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 .
Status of the Claims
The Amendment filed January 2, 2026 has been entered. Claim 79 has been amended. Claims 84-96 have been withdrawn previously; claims 1-74, 76-77, and 82-83 have been cancelled previously. Claims 75, 78-81, and 97-103 are examined herein.
Status of the Rejection
Applicant’s amendments to the claims have partially overcome the claim objection previously set forth in the Non-Final Office Action mailed October 2, 2025.
New grounds of claim objection are necessitated by the amendment as outlined below.
All 35 U.S.C. § 101 and 103 rejections from the previous office action are essentially maintained and modified in response to the amendment.
Claim Objection
Claim 79 is objected to because of the following informalities:
Claim 79: please amend “measuring at least one parameter indicative of the sensed value of pressure, temperature, or the optical signal over time during the detecting step” to – measuring the at least one parameter indicative of the sensed value of pressure, temperature, or the optical signal over time during the detecting step--.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 75, 78-81, and 97-103 are rejected under 35 USC § 101.
Regarding independent claim 75, Claim 75 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim 75 is directed to a method for quality control of a capillary electrophoresis run on a sample, the method comprising ”performing an analysis on at least a portion of the first set of values, wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold”, “performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold”; and “in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold”. Each of the analysis steps is a determination step that can be performed as a mental process and comparing first/second noise metrics to respective first/second pre-determined thresholds is also a mental process of comparing. The additional steps recited in claim 75 are routine and conventional steps for capillary electrophoresis analysis of a sample solution containing biological molecules, as evidenced by the prior arts of Goudberg et al. (US20060070880A1) and Majlof et al. (US20110290648A1) in the following prior art rejection under 35 U.S.C. 103.
Claim 75 is Ineligible due to the following analysis:
Step 1 (Statutory Category)
Claim 75 is directed to a method for quality control of a capillary electrophoresis run on a sample, therefore, it is directed to a statutory category, i.e., a method/process (Step 1: YES).
Step 2A, Prong-1 (the claim(s) is evaluated to determine whether it is directed to a judicial-exception/abstract-idea)
Claim 75 recites the abstract ideas of ”performing an analysis on at least a portion of the first set of values, wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold”, “performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold”; and “in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold”. Each of the analysis steps is a determination step that can be performed as mental process and comparing the first/second noise metrics to the first/second pre-determined thresholds is also a mental process of comparing. Therefore, it is directed to a judicial exception/abstract-idea (Step 2A, Prong-1: YES).
Step 2A, Prong-2 (the claim(s) is evaluated to determine whether the judicial-exception/abstract-idea is integrated into a Practical Application)
The first and second noise metrics are compared to the first and second pre-determined thresholds, respectively, and when either the first or second noise metric exceeds the respective first/second pre-determined threshold then an action is performed to indicate a quality issue. Performing any action to indicate a quality issue is not particular and is therefore not a particular practical application, and at best could be considered generally linking the abstract idea to the field of endeavor. As evidenced by the specification and claim 97, the actions can include setting a flag or sending a warning (or any signal). Therefore, providing an output/signal does not integrate the exception into a practical application because outputting the determined information is insignificant post-solution activity, similar to the alarm in Parker v. Flook. See MPEP 2106.04(d) and 2106.05(g).
The claim recites measuring at least one parameter indicative of pressure using a plurality of first sensors during polymer loading into a capillary of a capillary electrophoresis instrument; transferring a sample solution comprising one or more biological molecules to the capillary and detecting the one or more biological molecule; measuring at least one parameter indicative of pressure, temperature, or an optical signal using a plurality of second sensors during the detecting step. These steps are performed to gather data that is then used in the abstract idea of analysis/determining. Note that data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application (See MPEP 2106.05(g)). As explained above, performing an action to indicate a quality issue is insignificant post-solution activity, similar to the alarm in Parker v. Flook. See MPEP 2106.04(d) and 2106.05(g).
(Step 2A, Prong-2: NO).
