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 .
Response to Amendment
The Amendment filed 08/17/2026 in response to the Non-Final Office Action mailed 05/15/2026 has been entered.
Claims 21-40 are currently pending in U.S. Patent Application No. 18/808,889 and an Office action on the merits follows.
Drawings
Examiner acknowledges Applicant’s replacement drawing received on 08/17/2026, for Fig. 19 and removing those non-disclosed labels 1936A-D. The replacement drawing(s) is/are considered acceptable.
Terminal Disclaimer
The terminal disclaimer filed on 08/17/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US 12,106,828 and/or US 11,423,306 has been reviewed and is accepted. Rejections to the claims under Double Patenting, now rendered moot, are withdrawn.
Response to 35 USC § 101 Rejections
Applicant’s remarks (08/17/2026) as found on pages 15-18 of 23 and concerning rejections under 35 U.S.C. § 101 have been considered and determined persuasive. Applicant’s competing analysis seeks to exclude all limitations of the claim, steps/limitations (1)-(4), from being considered as ‘reciting’ an exception, and further draws at least (3) ‘adjust[ing]’ and (4) ‘determin[ing]’ as being analogous to step(s) (e) and (f) of the July 17, 2024 PEG Example 48 claim 3, for which steps (e) and (f) were ‘additional elements’ that served for integration (answering ‘directed to’) at Prong Two of Step 2A. From the recent PEG:
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To be clear, Applicant’s remarks in part assert that all (1)-(4) are ‘additional elements’ for reasons similar to those determining (f) as an ‘additional element’ at Prong One (which would circumvent a Prong Two analysis entirely). Examiner respectfully disagrees with that finding/analysis, and continues to assert that at least “generating, utilizing a progressive decay function, cycle-dependent coefficients” can fairly and should be drawn to a mathematical operation for Prong One analysis purposes. The previously supplied analysis (at Prong One of 2A) for that final (4) ‘determine’ is similarly reserved (see page 8 of the Non-Final Office Action, which previously assigned ‘3)’ to that ‘determine’ step now dubbed ‘(4)’ in Applicant’s accompanying remarks/analysis), in view of a reading wherein the final step may constitute a mentally performed classification/clustering step (if not also drawn under the mathematical operations grouping) (e.g. a visual/mental analysis of a plot such as Fig. 13B or 27C of Ballinger et al. (US 2021/0334957 A1) (cited by Applicant)). Applicant’s remarks regarding that (3) ‘adjust[ing]’ recited however do appear to warrant an analysis similar to that of Example 48 claim 3 step (e), even if determining an intensity of a tag (essentially a classification step) alone, does not actually produce anything comparable to (as recited) that transcript required by (f) of Example 48 claim 3. If (3) as recited can be identified as an ‘additional element’ for Prong Two purposes, Examiner is persuaded by Applicant’s accompanying remarks asserting it is that/ those recited limitation(s) that serve to realize the disclosed improvement (MPEP 2106.05(a)) given that half of the (2) ‘generat[ing]’ that is also an ‘additional element’ – i.e. “that account for signal decay as a function of distance between labeled nucleotide bases and the solid-state imaging device at different sequencing cycles of a sequencing run”. Stated differently, even if previously utilized coefficients could not and/or generally did not account for that as now required by the claim(s) (a novel calculation per se, would be ineligible), the manner in which they are then used (3-4) when considered as a combination in the aggregate, may serve to ensure the improvement is not to the exception itself. See Applicant’s remarks regarding the disclosed improvement, reproduced below.
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Examiner notes that one or more of the abovementioned limitations is/are being rejected under 35 U.S.C. 112, and if upon resolution of those related issues it is clear that one or more of the abovementioned limitations ((3) in particular (and the abovementioned portions of (2)) if that/those is/are the ‘additional element(s)’ that as recited realize(s) the disclosed improvement) constitute no more than ‘applying’ a broadly recited ML model (MPEP 2106.05(f) as distinguished from (a)), in a field-of-use (MPEP 2106.05(h)) relying upon biosensor 250 but only for a measured signal acquisition (necessary data collection 2106.05(g)) not meeting the requirements for improvements related to any particular machine as defined in 2106.05(b), rejection(s) under 35 U.S.C. § 101 may be appropriate. In view of the abovementioned considerations with reference to the identified/disclosed improvement and the preponderance of the evidence standard, corresponding rejections to the claim(s) under 35 U.S.C. § 101 are withdrawn.
