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 Applications, Amendments and/or Claims
This action is written in response to applicant's correspondence submitted 11/12/2025. In the paper of 11/12/2025, no claim amendments are newly presented. Instead, Applicant provided new arguments to traverse the rejections of the Non-Final Office action of 08/13/2025. Claims 40-46 and 51-53 are remain under review.
This paper also corrects some errors found in the Non-Final paper of 08/13/2025. Specifically, the provisional rejections of claims 47-50 are not reported correctly as moot. This office action also amends specific rejections under 35 U.S.C. 102(a)(1) which are now replaced instead with new rejection(s) under 35 U.S.C. 103.
Response to Arguments
Moot Rejection(s)
The rejection of claim 47 under 35 U.S.C. 102(a)(1) as being anticipated by Islam et al. (2012, Nature Protocols, 7(5), pp.813-828) is moot as claim 47 is canceled.
The rejection of claims 47-50 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,066,707 are moot as these claims are canceled.
The provisional rejection of claims 47-50 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/204,688 are moot as these claims are canceled.
The provisional rejection of claims 47-50 on the ground of nonstatutory double patenting as being unpatentable over claims 6-22 of copending Application No. 18/204,703 are moot as these claims are canceled.
Withdrawn Rejection(s)
The rejection of claim 40 under 35 U.S.C. 102(a)(1) as being anticipated by Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822) is withdrawn. A new rejection under 35 U.S.C 103 is presently instead.
Maintained Rejection(s)
The rejection of claim 40 under 35 U.S.C. 102(a)(1) as being anticipated by Islam et al. (2012, Nature Protocols, 7(5), pp.813-828) is maintained.
The rejection of claims 52-53 under 35 U.S.C. 103 as being unpatentable over Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822) as applied to claim 40 above, and further in view of Novak et al. (2011, Angewandte Chemie (International ed. in English), 50(2), 390, p.1-10) is maintained.
The rejection of claims 40-44 and 48-51 under 35 U.S.C. 103 as being unpatentable over Diehl et al. (2005, P.N.A.S., 102(45), pp.16368-16373) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822) is maintained.
The rejection of claims 40-46 and 51-53 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,066,707 is maintained.
The rejection of claims 52-53 under 35 U.S.C. 103 as being unpatentable over Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822) as applied to claim 40, further in view of Novak et al. (2011, Angewandte Chemie (International ed. In English), 50(2), 390, p.1-10) is maintained.
The provisional rejection of claims 40-46 and 51-53 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/204,688 is maintained.
The provisional rejection of claims 40-46 and 51-53 on the ground of nonstatutory double patenting as being unpatentable over claims 6-22 of copending Application No. 18/204,703 is maintained.
Argument(s)
Applicant’s arguments filed 11/12/2025 have been fully considered but they are not persuasive because of the following.
Concerning the rejection under 35 U.S.C. 102(a)(1) citing Islam et al. (2012, Nature Protocols, 7(5), pp.813-828), Applicant’s argument that Islam does not teach using a synthesizing target nucleic acid copies using a polymerase and only a forward primer that anneals at a first temperature; but rather only reports using two primers and that STRT-V3-T30VN oligo acts as a primer for capturing mRNA containing a polyA tail is not found to be persuasive (Remarks of 11/12/2025, last para of pg 4 and 1st para of pg 5) .
Islam teach a 3’ end extension of the poly-A containing capture primer, construed as STRT-V3-T30VN oligo until a point of template switching wherein at said point, the polymerase recognizes the presence of a barcoded TSO oligonucleotide comprising a 3’ trinucleotide GGG repeat at its end. The TSO oligo subsequently acts as a template that further directs a templated driven extension of extended STRT-V3-T30VN oligo.
Concerning the rejection under 35 U.S.C. 103 citing under Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822), Applicant’s argument that Kumaresan et al. does not teach using a synthesizing target nucleic acid copies using a polymerase and only a forward primer that anneals at a first temperature, is also not found to be fully persuasive. Applicant argues that in Kumaresan et al., reverse primers conjugated to the bead are extended and argues a distinction for reverse primer extension as requiring annealing to the 3’ end of the target nucleic acid sequence, said reverse primer comprising of a complementary sequence to the target nucleic acid. Applicant argues that the reverse primers taught by Kumaresan are distinct from and do extend opposite to the instant only forward primers.
