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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Jul. 30, 2026. Claims 1, 3-4, 7-20 and 23-25 are pending. Claims 1, 3-4 and 7-20 are withdrawn. Claims 23-25 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group II (Claims 23-25), directed to a device for detecting a target nucleic acid in a biological sample, in the reply filed on Mar. 23, 2026, is acknowledged. For the species election requirement, Applicant elects DNA and E. coli.
Accordingly, claims 1, 3-4 and 7-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
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 of this title, 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.
(Previous Rejection – Withdrawn) Claims 23-25 were rejected under 35 U.S.C. 102/103 as being unpatentable over Pabinger et al. (Biomolecular Detection and Quantification 1 (2014) 23–33).
This rejection is withdrawn in favor of the rejections below. Applicant’s arguments regarding the withdrawn rejection are moot.
Claim Rejections - 35 USC § 103
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 of this title, 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.
(New Rejection) Claims 23-25 are rejected under 35 U.S.C. 102/103 as being unpatentable over Pabinger et al. (Biomolecular Detection and Quantification 1 (2014) 23–33) and Ngatchou et al. (IEEE Transactions on Automation Science and Engineering, Volume: 3, Issue: 2, April 2006).
These claims are directed to a device for detecting a target nucleic acid in a biological sample, comprising:
- a reaction chamber, which in use receives the sample and reagents for performing amplification and fluorescent labelling of the amplification product;
- a light source which emits light at a wavelength corresponding to an excitation wavelength of the fluorescent label;
- a detector, for detecting fluorescence; and
- a user interface;
wherein the device is programmed to classify the biological sample as positive, negative or undetermined for the presence of the target nucleic and present the classification on the user interface, the classification being based on:
a) time to start of reaction, signaled by an increase in fluorescence, wherein the device monitors fluorescence over time to establish when fluorescence starts to increase relative to the time when the sample and reagents are combined, and wherein if an increase in fluorescence starts outside of a defined time window, the device classifies the sample as undetermined; and
b) peak fluorescence intensity, wherein if the peak fluorescence intensity does not exceed a predetermined threshold, the device classifies the sample as negative;
c) and optionally baseline fluorescence level, wherein if the baseline fluorescence level exceeds the predetermined threshold, the device classifies the sample as undetermined.
Pabinger is a review article on tools for the analysis of quantitative PCR (qPCR) data. Pabinger teaches that real-time quantitative polymerase-chain-reaction (qPCR) is a standard technique in most laboratories used for various applications in basic research. Analysis of qPCR data is a crucial part of the entire experiment, which has led to the development of a plethora of methods. The released tools either cover specific parts of the workflow or provide complete analysis solutions. The authors surveyed 27 open-access software packages and tools for the analysis of qPCR data. Reviewed packages and tools support the analysis of different qPCR applications, such as RNA quantification, DNA methylation, genotyping, identification of copy number variations, and digital PCR. They report an overview of the functionality, features and specific requirements of the individual software tools, such as data exchange formats, availability of a graphical user interface, included procedures for graphical data presentation, and offered statistical methods. In addition, the authors provide an overview about quantification strategies, and report various applications of qPCR.
The survey showed that most tools use their own file format and only a fraction of the currently existing tools support the standardized data exchange format RDML. To allow a more streamlined and comparable analysis of qPCR data, more vendors and tools need to adapt the standardized format to encourage the exchange of data between instrument software, analysis tools, and researchers. See Abstract.
Pabinger teaches that the quantification of target DNA in each cycle of a qPCR experiment is based on measuring the emission of a fluorescent reporter dye. Dyes that bind to double-stranded DNA and upon excitation emit light (e.g., SYBR Green) are the most widely used DNA dyes due to ease of use, cost efficiency, and generic detection. See page 24, right column, para 4.
Pabinger teaches that based on the detected fluorescent signal and the chosen experimental setup several analysis steps are needed to obtain biological meaningful results (see Fig. 2). First, based on the raw fluorescence values a baseline is subtracted from the raw data, which is a crucial step in qPCR data analysis. Next, the quantification cycle (Cq) value – previously known as the threshold cycle (Ct), crossing point (Cp), or take-off point (TOP) – can be calculated. In general, the Cq value represents the number of cycles needed to reach a set threshold fluorescence signal level. In addition, the raw fluorescence values can also be used for inferring the amplification efficiencies. Using the determined Cq value, quantification of nucleic acids can be performed by absolute quantification (via standard curve or digital PCR) or relative quantification (delta Cq). Finally, the quantification results can be tested for statistically significant differences and presented in a graphical way. See para bridging pages 24 and 25.
