DETAILED ACTION
Comments
The present application is being examined under the pre-AIA first to invent provisions. 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.
Claims 17-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 21 February 2025.
Claims 1-2 and 4-30 are pending in the application.
Claims 1-2, 4-16, and 30 are examined in the instant Office action.
Withdrawn Rejections
The rejections under 35 U.S.C. 101 are withdrawn in view of arguments on pages 10-12 of the Remarks. Specifically, while the claims recite judicial exceptions, the alleged mental steps regarding calculating cumulative intensities and signal interpretation recited in claim 1 are too complex to be conducted in the human mind.
The prior art rejections and double patenting rejections are withdrawn in view of amendments filed to the instant set of claims on 23 September 2025.
Priority
The instant application is a continuation of 16937464 (filed 7/23/2020). Application ‘464 is a continuation of application 15914356 (filed 3/7/2018). Application ‘356 is a continuation of application 14451876 (filed 8/5/2014). Application ‘876 is a continuation of application 13756760 (filed 2/1/2013). Application ‘760 claims benefit to provisional application 61703093 (filed 9/19/2012). Application ‘760 claims benefit to provisional application 61594480 (filed 2/3/2012).
Provisional applications ‘480 and ‘093 do not have possession of the mathematical expression in claim 2, six different wavelength measurements of claim 11, twelve analytes of claim 12 that are labeled with the six different fluorophores of claim 13, and the plurality of detectors in claim 16.
Provisional application ‘480 does not have possession of the fluorophores listed in claims 5-6.
Claims 2, 11-13, and 16 receive the benefit date of 2/1/2013.
Claims 5-6 receive the benefit date of 9/19/2012.
Claims 1, 4, 7-10, and 14-15 receive the benefit date of 2/3/2012.
Response to comments:
Applicant corrected to priority date designation of the claims in response to applicant’s comments on page 9 of the Remarks.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The following rejection is necessitated by amendment:
35 U.S.C. 103 Rejection #1:
Claims 1, 4-6, 12, and 30 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Larson et al. [US PGPUB 2011/0250597 A1] in view of Shalon et al. [Genome Research, volume 6, 1996, pages 639-645] in view of Vogelstein et al. [PNAS, volume 96, 1999, pages 9236-9241; on IDS].
Claim 1 is drawn to a system for detecting unique combinations of the presence or absence of multiple polynucleotide analytes in a sample volume. The system comprises a body configured to hold a sample volume comprising six hybridization probes corresponding to the multiple polynucleotide analytes wherein each probe comprises a fluorophore. The system comprises an excitation light source configured to excite the fluorophore in each hybridization probe to generate a signal if one of the polynucleotide analytes is present in the sample. The signal is generated by excitement of the fluorophore. The system comprises a detector to measure the signal. The system comprises a controller configured to perform the method of generating a wavelength measurement and a cumulative intensity measurement for the signal. The controller executed method comprises determining whether each polynucleotide analyte is present, based on the wavelength and cumulative intensity measurement wherein the method does not comprise mass spectrometry. The controller executed method requires that the number of wavelength values used to encode the analytes is less that the number of polynucleotide analytes. The system is part of a digital droplet system.
Claim 4 is further limiting comprising determining a copy number of polynucleotide analytes in the sample volume.
Claims 5-6 comprise use and analysis of FAM fluorophores.
Claim 12 is further limiting wherein the system comprises twelve polynucleotide analytes.
Claim 30 is further limiting wherein the method does not require melting curve analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3). Paragraph 47 of Larson et al. teaches FAM fluorophore analysis.
While Larson et al. teaches a system comprising three analytes, Larson et al. does not teach a system comprising six hybridization probes. Larson et al. does not teach that the system is part of a digital droplet system.
The document of Shalon et al. studies a DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization [title]. The abstract of Shalon et al. teaches a microarray of thousands of probes analyzed using fluorescent probe hybridization. Shalon et al. does not teach melting curve analysis.
