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 .
Status of the Claims
It is acknowledged that the Applicant amended claims 73, 74, and 77-79 and cancelled claims 87-89 in their response filed April 21, 2016.
Claims 73-86 and 90-97 are currently pending and have herein been examined.
Summary of Response to Applicant’s Arguments
This action is in response to the papers filed April 21, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant’s amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Regarding arguments concerning rejections under 35 U.S.C. 102(a)(1), the arguments have been fully considered. Due to the newly amended claim limitations (especially “and wherein said unique matching sequence is unique to the nucleic acid”), rejections under 35 U.S.C. 102(a)(1) have been withdrawn and the rejections under 35 U.S.C. 103 have been updated. Those rejections are set forth below.
Regarding arguments concerning rejections under 35 U.S.C. 112(b), the arguments have been fully considered. In view of amendments introduced into the claims, the previous grounds of rejection are considered moot. However, the newly amended claim limitation “and wherein said unique matching sequence is unique to the nucleic acid” (claim 73) has raised new 35 U.S.C. 112 issues, including issues of indefiniteness and new matter. Those rejections are set forth below.
Regarding arguments concerning double patenting rejections, the arguments have been fully considered. Due to the newly amended claim limitations (especially “and wherein said unique matching sequence is unique to the nucleic acid”), double patenting rejections have been modified and are set forth below.
Priority
Claims to the priority of PCT/US/2022/030370 and to the benefit of the provisional application 63/191,455 are acknowledged. The effective filing date of the claims under examination is considered to be May 21, 2021.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 73-86 and 90-97 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.
Due to amendments submitted April 21, 2026, newly amended claim 73 now requires that “said unique matching sequence is unique to the nucleic acid” (recited in the last two lines of step a) – this constitutes new matter. MPEP 2163(I)(B) states: “Thus, the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (an adequate description of a genus may not support claims to a subgenus or species within the genus).”
In the instant case, the specification as originally filed provides for two distinct molecular identifiers:
A ‘unique matching sequence’ as sort forth in the claims, which is comprised in the first oligonucleotide and complementary to a sequence in the second oligonucleotide. This unique matching sequence is only explicitly unique to gene or probe pair (par. 61)
A ‘barcode,’ which is described separately to the unique matching sequence, and which is comprised in the second oligonucleotide (par. 60). This barcode is described as unique per gene (par. 259) or per cell (par. 262)
In neither case is the molecular identifier (either the ‘unique matching sequence’ or the barcode) explicitly described as being unique to a single nucleic acid molecule. If the amended claim is meant to indicate that the unique matching sequence is unique to nucleic acids corresponding to a single gene or to a single probe pair, the claim must be amended to reflect that relationship. For the purposes of compact prosecution, rejections under 102 and 103 have been updated to address the limitations required by either interpretation of the newly amended claim.
The following is a quotation of 35 U.S.C. 112(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 73-97 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.
Claims 73-97 are rejected over the recitation of “and wherein said unique matching sequence is unique to the nucleic acid” in the last line of step a of claim 73, as being indefinite. In light of the specification (par. 60-61), it is not clear whether this limitation is meant to indicate that the unique matching sequence is unique to a single target molecule in a plurality of molecules, or if it is meant to indicate that the unique matching sequence is unique to a subset of nucleic acids sharing a single sequence (therefore being potentially ‘per gene’ or potentially ‘per probe pair’). As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim Rejections - 35 USC § 103
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 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.
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.
Claims 73-78, 84, 90-92, and 96 are rejected under 35 U.S.C. 103 as being unpatentable over Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156).
Bava et al. describes methods of identifying target molecules including nucleic acids (par. 6).
