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 .
The Applicants’ response to the office action filed on 13 February 2025 has been considered and acknowledged.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 February 2025 has been entered.
Status of the Application
Claims 51-58, 60 and 71-73 are under examination.
Sequence Non-compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §§ 1.821(d) because the Application contains at least 3 nucleotide sequences of ten or more nucleotides which are not marked with "SEQ ID NOs".
See Example I, sgRNA L, sgRNA R and primers, pg. 27-28; sgRNA species, pg. 30-31; Example II, spacers , pg. 32 of the instant specification.
The foregoing analysis should not to be deemed exhaustive, as there may be other polynucleotide or polypeptides disclosed which similarly require sequence identifiers. In accordance with 37 CFR 1.821(a), Nucleotide and/or amino acid sequences as used in § 1.821 through 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides. See the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures. Applicant must comply with the requirements of the sequence rules (37 CFR 1.821 - 1.825) before the application can be examined under 35 U.S.C. §§ 131 and 132.
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.
Tsai et al., Lebedev et al., Farmer et al. and Jinek et al.
Claim(s) 51- 58, 71 and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai et al. (WO2016028887; cited in IDS filed 25 July 2022) in view of Lebedev et al. (US20140038181); Farmer et al. (US20150225773) and Jinek et al. (WO2013176772).
Tsai et al. disclose methods for preparing a sequencing library comprising providing a nucleic acid sample and two guide RNA species wherein a first guide RNA targets one target region of the sample nucleic acid and the second guide RNA targets a second region of the sample nucleic acid; further contacting nucleic acid sample and two guide RNA species with cas9 endonuclease and incubating to allow cleavage of target nucleic acid facilitated by guide RNAs and cas9; attaching stem-loop adapters to cleaved target nucleic acid and subsequently subjecting resultant nucleic acid to sequencing (e.g. Entire Tsai reference and especially para 0007,pg. 3-4; an illustrative embodiment of methods for enriching for a target region of interest that comprises cleavage by two Cas9 endonucleases. Four different orientations of the two RNA-Cas9 complexes flanking the target region are shown as in para 0016,pg. 7; para 0066,pg. 35; para 0070, pg. 37; para 0120,pg. 63-64; Fig. 7).
Tsai et al. also teaches subjecting adapter-ligated target nucleic acid to amplification (e.g. Entire Tsai reference and especially para 0090, pg. 50; claim 15).
Tsai et al. teach the target nucleic acids are from natural and non-natural sources, including human and bacterial genomic DNA libraries as well as cloned DNA. Furthermore, Tsai et al. teach target nucleic acid is collected from cell lines or cell culture (e.g. Entire Tsai reference and especially …The target region(s) can comprise any region(s) of interest to the practitioner of the instant invention, e.g., a full-length repeat region from a genomic sample, a promoter region controlling expression of a gene of interest (which may or may not comprising a full-length repeat region), target regions from multiple chromosomes, target regions from homologous chromosomes, imprinted genes, splice isoforms, heterochromatic regions, euchromatic regions, genie regions, non-genic regions, regulatory regions, cloned nucleic acids, native nucleic acids, amplified nucleic acids, full haplotypes for a gene of interest, full alleles for a repeat expansion region, or nucleic acids from multiple sources, e.g., different genes, tissues, individual (e.g., cases and controls), barcoded nucleic acids, full-length genes and the corresponding m NA or cDNA sequences, and the like as in para 0008,pg. 4-5; para 0024-0025,pg. 9-10; target nucleic acid is collected from cell lines or cell culture as in para 0026, pg. 10-11; para 0120,pg. 63-64; para 0122,pg. 65).
