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 .
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 2-18 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.
On lines 3 and 5 of claim 2, the phrase “the binding slope” lacks antecedent basis. In addition, it is not clear what the phrase “binding slope” refers to in claim 2. Does the binding slope in claim 2 refer to a binding between a substance in the dilution factor (DF) calibrator material and a substance present in the photonic chip? It is not clear what exactly is being measured in the method to obtain a “binding slope” of the DF calibrator material in the control solution and the sample solution. On lines 3 and 5 of claim 2, the phrase “DF calibrator” is indefinite since it is not clear whether the abbreviation “DF” refers to dilution factor. On line 3 of claim 2, the “control solution” is indefinite since it is not clear what this control solution comprises. Does the control solution contain some substance in a known amount that is also present in the sample solution? On line 7 of claim 2, the phrase “the ratio” lacks antecedent basis. On line 10 of claim 2, the phrase “outputting a concentration of the analyte based on the calibrated dilution factor” is indefinite since it is not clear how a concentration of the analyte can be output when there is no positive step of measuring a concentration of the analyte using the calibrated dilution factor.
On line 1 of claim 3, the phrase “further comprising determine the concentration” should be changed to –further comprising determining the concentration—so as to make proper sense.
On line 3 of claim 11, the “control solution” is indefinite since it is not clear what this control solution comprises. Does the control solution contain some substance in a known amount that is also present in the sample solution? On lines 4 and 7 of claim 11, the phrase “the binding slope” lacks antecedent basis. In addition, it is not clear what the phrase “binding slope” refers to in claim 11. Does the binding slope in claim 11 refer to a binding between a substance in the dilution factor (DF) calibrator material and a substance present in the photonic chip? It is not clear what exactly is being measured in the method to obtain a “binding slope” of the DF calibrator material in the control solution and the sample solution. On line 9 of claim 11, the phrase “the ratio” lacks antecedent basis. On line 12 of claim 11, the phrase “outputting a concentration of the analyte based on the calibrated dilution factor” is indefinite since it is not clear how a concentration of the analyte can be output when there is no positive step of measuring a concentration of the analyte using the calibrated dilution factor.
On lines 8 and 10 of claim 12, the phrase “the binding slope” lacks antecedent basis. In addition, it is not clear what the phrase “binding slope” refers to in claim 12. Does the binding slope in claim 12 refer to a binding between a substance in the dilution factor (DF) calibrator material and a substance present in the photonic chip? It is not clear what exactly is being measured with the optical reader device to obtain a “binding slope” of the DF calibrator material in the control solution and the sample solution. On lines 8 and 10 of claim 12, the phrase “DF calibrator” is indefinite since it is not clear whether the abbreviation “DF” refers to dilution factor. On line 8 of claim 12, the “control solution” is indefinite since it is not clear what this control solution comprises. Does the control solution contain some substance in a known amount that is also present in the sample solution? On line 12 of claim 12, the phrase “the ratio” lacks antecedent basis.
Inventorship
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 2-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shastry et al (US 2019/0021704) in view of Stern et al (US 2018/0275058).
With regards to claims 2-3, 11 and 12, Shastry et al teach of a method and an optical reader device for reading a photonic chip to determine a concentration of an analyte (i.e. drug, biomarker, protein, etc.) in a sample fluid such as a saliva sample. The optical reader device comprises a holder configured to secure a photonic chip 3000 to be read by the reader device, a scan head 1004 within the reader device comprising a laser light source and an optical detector, and a controller configured to coordinate the scan head 1004, illumination of the laser light source, and detection by an optical detector (see paragraphs 0045, 0046 and 0202 in Shastry et al). The controller is configured to perform a method comprising passing a control sample containing a known amount of a fluorophore conjugated antibody into an assay well in the photonic chip that is coated with reagents such as antigens of the analytes being tested for with the photonic chip, wherein the coated antigens bind with binding agents comprising both the fluorophore conjugated antibody in the control sample and fluorophore conjugated antibodies added to a sample solution. The detectably labeled antibody from the control sample attaches to the antigens coated in an assay well of the photonic chip, and a detectable control signal of the binding reaction is measured by the optical detector over time and plotted on an X-Y graph to obtain a binding slope based on the signal intensity over time. A diluted sample, such as a saliva sample, is then passed into an assay well in the photonic chip that is coated with antigens of the analytes being tested for with the photonic chip, wherein the coated antigens in the assay well bind with free fluorophore conjugated antibodies added to the diluted sample that have not become bound to the analyte being tested for in the sample. A detectable sample signal of the binding reaction between the unbound fluorophore conjugated antibodies in the sample solution and the coated antigen in the assay well of the photonic chip is measured by the optical detector over time and plotted on an X-Y graph to obtain a binding slope based on the signal intensity over time. The binding slope of the control solution graph is compared to the binding slope of the sample solution graph in order to determine and calculate an amount of the analyte in the saliva sample (see paragraphs 0141 and 0182-0185 in Shastry et al). Shastry et al also teach of a method for calibrating a dilution factor and using the calibrated dilution factor when determining a concentration of an analyte in the saliva sample solution. A calibrated dilution factor is determined by adding a known quantity or concentration of a substance (i.e. a dilution factor (DF) calibrator material) to a dilution buffer, measuring the dilution factor calibrator material in the dilution buffer, adding a quantity of the dilution buffer containing the DF calibrator material to the saliva sample solution, measuring the dilution factor (DF) calibrator material in the diluted sample solution, and determining a calibrated dilution factor by dividing or obtaining a ratio of the known concentration of the DF calibrator material measured in the dilution buffer and the measured amount of the DF calibrator material in the diluted saliva sample solution. The calibrated dilution factor is then used to adjust a measured concentration of an analyte in the saliva sample so as to account for different dilutions of the saliva. See paragraphs 0128-0131 in Shastry et al, particularly paragraph 0131 where it states:
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Also, see Figure 9A, the abstract and paragraphs 0128-0131, 0141-0143 and 0182-0185 in Shastry et al. Shastry et al fail to specifically teach that the DF calibrator material added to the dilution buffer used to dilute the saliva sample in the method comprises a labeled binding agent, and that a binding slope of the DF calibrator material in both the dilution buffer (which is equivalent to the “control solution” in the instant claims) and the diluted saliva sample solution is measured and used to determine a calibrated dilution factor by obtaining a ratio of the slope of the DF calibrator in the sample solution and the slope of the DF calibrator in the dilution buffer (i.e. control solution).
Stern et al teach of an optical reader system and method for optically detecting analytes in a sample bound to a binding agent in a biochemical assay. The optical reader system comprises a housing comprising a holder to receive a microfluidic cartridge to which a sample is added, an excitation light source to generate incident light on the sample, and a photomultiplier detector configured to receive light emitted by a label associated with a binding agent bound to an analyte in the sample and produce a signal in response to the received light that corresponds to a concentration of the analyte in the sample (see the abstract in Stern et al). The cartridge comprises an assay chamber for receiving a sample, wherein the assay chamber contains labeled binding agents for an analyte in the sample immobilized to a surface of the chamber. Stern et al teach that in some embodiments, the sample is diluted in the assay chamber with a diluent comprising a dilution factor calibrator material, wherein the DF calibrator material comprises a known concentration an optical tracer. Dilution accuracy of the sample that occurs during a biomarker assay is obtained by determining and calibrating a dilution factor. This calibrated dilution factor is obtained by spiking a diluent with a known concentration of an optical tracer, wherein the optical tracer comprises a signal generating species (i.e. a chromophore, a fluorophore, etc.) conjugated to a binding detector species (i.e. an antibody, and an antigen, etc., see paragraph 0160 in Stern et al), measuring the known concentration of the optical tracer in the diluent by performing a binding assay where the binding detector species binds to its corresponding ligand (i.e. an antibody, antigen, etc.), diluting the sample with the diluent containing the known concentration of the optical tracer, optically measuring the tracer concentration in the diluted sample by detecting a binding reaction between the binding detector species of the tracer to its corresponding ligand (i.e. an antibody, antigen, etc.), and determining a calibrated dilution factor by obtaining a ratio of the known and/or measured pre-dilution amount of the optical tracer in the diluent to the measured amount of the optical tracer in the sample after dilution with the diluent. See paragraphs 0160-0165 in Stern et al. The optical tracer comprising the DF calibrator material is detected in both the diluent and the diluted sample by measuring fluorescent signals from the tracer using the detector of the optical reader system. See the abstract, Figure 1A, and paragraphs 0013, 0016-0020, 0160-0166, and the claims in Stern et al, particularly paragraph 0165 where it states:
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Based upon a combination of Shastry et al and Stern et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a labeled binding agent as the DF calibrator material added to the dilution buffer (which is equivalent to the “control solution” in the instant claims) in the method and device taught by Shastry et al for determining a calibrated dilution factor because Stern et al teach that labeled optical tracers comprising both a signal generating species (i.e. a chromophore, a fluorophore, etc.) conjugated to a binding detector species (i.e. an antibody, and an antigen, etc.) are known and useful as dilution factor calibrator materials added to diluents used to dilute a sample being analyzed for an analyte concentration and used to determine a calibrated dilution factor. It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure a binding slope of the DF calibrator material comprising a labeled binding agent in both the dilution buffer (which is equivalent to the “control solution” in the instant claims) and the diluted saliva sample solution taught by Shastry et al and use the binding slopes to determine a calibrated dilution factor by obtaining a ratio of the slope of the DF calibrator in the sample solution and the slope of the DF calibrator in the dilution buffer (i.e. control solution) because Shastry et al teach that the measurement of a binding slope between a labeled binding agent and its corresponding antigen or analyte allows for detectable optical signals to be collected over time, thus removing extraneous fluorescent signals not originating from the binding reaction from the measurement.
With regards to claims 4-5, Shastry et al teach that the DF calibrator material is added to both the dilution buffer (i.e. control solution) and the saliva sample solution. See paragraph 0131 in Shastry et al.
With regards to claim 6, Shastry et al teach that the dilution buffer (i.e. control solution) contains a known amount of the DF calibrator material. See paragraph 0131 in Shastry et al.
With regards to claim 7, Shastry et al teach that the DF calibrator material in the sample solution is diluted from a known concentration added to the sample solution. See paragraph 0131 in Shastry et al.
With regards to claims 8 and 13, the combination of Shastry et al and Stern et al fails to teach that determining the calibrated dilution factor comprises comparing the binding ratio to a database of empirically derived calibration factors. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine the calibrated dilution factor in the method taught by the combination of Shastry et al and Stern et al by comparing the binding ratio to a database of empirically derived calibration factors because Stern et al teach that the optical reader device can be connected to a remote database for transmitting, processing, storage and future access of data (see paragraph 0032 in Stern et al), and comparison of measured data in an analytical method to data stored in a database is widely used to determine an unknown variable in the method.
With regards to claim 9, Stern et al teach of dilution factor calibrator materials comprising a fluorophore labeled biomolecule or microparticle. See paragraph 0160 in Stern et al.
With regards to claim 10, Shastry et al teach of analyzing saliva sample solutions. See paragraphs 0094, 0117-0120 and 0130-0131 in Shastry et al.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shastry et al in view of Stern et al as applied to claims 2-13 above, and further in view of Rothberg et al (US 2016/036932). For a teaching of Shastry et al and Stern et al, see previous paragraphs in this Office action.
The combination of Shastry et al and Stern et al fails to teach that the controller of the optical reader device is configured to modulate the illumination of the laser light source with a shift signal having a frequency of 10 kHz or greater.
Rothberg et al teach of a method for reading optical signals from a photonic chip of a removable cartridge held in an optical reader comprising the steps of modulating an excitation signal for a laser of the optical reader to provide pulsed signals at a certain frequency, illuminating the photonic chip with the modulated pulsed signals, detecting an optical signal from the photonic chip, and generating an output signal from the optical signal. Rothberg et al teach that direct modulation of the laser’s output is done using a switching array of optical switches at different frequencies. See the abstract, and paragraphs 0107, 0311, 0314 and 0321-0322 of Rothberg et al.
Based upon a combination of Shastry et al, Stern et al and Rothberg et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the controller in the optical reader device taught by the combination of Shastry et al and Stern et al to modulate the illumination of the laser light source with a shift signal having a frequency of 10 kHz or greater because Rothberg et al teach that the modulation of a laser light source in an optical reader device with shift or pulse signals having different frequencies allows different chemical substances to be effectively measured and distinguished from one another in a sample.
Allowable Subject Matter
Claims 15-18 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims because the closest prior art references to Shastry et al and Stern et al, described above, fail to teach or fairly suggest an optical reader device comprising a controller configured to perform each of the operations recited in independent claim 12, and additionally configured to demodulate an output signal from the optical detector using a modulated pulsed excitation signal to form a demodulated output signal, wherein the demodulated output signal is proportional to a cosine of a phase difference between the modulated signal and the output signal.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Please make note of: McDevitt et al (US 2006/0257993) who teach of a portable device comprising a self-contained cartridge containing sensor elements and reagents for detecting analytes in samples; Lowe et al (US 2017/80420) who teach of an assay device and reader; and Emeric et al (US 2013/0162981) who teach of reader devices for optical and electrochemical test assays.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 January 28, 2026