Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Detailed Action
Summary
This is the Non-Final Office Action based on application 17/027206 RCE filed 01/13/2025.
Claims 2-21 have been elected, and fully considered.
Claim 1 is cancelled.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/12/2025 has been entered.
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.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 non-obviousness.
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).
Claims 2-5, 7-8, 12-13, & 16-21 are rejected under 35 U.S.C. 103(a) as being unpatentable over LEAMON in US 20050130173 in view of HOLMES in US 20130079236 and further in view of JONES in US 20030175780.
With respect to Claims 2-4, LEAMON et al. teach of a method for performing rapid DNA sequencing(abstract). More specifically, LEAMON et al. teach of the method for sequencing nucleic acids further including:
Fragmenting large template nucleic acid molecules to generate a plurality of fragmented nucleic acids, and
Attaching one strand of a plurality of the fragmented nucleic acids individually to beads (bead portion before attachment reads on “particles lacking a polynucleotide) generate single stranded nucleic acids attached individually to beads (reads on polynucleotide- enhanced particles, after attachment and on target polynucleotide bound to target) (paragraph 0321, 0338).
This reads on “preparing a particle sample wherein the particle sample includes a mixture of polynucleotide-enhanced particles and of particles lacking a polynucleotide,” at a first location.
Delivering a population of the single stranded fragmented nucleic acids attached individually to beads to an array of at least 10,000 reaction chambers on a planar surface, wherein a plurality of the wells that comprise no more than a one bead with on single stranded fragmented nucleic acid (paragraph 0338), and
Introducing streptavidin coated beads susceptible to attraction by a magnetic field (referred to herein as "magnetic streptavidin beads") to the bead mixtures (paragraph 0184-0185), and of using an enrichment process to remove beads that do not have any DNA attached thereto (paragraph 0027, & Figure 7).
This reads on “forming a polynucleotide enhanced particle sample…by enriching the sample,” at a second location,
And loading a sequencing device with the polynucleotide enhanced particle sample (loading into the wells), and performing a sequencing reaction simultaneously on a plurality of the reaction chambers (paragraph 0338).
LEAMON teaches that the sequencing device has a solid support/chip which is coupled to a bundle of optical fibers (which read on “sensor array,” on sequencing device, as claimed) that are used to detect and transmit light product, and that the bundle is varied to match the number of individual reaction chambers (paragraphs 0211-0214, 0311, 0332, 0335-0336). These bundles read on the claimed, “array of sensors,” in the sequencing device.
This “loading,” of the sequencing device with the sample happens at a “third location.
Even further, LEAMON teaches of the instant device/method being an “integrated,” system/device for nucleic acid sample preparation, nucleic acid amplification, and DNA sequencing (paragraph 0016), and further in Figure 1 G. shows the integrated device used in the instant invention (see figure 1G and paragraph 0021).
Therefore, LEAMON teaches of the claimed three step process. LEAMON further teaches of different device locations where these process steps occur at, for example- part of a first step of the process, sample prep occurs on a gel,” gel isolation of library,”; part of the PCR process occurs at a second location on a template and in a thermocycler, and the sequencing steps happen at a third location when they are loaded in for sequencing after annealing.
Though the terms, “first location,” “second location,” and “third location,” can be interpreted broadly and LEAMON teaches of these as shown above, in case the delineation between multiple “locations,’ is unclear, HOLMES is used to remedy this. Further, LEAMON does not teach of the claimed, “array of sensors,” in the sequencing device, or the “loading centrifuge,” that the sequencing device is loaded on to and then centrifuged.
HOLMES is used to remedy this and teaches of systems and devices for multi analysis(abstract). HOLMES further teaches of the system containing a plurality of modules, and each individual module comprises a centrifuge (paragraph 0071). HOLMES teaches that the plurality of modules are mounted on a support structure and that the modules can be separate stations/locations (so an integrated device having separate modules or locations as instantly claimed).
The modules/separate locations in HOLMES include a sample preparation station (which would be the “first location,” claimed instantly in the preparing step), an assay station (which would be the instant forming step, “second location,” instantly claimed), and/or a detection station (which would read on the instantly claimed, “third location,” wherein sensors are located for sensing/detecting) (paragraphs 0008, 0011, 0013, & 0014).
HOLMES further teaches that the sample preparation can involve preparation of particles (paragraph 1364, and also can involve samples (or particle enrichment) (paragraph 0362, 1087, 1557, 1644). HOLMES further teaches that the sample preparation modules can include multiple sample preparation stations (which would then amount to even more than the instantly claimed three locations).
HOLMES further teaches that one of the modules can be a nucleic acid sequencing module (paragraph 0069), and that the cartridges of the modules can contain multiple (an array of) sensors (paragraph 0318 & 0315-0318, 0368, 0337).
