FINAL ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Amendments and Status of the Claims
2. This action is in response to papers filed 1 April 2026 in which specification and claims 1, 8, 17, 20-21 were amended, claims 7, 18-19, and 22 were canceled, and new claims 23-24 were added. All of the amendments have been thoroughly reviewed and entered.
Any objections and any previous rejections not reiterated below are withdrawn in view of the amendments.
Applicant’s arguments have been thoroughly reviewed and are addressed following the rejections necessitated by the amendments.
3. Claims 1-6, 8-17, 20-21, and 23-24 are under prosecution.
4. This Office Action includes new rejections necessitated by the amendments.
Information Disclosure Statement
5. The Information Disclosure Statement filed 23 June 2026 is acknowledged and has been considered
Claim Rejections - 35 USC § 101
6. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
7. Claims 1-6, 8-17, 20-21, and 23-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. While the claims recite methods, the limitations are limited to providing a dataset and classifying based on additional mental steps, i.e., comprising to a threshold value. Thus, the claims are drawn to a judicial exception, in the form of an abstract idea, and are not integrated into a practical application because there are no further steps that utilize the data. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because, as noted above, the data is merely classified based on comparison to threshold values.
Determining whether the claimed subject matter is drawn to a judicial exception utilizes a two-prong procedure. The first prong determines whether the claimed subject matter is directed to a law of nature, a natural phenomenon, or an abstract idea. If the claimed subject matter recites an abstract idea, it is then determined whether the claimed subject matter is instead directed to an improvement to a technology. If the claimed subject matter recites a law of nature, it is then determined whether the claimed subject matter is instead directed to a patent-eligible application of the law of nature. If a claim is not directed to a natural phenomenon that is a nature-based product, then it is determined if the product limitation is markedly different from what occurs in nature.
The instant claims are drawn to a judicial exception of performing an abstract idea that can be performed as a series of mental steps; i.e., classifying a series of signals (intensity transition events or median dwell times) and comparing to threshold or maximum value (i.e., claims 1 and 20), with the remaining claims merely being drawn to either data gathering steps (e.g., claims 2-6, 8-9, and 12), additional data analysis (i.e., claims 10-11, 16-17, 21, and 23-24) or establishing parameters for the analysis (i.e., claims 13-15), each of which is similar to the abstract idea of comparing information of a sample or test subject to a control or target data at issue in Univ. of Utah Research Found. v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ 2d 1241 (Fed, Cir. 2014)) and the abstract idea of collecting information and analyzing it in Electric Power Group. LLC. v. Alstom (830 F3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016).
In the second prong it is determined whether the claimed subject matter includes significantly more than a judicial exception by integrating the judicial exception into a practical application; e.g., by further comprising an additional element or a combination of additional elements that are not routine or conventional.
In the instant case, the remaining method steps are drawn to routine and conventional “wet” steps; i.e., immobilizing a target to a solid support via a capture probe, and binding a detectably labeled query probe that repeatedly and transiently binds to the immobilized target (i.e., equilibrium binding and kinetic measurements).
Becker et al. (U.S. Patent Application Publication No. US 2008/0090246 A1, published 17 April 2008) discuss capture of nucleic acids analytes on solid supports and detection under equilibrium/kinetic conditions using labeled probes (paragraphs 0106, 0084, 0008, and 0011).
Blair et al. (U.S. Patent Application Publication No. US 2009/0042735 A1, published 12 February 2009) discuss capture of nucleic acids analytes on solid supports and detection under equilibrium/kinetic conditions using labeled probes (paragraphs 0104 and 0096).
Yershov et al. (U.S. Patent Application Publication No. US 2008/0076677 A1, published 27 March 2008) discuss capture of nucleic acids analytes on solid supports and detection under equilibrium/kinetic conditions using labeled probes (paragraphs 0019-0020).
Levicky et al. (TRENDS in Biotech., vol. 23, pages 143-149, published online 26 January 2005) discuss capture of nucleic acids analytes on solid supports and detection under equilibrium/kinetic conditions using labeled probes (Abstract and whole document).
Thus, the “wet” steps of the instantly claimed methods are routine can conventional (see also Becker, U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002, as discussed in the rejections below).
As discussed in MPEP 2106.04(II)(A)(2), “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.”
In the instant case, the claims recite no additional elements other than the data gathering and analysis, and therefore do not amount to significantly more than the judicial exception there are no other limitations beyond the judicial exception.