Larson et al. and Shalon et al. do not teach that the system is part of a digital droplet system.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the analyte algorithm to determine presence/absence patterns of Larson et al. by use of expanding the number of probes used in the analysis as in Shalon et al. wherein the motivation would have been that adding probes facilitates analytes of target analytes by yielding additional relevant data [abstract of Shalon et al.]. There would have been a reasonable expectation of success in combining Larson et al. and Shalon et al. because both studies are analogously applicable to analysis systems of multiple probes and target analytes using fluorophores.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the analyte algorithm to determine presence/absence patterns of Larson et al. and expanding the number of probes used in the analysis as in Shalon et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
35 U.S.C. 103 Rejection #2:
Claims 7-11 and 13-16 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Larson et al. in view of Shalon et al. in view of Vogelstein et al. as applied to claims 1, 4-6, 12, and 30 above, in further view of Sagner et al. [WO 2004/087950 A2; on IDS].
Claims 7-8 list the wavelength numbers to be analyzed.
Claims 9-10 teach that the encoding algorithm is non-degenerate.
Claim 11 is further limiting comprising up to six wavelength measurements and up to ten intensity measurements.
Claim 13 is further limiting wherein the twelve polynucleotide analytes are labeled using six fluorophores.
Claims 14-15 teaches encoding at least six polynucleotides into values or a matrix of color and intensity.
Claim 16 is further limiting wherein the at least one detector comprises a plurality of detectors.
The documents of Larson et al., Shalon et al., and Vogelstein et al. make obvious a system for detecting presence/absence patterns of a plurality of polynucleotide analytes, as discussed above.
Larson et al., Shalon et al., and Vogelstein et al. do not teach the aforementioned recited limitations.
The document of Sagner et al. studies an improved system for multi-color real time PCR [title]. The cover figure illustrates the system comprises an excitation light source and six detectors, each detecting at about a recited wavelength number. The six detectors in the cover figure of Sagner et al. result in a non-degenerate encoding of six wavelength and intensity measurements wherein each detector detects a different color and intensity (i.e. a matrix of color and intensity). Pages 31-34 of Sagner et al. list at least twelve polynucleotide analytes that are analyzed using six fluorophores corresponding to the color detected at the wavelength value of each of the six detectors.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the analyte algorithm to determine presence/absence patterns of Larson et al., the expanding the number of probes used in the analysis as in Shalon et al., and the digital droplet analysis of Vogelstein et al. by use of the apparatus of Sagner et al. wherein the motivation would have been that the six detector apparatus of Sagner et al. facilitates analysis of the polynucleotide analytes by expanding the perspectives with which the polynucleotide analytes are analyzed [cover figure of Sagner et al.].
Double Patenting
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.
The following rejection is necessitated by amendment:
Double Patenting Rejection #1:
Claims [1, 2, 12, or 30] and [1, 2, or 9] are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 20, respectively, of U.S. Patent No. 8,838,394 B2 [on IDS] in view of Larson et al. in view of Shalon et al. in view of Vogelstein et al. Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes. The claims of ‘394 do not teach the apparatus limitations, the six hybridization probes, and the requirement that the number of wavelength values used to encode the analytes is less than the number of polynucleotide analytes. The claims of ‘394 do not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3).
While Larson et al. teaches a system comprising three analytes, Larson et al. does not teach a system comprising six hybridization probes. Larson et al. does not teach that the system comprises digital droplet analysis.
The document of Shalon et al. studies a DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization [title]. The abstract of Shalon et al. teaches a microarray of thousands of probes analyzed using fluorescent probe hybridization. Shalon et al. does not teach melting curve analysis.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claims of ‘394 by use of the analyte algorithm to determine and apparatus of Larson et al. wherein the motivation would have been that Larson et al. uses less channels of wavelength to more efficiently analyze more types of analytes [paragraph 140 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claims of ‘394 and the analyte algorithm to determine and apparatus of Larson et al. by use of expanding the number of probes used in the analysis as in Shalon et al. wherein the motivation would have been that adding probes facilitates analytes of target analytes by yielding additional relevant data [abstract of Shalon et al.]. There would have been a reasonable expectation of success in combining the claims of ‘394, Larson et al., and Shalon et al. because all three studies are analogously applicable to analysis systems of multiple probes and target analytes using fluorophores.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claims of ‘394, the analyte algorithm to determine and apparatus of Larson et al., and the expanding the number of probes used in the analysis as in Shalon et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
Double Patenting Rejection #2:
Claim [1 or 9] is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,068,051 B2 [on IDS] in view of Larson et al. in view of Shalon et al. in view of Vogelstein et al. Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes. The claim of ‘051 does not teach the apparatus limitations, the seven hybridization probes, and the requirement that the number of wavelength values used to encode the analytes is less than the number of polynucleotide analytes. The claim of ‘051 does not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3).