HOLMES teaches that
HOLMES teaches that the system can include a biochip microarray for the sequencing (paragraph 1559, 1587, 1585) for sequencing, and that the sequencing device/module is centrifuged (paragraph 1171).
Therefore, HOLMES makes the instant claiming of a first location that is for preparing particle sample, a second location for enriching the sample, and a third location for sequencing and sensing/detecting obvious to one of ordinary skill in the art.
It would have been obvious to one of ordinary skill in the art to use the device and processing in modules/distinct locations as is done in HOLMES for the method of LEAMON due to the problems with known techniques of sample processing and diagnosis in that that diagnosis is delayed since devices are not portable and easy to use and due to the need in the art for an integrated portable/point of care system that can perform the multiple parts of most chemical/diagnostic assays (HOLMES, paragraphs 0003-0008, & 0308).
Further, it would have been obvious to one of ordinary skill in the art to use the array of sensors in a “Sequencing device,” as claimed due to the advantage this offers for detecting any chemical, audio, electromagnetic or other signal associated with the device and due to the advantage this would have for nucleic acid sequencing and amplification (paragraph 0368, 0318, 1662-1663).
LEAMON and HOLMES do not teach of loading a sequencing device into a centrifuge, nor do they teache of the sequencing device having an array of sensors on a chip.
JONES is used to remedy this. JONES teaches of a method and devices which are used to sequence DNA (abstract). JONES further teaches of the device being automated and integrated and that DNA segments are immobilized at site of a microtiter support or chip array (paragraph 0022, 0131). JONES further teaches of using chips and chip holders and supports and a stage the chips are on (paragraph 0034, 0130-0131, 0116, 0020, 0022 Fig. 9). The chips can be considered sequencing devices (this is shown in the instant application specification, paragraph 0119), and that transfer of reagents happens through centrifugal force (so the disk/turntable the chips are loaded onto can be considered a “loading centrifuge,” as claimed) (paragraph 0034, 0133, 0024, Figure 9).
JONES further teaches of the chip having a large number of sites or addresses, which will allow for the amplification of say 90,0000 DNA segments (so there is an array of sensors) (paragraph 0118, 0114, 0022). JONES even further teaches that the chip can consist of charged couple device (CCD), which contains a plurality of “pixels,” which can be considered and “array,” of sensors and therefore reads on the instantly claimed array of sensors on a chip (paragraph 0107).
It would have been obvious to one of ordinary skill in the art to load chips/ “sequencing devices,” into a centrifuge/rotator due to the advantage that rotating/centrifuging chips would offer for allowing fluid to flow across the array (JONES, paragraph 0024, 0034, 0131) and further it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use an array of sensors on the chip as is done in JONES in the methods and devices of LEAMON and HOLMES, due to the advantage these pixel sensors have in quantitatively detecting images of the distributed sample or reaction and due to the advantage that pixel sensors offer for analyzing a large amount of samples in parallel on a small chip (JONES, paragraph 0107).
With respect to Claim 5, LEAMON et al. teach of using PCR (paragraph 0018).
With respect to Claim 7, LEAMON et al. teach of using a thermal cycler (paragraph 0150, 0164-0165, 0590, 0626-0629 and Figure 6 B).
With respect to Claim 8, LEAMON et al. teach of introducing streptavidin coated beads susceptible to attraction by a magnetic field (referred to herein as "magnetic streptavidin beads") to the bead mixtures in this enriching step (paragraph 0184-0185).
LEAMON et al. further teach of applying a magnetic field (represented by a magnet) is applied near the reaction mixture, which causes all the "magnetic streptavidin beads/amplicon bound bead complexes" to be positioned along one side of the tube most proximal to the magnetic field. Magnetic beads without amplicon bound beads attached are also expected to be positioned along the same side. Beads without amplicons remain in solution. The bead mixture is washed and the beads not immobilized by the magnet (i.e., the empty beads) are removed and discarded. In step 6, the extended biotinylated primer strand is separated from the amplicon strand and the mixture is then washed and the supernatant, containing the amplicon bound beads, is recovered while the now unbound magnetic beads are retained by a magnetic field. The resultant enriched beads may be used for DNA sequencing (paragraph 0185).
With respect to Claim 12, LEAMON et al. teach of the claimed invention as shown in the above rejection. LEAMON et al. do not teach of controlling humidity and temperature. HOLMES et al. however teach of a system wherein there are sensors in the integrated device for temperature and humidity (paragraph 0336, 0376). It would have been obvious to one of ordinary skill to use a humidity and temperature sensor and enclose device parts in integrated housing due to the advantage this offers in allowing for temperature and humidity control for reactions (HOLMES, paragraph 0376).