While not specifically claimed as computer-implemented methods. the claimed subject matter also encompasses abstract ideas that could be computer mediated. Even generously interpreting the claims as somehow performing the abstract ideas on a generic computer would not an additional element that is significantly more than the abstract idea itself. In Alice Corp. Pty. Ltd. v. CLS Bank Int'l (573 U.S. 134 S.Ct. 2347, 110 USPQ2d 1976 (2014)) the Supreme Court reviewed the prior Benson, Flook, and Diehr decisions regarding claims directed to an abstract idea that include a step of using computers:
These cases demonstrate that the mere recitation of a generic computer cannot transform a patent-ineligible abstract idea into a patent-eligible invention. Stating an abstract idea “while adding the words ‘apply it’” is not enough for patent eligibility. Mayo, supra, at ___ (slip op., at 3). Nor is limiting the use of an abstract idea “‘to a particular technological environment.’” Bilski, supra, at 610–611. Stating an abstract idea while adding the words “apply it with a computer” simply combines those two steps, with the same deficient result. Thus, if a patent’s recitation of a computer amounts to a mere instruction to “implemen[t]” an abstract idea “on…a computer,” Mayo, supra, at ___ (slip op., at 16), that addition cannot impart patent eligibility. This conclusion accords with the pre-emption concern that undergirds our §101 jurisprudence. Given the ubiquity of computers, see 717 F. 3d, at 1286 (Lourie, J., concurring), wholly generic computer implementation is not generally the sort of “additional featur[e]” that provides any “practical assurance that the process is more than a drafting effort designed to monopolize the [abstract idea] itself.” Mayo, 566 U. S., at ___ (slip op., at 8–9).
Again, while only encompassing (but not claiming) a computer mediated method, it is noted that the court further stated:
Petitioner’s claims to a computer system and a computer-readable medium fail for substantially the same reasons. Petitioner conceded below that its media claims rise or fall with its method claims. En Banc Response Brief for Defendant-Appellant in No. 11–1301 (CA Fed.) p. 50, n. 3. As to its system claims, petitioner emphasizes that those claims recite “specific hardware” configured to perform “specific computerized functions.” Brief for Petitioner 53.But what petitioner characterizes as specific hardware-a “data processing system” with a “communications controller” and “data storage unit,” for example, see App. 954,958, 1257-is purely functional and generic. Nearly every computer will include a “communications controller” and “data storage unit” capable of performing the basic calculation, storage, and transmission functions required by the method claims. See 717 F. 3d, at 1290 (Lourie, J., concurring). As a result, none of the hardware recited by the system claims “offers a meaningful limitation beyond generally linking ‘the use of the [method] to a particular technological environment,’ that is, implementation via computers.” Id., at 1291 (quoting Bilski, 561 U. S., at 610–611). Put another way, the system claims are no different from the method claims in substance. The method claims recite the abstract idea implemented on a generic computer; the system claims recite a handful of generic computer components configured to implement the same idea. This Court has long “warn[ed] . . . against” interpreting §101 “in ways that make patent eligibility ‘depend simply on the draftsman’s art.’” Mayo, supra, at ___ (slip op., at 3) (quoting Flook, 437 U. S., at 593); see id., at 590 (“The concept of patentable subject matter under §101 is not ‘like a nose of wax which may be turned and twisted in any direction . . . ’”). Holding that the system claims are patent eligible would have exactly that result.
Because petitioner’s system and media claims added nothing of substance to the underlying abstract idea, that were found patent ineligible under §101.
The subject matter of the instant claims is, at best, broadly interpreted as encompassing a computer-mediated process directed to a judicial exception and, interpreted strictly as claimed, encompasses only an abstract idea combined with data gathering. There are no additional limitations in the claims providing significantly more that the judicial exception; e.g., any tangible use of the data or the use of any tangible machine or processor resulting in significant improvement to any technology..
The subject matter of the instant claims is therefore solely limited to a judicial exception and the claims are patent-ineligible.
Claim Rejections - 35 USC § 103
8. 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.
9. 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.
10. Claims 1-6 and 8-17 are rejected under 35 U.S.C. 103 as obvious over Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012).
