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 .
It is noted for the record that this Application has been transferred to Examiner Christine Jones in Art Unit 1682.
Status of the Claims
It is acknowledged that Applicant corrected the listing of claims in the reply, responsive to the Notice of Non-Compliant Amendment mailed March 30, 2026. It is acknowledged that applicant amended claims 1-23 (including amendments to claim language in claims 1,2, 4, 7, 8, 10, 12-20), added new claims 21-23, and withdrew claims 4 and 21-23 in the response filed May 29, 2026.
Claims 1-23 are currently pending. Claims 1-3 and 5-10 are currently under examination.
Summary of Response to Amendment
Any further amendments to the claims should have their status indicated as described in 37 C.F.R. 1.121.
This action is in response to the papers filed May 29, 2026. Applicant's remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
As a result of the amendments to the claims, prior objections, Improper Markush rejections, and the rejections under 35 U.S.C. 112(b) have been withdrawn or modified and new rejections under 35 U.S.C. 112(b) have been added to address indefiniteness of amended claim limitations.
As a result of the amendment of claim 1 to incorporate limitations of the original claim 4 (“at least one third functional chamber for RNA extraction containing an RNA capture reagent, wherein the RNA capture reagent in one of the third functional chamber is coated with an RNA probe of SEQ ID NO. 13, and the RNA capture reagent is a magnetic bead”), the scope of the invention has changed. For example, the claims now require the combination of the above-described limitation (from the original claim 4) and the limitations of claim 9. This change in scope has necessitated 35 U.S.C. 103 rejections under new combinations of references.
These rejections, as well as responses to Applicant’s arguments, are set forth below.
Priority
The effective filing date of the instant application is considered to be the actual filing date of January 20, 2022.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With regard to claim 7, the phrase “set above both sides of the micropump and the microvalve” renders the claim as indefinite because the metes and bounds of “set above both sides” are not defined. The micropumps and microvalves of the instant specification are three-dimensional objects with undefined axes (par. 67, Figure 6A). The term ‘above both sides’ does not adequately describe the location of the recited magnets because the micropumps and microvalves are not described as having only two sides, and because the term ‘above’ is a relative term without a clear and limiting definition in either the claims or the specification. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Regarding claim 10, the claim recites “the device of claim 12…,” but claim 12 is directed to a method with no recited device. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
If the claim is intended to recite “the device of claim 9,” as set forth in the original claims, the language must be amended to reflect that dependency. For the purposes of compact prosecution, claim 10 is interpreted to be dependent on claim 9.
Response to Arguments
In the response, Applicant amended claim 7 to replace the word “on” with the word “above” and argued that the amended claim was in compliance with written requirements.
The response has been carefully considered, but is not found persuasive. The newly substituted preposition is also indefinite, and therefore the claim remains unclear in scope. A modified rejection of claim 7 under 35 U.S.C. 112(b) is set forth above. To clarify further, the term ‘above’ is relative because the plane of reference has not been sufficiently described. Taking Fig. 6A as an example, par. 67 shows the pumps P1-P4 relative to several chambers in the microfluidic chip. Here, the magnets’ positions are not shown, and the specification allows that they may be positioned ‘above and aligned with micropumps and microvalves.’ However, neither the claims nor the specification require any particular frame of reference – the terms above/below may be used to describe positions along an axis according to the viewing frame of reference of Fig. 6A, or they may describe an axis which is perpendicular or otherwise skewed relative to axis of the viewing frame of reference. Furthermore, the pumps are shown in Fig. 6A as flat circles (potentially corresponding to flattened cylinders in an actual microfluidic chip), and therefore do not have only two sides, as required by the language “both sides” in claim 7. Therefore, claim 7 remains rejected under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-3, 5, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Broughton et al. (WO 2020/257356 A2) in view of Yuan et al. (CN111893213A, 2020; with English translation), Chen et al. 2020 (CN111778359A, 2020), and Adams et al. (published March 10, 2015; Adams et al. ACS Appl Mater Interfaces. 2015 Mar 25;7(11):6062-9).
