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 Status of the Claims Claims 28-42 are pending and the subject of this FINAL Office Action. Claim Interpretations Claim 28 merely states that a sample is selected because it has a long:short cfDNA of <0.3 (i.e. much more short, apoptotic cfDNA than long necrotic cfDNA). A skilled artisan would be interested in such a sample because it indicates graft acceptance (whereas a higher number would indicate graft rejection, or other problems). In other words, the sample is merely selected and dd cf -DNA quantified. The claims do not require any specific assay, or any specific post “selecting” steps. The claims amounts to determining apoptotic cfDNA and necrotic cfDNA, then selecting a sample for any reason . The prior art is replete with examples of “selecting” samples that indicate low graft rejection (e.g. for further study such as biomarker analysis). For this reason, as explained below, Applicants’ claims are not allowable. Applicants are also reminded that their claims encompass any Alu fragments 171-300bp and 75-170bp, in any sample (e.g. elephant, dog, human, lion, giraffe, worm, etc.), using any primers, and any detection. Yet a single example is disclosed in the specification. Applicants are strongly encouraged to amend the claims accordingly. 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. Claims 28-30, 35-37 and 39-42 are rejected under 35 U.S.C. § 103 as being obvious over KHOJA (US 2017/0283788), in view of SCHUTZ (US 2016/0115541). This rejection is presented in the interest of compact prosecution to the extent the only example of the claimed invention is using Alu247:Alu115 to detect apoptosis and necrosis in transplant patients in order to determine transplant rejection (Spec., Example 8). SCHUTZ provides explicit motivation to look to short cfDNA versus longer cfDNA as a non-invasive, simple way to help determine transplant rejections using donor-derived cfDNA quantities ( GcfDNA ). . . . There is thus a need for sensitive, easily implemented techniques for early detection of transplant rejection. . . . the amount of graft DNA released by an organ into the circulation can be assessed and used as a biomarker for organ integrity. [ . . . ] The effect of early damage can be quantified by the determination of the GcfDNA (cp/mL), which shows a clear reduction over the first week after LTx . FIG. 10 shows the results obtained from an analysis of a marginal donor in comparison to the range seen in 14 other patients. The LTx of this marginal organ did show a good initial outcome and function, which is predicted by the rapid decrease of GcfDNA at the lower end of the whole group. In addition, the amount of necrosis of the graft can be assessed by estimating the length of the cfDNA, which is short if released by apoptotic cell damage and longer if of necrotic origin. By comparing the amount of cfDNA determined with a digital droplet PCR of short length with those determined with a PCR directed to a longer target, an apoptotic index can be defined. The higher that value is, the more cfDNA is of necrotic origin. FIG. 11 shows the time course during the first days after LTx ( paras . 0003, 0006 & 0098). In other words, SCHUTZ teaches that early detection of graft rejection is critical to proper treatment. In addition, “simple” detection is critical. To this end, SCHUTZ teaches one “simple” detection includes comparing short cfDNA to longer cfDNA to determine “an apoptotic index” and “[t]he higher that value is, the more cfDNA is of necrotic origin,” or donor transplant being rejected. “In addition [to GcfDNA quantification], the amount of necrosis of the graft can be assessed by estimating the length of the cfDNA, which is short if released by apoptotic cell damage and longer if of necrotic origin” (para. 0098; see Fig. 11). The values of long:short cfDNA in Figure 11 show less than 0.3. Thus, SCHUTZ discloses selecting at least one sample of which a ratio of the amount of the long cfDNA fragment over the short cfDNA fragment is less than 0.3 and quantifying the amount of donor-derived cell- free DNA in the selected sample. SCHUTZ does not explicitly teach the fragments amplified are Alu repeats. However, SCHUTZ suggests repetitive elements were known options as opposed to SNPs (para. 0037); and the prior art teaches well-known Alu-based methods to do so. For example, KHOJA teaches qPCR detection of Alu247:Alu115 in blood samples to detect apoptosis and necrosis (paras. 0004, 0028, 0032-33). The cfDNA is extracted (Title, para. 0023, 0028, as examples). The cfDNA is quantified (para. 0032, for example). KHOJA teaches that shorter amplicons are indicative of apoptosis and necrosis, which are present in transplant rejection recipients (paras. 0004, 0024, 0033). Thus, a skilled artisan would have been motivated to substitute alu-based cfDNA analysis for the SNP-based size analysis of SCHUTZ. As to claim 39, KHOJA teaches using standard curve (paras. 0028-30). KHOJA explicitly teaches to detect cell lysis in cfDNA using human actin gene 67 bp versus 411 bp amplicons; and Alu115 and Alu247 to measure cell lysis using cfDNA (paras. 0024-28). As to claims 28-30, 35-37 and 46-47, KHOJA provide motivation for qPCR detection of Alu247:Alu115 using SEQ ID NO: 1 in blood samples to detect transplant rejection (paras. 0004, 0028, 0032-33). The cfDNA is extracted (Title, para. 0023, 0028, as examples). The cfDNA is quantified (para. 0032, for example). KHOJA explicitly explains that transplant rejection status can be detected using cfDNA integrity: Detection and/or quantitation of certain biomarkers such as cell free DNA (cfDNA) in biological samples like blood, saliva, sputum, stool, urine, or tissue can help to diagnose disease, establish a prognosis, and/or aid in selecting or monitoring treatment . . . . cfDNA is also becoming increasingly important as a marker for early detection of transplant/allograft rejection, since the cfDNA that is shed from donor tissue is readily identifiable by donor-specific genetic sequence variations (De Vlaminck et al. (2013) Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection. Sci Transl Med 6(241):241ra77; Snyder et al. (2011) Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci USA 108(15):6229-6234). ( para . 