Regarding claim 1, Becker teaches methods comprising immobilizing a target analyte to a solid support via a capture probe, which is then contacted with a detectably labeled query probe (paragraphs 0012-0013). Becker further teaches the method study association rates of polynucleotides (Title) by obtaining signals (paragraph 0040), wherein the signals are measured in an 8 minute time interval, as well as measuring disassociation constants (k2, paragraph 0114) and association constants (i.e., k1; paragraph 0114); thus, there is a repeated transient association because the binding involves both association and dissociation. Becker also teaches producing a dataset (i.e., data points) based in the kinetic data (paragraph 0155), and that the methods have the added advantage of being applicable to DNA:DNA, RNA:DNA, and RNA:RNA reactions systems (paragraph 0009). Thus, Becker teaches the known techniques discussed above.
Becker does not teach time-resolved intensity measurements.
However, Watkins et al. describe methods comprising providing a data set describing time resolved intensity measurements (Title and Figure 1), counting the number of events (i.e., photons; Figure 2), wherein the transitions are classified into groups (Section 2.3), numbering the intensity states (Section 2.3) and thresholding (Introduction). Watkins et al. further teach studying molecules one at a time (Section 1), the methods have the added advantage of dramatically increased amounts of extracted information (page 627, first paragraph). Thus, Watkins et al. teach the known techniques discussed above.
It is noted that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments (see MPEP § 2123). Thus, the teaching of Watkins et al. that the thresholding has limitations (Abstract) encompasses embodiments utilizing thresholding.
In addition, Zhong et al. teach methods of obtaining time-resolved signals (paragraph 0138), including from a plurality of discrete sources of signals (paragraph 0104), which are examined individually (paragraph 0130). Zhong et al. further teach counting the events (i.e., colleting 1000 data points; paragraph 0205; see also counting photons, paragraph 0083). Zhong et al. also teach detection of labels based on upon their retention (i.e., dwell) time (paragraph 0099), median (i.e., average) signals above baselines (paragraph 0190), and classifying signals based on thresholds (paragraphs 0067-0068). Zhong et al. further teach averaging over a period of time to obtain a high signal to noise ratio (paragraph 0127). Thus, if would have been obvious to determine the number of signals exceed a threshold and that a dwell time exceeds a mean (i.e., average) threshold. Zhong et al. also teach the methods have the added advantage of allowing determination of the significance of the signal (paragraphs 0067-0068). Thus, Zhong et al. teach the known techniques discussed above.
It is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, any order of steps is an obvious variant of the steps of the cited prior art.
MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, counsel’s mere arguments cannot take the place of evidence in the record.
It is noted that the Response above should not be construed as an invitation to file an after final declaration. See MPEP 715.09.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Becker, Watkins et al. and Zhong et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantages of:
A. Being applicable to DNA:DNA, RNA:DNA, and RNA:RNA reactions systems as explicitly taught by Becker (paragraph 0009);
B. Producing dramatically increased amounts of extracted information as explicitly taught by Watkins et al. (page 627, first paragraph); and
C. Allowing determination of the significance of a signal as explicitly taught by Zhong et al. (paragraphs 0067-0068).
In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in assays useful for detecting hybridization reactions.
Regarding claim 2, the method of claim 1 is discussed above. Watkins et al. teach consecutive events (e.g., states; Section 2.3.2).
Regarding claims 3-4, the method of claim 1 is discussed above. Watkins et al. teach the use of Poisson statistics (“Concluding Remarks”), as do Zhong et al. (paragraph 0139), which is a continuous-time stochastic process as defined by page 26 of the instant specification (i.e., claim 3).
Regarding claim 5, the method of claim 1 is discussed above. Watkins et al. teach defined time intervals (e.g., Figure 1), as do Zhong et al. (paragraph 0159).
Regarding claims 6 and 8, the method of claim 1 is discussed above. Becker teaches the signals are measured in an 8 minute time interval (i.e., claim 6), disassociation constants (k2, paragraph 0114) of .000833 per second (i.e., claim 8; paragraph 0115).
It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
It is also noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
Regarding claims 9-10, the method of claim 1 is discussed above. Watkins et al. the use of hidden Markov models for analyzing data (“Introduction”).
Regarding claims 9 and 11-13, the method of claim 9 is discussed above. Zhong et al. teach analyzing the data comprises identifying signals based on an exceeded threshold value (i.e., claims 9 and 11; paragraph 0072), including a background value (i.e., claim 12; paragraph 0069) and the use of 1.25 standard deviations (i.e., claim 13; paragraph 0150).
Regarding claim 14, the method of claim 1 is discussed above.
