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 .
Election/Restrictions
It is acknowledged that Applicant elected without traverse claims 1-7, 9, 10, 14-16, 25, and 26 and the species: (a) a first form of FHO and (b) at least one label linked to the target-dependent fragment and/or the first form of FHO in the reply filed on July 10, 2026.
Claims 1-7, 9, 10, 14-16, 25, 26, 28-32, 34, 36, and 37 are currently pending.
Claims 28-32, 34, 36, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 10, 2026.
Although Applicant identified the elected species readable on claim 25, the recited “second duplex” is formed from the unelected ‘second form of FHO.’ Thus, claim 25 is also withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim.
Claims 1-7, 9, 10, 14-16, and 26 are herein examined.
Priority
It is acknowledged that the instant application is a 371 of international PCT Application No. PCT/KR2022/013921, filed September 16, 2022.
Acknowledgment is made of applicant's claim for foreign priority based on Korean application 10-2021-0125068, filed September 17, 2021. It is noted, however, that the foreign priority date is the effective filing date of the claimed invention if:
the foreign application supports the claimed invention under 112(a), and
the applicant has perfected the right of priority by providing
a certified copy of the priority application, and
a translation of the priority application (if not in English)
In the instant case, the applicant has submitted a certified copy of the priority application, but it is not in English and the examiner cannot determine if it supports the claimed invention. The effective filing date of the application is considered to be September 16, 2022, which is the filing date of the PCT Application.
Claim Rejections - 35 USC § 112
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 1-7, 9, 10, 14-16, and 26 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 1-7, 9, 10, 14-16, and 26 are rejected for the recitation of “a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence” in claim 1 as indefinite. It is not clear whether the tagging portion of the TO is intended to have both a ‘non-hybridizing nucleotide sequence’ and ‘the target nucleic acid sequence’ or if the tagging portion is intended merely to have a ‘nucleotide sequence which does not hybridize to the target nucleic acid sequence.’ Likewise, the following recitations are unclear
“a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence” (claim 1)
“a capturing portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO” (claim 1)
“an upstream primer comprising a hybridizing nucleotide sequence with the target nucleic acid sequence” (claim 10)
As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter. For the purposes of examination, these recitations will be interpreted to mean that each portion contains a sequence which does (or does not) hybridize to another portion of another oligonucleotide.
Claim 2 is rejected for the recitation of “located at a site of 2 to 5 nucleotides apart from the 3’-end” as indefinite. It is not clear whether the site of the first synthetic unnatural base is intended to be 2 to 5 nucleotides long and distant from the 3’-end, or whether it is intended to be ‘located at a site which is 2 to 5 nucleotides distant from the 3’-end.’ As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter. For the purposes of examination, the limitation will be interpreted to mean ‘located at a site which is 2 to 5 nucleotides distant from the 3’-end.’
Claim 10 is rejected because the use of the relative term ‘upstream’ renders the claim indefinite. The claim recites that the “upstream primer is located upstream the 5’ direction of the TO.” ‘Upstream’ is generally defined as a region in DNA or RNA which is located in the 5’ direction from a reference point. However, in claim 10 the reference point is unclear because there are multiple (reverse-complementary) oligonucleotides involved in the reaction. Thus, the limitation could indicate that the upstream primer binds to a position on the target nucleic acid which is 5’ from the TO’s binding site (which is in line with the art-derived definition of upstream primer) OR it could mean that the upstream primer binds to a position on the target nucleic acid which is adjacent to the 5’ end of the TO (and so 3’ or DOWNSTREAM of the TO – see portion of Fig. 1 below). The latter interpretation may be better understood as “the upstream primer binds to a site on the target nucleic acid which is 3’ of the site on the target nucleic acid which is bound by the TO.” Clarification is requested.
PNG
media_image1.png
171
410
media_image1.png
Greyscale
Claim 14 is rejected for the recitation of “downstream primer” because the term “downstream” is a relative term that renders the claim indefinite. There is no indication of which oligonucleotide is bound by the downstream primer, and (as discussed for claim 10) it is possible that the term “downstream” is being used here in a way which is contradictory to its meaning in the art (the art definition being ‘binding at a position on a target which is 3’ relative to another point of reference on the target’). As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter. Clarification is requested.