Regarding claim 73, Bava teaches a method comprising contacting a cell comprising a target nucleic acid with at least one pair of oligonucleotides, comprising a first oligonucleotide which has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide which has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region, as well as a first end and a second end (Figure 12). Bava teaches that the first complementarity region is complementary to a first portion of said nucleic acid, the second complementarity region is complementary to the fourth complementarity region, the third complementarity region is complementary to said sixth complementarity region, the fifth complementarity region is complementary to a second portion of the target nucleic acid, and that the second oligonucleotide comprises a unique matching sequence which hybridizes to the first oligonucleotide (Figure 12, par. 6). In the reference, complementarity regions 1 and 5 are named CR1 and CR1’ respectively (and they bind adjacent regions on the target nucleic acid, see Figure 12), complementarity regions 2 and 3 are comprised in CR2 (they are immediately adjacent as shown in Figure 12, step 1), and complementarity regions 4 and 6 are comprised in CR2’ as a ‘split’ region (see par. 6). The CR2’ split regions make up a matching sequence in the second oligonucleotide which hybridizes to the first oligonucleotide (Figure 12, step 1 and par. 6). Bava teaches ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule and amplifying the circular nucleic acid molecule to generate one or more amplicons (Fig. 12). Bava also teaches imaging amplicons to identify the target nucleic acid (par. 244).
Bava teaches a unique matching sequence (in the form of the ‘UBA’ or ‘Sequence Tag’/’SeqTag’) which is unique for the target nucleic acid (implicitly, shared between nucleic acids having the same sequence) and comprised in the second oligonucleotide (par. 111). Bava teaches a ‘unique counter tag’, which is unique to a single target molecule within a plurality of molecules (and not shared between nucleic acids having the same sequence; par. 36). Bava also teaches other unique sequences, including a sample identification barcode optionally included in the first oligonucleotide (par. 7) and a cell-originating barcode or COB (par. 6).
Bava does not explicitly teach that a target-specific unique sequence is comprised in the portion of the second oligonucleotide which hybridizes to the first oligonucleotide. However, Bava does teach that probes may bind in both confirmation-specific and sequence-specific manners, and that they may bind to combinations of molecules, including the target molecule and a target-molecule surrogate (par. 100). Given that here are a finite number of solutions (a finite number of positions with the first and second oligonucleotide), it would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of the detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
Regarding claim 74, Bava does not explicitly teach a second pair of oligonucleotides comprising a unique matching sequence which is different than the unique matching sequence of the first pair of oligonucleotides. However, Bava does discuss multiple sets of probes with at least two members each, and a given set of probes binding to the same target molecule in a confirmation-specific manner (par. 196). Given that there are a finite number of solutions (i.e. the same unique matching sequence for each pair or different unique matching sequences between two pairs), and there is no evidence of unexpected results, it would have been obvious to a person with ordinary skill in the art to try including different unique matching sequences in different sets/pairs of oligonucleotides, in order to achieve high specificity of binding in the probe complex (par. 86). This would be desirable for reducing background and improving signal-to-noise ratios (par. 113).
Regarding claims 75 and 76, Bava teaches at least two pairs of oligonucleotides binding to the same nucleic acid (par. 114) or to different nucleic acids (par. 7, 114).
Regarding claim 77, Bava teaches the method of claim 73 as discussed above using more than one pair of oligonucleotides (pars. 7, 114).
Regarding claim 78, Bava teaches multiple rounds of imaging (par. 244).
Regarding claim 84, Bava teaches complementarity regions 1 and 5 (the target binding regions) with melting temperatures between 50-72ºC (par. 115).
Regarding claims 90 and 91, Bava teaches complementarity regions 4 and 6 which comprise a first and second portion of a unique matching sequence which hybridizes to the first oligonucleotide (Figure 12, par. 6).
Regarding claims 92 and 96, Bava teaches complementarity regions 1 and 5 (the target binding regions) having lengths between 19-25 nucleotides (pars. 85, 109).
Claims 73-79, 84, and 90-97 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (published July 27, 2018; Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691) in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156).
Wang et al describes methods of identifying nucleic acids using SNAIL probes and primers (Fig. 1).