It is reiterated that the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Thus, the claimed number merely represents routine optimization of the number of transition events.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
Regarding claim 15, the method of claim 1 is discussed above. Becker further teaches negative controls, in the form of no polymer control sets (paragraph 0148).
Regarding claim 16, the method of claim 1 is discussed above. Zhong et al. teach calculating the amount of time (i.e., the signal duration) above a threshold (paragraph 002); by calculating the signal duration, the dwell time is known.
Regarding claim 17, the method of claim 1 is discussed above. Zhong et al. teach identifying the results; i.e., determining if a base calling signal is accurate; paragraph 0092).
11. Claims 3 and 14 are rejected under 35 U.S.C. 103 as obvious over Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, and further in view of Lakin et al. (J. R. Soc. Interface, vol. 9, pages 1470-1485, published online 4 January 2012).
It is noted that while claim 14 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claims 3 and 14, the method of claim 1 is discussed above in Section 10.
Watkins et al. teach the two states have a different signal intensity (i.e., jumps; Abstract), as do Zhong et al. (paragraph 0208).
None of the previously cited prior art teaches continuous stochastic transitions (i.e., claim 3).
However Lakin et al. teach measuring DNA transitions (e.g., using fluorophores, Section 2.1), wherein continuous stochastic logic is applied to nearing transitions, which has the added advantage of being part of the appropriate model for reactions at a molecule level (i.e., claim 3; Section 2.3). Lakin et al. also teach threshold levels of 10 (i.e., claim 14), which has the added advantage of a high probability of consensus (Section 3.4). Thus, Lakin et al. teach the known techniques discussed above.
It is reiterated that the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Thus, the claimed number merely represents routine optimization of the threshold number.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Lakin et al. with the previously cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of being part of the appropriate model for reactions ad a molecule level and a high probability of consensus as explicitly taught by Lakin et al. (Section 2.3 and Section 3.4, respectively). In addition, it would have been obvious to the ordinary artisan that the known techniques of Lakin et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Lakin et al. predictably result in confirmation of significant signals.
12. Claim 15 is rejected under 35 U.S.C. 103 as obvious over Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, and further in view of Singer et al. (U.S. Patent No. 5,866,331, issued 2 February 1999).
It is noted that while claim 15 has been rejected as described above, the claim is also obvious using the interpretation outlined below.
Regarding claim 15, the method of claim 1 is discussed above in Section 10.
While Zhong et al. teach hybridization reactions (paragraph 0102), none of the previously cited prior art teaches the standard deviations related to negative controls.
However, Singer et al. teach hybridization protocols where the threshold is determined using calculating the threshold based on the mean and standard deviation using a negative control (column 2, lines 40-55), which has the added advantage of allowing accurate determination of total emission intensity (Abstract). Thus, Singer et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Singer et al. with the previously cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantage of allowing accurate determination of total emission intensity as explicitly taught by Singer et al. (column 2, lines 40-55). In addition, it would have been obvious to the ordinary artisan that the known techniques of Singer et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Singer et al. predictably result in improved accuracy of signal intensity.
13. Claims 20-21 and 23 are rejected under 35 U.S.C. 103 as obvious over Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012), and Zudaire Ubani et al. (U.S. Patent Application Publication No. US 2005/053950 A1, published 10 March 2005).
Regarding claims 20 and 23, Becker teaches methods comprising immobilizing a target analyte to a solid support via a capture probe, which is then contacted with a detectably labeled query probe (paragraphs 0012-0013). Becker further teaches the method study association rates of polynucleotides (Title) by obtaining signals (paragraph 0040), wherein the signals are measured in an 8 minute time interval, as well as measuring disassociation constants (k2, paragraph 0114) and association constants (i.e., k1; paragraph 0114); thus, there is a repeated transient association because the binding involves both association and dissociation. Becker also teaches producing a dataset (i.e., data points) based in the kinetic data (paragraph 0155), and that the methods have the added advantage of being applicable to DNA:DNA, RNA:DNA, and RNA:RNA reactions systems (paragraph 0009). Thus, Becker teaches the known techniques discussed above.
Becker does not teach time-resolved intensity measurements.
However, Watkins et al. describe methods comprising providing a data set describing time resolved intensity measurements (Title and Figure 1), counting the number of events (i.e., photons; Figure 2), wherein the transitions are classified into groups (Section 2.3), numbering the intensity states (Section 2.3) and thresholding (Introduction). Watkins et al. further teach studying molecules one at a time (Section 1), the methods have the added advantage of dramatically increased amounts of extracted information (page 627, first paragraph). Thus, Watkins et al. teach the known techniques discussed above.
