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 .
DETAILED ACTION
Pursuant to a preliminary amendment filed June 2, 2026, claims 1-4, 6, 9, 12, 15, 18, 20, 22, 24, 26, 31, 34, 36, 38, 40, 65 and 66 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group II without traverse, claims 1-6, 9, 12, 15, 18, 20, 22, 24, 26, 31, 34, 36, 38 and 40 directed to a method of preparing a nucleic acid sample; and Applicant’s election of Species without traverse as follows:
Species (A): wherein the up to ten (10) enzymes comprise:
Enzymes excising one or more damaged bases from the sample: formamido-pyrimidine
[fapy]-DNA glycosylase (Fpg); uracil-DNA glycosylase (UDG); T4 pyrimidine DNA glycosylase (T4 PDG), and endonuclease VIII (Endo VIII);
Cleaving one or more abasic sites to produce resulting ends, and processing the resulting ends to be compatible with extension by a DNA polymerase and/or ligation by a DNA ligase: endonuclease IV (EndoIV);
Digesting 5' overhangs: exonuclease VII (Exo VII);
Contacting the sample with one or more of: a DNA-dependent DNA polymerase lacking both strand displacement and 5’ exonuclease activity, but capable of fill-in of single-stranded segments of the sample, and digesting 3’ overhangs of the sample: Klenow fragment (exo-);
Enzyme capable of phosphorylating 5’ ends of strands within the sample: T4 polynucleotide kinase (T4 PNK); and
DNA ligase capable of sealing nicks: not elected (claim 1);
Species (B): method of claim 1 further comprising an additional step such as, for example, further comprising (d) preparing the sample for adapter ligation (claim 2);
Species (C): wherein the sample is contacted with an enzyme capable of incorporated deoxyadenosine monophosphate (dAMP) to the 3’ end of a strand (claim 3); and
Species (D): wherein at least one strand of the sample has a 5’ overhang of at least 10 nucleobases in length (claim 34), in the reply filed June 2, 2026 is acknowledged.
Claims 58 and 62 (now canceled) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 6, 9, 12, 15, 26, 36, 38 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1-4, 18, 20, 22, 24, 31, 34, 65 and 66 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed June 9, 2023 is a 35 U.S.C. 371 national stage filing of International Application PCT/US2021/062936, filed November 4, 2021, which claims the benefit of US Provisional Patent Applications: 63217007, filed June 30, 2021; 63191914, filed May 21, 2021; 63191320, filed May 20, 2021; 63143397, filed January 29, 2021; and 63124700, filed December 11, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on October 30, 2023 and March 31, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Objections
Claims 3 and 4 are objected to because of the following informalities: Claims 3 and 4 recite terms such as “dNTPs” and "dA”, where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-4, 18, 20, 22, 24, 31, 34, 65 and 66 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “at least a portion” in claim 1, lines 1-2 because a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Instant claim 1 recites a broad range of “at least”, while also reciting a narrow range of “a portion,” which is a narrow range or limitation and, thus, the metes and bounds of the claim cannot be determined.
Claims 1, 3 and 31 are indefinite for the recitation of the term “contacting the sample” such as recited in claim 1, lines 4, 10, and 16 because it is unclear whether the term refers to contacting an unreacted sample within a reaction vessel in each of (a), (b) and (c) with an enzyme as recited; or whether the term refers to contacting a product of an enzymatic or processing step of the previously treated sample with an additional enzyme and, thus, the metes and bounds of the claim cannot be determined.
Claims 1-3, 31, 34 and 66 is indefinite for the recitation of the term “the sample” such as recited in claim 1, lines 2, 4, 10, 12, 15 and 16. There is insufficient antecedent basis for the term “the sample” in the claim because claim 1, line 1 recites the term “a nucleic acid sample.” The Examiner suggests that Applicant amend the claim to recite, for example, “the nucleic acid sample” and/or a designation indicating the structure of the nucleic acid after contact with one or more enzymes as recited.