Response to 35 USC §§ 102 and 103 Rejections
Applicant’s arguments identifying deficiencies in JIANG et al. (US 2020/0010888 A1) (US 2013/0316918 A1 featuring same/supporting disclosure alternatively applicable under 102(a)(1)) and/or Garcia et al. (US 2012/0020537 A1) in view of the amended language requiring the determined coefficients to “account for signal decay as a function of distance between labeled nucleotide bases and the solid-state imaging device at different sequencing cycles of a sequencing run”, have been considered and determined persuasive. More specifically, Examiner fails to recognize any inaccuracies associated with Applicant’s characterization of Jiang as identified at remarks page 21 paragraph 2, and Jiang as may otherwise be applied to the claims as amended. Jiang does not appear to disclose any ‘distance’ as a factor in ultimately deriving any scale factor for adjusting/correcting intensity values so as to arrive at more accurate color/base calls. Garcia features significant disclosure describing detected distances between features, distance measures in determining cluster radius ([0152-0157]), a distance consideration in that ‘Chastity Determination’ for neighboring spot detections ([0159], see also [0057] “(i) discarding the spot being analyzed if another spot has been previously assigned within a first radius; and (ii) discarding the spot being analyzed if another spot has been previously assigned within a second radius and the base calls for the spot meet a threshold chastity value”), and intensity decay broadly (appearing to correspond to e.g. Applicant’s 625), among others, as factors influencing transforms/matrices for adjusting/optimizing measured information, however Examiner cannot conclusively determine Garcia as applicable, and/or the recited claim(s) as distinguished over the teachings of Garcia, absent a better understanding of how the claim(s) as amended can/should be permissibly interpreted – see the corresponding issues raised under 35 U.S.C. 112 below. Corresponding rejections to the claims are withdrawn in the interim.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim(s) 21-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Independent claim(s) 21(system)/30(CRM)/37(method) as amended now require the cycle-dependent coefficients to ‘account for signal decay as a function of distance between labeled nucleotide bases and the solid-state imaging device at different sequencing cycles of a sequencing run’. Applicant’s remarks accompanying amendment fail to specify where in Applicant’s Specification support for the abovementioned limitation/new matter may be found, and consideration/review of Applicant’s Specification has failed to locate such support and/or affirmatively resolve matters related to whether potentially supporting disclosure is sufficient for meeting written description requirement (see e.g. MPEP 2163 sub-section (B) New or Amended Claims). The term ‘distance’ does not appear ipsis verbis in Applicant’s Specification (see pgpub US 2025/0095785 A1), and while this fact alone does not necessarily prove a lack of supporting disclosure (see Non-Final at page 5, neither is “cycle-dependent” disclosed ipsis verbis), it fails to assist in Examiner’s attempts to identify where supporting disclosure does exist, as required for resolving matters of sufficiency. Furthermore, the recited language gives rise to questions regarding how the recited distance is/can vary, and how such a variation is/can be determined, because all fluorescently-labeled/tagged molecules/ bases are understood to sit uniformly bound to the surface of the sample area, and as such their Z-axis distance to/from the solid-state imaging device appears functionally static and substantially identical. Applicant’s disclosure identifies Coefficient Determiner 1722 as being the means by which four different types of coefficients are determined – to include “coefficients for the decay function” as presently recited. Pgpub at [0194] appears to disclose that one or more of these coefficients may be determined “by applying gradient descent to the signal presence ground truth for the pixel and the measured intensities for the sequence of the sampling events for the pixel”, suggesting that any of the disclosed coefficients may be determined by some ML model trained in a supervised fashion, and on the basis of an input measured intensity. Prosecution history(ies) has/have previously suggested the manner in which the term “pixel” is not understood to be in the image domain, but instead a physical component/area of the device (biosensor 250) itself (e.g. pixel area 206’ of sensor 206), but even and particularly in view of this consideration, it is not clear how any predetermined or otherwise inferred ‘distance between labeled nucleotide bases and the solid-state imaging device’ is/can be used to determine decay function and/or decay function determined coefficients. Nor is it clear what those distances are typically, and/or what then are the resultant/corresponding coefficients as recited. Applicant’s Fig. 2 regarding biosensor 250 is reproduced below, to further illustrate how all fluorescently-labeled nucleotide bases are understood to sit uniformly bound to the surface of the sample area with non-varying Z-axis distances from respective sensors 206, 208, 210, etc..
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Does Applicant intend for ‘labeled nucleotide bases’ to refer to labels of training samples for a supervised training (i.e. labeled images), distinct from any fluorescently-labeled (pgpub [0022], [0052]) molecule/nucleotide existing in the/a sample well? If so, what is the recited distance, and how can it be between some aspect/feature of a training sample and the sensor itself? Does the recited distance differ for overhead vs. substrate sensor embodiments? Pgpub at [0080] discloses “d” as an estimated decay vector, [0076] features an equation modeling its approximated contribution to a measured intensity, and [0125] discloses generally that intensity decay can be corrected on a ‘position-dependent basis’, but none of these sufficiently resolve what the recited distance(s) is/are with respect to the recited solid-state imaging device.
Absent readily identifiable and requisite support in Applicant’s disclosure, even a plain meaning interpretation of the language in question does not appear supported, as a matter distinct from those identified below regarding clarity/definiteness. MPEP 608.04(a) prescribes considering the limitation in question, for the purposes of Examination (e.g. any prior-art based rejection(s)), under an assumption that Applicant will be able to identify the necessary support (without modification to the language recited) as it exists in Applicant’s disclosure. Such an examination however is effectively precluded for the instance that the scope of the limitation in question cannot also be resolved – see the accompanying 112(b) rejection(s) below.