It is reiterated that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Thus, the teaching of Watkins et al. that the thresholding has limitations (Abstract) encompasses embodiments utilizing thresholding.
In addition, Zhong et al. teach methods of obtaining time-resolved signals (paragraph 0138), including from a plurality of discrete sources of signals (paragraph 0104), which are examined individually (paragraph 0130). Zhong et al. further teach counting the events (i.e., colleting 1000 data points; paragraph 0205; see also counting photons, paragraph 0083). Zhong et al. also teach detection of labels based on upon their retention (i.e., dwell) time (paragraph 0099), median (i.e., average) signals above baselines (paragraph 0190), and classifying signals based on thresholds (paragraphs 0067-0068). Zhong et al. further teach averaging over a period of time to obtain a high signal to noise ratio (paragraph 0127). Thus, if would have been obvious to determine the number of signals exceed a threshold and that a dwell time exceeds a mean (i.e., average) threshold. Zhong et al. also teach the methods have the added advantage of allowing determination of the significance of the signal (paragraphs 0067-0068). Thus, Zhong et al. teach the known techniques discussed above.
It is reiterated that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Thus, any order of steps is an obvious variant of the steps of the cited prior art.
Applicant is again cautioned to avoid merely relying upon counsel’s arguments in place of evidence in the record, and that the Response above should not be construed as an invitation to file an after final declaration.
Becker discusses using graphs and target (i.e., polynucleotide) concentrations (e.g., paragraph 0113). Watkins et al. describe counting the number of events (i.e., photons; Figure 2), as do Zhong et al. (i.e., colleting 1000 data points; paragraph 0205; see also counting photons, paragraph 0083).
None of the previously cited references teach counting (i.e., quantitating) analytes (i.e., claim 20) or standard curves (i.e., claim 23).
However, Zudaire Ubani et al. teach methods wherein the amount (i.e., abundance) of target immobilized (i.e., on an array) oligonucleotides are determined (paragraph 0110), and wherein standard curves are used to count (i.e., quantitate) the number of nucleic acids, which has the added advantage of allowing determination of an unknown amount of nucleic acid (paragraph 0089). Thus, Zudaire Ubani et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Becker, Watkins et al. and Zhong et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in methods having the added advantages of:
A. Being applicable to DNA:DNA, RNA:DNA, and RNA:RNA reactions systems as explicitly taught by Becker (paragraph 0009);
B. Producing dramatically increased amounts of extracted information as explicitly taught by Watkins et al. (page 627, first paragraph);
C. Allowing determination of the significance of a signal as explicitly taught by Zhong et al. (paragraphs 0067-0068); and
D. allowing determination of an unknown amount of nucleic acid as explicitly taught by Zudaire Ubani et al. (paragraph 0089).
In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in assays useful for detecting hybridization reactions.
Regarding claim 21, the method of claim 20 is discussed above. Zhong et al. teach identifying the results; i.e., determining if a base calling signal is accurate; paragraph 0092).
14. Claim 24 is rejected under 35 U.S.C. 103 as obvious over Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, alternatively further in view of Rao et al. (U.S. Patent Application Publication No. US 2008/0200342 A1, published 21 August 2008).
Regarding claim 24, the method of claim 1 is discussed above in Section 10.
Zhong et al. also teach the use of correlation coefficients (paragraph 0199).
While Zhong et al. do not teach the value thereof, it is reiterated that the courts have found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Thus, the claimed number merely represents routine optimization of the desired value of the correlation coefficient.
Alternatively, Rao et al. teach methods or processing data from immobilized capture molecules (i.e., arrays; paragraph 0082), comprising the use of correlation coefficients with signal intensity and time intervals, wherein the correlation coefficient has a value of greater than 0.98 (paragraph 0256). Thus, Rao et al. each the known techniques discussed above.
It would therefore have alternatively been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Rao et al. with the previously cited prior art to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method utilizing a strong value of the correlation coefficient as explicitly taught by Rao et al. (paragraph 0256 In addition, it would have been obvious to the ordinary artisan that the known techniques of Rao et al. could have been combined with the previously cited prior art with predictable results because the known techniques of Rao et al. predictably result in a useful benchmark value of the correlation coefficient.
Double Patenting
15. 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.
16. Claims 1-6 and 8-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,093,967 B2 in view of Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004) and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012).