Claim 15 is rejected for the recitation of “at least one label linked to the target-dependent fragment and/or the first form of FHO” because, in the case that there are multiple labels, if the labels are linked to both the fragment and the FHO, it is unclear whether the claim is requiring that the SAME label or labels are present on both. That is, if labels X and Y are used, must the FHO and fragment both be bound to X and Y, or may the FHO be bound to X and the fragment to Y? As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter.
Claim 16 is rejected for the recitation of “the first duplex provides a detectable signal” and “detected by measuring a signal” because it is unclear if these signals are intended to be the same (i.e. it is not clear whether there are multiple signals which are detected or just one). As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter. If what is meant is that ‘the presence of the extended strand in step (c) is detected by measuring the detectable signal provided from the cleave of the first duplex,’ the claims must be amended to reflect that meaning.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 2, 5-7, 9, 10, 14, and 15 are rejected as unpatentable over Chun (published May 2, 2013; Patent Application Publication No. US 2013/0109588) in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Regarding claim 1, Chun teaches a method for detecting a target nucleic acid sequence (Abstract). Chun teaches that the method comprises the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (par. 45, step (a); Fig. 1). In Chun, the TO is referred to as a probing and tagging oligonucleotide or PTO.
Chun teaches that the method comprises the steps of: (a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (par. 45, step (b); par. 91); (b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (par. 45, step (c)-(d); Fig. 2); (c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (par. 45, step (f)). In Chun, the FHO is called a capturing and templating oligonucleotide or CTO.
Chun teaches that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (par. 45, step (b)). Chun teaches an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (par. 45, step (c)). Chun teaches that the capturing portion of the FHO comprises a second synthetic unnatural base capable of base pairing with the first synthetic unnatural base in the target-dependent fragment, and that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (par. 45, step (c)-(d)).
Regarding claim 5, Chun teaches that the first synthetic unnatural base is selected from S, B, K, X, J (par. 207). For clarity, iso-C and iso-G are alternative terms for S and B (consistent with teachings of the instant PGPub – par. 163)
Regarding claim 6, Chun teaches that the first synthetic unnatural base is any base of a pair selected from the group consisting of S-B base pair and K-X base pair (par. 207). For clarity, iso-C and iso-G are alternative terms for S and B (consistent with teachings of the instant PGPub – par. 163)
Regarding claim 7, Chun teaches that the tagging portion of the TO may be from 5 to 50 nucleotides in length (par. 70).
Regarding claim 9, Chun teaches that the enzyme having nuclease activity is an enzyme having 5' nuclease activity (par. 45, step (b)).
Regarding claim 10, Chun teaches that the method is performed in the presence of an upstream primer comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (par. 45, 77), and the upstream primer is located upstream of the TO (par. 75).
Regarding claim 14, Chun teaches that the method is performed in the presence of a downstream primer (par. 86).
Regarding claim 15, Chun teaches that the first duplex provides a detectable signal by at least one label linked to the target-dependent fragment and/or the first form of FHO (par. 45, step (e)), and the presence of the extended strand in step (c) is detected by measuring a signal provided from the first duplex (par. 45, step (f)).
Regarding claim 1, Chun does not explicitly teach that the target-dependent fragment comprises the first synthetic unnatural base. However, Chun does teach that the TO (from which the target-dependent fragment is derived) may comprise a synthetic unnatural base (par. 237), and also that the extended product of the target-dependent fragment may comprise the first unnatural base (par. 205). Furthermore, Chun’s disclosure is concerned with reducing false positive detection of nucleic acids by reducing non-specific hybridization (par. 4-5).
Prudent teaches complementary synthetic unnatural bases in oligonucleotide binding pairs (par. 10, 23).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Chun and Prudent. One would have been motivated to position the synthetic unnatural bases in the fragment and the FHO because Prudent suggests that unnatural bases may be placed at any corresponding position in an oligonucleotide pair (Prudent: par. 23), which would include the claimed cleaved tagging portion of the TO. This would have the benefit of improving the annealing specificity between the target-dependent fragment and the FHO and reducing non-specific hybridization (Prudent: par. 122). One would have reasonable expectation of success because both Chun and Prudent are concerned with non-specific hybridization (Chun: par. 5; Prudent: par. 122), and because methods for the preparation of suitable oligonucleotides comprising synthetic unnatural bases are known (Prudent: par. 24-25, 90, 114; Chun: par. 207)
Regarding claim 2, Chun does not explicitly teach that the first synthetic unnatural base is located at a site of 2 to 5 nucleotides apart from the 3'-end of the tagging portion of the TO.