The Office disagrees with this characterization of Kumaresan’s teachings.
Kumaresan et al. as evidenced by Dressman et al. teach a first single primer extension of non-biotinylated forward primer free in solution of an aqueous droplet compartment which generates copies of single strand templates that will be needed to anneal to bead conjugated reverse primers.
Concerning the reverse primers that are conjugated to a bead and extended, the Office has not concluded that the single copy template that anneals to bead conjugated reverse primer actually allow the reverse primers to truly act as reverse primers. To confirm how the reverse primer is extended, the Office would need to find the sequence of the reverse primer and the sequence of template and verify that the reverse primers anneal at or near the 3’ end of the bound template and the reverse primer become extended at the 3’ end of the primer.
Further, Figure 1B on pg 3523 of Kumaresan et al. as evidenced by Dressman shows/indicate a first initiation reaction where a single target nucleic acid copy anneals to a free non-biotinylated forward primer of an aqueous compartment, the forward primer is extended to synthesize copies of template. Kumaresan the teach subsequent annealing of the template/template copies to reverse primer conjugated to the bead and a subsequent annealing of and extension of the dye labeled forward primers on the bead.
Applicant argues against Dressman because Dressman explicitly reports using BOTH forward and reverse primers during PCR. Dressman states "a small amount of nonbiotinylated forward primer identical in sequence to the biotinylated oligonucleotide coupled to the beads was included in the reactions" and "an excess of the reverse primer was included in the aqueous compartment" (Dressman, page 8819, Step 3). The Office does not find these arguments to be persuasive. The limitation “ONLY” in claim 40 does not exclude the presence of reverse primer. However, Applicant is correct that not every copy of target nucleic acids would be from forward primer extension.
Still, the claim’s limitation of providing a single primer extension is prima facie obvious over Kumaresan as evidenced by Dressman et al. who teach asymmetric amplification using very limited amounts of one of the primers since the miniscule/limited concentration of reverse primers is very quickly exhausted, is operationally required in asymmetric amplifications, and the extension of reverse primers would not primarily drive the synthesis of copies of target nucleic acids but that of the ONLY forward primers would. It is suggested that claim 40 explicitly require the lack of presence of reverse primers.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 40 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Islam et al. (2012, Nature Protocols, 7(5), pp.813-828).
Regarding claim 40, Islam et al. teach a method of detecting a target nucleic acid, the method comprising:
obtaining a sample comprising target nucleic acid;
synthesizing copies of the target nucleic acid with polymerase and only a forward primer that anneals to the target nucleic acid at a first temperature;
amplifying the copies to yield amplification product via polymerase chain reaction (PCR) using a PCR primer pair that anneals to the copies at a second temperature that differs by at least about 10 ºC from the first temperature; and
analyzing the amplification product to detect the target nucleic acid.
Specifically, Islam et al. teach a reverse transcription assay that provides a polymerase and only a forward primer (i.e. STRT-V3-T30VN oligo used in steps 12-15: see pg 818-819) for synthesizing copies of the target nucleic acid. Islam et al. teach that STRT-V3-T30VN oligo anneals to the target nucleic acid at a first temperature (see pg 819, step 15, wherein the annealing occurs at a temperature of 42 ºC for 45 min).
Islam et al. teach a PCR assay using a primer pair for amplifying the copies to yield amplification product. Islam et al. teach annealing of the primer pair at a second temperature that differs by at least about 10 ºC from the first temperature (see pg 820, steps 26-32: annealing occurs in step 31 at 65 ºC for 30 sec).
Islam et al. teach analyzing the amplification product to detect the target nucleic acid (pg 812, steps 35-36).
Accordingly, Islam et al. teach the instant claim 40.
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.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822).
Regarding claim 40, Kumaresan et al. teach a method of detecting a target nucleic acid (see abstract, wherein Kumaresan teach target nucleic acid is glyceraldehyde 3 phosphate dehydrogenase (GAPDH) gene in human lymphocyte cells or the gyr B gene in bacterial Escherichia coli K12 cells).
Kumaresan et al. indicates a scheme for their method as shown on pg 3523, Figs. 1A, 1B (also reproduced below).