Furthermore, Tsai et al. teach their methods can be used for analysis of a single target region or multiplexed for analysis of multiple target regions(e.g. Entire Tsai reference and especially para 0032-0033, pg. 13-14;… Further, although in the interest of clarity, many embodiments herein are described with reference to a single target region, it will be clear that these methods are extendable to enrichment of more than one target region in a complex mixture. For example, the methods can be used to enrich for two or more target regions. In certain embodiments, the methods are used to enrich for multiple target regions that correspond to a single metabolic pathway or disease process in an organism, or to fragments of a single organism's genome in a metagenomic sample… as in para 0043,pg. 19-20;… Further, although in the interest of clarity, many embodiments herein are described with reference to a single target region, it will be clear that these methods are extendable to enrichment of more than one target region in a complex mixture. For example, the methods can be used to enrich for two or more target regions as long as sgRNAs or crRNA:tracrRNA complexes can be designed to target such regions. In certain embodiments, the methods are used to enrich for multiple target regions that correspond to a single metabolic pathway or disease process in an organism, to fragments of a single organism's genome in a metagenomic sample, to specific viral subpopulations in a mixed viral sample, or to diagnostic markers, e.g., for disease susceptibility or drug response… as in para 0065,pg.34).
Therefore, Tsai et al. teach methods are known in the art comprising providing a mixture comprising target DNA molecule, one or more endonucleases, a first guide RNA molecule, a second guide RNA molecule, and sequencing adapters, wherein the first guide RNA molecule and second guide RNA molecule have sequence complementarity with sites flanking one or more regions in the target DNA molecule; subjecting to experimental conditions to permit one or more endonucleases to cleave the target DNA molecule at the sites which are hybridized with the first guide RNA molecule and second guide RNA molecule, thereby generating DNA fragments; and attaching the sequencing adapters to the DNA fragments to yield a set of DNA molecules as required by claim 51.
As noted above, Tsai et al. teach incubating target nucleic acid molecules with cas9 nuclease to facilitate cas9- mediated cleavage of target nucleic acid and to generate target nucleic acid fragments to which stem-loop adapters are ligated. The resultant stem-loop adaptor ligated target nucleic acid fragments are sequenced (e.g. para 0007, pg. 3-4; para 0066, pg. 35; para 0070, pg. 37; para 0120, pg. 63-64).
However, Tsai et al. do not expressly teach thermocycling as required by claim 51.
Regarding the limitations: contacting the DNA with a composition comprising a thermophilic DNA ligase, subjecting the DNA and the composition to PCR-free thermal cycling to allow cleavage of the DNA at the specific sites flanking the regions of interest by the endonuclease, wherein following cleavage heat denaturing is used to remove the endonuclease from cleaved DNA fragments as recited in claim 51:
Lebedev et al. teach methods comprising ligation are known, wherein the reaction is facilitated with a thermophilic ligase and a thermocycler under temperature conditions that are not used for PCR. Furthermore, Lebedev et al. teach experimental conditions, such as reaction temperature, are optimized ( e.g. Entire Lebedev reference and especially, para 0372-0373,pg. 30; Tth ligase as in Example 7, pg. 36; Example 8 ... The reaction mixture (50 uL) is prepared on ice by mixing 10 uL of 5xLCR buffer {250 mM Tris-HCl (pH 7.5), 50 mM MgC12 , 5 mM dithiothreitol, 125 μg/ml bovine serum albumin}, 5 uL of 10 mM cofactor (ATP or NAD+ ), 5 uL of 10 uM of each OXT-substituted or unsubstituted probes, 5 uL of DNA target (variable copy number), 15 uL of water and 5 uL ( 400 U/mL; 2 U total) of thermostable DNA ligase. The reaction mixture is overlaid with oil, and the reaction is activated by placing tube into a thermocycler at 95° C. for 5 min and incubated for 60 cycles consisting of 20 sat 95° C. and 30s at 55°-65° C. The exact ligation temperature depends on the length and composition of the oligonucleotide probes... as in para 0427,pg. 36; The reaction mixture (50 uL) is prepared on ice by mixing 10 uL of 5xLCR buffer {250 mM Tris-HCl (pH 7.5), 50 mM MgC12 , 5 mM dithiothreitol, 125 μg/ml bovine serum albumin}, 5 uL of 10 uM of each donor and acceptor probes, 15 uL of water, 5 uL of DNA target (variable copy number),5 uL ( 400 U/mL; 2 U total) of thermostable DNA ligase and 5 uL of 10 mM SC (substituted ATP or NAD+ ). The reaction mixture is overlaid with oil, and reaction is activated by placing tube into a thermocycler at 95° C. for 5 min and incubated for 60 cycles consisting of 20 sat 95° C. and 30s at 55°-65° C. The exact ligation temperature depends on the length and composition of the oligonucleotide probes... as in para 0428, pg. 36-37; The reaction mixture (50 uL) is prepared on ice by mixing 10 uL of 5xLCR buffer {250 mM Tris-HCl (pH 7.5), 50 mM MgC12 , ... 5 uL of 10 uM of acceptor probe, 5 uL of OXTSADI, 5 uL of DNA target (variable copy number), 20 uL of water and 5 uL (400 U/mL; 2 U total) of thermostable DNA ligase. The reaction mixture is overlaid with oil, and reaction is activated by placing tube into a thermocycler at 95° C. for 5 min and incubated for 60 cycles consisting of20 sat 95° C. and30 sat 55°-65° C. The exact ligation temperature depends on the length and composition of the oligonucleotide probes ... as in para 0429, pg. 37; Example 12,para 0439,pg. 39).
