jiang. The ordinary artisan would have had a reasonable expectation of success in view of the teachings throughout Jiang regarding the production and analysis of WTA products. Thus, the method of claim 3 is prima facie obvious.
12. Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Wille et al. US 2006/0281092 A1; IDS reference) in view of Vestheim et al. (Methods in Molecular Biology 2011; 687: 265-274; IDS reference) and also in view of Behlke et al. (US 2015/0218620 A1) and further in view of Jiang et al. (Cellular and Molecular Life Sciences 2015; 72: 3425-3439) and further in view of Parameswaran et al. (Nucleic Acids Research 2007; 35: e130; IDS reference).
As discussed above, the teachings of Wille in view of Vestheim and Behlke render obvious the methods of claims 1, 2, and 4-9.
Regarding claims 10 and 11, Wille teaches that cDNA amplified by the disclosed method may be further analyzed (e.g., by microarray analysis) (see, e.g., para. 70 and Examples 6 & 7 at paras. 139-147), but the reference does not disclose sequencing or adding sequencing adapters via the amplification primers. Vestheim and Behlke do not remedy this deficiency.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious to sequence the double-stranded cDNA amplicons (or products thereof) resulting from practicing the method suggested by Wille in view of Vestheim and Behlke and to use the amplification primers to add sequencing adapters. As discussed above with regard to claim 3, Jiang provides motivation to use WTA products in the method suggested by Wille in view of Vestheim and Behlke. The ordinary artisan also would have been motivated to sequence the double-stranded cDNA produced during WTA (or products thereof) since Jiang teaches that next-generation sequencing is suitable for analysis of such amplicons and would have had a reasonable expectation of success since many such methods were available (p. 3426). In doing so, the ordinary artisan also would have been motivated to add sequencing adapters to the double-stranded cDNA (or products thereof) since Jiang teaches that adapter addition is part of such sequencing methods (p. 3426, col. 1). The ordinary artisan would have been motivated to use amplification primers for adapter addition since Parameswaran taught that this was a suitable way to add adapters to nucleic acids to be sequenced in a high-throughput method (Fig. 1) and would have had a reasonable expectation of success in view of guidance in Paramewaran concerning primer design and amplification conditions (pages 2-5). Thus, the methods of claims 10 and 11 are prima facie obvious.
Double Patenting
13. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,319,583 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘583 patent overlap in scope with the instant claims and recite or suggest all of their features.
The instant claims are drawn to a method of selective amplification. The method comprises amplification of at least one target nucleic acid present in a sample that also contains at least one undesirable nucleic acid species. The amplification is conducted using one or more amplification primers and also a blocking oligonucleotide that is unable to function as a primer for a polymerase. Further, the blocking oligonucleotide specifically binds to at least one of the undesirable nucleic acid species within 100 nucleotides of the 5’ end of said undesirable nucleic acid species.
Claims 1-17 of the ‘583 patent are also drawn to a method for selectively amplifying a target nucleic acid present in a sample that also contains at least one undesirable nucleic acid species. Claim 1 of the ‘583 patent recites all of the limitations set forth in the instant claim 1 except for the requirement in amended instant claim 1 for removing a complex formed between the blocking oligonucleotide and an undesirable nucleic acid by binding an affinity moiety on the blocking oligonucleotide to a solid support comprising a binding partner of the affinity moiety. This would have been obvious, though, because the ordinary artisan would have recognized that such complexes should be removed to prevent them from interfering with the amplification reaction. In doing so, the ordinary artisan would have recognized that a solid support comprising a binding partner of an affinity moiety contained in the blocking oligonucleotide could be used for this purpose since this was a conventional way of removing nontarget nucleic acids from a sample. Thus, the instant claim 1 is not patentably distinct from the claims of the ‘583 patent.
The limitations of the instant claim 2 are met by claim 14 of the ‘583 patent.
The instant claim 3 requires the sample molecules to comprise whole transcriptome amplification products. The claims of the ‘583 patent do not recite this limitation, but they broadly encompass any type of sample nucleic acid. See, e.g., claim 1 of the ‘583 patent. Therefore, the ordinary artisan would have recognized that any desired type of sample nucleic acid (e.g., whole transcriptome amplification products) could be used.
The limitations of the instant claim 4 and 5 are recited in claims 6 and 5, respectively, of the ‘583 patent.
The limitations of the instant claim 6 are met by claim 3 of the ‘583 patent.
The limitations of the instant claim 7 are recited in claim 7 of the ‘583 patent.
The instant claim 8 requires the blocking oligonucleotide to be 10-50 nucleotides in length. The claims of the ‘583 patent do not specify the length of the blocking oligonucleotide, but the ordinary artisan would have recognized that any desired length could be used, so long as the blocking oligonucleotide is able to hybridize to undesirable nucleic acids as required by the claim. The ordinary artisan also would have recognized the claimed length range of 10-50 nucleotides as typical for oligonucleotides used in amplification reactions.
The limitations of the instant claim 9 are recited in claim 4 of the ‘583 patent.
The limitations of the instant claim 10 are recited in claim 1 of the ‘583 patent.
The limitations of the instant claim 11 are recited in claim 12 of the ‘583 patent.
Conclusion
15. No claims are currently allowable.
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 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