Figs. 1A-1B of page 3523
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The method of Kumaresan et al. comprises:
obtaining a sample comprising target nucleic acid (pg 3525, left col. last para: 380 bp region of puc18 plasmid amplified);
synthesizing copies of the target nucleic acid with polymerase and only a forward primer (Fig. 1B above);
amplifying the copies to yield amplification product (Fig. 1B); and
analyzing the amplification product to detect the target nucleic acid (pg 3524, left col., Experimental Section, subsection entitled “Droplet PCR and Product quantitation”).
Dressman et al. teaches the BEAMing method as sequentially comprising steps 1-6, wherein the steps are: step 1 (coupling oligonucleotides to beads), step 2 (preparing microemulsions), step 3 (PCR cycling), step 4 (Magnetic capture of beads), step 5 (Sequence differentiation) and step 6 (Flow cytometry).
On page 8819, about step 3, Dressman teach:
“Step 3: PCR Cycling. PCR priming by oligonucleotides coupled to beads was found to be very inefficient compared with the priming by the same oligonucleotides when free in solution.
For this reason, a small amount of nonbiotinylated forward primer identical in sequence to the biotinylated oligonucleotide coupled to the beads was included in the reactions. This facilitated the first few rounds of amplification of the single template within each aqueous compartment.
In the absence of additional primer, no detectable amplification on the beads was generated. Conversely, if too much additional primer was included, no amplification on the beads occurred because of competition with the primers in solution. An excess of the reverse primer was included in the aqueous compartment to maximize the probability that bead-bound oligonucleotides extended by polymerase would serve as templates for further amplification cycles” (ppg 8819).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention that apply a teaching of the method of Kumaresan et al. which provides a limited amount of nonbiotinylated forward primer in each aqueous compartment to promote a few rounds of single primer amplification of the single template copy within each aqueous compartment, thereby optimize subsequent amplifications of single templates that would bind the reverse primer conjugated to the bead.
In view of the combined teachings and suggestions of all of the cited prior art references, the instant claim 40 is prima facie obvious.
Claims 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over Kumaresan et al. (2008, Analytical chemistry, 80(10), pp.3522-3529) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822) as applied to claim 40 above, and further in view of Novak et al. (2011, Angewandte Chemie (International ed. in English), 50(2), 390, p.1-10).
The teachings of Kumaresan et al as it concerns claim 40 are provided above.
Regarding claims 52-53, Kumaresan et al. teach their method as comprising diluting and partitioning the sample into reaction partitions, performing the synthesizing, amplifying within reaction partitions that are droplets.
However, Kumaresan et al. do not teach analyzing in the reaction partitions, and digitally counting the presence or absence of the target in the partitions using fluorescent probes.
Novak et al. teach provide agarose droplets for the purpose of performing the synthesizing, amplifying and analyzing of the amplification products within reaction partitions, and digitally counting the presence or absence of the target in the partitions using fluorescent probes (page 4, 3rd para).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Kumaresan et al. by applying the teachings of Novak et al., and thereby substitute agarose emulsion instead for encapsulation of the test target nucleic acid and forward primer and the primer pair for generating amplification product so as to be able amplify and to count the amplified target nucleic acid within the partition.
One of ordinary skill in the art would have had a reasonable expectation of success at combining/applying the teachings of the cited prior art references as the combinations would have yielded the same predictable results in a manner as indicated by the teachings.
In view of the combined teachings and suggestions of all of the cited prior art references, the instant claims 52-53 are prima facie obvious.
Claims 40-44 and 48-51 are rejected under 35 U.S.C. 103 as being unpatentable over Diehl et al. (2005, P.N.A.S., 102(45), pp.16368-16373) as evidenced by Dressman et al. (2003, P.N.A.S., 100(15), pp.8817-8822).
Diehl et al. (claims 40-43, 48-50)
Regarding claims 40-43 and 48-50, Diehl et al. is directed to a method of detecting and quantitating mutations in the plasma of patients with colorectal tumors (see title, pg 16368). Diehl et al. developed an assay that detects mutant adenomatous polyposis coli (APC) DNA molecules in the plasma of patients with advanced colorectal cancers (abstract). The median number of APC DNA fragments in such patients was 47,800 per ml of plasma (i.e. cell-free DNA), of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules (abstract).
Diehl et al. indicates a scheme for their method as shown on pg 16371, Fig. 2 (also reproduced below).
