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 .
Claim Rejections - 35 USC § 112
Note that dependent claims will have the deficiencies of base and intervening claims.
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 1-4 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention:
a) claim 1 recites the limitation "a sample injection step of injecting the sample into the capillary containing the sieving matrix charged in the sieving matrix filling step; . . . . [italicizing by the Examiner]" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
b) claim 1 recites the limitation "a sample injection step of injecting the sample into the capillary containing the sieving matrix charged in the sieving matrix filling step; . . . . [italicizing by the Examiner]" in lines 5-6. It is not clear how to understand Applicant’s use of the word “charge” here. Does Applicant mean that the capillary has been charged, that is, filled, with sieving matrix or has an electrical charge imparted to the sieving medium? If Applicant is being his own lexicographer please heed MPEP 2173.05(a).
c) claim 4 requires “. . . ., a repreparation display step of outputting a display to prompt repreparation of the sample, wherein after proceeding to the reading step after the analysis condition adjustment step is performed, if the analysis result is determined to be abnormal again in the abnormality determination step, the method proceeds to the repreparation display step. [italicizing by the Examiner]” It is not clear what is meant by the phrase “repreparation of the sample”. What is the scope of this phrase, are all of the previously performed preparation steps be repeated? One or two examples of such “repreparation of the sample” would be helpful in better understanding the phrase. The only occurrence in Applicant’s originally filed specification of “sample repreparation” is the following in paragraph [0040]
PNG
media_image1.png
528
1258
media_image1.png
Greyscale
If Applicant is being is own lexicographer with regarding “repreparation” please heed MPEP 2173.05(a).
d) claim 4 recites the limitation "prompt repreparation of the sample [underlining by the Examiner] " in line 2. There is insufficient antecedent basis for this limitation in the claim as there is no initial repreparation of the sample.
e) claim 10 requires “. . . ., wherein when determining the analysis result to be abnormal even if reanalyzing the sample under the adjusted analysis condition, the control section outputs a display to prompt sample repreparation to the display section. [italicizing by the Examiner]” It is not clear what is meant by the phrase “sample repreparation”. What is the scope of this phrase, are all of the previously performed preparation steps be repeated? One or two examples of such “sample repreparation” would be helpful in better understanding the phrase. The only occurrence Applicant’s originally filed specification of “sample repreparation” is the following in specification paragraph [0040]
PNG
media_image1.png
528
1258
media_image1.png
Greyscale
If Applicant is being is own lexicographer with regarding “repreparation” please heed MPEP 2173.05(a).
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, 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.
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.
Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Aritome et al. US 2021/0156821 A1 (hereafter “Aritome”) in view of Mark Perlin US 6,807,490 B1 (hereafter ‘Perlin”), Yamamoto et al. US 2001/0040096 A1 (hereafter “Yamamoto”), Thomas Casavant US 5,904,822 (hereafter “Casavant”) or Liu et al.
US 2004/0048276 A1 (hereafter “Liu”) or Asp et al. US 6,468,409 B1 (hereafter “Asp”), and in view of Harada et al. US 2022/0236220 A1 (hereafter “Harada”) or Oishi et al.
US 2010/0006436 A1 (hereafter “Oishi”), and in view of Majumdar et al.
US 2020/0003728 A1 (hereafter “Majumdar”), Asp, and Chen et al. US 5,569,366 (hereafter “Chen”).
