DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed June 21, 2023. Currently, claims 1-18 are pending.
Priority
This application claims priority
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Drawings
The drawings are acceptable.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claim 5 is 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 pre-AIA the applicant regards as the invention.
Claim 5 recites “the at least one protected nucleic acid comprises the target”. Claim 1 does not provide at least one protected nucleic acid. Thus, “the at least one protected nucleic acid lacks proper antecedent basis.
Claim Rejections - 35 USC § 102
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.
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.
Claim(s) 1-7, 9-11, 14-16, 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carpenter et al. (WO2016/100955, June 23, 2016).
Carpenter teaches adding linkers to a sample (see Y-shaped linkers ligated). Carpenter teaches protecting target nucleic acid with a library of anti-human guide RNAs complexed with Cas9 (i.e. at least two Cas endonuclease complexes). Carpenter teaches using exonuclase III to degrade one DNA strand. Carpenter teaches a method of removing unwanted DNA after Cas9-mediated cleavage by using Exonuclase Bal-31 to degrade cleaved DNA while leaving the uncut DNA of interest intact (Example 8, page 68-69). Carpenter teaches “after” exonuclease Bal-31 incubation, the reaction is heat inactivated (i.e. deactivated) (page 69, para 259). Carpenter teaches that the unwanted DNA may account for nearly 95% of DNA (see Example 9, page 70). Carpenter also teaches that libraires may subjected to ligating adapters for downstream analysis. (page 67, para 250). Therefore Carpenter teaches each limitation of the claimed invention as illustrated below in Figure 8.
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With respect to Claim 10-11, Carpenter teaches resiulting libraries may be subjected to sequencing or purification by column or PCR-ampflication (para 255).
With respect to Claims 14-15, Carpenter teaches the samples may be derived from human blood. With respect to Claim 16, Carpenter also teaches using mouse samples (para 43).
Claim Rejections - 35 USC § 103
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 1-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shuber et al. (US10,527,608, January 7, 2020) or Shuber et al (US 10,081,829, September 25, 2018) in view of in view of Carpenter et al. (WO2016/100955, June 23, 2016).
Shuber ‘608 teaches methods for rare event detection for detecting DNA by using binding proteins to protect those features of interest while digesting unprotected DNA in a sample. Shuber teaches protecting a segment of nucleic acid in a sample by introducing Cas endonuclease/guide RNA complexes that binds to targets, digest unprotected nucleic acid by exposing the unprotected nucleic acid to exonuclase and detecting the target (see Claim 1). Shuber teaches the Cas endonuclease/guide RNA target regions.
Shuber ‘829 teaches methods of detecting nucleic acid by protecting nucleic acids using a first and second Cas endonuclease and digesting unprotected nucleic acids with exonuclease (see Claim 1). Shuber ‘829 teaches the first and second Cas endonucleases are different. Shuber ‘829 teaches the target is a pathogen.
Neither Shuber teaches deactivating the exonuclease following digestion.
However, Carpenter teaches it is desirable to remove cut fragments prior to PCR amplification or sequencing. Carpenter teaches a method of removing unwanted DNA after Cas9-mediated cleavage by using Exonuclease Bal-31 to degrade cleaved DNA while leaving the uncut DNA of interest intact (Example 8, page 68-69). Carpenter teaches “after” exonuclease Bal-31 incubation, the reaction is heat inactivated (i.e. deactivated) (page 69, para 259). Carpenter teaches that the unwanted DNA may account for nearly 95% of DNA (see Example 9, page 70).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the Cas-9 detection method including removing unwanted DNA after the Cas-9 mediated cleavage with exonucleases as taught by Shuber and then deactivate the exonuclease for subsequent detection of the protected nucleic acids. The ordinary artisan would have been motivated to have removed the unwanted DNA to remove background for the further processing of the DNA analysis and then deactivated the exonuclease before further detection such as PCR or sequencing.
Claim(s) 1-12, 14, 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Church et al. (WO2017/72860, October 5, 2017) in view of Carpenter et al. (WO2016/100955, June 23, 2016).
Claim(s) 1-12, 14, 16-18 is/are under 35 U.S.C. 103 as being unpatentable over Church et al. (US2019/0112599, published April 18, 2019 and priority March 31, 2016) in view of Carpenter et al. (WO2016/100955, June 23, 2016).
The disclosure of the WO and the US Publication are the same. The numbering refers to the PG Publication.
Church teaches method for single tube preparation of sequencing libraries using Cas9. As seen in Figure 1B below, double stranded DNA was combined with Cas9 pre-complexed with one or more pairs of fragmentation gRNAs, adapter oligonucleotides and DNA ligase. Figure 1B illustrates multiple 1a, 1b, 2a, 2b cas9 endonucleases with different guide RNAs (limitations of Claim 6-8)(see para 34-35). The targeted DNA was fragmented. The tube was denatured to 95C which removes Cas9 from the fragmented DNA (i.e. deactivating the exonuclease) and adding adapter oligonucleotides with ligase for detecting of the nucleic acid (para 12). The single tube/single reaction method is for preparation of next generation sequencing libraries and use in indexing PCR reactions (para 14).