Fig. 2, Diehl, page 16371
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The method of Diehl et al. comprises:
obtaining a sample comprising target nucleic acid (see pg 16368, right col., section entitled “Materials and Methods”, para entitled “Sample Collection, DNA Extraction, and Sequencing”);
synthesizing copies of the target nucleic acid with polymerase and only a forward primer (see pg 16369, left col., section entitled “BEAMing”: wherein Diehl et al discloses use of 0.05 µM forward primer and 8 µM reverse primer so as to synthesize additional copies of target nucleic acids: Dressman et al. further explains (see below) why at these primer concentrations, amplification is essentially one that uses only one of the two primers);
amplifying the copies to yield amplification product (see pg 16368, right col., section entitled “Materials and Methods”, para entitled “Real-Time PCR” and pg 16369, left col., first para: or see the SBE extensions of Fig. 2B on page 16371); and
analyzing the amplification product to detect the target nucleic acid (see pg 16370, table 1 and pg 16369, left col., first para: wherein Diehl et al. discloses PicoGreen dsDNA quantitation and pg 16369, right col., section entitled “Development of a quantitative assay for detection of rare mutations”).
Dressman et al.
Regarding claim 40, Dressman et al. teaches the BEAMing method as sequentially comprising steps 1-6, wherein the steps are: step 1 (coupling oligonucleotides to beads), step 2 (preparing microemulsions), step 3 (PCR cycling), step 4 (Magnetic capture of beads), step 5 (Sequence differentiation) and step 6 (Flow cytometry).
On page 8819, about step 3, Dressman teach:
“Step 3: PCR Cycling. PCR priming by oligonucleotides coupled to beads was found to be very inefficient compared with the priming by the same oligonucleotides when free in solution.
For this reason, a small amount of nonbiotinylated forward primer identical in sequence to the biotinylated oligonucleotide coupled to the beads was included in the reactions. This facilitated the first few rounds of amplification of the single template within each aqueous compartment.
In the absence of additional primer, no detectable amplification on the beads was generated. Conversely, if too much additional primer was included, no amplification on the beads occurred because of competition with the primers in solution. An excess of the reverse primer was included in the aqueous compartment to maximize the probability that bead-bound oligonucleotides extended by polymerase would serve as templates for further amplification cycles” (ppg 8819).
Diehl et al. (claims 44 and 48-51)
Regarding claim 44, Diehl et al. teach partitioning the sample into reaction partitions and performing the synthesizing and the amplifying steps in the reaction partitions (pg 16369, left col. section entitled “BEAMing”).
Further regarding claims 48-50, Diehl et al. teach wherein the target nucleic acid comprises ctDNA, and is a marker for a clinical condition, and the method further comprises reporting the presence of the clinical condition in a subject. Diehl et teach method evaluate the susceptibility of a clinical condition to a treatment and includes reporting the presence of cancer in a subject (abstract and pg 16373, left col., 3rd para and pg 16373, right col., 2nd- 4th para).
Regarding claim 51, Diehl et al. teach each of the synthesizing and the amplifying steps include cycling between at least a denaturation temperature (@ 98°C) and an elongation temperature (@ 72°C) (pg 16368, right col., section entitled “Materials and Methods”, para entitled “Real-Time PCR”: wherein cycling conditions taught by Diehl et al. are:
98°C for 1 min (the instant denaturation);
98°C for 10 s, 70°C for 10 s, and 72°C for 10 s 3 times;
98°C for 10 s, 67°C for 10 s, and 72°C for 10 s 3 times;
98°C for 10 s, 64°C for 10 s, and 72°C for 10 s 3 times and
98°C for 10 s, 61°C for 10 s, and 72°C for 10 s 30 times).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to provide the method of Diehl et al. or Dressman et al. using a forward primer for an initial synthesis of template copies of a target nucleic acid and further use an additional primer for generating amplification product of the template copies so as to be able amplify and to count the amplified target nucleic acid within the partition.
One of ordinary skill in the art would have had a reasonable expectation of success at combining/applying the teachings of the cited prior art references as the combinations would have yielded the same predictable results in a manner as indicated by the teachings.
In view of the combined teachings and suggestions of all of the cited prior art references, the instant claims 40-44 and 48-51 are prima facie obvious.
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 40-46 and 51-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,066,707.