Addressing claim 1, Aritome discloses a method of analyzing features involved in a sample by electrophoresing the sample using a capillary and a sieving matrix (see the title, Figure 8 and paragraphs [0036]-[0048]. Note that one of ordinary skill in the art would understand that the phoresis medium referred to in these paragraphs may be a sieving medium – “In recent years, a capillary electrophoresis device in which a capillary is filled with a phoresis medium such as a polymer gel and a polymer solution is widely used as an electrophoresis device.” See paragraph [0002].), the method comprising:
a reading step of reading an analysis condition (this reading step is implied by step S13 in Figure 8 (“Temperature Control of Capillary”) and related paragraph [0039]- “In step S13, the capillary array 101 set inside is kept at a constant temperature by the thermostat oven unit 113.” The analysis condition implicitly read is temperature.);
a sieving matrix filling step of filling the capillary with the sieving matrix (note step S15 in Figure 8 (“Solution Delivery of Phoresis Medium” ). Also note the following in paragraph [0041], “The control section 600 drives the solution-delivering mechanism 106, and presses and slides the seal 502 of the phoresis medium container 102 upward by the plunger 302, thereby delivering the phoresis medium 506 sealed in the phoresis medium container 102 to individual capillary 401 via the capillary head 403.”);
a sample injection step of injecting the sample into the capillary containing the sieving matrix charged in the sieving matrix filling step (note step S17 in Figure 8 (“Sample Introduction” ). Also note the following in paragraph [0043], “ Here, the control section 600 controls the power source 408 to apply a high voltage to the capillary array 101, and introduces a sample to the tip of each capillary 401.” );
an electrophoresing step of electrophoresing the sample in the sieving matrix, the sample being injected in the sample injection step (note step S19 in Figure 8 (“Electrophoresis”). Also note the following in paragraph [0045], “Here, the control section 600 controls the power source 408 to apply the high voltage to the capillary array 101, whereby electrophoresis is performed.”); and
an analysis condition adjustment step of adjusting the analysis condition (this step is implied by step S13 in Figure 8 (“Temperature Control of Capillary”) and related paragraph [0039]- “In step S13, the capillary array 101 set inside is kept at a constant temperature by the thermostat oven unit 113.”1).
Aritome, though, does not disclose “a signal height determination step of determining whether a signal height detected by a detection unit during application of laser light in the electrophoresing step is less than a predetermined threshold; . . . . “ As a first matter, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the light source in Aritome (see paragraph [0031]) be a laser because Aritome discloses fluorescence detection (again see paragraph [0031]) and laser light is a well-known means in the electrophoresis art for applying excitation light to a compound that inherently fluoresces at a certain wavelength or is labeled to do so. See, for example, Perlin col. 1:13-20 and col. 2:64 – col. 3:1-12; and Yamamoto the title and paragraph [0005]. Put another way, to have the light source in Aritome be a laser light is prima facie obvious, in light or Perlin and Yamamoto, as simple substitution of one known element (light source for fluorescence excitation) for another to obtain predictable results. See MPEP 2143(I)(B). Cavasant discloses methods and apparatus for analyzing gels (sieving matrices). See the title. The method includes monitoring band intensity and comparing intensity of all bands. See Figure 3E. The method also includes a No-Call Cut-off feature. “The No-Call Cut-off feature determines the minimum signal intensity, resulting from staining the gel and displaying the straightened gel image on display unit 53, that is called a (real) band by the system; below the minimum signal intensity level the system gives a "no-call" response, i.e. the region of the gel giving a sub-minimal signal intensity is considered not to be a band and is not included in the analysis. The No-Call Cut-off feature is dependent on the determination by band intensity monitoring unit 41 and band average intensity comparison unit 44 of the relative signal intensity of a given band of the gel sub-image compared with the average signal intensity of all bands of the gel sub-image. As an example, when the No-Call Cut-off parameter is set at a value of 0.85, a given band of the gel sub-image must provide a signal intensity which is at least 85% that of the average signal intensity for all bands of that gel sub-image. [italicizing by the Examiner]” See Cavasant col. 18:10-48.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the method of Aritome as modified by Perlin and Yamamoto to include a signal height determination step as taught by Cavasant because
(1) Aritome discloses optical detection (see Aritome paragraph [0031]);
(2) the No-Call Cut-off feature of Cavasant will allow the method of Aritome to perform automated removal of the peaks from electropherograms that are very likely to be false positives of analytes of interest (“no-calls”; see again Cavasant col. 18:10-48), which will result in a more accurate determination of the presence of sample components of interest.
Alternatively, Liu discloses a capillary electrophoresis method for determining the presence of a methylated cytosine in a first sample comprising a first nucleotide containing compound. See the title, Abstract, and Figure 3a. This method includes an automated comparison process that identifies a peak “by, for example, establishing an intensity threshold that is greater than the average intensity in the electropherogram. Fluorescence data that have an intensity greater than the threshold intensity are identified as peaks.” See paragraph [0125]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the method of Aritome as modified by Perlin and Yamamoto to include a signal height determination step as taught by Liu because this will allow the method of Aritome to perform automated removal of the peaks from electropherograms that are very likely to be false positives of analytes of interest, which will result in a more accurate determination of the presence of sample components of interest.