Claim 2 is indefinite for the recitation of the term “adding dAMP to the 3’ ends…or blunting ends of the sample” such as recited in claim 2, line 5 because the structure of “the sample” that undergoes preparation for adapter ligation is unclear. For example, it is unclear whether step (d) is carried out on a nucleic acid sample that has not been contacted with any of the enzymes as recited in steps (a)-(c) (e.g., an unreacted sample); or whether step (d) is carried out on nucleic acids in the sample after contact with one or more enzymes as recited in claim 1(a)-(c) (e.g., nucleic acids that have had damaged bases excised, abasic sites cleaved, 3’ overhangs digested, 5’ ends digested, 5’ ends phosphorylated, and/or nicks sealed) and, thus, the metes and bounds of the claim cannot be determined.
Claims 4 and 66 are indefinite for the recitation of the terms “enzymes” and/or “the enzyme” such as recited in claim 4, line 1. There is insufficient antecedent basis for the terms “enzymes” and/or “the enzyme” in the claims because claim 1, line 4 recites the term “the one or more enzymes.”
Claims 4, 18, 20, 22, 24 and 31 are indefinite for the recitation of the terms “step” or “steps” such as recited in claim 4, line 2. There is insufficient antecedent basis for the term “step” in the claims because claims 4, 18, 20, 22, 24 and 31 depend from claim 1 or claims 1-3, wherein claims 1 and 2 recite the terms (a), (b), (c), and (d). Moreover, claims 1-3 do not recite wherein the reaction is heated or cooled and, thus, the metes and bounds of the claim cannot be determined.
Claim 31 is indefinite for the recitation of the term “(a) comprises contacting the sample with one or more enzymes…and exonuclease” such as recited in claim 31, lines 1-8 because claim 31 depends from instant claim 1, wherein claim 1 already recites what (a) comprises (e.g., contacting the sample to one or more enzyme capable of…digesting 5’ overhangs), such that dependent claim 31 cannot recite that (a) comprises something different. The Examiner suggests that Applicant amend claim 31 to recite, for example, “wherein the one or more enzymes capable of…comprise endonuclease IV…and ExoVII.”
Claim 34 is indefinite for the recitation of the term “at least one strand of the sample has a 5’ overhang” such as recited in claim 34, lines 1-2 because it is unclear whether the term “the sample” refers to unreacted sample nucleic acids; whether the term refers to a sample that has been contacted with one or more enzymes as recited in claim 1; and/or whether some or all of the 5’ overhangs have been digested and, thus, the metes and bounds of the claim cannot be determined.
Claim 65 is indefinite insofar as it ultimately depends from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4, 18, 20, 22, 24 and 31 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 recites (in part): “wherein enzymes and/or dNTPs used in steps (a)-(c) are substantially removed from the reaction vessel prior to dA-tailing” in lines 1-2, wherein claim 4 depends from instant claim 1-3, such that claim 1-3 do not recite “steps”; and/or the presence of a reaction vessel. Thus, claim 4 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 18, 20, 22, 24 and 31 recite (in part): “step” such as recited in claim 18, line 1 because the claims 18, 20, 22, 24 and 31 depend from instant claim 1, wherein claim 1 does not recite “steps”, but instead recites (a), (b), (c). Moreover, claims 1-3 do not recite wherein the reaction is heated or cooled. Thus, claims 18, 20, 22, 24 and 31 are improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 31 recites (in part): “wherein step (a) comprises contacting the sample with one or more enzymes selected from the group consisting of: (1) endonuclease IV…(T4 PDG)” in lines 1-6, wherein claim 31 depends from instant claim 1, such that claim 1 already recites what (a) comprises (e.g., contacting the sample to one or more enzyme capable of…digesting 5’ overhangs), such that dependent claim 31 cannot recite that (a) comprises something different. Thus, claim 31 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 18, 20, 24, 31, 34 and 66 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Joung et al. (hereinafter “Joung”) (US Patent No. 10738303, issued August 11, 2020; also as US20180245071, published August 30, 2018).