Therefore, as Tsai et al. and Lebedev et al. teach ligation for attachment of oligonucleotides to target , it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Tsai et al. to include using thermophilic ligase and PCR free thermocycling, wherein reaction temperature is optimized, as taught by Lebedev et al. because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method comprising providing conditions for ligase-mediated attachment of oligonucleotides to target nucleic acid.
Regarding cleavage conditions as recited in claim 51:
Farmer et al. teach conditions for cas9- mediated cleavage include incubation at a temperature of 37°C for one hour (e.g. para 0053-0054, pg. 6; para 0099,pg. 12; para 0104,pg. 13). Farmer et al. also teach providing equipment to maintain a desired temperature for a suitable period of time, including a thermocycler (e.g. para 0077-0078, pg. 9).
Furthermore, Jinek et al. teach Cas9 mediated assays wherein reaction mixture comprising Cas9 is incubated at 37°C for 1 hr and then Cas9 cleavage is stopped by incubating the reaction mixture for 5min at 95°C(e.g. para 00524, pg. 142).
The instant specification discloses embodiments wherein Cas9 is heat denatured at 95°C (e.g. 2nd para, pg. 6).
Therefore, although Farmer et al. do not expressly teach incubation conditions for Cas9- mediated cleavage using a thermocycler, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Farmer et al. comprising providing a temperature of 37°C for one hour to facilitate cas9- mediated cleavage as taught in one embodiment of Farmer to include using a thermocycler as taught in another embodiment of Farmer because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method comprising providing conditions for Cas9-mediated cleavage of target nucleic acid.
Furthermore, as Tsai et al., Farmer et al. and Jinek et al. all teach Cas9- mediated assays, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Tsai et al. and Lebedev et al. comprising thermophilic ligase-mediated attachment of oligonucleotides to target nucleic acid using non- PCR thermocycling conditions, wherein reaction temperature is optimized, and Cas9- mediated cleavage of target nucleic acid to include providing a temperature of 37°C for one hour using a thermocycler as taught by Farmer et al. and to include ending Cas9 cleavage by incubating the reaction mixture for 5min at 95°C as taught by Jinek et al. because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method comprising providing conditions for Cas9-mediated cleavage of target nucleic acid. Furthermore, Lebedev et al. teach experimental conditions, such as reaction temperature, are optimized.
Therefore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious the limitations: a method of preparing a sequencing library from a target DNA comprising the steps of: contacting the DNA with a composition comprising an endonuclease, a first guide RNA, a second guide RNA, a thermophilic ligase, and sequencing adapters, wherein the first guide RNA and the second guide RNA[[s]] guide the endonuclease to specific sites flanking regions of interest in the DNA, subjecting the DNA and the composition to PCR free thermal cycling to allow cleavage of the DNA at the specific sites flanking the regions of interest by the endonuclease, wherein following cleavage heat denaturing is used to remove the endonuclease from cleaved DNA fragments, and subjecting the DNA and the composition to a temperature to allow the cleaved DNA fragments to anneal and to allow ligation of the cleaved DNA fragments including the regions of interest with the sequencing adapters to generate a sequencing library as required by claim 51.