Regarding claim 73, Wang describes a method comprising contacting a cell with a target nucleic acid with a first pair of oligonucleotides where the first oligonucleotide of that pair has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region, as well as a first end and a second end (Figure 1A). Wang describes that the first complementarity region is complementary to a first portion of said nucleic acid, the second complementarity region is complementary to the fourth complementarity region, the third complementarity region is complementary to said sixth complementarity region, the fifth complementarity region is complementary to a second portion of the target nucleic acid, and that the second oligonucleotide comprises a unique matching sequence which hybridizes to the first oligonucleotide (Figure 1A). In the reference’s case, complementarity regions 1 and 5 are the parts of the first and second oligonucleotides which bind to adjacent regions on the target nucleic acid (see Figure 1A). Complementarity regions 2 and 3 are the immediately adjacent but distinct regions of the first oligonucleotide or ‘primer’ (Figure S1), which bind to the complementarity regions 4 and 6 on either end of the second oligonucleotide, or ‘padlock.’ Complementarity regions 4 and 6 (shown with two double-sided red arrows in Figure S1) make up the matching sequence that hybridizes to the first oligonucleotide (Figure S1). Wang teaches ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule and amplifying the circular nucleic acid molecule to generate one or more amplicons (Fig. 1A). Wang also teaches imaging the amplicons to identify the target nucleic acid (Fig. 1C-E).
Wang teaches a unique sequence (‘barcode’ or ‘gene-unique identifier’) which is unique for the target nucleic acid (implicitly: shared between nucleic acids having the same sequence) and comprised in the second oligonucleotide (front page, col. 3, 1st par.; Figure on front page).
Regarding claim 73, Wang does not explicitly teach that the unique sequence is comprised in the portion of the second oligonucleotide which hybridizes to the first oligonucleotide.
Bava teaches a unique matching sequence (in the form of the ‘UBA’ or ‘Sequence Tag’/’SeqTag’) which is unique for the target nucleic acid (implicitly, shared between nucleic acids having the same sequence) and comprised in the second oligonucleotide (par. 111). Bava teaches a ‘unique counter tag’, which is unique to a single target molecule within a plurality of molecules (and not shared between nucleic acids having the same sequence; par. 36). Bava also teaches other unique sequences, including a sample identification barcode optionally included in the first oligonucleotide (par. 7) and a cell-originating barcode or COB (par. 6).
Bava does not explicitly teach that a target-specific unique sequence is comprised in the portion of the second oligonucleotide which hybridizes to the first oligonucleotide. However, Bava does teach that probes may bind in both confirmation-specific and sequence-specific manners, and that they may bind to combinations of molecules, including the target molecule and a target-molecule surrogate (par. 100). Given that here are a finite number of solutions (a finite number of positions with the first and second oligonucleotide), it would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of the detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
Regarding claims 74-76, Wang does not explicitly teach a second pair of oligonucleotides comprising a unique matching sequence which is different than the unique matching sequence of the first pair of oligonucleotides, where the two pairs bind to different targets or to the same target.
Bava teaches methods of identifying target molecules including nucleic acids (par. 6).
Regarding claim 74, Bava does not explicitly teach a second pair of oligonucleotides comprising a unique matching sequence which is different than the unique matching sequence of the first pair of oligonucleotides. However, Bava does discuss multiple sets of probes with at least two members each, and a given set of probes binding to the same target molecule in a confirmation-specific manner (par. 196). Given that there are a finite number of solutions (i.e. the same unique matching sequence for each pair or different unique matching sequences between two pairs), and there is no evidence of unexpected results, it would have been obvious to a person with ordinary skill in the art to try including different unique matching sequences in different sets/pairs of oligonucleotides, in order to achieve high specificity of binding in the probe complex (par. 86). This would be desirable for reducing background and improving signal-to-noise ratios (par. 113).
Regarding claims 75 and 76, Bava teaches at least two pairs of oligonucleotides binding to the same nucleic acid (par. 114) or to different nucleic acids (par. 7, 114).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention, to combine the teachings of Wang and Bava, in order to reduce variability and improve sensitivity (par. 114).
Regarding claim 77, Wang teaches using more than one pair of oligonucleotides (Figure 1A; pg. 4, col 3, 1st full par.).
Regarding claim 78, Wang teaches multiple rounds of imaging (Figure 1E).