Regarding claim 1, Joung teaches the sensitive, unbiased methods for genome-wide detection of potential CRISPR-Cas9 off-target cleavage sites from cell type-specific genomic DNA samples (interpreted as at least partially double-stranded, claim 1) (Abstract). Joung teaches methods for preparing a library of covalently closed circular double-stranded DNA fragments including providing dsDNA, such as genomic DNA (gDNA) from a cell type or organism of interest or synthetic DNA (interpreted as a double-stranded sample); randomly shearing the DNA to a defined average length, e.g., an average length of about 200 500 bps, such as about 300 bps, to provide a population of DNA fragments; optionally preparing the fragments for end-ligation, e.g., by end-repairing and/or A-tailing the sheared DNA (interpreted as A-tailing; and enzymes substantially removed); ligating to the ends of the fragments a stem-loop adapter comprising at least a single deoxyuridine adjacent to or within a loop sequence comprising a palindromic sequence (interpreted as ligating adaptors), to prepare a population of ligated linear dsDNA fragments; contacting the library with an exonuclease (e.g., a cocktail such as Lambda exonuclease and/or E. coli Exonuclease I) to degrade any remaining linear fragments with unligated ends, to produce a purified population of ligated linear dsDNA fragments; contacting the library with enzymes that nick the ligated dsDNA fragments at the deoxyuridine and to remove a 3' terminal phosphate, such as with uracil DNA glycosylase (UDG) and/or endonuclease VIII, a DNA glycosylase-lyase (interpreted as excising damaged bases with UDG and/or Endo VIII), to nick the DNA at the deoxyuridine and T4 Polynucleotide Kinase to remove a 3' terminal phosphate (interpreted as T4 PNK); incubating the nicked linear dsDNA fragments under conditions sufficient to promote intramolecular ligation and formation of circular DNA molecules; and purifying the ligated fragments using an exonuclease, thereby preparing a library of covalently closed fully circular double-stranded DNA fragments (interpreted as contacting with UDG, Endo VIII, DNA glycosylase-lyase, and T4 PNK; and excising, phosphorylating; cleaving abasic sites; A-tailing with dNTPs and enzymes substantially removed, claims 1 and 4) (col 2, lines 14-43). Joung teaches kits for use in the method including one or more of the following: hairpin adapters; reagents and/or enzymes for end repair and
A tailing (e.g., T4 polymerase, Klenow fragment, T4 Polynucleotide Kinase (PNK), and/or Taq DNA Polymerase); exonuclease; uracil DNA glycosylase (UDG) and/or endonuclease VIII, a DNA glycosylase lyase, e.g., the USER (Uracil-Specific Excision Reagent) Enzyme mixture; purified nuclease, e.g., cas9 protein; guide RNA (e.g., control gRNA); and gDNA template (e.g., control gDNA template) (interpreted as comprising T4 PNK, UDG, USER, endo VIII, Klenow fragment, DNA polymerase, adaptors, and enzymes for A-tailing, claims 1 and 2) (col 17, lines 10-20). Joung teaches that adapter-ligated DNA was treated with a mixture of Lambda Exonuclease (NEB) and E. coli Exonuclease I (NEB), then with USER enzyme (NEB) and T4 polynucleotide kinase (NEB), wherein DNA was circularized with T4 DNA ligase, and treated with PlasmidSafe ATP-dependent DNase to degrade remaining linear DNA molecules (interpreted as comprising adapter ligation using T4 DNA ligase; and where the enzymes are substantially removed, claims 1 and 4) (col 18, lines 12-19).
