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 .
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Status
Claims 1-35 are pending.
Claims 1-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/10/2025.
Claims 15-35 are being examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Remarks
The Remarks submitted on 12/8/2025 do not address the references in the specification that are not present in an IDS, and no IDS has been submitted. Therefore, the references present in the specification not present in an IDS remain unconsidered unless listed on form PTO-892 by the examiner.
Drawings
The submission of replacement drawings for Figure 8 (specifically 8B) to include only black and white is acknowledged. The objection to the drawings is withdrawn.
Nucleotide and/or Amino Acid Sequence Disclosures
The amendment to the specification to include an Incorporation by Reference paragraph for the sequence listing is acknowledged (placed into a new paragraph at the end of the specification, paragraph [0079]).
Specification
The objection to the disclosure for improper notation of SEQ ID NOs and the embedded hyperlink in paragraph [0039] is withdrawn in light of Applicant’s amendments to the specification.
It is acknowledged that the Applicant has amended the specification to include proper notation of the trade name/mark “Sigma-Aldrich” in paragraph [0075]. Other tradenames/marks remain unmarked in the disclosure (e.g., “Maverick Blue” in paragraph [0077]). While improper notation of trade names or marks used in commerce is not a formal objection, it is still proper to notify Applicant that unmarked trade names and marks remain in the specification.
Claim Objections
Withdrawn Claim Objections
The objection to claims 15, 16, 19, 24, and 28 for informalities as laid out in the Office Action of 9/9/2025 is withdrawn in light of Applicant’s amendments to the claims.
New Claim Objections
Claims 18, 22-23, 24, 29-30, and 33 are objected to because of the following informalities:
Claim 18 reads “performing the reaction to amplify a biological marker of interest” and should read “performing the reaction to amplify [[a]]the biological marker of interest” since the amplified biological marker of interest is already defined in claim 15.
Claims 22 and 23 read “wherein detecting the presence of amplified biological marker” and should read “wherein detecting the presence of the amplified biological marker” to remain consistent throughout the claims.
Claim 24 reads “amplifying the target nucleic acids” and should read “amplifying the one or more target nucleic acids” to remain consistent throughout the claim.
Claim 29 reads “wherein a plurality of SARS-CoV-2 variants is detected” and should read “wherein a plurality of SARS-CoV-2 variants [[is]]are detected”.
Claim 30 reads “wherein the one or more target nucleic acids that may be present”. There is an unnecessary extra space between “acids” and “that” that should be removed.
Claim 33 reads “performing melting curve analysis on the amplified target nucleic acids” and should read “performing melting curve analysis on the one or more amplified target nucleic acids”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112b - Indefiniteness
Withdrawn: The rejections of claims 15-35 under 35 USC 112(b) as laid out in the Office Action of 9/9/2025 are withdrawn in light of Applicant’s amendments to the claims, with the exception of the maintained rejections below.
Maintained: Claims 24-35 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.
Claim 24 recites the limitation "the fluorescence emission signal" in line 22. There is insufficient antecedent basis for this limitation in the claim. This lack of antecedent basis could be overcome by amending the claim to read “detecting [[the]]a fluorescence emission signal from a fluorescent dye”.
Claims 25-35 depend from claim 24, inherit these deficiencies, and are rejected on the same basis.
Response to Remarks
Most informalities were addressed in the amended claims. However, no amendment was made to rectify the lack of antecedent basis as noted above regarding “the fluorescence emission signal” and no argument was provided against said rejection. Therefore, the rejection to claims 24-35 is maintained.
Claim Rejections - 35 USC § 112d – Failure to Further Limit
The rejection of claims 25 and 33 under 35 USC 112(d) for failure to further limit is withdrawn in light of Applicant’s amendments to the claim.
Claim Rejections - 35 USC § 103
Withdrawn: The rejection of claims 15-35 as presented in the Office Action of 9/9/2025 under 35 USC 103 are withdrawn in light of Applicant’s amendments to the claims. New rejections to address the amendments are presented below.
New (Necessitated by Amendments):
Claims 15-16, 19-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025) and Woudenberg (Woudenberg et al., US 7,235,406 B1).