Broughton et al. teaches “a microfluidic cartridge for detecting a target nucleic acid comprising: an amplification chamber fluidically connected to a valve; a detection chamber fluidically connected to the valve, wherein the valve is connected to a sample
metering channel; a detection reagent chamber fluidically connected to the detection chamber via a resistance channel---” (see Broughton pg. 41, [0273]). In Broughton et al., the cartridge is also referred to as a “chip”. Broughton further teaches the device was for SARS-CoV-2 detection (pg.7, [0030]).
Regarding claim 1, Broughton et al. teaches the microfluidic chip comprises a plurality of functional chambers (pg. 1, [0003] and Fig 5, e.g.), a flow control module for transporting the sample (pg. 1, [0003]) and a temperature control module (pg. 4, [0019], continued on pg.5) for controlling temperature (pg. 172, [0476]). The reference refers to a flow control module as a sample metering channel and refers to controlling temperature as thermoregulation. Broughton et al. teaches the chambers were used for loading a sample or reagent (pg. 359, [0891]) and the chambers comprised a LAMP composition (pg. 5, [0022], last sentence). The reference refers to a LAMP composition as LAMP reagents. Broughton further teaches the microfluidic chip comprises a flow control module for transporting the sample, the reagent, the buffer, or the mixture thereof between the chambers, and a temperature control module for controlling and/or keeping a temperature during a reaction (pg. 194, [0524] continued from pg. 193).
Broughton et al. teaches the automated extraction of RNA (par. 803; Figure 107D), multiple chambers for sample preparation (par 464), and specific chambers for sample extraction (par. 644). This is interpreted to comprise the embodiment “at least one third functional chamber for RNA extraction” as required by the claim.
Regarding claim 2, Broughton et al. teaches wherein the temperature during the reaction of LAMP was in a range of 60ºC to 65ºC (pg. 271, [0664]).
Regarding claim 3, Broughton et al. teaches wherein the chambers further comprise at least one second functional chamber for loading the sample and/or conducting viral lysis (Pg. 2, [0006]; par. 525, Fig. 46).
Regarding claim 5, Broughton et al. teaches wherein the temperature control
module comprises: a thermoelectric cooler, a relay configured to turn on the thermoelectric cooler for heating or to turn off the thermoelectric cooler for cooling, and a thermocouple (Fig.135 and Fig. 135 description, [0518]). In Broughton et al., a thermoelectric cooler is referred to as a “heater”, a relay is referred to as a “power control”, and a thermocouple is referred to as “a temperature feedback or a PID loop” [0518].
Regarding claim 6, Broughton et al., teaches wherein the microfluidic chip
further comprises: a fourth functional chamber having a micropump for mixing ([0465] continued from pg.167), and a microvalve arranged between any two adjacent ones of the chambers ([0474] and pg.168, [0465], continued from pg.167).
Regarding claim 9, Broughton et al. teaches that the LAMP composition (par. 50) may further comprise a fluorescent dye (par. 367, 745), and that the integrated microfluidic device further comprises an optical detection module for exciting the fluorescent dye to generate a fluorescent signal and detecting the fluorescence signal (pg. 890).
Regarding claims 1 and 2, Broughton et al. does not teach (i) wherein the LAMP composition in each of the first functional chambers comprise primers of: SEQ ID Nos. 1 to 4.
However, Yuan et al. (CN111893213A, 2020) teaches “---specific screening and identification primers, identification methods and identification kits for screening and identifying novel coronaviruses.” (pg. 1, [0002]).
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Regarding claims 1 and 2, Yuan et al. teaches (i) LAMP primers that comprise SEQ ID No.1 (see Example 1, Page 9, and Table 2, nCoV-ORF1ab-F34). Yuan refers to the RdRp gene as the ORF1ab gene (pg. 3, [0011]). Therefore, the primer taught by Yuan et al. can amplify the same target region of the RdRp gene as SEQ ID No. 1 of the claimed invention. The alignment of SEQ ID No.1 and the corresponding primer taught by Yuan is shown above.