Regarding claims 2-4, Joung teaches preparing the fragments for end-ligation such as by end-repairing and/or A-tailing the sheared DNA, ligating to the end of the fragments a stem-loop adapter (interpreted as preparing the sample for adapter ligation by A-tailing, claim 1) (col 2, line 21-24). Joung teaches contacting the sample with one or more exonucleases (e.g., bacteriophage lambda exonuclease, E.coli ExoI, PlasmidSafe ATP-dependent exonuclease), sufficient to degrade any dsDNA molecules that are not circular; treating the sample with a nuclease to induce site-specific cleavage (e.g., of on- and/or off-target sites, e.g., to induce blunt or staggered/overhanging ends) optionally end-repairing and then A-tailing the resulting ends; ligating a sequencing adapter comprising a first region of about 12 nucleotides (interpreted as blunting ends; enzymes for A-tailing; and ligating adaptors, claims 2 and 3) (col 3, lines 11-19). Joung teaches that purified genomic DNA was sheared with a Covaris S200 instrument to an average length of 300 bp, end-repaired, A-tailed, and ligated to uracil (interpreted as A-tailing, including dNTPs, claim 4) (col 18, lines 6-9). Joung teaches A-tailing DNA using Kapa A-tailing enzyme, total master mix, end repair with beads, and cleanup by adding SPRI solution (interpreted as comprising dNTPs in the master mix; using an enzyme to A-tail; and substantially removing enzymes (a)-(c) from the reaction vessel, claims 2-4) (col 33, lines 25-34).
Regarding claim 18, Joung teaches treatment with Lambda exonuclease/E. coli exonuclease, wherein the reaction is incubated at 37oC (interpreted as being between about 32-42oC, claim 18) (col 32, Reaction 4, lines 35-45).
Regarding claim 20, Joung teaches treatment with USESR/T4 PNK, wherein the reaction is incubated at 37oC (interpreted as being between about 32-42oC, claim 20) (col 32, Reaction 5, lines 46-56).
Regarding claim 24, Joung teaches treatment with KAPA A-tailing enzyme, wherein the reaction is incubated at 30oC (interpreted as being between about 18-69oC, claim 24) (col 34, lines 51-65).
Regarding claim 31, contacting the library with enzymes that nick the ligated dsDNA fragments at the deoxyuridine and to remove a 3' terminal phosphate, such as with uracil DNA glycosylase (UDG) and/or endonuclease VIII, a DNA glycosylase-lyase (interpreted as excising damaged bases with UDG and/or Endo VIII), to nick the DNA at the deoxyuridine and T4 Polynucleotide Kinase to remove a 3' terminal phosphate (interpreted as T4 PNK); incubating the nicked linear dsDNA fragments under conditions sufficient to promote intramolecular ligation and formation of circular DNA molecules; and purifying the ligated fragments using an exonuclease, thereby preparing a library of covalently closed fully circular double-stranded DNA fragments (interpreted as contacting a sample with one or more enzyme including EndoVIII and UDG, claim 31) (col 2, lines 31-43).
Regarding claim 34, Joung teaches that the adaptors include a random variety of 1, 2, 3, 4, or more nucleotide overhangs on the 5’ or 3’ ends (interpreted of encompassing a 5’ overhang of at least 10 nucleobases in length, claim 34) (col 12, lines 26-27).
Regarding claim 66, Joung teaches that overhangs are released with a mixture of USER enzyme and T4 PNK (interpreted as T4 PNK, claim 66) (col 5, lines 24-25).
Joung does not specifically exemplify where (c) is carried out at a temperature between 30-70oC (claim 22); and where the DNA-dependent DNA polymerase comprises Klenow fragment (exo-) (claim 65, in part).
Joung meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 for
the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 18, 20, 22, 24, 31, 34, 65 and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Joung et al. (hereinafter “Joung”) (US Patent No. 10738303, issued August 11, 2020; also as US20180245071, published August 30, 2018) in view of Toro et. al. (hereinafter “Toro”) (US Patent Application Publication 20190352635, published November 21, 2019; effective filing date February 4, 2016) as evidenced by Polbase (Polbase, 2026, 1-14).