Alternatively, Asp discloses an electrophoresis method and apparatus of optically detecting substances. See the title, Abstract, and Figure 1. “In a second embodiment of the invention, the illumination varying circuit 9 is adapted to sample the signal from the photodetector 7, and to compare successive samples. In dependence on that sample comparison, the illumination varying circuit 9 is adapted to control the laser diode 1 to either increase or decrease its output power.” See Asp col. 3:2-23. Also see claim 1. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the method of Aritome as modified by Perlin and Yamamoto to include a signal height determination step as taught by Asp because this will eliminate the problem of the detection signal from a photodetector being smaller than a predetermined reference value because of an abnormal intensity of the excitation light. See Asp col. 1:10-55.
Aritome as modified by Cavasant or Liu or Asp does not disclose “an abnormality determination step of statistically determining whether an analysis result obtained in the electrophoresing step is abnormal by comparing the analysis result with another analysis result obtained under the same analysis condition; . . . . .”
Harada discloses a microchip electrophoresis device having a controller programmed to statistically determine (by using relative deviation data) whether the microchip is in a usable state, that is, whether it has an abnormality, by comparing an analysis result obtained in the electrophoresing step with another analysis result obtained under the same analysis condition. See in Harada the title, Abstract, Figure 2, and paragraph [0022]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform an abnormality determination step as taught by Harada in the method of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp because this will “prevent electrophoresis analysis from being performed using a microchip [or capillary device] in a state unsuitable for use in electrophoresis analysis.” See Harada paragraphs [0003], [0004], and [0006].
Alternatively, Oishsi discloses a hemoglobin measurement method and electrophoresis apparatus. See the title. The method involves statistically determining the coefficient of variation of the hemoglobin determination (analysis result) or determining within-run reproducibility of electropherograms by using standard deviation data. See paragraphs [0212]-[0215]. One of ordinary skill in the art would understand that a too large statistical indicator, such as coefficient of variation, would indicate an abnormality in the analysis result as Oishi states, “As shown in Table 2, the CV value indicating the data variation obtained by the within-run reproducibility test under the measurement conditions of Example 1 was as good as about 1%. The results of Examples 2 and 3 were also favorable like in Example 1. On the contrary, the CV value obtained by the measurement conditions of Comparative Example 2 was remarkably large and completely unsatisfactory for use in control of the HbA1c value of diabetics. [italicizing by the Examiner]” See Oishi paragraph [0230]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform an abnormality determination step as taught by Oishi in the method of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp because this will help prevent anyone relying upon the analysis result to make a possibly wrong decision, especially a medical treatment decision, due to the result having a high likelihood of being inaccurate.
As for performing, as required by claim 1, “an analysis condition adjustment step of adjusting the analysis condition, wherein if the signal height is determined to be less than the predetermined threshold in the signal height determination step, and if the analysis result is determined to be abnormal in the abnormality determination step, in the analysis condition adjustment step, an application condition of a voltage to the capillary by a power supply during injection of the sample or an application condition of the laser light by the detection unit is adjusted to a condition under which intensity of a signal detected by the detection unit increases, and then the method proceeds to the reading step again... [italicizing by the Examiner]”, in Aritome alone, as indicated earlier in this claim rejection, the analysis condition adjustment step involves adjusting the temperature during analysis. However, Asp does disclose appropriately adjusting (increasing or decreasing) the laser light of the detection unit if the signal height is determined to be less than the predetermined threshold in the signal height determination step or if the analysis result is determined to be abnormal in the abnormality determination step. See Asp the Abstract, col. 3:2-23, and claim 1. Majumdar discloses automated quality control and spectral error correction for sample analysis instruments such as a capillary electrophoresis device. See the title, Abstract, and Figure 1. One of the corrective actions that may be taken to evolve an abnormality determination is adjusting the electrophoresis run current or voltage. See Majumdar paragraphs [0157](especially the last sentence), [0168](especially the last sentence), [0243], [0245], and [0252]. Chen discloses that the electrophoresis voltage is not only a result effective variable (determining migration time), but can a cause of abnormality by raising the electrophoresis temperature detrimentally high or by set at a value that results in no separation of sample composition components. See in Chen the Abstract and col. 6:33-44. Thus, in light of these disclosures of Asp, Majumdar, and Chen, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform the claimed analysis condition adjustment step in the method of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi, because this step may be able to satisfactorily resolve or at least compensate for the abnormality by the more convenient and time-saving changing an electrophoresis operational condition (laser light intensity or voltage applied to the capillary) rather having to shut down the electrophoresis system and clean or even replace one or more parts.