Regarding claim 79, Wang teaches embedding sample in a hydrogel (pg. 1, col 3, 2nd full par.).
Regarding claims 84, 92, and 96, Wang teaches complementarity regions 1 and 5 (the target binding regions) with lengths of 19-25 nucleotides and with melting temperatures between 50-72ºC (Fig. S1(A), legend).
Regarding claims 90 and 91, Wang teaches complementarity regions 4 and 6 which comprise a first and second portion of a unique matching sequence which hybridizes to the first oligonucleotide (Figure S1(A) and legend).
Regarding claims 93-95 and 97, Wang teaches split complementarity regions 2 and 3 between 4-8 nucleotides in length (Figure S1(A) and legend). Although the reference does not explicitly teach that immediately adjacent complementarity regions 4 and 6 are 4-8 nucleotides long, they bind to complementarity regions 2 and 3, and therefore share the same length.
Claims 79-83 are rejected under 35 U.S.C. 103 as being unpatentable over Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156) as applied to claim 73 above, and further in view of Moffitt et al. (published May 17, 2018; WO 2018089438 A1).
Bava teaches the limitations of claim 73, as discussed in the rejection under 35 U.S.C. 103 above.
Regarding claims 79-83, Bava does not teach a sample embedded in a hydrogel, nor a gel adaptor or mRNA retention oligonucleotides.
Moffitt teaches a method of identifying nucleic acids in situ which employs multiple sets of oligonucleotides for both anchoring and imaging.
Regarding claim 79, Moffitt teaches embedding a biological sample in hydrogel (pg. 5, ln 23-30; pg. 6 ln 12-27).
Regarding claims 80 and 81, Moffitt teaches contacting a sample with a gel adaptor oligonucleotide with a 5' end and a 3' end, wherein either the 3’ or 5' end is modified to link to a hydrogel embedding the sample (pg. 11, ln 2-5). Moffitt does not recite a binding site for the gel adaptor oligonucleotide adjacent to the first complementarity region of the first of a pair of oligonucleotides which bind to a nucleic acid target. However, Moffitt does recite a gel adaptor nucleotide binding to a target through an intermediary binding component (pg. 12, ln 22-26; pg. 39, example 4), as well as gel adaptor nucleotides complementary to a common binding site (pg. 13, ln 18-21). It would have been obvious to a person with ordinary skill in the art to try including a common binding site on the first oligonucleotide instead of the target nucleic acid itself, as there are a finite number of solutions (i.e. a binding site meant to anchor target nucleic acids residing on the target nucleic acid itself or an oligonucleotide in a target-binding complex), and there is no evidence of unexpected results. One would have been motivated to do so, in order to clear a sample of background while retaining desired target nucleic acids for analysis (pg. 15, ln 4-7).
Regarding claims 82 and 83, Moffitt teaches an mRNA retention oligonucleotide with a 5’ or 3’ modification which links to the hydrogel and a unique hybridization sequence (pg. 11, ln 2-5), as well as a polyT tail comprised of interleaved LNA thymine bases (pg. 11, ln 6-16). In one embodiment, the mRNA retention oligonucleotide is used in combination with the gel adaptor oligonucleotide during in situ analysis of RNA (pg. 39-40: Example 4).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention, to combine the teachings of Bava and Moffitt in order to facilitate detection of nucleic acids of interest while removing components of the sample which may contribute to background noise (pg. 5 ln 1-9).
Claims 80-83 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (published July 27, 2018; Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691) in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156), as applied to claim 73 and 79 above, and in view of Moffitt et al. (published May 17, 2018; WO 2018089438 A1).
Wang and Bava teach the limitations of claims 73 and 79, as discussed in the rejection under 35 U.S.C. 103 above.
Regarding claims 80-83, Wang does not teach gel adaptor or mRNA retention oligonucleotides.
Moffitt teaches a method of identifying nucleic acids in situ which employs multiple sets of oligonucleotides for both anchoring and imaging.