Regarding claim 15: Mitra teaches a method of analyzing a nucleic acid from a biological sample via amplification of said nucleic acid (paragraph [0005] and paragraph [0071]). Mitra teaches a device that consists of a sample receiving module with a fluid container (paragraph [0003]) that is operatively coupled to a receiving cartridge with one or more reaction chambers that can facilitate measurement of optical properties of a sample (paragraph [0004]). The “sample receiving module” or “sample collection device” reads on sample collection port. The sample receiving module can be sealed with a cap that contains a pressurizing component, or “plunger” (paragraph [0092-0093] and [paragraph [0117]). The sample receiving module contains a bottom opening that is sealed from the reaction chamber by a frangible seal which can be broken by pressurizing the fluid within the sample preparation chamber with the pressurizing component, or “plunger” (paragraph [0110]). Additionally, Mitra teaches that there may be a separate “preparation module” operably coupled to the sample receiving module with a “vent” in between (preparation module reads on sample preparation chamber; paragraph [0154]). The biological sample is placed within the sample receiving module, the sample receiving module is sealed with a cap containing a plunger that serves to close the collection opening of the sample receiving module, and the biological sample is then transferred into the sample preparation module via a vented connection, allowing fluid connection between the bottom of the sample receiving module and the preparation module (paragraph [0154] and Fig 13). Once the sample is within the reaction chamber, Mitra teaches amplifying the target biological marker and detecting the presence of the amplified biological marker of interest (paragraphs [0340]).
Mitra does not teach that the sample collection port has a bottom opening sealed by a plug member that is then dislodged by the plunger assembly coming into contact with the plug member to open a fluid connection between the sample collection port and the sample preparation chamber. Mitra teaches seals between separate chambers consisting of valves that can be re-sealable or seals that can be breakable (paragraph [0077]).
Stordeur rectifies this by teaching of a two-chamber system in which one fluidic chamber is separated from a second chamber and fluid from one chamber is prevented from entering the second chamber by a physical barrier (i.e., a plug; paragraph [0119] and Fig 12). Stordeur teaches that the plug can be dislodged by exerting physical force in the form of a plunger assembly, which dislodges the plug and allows releasing of fluid from the first chamber into the second chamber (paragraph [0300]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra to use a plug to seal the bottom of the sample collection port, as taught by Stordeur. One would be motivated to use a plug as a physical barrier that may be displaced upon physical exertion of force given the assertion by Stordeur that this allows one to pick “an appropriate time” at which to initiate the preparation of the sample for a reaction (paragraph [0122]). One would have a reasonable expectation of success given that Stordeur successfully demonstrates the dislodging of a plug member using a movable plunger assembly similar to that employed by Mitra.
Mitra in view of Stordeur do not teach that the sample preparation chamber and the reaction chamber are maintained under vacuum. Stordeur teaches that vacuum (negative pressure) can be used to relieve the build up of pressure in the system that is created by introduction of a sample (paragraph [0104]) and that use of a vacuum between one chamber and another allows for the introduction of a precise volume of sample liquid (paragraph [0105]).
Woudenberg rectifies this deficiency by teaching maintenance of the sample-distribution network (multiple different chambers) under vacuum in a device used for testing a sample for the presence or absence of target analytes (Abstract and col 6, ln 39-51).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur to place the sample preparation chamber and the reaction chamber under vacuum as taught by Woudenberg. One would be motivated to do so given the teaching by Woudenberg that this allows fluid to be pushed through the device without the need for the connection of an external pump and results in a quick and efficient distribution of sample to the detection chamber (reads on reaction chamber; col 6, ln 45-51). One would have a reasonable expectation of success given that both Mitra and Stordeur discuss creation of negative pressure (vacuum) within their respective device systems, albeit through different means.
Regarding claim 16: Mitra teaches a frangible seal between separate chambers that is frangible and can be broken by pressurization of a fluid performed by a movable plunger assembly, as cited above. Mitra specifically teaches the frangible seal being between a sample collection port and reaction chamber (paragraph [0110]). However, Mitra also teaches “using the pressure within the device to push the diluted prepared sample out of the [preparation module]” and into the reaction chamber for further analysis, implying that a frangible seal is broken to allow passage into a reaction chamber (paragraph [0154]).
