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 .
Applicant’s amendment filed on January 7, 2026 is acknowledged and has been entered. Claims 1 and 4-17 have been amended. Claims 1-17 are pending.
Claims 1-17 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made FINAL
Previous Grounds of Rejection
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61395850, 61398159, 61426208, 61462972, 61448547, 61571248, 61675020, 61683331, 62147377 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application 61395850 teaches multiplex amplification and sequencing, but does not teach a processor or a system, as claimed. Application 61462972 only teaches cell free DNA, as claimed and does not provide support for any of the other features of the claimed system. Application 61571248 only teaches high throughput sequencing and cell free DNA, as claimed, and does not teach the other features of the claim, including a processor or simultaneous or multiplex amplification. Each of 61398159, 61426208, 61448547 teach the sequencing, processor and multiplex but not the inclusion of 100 primers or more, as claimed, as part of the reaction chamber. The earliest priority document that provides full support for the claimed invention is 61516996 which has a priority date of April 12, 2011.
Claim Rejections - 35 USC § 112 – written description – withdrawn
Applicant’s amendments were sufficient to overcome this rejection
Claim Rejections - 35 USC § 112
Applicant’s amendment to the claims was sufficient to obviate the concern regarding means plus function claim language.
New Grounds of Rejection
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 22, 2025 and March 5, 2026 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim(s) 1-2, 4-10 and 14-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Braverman et al. (US 20090105959 A1; April 2009) in view of May et al. (US PgPub 20140227691; August 2014).
With regard to claim 1, Braverman teaches a system for amplifying and sequencing DNA, comprising:
(a) a reaction chamber
(b) a sequencer for performing high-throughput sequencing of the amplified SNP loci from the subject and the genetically distinct individual (p 7, where the systems useful for the techniques within Braverman are described as including automation, sequencing and processing; paragraph 4 and 47, for example, where high throughput sequencing is described); and
(c) a computer processor programmed for receiving an output resulting from an amount of the DNA from the genetically distinct individual present in the biological sample that has been determined using the amount of one or more alleles at the SNP loci from the genetically distinct individual in sequence reads produced by the sequencer (p 7, paragraph 65-70, where computer processor power is described in detail).
With regard to claim 14, Braverman teaches a system for amplifying and sequencing DNA, comprising:
(a) a reaction chamber;
(b) a sequencer for performing high-throughput sequencing of the amplified SNP loci from the subject and the genetically distinct individual (p 7, where the systems useful for the techniques within Braverman are described as including automation, sequencing and processing; paragraph 4 and 47, for example, where high throughput sequencing is described);
(c) a computer processor programmed for receiving an output resulting from an amount of the DNA from the genetically distinct individual in the biological sample that has been determined using the quantity of each allele at the SNP loci from the genetically distinct individual in sequence reads produced by the sequencer and an expected quantity of each allele at the SNP loci for different DNA fractions (p 7, paragraph 65-70, where computer processor power is described in detail).
With regard to claim 16, Braverman teaches a system for sequencing DNA, comprising:
(a) a sequencer for performing high-throughput sequencing of more than 100 amplified SNP loci from a genetically distinct individual, wherein the more than 100 SNP loci are amplified from cell-free DNA in a single reaction volume using more than 100 PCR primer pairs, wherein the cell-free DNA is extracted from a biological sample of a subject and comprises DNA from the subject and DNA from the genetically distinct individual, wherein neither the subject nor the genetically distinct individual is a fetus, and wherein the cell-free DNA comprises DNA from a transplant (p 7, where the systems useful for the techniques within Braverman are described as including automation, sequencing and processing; paragraph 4 and 47, for example, where high throughput sequencing is described); and
(b) a computer processor programmed for receiving an output resulting from an amount of the DNA from the genetically distinct individual present in the biological sample that has been determined using the amount of one or more alleles at the SNP loci from the genetically distinct individual in sequence reads produced by the sequencer (p 7, paragraph 65-70, where computer processor power is described in detail).
Regarding claims 1-2, 4-10 and 14-15, while Braverman teaches all of the features of the systems, Yin does not particularly and specifically teach the inclusion of cell free DNA or the inclusion of 100 primer pairs.
With regard to claim 1, May teaches cell-free DNA at more than 100 SNP loci in a single reaction volume using more than 100 PCR primer pairs, the more than 100 PCR primer pairs configured to amplify cell-free DNA in a single reaction volume in the reaction chamber,
wherein the cell free DNA is extracted from a biological sample of a subject and comprises DNA from the subject and DNA from a genetically distinct individual, wherein neither the subject nor the genetically distinct individual is a fetus, and wherein the cell-free DNA comprises DNA from a transplant (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 2, May teaches a system of claim 1, wherein the biological sample is a blood, serum, plasma, or urine sample (paragraph 136, where the sample source is described).
With regard to claim 4, May teaches a system of claim 1, wherein the primer pairs are each designed to amplify less than about 100 bp of DNA (paragraph 108-110, where length of sample fragments are described).
With regard to claim 5, May teaches a system of claim 1, wherein the primer pairs are each designed to amplify less than about 80 bp of DNA (paragraph 108-110, where length of sample fragments are described).