Yuan further teaches “It can be seen that how to obtain a SARS-CoV-2 nucleic acid detection method with simple equipment, easy operation, high sensitivity and specificity is an urgent problem that needs to be solved in the fight against the new coronavirus epidemic. In order to solve the problems in the prior art, the inventors conducted repeated experiments and explorations, compared the published full-length sequences of SARS-Co V2, SARS-Co V, MERS-CoV and other SARS-like viruses, selected the S gene and ORF1ab gene sequence specific regions of the SARS-Co V2 virus as detection targets, designed a set of LAMP primers with high sensitivity and good specificity, and explored the LAMP amplification system and procedure that can simultaneously detect the S gene and ORF1ab gene specific regions, and established a kit and method that can quickly, simply, highly sensitive and highly specific detect SA RS-Co V2.” (pg. 3, [0009]-[0011].
One of ordinary skill in the art, upon reading Yuan, would have recognized the desirability of trying the RdRp gene primers comprising SEQ ID No.1 in the LAMP composition taught by Broughton to provide primers that have high sensitivity and specificity ([0009]).
It would have been prima facie obvious, before the effective filing date of the claimed invention to have modified the LAMP composition taught by Broughton so as to include the RdRp primer comprising SEQ ID No.1 taught by Yuan because Yuan teaches that the primer was designed to target ORF1ab gene sequence- specific regions of the SARS-CoV2 virus in LAMP with high sensitivity and good specificity (pg. 3 [0011]).
Thus, it would have been obvious to one of ordinary skill in the art to try the RdRp gene primers taught by Yuan et al. comprising SEQ ID No.1 in the LAMP composition taught by Broughton to provide excellent performance in clinical detection, with a clinical sample detection compliance rate of 100 % (pg. 7 [0043]).
Regarding claims 1 and 2, the combined teachings of Broughton et al. in view of Yuan et al. does not teach (i) wherein the first functional chambers contain primers of SEQ ID Nos. 2 to 4.
However, Chen et al. 2020 teaches “--- an integrated microfluidic LAMP system for rapidly detecting a target nucleic acid fragment. One subject of the invention is to provide a kit for rapidly detecting a target nucleic acid fragment, the target nucleic acid fragment comprising a purification recognized fragment and an amplification specific fragment, which kit comprises: a magnetic bead linked to an oligonucleotide being able to hybridize to the purification recognized fragment; an inner primer pair and an outer primer pair being specific to the amplification specific fragment and suitable for loop-mediated isothermal amplification; and reagents for loop-mediated isothermal amplification.” (see Summary of the Invention, [0009] – [0013]).
Regarding claim 1 and claim 2, Chen et al. 2020 teaches (i) RT-LAMP primers for the RdRp gene (pg.19 [0114]) that comprise SEQ ID No. 2 and SEQ ID No.4. Chen et al. 2020 further teaches a primer that is functionally equivalent to SEQ ID No. 3. It is therefore inherent that this primer will amplify the same target region of the RdRp gene as SEQ ID No. 3 (pg.19 [0114]). These primers are shown in rows 2 – 4 of Table 5 of the original document (pg. 13, continued on page 14, [0110]).
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A copy of this table is shown below:
The alignments of SEQ ID Nos. 2, 3 and 4 of the instant invention to the corresponding primers taught by Chen et al 2020 are shown below:
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Chen et al. 2020 further teaches “The sequences of the fragments used for detection on the RdRp gene and N gene need to be different from the gene sequences of other pathogens (cannot form complementary binding), and the fragments used for
detection on these two genes need to be suitable for LAMP amplification. Not all unique fragments on the RdRp gene and the N gene can be used for LAMP amplification.
