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 .
Interview Summary
The Examiner would like to note the inclusion of the Applicant’s interview summary regarding the telephonic interview on October 14th, 2025. With the inclusion of this summary, the interview record is complete.
Response to Amendment
The amendment filed October 27th, 2025 is acknowledged. Regarding the Office Action mailed June 26th, 2025:
The objections to the drawings are withdrawn in view of the remarks noting the submission of black and white replacement drawings filed February 21st, 2022.
The objections to the specification are withdrawn in view of the amendments.
Maintained or modified rejections are set forth below, as necessitated by the amendments. New grounds of rejection are also set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1 and 79 have been amended. Claims 2-4 and 19-78 have been canceled. Claims 1, 5-18, 79-83 are pending. Claims 1, 5-18, and 79-83 are under examination and discussed in this Office action.
Claim Interpretation - Maintained
Instant claims 1, 5-18, and 79-83 are drawn to a system that includes a purification instrument and an automated sequencing instrument (i.e. apparatus). MPEP 2114 makes it clear that while features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function. "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987).
The recitation of “to determine variant calls when starting with 6 samples including cfTNA and using a targeted assay with one nucleic acid pool per sample” of claim 1 has been interpreted as an intended use limitation. This does not further define the device because it does not claim further structural components specific to determining variant calls for cfTNA.
Response to Arguments
In regards to the Examiner’s statement of claim interpretation, the Applicant argues that claim 1 defines the performed of the instrument based on quality and time, with the referenced language providing context for the performance and therefore not being intended use (Page 13 of the Remarks filed October 27th, 2025). The Applicant then argues that the recitation in claim 1 of “performance of at least 98.5% raw read accuracy and a total instrument run time across both the purification instrument and the automated sequencing instrument in a range of 16 hours to 22 hours to determine variant calls when starting with 6 samples including cfTNA and using a targeted assay with one nucleic acid pool per sample” is not representative of an intended use, but a “performance characteristic defined for the sequencing system. In other words, for a given number of samples of a particular type, the sequencing system can provide variant calls with a specific accuracy within a specific time” (Page 13 of the Remarks filed October 27th, 2025). The Applicant further states that the recited language is a performance characteristic of the device claimed and implies structure (Page 13 of the Remarks filed October 27th, 2025).
In response, the Examiner would like to focus on the statement by the Applicant saying “for a given number of samples or a particular type, the sequencing system can provide variant calls with a specific accuracy within a specific time”.
This statement is implying an intended use of the device because the parameters mentioned are dependent on how the sequencing system is intended to be used. Sample type and the required quality of output can be assumed to affect the variant calls produced by the system, along with the specific accuracy within a specific time.
Also, as will be addressed later, the provided art generally teaches the claimed time range and read accuracy of the system.
In addition, 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)). Counsel’s arguments do not provide any evidence of how the structures of the system as claimed are any different from the structures of the cited prior art, or as to how any alleged improved function would be obtained.
Further, the fact that the inventor has allegedly recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Therefore, the interpretation of “to determine variant calls when starting with 6 samples including cfTNA and using a targeted assay with one nucleic acid pool per sample” of claim 1 as an intended use limitation is still reasonable as it does not claim further structural components specific to determining variant calls for cfTNA.
Claim Interpretation – New – Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
The claims contain the following limitation:
Claim 1 recites “the purification instrument configured to receive samples including cell-free total nucleic acid (cfTNA) and to provide the one or more extracted polynucleotide samples”.
Thus, the cited limitation is drawn to a generic means plus function. However, this limitation is not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because a review of the specification yields no limiting definition of the generically claimed means.
If applicant intends to have this limitation interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant should indicate where in the specification the specific structure is indicated.
Claim Rejections - 35 USC § 103 – Modified – Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 5, and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), in view of ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited).