Prudent teaches pairs of oligonucleotides having complementary unnatural bases (par. 21), where the unnatural base is located 1-3 nucleotides or 4-10 nucleotides from the 3’-end of the oligonucleotide or within 5 nucleotides of the 3’ terminal nucleotide (par. 10, 23). This overlaps the claimed range of 2 to 5 nucleotides away from the 3’-end with sufficient specificity that the limitation is considered to have been met. Please note that the 3’-end of the tagging portion of the TO may also be considered the 3’-end of the target-dependent fragment (see instant Fig. 1).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to place the unnatural base 2 to 5 nucleotides from the 3’ end of the tagging portion of the TO because Prudent suggests that an unnatural base may be placed at any position in an oligonucleotide, including positions explicitly within the claimed range (par. 23). One would have had reasonable expectation of success because suitable unnatural bases and methods of incorporating them are known (e.g. Chun: par. 206-208).
Claim 3 is rejected as unpatentable over Chun (published May 2, 2013; Patent Application Publication No. US 2013/0109588) in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694), as applied to claim 1 above, and further in view of Marshall (published Oct. 17, 2002; Patent Application Publication No. US 20020150900)
Chun and Prudent teach the limitations of claim 1, as discussed above.
Regarding claim 3, Chun does not explicitly teach that the tagging portion of the TO further comprises 1 to 5 additional synthetic unnatural bases. Prudent teaches that oligonucleotide pairs may have one or more complementary synthetic unnatural base pairs (par. 111).
Marshall teaches unnatural base pairs which contribute to the formation of oligonucleotide duplexes (par. 91; Fig. 1 – parts 114 and 130), which may be present as a plurality (par. 112).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to optimize the number of unnatural bases because Marshall demonstrates that the number of unnatural bases in an oligonucleotide is a results-effective variable (par. 112). One would have had reasonable expectation of success because Marshall explicitly contemplates and tests embodiments having oligonucleotide pairs each comprising more than one unnatural base (par. 65, 314).
Claim 4 is rejected as unpatentable over Chun (published May 2, 2013; Patent Application Publication No. US 2013/0109588) in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694), as applied to claim 1 above, in view of Marshall (published Oct. 17, 2002; Patent Application Publication No. US 20020150900), as applied to claim 3 above, and further in view of Kimoto (published online Dec. 10, 2008; Kimoto et al. Nucleic Acids Res. 2009 Feb;37(2):e14).
Chun and Prudent teach the limitations of claim 1, as discussed above. Chun, Prudent, and Marshall teach the limitations of claim 3, as discussed above.
Regarding claim 4, the combined references do not explicitly teach that the first and 1 to 5 additional synthetic unnatural bases are positioned 1 to 10 nucleotides apart from each other.
Kimoto teaches the use of the unnatural base pair Px-Ds (pg. 3, col 2, 2nd to last par.). Regarding claim 4, Kimoto teaches detection of oligonucleotides comprising a plurality of such unnatural bases, separated by 4-12 nucleotides (pg. 6, col. 1, last par.; Figure 4a-c). This overlaps the claimed range of 1 to 10 nucleotides with sufficient specificity that the limitation is considered to have been met.
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to optimize the number of intervening nucleotides between unnatural bases because Kimoto teaches that this number is a results-effective variable (pg. 6, col. 1, last par.; Figure 4b). One would have had reasonable expectation of success because Kimoto synthesized and assessed appropriately spaced unnatural bases in oligonucleotides (Fig. 4a-b).
Claim 16 is rejected as unpatentable over Chun (published May 2, 2013; Patent Application Publication No. US 2013/0109588) in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694), as applied to claim 1 above, and further in view of Lee (published Aug. 27, 2020; Patent Application Publication No. US 20200270679).
Chun and Prudent teach the limitations of claim 1, as discussed above.
Regarding claim 16, the combined references do not explicitly teach that the first duplex comprises a cleavage site to be cleaved by a nucleolytic enzyme, the first duplex provides a detectable signal by cleavage at the cleavage site, and the presence of the extended strand in step (c) is detected by measuring a signal provided from cleavage of the first duplex. Chun instead teaches a method in which detectable signal is produced upon hybridization of an oligonucleotide which creates distance between quencher and reporter (par. 45, step f).