Claim Rejections - 35 USC § 112
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.
Claims 21-40 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 21-40 as amended (independent claims 21(system)/30(CRM)/37(method), as well as corresponding dependent claims 23-29, 31-36, 38-39) require the generation of cycle-dependent coefficients that ‘account for signal decay as a function of distance between labeled nucleotide bases and the solid-state imaging device at different sequencing cycles of a sequencing run’, for which POSITA would not readily recognize
1) how (outside of ‘using’/‘utilizing’ an undefined function) such coefficients may be generated/determined;
2) what coefficients are/would be sufficient for (and similarly insufficient for) such an accounting as recited given the breadth/genus embodiment(s) of the recited solid-state imaging device (‘overhead’ sensor embodiments vs. ‘substrate sensor’); and
3) what the distance as recited is (given no explicitly disclosed ‘distance’) and/or how it may be determined/known given no recited details regarding the solid-state imaging device/biosensor 250 upon which the distance in question is based.
As identified in the 112(a) written description rejection above, supporting disclosure that might resolve these issues has not been identified, and with reference to Applicant’s Fig. 2 illustrating solid-state imaging device/biosensor 250, all fluorescently-labeled/tagged molecules/ bases are understood to sit uniformly bound to the surface of respective sample areas, and as such their Z-axis distances to/from the solid-state imaging device appears functionally static and substantially identical. If Applicant does not intend for the distance in question to be that Z-axis distance between e.g. 206A (fluorescently-labeled/tagged strands) and sensor 206 for example, then it is unclear which sub-component of device 250 is referenced/involved – in any measure of distance between that and a ‘labeled nucleotide base’. Applicant’s disclosure associated with Coefficient Determiner/means 1722 additionally gives rise to questions regarding whether or not Applicant intends for ‘labeled’ nucleotide bases to not refer to a fluorescently-labeled/tagged base/molecule, but instead a ‘label’ of training samples for a supervised training (e.g. labeled images for a machine learning model that receives images as input), and what the recited distance is then accordingly (if the labels exist in image space/domain, since the sensor itself does not, even if some distance may be determined from an associated image (if Applicant asserts the distance in question is also measurable from/reflected in an image)).
MPEP 2173.02 reinforces an understanding that while “absolute precision is unattainable”, the threshold requirements for clarity and precision involve an inquiry of those factors (A)-(C) as identified in § 2173.02 sub-section II – explicitly including any confounding elements in the Specification/figures – like those identified/referenced above. The claims as amended fail to serve their notice function as required by the statute, given at least the manner in which it is unclear what the coefficients must account for in view of that ambiguously recited distance, and a lack of (identified/identifiable) supporting disclosure. The definiteness requirement "mandates clarity" Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910, 110 USPQ2d 1688, 1693 (2014). MPEP § 2173.02 (emphasis added):
If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, is appropriate. See IBSA Institut Biochimique, S.A. v. Teva Pharm. USA, Inc., 966 F.3d 1374, 1378-81, 2020 USPQ2d 10865 (Fed. Cir. 2020) (The court affirmed a district court’s finding of indefiniteness based upon a detailed analysis of the claim language itself as well as intrinsic and extrinsic evidence);
See also MPEP 2173.02 sub-section I, identifying how claims under examination are construed differently and with a potentially lower threshold for ambiguity.
During prosecution the Office construes claims by giving them their broadest reasonable interpretation consistent with the specification in an effort to establish a clear record of what the applicant intends to claim. Such claim construction during prosecution may effectively result in a lower threshold for ambiguity than a court's determination. Packard, 751 F.3d at 1323-24, 110 USPQ2d at 1796-97 (Plager, J., concurring). However, applicant has the ability to amend the claims during prosecution to ensure that the meaning of the language is clear and definite prior to issuance or provide a persuasive explanation (with evidence as necessary) that a person of ordinary skill in the art would not consider the claim language unclear. In re Buszard, 504 F.3d 1364, 1366, 84 USPQ2d 1749, 1750 (Fed. Cir. 2007)
Examiner additionally notes no corresponding prior-art based rejection(s) to the instant claim(s) are supplied below in view of the abovementioned ambiguities, and that a more complete search and consideration will likely be warranted upon correction/clarification. With reference to MPEP § 2143.03 an examiner should not simply speculate about the meaning of the claim language and then enter an obviousness rejection in view of that speculative interpretation. See also MPEP § 2173.06 describing where there is a great deal of confusion and uncertainty as to the proper interpretation of the limitations of a claim, it would not be proper to reject such a claim on the basis of prior art. In re Steele, 305 F.2d 859,134 USPQ 292 (CCPA 1962).
Conclusion
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.
Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IAN L LEMIEUX whose telephone number is (571)270-5796. The examiner can normally be reached Mon - Fri 9:00 - 6:00 EST.
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/IAN L LEMIEUX/Primary Examiner, Art Unit 2669
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