Regarding claims 19 and 20: Mitra teaches that the biological markers can be a nucleic acid target and that the reaction chamber contains primers that are configured to amplify these nucleic acid targets (paragraph [0071 and 187]). Mitra teaches that these primers and detection reagents within the reaction chamber can be in dried form (paragraphs [0184-0187]).
Regarding claim 22: Mitra teaches that the biological markers can be amplified in the presence of fluorescent dyes (paragraph [0184]) and the output of the amplification can then be detected within the reaction chamber using sensors configured to detect wavelengths of light emitted from the reaction chamber (paragraph [0205]) through fluorescence spectroscopy methods (paragraph [0340]).
Claims 17-18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025) and Woudenberg (Woudenberg et al., US 7,235,406 B1) as applied to claims 15-16, 19-20, and 22 above, and further in view of Williams (Williams et al., US 2009/0221059 A1; cited on IDS of 5/27/2025).
The teachings of Mitra in view of Stordeur and Woudenberg as they apply to claims 15-16, 19-20, and 22 are detailed above. Relevant to the instantly rejected claims, Mitra in view of Stordeur and Woudenberg teach a nucleic acid analysis method in which a biological sample is collected into a sample collection port, transferred from there into a sample preparation chamber, and subsequently transferred into a reaction chamber for analysis of a biological marker within a biological sample. Mitra in view of Stordeur and Woudenberg teach that these primers and detection reagents within the reaction chamber can be in dried form (Mitra, paragraphs [0184-0187]).
Mitra in view of Stordeur do not teach that the sample preparation chamber is heated (claim 17) or that the dried reaction and detection reagents are prepared by air drying (claim 21).
Williams rectifies this by teaching a method in which a processing chamber, which is separate from a reaction chamber, is heated prior to transfer of the sample solution into a reaction chamber (claim 17; paragraph [0015]). Williams teaches heating the process chamber with the biological sample to 85 degrees Celsius before transfer to the reaction chamber (paragraph [0626]). This temperature would be sufficient to deactivate enzymes that may be present in the sample. Williams teaches that the sample can then be moved to a PCR reaction zone (paragraph [0356]) which contains PCR reagents which have been dried down (paragraph [0357]). Williams teaches air drying the reagents to prepare said dried down or lyophilized reagents within the reaction chamber (claim 21; paragraph [0579]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur and Woudenberg with the method of Williams. One would be motivated to heat the sample preparation chamber given the assertion by Williams that this sufficiently lyses the cells of a biological sample to release biological markers of interest into solution (paragraph [0558 and 0626]). One would be motivated to air dry the dried reagents for the PCR reaction given the assertion by Williams that dried PCR reagent pellets are stable for up to 2 years at room temperature (paragraph [0574]). One would have a reasonable expectation of success given that Williams successfully provides heating elements that can be isolated to just sample preparation chambers and that Williams successfully prepares dried PCR reagents that have similar sensitivity as compared to wet reagents (paragraph [0574]).
Regarding claim 18: Mitra teaches sealing the reaction chamber before performing an amplification of biological markers (paragraph [0414]).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025) and Woudenberg (Woudenberg et al., US 7,235,406 B1) as applied to claims 15-16, 19-20, and 22 above, and further in view of Robey (Robey et al., WO 2004/111186 A2; cited on PTO-892 of 9/9/2025).
The teachings of Mitra in view of Stordeur and Woudenberg as they apply to claims 15-16, 19-20, and 22 are detailed above. Relevant to the instantly rejected claims, Mitra in view of Stordeur and Woudenberg teach a method of analyzing a biological marker (nucleic acids) from a biological sample via detection of amplification in a reaction chamber. Mitra in view of Stordeur and Woudenberg teaches detecting amplification products through the use of fluorescent spectroscopy methods (Mitra, paragraph [0340]).
