Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of the Claims
Claims 1-20 are pending and the subject of this FINAL Office Action.
Large IDS With Multiple Irrelevant References
Applicants filed a 80 pages of IDS with over 1,000 listed references. First, it is impossible to search in detail through all 1,000-plus references in any reasonable amount of time. Second, this is not the first application in this family of applications; in fact, there are over 100 others. Applicants have had ample opportunity to winnow their IDS down to only claim-relevant references. Furthermore, after a random skim of the references within the incredibly limited time allotted to the Examiner, the Examiner determines that many of the references are irrelevant to the claimed subject matter, having nothing to do with the allele-frequency system claimed. Which leads to the larger problem: which references are relevant, and why were these seemingly irrelevant references filed? Before filing an IDS, Applicants have a duty to examine the references themselves and determine which references are reasonably pertinent to the claimed invention. If any particular preference(s) is/are directly pertinent to the claimed invention, then Applicants are encouraged to point this out in the form of a new IDS.
The filing fecundity continues with an IDS filed 03/11/2026 and another filed 07/07/2026.
Priority
The claims receive a priority date of 05/18/2011 because the non-provisional application (13/300235) filed on that date is the first priority document to disclose a single system comprising a sequencer and a computer processer programmed to receive the sequencing reads, quantify the sequencing reads corresponding to each allele at the polymorphic loci, and measure the amount of DNA from the first individual in the biological sample of the second individual based on allele frequencies at a plurality of the polymorphic loci.
Response to Arguments
The Examiner does not understand Applicants response because it fails to assert any facts, rather only unclear statements. For example, “Applicant does not acquiesce to the Examiner's assertion that the '235 Application is ‘the first priority document’ to disclose the claims subject matter.” This seems to be a statement that Applicant traverses the priority date conclusion. Yet, no facts are provided to support this possible traversal. Yet again, Applicants assert “however, the priority issue is ultimately
not dispositive as the pending claims are novel and nonobvious over the cited prior art.” This is only Applicants’ opinion. Thus, it receives little weight as a complete argument (facts missing).
Claim interpretations
Claim 1 is directed to a system (i.e. product) with the following generic structure:
A sequencer; and
computer processer programmed to receive sequencing reads, quantify the sequencing reads corresponding to any alleles at any polymorphic loci, and measure the amount of DNA based on allele frequencies at a plurality of the polymorphic loci.
All other claims merely recite intended uses of the system; thus, they fail to distinguish the system over the prior art.
Claim Rejections - 35 USC § 102 - Maintained
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
(A) A person shall be entitled to a patent unless –
(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; or
(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.
Claims 1-20 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by DHALLAN (US 7,332,277).
As to claim 1, DHALLAN teaches a system comprising a sequencer (cols. 63-65, describing sequencing analysis using sequencer); and computer processer programmed to receive sequencing reads, quantify the sequencing reads corresponding to any alleles at any polymorphic loci, and measure the amount of DNA based on allele frequencies at a plurality of the polymorphic loci (GeneScan or ImageQuant programming; col. 65, l. 29 – col. 66, l. 20). Specifically, DHALLAN teaches
In one embodiment, the ratio of alleles at a heterozygous locus of interest can be calculated. The intensity of a nucleotide at the loci of interest can be quantified using any number of computer programs including but not limited to GeneScan and ImageQuant. For example, for a heterozygous SNP, there are two nucleotides, and each should be present in a 1:1 ratio. In a preferred embodiment, the ratio of multiple heterozygous SNPs can be calculated.
In one embodiment, the ratio for a variable nucleotide at alleles at a heterozygous locus of interest can be calculated. The intensity of each variable nucleotide present at the loci of interest can be quantified using any number of computer programs including but not limited to GeneScan and ImageQuant. For example, for a heterozygous SNP, there will be two nucleotides present, and each may be present in a 1:1 ratio. In a preferred embodiment, the ratio of multiple heterozygous SNPs can be calculated
(col. 65, ll. 30-47).
Claims 1-20 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by RAVA (US 2012/0010085).
As to claim 1, RAVA teaches a system comprising a sequencer (para. 0189); and computer processer programmed to receive sequencing reads, quantify the sequencing reads corresponding to any alleles at any polymorphic loci, and measure the amount of DNA based on allele frequencies at a plurality of the polymorphic loci (para. 0190). Specifically, RAVA teaches
c. Analysis of Sequencing Data for the Determination of Fetal Fraction
Upon completion of sequencing of the sample, the Illumina “Sequencer Control Software” transferred image and base call files to a Unix server running the Illumina “Genome Analyzer Pipeline” software version 1.51. the 36 bp reads were aligned to an artificial reference genome e.g. a SNP genome, using the BOWTIE program. The artificial reference genome was identified as the grouping of the polymorphic DNA sequences that encompass the alleles comprised in the polymorphic target sequences. For example, the artificial reference genome is a SNP genome comprising SEQ ID NOs: 1-56. Only reads that mapped uniquely to the artificial genome were used for the analysis of fetal fraction. Reads that matched perfectly to the SNP genome were counted as tags and filtered. Of the remaining reads, only reads having one or two mismatches were counted as tags and included in the analysis. Tags mapped to each of the polymorphic alleles were counted, and the fetal fraction was determined as a percent of the ratio of the number of tags mapped to the major allele i.e. maternal allele, and the number of tags mapped to the minor allele i.e. fetal allele.
(id.)
Response to Arguments
The rejections are maintained because the Examiner would love to know how a sequencer is programmed for particular amplicons, and what structural features of the sequencer this requires. In fact, a sequencer merely sequences whatever is placed on/in it, that the sequencer is capable of sequencing. For example, a nanopore sequencer can be set up to sequence single-stranded sequence of short or long lengths, regardless of the target sequence. The fact that a sequence may contain sequences from first and second individuals, or “polymorphic loci” (not actual polymorphisms, just loci that may have one), or even cell-free DNA, is irrelevant to the sequencer. Nor are the DNA molecules on/in the sequencer; much less any specific sizes, sequences, or other structural features of the DNA molecules required in the claims which would set them apart from the prior art. At best, the “computer processor” may be programmed to analyze the sequencer reads, but this is irrelevant to the sequencer. Here, the “computer processor” is merely “programmed to receive the sequencing reads, quantify the sequencing reads corresponding to each allele at the polymorphic loci, and measure the amount of DNA from the first individual in the biological sample of the second individual based on allele frequencies at a plurality of the polymorphic loci.” As previously explained, the prior art teaches this basic functioning of a processor.
Prior Art
The following prior art also teaches system with sequencer and programmed processor for allele frequency determination: US 2010/0273219; US 20080044831 (para. 0394); US 20170039318 (claim 1); US20090099789.
THIS ACTION IS MADE FINAL. 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 Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 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, Gary Benzion can be reached at (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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/AARON A PRIEST/Primary Examiner, Art Unit 1681
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