Both sets of claims are drawn to analyzing time resolved data, Poisson processes, dwell ties, thresholds, standard deviations, negative controls, etc. Any additional imitations of the ‘967 claims are encompassed by the open claim language “comprising” found in the instant claims.
The additional limitations of the instant claims, and the reasons for combining, are discussed above.
17. Claims 3 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,093,967 B2 in view of Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004) and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, and further in view of Lakin et al. (J. R. Soc. Interface, vol. 9, pages 1470-1485, published online 4 January 2012) based on the citations and rationale provided above.
18. Claim 15 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,093,967 B2 in view of Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004) and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, and further in view of Singer et al. (U.S. Patent No. 5,866,331, issued 2 February 1999).
19. Claims 20-21 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,093,967 B2 in view of Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004), Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012), and Zudaire Ubani et al. (U.S. Patent Application Publication No. US 2005/053950 A1, published 10 March 2005)
Both sets of claims are drawn to analyzing time resolved data, Poisson processes, dwell ties, thresholds, standard deviations, negative controls, etc. Any additional imitations of the ‘967 claims are encompassed by the open claim language “comprising” found in the instant claims.
The additional limitations of the instant claims, and the reasons for combining, are discussed above.
20. Claim 24 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,093,967 B2 in view of Becker (U.S. Patent Application Publication No. US 2002/0164614 A1, published 7 November 2002), Watkins et al. (J. Phys. Chem. B., vol. 109, pages 617-628, published online 14 December 2004) and Zhong (U.S. Patent Application Publication No. US 2012/0015825 A1, published 19 January 2012) as applied to claim 1 above, alternatively further in view of Rao et al. (U.S. Patent Application Publication No. US 2008/0200342 A1, published 21 August 2008). based on the citations and rationale provided above.
Response to Arguments
21. Applicant's arguments filed 1 April 2026 (hereafter the “Remarks”) have been fully considered but they are not persuasive for the reasons discussed below.
A. Pages 8-9 of the Remarks discussed the amendments, the specification, and drawings, and summarize the art used to reject the claims.
It is noted that Applicant has explicitly stated there is no intention to have color drawings; the drawings filed 6 September 2022 are therefore accepted.
B. Applicant argues on pages 10-12 of the Remarks that the claims are not drawn to an abstract idea, that the metal process grouping does not encompass the claimed method, and that the mathematics are not abstract.
However, in particular with respect to claim 1, the intensity events are classified based on comparison to threshold values. This is easily performed as a mental step (i.e., is X greater than Y?). In addition, the claims do not actually do anything further with the data beyond the initial evaluating of the events against thresholds; e.g., the data is not used to indicate anything. Thus, the claims are clearly drawn to abstract ideas.
C. Applicant argues on pages 12-13 of the Remarks that the claims as a whole have not been taking into consideration.
With respect to Applicant’s arguments about claims 3-4, as noted above, these are merely data gathering steps. The limitations of claim 7 also refer to a naturally phenomenon (i.e., reversible binding of a probe to a target) and data gathering thereof. Claim 10 is drawn to abstract mathematical data analysis (and not data gathering, as argued by Applicant). Thus, all of the method steps are either drawn to routine and conventional wets steps, data gathering, or abstract data analysis, as discussed above.
D. Applicant argues on pages 13-14 of the Remarks that the claims are an improvement to single molecule detection technology.
It is noted that the features upon which applicant relies (i.e., single molecule detection) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Specifically, none of the claims are limited to detection of single molecules.
With respect to improvements in technology, it is reiterated from above that the claims do not actually do anything further with the data beyond the initial evaluating of the events against thresholds; e.g., the data is not used to indicate anything. Thus, the claims are clearly drawn to abstract ideas and do not represent any type of improvement.
E. Applicant argues on page 15 of the Remarks that the Office implicitly acknowledges that the claims are not mental steps.
This assumption is erroneous. Just because an calculation could be performed by a computer is no admission, implicit or otherwise, that it cannot be performed in the human mind. A computer can calculate the sum of 3 and 5, and so can a person.
F. Applicant argues on pages 15-16 of the Remarks that the claims are amended to integrate into a practical application.
It is reiterated that the few “wet” steps of the claimed methods are routine and conventional, as evidenced by the prior art cited above.
It is also reiterated from above that the claims do not actually do anything further with the data beyond the initial evaluating of the events against thresholds.
