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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/13/2026 has been entered.
The claims dated 2/13/2026 are under consideration.
The amendments and arguments presented in the papers filed 2/13/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/16/2025 listed below have been reconsidered as indicated.
a) The rejections of claim(s) 1-21 under 35 U.S.C. 103 as being unpatentable over Sparks (US 2012/0034685 A1) and Stoughton (US 2008/0070792 A1) are withdrawn in view of the amendments to the claims.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below.
Drawings
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 3, 4, 5, 7, 8, 9, 16, 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US 2009/0117552) in view of Mir (US 2004/0248144 A1).
The following are new rejections necessitated by the amendments to the claims.
Regarding claims 1, 2, 3, 7, 16, 17 and 18, Wu teaches a method for detection and quantification of target nucleic acids in a sample. See entire document.
Relevant to step (a), Wu teaches “contacting a first and second probe set to a genetic sample” by hybridizing two sets of probes, one for detection of a normal allele and another one for a mutant allele (para. 160-162).
The first and second probe sets each include:
a “tagging probe” in the form of a first probe composed of a 5' end sequence part for hybridisation to a PCR primer as a “second primer binding site” and a 3' end sequence part for hybridisation to the target nucleic acid as a “nucleic acid region of interest” (para. 160); and
a “labeling probe” in the form of a second probe composed of a 5' end sequence part for hybridisation to the target nucleic acid “nucleic acid region of interest”, and a 3' end sequence part for hybridisation with a PCR primer as a “first” or “third” “primer binding site” depending on the set, which is a portion that does not hybridize with the target (para. 160).
Either probe may include an “affinity tag” in the form of an intermediate sequence complementary to the detector oligonucleotide on the array is present in between 5' and 3' end sequence parts (para. 45-46 and 160). The “tagging probe” and “labeling probe” of Wu hybridize adjacent to one another (Fig. 1 and 2; Abstract; and paras. 12, 23 and 43).
Relevant to step (b), Wu teaches ligating the hybridized probe sets (Fig. 1 and 2; and para. 162).
Relevant to step (c), Wu teaches amplifying the “first and second ligated probe sets” by amplifying the ligation-mediated probe such that the PCR products were labelled using a forward primer with Cy5 modification (para. 162; and Fig. 2). The primers hybridize with the 5' end sequence part for hybridisation to a PCR primer of the first probe and 3' end sequence part for hybridisation with a PCR primer of the second probe.
Relevant to step (d), Wu teaches immobilizing the ligation-mediated probe via the intermediate sequence by hybridizing it to the detector oligonucleotide on an array substrate (para. 164). The detector oligonucleotides are arranged within spots or predefined regions as demonstrated in Figs. 3 and 4.
Relevant to step (e), Wu teaches determining the amounts of different targets by detecting signals from the label (para. 91 and 164-167).
Relevant to step (f), Wu teaches comparing signals to determine a genetic variation in the sample (para. para. 91 and 164-167).
Wu does not specifically teach the “first and second labels are different” or determining “a first count” and “a second count” of individual molecules immobilized ligation-mediated probes by “counting individual molecules” of the “first labels” and “second labels”.
However, Mir teaches arrays for spatially addressable low density molecular arrays in single molecule detection.
Regarding claim 1, Mir teaches the concept of using different signals from different labels to differentiate between SNPs (para. 76, 83 and 108) and labeled primers (para. 385).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have modified the labeling primers of Wu such that they had different sequences and labels so that different targets, e.g., different alleles, may be differentiated based on signal as described by Mir.
Mir further teaches an array for capturing and detecting single molecules (para. 42, 55), 65), which enables accurate quantitation of expression levels by single molecule counting (para. 99) and the single molecule approach enables direct counting and classification of individual events (para. 246).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have modified the method of Wu by incorporating the array and single molecule counting of Mir to detect the different target nucleic acids. One would have been motivated to do so because it enables accurate quantitation of expression levels by single molecule counting and direct counting and classification of individual events as described by Mir.