The instant claim 40 is directed to a method of detecting a target nucleic acid, the method comprising:
obtaining a sample comprising target nucleic acid;
synthesizing copies of the target nucleic acid with polymerase and only a forward primer;
amplifying the copies to yield amplification product; and
analyzing the amplification product to detect the target nucleic acid.
while
Claims 1-13 of U.S. Patent No. 11,066,707 are directed to methods for detection of the presence of a target nucleic acid sequence or detection of the presence of a variant sequence in a target nucleic acid sequence in a sample comprising the steps of
a) providing a sample comprising template nucleic acids, and at least a pair of primers specifically capable of amplification of the target nucleic acid sequence, wherein the set of primers at least comprises a primer-H and a primer-L,
e) performing an asymmetric incremental polymerase reaction (AIPR) comprising the steps of:
i) incubating the partitioned PCR reactions at a denaturation temperature, thereby denaturing DNA to single-stranded molecules,
ii) incubating the partitioned PCR reactions at a high annealing temperature allowing annealing of primer-H, but not of primer-L,
f) performing a polymerase chain reaction (PCR) comprising the steps of:
1) incubating the partitioned PCR reactions from step e) at a denaturation temperature, thereby denaturing DNA to single-stranded molecules,
2) incubating the PCR at a low annealing temperature allowing annealing of both primer-H and primer-L,
3) incubating the PCR at the elongation temperature thereby allowing extension of all annealed primers,
g) detecting whether the PCR product comprises the target nucleic acid sequence or the variant sequence in the target nucleic acid sequence.
Although the claims at issue are not identical, they are not patentably distinct from each other because both methods are for detecting target nucleic acids and both methods comprise a preamplification to synthesize copies of the target nucleic acid and an amplification to generate amplification products and an analysis step to detect the target nucleic acid.
Claim 1, steps of (a) and (e) of US Patent No. 11,066,707 are construed as providing a single primer (since an asymmetric incremental amplification recited).
The methods of US Patent No. 11,066,707 are construed as anticipating the instant method as presently claimed.
Claims 40-46 and 51-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/204,688.
The instant claim 40 is directed to a method of detecting a target nucleic acid, the method comprising:
obtaining a sample comprising target nucleic acid;
synthesizing copies of the target nucleic acid with polymerase and only a forward primer;
amplifying the copies to yield amplification product; and
analyzing the amplification product to detect the target nucleic acid.
while
claims 1-24 of copending Application No. 18/204,688 are directed to methods comprising:
identifying sequences under-represented in a sample;
performing a pre-amplification reaction to increase abundance of copies of the identified sequences within the sample;
performing an exponential amplification reaction on nucleic acids from the sample; and
analyzing the sample for the identified sequences.
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to methods of detecting nucleic acids comprising a preamplification to synthesize copies of the target nucleic acid and an amplification to generate amplification products and an analysis step to detect the target nucleic acid.
The preamplification reaction of copending Application No. 18/204,688 provides a single primer (claim 2: linear amplification recited; claims 12-14: asymmetric incremental amplification recited).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 40-46 and 51-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-22 of copending Application No. 18/204,703.
The instant claim 40 is directed to a method of detecting a target nucleic acid, the method comprising:
obtaining a sample comprising target nucleic acid;
synthesizing copies of the target nucleic acid with polymerase and only a forward primer;
amplifying the copies to yield amplification product; and
analyzing the amplification product to detect the target nucleic acid.
while
Claims 6-22 of copending Application No. 18/204,703 is directed to a method for variant detection, the method comprising the steps of:
providing a sample comprising one or more target nucleic acids;
performing pre-amplification to increase abundance of the target nucleic acid in the sample;
aliquoting the sample into a plurality of subsamples;
conducting polymerase chain reaction (PCR) on the subsamples; and
detecting the target nucleic acids.
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to methods of detecting nucleic acids comprising a preamplification to synthesize copies of the target nucleic acid and an amplification to generate amplification products and an analysis step to detect the target nucleic acid.
The preamplification reaction of copending Application No. 18/204,703 uses a single primer (see claims 6-9: asymmetric incremental amplification recited).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLAYINKA A OYEYEMI whose telephone number is (571)270-5956. The examiner can normally be reached Monday -Thursday: 9:00 am - 5:00 pm, EST.
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OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681 /GARY BENZION/Supervisory Patent Examiner, Art Unit 1681