Regarding claims 80 and 81, Moffitt teaches contacting a sample with a gel adaptor oligonucleotide with a 5' end and a 3' end, wherein either the 3’ or 5' end is modified to link to a hydrogel embedding the sample (pg. 11, ln 2-5). Moffitt does not recite a binding site for the gel adaptor oligonucleotide adjacent to the first complementarity region of the first of a pair of oligonucleotides which bind to a nucleic acid target. However, Moffitt does recite a gel adaptor nucleotide binding to a target through an intermediary binding component (pg. 12, ln 22-26; pg. 39, example 4), as well as gel adaptor nucleotides complementary to a common binding site (pg. 13, ln 18-21). It would have been obvious to a person with ordinary skill in the art to try including a common binding site on the first oligonucleotide instead of the target nucleic acid itself, as there are a finite number of solutions (i.e. a binding site meant to anchor target nucleic acids residing on the target nucleic acid itself or an oligonucleotide in a target-binding complex), and there is no evidence of unexpected results. One would have been motivated to do so, in order to clear a sample of background while retaining desired target nucleic acids for analysis (pg. 15, ln 4-7).
Regarding claims 82 and 83, Moffitt teaches an mRNA retention oligonucleotide with a 5’ or 3’ modification which links to the hydrogel and a unique hybridization sequence (pg. 11, ln 2-5), as well as a polyT tail comprised of interleaved LNA thymine bases (pg. 11, ln 6-16). In one embodiment, the mRNA retention oligonucleotide is used in combination with the gel adaptor oligonucleotide during in situ analysis of RNA (pg. 39-40: Example 4).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention, to combine the teachings of Wang and Bava with the teachings of Moffitt in order to facilitate detection of nucleic acids of interest while removing components of the sample which may contribute to background noise (pg. 5 ln 1-9).
Claims 85 and 86 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (published July 27, 2018; Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691), in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156), as applied to claims 73 and 84 above, in view of Carlson et al. (published November 21, 2019; WO 2019222284 A1).
Wang and Bava teach the limitations of claims 73 and 84, as discussed above.
Regarding claim 86, Wang teaches amplicons comprising a barcode (Fig. 1A). In this case, Wang’s ‘gene-unique identifier’ sequence in the amplicon serves as the barcode.
Regarding claim 85, Wang and Bava do not teach the use of an antioxidant buffer as an antifade reagent.
Carlson teaches methods for identifying nucleic acids, including the use of STARmap for detection and sequencing of RNA in situ.
Regarding claim 85, Carlson teaches the use antioxidant antifade buffers (pg. 120, par. 393).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Wang and Bava with the teachings of Carlson in order to mitigate photodamage while using the STARmap protocol (pg. 120, par. 393).
Claims 85 and 86 are rejected under 35 U.S.C. 103 as being unpatentable over Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156), as applied to claims 73 and 84 above, and further in view of Carlson et al. (published November 21, 2019; WO 2019222284 A1)
Bava teaches the limitations of claims 73 and 84, as discussed above.
Regarding claim 86, Bava teaches amplicons comprising a barcode (par. 112, as a ‘SeqTaq’).
Regarding claim 85, Bava does not teach the use of an antioxidant buffer as an antifade reagent.
Carlson teaches methods for identifying nucleic acids, including the use of STARmap for detection and sequencing of RNA in situ.
Regarding claim 85, Carlson teaches the use antioxidant antifade buffers (pg. 120, par. 393).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Bava and Carlson in order to mitigate photodamage while using the STARmap protocol (pg. 120, par. 393).
Claims 93-95 and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156), as applied to claim 73 above, and further in view of Wang et al. (published July 27, 2018; Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691).
Bava teaches the limitations of claim 73, as discussed above.
Regarding claims 93-95 and 97, Bava does not teach complementarity regions 2, 3, 4, and 6 having a length of 4-8 nucleotides
Wang teaches the identification of nucleic acids using SNAIL probe sets in a predecessor method to STARmap 2 called STARmap (Abstract).
