DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claims 6-7, 9 and 13 have been canceled. Claims 1-5, 8, 10-12 and 14-24 are pending and under examination. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.” Claim s 21-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claim(s) recite(s) to (1) measuring natural molecules from a subject, i.e. DNA (cell-free nucleic acid cfDNA) in samples, and (2) correlating the presence or level of the cfDNA for a disease, such as cancer or a disease state . Therefore, the natural relationship is the cfDNA biomarker(s) correlating with a “condition” as law of nature under judicial exception. (See Mayo Collaborative Servs. v. Prometheus Laboratories, Inc. , 132 S.Ct. 1289 (2012). This judicial exception is not integrated into a practical application because no extra step or procedure is recited . The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because steps of obtaining samples, applying nanoparticles to sample followed by isolating and analyzing corona-associated with cfDNA are well-understood, routine, conventional activity in the field and add insignificant extra-solution activity to the judicial exception. For instance, the specification illustrates by Farokhzad (I) (US 20180172694; see example 8, Figures 61-64), Huo (US 20130052661; claims 1-20; section 0023 and 0012), Farokhzad (II)(US 20210072255; Figures 61-64), Ma ((WO2019209888; section 0012-0013, 0043, 0047, 0048, 0087, 0089-0095; claim 11), Lee (KR20160105139 English machine translation ; section 0010-0013) and Huang (Nanotheranostics 2017 1:80-102; at page 89-90 ; see Materials and Methods ). These steps are recited at a high level of generality, and are necessary data gathering steps that feed into the determining step. One cannot do the determining step without getting the data. This weighs against it being significantly more. . Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claims 5, 8, 14 and 19 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. As to claim 5, last second line, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). last second line, last second line, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). As to claim 8, line 3-4, last second line, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). As to claim 14, line 3, last second line, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). As to claim 19, last second line, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claim 1-5, 8, 10-12 and 14-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11, 13-14, 16-17 and 19-21 of copending Application No. 18041131 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co - pending 131’ application directs to essentially same method of identifying cell free nucleic acid in a sample from a subject by incubating blood or serum samples with a plurality of nanoparticle to form corona biomolecule complex followed by analyzing the cell free DNA (cfDNA)(see claim 17 in 131’ application) . In additional, 131’ application also uses intravenous injection of administering nanoparticles to the subject. Moreover, 131’ application also teaches applying the detection method for diagnosis a or monitoring cancer progression or treament in a subject. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claim (s) 1-5, 8, 10-16, 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ma (WO2019209888; IDS reference) in view of Mortimer (US 20210115502) . Ma teaches a method of using genomic data , e.g. profiling or signatures for evaluating a subject in a disease state (Title, Abstract, section 0044, 0057-0058) . The method taught by Ma includes collecting a biological sample from the subject and contacting a plurality of nanoparticles to allow the formation of corona biomolecule complex between the targets and the nanoparticle followed by isolating and analyzing the target biomolecules (see section 0012-0013, 0043, 0047, 0048, 0087, 0089-0095). Ma teaches analyzing polynucleotide profiling from the sample for assessment of cancer diseases (section 0089-0095) . Ma teaches that the target biomolecule for polynucleotide profiling can be cell free DNA (0096). Although Ma states that c f DNA can be a potential biomarker to be measured, it does not serve to anticipate the claimed invention because there would be some picking and choosing required to arrive at the claimed invention. However cfDNA has been discovered and studied for decades, particularly in its association with the diagnosis, progression and therapy of cancers. Mortimer teaches isolating and analyzing cfDNA, e.g. methylation which has been shown as indicative of various cancers or other diseases , from blood samples of cancer patients (section 0498 ; 0349 ). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Mortimer to measure and detect c f DNA for further diagnosis of cancer because the known association with cfDNA and cancer and one ordinary skilled person in the art would have been motivated to use cfDNA as a diagnosis tool for identification of cancer with reasonable expectation of success. As to claim 2-3, Ma teaches that the administering the nanoparticles can be performed by intravenous, intradermal, or intramuscular injection (see section 0061). As to claim 4, the contacting of biological samples with nanoparticles includes incubation to allow the adsorbing of target biomolecules to the nanoparticles. As to claim 5, the biological samples include blood and plasma (see above). As to claim 8, Ma teaches that the nanoparticles can be of gold, silver, platinum, palladium, superparamagnetic, or liposome and the surface of the nanoparticles can be modified with negative or positive charges (section 0013 ; 0192 ). As to claim 12, the isolating and analyzing biomolecules procedures involve removing (washing) the unbound/undesired components from the samples ( Ma, section 0050, 0057-58, 0118) . As to claim 14, 19, and 21-22, Ma teaches that the data collected from the analysis can be used for diagnosis of variety of disease, such as cancer, inflammatory disease, atherosclerosis, neurological diseases (section 0089-0095). As to claims 15-16, the determination of biomolecules including quantitation the amount of nucleic acid in the sample ( Ma, section 0044). As to claim 18, particular portion or fragments of a nucleic acid is considered a biomarker for diagnosis purpose (section 0048, 0057). Ma teaches storing sequencing data for individual’s test results (section 0158). Moreover Mortimer also teaches different fragments of nucleic acid as biomarkers (section 0349). As to claims 20, 23-24, Ma teaches using the biomarkers for monitoring of a treatment response to a therapy (section 0129, 0144). Using control (or reference) for comparison is also taught (Ma, section 0124, 0129, 0135, 0141, 0144, 0147). Moreover, Mortimer teaches that the level of cfDNA methylation is also indicative of the diseases (section 0054-55; 0071; 0160, 0193; 0238) and can be used for monitoring response to treatment of a disease (section 0354-0355) . Claim (s) 1, 4-5, 8, 10-16, 18- 24 are rejected under 35 U.S.C. 103 as being unpatentable over Huo (US20130052661) in view of Mortimer. Huo teaches analyzing biomarkers in a biological fluid sample. Huo teaches incubating a plurality of nanoparticles ( without specific probes thereon) with the sample to form corona biomolecule complex for detecting biomolecule targets , e.g. protein or nucleic acid biomarkers, associated with disease s, e.g. cancer (section 0009, 0012, 0016, 0023). However Huo does not explicitly utiliz e “cell-free nucleic acid” (cfDNA) for analysis. As has been shown above that Mortimer teaches isolating and analyzing cfDNA, e.g. methylation which has been shown as indicative of various cancers or other diseases, from blood samples of cancer patients (section 0498; 0349). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Mortimer to measure and detect cDNA for further diagnosis of cancer because the known association with cfDNA and cancer and one ordinary skilled person in the art would have been motivated to use cfDNA as a diagnosis tool for identification of cancer with reasonable expectation of success. As to claim 4, the contacting of biological samples with nanoparticles includes incubation to allow the adsorbing of target biomolecules to the nanoparticles. As to claim 5, the biological samples include blood and plasma (see above). As to claim 8, the nanoparticles can be of gold or silver possessing a charge for absorbing biomolecules on its surface (section 00 23 ). As to claim 12, it would have been prima facie obvious to one ordinary skilled in the field to remov e ( or wash) the unbound/undesired components from the samples. As to claim 14, 19, and 21-22, Huo also teaches using the results for diagnosis of cancer (section 0023, 0033-0034). As to claims 15-16, the determination of biomolecules including quantitation the amount of nucleic acid in the sample (section 0023). Moreover, Mortimer teaches that the level of cfDNA methylation is also indicative of the diseases (section 0054-55; 0071; 0160, 0193; 0238) and can be used for monitoring response to treatment of a disease (section 0354-0355). Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT CHANGHWA J CHEU whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0814 . 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