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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/14/2025 has been entered.
This Office Action is in reply to Applicants’ correspondence of 01/14/2025 and the Election of 08/13/2025.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put this application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is NON-FINAL.
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Claim 6 (directed to the particular measure of “concentration”) remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as set forth on page 2 of the Office Action of 05/10/2023.
An Election was made without traverse in the reply filed on 02/28/2023.
Applicants’ Election of the particular marker that is “the first SNP listed in Table 1 (Name: S43, GA002729)”, in the reply of 08/13/2025 is acknowledged.
In light of the Examiner’s search and Examinations of the elected SNP, the species election requirement as set forth in the Office Action of 07/31/2025 is withdrawn.
New Claim Rejections - 35 USC § 112 – Indefiniteness
Necessitated by Claim Amendments
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 13 and 14 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.
Claims 13 and 14 are unclear over the recitation of limitations requiring SNPs “set forth in Table 1”. MPEP 2173.05(s) provides guidance regarding references to figures of tables in claims:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)
In the instant case the rejection may be addressed by referencing the name of the SNPs, as consonant with the disclosure, in the text of the claims.
Maintained Claim Rejections - 35 USC § 103
Modified as Necessitated by Claim Amendments
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.
Claim(s) 1-5, 7, 8, 10, 12 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snyder et al (2011) (cited on the IDS of 10/15/2021), in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012), Gineikiene et al (2009) (cited on the IDS of 10/15/2021) and Wilm et al (2012).
Snyder et al teaches genome wide analysis of cell free DNA in plasma samples of heart transplant recipients to detect alleles of SNPs originating from donor graft material and endogenous recipient cell free DNA.
Relevant to the limitations of rejected claim 1, Snyder et al teaches detection of SNP content for which the recipient is homozygous for a first allele (e.g.: A/A) and the donor is either heterozygous (e.g.: A/T) or homozygous (e.g.: T/T) (relevant to claim 5) for the alternate allele (e.g.: p.6231 - Sequencing-Based Donor DNA Quantitation). Snyder et al teaches whole genome sequence analysis, and provides counts of sequences to calculate donor DNA percentage in the cell-free sample; the reference teaches that sequencing provided a value for the number of donor SNP alleles in the sample (e.g.: p.6234 – Sequencing) (relevant to claim 4). Snyder teaches that SNP alleles are identified in the recipient (e.g.: p.6234 - Patient genotyping and library preparation), alleles from donor and recipient are quantified in cell free DNA from plasma are quantified to monitor transplant status (e.g.: Figure 4) (relevant to claim 12). Snyder et al thus teaches the detection of the percentage of donor SNP alleles in cell free DNA from a recipient blood sample after transplantation of donor tissue (e.g.: Fig. 4).
Relevant to claim 2, Snyder et al teaches amplifying cfDNA from plasma samples to create a library.
Relevant to claim 3, Snyder et al teaches that genotyping was performed using whole blood, which includes peripheral blood leukocytes.
Relevant to claim 5, Snyder et al teaches that homozygous donor SNPs were detected (e.g.: Fig S3).
Relevant to claim 8, Snyder et al provides an analysis of the samples at least 5 days after transplantation (e.g.: Fig 4; p.6233 - Posttransplant monitoring and clinical sample collection).
Relevant to the limitations of claim 7, Snyder et al teaches the analysis of multiple samples taken at successive time points (e.g.: Figure 1; p.6233 - Posttransplant monitoring and clinical sample collection).
Relevant to the limitations of claim 16, Snyder et al teaches that donor DNA levels of 1% or less can be detected in a transplant recipient (e.g.: Fig. 4).