Regarding claims 93-95 and 97, Wang teaches split complementarity regions 2 and 3 between 4-8 nucleotides in length (Figure S1(A) and legend). Although the reference does not explicitly teach that immediately adjacent complementarity regions 4 and 6 are 4-8 nucleotides long, they bind to complementarity regions 2 and 3, and therefore share the same length.
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the teachings of Bava and Wang, in order to reduce primer-padlock hybridization in favor of binding to the target molecule (Wang: Fig. S1, legend).
Response to Arguments Concerning Rejections over 35 U.S.C. 103
In the response filed April 21, 2026, Applicant amended claims 73, 74, and 77-79. In the response, Applicant argued that claim 73 was novel over Bava and over Wang because neither met all limitations of the claim. Applicant argued that neither Bava nor Wang specifically teaches "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid," as recited in claim 73. Applicant argued that the rejections under 35 U.S.C. 103 were invalid because the claims in questions all depend from and include all of the elements of claim 73 and none of the references alone or in combination taught every element of claim 73, let alone all of the limitations of the rest of the claims.
These arguments have been fully considered. As a result of the Applicant’s amendments filed April 21, 2026, the rejections under 35 U.S.C. 102(a)(1) were withdrawn and the rejections under 35 U.S.C. 103 were updated to address newly amended limitations. These modified rejections address all of the elements of the claims, as discussed in the modified rejections above.
Double Patenting
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.
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Claims 73-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,008,608 in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of analyzing nucleic acids (ref claim 1). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides (ref claim 1)
wherein a first oligonucleotide has a first complementarity region that hybridizes to the target, and a second oligonucleotide has a fifth complementarity region which hybridizes to the target, and they hybridize to sites on the target which are adjacent (ref claim 1), and wherein
the first oligonucleotide has a complementarity region which hybridizes to a fourth and sixth complementarity region of the second oligonucleotide to form a matching sequence (ref claims 1),
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 1)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 1)
imaging amplicons to identify the target nucleic acid (ref claim 1, 13)
Although the reference patent does not explicitly say that the method is directed to identification of a nucleic acid target, its claims are directed toward sequencing, which is a manner of identification. Although the reference patent does not teach distinct complementarity regions 2 and 3 in the first oligonucleotide which bind to the second oligonucleotide, CR2 on the first oligonucleotide may be viewed as two immediately adjacent binding sites, consistent with that limitation. The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, it does teach that the second oligonucleotide comprises a unique sequence (claim 14), and Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
Claims 73-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,982,271, in view of Wang et al. (Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691) and in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of identifying nucleic acids (ref claim 1). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides (ref claim 1)
wherein a first oligonucleotide has a first complementarity region that hybridizes to the target, and a second oligonucleotide has a fifth complementarity region which hybridizes to the target, and they hybridize to sites on the target which are adjacent (ref claim 1), and wherein
the first oligonucleotide has a complementarity region which hybridizes to a fourth and sixth complementarity region of the second oligonucleotide to form a matching sequence (ref claims 1),
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 1)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 1)
using amplicons to identify the target nucleic acid (ref claim 1, 13)
Although the reference application does not teach distinct complementarity regions 2 and 3 in the first oligonucleotide which bind to the second oligonucleotide, CR2 on the first oligonucleotide may be viewed as two immediately adjacent binding sites, consistent with that limitation. Although the reference claims do not include a requirement for imaging, they are directed towards sequencing of amplicons generated from SNAIL probe sets, and it would be obvious to sequence such amplicons using methods such as SEDAL which require imaging (Wang: Fig. 1). One would, for example, be motivated to do so in order to reduce error accumulation during sequencing (Wang: pg. 4, col. 1, 2nd par.). The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
Claims 73-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,359,253, in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of identification of nucleic acids (ref claim 1). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides wherein a first oligonucleotide has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region (ref claim 1),
The first complementarity region is complementary to a first portion of said nucleic acid, the second complementarity region is complementary to the fourth complementarity region, the third complementarity region is complementary to the sixth complementarity region, the fifth complementarity region is complementary to a second portion of the target nucleic acid (ref claim 1)