With regard to claim 6, May teaches a system of claim 1, wherein the primer pairs are each designed to amplify about 65-80 bp of DNA (paragraph 108-110, where length of sample fragments are described).
With regard to claim 7, May teaches a system of claim 1, wherein more than 200 SNP loci are amplified in a single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 8, May teaches a system of claim 1, wherein more than 500 SNP loci are amplified in a single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 9, May teaches a system of claim 1, wherein more than 1000 SNP loci are amplified in a single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 10, May teaches a system of claim 1, wherein more than 2000 SNP loci are amplified in a single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 14, May teaches a system comprising the more than 100 PCR primer pairs configured to amplify more than 100 SNP loci on one or more chromosomes expected to be disomic in a single reaction mixture in the reaction chamber, wherein the reaction mixture comprises cell-free DNA extracted from a biological sample of a subject comprising DNA of mixed origin, wherein the DNA of mixed origin comprises DNA from the subject and DNA from a genetically distinct individual, wherein neither the subject nor the genetically distinct individual is a fetus, wherein the DNA of mixed origin comprises DNA from a transplant, and wherein one or more of the amplified SNP loci each comprises an allele present in the genetically distinct individual but not the subject (paragraph 136, where the sample source is described ;paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 15, May teaches a system of claim 14, wherein the biological sample is a blood, serum, plasma, or urine sample, wherein more than 500 SNP loci are amplified in a single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 17, May teaches a system of claim 16, further comprising a reaction chamber comprising the more than 100 PCR primer pairs, the more than 100 PCR primer pairs configured to amplify the cell-free DNA at the more than 100 SNP loci in the single reaction volume in the reaction chamber (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Braverman to include cell free nucleic acids and a plurality of primers as taught by May to arrive at the claimed invention with a reasonable expectation for success. Braverman teaches “Some exemplary embodiments of systems and methods associated with Sample preparation and processing, generation of sequence data, and analysis of sequence data are generally described below, some or all of which are amenable for use with embodiments of the presently described invention. In particular the exemplary embodiments of systems and methods for preparation of template nucleic acid molecules, amplification of template molecules, generating target specific amplicons and/or genomic libraries, sequencing methods and instrumentation, and computer systems are described” (paragraph 46, where the systems are described). May teaches “provides methods for selectively enriching a biological sample for short nucleic acids, such as fetal DNA in a maternal sample or apoptic DNA in a biological sample from a cancer patient and for subsequently analyzing the short nucleic acids for genotype, mutation, and/or aneuploidy” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Braverman to include cell free nucleic acids and a plurality of primers as taught by May to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 3 and 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Braverman et al. (US 20090105959 A1; April 2009) in view of May et al. (US PgPub 20140227691; August 2014) as applied over claims 1-2, 4-10 and 14-17 and further in view of Struble et al. (US PgPub 20220157400 A1; May 2022).
With regard to claim 3, Struble teaches a system of claim 1, wherein the cell-free DNA is extracted from a biological sample of a subject using size selection to enrich for shorter cell-free DNA (paragraph 56, where the samples include cell-free DNA).
With regard to claim 11, Struble teaches a system of claim 1, wherein SNP loci on chromosome 1 are amplified in the thermocycler (paragraph 8-9 of PgPub where autosomes and sex chromosomes are analyzed).
With regard to claim 12, Struble teaches a system of claim 1, wherein SNP loci on chromosome 2 are amplified in the thermocycler (paragraph 8-9 of PgPub where autosomes and sex chromosomes are analyzed).
With regard to claim 13, Struble teaches a system of claim 1, wherein SNP loci on chromosome 3 are amplified in the thermocycler (paragraph 8-9 of PgPub where autosomes and sex chromosomes are analyzed).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Braverman and May to include a device which is capable of analyzing SNP loci on chromosomes 1, 2 or 3 as taught by Struble to arrive at the claimed invention with a reasonable expectation for success. Yin teaches “we report our NGS-HLA typing experience performed on buccal DNA isolated from NMDP registry donors. Of the 10,063 samples tested over the one-year period, robust PCR amplification was accomplished in 9,842 samples (97.8%). Overall, a typing accuracy of 99.8% was achieved based on independent testing of 265 blind QC samples embedded into the study cohort” (p 11). Further, while Struble teaches samples that include cell free DNA, Struble also teaches “the methods utilize multiplexed amplification and detection of selected nucleic acid regions on the sex chromosomes and one or more autosomes (i.e., autosomes) to calculate the frequency of the X and Y chromosomes in relation to the percent fetal nucleic acid contribution in a maternal mixed sample. Relative quantities of the selected nucleic acid regions are determined for genomic regions of interest (e.g., sex chromosomal sequences as well as sequences from one or more autosomal chromosome sequences) using the analytical methods as described herein” (paragraph 8-9). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Braverman and May to include a device which is capable of analyzing SNP loci on chromosomes 1, 2 or 3 as taught by Struble to arrive at the claimed invention with a reasonable expectation for success.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-17 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed. All claims stand rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached on 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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