Addressing claim 5, Aritome discloses a capillary electrophoresis device (see the title), comprising:
a capillary (any of the capillaries in capillary array 101 in Figure 1 and paragraph [0024]) to be filled with a sieving matrix (see paragraphs [0036]-[0048]. Note that one of ordinary skill in the art would understand that the phoresis medium referred to in these paragraphs may be a sieving medium – “In recent years, a capillary electrophoresis device in which a capillary is filled with a phoresis medium such as a polymer gel and a polymer solution is widely used as an electrophoresis device.” See paragraph [0002].);
a power supply that applies a voltage to the capillary to electrophorese a sample (note power source 408 in Figure 6 and the following in paragraph [0034], A negative high voltage is applied from a power source 408 to the other end of each capillary via the load header 406 and the SUS pipe 407, whereby a sample introduced to the negative-electrode-side tip of each capillary is moved in the capillary by electrophoresis and is detected by the detection section 402.“ ) ; and a detection unit (402 in Figure 6 and paragraph [0034]) that detects a signal when light is applied to the sample being electrophoresed in the capillary (see the sentence from paragraph [0034] reproduced just above regarding the “power supply”); and
a control section (600 in Figure 6 and paragraph [0034]) that controls operations of the power supply and the detection unit (see paragraph [0045] ), and calculates an analysis result (this feature is implied by the following, “One [Once] analysis is completed by analyzing the data detected by this series of movements.” See paragraph [0048].).
Aritome, though, does not disclose that the light applied to the sample being electrophoresed in the capillary is laser light. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the light source in Aritome (see paragraph [0031]) be a laser because Aritome discloses fluorescence detection (again see paragraph [0031]) and laser light is a well-known means in the electrophoresis art for applying excitation light to a compound that inherently fluoresces at a certain wavelength or is labeled to do so. See, for example, Perlin col. 1:13-20 and col. 2:64 – col. 3:1-12; and Yamamoto the title and paragraph [0005]. Put another way, to have the light source in Aritome be a laser light is prima facie obvious, in light or Perlin and Yamamoto, as simple substitution of one known element (light source for fluorescence excitation) for another to obtain predictable results. See MPEP 2143(I)(B).
Aritome also does not disclose
wherein the control section:
determines whether a signal height detected by the detection unit is less than a predetermined threshold, and compares the calculated analysis result with another analysis result obtained under the same analysis condition and thus statistically determines whether the calculated analysis result is abnormal; and
when determining the calculated signal height to be less than the predetermined threshold, and when determining the analysis result to be abnormal, adjusts an application condition of a voltage to the capillary by the power supply during injection of the sample or an application condition of the laser light by the detection unit to a condition under which intensity of the signal detected by the detection unit increases, and operates the power supply and the detection unit under the adjusted analysis condition and performs reanalysis.
Cavasant discloses methods and apparatus for analyzing gels (sieving matrices). See the title. The method includes monitoring band intensity and comparing intensity of all bands. See Figure 3E. The method also includes a No-Call Cut-off feature. “The No-Call Cut-off feature determines the minimum signal intensity, resulting from staining the gel and displaying the straightened gel image on display unit 53, that is called a (real) band by the system; below the minimum signal intensity level the system gives a "no-call" response, i.e. the region of the gel giving a sub-minimal signal intensity is considered not to be a band and is not included in the analysis. The No-Call Cut-off feature is dependent on the determination by band intensity monitoring unit 41 and band average intensity comparison unit 44 of the relative signal intensity of a given band of the gel sub-image compared with the average signal intensity of all bands of the gel sub-image. As an example, when the No-Call Cut-off parameter is set at a value of 0.85, a given band of the gel sub-image must provide a signal intensity which is at least 85% that of the average signal intensity for all bands of that gel sub-image. [italicizing by the Examiner]” See Cavasant col. 18:10-48.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the control section of Aritome as modified by Perlin and Yamamoto to be able to perform a signal height determination step as taught by Cavasant because
(1) Aritome discloses optical detection (see Aritome paragraph [0031]);
(2) the No-Call Cut-off feature of Cavasant will allow the method of Aritome to perform automated removal of the peaks from electropherograms that are very likely to be false positives of analytes of interest (“no-calls”; see again Cavasant col. 18:10-48), which will result in a more accurate determination of the presence of sample components of interest.