Regarding instant claim 1, Illumina I teaches a sequencing system comprising an automated sequencing instrument (slide 9) adapted to determine variant calls (slide 10) for one or more extracted polynucleotide samples (slide 23), which reasonably also teaches that the sequencing instrument is configured to receive one or more extracted polynucleotide samples, with a performance of at least 98.5% raw read accuracy (slide 24) and an automated sequencing instrument run time in a range of 16 hours to 22 hours (slide 26).
Illumina I does not additionally teach a purification instrument, the purification instrument to receive samples including cell-free total nucleic acid (cfTNA) and to provide the one or more extracted polynucleotide samples.
ExiPrepTM96 Lite, in a reasonably pertinent field, teaches a purification instrument (Page 2), the purification instrument to receive samples including cell-free total nucleic acid (cfTNA) and to provide the one or more extracted polynucleotide samples (Page 2). Depending on the type of extraction being performed, ExiPrepTM96 Lite teaches that the run time of the instrument can take between 3 minutes and one and a half hours (Page 3). When added together with the run times of Illumina, a total instrument run time of both instruments can fall between 16 and 22 hours. Furthermore, ExiPrepTM96 Lite extracted samples can be used for next generation sequencing when using the appropriate extraction kit (Page 12).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the automated sequencing instrument of Illumina I with the purification instrument of ExiPrepTM96 Lite. Since ExiPrepTM96 Lite teaches on a purification instrument that can prepare samples for downstream applications, which is reasonably pertinent to samples that will undergo sequencing, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because automated nucleic acid extraction reduces human error (ExiPrepTM96 Lite, Page 3).
The recitation of “a total instrument run time across both the purification instrument and the automated sequencing instrument in a range of 16 hours to 22 hours” of instant claim 1 can been interpreted as an intended use limitation. In Illumina I, different examples are provided that show the variability in instrument run time depending on run conditions. One example shows 1x36 base pairs with an instrument run time of 6.5 hours (slide 15, includes sequencing and variant calling). In another example, 2x76 base pairs has an instrument run time of 16.5 hours, which falls within the instrument run time of the instant claim (slide 26, includes sequencing and variant calling). In ExiPrepTM96 Lite, different examples are provided that show the variability in instrument run time depending on the extracted material. One example shows a cfDNA extraction can take 40 minutes (Page 3), while a general DNA extraction can take 30 minutes (Page 3). Given the differences in the runs (1x36 vs 2x76 and 30 min vs 40 min), the instrument run time can be attributed to how much sequencing information a user wants to acquire and analyze, and what kind of material is to be extracted. Therefore, run time is dependent on how the system is intended to be used.
Neither of these references teaches wherein the automated sequencing instrument comprises a preparation deck to prepare one or more modified extracted polynucleotide sample for loading, a loading station to load the one or more modified extracted polynucleotide samples on a substrate, and a sequencing station to detect nucleotide incorporation, and a three-axis pipetting system.
Fort, in a reasonably pertinent field, teaches on a preparation deck to prepare one or more modified extracted polynucleotide samples for loading, with a loading station to load the one or more modified extracted polynucleotide samples on a substrate, for automated nucleic acid detection (Pages 14-15, paragraph [0053]; Pages 17-18, paragraph [0062]-[0066]; Figure 3). Fort also teaches a three-axis pipetting apparatus in the form of a SCARA robotic arm with an attached pipetting apparatus (Pages 16-17, paragraph [0059]; Page 17, paragraph [0061]; Figure 5 and 6).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the automated sequencing system of Illumina I with the preparation deck with a loading station and pipetting apparatus of Fort. Since the device of Fort is directed towards nucleic acid analysis, which is reasonably pertinent to the automated sequencing system of Illumina I, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because the system of Fort minimizes pipetting and reduces hands-on time while achieving the same results as a manual system (Page 14, paragraph [0050]; Pages 14-15, paragraph [0053]).
None of the above cited references teach wherein the automated system includes a sequencing station to detect nucleotide incorporation.
