Detailed Action
► Claim(s) 1-18 as presented in the paper(s) filed 01 JUL 2022 is/are pending.
► The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
35 U.S.C. 102
► The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that may 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.
35 U.S.C. 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.
Claim Rejection(s) under 35 U.S.C. 102
► Claim 1-2, 7-8, 10-12 and 17-18 is/are rejected under 35 U.S.C. 102(a)(2) or (a)(1) as being anticipated by Steemers et al.[US 20050181394- hereinafter “Steemers”]
As regards Claim 1,Steemers teach the method of Claim 1, see for example para 155, recited below, which teaches removing unwanted DNA fragments by forming dsDNA using probes hybridizing to undesired ssDNA fragment and treating with DNase.
[0155] Undesired fragments that form double stranded species, for example, in Cot analysis or genome fragment reannealing, can be separated from single stranded species based on different properties of single and double stranded nucleic acids. In a particular embodiment, enzymes that preferentially cleave double stranded DNA can be used. For example, DNAse I can cleave double-stranded DNA 100 to 500 fold faster than single stranded DNA under known conditions. Accordingly, undesired fragments can be removed by treatment with Cot oligonucleotides or by fragment reannealing, and treatment with DNAse I under conditions in which undesired fragments preferentially form double stranded species and get cleaved. Furthermore, other enzymes that preferentially modify, cleave or bind to double stranded species compared to single stranded species can be used to separate the species in a method of the invention such as sequence specific restriction endonucleases or Kamchatka crab duplex-specific endonuclease.
As regards Claim(s) 7-8, note that Steemers teach the use of Kamchatka crab duplex-specific endonuclease (i.e. double stranded endonuclease see at least para 155 recited directly above.
As regards Claim(s) 11-12, Stemmers further teach analyzing nucleic acids by genotyping, see at least para 7 in Stemmers.
As regards Claim(s) 17-18, Stemmers further teach denaturing genomic DNA by heat, see at least para 70. Other methods of denaturing genomic DNA including treatment with a basic solution (Official Notice) were known.
Claim Rejection(s) under 35 U.S.C. 103
► Claim(s) 3-6 rejected under 35 U.S.C. 103 as being unpatentable over Steemers in view of Hermann et al.[ Biotechniques 29: 1176-1180(2000) – herein after “Hermann”] and Chen et al [US 2009/0181360 - hereinafter Chen].
As regards Claim(s) 3-6, Steemers teach removing undesired fragments from nucleic acid samples by hybridization of a probe(s) to the undesired fragment followed by DNase digestion. While Stemmers teach primer extension of a primer, these inventors do not expressly teach forming a dsDNA comprising the undesired by primer extension from a flanking primer as required by Claims 3-6. However it was well known to form dsDNA comprising a double stranded DNA sequence of interest by primer extension from a flanking primer(s). Consider at least Herman, who teach, in part, the formation of a double stranded DNA of interest by primer extension from a flanking primer(s), see the entire document. Chen teach multiplexed primer extension reactions. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to modify the method of Stemmers wherein the undesired sequence targeted for elimination by DNase digestion is formed by the extension of primer(s) flanking the undesired sequence(s) rather than being formed by probe hybridization as taught Stemmers. Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
► Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Steemers as applied above against Claim 1 and 8 in view of Engler et al [PLoS one 4(5) :e5553 (2009) – hereinafter “Engler”] or Lanes et al.. [US 2011020878 – hereinafter “Lanes”]..
.
Claim 9 is drawn to an embodiment of the method of Claim 8 wherein the method further comprises deactivating the enzyme.
Steemers teach the method of Claim(s) 1 and 8 comprising most of the limitations of Claims 1 and 8 for at least the reason(s) as outlined above except these inventor fail to teach inactivating the enzymes (e.g. double strand specific endonuclease - Kamchatka crab DNase) However, it was routine and well known in the art to inactivate/remove digesting enzyme proteins, including DNases, at the conclusion of assays in order to prevent said enzymes from interfering with downstream applications. Consider for example Engler and/or Lanes.
For example. Engler teach a method of inactivating enzymes at the conclusion of a DNA shuffling protocol by heat inactivation, see especially the first full para on pg.3.