Alternatively, Liu discloses a capillary electrophoresis method for determining the presence of a methylated cytosine in a first sample comprising a first nucleotide containing compound. See the title, Abstract, and Figure 3a. This method includes an automated comparison process that identifies a peak “by, for example, establishing an intensity threshold that is greater than the average intensity in the electropherogram. Fluorescence data that have an intensity greater than the threshold intensity are identified as peaks.” See paragraph [0125]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the control section of Aritome as modified by Perlin and Yamamoto to be able to perform a signal height determination step as taught by Liu because this will allow the control section of Aritome to perform automated removal of the peaks from electropherograms that are very likely to be false positives of analytes of interest, which will result in a more accurate determination of the presence of sample components of interest.
Alternatively, Asp discloses an electrophoresis method and apparatus of optically detecting substances. See the title, Abstract, and Figure 1. “In a second embodiment of the invention, the illumination varying circuit 9 is adapted to sample the signal from the photodetector 7, and to compare successive samples. In dependence on that sample comparison, the illumination varying circuit 9 is adapted to control the laser diode 1 to either increase or decrease its output power.” See Asp col. 3:2-23. Also see claim 1. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to modify the control section of Aritome as modified by Perlin and Yamamoto to be able to perform a signal height determination step as taught by Asp because this will eliminate the problem of the detection signal from a photodetector being smaller than a predetermined reference value because of an abnormal intensity of the excitation light. See Asp col. 1:10-55.
Aritome as modified by Cavasant or Liu or Asp does not disclose “an abnormality determination step of statistically determining whether an analysis result obtained in the electrophoresing step is abnormal by comparing the analysis result with another analysis result obtained under the same analysis condition; . . . . .”
Harada discloses a microchip electrophoresis device having a controller programmed to statistically determine (by using relative deviation data) whether the microchip is in a usable state, that is, whether it has an abnormality, by comparing an analysis result obtained in the electrophoresing step with another analysis result obtained under the same analysis condition. See in Harada the title, Abstract, Figure 2, and paragraph [0022]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to be able to perform an abnormality determination step as taught by Harada using the control section of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp because this will “prevent electrophoresis analysis from being performed using a microchip [or capillary device] in a state unsuitable for use in electrophoresis analysis.” See Harada paragraphs [0003], [0004], and [0006].
Alternatively, Oishsi discloses a hemoglobin measurement method and electrophoresis apparatus. See the title. The method involves statistically determining the coefficient of variation of the hemoglobin determination (analysis result) or determining within-run reproducibility of electropherograms by using standard deviation data. See paragraphs [0212]-[0215]. One of ordinary skill in the art would understand that a too large statistical indicator, such as coefficient of variation, would indicate an abnormality in the analysis result as Oishi states, “As shown in Table 2, the CV value indicating the data variation obtained by the within-run reproducibility test under the measurement conditions of Example 1 was as good as about 1%. The results of Examples 2 and 3 were also favorable like in Example 1. On the contrary, the CV value obtained by the measurement conditions of Comparative Example 2 was remarkably large and completely unsatisfactory for use in control of the HbA1c value of diabetics. [italicizing by the Examiner]” See Oishi paragraph [0230]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to be able to perform an abnormality determination step as taught by Oishi using the control section of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp because this will help prevent anyone relying upon the analysis result to make a possibly wrong decision, especially a medical treatment decision, due to the result having a high likelihood of being inaccurate.
As for performing, as required by claim 1, “an analysis condition adjustment step of adjusting the analysis condition, wherein if the signal height is determined to be less than the predetermined threshold in the signal height determination step, and if the analysis result is determined to be abnormal in the abnormality determination step, in the analysis condition adjustment step, an application condition of a voltage to the capillary by a power supply during injection of the sample or an application condition of the laser light by the detection unit is adjusted to a condition under which intensity of a signal detected by the detection unit increases, and then the method proceeds to the reading step again... [italicizing by the Examiner]”, in Aritome alone, as indicated earlier in this claim rejection, the analysis condition adjustment step involves adjusting the temperature during analysis. However, Asp does disclose appropriately adjusting (increasing or decreasing) the laser light of the detection unit if the signal height is determined to be less than the predetermined threshold in the signal height determination step or if the analysis result is determined to be abnormal in the abnormality determination step. See Asp the Abstract, col. 3:2-23, and claim 1. Majumdar discloses automated quality control and spectral error correction for sample analysis instruments such as a capillary electrophoresis device. See the title, Abstract, and Figure 1. One of the corrective actions that may be taken to evolve an abnormality determination is adjusting the electrophoresis run current or voltage. See Majumdar paragraphs [0157](especially the last sentence), [0168](especially the last sentence), [0243], [0245], and [0252]. Chen discloses that the electrophoresis voltage is not only a result effective variable (determining migration time), but can a cause of abnormality by raising the electrophoresis temperature detrimentally high or by set at a value that results in no separation of sample composition components. See in Chen the Abstract and col. 6:33-44. Thus, in light of these disclosures of Asp, Majumdar, and Chen, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to be able to perform the claimed analysis condition adjustment step using the control section of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi, because this step may be able to satisfactorily resolve or at least compensate for the abnormality by the more convenient and time-saving changing an electrophoresis operational condition (laser light intensity or voltage applied to the capillary) rather having to shut down the electrophoresis system and clean or even replace one or more parts.