With respect to Claims 13, LEAMON et al. teaches of the claimed invention as shown in the above rejection. LEAMON and PIEPENBURG et al. do not teach of sanitizing with a US source. HOLMES et al. is used to remedy this and more specifically teaches of sterilization by UV radiation, specifically of fluid handling components. It would have been obvious to one of ordinary skill in the art to sterilize as is done in HOLMES in the methods of LEAMON due to the advantage this would offer with respect to reusability of the device (HOLMES, paragraph 1108, 0335).
With respect to Claims 16, LEAMON et al. teach of the claimed invention as shown in the above rejection. LEAMON et al. teach of the device including a CCD camera that is used for detection of the picotiter plate (paragraph 0020, 0723-0724, 0726, 0812), and also of an associated pipetting system (paragraph 0810). LEAMON does not call out calibrating position of pipette system using a vision system.
HOLMES et al. is used to remedy this. HOLMES et al. teach that the camera(vision system) is used to detect images and determine whether device components are positioned properly or where device components like the pipettes are positioned(paragraph 1238). It would have been obvious to one of ordinary skill in the art to use a camera/vision system to determine positioning of device components due to the advantage this offers with respect to adjust components locations if needed (HOLMES, paragraph 1238).
With respect to Claims 17, LEAMON teaches of the claimed invention as shown in the above rejection. LEAMON et al. teach of the device including a CCD camera that is used for detection of the picotiter plate (paragraph 0020, 0723-0724, 0726, 0812), and also of an associated pipetting system (paragraph 0810). LEAMON does not call out calibrating position of pipette system using a vision system.
HOLMES et al. is used to remedy this. HOLMES et al. teach that the camera (vision system) is used to detect images and determine whether device components are positioned properly or where device components like the pipettes are positioned (paragraph 1238). It would have been obvious to one of ordinary skill in the art to use a camera/vision system to determine positioning of device components due to the advantage this offers with respect to adjust components locations if needed.
With respect to Claim 18, LEAMON teach of amplifying and emulsion (paragraph 0018).
With respect to Claim 19, LEAMON teach of amplifying and emulsion (paragraph 0018). HOLMES teaches that one of the modules can be a nucleic acid sequencing module (paragraph 0069). HOLMES further teaches of the centrifuge having a bucket or buckets that can hold the modules and of rotating the modules in the buckets/centrifuging/spinning the buckets holding the modules (paragraph 1157, 1162, 1171, & 1158-1161 among others). HOLMES further teach of the multiple claims stations (paragraphs 0008, 0011, 0013, & 0014). This makes the claimed centrifuging after amplifying the emulsion obvious to one of ordinary skill in the art.
With respect to Claim 20, HOLMES further teaches of the centrifuge having a bucket or buckets that can hold the modules and of rotating the modules in the buckets/centrifuging/spinning the buckets holding the modules (paragraph 1157, 1162, 1171, & 1158-1161 among others) and that each modules can have a centrifuge (paragraph 0071).
With respect to Claim 21, HOLMES further teaches of the centrifuge having a bucket or buckets that can hold the modules and of rotating the modules in the buckets/centrifuging/spinning the buckets holding the modules (paragraph 1157, 1162, 1171, & 1158-1161 among others) and that each modules can have a centrifuge (paragraph 0071). HOLMES further teaches of depositing sample in the sequencing device containers (paragraph 0371, 0303).
Claims 6 & 9-11 are rejected under 35 U.S.C. 103(a) as being unpatentable over LEAMON in US 20050130173 in view of HOLMES and further in view of JONES in US 20030175780 and further in US 20130079236 of PIEPENBURG in US 20080293045.
With respect to Claim 6, LEAMON, HOLMES, and JONES teach of the claimed invention as shown above. They do not teach of the use of RPA.
PIEPENBURG teaches of a method for recombinase polymerase amplification (RPA)(abstract). PIEPENBURG further teach that the RPA is fully integrated (paragraph 0012, 0413, 0806, Figure 63, 0978). PIEPENBURG et al. further teach of an integrated device with more than 3 “locations,” where the sample can be prepared/placed (labeled- “Sample), and where other reaction parts can happen such as amplification control and flow control (See Figure 63 A-C, paragraph 0089, 0443).
As applicant has instantly claimed the three different locations broadly and has not specified other reaction requirements or device specifications of these locations, through broadest reasonable interpretation, this device reads on the claimed “locations,”. It would have been obvious to one of ordinary skill in the art filing date of to use the device have integrated components/parts for RPA for PIEPENBURG in the method of LEAMON, HOLMES, and JONES due to the shown effectiveness of this technique and due to the need in the art for improvements on PCR (PIEPENBURG, paragraph, 0443, 0002-0014).
PIEPENBURG et al. further teach of using RPA (abstract). It would have been obvious to one of ordinary skill in the art to use RPA as is done in PIPENBURG in the methods of LEAMON, HOLMES, and JONES due to the need in the art to integrate RPA reactions (PIPENBURG, paragraph 0012-0013).