Among them, the unique fragments on the RdRp gene and the N gene refer to the fragments that do not or are not easily complementary to the genes of other pathogens, also known as specific fragments. During the research process of the present inventors, some specific fragments were found on the RdRp gene, and some specific fragments were also found on the N gene. The inventors designed LAMP primers for the above-mentioned specific fragments and verified the amplification effect through a large number of experiments. The results showed that: only a specific fragment on the RdRp gene can be successfully amplified by LAMP (we call this fragment the RdRp gene detection target fragment), and the first primer combination of this scheme is designed to achieve the detection of the RdRp gene.” (pg. 5, 172-185).
One of ordinary skill in the art, upon reading Chen et al. 2020, would have recognized the desirability of utilizing the RdRp gene primers comprising SEQ ID Nos. 2-4 in the LAMP composition taught by Broughton et al. in view of Yuan et al. to provide primers that are different from the gene sequences of other pathogens and also suitable for LAMP amplification.
It would have been prima facie obvious, before the effective filing date of the claimed invention to have modified the LAMP composition taught by Broughton et al. in view of Yuan et al. so as to include the RdRp primers taught by Chen et al. 2020 comprising SEQ ID Nos. 2-4 because Chen et al. 2020 teaches that the primers amplify a unique fragment of the RdRp gene and are also suitable for LAMP (pg. 5, 176-179).
Thus, it would have been obvious to one of ordinary skill in the art to try the RdRp gene primers taught by Chen et al. 2020 comprising SEQ ID Nos. 2-4 in the LAMP composition taught by Broughton et al. in view of Yuan et al. to provide a LAMP composition that can successfully amplify the RdRp gene fragment (pg. 5, 182-184).
Regarding claim 1, Broughton, Yuan, and Chen 2020 do not explicitly teach an RNA capture reagent contained in a chamber for RNA extraction, wherein the RNA capture reagent is coated with an RNA probe and wherein the RNA capture reagent is a magnetic bead.
Adams teaches RNA capture reagents, wherein the RNA capture reagents are coated with RNA probes, and wherein the RNA capture reagent is a magnetic bead (pg. 6062, par. 1-2 of Introduction).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Broughton, Yuan, and Chen 2020 with the teachings of Adams. One would have been motivated to do so in order to purify nucleic acid biomarkers from patient samples which may contain inhibitory contaminants (pg. 6062, col. 1, par. 1). One would have had reasonable expectation of success because Broughton teaches the use of similar magnetic bead systems within a microfluidic device (par. 519) and because Adams demonstrates that pathogen- and sequence- specific probes coated on magnetic beads successfully enrich viral RNA (pg. 6067, col. 1, par. 3).
Regarding claim 1, Broughton, Yuan, and Adams do not teach an RNA probe of SEQ ID NO. 13. However, Adams et al. does teach the use of surface-functionalized magnetic beads which enrich target RNA by a coating of probes complementary to an appropriate region of a target viral gene (pg. 6063, col. 1, par. 2-3).
Chen et al. 2020 teaches the targeting of the RdRp gene of SARS-CoV-2 using probes and primers specific to the sequence shown below (Chen: Fig. 1):
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Chen et al. 2020 does not specifically teach a probe of SEQ ID NO. 13. However, SEQ ID NO. 13 is complementary to a sequence within Chen’s target region that would be amplified by the LAMP primers. The grey dashed-line box in the above figure indicates that region. For further clarity, Chen’s region of interest contains a sequence ACATACAACGTGTTGTAG which would hybridize to a sequence containing the reverse complement sequence CTACAACACGTTGTATGT. Said reverse complement sequence is the same as a sequence of SEQ ID NO. 13, as shown in the alignment below:
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It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to use magnetic beads of Adams, coated in probes specific to the RdRp sequence of SARS-CoV-2 recited in Chen 2020, for timely detection of COVID-19 infection and transmission (pg. 1, last par.). One would have had reasonable expectation of success because Adams demonstrates that pathogen- and sequence- specific probes coated on magnetic beads successfully enrich viral RNA (pg. 6067, col. 1, par. 3), and Chen demonstrates sequences of SARS-CoV-2 for design of said probes were known (Chen: Fig. 1, shown above). Further, given that there are a finite number of solutions (i.e. a finite number of probe sequences suitable for enrichment of relevant target SARS-CoV-2 RNA) and there is no evidence of unexpected results, it would have been obvious to a person with ordinary skill in the art to try a probe corresponding to a sequence of SEQ ID NO. 13. The design and optimization of such probes would be conventional, using publicly available knowledge of the appropriate target sequence and facilitated by routinely used tools such as NCBI’s BLAST (Chen 2020: par. 83, ln. 487-488).