While Larson et al. teaches a system comprising three analytes, Larson et al. does not teach a system comprising six hybridization probes. Larson et al. does not teach that the system comprises digital droplet analysis.
The document of Shalon et al. studies a DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization [title]. The abstract of Shalon et al. teaches a microarray of thousands of probes analyzed using fluorescent probe hybridization.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘051 by use of the analyte algorithm to determine and apparatus of Larson et al. wherein the motivation would have been that Larson et al. uses less channels of wavelength to more efficiently analyze more types of analytes [paragraph 140 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘051 and the analyte algorithm to determine and apparatus of Larson et al. by use of expanding the number of probes used in the analysis as in Shalon et al. wherein the motivation would have been that adding probes facilitates analytes of target analytes by yielding additional relevant data [abstract of Shalon et al.]. There would have been a reasonable expectation of success in combining the claims of ‘051, Larson et al., and Shalon et al. because all three studies are analogously applicable to analysis systems of multiple probes and target analytes using fluorophores.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘051, the analyte algorithm to determine and apparatus of Larson et al., and the expanding the number of probes used in the analysis as in Shalon et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
Double Patenting Rejection #3:
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,770,170 B2 [on IDS] in view of Larson et al. in view of Shalon et al. in view of Vogelstein et al. Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes. The claim of ‘170 does not teach the apparatus limitations, the five polynucleotide analytes, and the requirement that the number of wavelength values used to encode the analytes is less than the number of polynucleotide analytes. The claim of ‘170 does not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3).
While Larson et al. teaches a system comprising three analytes, Larson et al. does not teach a system comprising five polynucleotide analytes. Larson et al. does not teach that the system comprises digital droplet analysis.
The document of Shalon et al. studies a DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization [title]. The abstract of Shalon et al. teaches a microarray of thousands of probes analyzed using fluorescent probe hybridization.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘170 by use of the analyte algorithm to determine and apparatus of Larson et al. wherein the motivation would have been that Larson et al. uses less channels of wavelength to more efficiently analyze more types of analytes [paragraph 140 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘170 and the analyte algorithm to determine and apparatus of Larson et al. by use of expanding the number of probes used in the analysis as in Shalon et al. wherein the motivation would have been that adding probes facilitates analytes of target analytes by yielding additional relevant data [abstract of Shalon et al.]. There would have been a reasonable expectation of success in combining the claim of ‘170, Larson et al., and Shalon et al. because all three studies are analogously applicable to analysis systems of multiple probes and target analytes using fluorophores.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘170, the analyte algorithm to determine and apparatus of Larson et al., and the expanding the number of probes used in the analysis as in Shalon et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
Double Patenting Rejection #4:
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,866,768 B2 in view of Larson et al. in view of Vogelstein et al. Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes. The claim of ‘768 does not teach the apparatus limitations, the plurality of analytes, and the requirement that the number of wavelength values used to encode the analytes is less than the number of polynucleotide analytes. The claim of ‘768 does not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3).
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘768 by use of the analyte algorithm to determine and apparatus of Larson et al. wherein the motivation would have been that Larson et al. uses less channels of wavelength to more efficiently analyze more types of analytes [paragraph 140 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘768 and the analyte algorithm to determine and apparatus of Larson et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
Double Patenting Rejection #5:
Claims 1 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13, respectively, of U.S. Patent No. 11,827,921 B2 in view of Larson et al. in view of Vogelstein et al. Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes wherein the number of analytes is greater than the number of wavelength values used to encode the analytes. The claims of ‘921 do not teach the apparatus limitations. The claims of ‘921 do not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claims of ‘921 by use of the laser, detector, and controller of Larson et al. wherein the motivation would have been that the hardware of Larson et al. facilitates analysis of the analytes [Figure 3 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘921 and the analyte algorithm to determine and apparatus of Larson et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
The following rejection is necessitated by amendment:
Double Patenting Rejection #6:
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/885,037 in view of Larson et al. in view of Shalon et al. in view of Vogelstein et al.