The first complementarity region hybridizes to a site on the target which is adjacent to the site hybridized by the fifth complementarity region (ref claim 28)
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 21)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 1)
imaging amplicons to identify the target nucleic acid (ref claim 1)
Although the reference application does not explicitly say that the second oligonucleotide has a unique matching sequence which hybridizes to the first oligonucleotide, complementarity regions 4 and 6 are a sequence which binds to the complementarity regions 2 and 3 in the first oligonucleotide and thus can be said to be a unique matching sequence between the pair (ref claim 1). The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, it does teach that the second oligonucleotide comprises a unique sequence (claim 14), and Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
Claims 73-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 96-121 of Application No. 18/561,262 in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of identification of nucleic acids (ref claim 107). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides wherein a first oligonucleotide has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region, as well as a first end and a second end (ref claim 110),
The first complementarity region is complementary to a first portion of said nucleic acid, the second complementarity region is complementary to the fourth complementarity region, the third complementarity region is complementary to said sixth complementarity region, the fifth complementarity region is complementary to a second portion of the target nucleic acid (ref claim 110)
The first complementarity region hybridizes to a site on the target which is adjacent to the site hybridized by the fifth complementarity region (ref claim 110)
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 112)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 110)
imaging amplicons to identify the target nucleic acid (ref claim 110)
Although the reference application does not explicitly say that the second oligonucleotide has a unique matching sequence which hybridizes to the first oligonucleotide, complementarity regions 4 and 6 represent a sequence which hybridizes to the complementarity regions 2 and 3 in the first oligonucleotide and thus can be said to be a unique matching sequence between the pair (ref claim 110). The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 73-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-75 of Application No. 17/768,996 in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of identification of nucleic acids (ref claim 49). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides (ref claim 49)
wherein a first oligonucleotide has a first complementarity region that hybridizes to the target, and a second oligonucleotide has a fifth complementarity region which hybridizes to the target (ref claims 50, 51),
The first complementarity region hybridizes to a site on the target which is adjacent to the site hybridized by the fifth complementarity region (ref claim 52)
the first oligonucleotide has a second and third complementarity region which hybridize to a fourth and sixth complementarity region of the second oligonucleotide (ref claims 53-54)
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 55)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 49)
imaging amplicons to identify the target nucleic acid (ref claim 49)
Although the reference application does not explicitly say that the second oligonucleotide has a unique matching sequence which hybridizes to the first oligonucleotide, complementarity regions 4 and 6 are a sequence which binds to the complementarity regions 2 and 3 in the first oligonucleotide and thus can be said to be a unique matching sequence between the pair (ref claim 50, 53-54). The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, it does teach a target-specific unique sequence (claim 61-62), and Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 73-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Application No. 19/390,190, in view of Wang et al. (Wang et al. Science. 2018 Jul 27;361(6400):eaat5691. doi: 10.1126/science.aat5691) in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides (ref claim 6) wherein a first oligonucleotide has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region, as well as a first end and a second end (ref claim 15-19),
The first complementarity region is complementary to a first portion of said nucleic acid (ref claim 15), the second complementarity region is complementary to the fourth complementarity region (ref claim 18), the third complementarity region is complementary to said sixth complementarity region (ref claim 19), the fifth complementarity region is complementary to a second portion of the target nucleic acid (ref claim 16)
The first complementarity region hybridizes to a site on the target which is adjacent to the site hybridized by the fifth complementarity region (ref claim 17)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 9, 20)
imaging amplicons to identify the target nucleic acid (ref claim 1, 11)
While the reference application does not explicitly say that the second oligonucleotide has a unique matching sequence which hybridizes to the first oligonucleotide, there is a sequence in the second oligonucleotide which hybridizes to the first oligonucleotide (ref claim 15, 18-19) which can be said to be a unique matching sequence between the pair. While the reference claims do not explicitly teach ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule, such a step would be an obvious embodiment of the claims and a routine technique for amplification reactions (see Wang: Figure 1A). Although the claims are directed toward a system, the system as claimed would employ the method of the instant application. The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 73-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Application No. 19/362,262 in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156). Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed to methods of identifying nucleic acids (ref claims 1, 7-8, 15-20). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides wherein a first oligonucleotide has a first complementarity region, a second complementarity region, and a third complementarity region; and a second oligonucleotide has a fourth complementarity region, a fifth complementarity region, and a sixth complementarity region (ref claim 1),