Table 1 of Pabinger lists software packages and tools for the analysis of qPCR data. It teaches that for each tool its corresponding application area is specified, divided into: Cq calculation, normalization, quantification, CNV, and dPCR. The input type can either be precalculated Cq values (Cq) or raw fluorescence values (Raw). For each tool the supported operating system or the underlying framework is specified. Frameworks are often available on different operating systems allowing the package to run on several platforms. GUI specifies the existence of a graphical user interface for data input and output. ABI, Applied Biosystems format; ABT, Lightcycler export format; CSV, comma separates values, FLO, Lightcycler export format; REX, Rotor Gene export format; R format, encompasses all import and export formats provided by the default R installation and auxiliary R packages (e.g., PDF, SVG, HTML, and XLS). See Table 1 legend.
Ngatchou describes the development of a real-time polymerase chain reaction testbed for the analysis of up to 48 1- to 2- uL reactions in glass capillaries. The testbed features a laser-induced fluorescence scanner with high-sensitivity photomultiplier tubes for the detection of three spectral wavelengths. The scanner has a detection threshold of 1–nM fluorescein in a 1- uL detection volume. Peltier-effect thermoelectric elements are used to control thermal cycles with a slew rate of 3 C/s, and a set point tracking accuracy of 0.5 C. Analyzer design and performance are presented. See Abstract.
Table 1 of Ngatchou shows subsystems of a panel of RT-PCR instruments from different vendors. See below:
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Fig. 3 of Ngatchou show a block diagram of subsystems typically contained in a qPCR cycler, including a thermal system for temperature control, optical system including light source and filters, and a PC (user interface). See below.
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Ngatchou teaches that a high-level view of real-time PCR instruments reveals a generic architectural similarity. They all have: a) a thermal subsystem, or thermal cycler, necessary to bring the reaction chamber or reaction vessels which contain the PCR mix to the various temperatures specified in the PCR protocol; and b) an optoelectronic subsystem that comprises an excitation light source, optical filters, and focusing elements, and photodetection sensors for monitoring the amplification products by means of real-time detection of fluorescence emitted by probes in the PCR mix. In all cases, sample format, detection modality, and biochemistry requirements are critical constraints for subsystem design and integration. See page 142, left column, para 2.
Ngatchou further teaches the user interface of the RT-PCR instruments. It teaches that The LabVIEW control program user interface allows the user to specify the thermal cycling conditions, as well as the desired sampling rate, length of observation window, and number of samples to acquire per capillary [Fig. 4(a)]. During the experiment, a bar graph display shows the most recent fluorescence reading for each capillary acquired from all three PMTs. A real-time chart shows the fluorescence measurements since the beginning of the experiment [Fig. 4(b)]. All measurements and other information (capillary identifier, timing information, phase, and cycle number) are stored in the unique experimental data log in a text file format. In this format, the fluorescence emission data are available for analysis both during (in real time) and after the completion of the qPCR run. LabVIEW and MATLAB are used for prototype development, when prototypes and protocols are sufficiently well developed then specifications are drafted and the functionality is ported to fully integrated Windows applications for integration within the ACAPELLA-A5K system. See page 145, para spanning left and right columns.
Accordingly, both Pabinger and Ngatchou teaches the devices, e.g., cyclers from various suppliers, used for qPCR, which are expected to comprise (1) a reaction chamber, which in use receives the sample and reagents for performing amplification and fluorescent labelling of the amplification product; (b) a light source which emits light at a wavelength corresponding to an excitation wavelength of the fluorescent label; (c) a detector, for detecting fluorescence; and (d) a user interface. They further teach that the qPCR results are analyzed by software programs supplied with the qPCR devices for the detection and quantification of nucleic acid in test samples. However, even if Pabinger and Ngatchou teach that various software programs exist in controlling the instruments and data analysis, they are silent on exactly the way classification of the biological sample as claimed. It is noted that the claimed classification is based on the data generated of a qPCR instrument.
One of skill in the art would have found it obvious classify a biological sample as positive, negative, or undermined based on the qPCR assay results. As to how the classification is made, one of skill in the art would found it obvious that such classification, may be made according to various aspects, such as experimental conditions, specific instrument and/or software setting, researcher preferences, etc. In other words, the claimed process for classification of biological sample based on qPCR assay results can be arrived in routine experimental optimization or based on experimental need, and is well within the purview of one of ordinary skill in the art.
Claim 24 further specifies a filter which filters light at wavelengths emitted by the light source, and wherein there is no direct line of sight between the light source and detector; Claim 25 further specifies that the reaction chamber comprises a well in a heating block and wherein an insulative layer at least partially surrounds the heating block.
It is well known in the art that light cyclers contain filter modules (or filter cubes) with multiple filters to produce lights of different wavelengths for excitation of different fluorescent dyes, that light does not have to travel in a direct line of sight between the light source and the detector, its path can be altered by reflective mirrors to get around obstacles, and that qPCR thermal cyclers must contain heaters to increase the temperatures during temperature cycles and such heaters may need to be insulated to increase temperature control efficiency, as taught in Ngatchou.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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