0004). KHOJA also explains that apoptotic cfDNA is a known marker of transplant rejections (para. 0033). KHOJA further explains that short amplicons (e.g. 67bp) indicate apoptotic cfDNA, whereas long amplicons (e.g. 411 bp) indicate cell-origin cfDNA (e.g. necrotic cell death) ( id. ). Although this assay does not include a long Alu and short Alu within the claimed short range (75-170 bp) and long range (171-300 bp), yet KHOJA provides motivation to substitute it. KHOJA discloses another known Alu-based assay for distinguishing short (115 bp) and long (247 bp) cfDNA (para. 0028). Thus, KHOJA discloses Alu-based cfDNA ratios within the claimed short range (75-170 bp) and long range (171-300 bp) to determine cell death and apoptosis (claimed “cell lysis”). In sum, a skilled artisan reading KHOJA would conclude that the cfDNA integrity analysis using Alu247:Alu115 “is indicative of the amount of cell lysis in the sample,” as claimed (instant claim 28); and “indicative” of transplant rejection (e.g. instant claim 47). As to claims 39 and 41-43, KHOJA teaches using standard curve (paras. 0028-30). In sum, a skilled artisan reading KHOJA would have found it prima facie obvious before the effective filing date to substitute familiar cfDNA size ratios using Alu assays to determine cell lysis, including in transplant recipients, for the SNP assays of SCHUTZ with a reasonable expectation of success. Claim 38 is rejected under 35 U.S.C. § 103 as being unpatentable over KHOJA, in view of SCHUTZ, in further view of WEISS (US 20040136967 A1). It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to apply familiar white blood cell spiking to the techniques of KHOJA with a reasonable expectation of success. As to claim 28, KHOJA in view of SCHUTZ teach the elements of these claims as explained above. KHOJA in view of SCHUTZ does not explicitly teach white blood cell spiking. However, WEISS teaches to spike cell samples for downstream analysis with 500 cells as a known option in the art of PCR detection controls (para. 0052). Thus, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to apply familiar white blood cell spiking for qPCR to provide sample and qPCR controls with a reasonable expectation of success. Claims 31-33 are rejected under 35 U.S.C. § 103 as being unpatentable over KHOJA, in view of SCHUTZ, in further view of SUNAMI (WO 2006/128192 A2). It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to apply familiar qPCR probe design to the Alu247 and Alu 115 sequences of KHOJA to yield the probes of SEQ ID NOS: 1, 10 and 13 with a reasonable expectation of success. As to claims 28-30, KHOJA, in view of SCHUTZ teach the elements of these claims as explained above. KHOJA, in view of SCHUTZ does not explicitly teach using qPCR probes such as SEQ ID NOS: 1, 10 and 13. However, KHOJA explicitly teaches to use familiar qPCR technique to detect Alu247:Alu115 (paras. 0024-30). To this end, a familiar option other than SYBR-based qPCR of KHOJA was Taqman or probe-based qPCR of SUNAMI. SUNAMI teaches to use probe-based qPCR to detect Alu247:Alu115 using familiar qPCR probe designs (pgs. 12, 59). SUNAMI further teaches the sequences of Alu247 and Alu115 to makes these probes (Figs. 6, 11). In other words, a skilled artisan of ordinary creativity would have been motivated to apply familiar qPCR probe design parameters to yield the following probes: Query Instant SEQ ID NO: 1/ Sbjct SUNAMI Figs. 6, 11 Thus, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date to apply familiar qPCR probe design parameters and familiar Alu sequences to design the qPCR probe of SEQ ID NO: 1 with a reasonable expectation of success. Allowable Subject Matter Claim 34 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 2nd paragraph, set forth in this Office action. Claim 34 would be allowable over the prior art because the prior art fails to teach or suggest to detect cell lysis using Alu175:Alu79 using qPCR probes SEQ ID NOS: 10 (Alu175) and 13 (Alu79). Claim 34 also passes subject matter eligibility test because this combination of probes is non-routine. Possible Double Patenting The following may be the basis of double patenting depending on claim amendments: US 12084720; US 18/756518. Prior Art The following prior art also teaches to detect apoptotic and necrotic cell death using long (necrotic) versus short (apoptotic) circulating DNA in transplant recipients: US 20150211070; WO 2018000031. The following prior art is only a sampling of the prior art pertinent to Alu247:Alu115 detection: US 20090280479; US 20160186239; US 20170152561; US 20170218458; US 20180288982; Hao et al, Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer, Br J Cancer. 2014 Oct 14;111(8):1482-9. doi : 10.1038/bjc.2014.470. Epub 2014 Aug 26. Conclusion No claims are allowed. This is a CON of applicant's earlier Application No. 16/597559. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the earlier application. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Aaron Priest whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-1095 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 8am-6pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT Gary Benzion can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-0782 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AARON A PRIEST/ Primary Examiner, Art Unit 1681