Lane teach inactivating DNase in an method of removing contaminating dsDNA from RNA samples to be reverse transcribed and detected by RT-PCR, in subsequent steps, see the abstract and especially para 19 which is recited below :
[0019] DNases that are more thermolabile have also been described. WO99/007887 discloses a DNase isolated from Pandalus borealis that is substantially irreversibly inactivated after 2 mins at 94.degree. C. This same enzyme is also substantially irreversibly inactivated after 15 minutes at 65.degree. C. Anisimova et al (Biotechnology Letters; 2009, 31: 251 to 257) describe a randomly mutated version of king crab DNase (Kamchatka crab, Paralithodes camtschaticus) that is inactivated after incubation for 10 minutes at 65.degree. C., although inactivation can be achieved at temperatures as low as 55.degree. C. after 10 minutes if the inactivation additives DTT (1-4 dithiothreitol) and EDTA are used.
► Claim(s) 13-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Steemers as applied above against Claim 1 and 12 in view of Umbarger et al.[US 2015/0111208 – hereinafter “Umbarger”] and Pareek et al. [J. of Appl. Genetics 52:413(2011) – hereinafter “Pareek”].
Claim 13 is drawn to an embodiment of the method of Claim 12 wherein the assay comprises the use of molecular inversion probe capture. .
Steemers teach a method of genomic analysis which comprises removing undesired/unwanted segments from genomic DNA to be analyzed as outline above in the rejection of Claim 1 over Steemers. That said, Steemers does not teach genomic analysis using molecular inversion probe capture as required by Claim 13. However the analysis of genomic DNA by molecular inversion probe capture technology was well known , consider at least para 49. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to modify the method of Stemmers wherein the genomic DNA following undesired sequence removal is by the molecular inversion probe capture technology rather than by the genotyping method of Steemers. Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
As regards Claim14-15, note that Pareek teach genomic analysis by sequencing including by sequencing via the Sanger method, see Column 2 on pg. 414 and by Next generation sequencing platforms.
As regards Claim 16, note that Umbarger teach including paralogous sequences in their analysis but elimination of said paralogous data from the final sequences reported, see at least the abstract and paras 6-7 in Umbarger.
Non-Statutory Obviousness-type 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). It is noted that the doctrine of double patenting is also designed to protect third parties from harassment by multiple patent owners in connection with the same invention.
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). 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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
NSODP Rejection(s)
► Instant Claim 1-4, 6-18 is/are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1-16 of U.S. Patent No. 11,408,024 -hereinafter US-024’ in view of Umbarger. Although the conflicting claims are not identical, they are not patentably distinct from each other. The scope encompassed by the invention recited in Claims 1-18 falls with the scope encompased by the invention recited in Claims 1-16 of US -024’.
As regards Instant Claim 1, the Claims of US-024’ teach a method removing unwanted nucleic acids (i.e. parlogous gene sequences) from a sample. The Claims of US-024’ do not expressly teach that the unwanted sequence(s) are prologous sequenes However the claims of US-024’ do teach the removal of paralogs, which as taught by Umbarger are sequences which can confound DNA sequencing data analysis (i.e. are unwanted sequences) and are therefore removed/excluded from sequencing data reads by the methods disclosed therein. See the abstract of Umbarger, as well as paras 20-137.
As regards Instant Claim 7-18, note Claim 1-16 and in US-024’.
► Instant Claim(s) 5 is/are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1-16 of US-024’ in view of Umbarger as applied above and further in view of Chen.
Instant Claim 5 is drawn to an embodiment of the method of Claim 1 which requires the use of a plurality of primers to extend into a plurality of sequence portions.
Chen teach multiplexed primer extensions, see at least para 34.
Conclusion
C. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ethan Whisenant whose telephone number is (571) 272-0754. The examiner can normally be reached Monday-Friday from 8:30 am -5:30 pm EST or any time via voice mail. If repeated attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anne Gussow, can be reached at (571) 272-6047.
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/ETHAN C WHISENANT/Primary Examiner, Art Unit 1683 ethan.whisenant@uspto.gov
EXAMINER SEARCH NOTES
05 NOV 2025 - ECW
Databases searched: All available via PE2E SEARCH
CAplus, Medline and BIOSIS via STNext; and Google Scholar (note the search terms used below)
Reviewed the parent(s), if any, and any search(es) performed therein : see the BIB data sheet
Reviewed, the search(es), if any, performed by prior examiners including any international examiners.
Planned Search
Search terms:
All Inventor(s) e.g. Gole J?/au
DNA or genomic DNA or gDNA or RNA or nucleic
Unwanted or undesired
Paralog$ or ortholog$ or pseudogene$ or repetitive
Remov$ or degrad$ or eliminat$
Nuclease or DNase or RNase or endonuclease
genotype$ or sequenc$ or amplify$
multiplex$
denature$
primer extension
flank$
► See the Examiner’s PE2E SEARCH notes/strategy in IFW