Lee teaches a duplex which comprises a cleavage site to be cleaved by a nucleolytic enzyme, where the duplex provides a detectable signal by cleavage at the cleavage site, and where the presence of an extended strand is detected by measuring a signal provided from cleavage of the duplex (par. 285). Lee also teaches separation of fluorescent and quencher moieties by conformation change and distance achieved through hybridization (par. 188)
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to substitute the hybridization/distance method for the cleavage method because the methods are used for the same purpose (i.e. generating detectable signal through separation of quencher/fluorophore pairs) and can therefore be considered functional equivalents. One would have had reasonable expectation of success because Lee discusses how cleavage may be achieved (par. 285-286, 293, 296).
Claim 26 is rejected as unpatentable over Chun (published May 2, 2013; Patent Application Publication No. US 2013/0109588) in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694), as applied to claim 1 above, and further in view of Wojciechowski (published Dec 2011; Wojciechowski & Leumann. Chem Soc Rev. 2011 Dec;40(12):5669-79).
Chun and Prudent teach the limitations of claim 1, as discussed above.
Regarding claim 26, the combined references do not explicitly teach that a Tm value of the first duplex is 0.5 to 10°C higher than a Tm value of a duplex in which the first and second synthetic unnatural bases comprised in the first duplex are substituted with natural bases.
Wojciechowski teaches that the Tm value of a duplex having an unnatural base pairing may have a melting temperatures 3.2ºC – 9ºC higher than that of a duplex having natural base pairing (e.g. see pg. 5671, col. 2, par. 2; pg. 5673, col. 1, 1st par.).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to optimize the melting temperature of the duplex to arrive at a Tm which is 0.5ºC to 10ºC higher than a Tm value of a duplex lacking a synthetic unnatural base pair because each of the combined references teaches that Tm is a results-effective variable in designing oligonucleotide pairs (e.g. Chun: par. 126; Prudent: par. 91-94). One would have had reasonable expectation of success because Wojciechowski demonstrates that Tm is affected by synthetic unnatural base pairs (as discussed 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.
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.
Claims 1-7, 9, 10, 14-16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of Patent No. 8,809,239, in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to methods for detecting a target nucleic acid. Both sets of claims require:
the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (claim 1 – referred to as a probing and tagging oligonucleotide or PTO);
that the method comprises the steps of:
(a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (claim 1, step (b));
(b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (claim 1, step (c) – called a capturing and templating oligonucleotide or CTO);
(c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (claim 1, step (f)).
that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (claim 1, step (b));
an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (claim 1, step (c))
that the capturing portion of the FHO comprises a synthetic unnatural base capable of base pairing with a first synthetic unnatural base in the extended target-dependent fragment (claim 12)
that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (claim 1, step (c) – (d))
Although the reference does not explicitly require that the target-dependent fragment (and not its extended product) comprises the first synthetic unnatural base, it would be obvious to one with ordinary skill in the art to configure the complementary unnatural bases in such a way because Prudent suggests that an unnatural base pair may be placed at any corresponding positions in an oligonucleotide pair (par. 23).
Claims 1-7, 9, 10, 14-16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of Patent No. 9,868,980, in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to methods for detecting a target nucleic acid. Both sets of claims require:
the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (claim 1 – referred to as a probing and tagging oligonucleotide or PTO);
that the method comprises the steps of:
(a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (claim 1, step (b));
(b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (claim 1, step (c) – called a capturing and templating oligonucleotide or CTO);
(c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (claim 1, step (f)).
that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (claim 1, step (b));
an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (claim 1, step (c))
that the capturing portion of the FHO comprises a synthetic unnatural base capable of base pairing with a first synthetic unnatural base in the extended target-dependent fragment (claim 7)
that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (claim 1, step (c) – (d))
Although the reference does not explicitly require that the target-dependent fragment (and not its extended product) comprises the first synthetic unnatural base, it would be obvious to one with ordinary skill in the art to configure the complementary unnatural bases in such a way because Prudent suggests that an unnatural base pair may be placed at any corresponding positions in an oligonucleotide pair (par. 23).