Mitra in view of Stordeur and Woudenberg do not teach performing melting curve analysis on the biological marker of interest.
Robey rectifies this by teaching detection of target microbe biological markers within a biological sample using melting curve analysis during amplification (Abstract and pg 23).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur and Woudenberg with the method of Robey. One would be motivated to perform a melting curve analysis given the assertion by Robey that this allows one to measure and confirm presence or absence of a particular target sequence (given that the sequence of a particular biological marker determines its melting point) and that it also allows one to quantify the amount of the target in the sample (pg 23). One would have a reasonable expectation of success given the teaching by Robey that fluorescence measurements for a melting curve analysis can occur simultaneously with fluorescence measurements during PCR amplification cycling (pg 23).
Claims 24-25 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025), Woudenberg (Woudenberg et al., US 7,235,406 B1), and Gwynn (Gwynn et al., US 2013/0132006 A1; cited on PTO-892 of 9/9/2025).
Regarding claims 24 and 25: Mitra teaches a method of analyzing a nucleic acid from a biological sample via amplification of said nucleic acid (paragraph [0005] and paragraph [0071]). Mitra teaches a device that consists of a sample receiving module with a fluid container (paragraph [0003]) that is operatively coupled to a receiving cartridge with one or more reaction chambers that can facilitate measurement of optical properties of a sample (paragraph [0004]). The “sample receiving module” or “sample collection device” reads on collection port. The sample receiving module can be sealed with a cap that contains a pressurizing component, or “plunger” (paragraph [0092-0093] and [paragraph [0117]). The sample receiving module contains a bottom opening that is sealed from the reaction chamber (reads on amplification chamber) by a frangible seal which can be broken by pressurizing the fluid within the sample collection chamber with the pressurizing component, or “plunger” (paragraph [0110]). Additionally, Mitra teaches that there may be a separate “preparation module” operably coupled to the sample receiving module with a “vent” in between (preparation module reads on sample preparation chamber; paragraph [0154]). The biological sample is placed within the sample receiving module, the sample receiving module is sealed with a cap containing a plunger, and the biological sample is then transferred into the sample preparation module via a vented connection, allowing fluid connection between the bottom of the sample receiving module and the preparation module (paragraph [0154] and Fig 13). Once the sample is within the reaction chamber, Mitra teaches sealing the reaction chamber before performing an amplification of biological markers (paragraph [0414]). Mitra teaches that the biological markers can be a nucleic acid target and that the reaction chamber contains primers that are configured to amplify these nucleic acid targets (paragraph [0071 and 187]). Mitra teaches amplifying the target biological marker and detecting the presence of the amplified biological marker of interest (paragraphs [0340]). Mitra teaches that the biological markers can be amplified in the presence of fluorescent dyes (paragraph [0184]) and the output of the amplification can then be detected within the reaction chamber using sensors configured to detect wavelengths of light emitted from the reaction chamber (paragraph [0205]) through fluorescence spectroscopy methods (paragraph [0340]). Mitra teaches that the data from sensors (such as fluorescent sensors) can be communicated to a CPU via an operating system (paragraph [0203] and that these analysis results can then be transmitted to a mobile phone (paragraph [0208]).
Mitra does not teach that the sample collection port has a bottom opening sealed by a plug member that is then dislodged by the plunger assembly coming into contact with the plug member to open a fluid connection between the sample collection port and the sample preparation chamber. Mitra teaches seals between separate chambers consisting of valves that can be re-sealable or seals that can be breakable (paragraph [0077]).
Stordeur rectifies this by teaching of a two-chamber system in which one fluidic chamber is separated from a second chamber and fluid from one chamber is prevented from entering the second chamber by a physical barrier (i.e., a plug; paragraph [0119] and Fig 12). Stordeur teaches that the plug can be dislodged by exerting physical force in the form of a plunger assembly, which dislodges the plug and allows releasing of fluid from the first chamber into the second chamber (paragraph [0300]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra to use a plug to seal the bottom the sample collection port, as taught by Stordeur. One would be motivated to use a plug as a physical barrier that may be displaced upon physical exertion of force given the assertion by Stordeur that this allows one to pick “an appropriate time” at which to initiate the preparation of the sample for a reaction (paragraph [0122]). One would have a reasonable expectation of success given that Stordeur successfully demonstrates the dislodging of a plug member using a movable plunger assembly similar to that employed by Mitra.