Claims 4 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Aritome in view of Perlin and Yamamoto, and in view of Cavasant or Liu or Asp, and in view of modified by Harada or Oishi as applied to claims 1 and 5 above, and further in view of Matsumoto et al. US 2007/0134706 A1 (hereafter “Matsumoto”) and Krane et al. US 2004/0215401 A1 (hereafter “Krane”).
Addressing claim 4, Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi does not disclose “a repreparation display step of outputting a display to prompt repreparation of the sample, wherein after proceeding to the reading step after the analysis condition adjustment step is performed, if the analysis result is determined to be abnormal again in the abnormality determination step, the method proceeds to the repreparation display step.”
As a first matter, Matsumoto discloses gene information and display method and apparatus. See the title, Abstract, Figure 6 (noting Display Unit 601 therein), and paragraph [0083] . It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide a display as taught by Matsumoto for use with the method of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi because it allows complicated analysis of electropherogram peaks to aided by visual imaging techniques, such as overlaying images and color coding the peaks. See in Matsumoto Figures 9-25 and 27-40, and paragraphs [0045]-[0047] and [0049]-[0061].
Krane discusses computerized analysis of forensic DNA evidence. See the title. Krane discloses a way to classify electropherogram peaks as to whether that are actually DNA peaks or are false peaks due an electrophoresis system abnormality, such as “[a]ir bubbles, urea crystals, dye blobs, voltage spikes, and sample contamination . . . .” See Krane paragraphs [0111]-[0118] and [0145]. If the system abnormality is sample contamination, then it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the method of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi output a display to prompt repreparation of the sample so that a clean sample may be electrophoresed, which will allow for a more acuate analysis of the sample..
Addressing claim 10, Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi does not disclose “a display section that displays an analysis result, wherein when determining the analysis result to be abnormal even if reanalyzing the sample under the adjusted analysis condition, the control section outputs a display to prompt sample repreparation to the display section.”
As a first matter, Matsumoto discloses gene information and display method and apparatus. See the title, Abstract, Figure 6 (noting Display Unit 601 therein), and paragraph [0083] . It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide a display as taught by Matsumoto in the capillary electrophoresis device of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi because it allows complicated analysis of electropherogram peaks to aided by visual imaging techniques, such as overlaying images and color coding the peaks. See in Matsumoto Figures 9-25 and 27-40, and paragraphs [0045]-[0047] and [0049]-[0061].
Krane discusses computerized analysis of forensic DNA evidence. See the title. Krane discloses a way to classify electropherogram peaks as to whether that are actually DNA peaks or are false peaks due an electrophoresis system abnormality, such as “[a]ir bubbles, urea crystals, dye blobs, voltage spikes, and sample contamination . . . .” See Krane paragraphs [0111]-[0118] and [0145]. If the system abnormality is sample contamination, then it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the control section of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi be able to output the display to prompt repreparation of the sample so that a clean sample may be electrophoresed, which will allow for a more acuate analysis of the sample.
Allowable Subject Matter
Claims 2 and 3 would be allowable if rewritten to overcome the rejections 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.