With respect to Claim 9, LEAMON and HOLMES teach of the claimed invention as shown above. They do not teach that a chip is loaded in the method. PIEPENBURG et al. teach that a chip can be used/loaded for this method (paragraph 0243, 0260).
It would have been obvious to one of ordinary skill in the art to load chips as is done in PIPENBURG in the methods of LEAMON and HOLMES due to the advantage chips offer for immobilizing compounds (PIPENBURG, paragraph 0243).
With respect to Claim 10, LEAMON et al. teach of detecting sequencing byproducts (paragraph 0247, 0249 0338, 0814, Claim 7). HOLMES also teaches of detection of products of amplification (this can be considered byproducts of sequencing)(paragraph 0916, 1453).
With respect to Claim 11, LEAMON et al. teach of enriching including changes in pH (paragraph 0185).
Claims 14-15 are rejected under 35 U.S.C. 103(a) as being unpatentable over LEAMON in US 20050130173 in view of HOLMES in US 20130079236 and further in view of JONES in 20030175780 and further in view HOUDE in US 20040002126.
With respect to Claims 14, LEAMON and HOLMES and JONES et al. teach of the claimed invention as shown in the above rejection. LEAMON and HOLMES et al. do not teach of filtering the air supply of system. HOUDE is used to remedy this.
HOUDE et al. teach of a system for detecting microorganisms in a liquid environment(abstract), and more specifically teach of the device being an integrated system (paragraph 0006), and of using HEPA filter to filter the air. It would have been obvious to one of ordinary skill in the art to use a HEPA filter as is done in HOUDE in the methods of LEAMON and HOLMES and JONES due to prevent the passage of viruses and other microorganisms (HOUDE, paragraph 0067).
With respect to Claims 15, LEAMON and HOLMES et al. teach of the claimed invention as shown in the above rejection. LEAMON and HOLMES et al. do not teach of filtering the air supply of system using HEPA filter. HOUDE is used to remedy this.
HOUDE et al. teach of a system for detecting microorganisms in a liquid environment(abstract), and more specifically teach of the device being an integrated system (paragraph 0006), and of using HEPA filter to filter the air. It would have been obvious to one of ordinary skill in the art to use a HEPA filter as is done in HOUDE in the methods of LEAMON and HOLMES due to prevent the passage of viruses and other microorganisms (HOUDE, paragraph).
Response to Arguments
Applicant's arguments filed 12/12/2025 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues about the LEAMON reference and specifically argues that LEAMON doesn’t teach of the sequencing device having an array of sensors on a chip.
With respect to this. The examiner points out that “sequencing device,” can be interpreted very broadly, and the “sequencing,” does not mean that the device actually has to be used for sequencing, it is just what applicant calls it, so LEAMON does in fact teach of a sequencing device as shown above. Further—the examiner notes that a 103 rejection was made, so LEAMON does not need to teach of each and every aspect of what is claimed.
Applicant further argues that the JONES reference also does not teach of the claimed array of sensors on a chip. The examiner disagrees. JONES teaches that the chip can consist of charged couple device (CCD), which contains a plurality of “pixels,” which can be considered and “array,” of sensors and therefore reads on the instantly claimed array of sensors on a chip (paragraph 0107).
Applicant argues that the JONES references requires “automated detection,” and that this suggests that an external detection apparatus such as a scanner or imaging system may be used to obtain results as reactions occur and there therefore, there is not suggestions of on-chip signal detection. The examiner disagrees again, since the pixels taught by JONES can be considered through broadest reasonable interpretation as an array of sensors on the chip. Further, though an “on-chip,” detection step is not claimed, JONES is considered to teach of this as well.
Applicant also argues that JONES and LEAMON require different detection mechanisms, specifically that LEAMON is designed around remote CCD and JONES does not teach that chips can be outfitted with sensor elements. Again, the examiner disagrees. Both JONES and LEAMON deal with CCD detection and as shown above, JONES teaches of the pixels being on the chip.
Further, JONES gives good reason for combination with LEAMON. Specifically, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use an array of sensors on the chip as is done in JONES in the methods and devices of LEAMON and HOLMES, due to the advantage these pixel sensors have in quantitatively detecting images of the distributed sample or reaction and due to the advantage that pixel sensors offer for analyzing a large amount of samples in parallel on a small chip (JONES, paragraph 0107) (which would give a distinct advantage over any remote CCD/pixel sensing detection in LEAMON).
Therefore, the examiner disagrees that LEAMON would be fundamentally altered and that modifying or incorporating a sensor array on a chip would result in a significant departure from its core detection strategy. This is especially true with respect to the very broad instant claimed language.
It is further noted, that applicant hasn’t provided any arguments with respect to the HOLMES reference, which was used in both the instant and prior office actions.
All claims remain rejected.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758