Mitra in view of Stordeur do not teach that the sample preparation chamber and the amplification chamber are maintained under vacuum. Stordeur teaches that vacuum (negative pressure) can be used to relieve the build-up of pressure in the system that is created by introduction of a sample (paragraph [0104]) and that use of a vacuum between one chamber and another allows for the introduction of a precise volume of sample liquid (paragraph [0105]), but does not explicitly state that chambers are maintained under vacuum.
Woudenberg rectifies this deficiency by teaching maintenance of the sample-distribution network (multiple different chambers) under vacuum in a device used for testing a sample for the presence or absence of target analytes (Abstract and col 6, ln 39-51).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur to place the sample preparation chamber and the amplification chamber under vacuum as taught by Woudenberg. One would be motivated to do so given the teaching by Woudenberg that this allows fluid to be pushed through the device without the need for the connection of an external pump and results in a quick and efficient distribution of sample to the detection chamber (reads on amplification chamber; col 6, ln 45-51). One would have a reasonable expectation of success given that both Mitra and Stordeur discuss creation of negative pressure (vacuum) within their respective device systems.
Mitra in view of Stordeur and Woudenberg teach that the biological markers can be amplified in the presence of fluorescent dyes (Mitra, paragraph [0184]) and the output of the amplification can then be detected within the reaction chamber using sensors configured to detect wavelengths of light emitted from the reaction chamber (Mitra, paragraph [0205]) through fluorescence spectroscopy methods (Mitra, paragraph [0340]). However, Mitra in view of Stordeur and Woudenberg does not teach that the fluorescence is excited by a laser diode or that the emission is detected by a multi-channel spectrometer.
Gwynn rectifies this by teaching a method of biological sample analysis using an optical detection system for PCR processing (Abstract). Gwynn teaches that fluorescence is excited by a laser diode (paragraph [0712]) and that the optical detector is a multi-channel spectrometer (paragraph [0714]) that can detect light ranging from 400nm to 800nm (this reads on wavelengths from approximately 350nm to 1000nm; paragraph [0710]). Additionally, Gwynn teaches that the multi-channel spectrometer can detect up to 7 different dyes (paragraph [0710]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur and Woudenberg to include a laser diode and a multi-channel spectrometer, as taught by Gwynn. One would be motivated to use a multi-channel spectrometer given the assertion by Gwynn that using a multi-channel detector enables “simultaneous reading of multiple optical fibers and reduce[s] the need for switching” (paragraph [0714]). One would have a reasonable expectation of success given that Gwynn demonstrates successful use of a multi-channel spectrometer to measure outputs of PCRs in detecting a biological marker of interest.
Regarding claim 30: Stordeur teaches that the biological sample can originate from a human and contain human nucleic acids (paragraph [0096]) and that the target can be human sequences of genes such as IL-2 (paragraph [0372]).
Regarding claim 31: Mitra teaches that the biological markers can be a nucleic acid target and that the amplification chamber contains primers that are configured to amplify these nucleic acid targets (paragraph [0071 and 187]). Mitra teaches that these primers and detection reagents within the amplification chamber can be in dried form (paragraphs [0184-0187]).
Claims 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025), Woudenberg (Woudenberg et al., US 7,235,406 B1), and Gwynn (Gwynn et al., US 2013/0132006 A1; cited on PTO-892 of 9/9/2025) as applied to claims 24-25 and 30-31 above, and further in view of Snyder (Snyder et al., WO 2020/252084 A1).
The teachings of Mitra in view of Stordeur, Woudenberg, and Gwynn as they apply to claims 24-25 and 30-31 are detailed above. Relevant to the instantly rejected claims, Mitra in view of Stordeur, Woudenberg, and Gwynn teach systems for performing a method of detecting pathogens in biological samples via optical detection of amplification products (Mitra, paragraph [0190]; Stordeur, paragraph [0230]; Woudenberg, col 2, ln 1-3; Gwynn, paragraph [0442]).