Nobile, in the same field of endeavor, teaches an apparatus for sequencing that includes a sequencing station to detect nucleotide incorporation (Page 12, paragraph [0069]; Figure 7A: reference character 734).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the automated sequencing system of Illumina I with the sequencing station of Nobile. Since Illumina I and Nobile are in the same field of endeavor, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it may be used to carry out pH-based nucleic acid sequencing (Nobile, Page 12, paragraph [0069]).
Regarding instant claim 5, Illumina I teaches the raw read accuracy is at least 99.0% Raw Read Accuracy (slide 24).
Regarding instant claim 6, Illumina I teaches the raw read accuracy is at least 99.1% (slide 24).
Claim(s) 7-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Wu et al. (Phasing amplicon sequencing on Illumina Miseq for robust environmental microbial community analysis, BMC Microbiology, 2015, 15, 125; previously cited).
Regarding instant claim 7, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach that the performance is further characterized by a Q20 median read length of at least 100 bases and not greater than 450 bases. Wu, using the sequencing system of Illumina I, teaches a Q20 mean read length of at least 100 bases and not greater than 450 bases (Figure 3C). It should be noted that the measures median and mean are used interchangeably in this rationale. Assuming a normal distribution of data output from the sequencing system, it would be obvious to one of ordinary skill in the art that the median and the mean of the data are known alternatives and would be roughly equivalent in value. It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of a Q20 mean read length of at least 100 bases and not greater than 450 bases because it is the same system used in Wu. Since the systems of Illumina I and Wu are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 8, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach a Q20 mean read length of at least 102 bases and not greater than 300 bases. Wu, using the sequencing system of Illumina I, teaches the Q20 median read length is at least 102 bases and not greater than 300 bases (Figure 3C). It should be noted that the measures median and mean are used interchangeably in this rationale. Assuming a normal distribution of data output from the sequencing system, it would be obvious to one of ordinary skill in the art that the median and the mean of the data are known alternatives and would be roughly equivalent in value. It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of a Q20 mean read length of at least 102 bases and not greater than 300 bases because it is the same system used in Wu. Since the systems of Illumina I and Wu are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 9, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach a Q20 mean read length of at least 104 bases and not greater than 300 bases. Wu, using the sequencing system of Illumina I, teaches the Q20 median read length is at least 104 bases and not greater than 300 bases (Figure 3C). It should be noted that the measures median and mean are used interchangeably in this rationale. Assuming a normal distribution of data output from the sequencing system, it would be obvious to one of ordinary skill in the art that the median and the mean of the data are known alternatives and would be roughly equivalent in value. It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of a Q20 mean read length of at least 104 bases and not greater than 300 bases because it is the same system used in Wu. Since the systems of Illumina I and Wu are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Claim(s) 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Illumina II (AmpliSeq for Illumina BRCA Panel [online]. Illumina, [July 2018] [retrieved on October 2nd, 2024]. Retrieved from: elta90mg.com/uploads/files/ampliseq-for-illumina-brca-panel-data-sheet-770-2017-029.pdf; previously cited).
Regarding instant claim 10, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach that the performance is further characterized by a uniformity of coverage for an amplicon library of at least 97%. Illumina II, using the sequencing system of Illumina I, teaches the performance is further characterized by a uniformity of at least 97% (Figure 1, the red dots). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of uniformity is at least 97% because it is the same system used in Illumina II. Since the systems of Illumina I and Illumina II are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 11, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach the uniformity is at least 98%. Illumina II, using the sequencing system of Illumina I, teaches the uniformity is at least 98% (Figure 1, the red dots). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of uniformity is at least 98% because it is the same system used in Illumina II. Since the systems of Illumina I and Illumina II are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 12, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach the uniformity is at least 98.5%. Illumina II, using the sequencing system of Illumina I, teaches the uniformity is at least 98.5% (Figure 1, the red dots). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of uniformity is at least 98.5% because it is the same system used in Illumina II. Since the systems of Illumina I and Illumina II are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Claim(s) 13-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Gaio et al. (Hackflex: low cost Illumina sequencing library construction for high sample counts [online]. bioRxiv, [September 2019] [retrieved on October 2nd, 2024]. Retrieved from: doi.org/10.1101/779215; previously cited).