Snyder et al exemplifies the analysis of whole genome SNP content to detect recipient and donor cell free DNA in transplant recipient samples to monitor graft rejection. Snyder et al does not specifically teach that the analysis is performed without genotyping a donor specific sample. However, the identification of donor allele content in a sample from a transplant recipient that is homozygous for a particular allele, without genotyping a donor specific sample would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made. For example, the skilled artisan would have recognized that if a transplant recipient was homozygous for a particular allele at a particular SNP position (which is an aspect of the analysis explicitly taught by Snyder et al), then detecting a different allele in a cfDNA sample from the recipient would be detection of an allele from the donor organ. The skilled artisan would recognize that where the recipient genome can only provide a single particular allele (i.e.: the allele for which the recipient is known to be homozygous), then any detected non-recipient allele would originate from the separate genome of the transplanted organ (i.e.: from the donor genome). The skilled artisan would be motivated to perform the methods without analysis of a separate donor sample because the skilled artisan would recognize that the step was not needed to identify donor alleles in a homozygous recipient, and thus would make form a more efficient analysis with less steps. The skilled artisan would have a reasonable expectation of success base on the expressed teachings of Snyder et al (e.g.: p.6229) that “…organ-specific donor DNA is detectable in the plasma of heart transplant recipients and that this genetic signature increases substantially before rejection events.”
Snyder et al does not teach detection of allele content using targeted DNA sequencing. However, the use of targeted DNA sequence to collected allele content data for establishing the fractional amount of DNA from a particular source in a sample with a mixture of DNA from different sources was known in the prior art and is taught by Jiang et al.
Jiang et al teaches methods related to quantifying the amount of DNA from a particular source in a mixed sample using a statistical model to deduce a fractional DNA concentration directly from targeted MPS data. Jiang et al exemplifies the detection of fetal DNA in a maternal sample that comprises maternal DNA and fetal DNA (similar to the recipient and donor DNA, respectively, of the claimed methods). Particularly relevant to the claims, Jiang et al teaches that sequencing is used to determine the amount of fetal DNA in a maternal blood sample without using any fetal or paternal genotype information (e.g.: p.2884 – left col), that samples are analyzed at SNPs for which the maternal genotype is homozygous (e.g.: p.2887), and that different genotype combinations can be analyzed (e.g.: Figure 1).
Additionally relevant to the methods of the claims, WO 2012/019200 teaches that a sample from a transplant patient may be any fluid or tissue which contains cell free nucleic acids from both the donor cells and the cells of the patient (e.g.: paras 53 and 211), that polymorphic loci that are homozygous in one source and heterozygous in the other source can be used to quantitate the nucleic acids arising from each source (e.g.: para 93) and that method can be performed without using prior genotypic knowledge of the minor contributing source (e.g.: para 220).
Snyder et al does not specifically teach that homozygous recipient SNPs are selected to have a minor allele frequency of 0.4 or greater and that the SNP content is detected by targeted DNA sequencing. However, both Jiang et al (e.g.: Abstract; targets massively parallel sequencing) and WO 2012/019200 (e.g.: paras 132-134, 219) teach quantifying sample contribution in a mixed sample using a targeted analysis (including targeting sequencing, as taught et Jiang et al) of polymorphic loci. And the particular analysis of SNPs with a minor allele frequency of 0.4 or greater in the context of identifying the source of a detecting genentic material was known in the prior art and is taught by Gineikiene et al.
Gineikiene et al teaches the use of PCR methods to detect SNPs related to source (i.e.: donor or recipient) of genetic material. Relevant to the instantly rejected claims, Gineikiene et al teaches that biallelic SNPs with allele frequencies of 0.4 to 0.6 are most informative, and if primers and probes can be made for the locus, then virtually any biallelic SNP locus with allele frequencies of 0.4 to 0.6 could be used for genotype identification in a transplant pair.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have modified the sequencing-based SNP allele detection methods for quantifying an amount of donor DNA in a cell-free sample taught by Snyder et al to have included the allele detection and quantification by targeted sequencing as exemplified by Jiang et al and as suggested by WO 2012/019200, and to have included the targeted detection of alleles of SNPs with a minor allele frequency of 0.4 or greater as taught by Gineikiene et al. The skilled artisan would be motivated to use targeted analysis of the SNPs of Gineikiene et al based on the expressed teachings of Gineikiene et al which establish that targeted detection of such SNP alleles, as exemplified by Gineikiene et al, could be used for genotype identification in a transplant pair. The skilled artisan would have a reasonable expectation of success in the detection of alternate alleles of donor origin (i.e.: detecting an allele that is different than an allele for which the recipient is homozygous) based on the prior art teaching of Wilm et al which provides for the sensitive detection of variant alleles in data produced from massively parallel sequencing techniques.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 103 as rendered obvious by the cited prior art as set forth above. Applicants’ arguments (p.5-10 of the Remarks of 01/14/2025) have been fully and carefully considered but are not persuasive to withdraw the rejection.