Claim(s) 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Broughton et al. (WO2020257356A2) in view of Yuan et al. (CN111893213A, 2020), Chen et al. 2020 (CN111778359A, 2020), and Adams (ACS Appl Mater Interfaces. 2015 Mar 25;7(11):6062-9), as applied to claims 1 and 6 above, and further in view of Tanner et al. (US10968493B, 2020) and Chen et al. 2012 (US 2012/0141989A1).
Broughton, Yuan, Chen 2020, and Adams teach the limitations of claims 1 and 6, as discussed above.
Regarding claim 7, Broughton, Yuan, Chen 2020, and Adams do not teach wherein the flow control module is a magnetic control module comprising a permanent magnet and an electromagnet respectively set on both sides of the micropump and the microvalve.
However, Chen et al. 2012 teaches “--- an integrated microfluidic LAMP system for rapidly detecting a target nucleic acid fragment.” (pg. 2 [0009]). Chen et al. 2012 further teaches “A microfluidic control module comprising two sets of pneumatic micro-pumps with three PDMS membranes and a floating block structure is used to precisely transport biosamples and to prevent backflow. The time-phased deformation of successive PDMS membranes underneath the microchannel generates a peristaltic effect that drives the liquid along the microchannel when the compressed air fills up the interconnected air chambers sequentially. Two essential parameters including the driving frequency (fd) of the electromagnetic valve (EMV) and the applied compressed air pressure can be used to control the flow pumping rate for sample transport.” (pg. 6 [0073]). Chen et al. 2012 further teaches “The microfluidic chip also known as a lab-on-a chip, and the use of microfluidic chip for biomedical detection or analysis has advantages of reduced manual error, increased system stability, reduced energy consumption and reduced amount of samples, reduced the capacity and time-saving.” (pg.3 [0043]).
Regarding claim 7, Chen et al. 2012 teaches the flow control module is a magnetic control module comprising a permanent magnet and an electromagnet respectively set on both sides of the micropump and the microvalve (pg. 4 [0045]). Chen et al. 2012 refers to a flow control module as a microfluidic control module and the electromagnet as a magnetic stage.
Chen et al. 2012 further teaches “Despite the attractiveness of the LAMP technique, there are still some potential draw backs in developing rapid diagnostic devices utilizing these state-of-the-art laboratory techniques.” --- More importantly, bio-sample pre-treatment processes prior to analysis such as DNA/RNA extraction are always required and need to be performed by experienced personnel. Therefore, there is a great need to develop an integrated sample-to-answer system to carry out all the diagnostic processes with a high specificity and sensitivity, in an automatic manner.” (pg. 1 [0008], cont’d on pg.2).
One of ordinary skill in the art, upon reading Chen et al. 2012 , would have recognized the desirability of trying a magnetic control module comprising a permanent magnet and an electromagnet respectively set on both sides of the micropump and the microvalve to control the flow pumping rate for sample transport.
It would be obvious before the effective filing date of the instant application to have modified the method taught by Broughton, Yuan, Chen 2020, and Adams to have used the magnetic control module comprising a permanent magnet and an electromagnet respectively set on both sides of the micropump and the microvalve because taught by Chen et al. 2012 because Chen et al. 2012 teaches the driving frequency (fd) of the electromagnetic valve (EMV) is essential to control the flow pumping rate for sample transport (pg. 6 [0073]).
Thus, it would have been obvious to one of ordinary skill in the art to try the magnetic control module comprising a permanent magnet and an electromagnet respectively set on both sides of the micropump and the microvalve to further develop an integrated sample-to-answer system to carry out all the diagnostic processes with a high specificity and sensitivity, in an automatic manner (pg.1 [0008], cont’d on pg.2).