Regarding instant claim 13, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach that the performance is further characterized by an average percent reads on target of at least 97%. Gaio, using the sequencing system of Illumina I, teaches the performance is further characterized by an average percent reads on target of at least 97% (Page 10, paragraph 1). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of average percent reads on target of at least 97% because it is the same system used in Gaio. Since the systems of Illumina I and Gaio are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 14, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach the average percent reads on target of at least 98%. Gaio, using the sequencing system of Illumina I, teaches an average percent reads on target of at least 98% (Page 10, paragraph 1). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of average percent reads on target of at least 98% because it is the same system used in Gaio. Since the systems of Illumina I and Gaio are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 15, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach the average percent reads on target of at least 98.1%. Gaio, using the sequencing system of Illumina I, teaches an average percent reads on target of at least 98.1% (Page 10, paragraph 1). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of average percent reads on target of at least 98.1% because it is the same system used in Gaio. Since the systems of Illumina I and Gaio are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Claim(s) 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Kastanis et al. (In‐depth comparative analysis of Illumina® MiSeq run metrics: Development of a wet‐lab quality assessment tool, Molecular Ecology Resources, 2019, 19, 377-387; previously cited).
Regarding instant claim 16, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach that the performance is further characterized by a total reads in a range of 13 million bases to 100 million bases. Kastanis, using the sequencing system of Illumina I, teaches the performance is further characterized by a total reads in a range of 13 million bases to 100 million bases (Table 2, see total reads row). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of total reads in a range of 13 million bases to 100 million bases because it is the same system used in Kastanis. Since the systems of Illumina I and Kastanis are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 17, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach total reads in a range of 13 million bases to 60 million bases. Kastanis, using the sequencing system of Illumina I, teaches total reads in a range of 13 million bases to 60 million bases (Table 2, see total reads row). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of total reads in a range of 13 million bases to 60 million bases because it is the same system used in Kastanis. Since the systems of Illumina I and Kastanis are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 18, while Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system as described in the above 103 rejection. Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, does not teach total reads in a range of 14.5 million bases to 25 million bases. Kastanis, using the sequencing system of Illumina I, teaches total reads in a range of 14.5 million bases to 25 million (Table 2, see total reads row). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the system of Illumina I would have the property of total reads in a range of 14.5 million bases to 25 million bases because it is the same system used in Kastanis. Since the systems of Illumina I and Kastanis are the same, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Claim 79 is rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Ramsey (US20150211048A1; previously cited).
Regarding instant claim 79, Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system of claim 1.
None of these references teach wherein the loading station utilizes magnetic loading to load samples into wells of a sequencing chip.
Ramsey, in a reasonably pertinent field, teaches a microfluidics device with a plurality of wells wherein the wells are loaded with magnetic beads using magnetic force (Page 9, paragraph [0088]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the automated sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile with the magnetic well loading of Ramsey. Since Ramsey teaches on the use of a microfluidics device for nucleic acid analysis, which is reasonably pertinent to the automated sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because magnetic loading can greatly speed delivery of beads to wells (Ramsey, Page 9, paragraph [0087]). While Ramsey further attests that previous work showed unsuccessful magnetic loading with multiple loading in non-optimized geometries (Page 9, paragraph [0087]), Ramsey’s own experimentation resulted in single beads loading in a bead well ~80% to greater than 90% of the time, suggesting successful loading with the described device (Page 10, paragraph [0097]).
Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of Toumazou et al. (A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell, Philosophical Transactions of The Royal Society, March 2014, 1-12; previously cited).
Regarding instant claim 80, Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system of claim 1.
None of these references teach wherein the automated sequencing instrument comprises a sensor array including ion-sensitive field effect transistors (ISFETs) for detecting nucleotide incorporations.