Regarding claim 4, Mir further teaches determining haplotype information for each chromosome (para. 24 and 745), meaning that “nucleic acid regions of interest” are on different chromosomes.
Regarding claim 5, Wu teaches genetic variation in copy numbers of targets (para. 4C and 4D).
Regarding claim 8, Wu teaches the target nucleic acids have variations, such as point mutations, deletions, insertions or inversions (para. 6, 91 and 109).
Regarding claim 9, Wu teaches the sample is free cellular DNA (para. 77 and 78).
Claim(s) 6, 10, 11, 12, 13, 14, 15 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US 2009/0117552) in view of Mir (US 2004/0248144 A1) as applied to claim 1 above and in further view of Sparks (US 2012/0034685 A1; previously cited).
Regarding claims 6, 10, 11, 12, 13, 14, 15 and 21, the combination of Wu and Mir renders obvious the elements of claim 1 as required by claim 6 as described above.
The combination does not teach the additional elements specific to dependent claims 6, 10, 11, 12, 13, 14, 15 and 21.
Sparks teaches assay systems and methods for detection of copy number variation at one or more loci and polymorphism detection at one or more loci in a mixed sample from an individual (Abstract). The assay of Sparks is analogous to that of Wu.
Regarding claim 6, Sparks teaches an aneuploidy as a genetic variation (paras. 29, 39, 44, 45 and 46).
Regarding claim 10, Sparks teaches the subject is a pregnant female (para. 96).
Regarding claim 11, Sparks teaches the genetic sample is a mixture of fetal and maternal DNA (para. 96).
Regarding claim 12, Sparks teaches determining the presence or absence of a genetic variation in a fetus based on the comparison of data (para. 159 and 160).
Regarding claim 13, Sparks teaches determining the fetal fraction within a maternal sample having mixed sources of DNA (para. 171, 213 and 214).
Regarding claim 14, Sparks teaches the sample includes DNA from cancer cells and is used to detect the presence of cancer (para. 209-210).
Regarding claim 15, Sparks teaches the sample includes DNA from a transplanted organ and determining the amount of DNA from the transplantation (para. 212).
Regarding claim 21, Spark teaches that probe sets hybridize to different alleles found at a single genetic loci (Fig. 3).
It would have been prima facie obvious to the ordinary at the time of invention to have modified the method suggested by Wu and Mir by incorporating the various samples of Sparks in place of the samples of Wu. One would have been motivated to do so because the samples of Sparks are of interest in different clinical contexts. The modification has a reasonable expectation of success as it simply substitutes on known sample for another known sample. One would have been motivated to use the particular probe set design of Sparks for the probe sets of Wu because it is a well characterized design for genotyping SNPs, which is of interest Wu. The modification has a reasonable expectation of success as the probe design of Sparks and Wu are obvious variants of one another that are both used for the same purpose, i.e., genotyping a sample.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US 2009/0117552) in view of Mir (US 2004/0248144 A1) as applied to claim 1 above and in further view of Stoughton (US 2008/0070792 A1; previously cited).
Regarding claim 19, the combination of Wu and Mir renders obvious the elements of claim 1 as required by claim 19 as described above.
The combination does not teach the additional elements specific to dependent claim 19.
However, Stoughton teaches conducting genetic analysis, such as SNP genotyping to provide diagnostic results (Abstract). The assay of Stoughton is analogous to that of Wu.
Regarding claim 19, Stoughton teaches the tagging probe is the same between the sets (Fig. 5; and para. 92-94 and 182).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have utilized the probe design of Stoughton in the probe sets of Wu. One would have been motivated to do so because it is a well-characterized design for genotyping SNPs, which is of interest Wu. The modification has a reasonable expectation of success as the probe design of Stoughton and Wu are obvious variants of one another that are both used for the same purpose, i.e., genotyping a sample.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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