The teachings of Joung as applied to claims 1-4, 18, 20, 24, 31, 34 and 66 are described supra.
Joung does not specifically exemplify where (c) is carried out at a temperature between 30-70oC (claim 22); and where the DNA-dependent DNA polymerase comprises Klenow fragment (exo-) (claim 65, in part).
Regarding claim 22, Toro teaches methods for nucleic acid assembly, comprising: providing a predetermined nucleic acid sequence; providing a plurality of precursor double-stranded nucleic acid fragments, each precursor double-stranded nucleic acid fragment having two strands, wherein each of the two strands comprises a sticky end sequence (interpreted as partially double-stranded sample nucleic acid, claim 1) (paragraph [0004], lines 1-6). Toro shows in Figure 6 a workflow of nucleic acid synthesis performed to generate a plurality of target nucleic acid fragments, or oligonucleotides thereof, for assembly using sticky end, wherein an intended nucleic acid sequence or a library of precursor nucleic acid fragments is preselected for generation; wherein a structure comprising a surface layer 601 is provided, wherein chemistry of the surface is functionalized in order to improve the oligonucleic acid synthesis process; such that the workflow is divided generally into the following processes: (1) de nova synthesis of a single stranded oligonucleic acid library, (2) joining oligonucleic acids to form larger fragments, (3) error correction, (4) quality control, and (5) shipment (interpreting the surface to be adding to a reaction vessel, claim 1) (paragraphs [0073]-[0074]; Figure 6). Toro teaches methods where two or more of the cleavage, annealing and ligation reactions are performed concurrently within the same mixture and the mixture comprises a ligase, wherein the one or more of the various reactions is sped up or slowed down by adjusting the reaction conditions such as temperature, such that the reaction can thermocycle between a maximum and minimum temperature to repeatedly enhance cleavage, melting, annealing, and/or ligation, wherein the temperature ranges include from a high of 80o C, or from a low to 4o C, or from 4o C to 80o C; or the temperature ranges from a high of 60o C to a low of 16o C (corresponding to temperatures between about 30-70C, claims 18, 20, 22 and 24) (paragraph [0123]). It is noted that MPEP 2144.05(II)(A) states that: “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In the instant case, the reaction conditions such as temperature are influenced by several factors including the identity of the nucleic acid sample (e.g., structure, size, functional groups, etc.); the number and/or location of damaged bases that are being excised, cleaved, digested, contacted, and/or ligated; any additional reactants; other conditions such as the pH, reaction time, the presence and/or identity of any solvent, buffer, etc.; as well as, the specific enzyme, mixture of enzymes, and/or concentration of the enzyme(s) in a particular reaction.
Regarding claim 65 (in part), Toro teaches that methods are provided wherein a polymerase lacking 3' to 5' proof-reading activity is added during the amplification step, wherein the polymerase is a Family A polymerase, or wherein the polymerase is a Family B high fidelity polymerase engineered to tolerate base pairs comprising uracil, wherein an amplified plurality of single-stranded nucleic acid fragments are generated by any of the aforementioned methods (interpreted as comprising Klenow fragment (exo-), claim 65) (paragraph [0006], last 13 lines), wherein it is known that Klenow fragment exo- is a Family A enzyme as evidenced by Polbase (pg. 1, first full paragraph).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of generating a nucleic acid library as exemplified by Toro, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the method of enzymatically preparing a library of covalently closed fully circularized DNA fragments as disclosed by Joung to include the enzymes and/or reaction conditions as taught by Toro with a reasonable expectation of success in processing, repairing and/or assembling nucleic acid fragments using different enzymes and/or reaction conditions including Klenow fragment (exo-) to produce a starting population of DNA fragments for cleavage-specific enrichment and sequencing; and/or in enzymatically preparing a library of nucleic acid fragments with minimized numbers of DNA double-stranded breaks including converting randomly sheared gDNA into covalently closed circles.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 1-4, 18, 20, 22, 24, 31, 34, 65 and 66 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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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.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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