Toumazou, in a reasonably pertinent field, teaches a sensor array including ion-sensitive field effect transistors (ISFETs) for detecting nucleotide incorporations for nucleic acid sequencing (Page 5; Figure 3; Table 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified to have modified the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with the sensor array of Toumazou. Since Toumazou teaches on nucleic acid analysis, which is reasonably pertinent to the automated sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because ISFET technology is label-free, portable, scalable, and cost-effective (Toumazou, Page 5).
Claims 81-83 are rejected under 35 U.S.C. 103 as being unpatentable over Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited), in view of further considerations from Nobile (US20100300895A1; previously cited).
Regarding instant claim 81, Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system of claim 1.
None of these references as currently cited teach wherein the automated sequencing instrument comprises a flow cell having multiple lanes, wherein each lane is fluidically isolated from other lanes.
Nobile, in the same field of endeavor, teaches an apparatus for sequencing comprising a flow cell (Page 12, paragraph [0069]; Figure 7A). Nobile further teaches wherein on sensor can have multiple flow cells (e.g. multiple lanes) (Pages 8-9, paragraph [0057]; Figure 4E), wherein each lane is fluidically isolated from other lanes (Pages 8-9, paragraph [0057]; Figure 4E).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with the flow cell of Nobile. Since Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, and Nobile are in the same field of endeavor, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because the plurality of separate flow cells can use a single large sensor array (Nobile, Page 8-9, paragraph [0057]). In addition, it would have been obvious to one of ordinary skill in the art that the known components of Nobile could have been applied to the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with predictable results because the known components of Nobile predictably result in separate flow cell lanes for different samples.
Regarding instant claim 82, Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system of claim 1.
None of these references as currently cited teach wherein the automated sequencing instrument comprises a fluidic circuit configured to deliver reagents through multiple lanes of a flow cell, wherein the fluidic circuit includes valves to control reagent flow to individual lanes.
Nobile, in the same field of endeavor, teaches an apparatus for sequencing that comprises a fluidic circuit configured to deliver reagents through a flow cell, wherein the fluidic circuit includes valves to control reagent flow to the flow cell (Pages 3-4, paragraph [0032]; Figure 1A; Page 12, paragraph [0069]; Figure 7A). Nobile further teaches that the flow cell may have multiple lanes (Pages 8-9, paragraph [0057]; Figure 4E).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with the fluidics system of Nobile. Since Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, and Nobile are in the same field of endeavor, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because this fluidics system allows the apparatus to deliver different reagents to the flow cell and sensor array in a predetermined sequence, for predetermined durations, at predetermined flow rates (Nobile, Page 3-4, paragraph [0032]). In addition, it would have been obvious to one of ordinary skill in the art that the known components of Nobile could have been applied to the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with predictable results because the known components of Nobile predictably result in controlled distribution of reagents through the fluidics system and flow cell.
Regarding instant claim 83, Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, teaches the sequencing system of claim 1.
None of these references as currently cited teach wherein the automated sequencing instrument comprises a heater configured to control temperature of reagents prior to delivery to a sequencing chip.
Nobile, in the same field of endeavor, teaches an apparatus for sequencing that comprises a heater configured to control temperature of reagents prior to delivery to a sequencing chip on a flow cell (Page 10, paragraph [0063]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the sequencing system of Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, with the heater of Nobile. Since Illumina I, in view of ExiPrepTM96 Lite, Fort, and Nobile, and Nobile are in the same field of endeavor, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because heating the reagents before reading the flow cell allows the rate of flow and heat capacity of the fluid to be sufficient to remove excess heat generated by the sensors or analytical reactions (Nobile, Page 10, paragraph [0063]).
Response to Arguments
Applicant's arguments filed October 27th, 2025 have been fully considered but they are not persuasive.