Mitra in view of Stordeur, Woudenberg, and Gwynn do not specifically teach that the pathogen is a virus, specifically one such as Coronavirus.
Snyder rectifies this by teaching of a method of amplifying and detecting pathogen in biological samples (Abstract). Snyder specifically teaches that the pathogen can be a virus, bacteria or fungus (pg 23-24) and the target is a nucleic acid originating from said pathogen (claim 26; pg 24). Snyder teaches that the virus can be from the group consisting of Coronavirus, specifically SARS-CoV-2 (claims 27 and 28; pg 24, ln 12). Additionally, Snyder teaches that the methods taught therein can accomplish variant-level identification in which a specific strain is detected (claim 29; pg 64, ln 20-24). Snyder teaches that the PCR can be a multiplex PCR in which multiple nucleic acid targets can be amplified in parallel which enables determination of the “species” of the pathogen (pg 61, ln 21-28). Snyder defines the term “species” as encompassing “subspecies or strains” (which reads on variants, claim 29; pg 26, ln 19-31).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur, Woudenberg, and Gwynn to analyze SARS-CoV-2 and variants, as taught by Snyder. One would be motivated to do so given the assertion by Snyder that their methodology enables “early detection of biothreats in biological samples” from complex sample types such as blood (pg 1, ln 18-20). One would have a reasonable expectation of success given that Mitra describes that their methodology can be used for detecting pathogens and Snyder teaches detection of Coronavirus and subvariants using amplification means that would be readily compatible with the amplification detection as described by Mitra.
Claims 32 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025), Woudenberg (Woudenberg et al., US 7,235,406 B1), and Gwynn (Gwynn et al., US 2013/0132006 A1; cited on PTO-892 of 9/9/2025) as applied to claims 24-25 and 30-31 above, and further in view of Williams (Williams et al., US 2009/0221059 A1; cited on IDS of 5/27/2025).
The teachings of Mitra in view of Stordeur, Woudenberg, and Gwynn as they apply to claims 24-25 and 30-31 are detailed above. Relevant to the instantly rejected claims, Mitra in view of Stordeur, Woudenberg, and Gwynn teach that the biological markers can be a nucleic acid target and that the reaction chamber contains primers that are configured to amplify these nucleic acid targets (Mitra, paragraph [0071 and 187]). Mitra teaches that these primers and detection reagents within the reaction chamber can be in dried form (Mitra, paragraphs [0184-0187]). Additionally, Mitra in view of Stordeur, Woudenberg, and Gwynn teaches that fluorescence in an amplified sample is excited by a laser diode (Gwynn, paragraph [0712]) and that the optical detector is a multi-channel spectrometer (Gwynn, paragraph [0714]) that can detect light ranging from 400nm to 800nm (Gwynn, paragraph [0710]).Gwynn additionally teaches that ball lenses (relevant to claims 34-35) are included for coupling efficiency within the optical detection system (Gwynn, paragraph [0713]).
Mitra in view of Stordeur, Woudenberg, and Gwynn do not teach that the dried reagents in the reaction chamber are air dried (claim 32) and do not explicitly state that the ball lenses are used with both the laser diode and the multi-channel spectrometer (claims 34-35).