Regarding claim 8, Broughton et al. teaches the flow control module is a pneumatic combined electromagnetic control module (pg. 171 [0474]) comprising a vacuum pump (pg. 44 [0298] and Fig. 127A). In Broughton et al. a vacuum pump is referred to as a pump. Broughton et al. further teaches the flow control comprises a compressor (pg. 358 [0887] and Fig. 127A). Broughton et al. refers to a compressor as “--- a pneumatic pumping manifold that can apply pressure to individual cartridge chambers”. (pg. 358 [0887] and Fig. 163).
Broughton et al. further teaches wherein the microfluidic chip further comprises an air hole for air flow controlled by the pneumatic combined electromagnetic control module. (pg. 358 [0887] and Fig. 163). In Broughton et al., and air hole is referred to as a port.
Regarding claim 8, Broughton, Yuan, Chen 2020, and Adams do not teach wherein
the flow control module comprises an electromagnetic valve.
However, Chen et al. 2012 teaches the flow control module comprises an electromagnetic valve (pg. 6 [0073]).
One of ordinary skill in the art, upon reading Chen et al. 2012 , would have recognized the desirability of trying wherein the flow control module comprises an electromagnetic valve to control the flow pumping rate for sample transport.
It would have been prima facie obvious, before the effective filing date of the instant application, to have modified the method taught by Broughton, Yuan, Chen 2020, and Adams to have used an electromagnetic valve because Chen et al. 2012 teaches “Two essential parameters including the driving frequency (fd) of the electromagnetic valve (EMV) and the applied compressed air pressure can be used to control the flow pumping rate for sample transport.” (pg. 6 [0073]).
Thus, it would have been obvious to one skilled in the art to have the flow control module comprise an electromagnetic valve other to achieve reduced manual error, increased system stability, reduced energy consumption and reduced number of samples, reduced the capacity and time-saving. (pg.3 [0043]).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Broughton et al. (WO2020257356A2), Yuan et al. (CN111893213A, 2020), Chen et al. 2020 (CN111778359A, 2020), and Adams (ACS Appl Mater Interfaces. 2015 Mar 25;7(11):6062-9), as applied to claims 1 and 9 above, and further in view of Tan et al. (WO 2008/124104 A1).
Broughton, Yuan, Chen 2020, and Adams teach the limitations of claims 1 and 9, as discussed above.
Regarding claim 10, Broughton et al. teaches wherein the optical detection module comprises a light source ([0896] and FIG. 168). Broughton et al. refers to the light source as light-emitting diodes.
Regarding claim 10, Broughton, Yuan, Chen 2020, and Adams do not teach wherein the optical detection module comprises an objective lens, and a photomultiplier tube.
However, Tan et al. teaches “The present disclosure provides fully integrated microfluidic systems to perform nucleic acid analysis.” --- “The present disclosure also provides optical detection systems and methods for separation and detection of biological molecules. In particular, the various aspects of the invention enable the simultaneous separation and detection of a plurality of biological molecules, typically fluorescent dye-labeled nucleic acids, within one or a plurality of microfluidic chambers or channels.” (Abstract). Tan et al. further teaches “There is an unmet need for the development of instruments and technologies that would permit fully integrated (i.e., sample-in to results-out) focused nucleic acid analysis, defined as the rapid identification (by nucleic acid sequencing or fragment sizing) of a subset of a given human, animal, plant, or pathogen genome.” (pg. 1, lines 17-21).
Regarding claim 10, Tan et al. teaches wherein the optical detection module comprises an objective lens and a photomultiplier tube. Tan et al. refers to an objective lens as a lens and the photomultiplier tube as both a photomultiplier tube (PMT) detector.