Claims 6, 7, and 9 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:
a) the International Search Report for international application PCT/JP2022/028984 cites JP 2005-351690 A as a “Y” document against
claims 1-10 of that application, cites JP 62-251651 A as a “Y” document against
claims 1-10; cites JP 2008-122169 A as a “Y” document against claims 2 and 6-8; and cites JP 2012-68234 A as a “Y” document against claims 3-4 and 9-10. The corresponding International Preliminary Report on Patentability deems claims 1-7 and 9-10 to have novelty, but lack an inventive step over the aforementioned “Y” documents, which are referred to as Document 1 – Document 4, respectively. The corresponding Written Opinion, based on an English language translation obtained by the U.S. Examiner, likewise deems claims 1-7 and 9-10 to have novelty, but lack an inventive step over the aforementioned “Y” documents, also referred to as Document 1 – Document 4.
However, none of Document’s 1-42 disclose, as required by claim 1 of U.S. application 18/873963, the following features bounded by the dotted lines
PNG
media_image2.png
270
760
media_image2.png
Greyscale
PNG
media_image3.png
170
730
media_image3.png
Greyscale
For example, regarding any statistical determination Document 1 only discloses the following
PNG
media_image4.png
166
768
media_image4.png
Greyscale
See page 4 of the Document 1 translation.
Similarly, Documents 1-4 do not disclose, as required by claim 1 of U.S. application 18/873963, the following features bounded by the dotted lines
PNG
media_image5.png
346
782
media_image5.png
Greyscale
PNG
media_image6.png
110
748
media_image6.png
Greyscale
b) in claim 2 the combination of limitations includes the following underlined feature
PNG
media_image7.png
318
728
media_image7.png
Greyscale
Although Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi does not disclose a signal saturation determination step and a signal peak estimation step it would have been obvious to perform them in light of Bram et al. US 2020/0048696 A1 (hereafter “Bram”) paragraphs [0147], [0251], and [0252], which describe signal saturation resolution, there is no suggestion of in the analysis condition adjustment step, having the analysis condition the adjusted based on the peak estimated in the signal peak estimation step to an analysis condition under which no signal is saturated. Instead, a preprocessing step involving extrapolating peak saturation over regions where saturation occurred would be performed. See again Bram paragraph [0252]. King et al. US 2019/0353613 A1 (hereafter “King”) discloses methods for analyzing raw electropherogram data. These methods include dealing with signal saturation, though, by making use of shot exposure times and long exposure times. See King paragraphs [0103]-[0114].
c) in claim 3 the combination of limitations includes the following underlined feature
PNG
media_image8.png
238
756
media_image8.png
Greyscale
In contrast, in the method Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi once the analysis result is determined to be abnormal then corrective action would be taken to minimize or eliminate any likely source or error in the analysis result.
d) in claim 6 the combination of limitations includes the following underlined feature
PNG
media_image9.png
176
720
media_image9.png
Greyscale
Although Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi does not disclose wherein when the signal detected by the detection unit is saturated, the control section estimates a peak of a signal waveform, it would have been obvious to have the control section be able to do so in light of Bram paragraphs [0147], [0251], and [0252], which describe signal saturation resolution; however, there is no suggestion of having the analysis condition the adjusted based on the peak estimated in the signal peak estimation step to an analysis condition under which no signal is saturated. Instead, a preprocessing step involving extrapolating peak saturation over regions where saturation occurred would be performed. See again Bram paragraph [0252]. King et al. US 2019/0353613 A1 (hereafter “King”) discloses methods for analyzing raw electropherogram data. These methods include dealing with signal saturation, though, by making use of shot exposure times and long exposure times. See King paragraphs [0103]-[0114].
e) claim 7 depends from allowable claim 6.
f) in claim 9 the combination of limitations includes the following underlined feature
PNG
media_image10.png
182
710
media_image10.png
Greyscale
In contrast, in the capillary electrophoresis device of Aritome as modified by Perlin and Yamamoto, and by Cavasant or Liu or Asp, and as modified by Harada or Oishi, the control section is configured so that once the analysis result is determined to be abnormal then action would be taken to either resolve the abnormality or compensate for it.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER STEPHAN NOGUEROLA whose telephone number is (571)272-1343. The examiner can normally be reached on Monday - Friday 9:00AM-5:30 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan Van can be reached on 571 272-8521. 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.
/ALEXANDER S NOGUEROLA/ Primary Examiner, Art Unit 1795
1 So , the claimed “reading step” and the “analysis condition adjustment step” are implied sub-steps of step S13 in Aritome Figure 8.
2 The U.S. Examiner has obtained English language translations of Document 1 and Document 2.
US 2008/0110756 A1 is an English language equivalent to Document 3. US 2012/0037508 A1 is an English language equivalent to Document 4.
Prosecution Insights