Williams rectifies this by teaching a method in which a processing chamber, which is separate from a reaction chamber, is heated prior to transfer of the sample solution into a reaction chamber (paragraph [0015]). Williams teaches that the sample can then be moved to a PCR reaction zone (paragraph [0356]) which contains PCR reagents which have been dried down (paragraph [0357]). Williams teaches air drying the reagents to prepare said dried down or lyophilized reagents within the reaction chamber (claim 32; paragraph [0579]). Williams teaches that amplification products can be detected via excitation of fluorescent molecules with LEDs (paragraphs [0370 and 0378]) in combination with lenses for focusing the light and optical detectors for detecting different spectra (paragraph [0370]). Specifically, Williams teaches that a focusing lens is used with the laser diode (paragraph [0664]) and with the photodetector (claims 34-35; paragraph [0665]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur, Woudenberg, and Gwynn with the method of Williams. One would be motivated to air dry the dried reagents for the PCR reaction given the assertion by Williams that dried PCR reagent pellets are stable for up to 2 years at room temperature (paragraph [0574]). One would have a reasonable expectation of success given that Williams successfully prepares dried PCR reagents that have similar sensitivity as compared to wet reagents (paragraph [0574]). One would be motivated to use a ball lens (as taught by Gwynn) with both the laser diode and the spectrometer (as taught by Williams) given the assertion by Williams that usage of lenses allows focusing of the light for sensitive detection (paragraph [0370]). One would have a reasonable expectation of success given that both Williams and Gwynn successfully use lenses in their optical set up designs for detection of fluorescence.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Mitra (Mitra et al., US 2019/0083975 A1; cited on PTO-892 of 9/9/2025) in view of Stordeur (Stordeur et al., US 2009/0117646 A1; cited on PTO-892 of 9/9/2025), Woudenberg (Woudenberg et al., US 7,235,406 B1), and Gwynn (Gwynn et al., US 2013/0132006 A1; cited on PTO-892 of 9/9/2025) as applied to claims 24-25 and 30-31 above, and further in view of Robey (Robey et al., WO 2004/111186 A2; cited on PTO-892 of 9/9/2025).
The teachings of Mitra in view of Stordeur, Woudenberg, and Gwynn as they apply to claims 24-25 and 30-31 are detailed above. Relevant to the instantly rejected claims, Mitra in view of Stordeur, Woudenberg, and Gwynn teach a method of analyzing a biological marker (nucleic acids) from a biological sample via detection of amplification in a reaction chamber. Mitra in view of Stordeur, Woudenberg, and Gwynn teach detecting amplification products through the use of fluorescent spectroscopy methods (Mitra, paragraph [0340]). : Mitra in view of Stordeur, Woudenberg, and Gwynn teach an amplification device with means to perform a melting curve analysis. According to the specification, the means to perform this analysis include “a laser as a light source and a multi-channel spectrometer may be used for detection” (paragraph [0007] of the instant specification).
Mitra in view of Stordeur, Woudenberg, and Gwynn do not teach performing melting curve analysis on the biological marker of interest.
Robey rectifies this by teaching detection of target microbe biological markers within a biological sample using melting curve analysis during amplification (Abstract and pg 23).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Mitra in view of Stordeur, Woudenberg, and Gwynn with the method of Robey. One would be motivated to perform a melting curve analysis given the assertion by Robey that this allows one to measure and confirm presence or absence of a particular target sequence (given that the sequence of a particular biological marker determines its melting point) and that it also allows one to quantify the amount of the target in the sample (pg 23). One would have a reasonable expectation of success given the teaching by Robey that fluorescence measurements for a melting curve analysis can occur simultaneously with fluorescence measurements during PCR amplification cycling (pg 23).
Response to Remarks
Applicant's arguments filed 12/8/2025 (pages 14-16 of Remarks) have been fully considered but they are not deemed persuasive for the following reasons.
With regards to the new limitations added to the amended claims, new grounds of rejection have been presented above to address the inclusion of the reaction chamber and sample preparation chamber being under vacuum.
Applicant argues on page 15 of Remarks that Mitra teaches a vent connection between the sample preparation module and the sample receiving module, and that Stordeur lacks the collection port, sample preparation chamber maintained under vacuum, and a reaction chamber maintained under vacuum with a frangible seal. 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’s arguments against the rest of the claim rejections rely on their arguments against the references individually (addressed above) and on the new claim limitations included in the amendments that have now been addressed on new grounds as presented above in the new 103 rejections.
Double Patenting
The statutory type double patenting rejection over copending Application No. 19/235,412 is withdrawn.
Response to Remarks
It is acknowledged that there was a Preliminary Amendment submitted on June 11, 2025 which canceled claims 15-35 for the co-pending application 19/235,412. The amended claims are within the document labeled “Preliminary Amendment” in the application file wrapper.
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 KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683