Applicants have initially asserted that “there is no explanation in the of how the teachings of Wilm are applied” in the rejection. Here it is noted that the teachings of Wilm et al are applied (as set forth in the final sentence of the rejection) to show that the quantification of very low frequency allele content in mixed samples was known in the prior art, and thus there would be a reasonable expectation of success in modifying the methods of Snyder et al to incorporate the teachings of Jiang et al, WO 2012/019200 and Gineikiene et al for the quantification of donor alleles in a cell-free sample form a transplant recipient.
With regard to the teachings of Snyder et al as applied in the rejection, Applicants have argued (p.6-7 of the Remarks), that Snyder provides no way of quantifying donor DNA without first knowing which donor SNPs have the alternative allele relative to a homozygous SNP allele in the recipient, and that the teachings in Jiang and WO2012/019200 do not provide any further information that provides evidence that the claimed invention is obvious. With regard to the argument as it is applied to Snyder et al as provided in the rejection, the argument that Snyder provides no way of quantifying donor DNA without first knowing which donor SNPs have the alternative allele relative to a homozygous SNP allele in the, the argument appears to require an explicit teaching of the limitation in the cited prior art. It is well accepted that the decision in KSR forecloses Applicants’ argument that a specific teaching is required for a finding of obviousness, and that that use of common sense does not require a "specific hint or suggestion in a particular reference". See MPEP 2141.
Furthermore, the rejection is made in combination with the teachings of Jiang et al which explicitly teaches the use of target sequencing to determine the fraction of a particular portion (i.e.: fetal DNA) of a mixed sample (i.e.: fetal and maternal DNA) without prior knowledge of the genotype of the determined portion (i.e.: Jiang et al explicitly teaches that the paternal or fetal genotypes are not required to determine the fetal fraction). The examiner maintains that the skilled artisan in possession of the teachings of Snyder et al, and certainly in possession of the teachings of Snyder et al in view of Jiang et al, would recognize that the detection of donor derinved alleles in a transplant recipient can be performed using SNPs for which the recipient is homozygous, and the donor is homozygous or heterozygous for the alternative allele and that SNPs that provide an allele signal that is not the recipient’s allele are: (1) a marker for donor material; and (2) present in two groups of percentages (one that is twice as high as the other e.g., 2% vs 1 % where the higher percentage is homozygous in the donor transplant material, and the lower percentage indicates that the SNP is heterozygous in the donor material), where distribution of allele content in mixed samples is taught by Jiang et al (e.g.: Fig. 1; p.2888, right col).
For example, where Snyder et al teaches graft DNA at 3% in a rejection (e.g.: p.6233, left col) the analysis taught by Snyder et al, and Snyder et al in view of Jiang et al, would include detecting alleles at SNPs where (for these examples, SNP loci are a particular letter, different alleles are lowercase or uppercase, and recipient is bold versus donor is underlined (so the same allele of a SNP (e.g.: bold-capital ‘A’, underlined-capital ‘A’ is distinguishable in the text of the example (bold if from donor, underlined if from recipient), but would be molecularly indistinguishable in a biological sample):
97% 3%
Recipient Genotype Donor Genotype Sample
A/A A/a 98.5% (A+A); 1.5% a
B/B b/b 97% B; 3% b
And so, where the expected allele distribution in each case would be 100% for the recipient allele, detecting a variation in that expected 100% for SNPs ‘A’ and ‘B’ allows the determination that the donor DNA makes up 3% of the sample, which is relevant to the “quantifying” in step (b) of claim 1.