The Applicant argues that “the combination of cited references fails to teach or suggest a system specifically configured to achieve the claimed performance benchmark of completing variant calls within 16-22 hours with the recited raw read accuracy when starting with 6 cfTNA samples. This timing limitation reflects required structural capabilities rather than mere intended use” (Page 14 of the Remarks filed October 27th, 2025). The Applicant then argues that none of the provided references teach a system configured to achieve variant calls from 6 cfTNA samples within 16-22 hours total run time (Pages 14-15 of the Remarks filed October 27th, 2025). It is noted that there is no argument directed towards the references of Fort, Nobile, Ramsey, and Toumazou.
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 combination of Illumina I and ExiPrepTM96 Lite teaches variant calling within the claimed time frame with the recited raw read accuracy, as analyzed above. Furthermore, as has already been reiterated earlier, the recitation of “to determine variant calls when starting with 6 samples including cfTNA and using a targeted assay with one nucleic acid pool per sample” is indeed an intended use because of the reasons already stated earlier for Claim Interpretation. This does not then contribute to the structural limitations of the claimed system. Therefore, the art and motivations presented in regards to run time are still pertinent because, as already stated, run time of the system is dependent on the intended run conditions for a particular sequencing reaction. The cited sequencing system is capable of generally meeting the run time and accuracy requirements for a sequencing run as claimed.
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).
Furthermore, 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)). Counsel’s arguments do not provide any evidence of how the structures of the system as claimed are any different from the structures of the cited prior art, or as to how any alleged improved function would be obtained.
Finally, the fact that the inventor has allegedly recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Double Patenting – Modified – Necessitated by Amendment
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.
Claims 1, 5-18 and 79-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11905558B2 in view Illumina I (MiSeq Personal Sequencing System [online]. Illumina, [September 2011] [retrieved on October 2nd, 2024]. Retrieved from: www.illumina.com/Documents/seminars/presentations/2011_09_anderson.pdf; previously cited), ExiPrepTM96 Lite (ExiPrepTM96 Lite, Automated sample preparation for DNA, RNA, and Protein [online]. Bioneer, [February 2020] [retrieved on February 28th, 2025]. Retrieved from: https://s3-us-west-1.amazonaws.com/resource.bioneer.us/juan2/pagecat1/instrument/exiprep-96-lite/BR_ExiPrep96_Lite_2020.pdf; previously cited), Fort (WO2003097808A2; previously cited), and Nobile (US20100300895A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 1, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases.
The recitation of “the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors” is in essence a “species” of the generic invention of instant claim 1. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQd 2010 (Fed. Cir. 1993).
Claim 1 of from U.S. Patent No. 11905558B2 does not teach a sequencing system comprising a purification instrument. However, it does teach that the automated sequencing instrument comprises a preparation deck to prepare one or more extracted polynucleotide samples for loading, and a variation where this is carried out by a purification instrument is made obvious in light of ExiPrepTM96 Lite. ExiPrepTM96 Lite teaches a purification instrument (Page 2), the purification instrument to receive samples including cell-free total nucleic acid (cfTNA) and to provide the one or more extracted polynucleotide samples (Page 2). Furthermore, ExiPrepTM96 Lite extracted samples can be used for next generation sequencing when using the appropriate extraction kit (Page 12). This makes plain that a purification instrument is an obvious variant for the preparation deck.
Also, Claim 1 from U.S. Patent No. 11905558B2 does not teach a purification instrument and an automated sequencing instrument with a combined run time in a range of 16 hours to 22 hours. However, this variation is made obvious in light of Illumina I and ExiPrepTM96 Lite. In Illumina I, different examples are provided that show the variability in instrument run time depending on run conditions. One example shows 1x36 base pairs with an instrument run time of 6.5 hours (slide 15, includes sequencing and variant calling). In another example, 2x76 base pairs has an instrument run time of 16.5 hours (slide 26, includes sequencing and variant calling). In ExiPrepTM96 Lite, different examples are provided that show the variability in instrument run time depending on the extracted material. One example shows a cfDNA extraction can take 40 minutes (Page 3), while a general DNA extraction can take 30 minutes (Page 3). When added together with the run times of Illumina, a total instrument run time of both instruments can fall between 16 and 22 hours. However, given the differences in the runs (1x36 vs 2x76 and 30 min vs 40 min), the instrument run time can be attributed to how much sequencing information a user wants to acquire and analyze or what kind of material is to be extracted. Therefore, it would be obvious for the instrument run time of the instant claim to be longer if sequence amplicons were longer than those of the reference claim or performing multiple runs on the 6 samples of the instant claim versus 4 samples of the reference claim. In addition, it would be obvious for the instrument run time of the instant claim to be longer depending on the material that is being extracted. This makes plain that the run time of 16 hours to 22 hours is a result of intended use of the system.