Claims 1-7, 9, 10, 14-16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of Patent No. 9,683,259 in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to methods for detecting a target nucleic acid. Both sets of claims require:
the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (claim 1 – referred to as a probing and tagging oligonucleotide or PTO);
that the method comprises the steps of:
(a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (claim 1, step (b));
(b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (claim 1, step (c)-(d) – called a capturing and templating oligonucleotide or CTO);
(c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (claim 1, step (f)).
that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (claim 1, step (b));
an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (claim 1, step (c))
that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (claim 1, step (c) – (d))
Although the reference does not explicitly require that that the capturing portion of the FHO comprises a synthetic unnatural base capable of base pairing with a first synthetic unnatural base in the target-dependent fragment, it would be obvious to one with ordinary skill in the art to include unnatural bases as complementary pairs to improve annealing specificity and reduce non-specific hybridization (Prudent: par. 122) and to configure the complementary unnatural bases in the claimed manner because an unnatural base pair may be placed at any corresponding positions in an oligonucleotide pair (Prudent: par. 23).
Claims 1-7, 9, 10, 14-16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of Patent No. 11,447,814 in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to methods for detecting a target nucleic acid. Both sets of claims require:
the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (claim 1 – referred to as a probing and tagging oligonucleotide or PTO);
that the method comprises the steps of:
(a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (claim 1, step (a)-(b));
(b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (claim 1, step (d) – called a capturing and templating oligonucleotide or CTO);
(c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (claim 1, step (f)).
that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (claim 1, step (b));
an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (claim 1, step (c))
that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (claim 1, step (c) – (d))
Although the reference does not explicitly require that that the capturing portion of the FHO comprises a synthetic unnatural base capable of base pairing with a first synthetic unnatural base in the target-dependent fragment, it would be obvious to one with ordinary skill in the art to include unnatural bases as complementary pairs to improve annealing specificity and reduce non-specific hybridization (Prudent: par. 122) and to configure the complementary unnatural bases in the claimed manner because an unnatural base pair may be placed at any corresponding positions in an oligonucleotide pair (Prudent: par. 23).
Claims 1-7, 9, 10, 14-16, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 8, 10, 11, 13-16, 22-24, 26, and 29-32 of co-pending Application No. 14/904,170, in view of Prudent (published Nov. 15, 2007; Patent Application Publication No. US 20070264694).
Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to methods for detecting a target nucleic acid. Both sets of claims require:
the use of a tag oligonucleotide (TO), which comprises (i) a tagging portion comprising a non-hybridizing nucleotide sequence with the target nucleic acid sequence and (ii) a targeting portion comprising a hybridizing nucleotide sequence with the target nucleic acid sequence (claim 1 – referred to as a probing and tagging oligonucleotide or PTO);
that the method comprises the steps of:
(a) reacting the target nucleic acid sequence with a TO; wherein the reacting involves hybridization of the TO with the target nucleic acid sequence and cleavage of the TO depending on the presence of the target nucleic acid sequence to release a target-dependent fragment wherein the cleavage of the TO is performed by an enzyme having nuclease activity (claim 1, step (b));
(b) reacting the target-dependent fragment with a fragment-hybridizing oligonucleotide (FHO) to form a first duplex (claim 1, step (c) – called a capturing and templating oligonucleotide or CTO);
(c) detecting the presence of the extended strand in the first duplex; wherein the presence of the extended strand in the first duplex is indicative of the presence of the target nucleic acid sequence (claim 1, step (f)).
that the target-dependent fragment comprises the tagging portion or a part of the tagging portion of the TO (claim 1, step (b));
an FHO which is (i) a first form of FHO comprising, in a 3' to 5' direction, a capturing portion having a hybridizing nucleotide sequence with the target-dependent fragment and a templating portion having a non-hybridizing nucleotide sequence with the target-dependent fragment and the targeting portion of the TO (claim 1, step (c))
that the capturing portion of the FHO comprises a synthetic unnatural base capable of base pairing with a first synthetic unnatural base in the extended target-dependent fragment (claim 13)
that the target-dependent fragment is hybridized with the capturing portion of the FHO and is extended to generate an extended strand comprising an extension sequence complementary to the templating portion of the FHO, thereby inducing the formation of a first duplex between the extended strand and the FHO (claim 1, step (c) – (d))
Although the reference does not explicitly require that the target-dependent fragment (and not its extended product) comprises the first synthetic unnatural base, it would be obvious to one with ordinary skill in the art to configure the complementary unnatural bases in such a way because Prudent suggests that an unnatural base pair may be placed at any corresponding positions in an oligonucleotide pair (par. 23).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine M Jones whose telephone number is (571)272-2585. The examiner can normally be reached Monday - Friday, 8AM - 4PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.M.J./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights