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 .
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because:
(a) reference character “S1” has been used to designate both perform irradiation with excitation light and switch input to ADC to offset voltage and record zero level;
(a) reference character “S2” has been used to designate both detect detection light and perform switching of switch and input signal of lock-in circuit to ADC; and
(a) reference character “S3” has been used to designate both remove signal component corresponding to scattered light from detection signal corresponding to detection light and forcibly shift phase once.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim(s) 6, 7, and 13 is/are objected to because of the following informalities:
(a) in claim 6, “a value” on line(s) numbered 16 should probably be --said value--;
(b) in claim 7, “a value corresponding to the fluorescence lifetime” on line(s) numbered 21-22 should probably be --said value--; and
(c) in claim 13, “a value” on line(s) numbered 6 should probably be --said value--.
Appropriate correction is required.
Claim Interpretation
MPEP § 2111.01 states that “… Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms …”. Thus under a broadest reasonable interpretation, the greatest clarity is obtained when the specification (e.g., see “… value corresponding to the fluorescence lifetime (specifically, 1/fluorescence lifetime) which is a period of time taken until the intensity of fluorescence drops from the peak value to 1/e …” in paragraph 34 serves as a glossary for the claim term “a value corresponding to a fluorescence lifetime”.
The specification (e.g., see “… a commercial frequency (50 Hz or 60 Hz) …” in paragraph 34 serves as a glossary for the claim term “a commercial frequency”.
The specification (e.g., see “… when time region 1 is amplified by being multiplied by the multiplier "-1", an output of the time region 1 becomes a negative value due to "positive value x negative value" …” in paragraph 39 serves as a glossary for the claim term “individually amplifying each component of the divided detection signal”.
The specification (e.g., see “… when all the integrated values of the time regions 1 to 4 amplified by being multiplied by a predetermined multiplier are added together … individually amplifying each of the divided components, and synthesizing each of the amplified components …” in paragraph 40 serves as a glossary for the claim term “synthesizing each of the amplified components”.
The specification (e.g., see “… lock-in circuit utilizing an FPGA … instead of having all the operation frequencies to be the same as each other, for example, a frequency deviation between the lock-in circuit and the DDS during the total time in which the lock-in circuit is driven ten times can be reduced by performing setting such as setting the operation frequency of the FPGA to be higher than the operation frequency of the DDS for eight times out of ten times and setting the operation frequency of the FPGA to be lower than the operation frequency of the DDS for twice out of ten times …” in paragraph 79 serves as a glossary for the claim term “the signal processing unit is set by switching between the operation frequencies of two kinds at a predetermined proportion”.
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 pre-AIA 35 U.S.C. 112, 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.
Claim(s) 14 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: a detection antibody to a capturing antibody.
Claim Rejections - 35 USC § 102
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 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.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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.
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.
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.
Claim(s) 1, 3, 4, 10, and 11 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lakowicz et al. (US 5,504,337).
In regard to claim 1, Lakowicz et al. disclose an optical measurement device comprising:
(a) a light detection unit configured to detect detection light (e.g., “… It should be understood by one of ordinary skill that a plurality of channels, one for each respective monochromatic beam of light, would be employed. The emitted light at each color would be detected by an optical transducer, such as a photodetector 29 …” in the first column 10 paragraph) including second light generated from a sample irradiated with first light (e.g., “… fluorescence emission of the fluorophore associated with the cell or particle as a result of illumination by the laser beam will result when the wavelength of the laser light matches the absorption band of one or more fluorophores used …” in the last complete column 9 paragraph) and third light caused by the first light and having a phase equivalent to a phase of the first light (e.g., “… laser light scattered by the sample particles having no phase lag …” in the last column 17 paragraph);
(b) a signal processing unit configured to perform processing of a detection signal corresponding to the detection light (e.g., “… photodetector produces a pulsed current output voltage which, in conventional flow cytometry systems, are directed to a signal processing subsystem for fluorescence analysis … conventional hardware and software 30, currently capable of processing the pulse amplitude output …” in the second column 10 paragraph and the fourth column 12 paragraph); and
(c) a light source driving circuit configured to set a modulation frequency of a light source outputting the first light (e.g., “… controlling the generation of light pulses at a desired rate and width. An appropriate pulse rate for the preferred embodiment would be ≥4 MHz. Yet another light source structure may be found in the flow cytometer manufactured by Becton Dickinson Corporation, and sold under the trademark FACScan, where an air-cooled low-power 15 mW argon-ion laser operating at 488 nm, is used. The continuous light generated by the argon-ion laser would be externally modulated by an acousto-optical or electro-optical modulator to produce the desired pulsed or sinusoidal output …” in the first column 9 paragraph),
wherein the signal processing unit removes a signal component corresponding to the third light from the detection signal on the basis of a phase difference between the second light and the third light (e.g., “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …” in the first complete column 13 paragraph), and
wherein the light source driving circuit sets the modulation frequency of the light source (e.g., “… 20MHz …” in the first column 17 paragraph) to be lower than a value corresponding to a fluorescence lifetime (e.g., “… fluorescence lifetime of 24 ns …” in the last column 17 paragraph can also be labeled as a value of 1/24 ns = 1/24x10-9 s ≈ 41.7 MHz) indicating a period of time taken until an intensity of the second light drops from a peak value to 1/e (e.g., “… attenuation time of the emitted light (i.e. the fluorescence lifetime … typically 1/e or 63% of peak …” in the last column 2 paragraph).
MPEP § 2144.05 states that “… In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of “50 to 100 Angstroms” considered prima facie obvious in view of prior art reference teaching that “for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms].” The court stated that “by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.”). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range) …“.
Thus alternatively, a prima facie case of obviousness exists (MPEP § 2144.05) since the claimed “modulation frequency of the light source to be lower than a value” range overlap the “appropriate pulse rate for the preferred embodiment would be ≥4 MHz ” range disclosed by the cited prior art (e.g., see “… appropriate pulse rate for the preferred embodiment would be ≥4 MHz …” in the first column 9 paragraph).
In regard to claim 3 which is dependent on claim 1, Lakowicz et al. also disclose that the first light is excitation light for exciting the sample, wherein the second light is fluorescence emitted by the sample in response to the excitation light (e.g., “… fluorescence emission of the fluorophore associated with the cell or particle as a result of illumination by the laser beam will result when the wavelength of the laser light matches the absorption band of one or more fluorophores used …” in the last complete column 9 paragraph), and wherein the third light includes at least one of the excitation light and scattered light of the excitation light (e.g., “… laser light scattered by the sample particles having no phase lag …” in the last column 17 paragraph).
In regard to claim 4 which is dependent on claim 3, Lakowicz et al. also disclose that the light detection unit detects calibration processing light not including the second light and including the third light (e.g., “… lifetime varies with the presence or amount of the fluorophore …” in the last column 17 paragraph or alternatively it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that there is no second light when there is no “presence” “of the fluorophore”), and wherein the signal processing unit performs calibration processing for removing a signal component corresponding to the third light from the detection signal on the basis of a calibration signal corresponding to the calibration processing light and removes a signal component corresponding to the third light from the detection signal in consideration of a result of the performed calibration processing (e.g., “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …” in the first complete column 13 paragraph).
In regard to claim 10, Lakowicz et al. disclose an optical measurement method comprising:
(a) setting a modulation frequency of a light source (e.g., “… 20MHz …” in the first column 17 paragraph) outputting a first light to be lower than a value corresponding to a fluorescence lifetime (e.g., “… fluorescence lifetime of 24 ns …” in the last column 17 paragraph can also be labeled as a value of 1/24 ns = 1/24x10-9 s ≈ 41.7 MHz) indicating a period of time taken until an intensity of a second light generated from a sample irradiated with the first light drops from a peak value to 1/e (e.g., “… attenuation time of the emitted light (i.e. the fluorescence lifetime … typically 1/e or 63% of peak …” in the last column 2 paragraph);
(b) irradiating the sample with the first light (e.g., “… fluorescence emission of the fluorophore associated with the cell or particle as a result of illumination by the laser beam will result when the wavelength of the laser light matches the absorption band of one or more fluorophores used …” in the last complete column 9 paragraph);
(c) detecting (e.g., “… It should be understood by one of ordinary skill that a plurality of channels, one for each respective monochromatic beam of light, would be employed. The emitted light at each color would be detected by an optical transducer, such as a photodetector 29 …” in the first column 10 paragraph) detection light including the second light generated from the sample irradiated with the first light (e.g., “… fluorescence emission of the fluorophore associated with the cell or particle as a result of illumination by the laser beam will result when the wavelength of the laser light matches the absorption band of one or more fluorophores used …” in the last complete column 9 paragraph) and third light caused by the first light and having a phase equivalent to a phase of the first light (e.g., “… laser light scattered by the sample particles having no phase lag …” in the last column 17 paragraph); and
(d) removing a signal component corresponding to the third light from a detection signal corresponding to the detection light on the basis of a phase difference between the second light and the third light (e.g., “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …” in the first complete column 13 paragraph).
MPEP § 2144.05 states that “… In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of “50 to 100 Angstroms” considered prima facie obvious in view of prior art reference teaching that “for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms].” The court stated that “by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.”). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range) …“.
Thus alternatively, a prima facie case of obviousness exists (MPEP § 2144.05) since the claimed “modulation frequency of the light source to be lower than a value” range overlap the “appropriate pulse rate for the preferred embodiment would be ≥4 MHz ” range disclosed by the cited prior art (e.g., see “… appropriate pulse rate for the preferred embodiment would be ≥4 MHz …” in the first column 9 paragraph).
In regard to claim 11 which is dependent on claim 10, Lakowicz et al. also disclose detecting calibration processing light not including the second light and including the third light (e.g., “… lifetime varies with the presence or amount of the fluorophore …” in the last column 17 paragraph or alternatively it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that there is no second light when there is no “presence” “of the fluorophore”), and performing calibration processing for removing a signal component corresponding to the third light from the detection signal on the basis of a calibration signal corresponding to the calibration processing light and removing a signal component corresponding to the third light from the detection signal in consideration of a result of the performed calibration processing (e.g., “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …” in the first complete column 13 paragraph).
Claim(s) 2, 5-8, 12, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lakowicz et al. (US 5,504,337) in view of French et al. (US 2001/0019409).
In regard to claim 2 which is dependent on claim 1, the device of Lakowicz et al. lacks dividing the detection signal in units of predetermined times corresponding to the phase of the third light, individually amplifying each component of the divided detection signal, and synthesizing each of the amplified components. However, French et al. teach (paragraphs 50, 51, 53, 56, 58, and 114) that “… "phase bin" corresponding to a particular portion of a period … to perform heterodyning (or homodyning) operations using integrated photon pulses rather than analog charge … Two or more counters may be used to calculate phase and modulation (as described below) using the high-frequency signal … FIG. 3 shows a preferred implementation using four counters. Here, each counter captures photons for half a period, and each counter is delayed relative to the previous counter by 90 degrees … number of counted photons may be used to compute a frequency-domain quantity, such as phase and/or modulation, by Fourier transforming the numbers into the frequency domain. The Fourier transform can be used to separate harmonics of the excitation signal, which usually are unwanted, if four or more counters are used … phase Φ is the arctangent of the ratio of the quadrature and in-phase components:
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(5) … DC amplitude DC is the total number of photons, given by the sum of the number of photons counted in every phase bin: DC = θ1 + θ2 + θ3 + θ4 (7) … photon-counting frequency-domain measurements can be relatively insensitive to dark noise, background luminescence, scattering, absorption, and/or quenching, which may improve precision, accuracy, and robustness …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide “phase bin” for the signal processing unit in the device of Lakowicz et al. by dividing the detection signal in units of predetermined times corresponding to the phase of the third light, “each counter is delayed relative to the previous counter by 90 degrees” by individually amplifying each component of the divided detection signal, and calculate “DC amplitude” by synthesizing each of the amplified components in order to achieve “photon-counting frequency-domain measurements” so as to “be relatively insensitive to” “scattering” by removing a signal component corresponding to the third light from the detection signal.
In regard to claim 5 which is dependent on claim 4, while Lakowicz et al. also disclose (first complete column 13 paragraph) that “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …”, the device of Lakowicz et al. lacks an explicit description that the signal processing unit generates a lock-in switch signal having a phase shifted with respect to a cycle signal marking a cycle by an operation frequency of the signal processing unit according to the modulation frequency of the light source set by the light source driving circuit, outputs a signal component corresponding to the third light when the calibration signal and the switch signal are input, and adjusts the phase of the switch signal such that a voltage value of a signal component corresponding to the third light is within a predetermined range approximating zero in the calibration processing, and removes a signal component corresponding to the third light from the detection signal when the detection signal and the switch signal having the phase adjusted in the calibration processing are input. However, French et al. teach (paragraphs 44 and 60) that “… Frequency source 53 is configured to generate a frequency, which may be derived from or used to drive the light source, and which may be used to drive components of the sample and reference channels … "corrected" for instrumental factors giving rise to this difference to yield the measured values, for example, by measuring the apparent phase and modulation for a compound with known lifetime, calculating the correct phase and modulation, and deriving an instrument phase offset and instrument modulation factor. The measured phase will be the difference in the apparent phase and the instrument phase offset. Similarly, the measured modulation will be the product of the apparent modulation and the instrument modulation factor …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide calibration processing in the signal processing unit of Lakowicz et al., in order to achieve “the correct phase and modulation” for correcting “instrumental factors” such as the signal processing unit’s operation frequency having a cycle signal’s phase and the signal processing unit generates a lock-in switch signal “derived from” the light source driving circuit’s modulation frequency and adjusting any “instrumental” phase shift between the cycle and lock-in switch signals so that the third light is ~0 V for a corresponding third signal component.
In regard to claim 6 which is dependent on claim 5, while Lakowicz et al. also disclose (first complete column 13 paragraph) that “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …”, the device of Lakowicz et al. lacks an explicit description that the signal processing unit adjusts the phase of the switch signal such that the phase is delayed when the voltage value of a signal component corresponding to the third light is not within the predetermined range but is larger than a value within the predetermined range and adjusts the phase of the switch signal such that the phase advances when the voltage value of a signal component corresponding to the third light is not within the predetermined range but is smaller than a value within the predetermined range in the calibration processing. However, French et al. teach (paragraphs 44 and 60) that “… Frequency source 53 is configured to generate a frequency, which may be derived from or used to drive the light source, and which may be used to drive components of the sample and reference channels … "corrected" for instrumental factors giving rise to this difference to yield the measured values, for example, by measuring the apparent phase and modulation for a compound with known lifetime, calculating the correct phase and modulation, and deriving an instrument phase offset and instrument modulation factor. The measured phase will be the difference in the apparent phase and the instrument phase offset. Similarly, the measured modulation will be the product of the apparent modulation and the instrument modulation factor …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide calibration processing in the signal processing unit of Lakowicz et al., in order to achieve “the correct phase and modulation” for correcting “instrumental factors” such as the signal processing unit’s operation frequency having a cycle signal’s phase and the signal processing unit generates a lock-in switch signal “derived from” the light source driving circuit’s modulation frequency and adjusting any “instrumental” phase shift by advancing or delaying the lock-in switch signal relative to the cycle signal so that the third light is ~0 V for a corresponding third signal component.
In regard to claim 7 which is dependent on claim 6, the cited prior art is applied as in claim 1 above. Lakowicz et al. also disclose that the light source driving circuit sets the modulation frequency of the light source (e.g., “… 20MHz …” in the first column 17 paragraph) to be higher than a commercial frequency.
In regard to claim 8 which is dependent on claim 5, the device of Lakowicz et al. lacks that the signal processing unit generates, as the lock-in switch signals, a first signal, a second signal having a phase shifted with respect to the first signal by 90 degrees, a third signal realized by inverting the first signal, and a fourth signal realized by inverting the second signal using independently dedicated circuits. However, French et al. teach (paragraphs 50, 51, 53, 56, 58, and 114) that “… "phase bin" corresponding to a particular portion of a period … to perform heterodyning (or homodyning) operations using integrated photon pulses rather than analog charge … Two or more counters may be used to calculate phase and modulation (as described below) using the high-frequency signal … FIG. 3 shows a preferred implementation using four counters. Here, each counter captures photons for half a period, and each counter is delayed relative to the previous counter by 90 degrees … number of counted photons may be used to compute a frequency-domain quantity, such as phase and/or modulation, by Fourier transforming the numbers into the frequency domain. The Fourier transform can be used to separate harmonics of the excitation signal, which usually are unwanted, if four or more counters are used … phase Φ is the arctangent of the ratio of the quadrature and in-phase components:
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(5) … DC amplitude DC is the total number of photons, given by the sum of the number of photons counted in every phase bin: DC = θ1 + θ2 + θ3 + θ4 (7) … photon-counting frequency-domain measurements can be relatively insensitive to dark noise, background luminescence, scattering, absorption, and/or quenching, which may improve precision, accuracy, and robustness …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide “four” “phase bin” for the signal processing unit in the device of Lakowicz et al. wherein lock-in switch signals for “each counter is delayed relative to the previous counter by 90 degrees” so as to “be relatively insensitive to” “scattering” by removing a signal component corresponding to the third light from the detection signal.
In regard to claim 12 which is dependent on claim 11, while Lakowicz et al. also disclose (first complete column 13 paragraph) that “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …”, the method of Lakowicz et al. lacks an explicit description that generating a lock-in switch signal having a phase shifted with respect to a cycle signal marking a cycle in accordance with a modulation frequency of a light source, outputting a signal component corresponding to the third light when the calibration signal and the switch signal are input, and adjusting the phase of the switch signal such that a voltage value of a signal component corresponding to the third light is within a predetermined range approximating zero in the calibration processing; and removing a signal component corresponding to the third light from the detection signal when the detection signal and the switch signal having the phase adjusted in the calibration processing are input. However, French et al. teach (paragraphs 44 and 60) that “… Frequency source 53 is configured to generate a frequency, which may be derived from or used to drive the light source, and which may be used to drive components of the sample and reference channels … "corrected" for instrumental factors giving rise to this difference to yield the measured values, for example, by measuring the apparent phase and modulation for a compound with known lifetime, calculating the correct phase and modulation, and deriving an instrument phase offset and instrument modulation factor. The measured phase will be the difference in the apparent phase and the instrument phase offset. Similarly, the measured modulation will be the product of the apparent modulation and the instrument modulation factor …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide calibration processing in the signal processing unit of Lakowicz et al., in order to achieve “the correct phase and modulation” for correcting “instrumental factors” such as the signal processing unit’s operation frequency having a cycle signal’s phase and the signal processing unit generates a lock-in switch signal “derived from” the light source driving circuit’s modulation frequency and adjusting any “instrumental” phase shift between the cycle and lock-in switch signals so that the third light is ~0 V for a corresponding third signal component.
In regard to claim 13 which is dependent on claim 12, while Lakowicz et al. also disclose (first complete column 13 paragraph) that “… there exists a specific phase setting of the variable phase shifter that causes the autofluorescence signal to become equal to zero. This principal is applicable also to a combination of autofluorescent light and unrejected scattered radiation …”, the method of Lakowicz et al. lacks an explicit description that in the calibration processing, the phase of the switch signal is adjusted such that the phase is delayed when the voltage value of a signal component corresponding to the third light is not within the predetermined range but is larger than a value within the predetermined range, and the phase of the switch signal is adjusted such that the phase advances when the voltage value of a signal component corresponding to the third light is not within the predetermined range but is smaller than a value within the predetermined range. However, French et al. teach (paragraphs 44 and 60) that “… Frequency source 53 is configured to generate a frequency, which may be derived from or used to drive the light source, and which may be used to drive components of the sample and reference channels … "corrected" for instrumental factors giving rise to this difference to yield the measured values, for example, by measuring the apparent phase and modulation for a compound with known lifetime, calculating the correct phase and modulation, and deriving an instrument phase offset and instrument modulation factor. The measured phase will be the difference in the apparent phase and the instrument phase offset. Similarly, the measured modulation will be the product of the apparent modulation and the instrument modulation factor …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide calibration processing in the signal processing unit of Lakowicz et al., in order to achieve “the correct phase and modulation” for correcting “instrumental factors” such as the signal processing unit’s operation frequency having a cycle signal’s phase and the signal processing unit generates a lock-in switch signal “derived from” the light source driving circuit’s modulation frequency and adjusting any “instrumental” phase shift by advancing or delaying the lock-in switch signal relative to the cycle signal so that the third light is ~0 V for a corresponding third signal component.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lakowicz et al. in view of French et al. as applied to claim(s) 11 above, and further in view of Pache et al. (US 2013/0210028).
In regard to claim 14 which is dependent on claim 11 in so far as understood, while Lakowicz et al. also disclose that in the sample (e.g., “… compounds, mixtures, surfaces, solutions, emulsions, suspensions, mixtures, cell cultures, fermentation cultures, cells, tissues, secretions and/or derivatives or extracts thereof. Samples, as defined above, which can be used in methods of the present invention for sensing analytes based on fluorescence lifetimes also include samples that can be clear or turbid. Such samples to be measured according to the present invention require only that the fluorophore used be contacted with the sample such that the analyte to be sensed influences the lifetime of the fluorophore such that the lifetime varies with the presence or amount of the fluorophore …” in the first column 7 paragraph), a dripping portion for dripping a specimen (e.g., “… pass in a stream …” in the last complete column 8 paragraph), a holding portion for holding a fluorescent reagent (e.g., “… flow chamber 3 of the flow cytometer, in a manner well known in the art …” in the last complete column 8 paragraph), and a measurement portion for fixing the fluorescent reagent are disposed toward a downstream side from an upstream side (e.g., “… At the observation point each cell in the stream of cells is irradiated, and the resulting radiation emission from each cell is detected …” in the last complete column 8 paragraph), the method of Lakowicz et al. lacks an explicit description that the calibration processing light is detected by irradiating an area on the downstream side of a capturing antibody labeled with the fluorescent reagent in the sample with the first light. However, French et al. teach (paragraphs 44 and 60) that “… Frequency source 53 is configured to generate a frequency, which may be derived from or used to drive the light source, and which may be used to drive components of the sample and reference channels … "corrected" for instrumental factors giving rise to this difference to yield the measured values, for example, by measuring the apparent phase and modulation for a compound with known lifetime, calculating the correct phase and modulation, and deriving an instrument phase offset and instrument modulation factor. The measured phase will be the difference in the apparent phase and the instrument phase offset. Similarly, the measured modulation will be the product of the apparent modulation and the instrument modulation factor …” and Pache et al. teach (paragraphs 40 and 65) that “… a flow cell such as commonly used in flow cytometry applications may also be used to read the code of the microparticles as they fly through the flow cell. (See, for instance, Nolan, et al., Trends in Biotechnology, 20(1):9-12, 2002, and Wilson et al., "Encoded Microcarriers for HighThroughput Multiplexed Detection," Angew. Chem. Int. Ed., 45(37):6104-6117, 2006, especially at pages 6110-6111 and FIGS. 6 and 7, both of which are incorporated herein by reference in their entireties for all purposes) … encoded microparticles may be bound to various primary antibodies which are specific for a first antigenic determinant on the target …”. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to irradiate the first light to an area of the sample of Lakowicz et al. on the downstream side of “encoded microparticles may be bound to various primary antibodies which are specific for a first antigenic determinant on the target” in order to detect the calibration processing light so as to achieve “the correct phase and modulation”.
Allowable Subject Matter
Claim(s) 9 is/are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the instant application is deemed to be directed to a nonobvious improvement over the invention disclosed in US 5,504,337. The improvement comprises in combination with other recited elements, the signal processing unit is set by switching between the operation frequencies of two kinds at a predetermined proportion.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/ patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/ patents/apply/applying-online/eterminal-disclaimer.
Claim(s) 1 and 4 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 6 and 6 of U.S. Patent No. 12,287,288, respectively. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims in this application define an invention that is anticipated by an invention claimed in the patent.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 5,257,202 teaches a frequency domain fluorometer.
US 5,270,548 teaches a frequency domain fluorometer.
US 6,384,951 teaches a frequency domain fluorometer.
US 2003/0062485 teaches a frequency domain fluorometer.
US 2004/0126780 teaches fluorescence correlation spectroscopy.
US 2011/0168916 teaches a frequency domain fluorometer.
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/SL/
Examiner, Art Unit 2884
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884
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