This is a provisional nonstatutory double patenting rejection.
Both sets of claims are drawn to determining presence/absence patterns of a plurality of polynucleotide analytes. The claim of ‘037 does not teach the apparatus limitations, the five hybridization probes and analytes, and the requirement that the number of wavelength values used to encode the analytes is less than the number of polynucleotide analytes. The claim of ‘037 does not teach that the system comprises digital droplet analysis.
The document of Larson et al. studies digital analyte analysis [title]. Figures 1 and 3 of Larson et al. illustrate the sample volume, the excitation light source (i.e. a laser), and a detector used to measure the signal. Paragraph 140 of Larson et al. teaches an algorithm for analyzing the presence or absence of three target analytes using two fluorophores comprising wavelength (i.e. color) measurement and cumulative intensity (i.e. copy number) measurements. The number of wavelength values used to encode the polynucleotide analytes (i.e. 2) is less than the number of polynucleotide analytes (i.e. 3).
While Larson et al. teaches a system comprising three analytes, Larson et al. does not teach a system comprising five hybridization probes and analytes.
The document of Shalon et al. studies a DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization [title]. The abstract of Shalon et al. teaches a microarray of thousands of probes analyzed using fluorescent probe hybridization.
The document of Vogelstein et al. teaches a digital droplet system in the title, abstract, and Figure 1.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘037 by use of the analyte algorithm to determine and apparatus of Larson et al. wherein the motivation would have been that Larson et al. uses less channels of wavelength to more efficiently analyze more types of analytes [paragraph 140 of Larson et al.].
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘037 and the analyte algorithm to determine and apparatus of Larson et al. by use of expanding the number of probes used in the analysis as in Shalon et al. wherein the motivation would have been that adding probes facilitates analytes of target analytes by yielding additional relevant data [abstract of Shalon et al.]. There would have been a reasonable expectation of success in combining the claim of ‘037, Larson et al., and Shalon et al. because all three studies are analogously applicable to analysis systems of multiple probes and target analytes using fluorophores.
It would have been obvious to someone of ordinary skill in the art at the time of the instant invention to combine the presence absence algorithm of the claim of ‘037, the analyte algorithm to determine and apparatus of Larson et al., and the expanding the number of probes used in the analysis as in Shalon et al. by use of the digital droplet analysis of Vogelstein et al. wherein the motivation would have been that Vogelstein conducts DNA analysis on the droplet scale [Figure 1 of Vogelstein et al.].
Response to Arguments
Applicant's arguments filed 23 September 2025 have been fully considered.
Applicant argues that prior claim 3 has been cancelled and incorporated into independent claim 1. Applicant argues that since the prior claim 3 has not been rejected under prior art statutes, then claim 1 is now free of the prior art. This argument is not persuasive because claim 3 in the claim listing of 6 June 2025 is dependent from claim 2, wherein claim 2 is dependent from claim 1. Since prior claim 3 contains the novel mathematical expression of claim 2, claim 3 in the 6 June 2025 claim listing is free of the prior art. While applicant incorporates claim 3 of the claim listing of 6 June 2025 into claim 1, the novel limitations of claim 2 are not incorporated into claim 1. Consequently, the prior art rejection on claim 1 is newly applied and necessitated by amendment.
Applicant argues that due to the amendments to claim 1, the double patenting rejections have been overcome. The document of Vogelstein et al. has been added to each of the double patenting rejections to make each double patenting rejection newly applied and necessitated by amendment.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
No claim is allowed.
Claim 2 is free of the prior art because the prior art does not teach the recited mathematical expression.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/Primary Examiner, Art Unit 1686 5 October 2025