Thus, there is no practical application, nor any improvement, resulting from the methods as claimed.
G. Applicant argues on pages 17-18 of the Remarks that the claims produce a tangible result.
However, it is again reiterated that the claims do not actually do anything further with the data beyond the initial evaluating of the events against thresholds. Even the counting of claim 20 is something that can be performed mentally, and therefore still falls under the umbrella of an abstract idea.
H. Applicant’s amendments to the claims have resulted in the withdrawal of the indefiniteness rejections discussed on page 18 of the Remarks.
I. Pages 18-19 of the Remarks contain various citations of case law, but do not address how the claims fail to meet any of the cited standards.
J. It is noted that while the obviousness rejections above are new rejections necessitated by the amendments, any argument still relevant to the new rejections are addressed below.
K. In response to Applicant's arguments on pages 19-20 of the Remarks that the cited prior art is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Zhong et al. is related to methods of obtaining time-resolved signals (paragraph 0138), including from a plurality of discrete sources of signals (paragraph 0104), which are examined individually (paragraph 0130).
Watkins et al. also describe methods comprising providing a data set describing time resolved intensity measurements (Title and Figure 1), counting the number of events (i.e., photons; Figure 2), wherein the transitions are classified into groups (Section 2.3), numbering the intensity states (Section 2.3) and thresholding (Introduction). Watkins et al. further teach studying molecules one at a time (Section 1). Thus the references are from analogous areas of the prior art.
L. Applicant’s arguments on pages 20-21 of the Remarks regarding the physical assay are moot in view of the new rejections necessitated by the amendments.
M. Applicant agues on pages 21-22 of the Remarks that neither Watkins et al. nor Zhong et al. teach the claimed thresholding.
In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Specifically, the prior art of Watkins et al. is not relied upon for thresholding. Rather, as noted in the rejections above, the prior art of Zhong et al. is relied upon for teaching detection of labels based on upon there retention (i.e., dwell) time (paragraph 0099), median (i.e., average) signals above baselines (paragraph 0190), and classifying signals based on thresholds (paragraphs 0067-0068). Zhong et al. further teach averaging over a period of time to obtain a high signal to noise ratio (paragraph 0127). Thus, if would have been obvious to determine the number of signals exceed a threshold and that a dwell time exceeds a mean (i.e., average) threshold.
In addition, Applicant’s reference to “SiMREPS” offers no clarity to the arguments, as the term “SiMREPS” does not occur in either the instant specification or the cited prior art.
N. In response to Applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the reasons for combining are clearly articulated above.
In addition, it is also noted that the Supreme Court ruling for KSR Int’l Co. v. Teleflex, Inc. (No 04-1350 (US 30 April 2007) forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See Ex parte Smith (USPQ2d, slip op. at 20 (Bd. Pat. App. & Interf. June 25, 2007).
It is also noted that while Applicant alleges that the motivation to combine is generic, it is clear that an ordinary artisan would, upon finding an advantage in a prior art reference, would consequently by motivated to review the entire reference to see what it teaches, thereby providing a reasonable expectation of success.
O. With respect to the arguments on pages 23-24 of the Remarks, it is noted that Becker teaches the immobilization steps, as discussed in the rejections above.
P. Applicant argues on pages 24-25 that Larkin et al. is non-analogous art.
However, Applicant admits on page 24 of the Remarks that Larkin et al. is related to DNA hybridization (i.e., stand displacement). Larkin et al is principally relied upon for teaching the use of stochastic login and reasonable threshold levels as related to hybridization events, as discussed above. Thus, because Larkin et al. teach use of the claimed limitations as related to nucleic acid hybridization, the combination is appropriate.
It is reiterated that Applicant’s reference to “SiMREPS” offers no clarity to the arguments, as the term “SiMREPS” does not occur in either the instant specification or the cited prior art.
Q. Applicant’s arguments on pages 25-27 of the Remarks rely upon arguments addressed above, and discuss the new claims, which are rejected as discussed above.
It is reiterated that Applicant’s reference to “SiMREPS” offers no clarity to the arguments, as the term “SiMREPS” does not occur in either the instant specification or the cited prior art.
R. Applicant states on page 27 of the Remarks that a terminal disclaimer will be considered upon identification of allowable claims. Since the claims are not in condition for allowance, the nonstatutory double patenting rejections are maintained as discussed above.
Conclusion
22. No claim is allowed.
23. 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).
24. 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.
25. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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