As Tsai et al. teach the target material comprises nucleic acids from any source, including human genomic DNA as well as cloned DNA (e.g. para 0024-0025,pg. 9-10; para 0120,pg. 63-64; para 0122,pg. 65), the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 52.
As Tsai et al. also teach the target material comprises nucleic acids collected from cell lines or cell cultures (e.g. para 0026,pg. 10-11), the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 53.
As Tsai et al. also teach methods comprising anneal a first and a second guide RNA such that they flank a target region (e.g. para 0007,pg. 3-4; an illustrative embodiment of methods for enriching for a target region of interest that comprises cleavage by two Cas9 endonucleases. Four different orientations of the two RNA-Cas9 complexes flanking the target region are shown as in para 0016,pg. 7;Fig. 7), the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 54.
Furthermore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious the limitation: wherein said one or more endonucleases comprise Cas9 as required by claim 55.
Regarding claims 56 and 57:
Claims 56 and 57 further describe an alternative of claim 55 that is not required by the claimed invention. Therefore, insofar as claims 56 and 57 are each dependent from claim 55, art that meets the requirements of claim 55 is also meets claims 56 and 57.
Therefore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claims 56 and 57.
Furthermore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 58.
As at least Tsai et al. also teach their methods are used for analysis of multiple target regions (e.g. para 0032-0033, pg. 13-14; para 0043,pg. 19-20; para 0065,pg.34), the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 71.
Furthermore, as Jinek et al. teach Cas9 mediated assays wherein reaction mixture comprising Cas9 is incubated at 37°C for 1 hr and then Cas9 cleavage is stopped by incubating the reaction mixture for 5min at 95°C(e.g. para 00524, pg. 142), the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious claim 73.
Tsai et al., Lebedev et al., Farmer et al., Jinek et al. and Chavez et al.
Claims 56 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied to claims 51- 58, 71 and 73 above, and further in view of Chavez et al. (WO2015077318; cited in IDS filed 25 July 2022).
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied in the rejection above are incorporated in this rejection.
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious a method of preparing a sequencing library comprising incubating target nucleic acid with guide RNA molecules and cas9 nuclease to generate cleaved target nucleic acid, and subsequently contacting with thermophilic ligase and sequencing adapters to yield adapter-ligated target nucleic acid, using reaction conditions that optimize the reaction temperature.
However, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. do not expressly teach cas9 variants as recited in claims 56 and 57.
Prior to the effective filing date of the claimed invention, Chavez et al. teach cas9 variants are known in the art. Furthermore, Chavez et al. teach known cas9 variants include NM and ST1 cas9 variants (e.g. Entire Chavez reference and especially NM-Cas9 as in Example I pg. 11-16; ST1-Cas9 as in Example IV, pg. 17-18).
Furthermore, Chavez et al. teach cas9 systems in different cell strains are known including cell lines recited in claim 57(e.g. Entire Chavez reference and especially lines 1-36, pg. 9- lines 1-14, pg. 10).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. comprising a method of preparing a sequencing library using Cas9 nucleases to include NM-Cas9 and ST1-Cas9 variants and Cas9 systems of cell lines as taught by Chavez et al. because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a method of preparing a sequencing library comprising incubating target nucleic acid with guide RNA molecules and cas9 nuclease to generate cleaved target nucleic acid, and subsequently contacting with ligase and sequencing adapters to yield adapter-ligated target nucleic acid.
Therefore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al., Jinek et al. and Chavez et al. render obvious claims 56 and 57.
Tsai et al., Lebedev et al., Farmer et al., Jinek et al. and Fekete et al.
Claims 60 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied to claims 51- 58, 71 and 73 above, and further in view of Fekete et al. (US20150050653).
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied in the rejection above are incorporated in this rejection.
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious a method of preparing a sequencing library comprising incubating target nucleic acid with guide RNA molecules and cas9 nuclease to generate cleaved target nucleic acid, and subsequently contacting with thermophilic ligase and sequencing adapters to yield adapter-ligated target nucleic acid, using reaction conditions that optimize the reaction temperature.
However, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. do not expressly teach claims 60 and 72.
Prior to the effective filing date of the claimed invention, Fekete et al. teach in situ DNA analysis, including PCR of target nucleic acids directly in a cell sample, is known in the art. Furthermore, Fekete et al. teach the sample is fixed(e.g. Entire Fekete reference and especially para 0006-0007, pg. 1; para 0014-0017, pg. 2; para 0083-0101, pg. 6-8; fixed sample as in para 0038,pg. 3-4).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. . comprising a method of preparing a sequencing library to include in situ DNA analysis comprising PCR , directly in a cell sample as taught by Fekete et al. because this was a particular known technique recognized as part of the ordinary capabilities of one skilled in the art that was recognized for achieving the predictable outcome of a method of preparing a sequencing library.
Therefore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al., Jinek et al. and Fekete et al. render obvious claims 60 and 72.
Tsai et al., Lebedev et al., Farmer et al., Jinek et al., Dow et al. and Fekete et al.
Claims 60 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied to claims 51- 58, 71 and 73 above, and further in view of Dow et al. ("Inducible in vivo genome editing with CRISPR-Cas9." Nature biotechnology 33.4 (2015): 390-394.) and Fekete et al. (US20150050653).
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. as applied in the rejection above are incorporated in this rejection.
The combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. render obvious a method of preparing a sequencing library comprising incubating target nucleic acid with guide RNA molecules and cas9 nuclease to generate cleaved target nucleic acid, and subsequently contacting with thermophilic ligase and sequencing adapters to yield adapter-ligated target nucleic acid, using reaction conditions that optimize the reaction temperature.
However, the combined teachings of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. do not expressly teach claims 60 and 72.
In the embodiment wherein both Cas9 analysis and PCR are conducted directly in the cell:
Prior to the effective filing date of the claimed invention, Dow et al. teach that in situ analysis of Cas9- based genome editing is known in the art(e.g. Entire Dow reference and especially Abstract, pg. 1 of 7; Recent studies have described the application of CRISPR-Cas9–mediated genome editing in vivo using viral delivery or DNA transfection18–21… they enable rapid CRISPR-based editing to produce gene modifications and chromosomal rearrangements,… p 2nd para, pg. 4 of 7; Cloning and ESC targeting sections, Online Methods section, pg. 6- 7 of 7).
Furthermore, Fekete et al. teach other in situ DNA analysis, including PCR of target nucleic acids directly in a cell sample, is known in the art. Furthermore, Fekete et al. teach the sample is fixed(e.g. Entire Fekete reference and especially para 0006-0007, pg. 1; para 0014-0017, pg. 2; para 0083-0101, pg. 6-8; fixed sample as in para 0038,pg. 3-4).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Tsai et al., Lebedev et al., Farmer et al. and Jinek et al. comprising a method of preparing a sequencing library to include in situ DNA analysis comprising Cas 9- based genome editing as taught by Dow et al. and to include other in situ analysis , including PCR , directly in a cell sample as taught by Fekete et al. because these are particular known techniques recognized as part of the ordinary capabilities of one skilled in the art that was recognized for achieving the predictable outcome of a method of preparing a sequencing library.
Therefore, the combined teachings of Tsai et al., Lebedev et al., Farmer et al., Jinek et al., Dow et al. and Fekete et al. render obvious claims 60 and 72.
Response to the Arguments
Any rejection not reiterated or specifically addressed has been overcome by amendment. New rejections are set forth to address the amended claims.
However, previously cited references teach art relevant to the amended claims and therefore are included in the new rejections.
Regarding Applicants’ arguments that the previously cited art does not meet the requirements of the amended claims: these arguments are not persuasive. As discussed in the current rejections, the teachings of Lebedev et al. is applied to demonstrate that reaction with thermophilic ligase and reaction conditions using non-PCR thermocycling, wherein reaction temperature can be optimized, is known in the art.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHANA S KAUP whose telephone number is (571)272-6897. The examiner can normally be reached on M-F 7-10 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, HEATHER CALAMITA can be reached on 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SAHANA S KAUP/Primary Examiner, Art Unit 1684