Furthermore, the recitation of “to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases” of claim 1 from U.S. Patent No. 11905558B2 has been interpreted as an intended use limitation. This does not further define the device because it does not claim further structural components specific to determining variant calls for 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. Therefore, this recitation does not speak on the equivalent intended use limitation of instant claim 1, as detailed in the claim interpretation section.
Finally, Claim 1 from U.S. Patent No. 11905558B2 does not teach a three-axis pipetting apparatus. However, this variation is made obvious in light of Fort. Fort teaches a three-axis pipetting apparatus in the form of a SCARA robotic arm with an attached pipetting apparatus (Pages 16-17, paragraph [0059]; Page 17, paragraph [0061]; Figure 5 and 6). This makes plain that a three-axis pipetting system is an obvious variant for the system.
Regarding instant claim 5, claim 3 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 1, wherein the raw read accuracy is at least 99.0%.
Regarding instant claim 6, claim 4 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 3, wherein the raw read accuracy is at least 99.1%.
Regarding instant claim 7, claim 5 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 1, wherein the performance is further characterized by a Q20 median read length of at least 100 bases and not greater than 450 bases.
Regarding instant claim 8, claim 6 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 5, wherein the Q20 median read length is at least 102 bases and not greater than 300 bases.
Regarding instant claim 9, claim 7 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 6, wherein the Q20 median read length is at least 104 bases and not greater than 300 bases.
Regarding instant claim 10, claim 8 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 1, wherein the performance is further characterized by a uniformity of at least 97%.
Regarding instant claim 11, claim 9 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 8, wherein the uniformity is at least 98%.
Regarding instant claim 12, claim 10 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 9, wherein the uniformity is at least 98.5%.
Regarding instant claim 13, claim 11 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 1, wherein the performance is further characterized by an average percent reads on target of at least 97%.
Regarding instant claim 14, claim 12 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 11, wherein the average percent reads on target is at least 98%.
Regarding instant claim 15, claim 13 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 12, wherein the average percent reads on target is at least 98.1%.
Regarding instant claim 16, claim 14 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 1, wherein the performance is further characterized by a total reads in a range of 13 million bases to 100 million bases.
Regarding instant claim 17, claim 15 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 14, wherein the total reads is in a range of 13 million bases to 60 million bases.
Regarding instant claim 18, claim 16 from U.S. Patent No. 11905558B2 teaches the sequencing system of claim 15, wherein the total reads is in a range of 14.5 million bases to 25 million bases.
Regarding instant claim 79, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. The analysis for claim 1 in this double patenting rejection also applies to claim 79.
Regarding instant claim 80, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. The analysis for claim 1 in this double patenting rejection also applies to claim 80.
Regarding instant claim 81, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. The analysis for claim 1 in this double patenting rejection also applies to claim 81.
U.S. Patent No. 11905558B2 does not require wherein the automated sequencing instrument comprises a flow cell having multiple lanes, wherein each lane is fluidically isolated from other lanes.
However, Nobile teaches an apparatus for sequencing comprising a flow cell (Page 12, paragraph [0069]; Figure 7A). Nobile further teaches wherein on sensor can have multiple flow cells (e.g. multiple lanes) (Pages 8-9, paragraph [0057]; Figure 4E), wherein each lane is fluidically isolated from other lanes (Pages 8-9, paragraph [0057]; Figure 4E). Thus, Nobile teaches the known techniques discussed above.