The first complementarity region is complementary to a first portion of said nucleic acid, the second complementarity region is complementary to the fourth complementarity region, the third complementarity region is complementary to said sixth complementarity region, the fifth complementarity region is complementary to a second portion of the target nucleic acid (ref claim 1)
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 11)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 1, 12-13)
imaging amplicons to identify the target nucleic acid (ref claim 1, 7-8)
Although the reference does not explicitly recite that first complementarity region hybridizes to a site on the target which is adjacent to the site hybridized by the fifth complementarity region, it does claim that they both hybridize to the nucleic acid as well as each other (ref claim 1), meaning the first and fifth complementarity regions would hybridize to adjacent regions on the target molecule, making the reference’s claims consistent with the instant application’s limitations. While the reference application does not explicitly say that the second oligonucleotide has a unique matching sequence which hybridizes to the first oligonucleotide, there is a sequence in the second oligonucleotide which hybridizes to the first oligonucleotide (ref claim 1), which can be said to be a unique matching sequence between the pair. The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 73-97 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Application No. 19/213,523 in view of Bava et al. (published March 28, 2019; Patent Publication No. US 2019/0093156).. Although the claims at hand are not identical, they are not patentably distinct from each other. Both sets of claims are directed toward methods of identification of nucleic acids (ref claim 1). Both sets of claims require:
Contacting a cell with at least a pair of oligonucleotides (ref claim 1)
wherein a first oligonucleotide has a first complementarity region that hybridizes to the target, and a second oligonucleotide has a fifth complementarity region which hybridizes to the target, and the first and fifth regions bind to adjacent regions on the target (ref claim 1)
the first oligonucleotide has a second and third complementarity region which hybridize to a fourth and sixth complementarity region of the second oligonucleotide to form a matching sequence (ref claims 1)
ligating the first and second ends of the second oligonucleotide to one another to generate a circular nucleic acid molecule (ref claim 1)
amplifying the circular nucleic acid molecule to generate one or more amplicons (ref claim 1)
imaging amplicons to identify the target nucleic acid (ref claim 1, 12, 13)
Although the reference application does not teach distinct complementarity regions 2 and 3 in the first oligonucleotide which bind to the second oligonucleotide, CR2 on the first oligonucleotide (ref claim 1) may be viewed as two immediately adjacent complementarity regions (complementarity sites 2 and 3), making the reference’s claims consistent with the instant application’s limitations. The reference does not teach "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid." However, it does teach a target-specific unique sequence in either the first or the second oligonucleotide (claim 17), and Bava teaches target-specific unique sequences (par. 17, 111). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to try incorporating a target-specific sequence into the matching sequence between the first and second oligonucleotide. One would have been motivated to do so in order to ensure that the complex of the first and second oligonucleotide with the target was one of high specificity (par. 86). One would have had reasonable expectation of success in doing so because Bava demonstrates that unique sequences may be included in various elements of a detection system (for examples, see: par. 7; par. 17, last 6 lines; par. 111).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments Concerning Double Patenting Rejections
In the response filed April 21, 2026, Applicant amended claims 73, 74, and 77-79. In the response, Applicant argued that the instant application is patentably distinct from the patents and patent applications because none of the patents and patent applications met all limitations of the claim. Applicant argued that none of the patents and patent applications specifically states "wherein said second oligonucleotide comprises a unique matching sequence, wherein said unique matching sequence hybridizes to said first oligonucleotide and wherein said unique matching sequence is unique to the nucleic acid," as recited in claim 73
These arguments have been fully considered. As a result of the Applicant’s amendments filed April 21, 2026, the double patenting rejections were updated to include an additional reference to teach the newly amended limitation. These modified rejections are discussed above.
Conclusion
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.
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/C.M.J./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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