Tan et al. further teaches “The instrument comprises excitation and detection subsystems for interacting with and interrogating a sample.” (pg. 34, lines 5-10), and “The detection subsystem comprises one or more optical detectors, a wavelength dispersion device (which performs wavelength separation), and one or a series of optical elements including, but not limited to, lenses, pinholes, mirrors and objectives to collect emitted fluorescence from fluorophore-labeled DNA fragments that are present at the excitation/detection window.” Tan et al. further teaches “More than eight dyes can be detected by applying additional dichroic mirrors, bandpass filters and PMT.” (pg. 35 lines 8-10 and 14-17).
One of ordinary skill in the art, upon reading Tan et al., would have recognized the desirability of using an optical detection module comprising an objective lens and a photomultiplier tube to interact with and interrogate a sample.
It would have been prima facie obvious, before the effective filing date of the instant application, to have modified the method taught by Broughton, Yuan, Chen 2020, and Adams to have used the optical detection module comprising an objective lens and a photomultiplier tube taught by Tan et al. because Tan et al. teaches that “There is an unmet need for the development of instruments and technologies that would permit fully integrated (i.e., sample-in to results-out) focused nucleic acid analysis, defined as the rapid identification (by nucleic acid sequencing or fragment sizing) of a subset of a given human, animal, plant, or pathogen genome.” (pg. 1, lines 17-21).
Thus, it would have been obvious to one skilled in the art to try the optical detection module comprises an objective lens and a photomultiplier tube taught by Tan et al in the optical detection module of Broughton, Yuan, Chen 2020, and Adams in order to further develop instruments and technologies that would permit fully integrated (i.e., sample-in to results-out) focused nucleic acid analysis, of a subset of a pathogen genome.” (pg. 1, lines 17-21).
Response to Arguments
In the reply, Applicant provided arguments against the rejections under 35 U.S.C. 103 and amended claim 1 to incorporate limitations of the original claim 4. As the amendments in the response changed the scope of the invention and necessitated modified 35 U.S.C. 103 rejections, several of these arguments are now moot. Those arguments which are still pertinent to the rejections set forth in this office action are discussed below.
In the reply, Applicant argued that the primers according to Table 1 of Chen 2020 are inconsistent with the section of the sequence identified in the office action mailed May 29, 2025, and that therefore Chen does not disclose or teach SEQ ID NO. 13 as claimed in the instant application.
These arguments have been fully considered and are not found persuasive. The rejection of the claims requiring SEQ ID NO. 13 does not rely on the primers found in Table 1 of Chen. To reiterate and clarify, Chen teaches a sequence (in the location of primer binding) which would corresponds to SEQ ID NO: 13 because SEQ ID NO: 13 is complementary to it. Thus, Chen demonstrates both that it would be desirable to target the corresponding sequence (for example, using a probe according to the teachings of Adams), and that the target sequence was known before the effective filing date. See rejection over Broughton, Yuan, Chen 2020, and Adams in the 35 U.S.C. 103 rejections above for further discussion.
In the reply, Applicant further argued that undue experimentation and hindsight reconstruction would be required to select or arrive at SEQ ID No. 13 based solely on the teachings of the combined references.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). MPEP 2164.06 also states that:
“The quantity of experimentation needed to be performed by one skilled in the art is only one factor involved in determining whether "undue experimentation" is required to make and use the invention. "[A]n extended period of experimentation may not be undue if the skilled artisan is given sufficient direction or guidance." In re Colianni, 561 F.2d 220, 224, 195 USPQ 150, 153 (CCPA 1977). "‘The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed.’" In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (citing In re Angstadt, 537 F.2d 498, 502-04, 190 USPQ 214, 217-19 (CCPA 1976)). Time and expense are merely factors in this consideration and are not the controlling factors. United States v. Telectronics Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988), cert. denied, 490 U.S. 1046 (1989).”
Here, the rationales for obviousness were based only on knowledge which was publicly available before the filing date of the instant invention, and the experimentation required to arrive at the inventions is routine. Therefore, the applicant’s arguments are not considered to be persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine M Jones whose telephone number is (571)272-2585. The examiner can normally be reached Monday - Friday, 8AM - 4PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.M.J./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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