With respect to Claims 12-13, DNA was precipitated and supernatant was discarded and pellets were washed (Para 53). This was performed prior to the DNA was inputted to single tube for Cas9 library preparation (para 54).
With respect to Claim 14, the sample was human genomic DNA extracted from a tumor biopsy or other clinical tissue ((para 89). Claim 16, Church teaches the sample may be mammalian (para 21) or bacterial or viral DNA (para 47).
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Church does not teach adding an exonuclease to the sample to digest unprotected nucleic acids from the sample and then deactivating the exonuclease.
However, Carpenter teaches it is desirable to remove cut fragments prior to PCR amplification or sequencing. Carpenter teaches a method of removing unwanted DNA after Cas9-mediated cleavage by using Exonuclase Bal-31 to degrade cleaved DNA while leaving the uncut DNA of interest intact (Example 8, page 68-69). Carpenter teaches “after” exonuclease Bal-31 incubation, the reaction is heat inactivated (i.e. deactivated) (page 69, para 259). Carpenter teaches that the unwanted DNA may account for nearly 95% of DNA (see Example 9, page 70).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the single tube preparation of sequencing libraries of Church to remove unwanted DNA after the Cas-9 mediated cleavage. The ordinary artisan would have been motivated to have removed the unwanted DNA to remove background for the further processing of the DNA analysis.
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1-23 of Shuber et al. (US 10,527,608, January 7, 2020) in view of in view of Carpenter et al. (WO2016/100955, June 23, 2016).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined 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).
Claims 1-23 of Shuber ‘608 teaches methods for rare event detection for detecting DNA by using binding proteins to protect those features of interest while digesting unprotected DNA in a sample. Shuber teaches protecting a segment of nucleic acid in a sample by introducing Cas endonuclease/guide RNA complexes that binds to targets, digest unprotected nucleic acid by exposing the unprotected nucleic acid to exonuclase and detecting the target (see Claim 1). Shuber teaches the Cas endonuclease/guide RNA target regions.
Shuber does not claim deactivating the exonuclease following digestion.
However, Carpenter teaches it is desirable to remove cut fragments prior to PCR amplification or sequencing. Carpenter teaches a method of removing unwanted DNA after Cas9-mediated cleavage by using Exonuclease Bal-31 to degrade cleaved DNA while leaving the uncut DNA of interest intact (Example 8, page 68-69). Carpenter teaches “after” exonuclease Bal-31 incubation, the reaction is heat inactivated (i.e. deactivated) (page 69, para 259). Carpenter teaches that the unwanted DNA may account for nearly 95% of DNA (see Example 9, page 70).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the Cas-9 detection method including removing unwanted DNA after the Cas-9 mediated cleavage with exonucleases as taught by Shuber and then deactivate the exonuclease for subsequent detection of the protected nucleic acids. The ordinary artisan would have been motivated to have removed the unwanted DNA to remove background for the further processing of the DNA analysis and then deactivated the exonuclease before further detection such as PCR or sequencing.
Claims 1-18 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1-19 of Shuber et al (US 10,081,829, September 25, 2018) in view of in view of Carpenter et al. (WO2016/100955, June 23, 2016).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined 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).
Claims 1-19 of Shuber ‘829 teaches methods of detecting nucleic acid by protecting nucleic acids using a first and second Cas endonuclease and digesting unprotected nucleic acids with exonuclease (see Claim 1). Shuber ‘829 teaches the first and second Cas endonucleases are different. Shuber ‘829 teaches the target is a pathogen.
‘829 does not teach deactivating the exonuclease following digestion.
However, Carpenter teaches it is desirable to remove cut fragments prior to PCR amplification or sequencing. Carpenter teaches a method of removing unwanted DNA after Cas9-mediated cleavage by using Exonuclease Bal-31 to degrade cleaved DNA while leaving the uncut DNA of interest intact (Example 8, page 68-69). Carpenter teaches “after” exonuclease Bal-31 incubation, the reaction is heat inactivated (i.e. deactivated) (page 69, para 259). Carpenter teaches that the unwanted DNA may account for nearly 95% of DNA (see Example 9, page 70).
Therefore, it would have been prima facie obvious at the time the invention was made to have modified the Cas-9 detection method including removing unwanted DNA after the Cas-9 mediated cleavage with exonucleases as taught by Shuber ‘829 and then deactivate the exonuclease for subsequent detection of the protected nucleic acids. The ordinary artisan would have been motivated to have removed the unwanted DNA to remove background for the further processing of the DNA analysis and then deactivated the exonuclease before further detection such as PCR or sequencing.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wang et al. (Scientific Reports, Vol. 8, No. 14126, September 2018) teaches CRISPR typing PCR, a Cas9-based DNA detection method).
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Zhang et al. (Analytical and Bioanalytical Chemistry, Vol. 410, pages 2889-2900, 2018) teaches detecting of target DNA with a novel Cas9-sgRNAs associated reverse PCR (CARP) technique.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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 on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
November 9, 2025