Applicants next argue that Jiang et al exemplifies the detection of amounts of fetal DNA of 9.6-19.3% and 10.3-30.2%, thus not applicable to the detection of lower amounts of donor DNA in a transplant recipient. This argument is not persuasive where the rejected claims encompass quantifying any amount of donor derived DNA and Snyder teaches that higher amounts of donor-derived DNA may be found in cases of rejection (e.g.: 5%-8% in Figs 2 and 4) and teaches that sequencing may detect donor DNA levels less than 1%. Additionally, while Jiang does not exemplify the detection of amounts of fetal DNA as low as 1%, the reference explicitly teaches that “there is no practical limitation” with regard to the use of targeted massively parallel sequencing to deduce lower fractions of DNA content, where accuracy largely depends on the availability of sequencing counts (i.e. the number of SNP loci times the sequencing
depth).
Similarly, where Applicants argue (p.7 of the Remarks) that a particular exemplification of WO2012/019200 uses a methodology different than sequencing, the argument is not persuasive to withdraw the rejection which includes the teachings of both Snyder et al and Jiang et al. The Examiner maintains that the teaching of WO2012/019200 are relevant to the methods of the instant claim where the reference teaches (para 000219) targeted SNP analysis to detect DNA from a minor source in a mixed sample, and that “prior genotyping is not necessary prior to performing the assay, and the genotyping is performed simultaneously with the determination of copy number of selected loci within a mixed sample”, and further teaches that sequencing may be used in the SNP analysis (e.g.: para 000125):
The use of selected loci in the assay methods of the invention provides direct detection of loci for determination of copy number variation in one or more sources within the mixed sample. A distinct advantage of the invention is that the selected loci corresponding to copy number variation and/or polymorphisms can be further analyzed using a variety of detection and quantification techniques, including but not limited to hybridization techniques, digital PCR and high throughput sequencing determination techniques.
Applicants’ arguments continue (p.8 of the Remarks) with assertions about the required precision of the methods of claims, and the teachings of the specification demonstrating the quantification of graft DNA that is less than 1%. These arguments are not persuasive in view of the cited prior art which teaches the SNP sequencing based detection of less than 1% donor DNA in samples (e.g.: Snyder et al at Fig 4), teaches that targeted massively parallel sequencing can detect lower levels of DNA content with no practical limitations where accuracy largely depends on the availability of sequencing counts (e.g.: Jiang et al at page 2888), and teaches sequencing data can be used for the sensitive detection of low frequencies of alleles in a mixed sample (e.g.: Wilm et al, p.11193 - Sensitivity/specificity tradeoffs and detection limits).
Claim 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snyder et al (2011) (cited on the IDS of 10/15/2021) in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012), Gineikiene et al (2009) (cited on the IDS of 10/15/2021) and Wilm et al (2012), as applied to claims 1-5, 7, 8, 10, 12 and 16 above, and further in view of Lima et al (2006) (cited on the IDS of 10/15/2021).
The teachings of Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al are applied to instantly rejected claim 9 as they were previously applied to claims 1-5, 7, 8, 10, 12 and 16 above.
Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al does not specifically teach methods wherein a transplanted material is a marginal organ. However, the use of marginal organs in transplantation was known in the prior art and is taught by Lima et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have modified the methods taught by Snyder et al in view of Jiang et al, Gineikiene et al and Wilm to have analyzed rejection in the recipient of a marginal organ, as taught by Lima et al. The skilled artisan would have been motivated to use a marginal organ in transplantation based on the teachings of Liam et al that using such organs expands the organ pool and addresses issues related to organ shortage and prolonged waiting times.
Claim 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snyder et al (2011) (cited on the IDS of 10/15/2021) in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012), Gineikiene et al (2009) (cited on the IDS of 10/15/2021) and Wilm et al (2012), as applied to claims 1-5, 7, 8, 10, 12 and 16 above, and further in view of Gadi et al (2006).
The teachings of Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al are applied to instantly rejected claim 11 as they were previously applied to claims 1-5, 7, 8, 10, 12 and 16 above.
Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al does not specifically teach methods wherein a serum sample is analyzed. However, the detection of donor derived DNA in serum of a transplant recipient was known in the prior art and is taught by Gadi et al (e.g.: p.380 – Samples; Figure 1).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have modified the methods taught by Snyder et al in view of Jiang et al, Gineikiene et al and Wilm to have analyzed donor derived DNA in the serum of a transplant recipient as taught by Gadi et al. The skilled artisan would have been motivated to use serum based on the expressed teachings of Gadi et al that serum is a suitable source of donor DNA in a transplant recipient; thus the use of serum would have been the simple substitution of one known element for another with predictable results.