It therefore would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the claims of U.S. Patent No. 11905558B2 with the flow cell of Nobile. One of ordinary skill in the art would have been motivated to make this modification because the plurality of separate flow cells can use a single large sensor array (Nobile, Page 8-9, paragraph [0057]). In addition, it would have been obvious to one of ordinary skill in the art that the known components of Nobile could have been applied to the claims of U.S. Patent No. 11905558B2 with predictable results because the known components of Nobile predictably result in separate flow cell lanes for different samples.
Regarding instant claim 82, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. The analysis for claim 1 in this double patenting rejection also applies to claim 82.
U.S. Patent No. 11905558B2 does not require wherein the automated sequencing instrument comprises a fluidic circuit configured to deliver reagents through multiple lanes of a flow cell, wherein the fluidic circuit includes valves to control reagent flow to individual lanes.
However, Nobile teaches an apparatus for sequencing that comprises a fluidic circuit configured to deliver reagents through a flow cell, wherein the fluidic circuit includes valves to control reagent flow to the flow cell (Pages 3-4, paragraph [0032]; Figure 1A; Page 12, paragraph [0069]; Figure 7A). Nobile further teaches that the flow cell may have multiple lanes (Pages 8-9, paragraph [0057]; Figure 4E). Thus, Nobile teaches the known techniques discussed above.
It therefore would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the claims of U.S. Patent No. 11905558B2 with the fluidics system of Nobile. One of ordinary skill in the art would have been motivated to make this modification because this fluidics system allows the apparatus to deliver different reagents to the flow cell and sensor array in a predetermined sequence, for predetermined durations, at predetermined flow rates (Nobile, Page 3-4, paragraph [0032]). In addition, it would have been obvious to one of ordinary skill in the art that the known components of Nobile could have been applied to the claims of U.S. Patent No. 11905558B2 with predictable results because the known components of Nobile predictably result in controlled distribution of reagents through the fluidics system and flow cell.
Regarding instant claim 83, claim 1 from U.S. Patent No. 11905558B2 teaches a sequencing system comprising an automated sequencing instrument including a preparation deck to prepare one or more extracted polynucleotide samples for loading, a loading station to load the one or more modified extracted polynucleotides on a substrate, and a sequencing station, the sequencing station to detect nucleotide incorporation using ion-sensitive field effect transistors, the automated sequencing instrument adapted to determine variant calls for the one or more extracted polynucleotide samples with a performance of at least 98.5% raw read accuracy and a run time in a range of 5 hours to 14 hours to determine variant calls when sequencing 4 extracted polynucleotide samples using a targeted assay with one DNA pool per sample and an average amplicon size in a range of 100 to 120 bases. The analysis for claim 1 in this double patenting rejection also applies to claim 83.
U.S. Patent No. 11905558B2 does not require wherein the automated sequencing instrument comprises a heater configured to control temperature of reagents prior to delivery to a sequencing chip.
However, Nobile teaches an apparatus for sequencing that comprises a heater configured to control temperature of reagents prior to delivery to a sequencing chip on a flow cell (Page 10, paragraph [0063]). Thus, Nobile teaches the known techniques discussed above.
It therefore would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the claims of U.S. Patent No. 11905558B2 with the heater of Nobile. One of ordinary skill in the art would have been motivated to make this modification because heating the reagents before reading the flow cell allows the rate of flow and heat capacity of the fluid to be sufficient to remove excess heat generated by the sensors or analytical reactions (Nobile, Page 10, paragraph [0063]).
Response to Arguments
Applicant's arguments filed October 27th, 2025 have been fully considered but they are not persuasive. The arguments previously presented for the 103 rejection above are also applicable here, wherein Illumina I and ExiPrepTM96 Lite sufficiently make obvious the differences between claim 1 of the instant case and claim 1 of U.S. Patent No. 11905558B2.
Conclusion
All claims are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/ Examiner, Art Unit 1683
/Robert T. Crow/ Primary Examiner, Art Unit 1683