New Claim Rejections - 35 USC § 103
Necessitated by Newly Presented Claims
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snyder et al (2011) (cited on the IDS of 10/15/2021) in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012), Gineikiene et al (2009) (cited on the IDS of 10/15/2021) and Wilm et al (2012), as applied to claims 1-5, 7, 8, 10, 12 and 16 above, and further in view of Pakstis et al (2010).
The teachings of Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al are applied to instantly rejected claim 15 as they were previously applied to claims 1-5, 7, 8, 10, 12 and 16 above.
Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al does not specifically teach methods wherein the panel of SNPs preselected to have a minor allele frequency of 0.4 or greater across human populations comprises at least 40 SNPs. However, a panel more than 40 SNPs with global average heterozygosity >0.4 for use in individual identification was known in the prior art and is taught by Pakstis et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used the SNPs of Pakstis et al in the targeted sequencing of SNPs in the methods rendered obvious by Snyder et al in view of Jiang et al, Gineikiene et al and Wilm et al. The skilled artisan would have been motivated to use the SNPs of Pakstis et al based on the expressed teachings of Pakstis et al that such SNPs are have a heterozygosity of >0.4 and are universally applicable for individual identification, and the teachings of Gineikiene et al that biallelic SNPs with allele frequencies of 0.4 to 0.6 are most informative in determining donor DNA fractions.
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
Claims 1-5, 7-12 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,155,872 in view of Snyder et al (2011) (cited on the IDS of 10/15/2021) in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012) and Wilm et al (2012).
The claims of the conflicting patent are directed to the same detection of donor alleles in a sample from a transplant recipient. The conflicting claims do not require the analysis of alleles by targeted DNA sequencing, however the detection of donor alleles using sequencing was known in the art and is exemplified by Snyder et al, Jiang et al and WO 2012/019200, and the detection of low levels of variant alleles in high throughput sequencing data is supported by Wilm et al.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have performed the allele detection of the conflicting claims using the sequencings methods of Snyder et al as supported by Wilm et al. The skilled artisan would have recognized the methods of allele detection of Snyder et al as an alternative method to accomplish the same detection, and thus the use of sequencing in the methods of the conflicting claims would have been the simple substitution of one known element for another known element with predicable results.
Claims 15 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,155,872 in view of Snyder et al (2011) (cited on the IDS of 10/15/2021) in view of Jiang et al (2012) (cited on the IDS of 12/05/2023), WO 2012/019200 (Feb. 9, 2012) and Wilm et al (2012), as applied to claims 1-5, 7-12 and 16, and further in view of Pakstis et al (2010).
The teachings of 11,155,872 in view of Snyder et al, Jiang et al, Gineikiene et al and Wilm et al are applied to instantly rejected claim 15 as they were previously applied to claims 1-5, 7-12 and 16 above.
11,155,872 in view of Snyder et al, Jiang et al, Gineikiene et al and Wilm et al does not specifically teach methods wherein the panel of SNPs preselected to have a minor allele frequency of 0.4 or greater across human populations comprises at least 40 SNPs. However, a panel more than 40 SNPs with global average heterozygosity >0.4 for use in individual identification was known in the prior art and is taught by Pakstis et al.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used the SNPs of Pakstis et al in the targeted sequencing of SNPs in the methods rendered obvious by 11,155,872 in view of Snyder et al, Jiang et al, Gineikiene et al and Wilm et al. The skilled artisan would have been motivated to use the SNPs of Pakstis et al based on the expressed teachings of Pakstis et al that such SNPs are have a heterozygosity of >0.4 and are universally applicable for individual identification.
Response to Remarks
Applicants have acknowledged (p.9 of the Remarks of 01/14/2025) the rejection of claims for issues related to double patenting.
Conclusion
No claim is allowed.
Claims 13 and 14 are free of the prior art. While the prior art renders obvious the use of SNPs with a minor allele frequency of 0.4 or greater in the determination of donor DNA fraction in a sample, the prior art does not particularly teach the suitability of the SNPs of Table 1 in the claimed methods.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683