Step 2B (the claim(s) is evaluated to determine whether recites additional elements that amount to an inventive concept, or also, the additional elements are significantly more than the recited the judicial-exception/abstract-idea)
Claim 75 recites measuring at least one parameter indicative of pressure using a plurality of first sensors during polymer loading into a capillary of a capillary electrophoresis instrument; transferring a sample solution comprising one or more biological molecules to the capillary and detecting the one or more biological molecules; measuring at least one parameter indicative of pressure, temperature, or an optical signal using a plurality of second sensors during the detecting step; and performing an action to indicate a quality issue for the capillary electrophoresis run. As discussed earlier, these steps are done to gather data to be used in the abstract ideas and then provide output/signal which are insignificant extra-solution activity. Furthermore, these steps are routine and conventional steps for capillary electrophoresis analysis of a sample solution containing biological molecules, such as the prior arts of Goudberg et al. (US20060070880A1) and Majlof et al. (US20110290648A1) in the following prior art rejection under 35 U.S.C. 103. For example, Goudberg teaches applying a pressure to a polymer solution to load the polymer solution into a capillary of a capillary electrophoresis instrument, and measuring a first set of pressure values by a first plurality of sensors during polymer loading; transferring a sample solution comprising one or more biological molecules to the capillary; while the sample solution is in the capillary, detecting the one or more biological molecules; and performing an action to indicate a quality issue for the capillary electrophoresis run (the controller determines that the pump piston movement [which is correlated to pressure value] exceeds a predetermined threshold, and the controller can stop the pump piston and report an error or leak condition to alert an operator to take corrective action [para. 0044]). Majlof teaches multiple temperature sensors (32, 34, 36, 38, 40, and 42 in Fig.2) in thermal contact with the different sections of the electrophoresis capillary (a bundle of 8 capillaries having entering end 54 and exiting end 56 in Fig.2) for measuring temperature data of the different sections of the electrophoresis capillary during capillary electrophoresis [para. 0010, 0074, Fig.2], and the temperature data from discrete temperature sensors are then used by the temperature controller 220 to control temperature of the individual electrical paths using any of a variety of control algorithms to achieve a uniform temperature along the path of the capillaries [para. 0120, 0130]. Therefore, the independent claim 75 does not include additional steps significantly more, and/or, does not amount to more than the judicial-exception/abstract-idea itself and the claim is not patent eligible (Step 2B: NO).
Regarding dependent claims 78-81 and 97-103, claims 78-81 and 97-103 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 78-81 and 97-103 depend on the independent claim 75, therefore, they have the abstract idea of independent claim 75.
Claim 78 does not further integrate the determining step of claim 75 because there is still no action based on the determining of claim 75. Claim 78 also recites performing an analysis on the current trace which is an abstract idea of a mental observation (Step 2A prong 1). The measuring current is used to gather data and is insignificant extra solution activity (Step 2A prong 2). The performing an action “based on” the analysis on the current trace is not particular and is written at a high degree of generality – what is the action? Also, this is just generally applying the abstract idea per MPEP 2106.05(f), and not a particular practical application (Step 2A prong 2). This also doesn’t seem to add significantly more (step 2B)
Claims 79-80 discuss measuring at discrete times for gathering data, which does not integrate (Step 2A prong 2) or amount to significantly more (Step 2B).
Claim 81 recites further details of the determining (abstract idea), and would be evaluated similar to claim 78.
Claims 97-100, and 103 recite a list of the action, wherein most of the responsive actions are just a flag/warning/signal. Under step 2A prong 2, sending a warning/signal does not integrate the exception into a practical application because displaying is insignificant post-solution activity, similar to the alarm in Parker v. Flook. See MPEP 2106.04(d) and 2106.05(g).
Claim 101 and 102 recite closing the valve or discontinuing the transferring, which are not very particular and amount to just discontinue/stop the polymer loading and sample transferring.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 75, 79, 97-99, and 101-103 are rejected under 35 U.S.C. 103 as being unpatentable over Goudberg et al. (US20060070880A1), and in view of Kaplit (US20070143063A1), Majlof et al. (US20110290648A1), Gomi et al. (US20070278101A1), and Altria (Improved performance in capillary electrophoresis using internal standards, www.lcgceurope.com, September 2002).
Regarding claim 75, Goudberg teaches a method for quality control (a method for determining an error or leak condition to alert an operator to take corrective action [para. 0044]) of a capillary electrophoresis run on a sample (capillary electrophoresis of sample [para. 0022]), the method comprising:
measuring at least one parameter indicative of a sensed value of pressure over time by a first plurality of sensors during polymer loading into a capillary of a capillary electrophoresis instrument to obtain a first set of values of pressure (as polymer is pushed into the capillaries of a capillary electrophoresis instrument as shown in Fig.1, the pressure in the polymer flow path will be reduced and the stepper motor 160 can start again until the pressure reaches 1000 psi, at which point the stepper motor 160 stalls [para. 0022, 0043]; the controller 150 can maintain a constant fluid pressure level in the polymer flow path 31a through 31d during the drawing and filling operations described above by controlling the speed of movement of the pump piston 102 by controlling the drive current provided to the stepper motor 160 [para. 0043]; the controller 150 can monitor the speed of the pump piston 102 to detect a leak condition. The controller 150 determines that the pump piston movement exceeds a predetermined threshold, the controller 150 can stop the pump piston 102 and report an error or leak condition to alert an operator to take corrective action [para. 0044]; controlling a motor current to maintain a fluid pressure level in the polymer flow path [para. 0081]; monitoring the speed of the pump piston [para. 0082]; controlling the speed of the piston to maintain a fluid pressure level [claim 44]. Thus, at least one parameter indicative of a sensed value of pressure over time is measured by a first plurality of sensors [sensor for measuring a motor current in order to control the motor current to maintain a fluid pressure level; sensor for monitoring the speed of the pump piston to maintain a fluid pressure level] to obtain a first set of pressure values);
transferring a sample solution comprising one or more biological molecules to the capillary (a sample 4a containing one or more analyte molecules [e.g., a polynucleotide sample, such as a sample comprising DNA fragments of varying lengths] can be introduced to the capillaries 3a through their injecting ends 3b [para. 0057]);
while the sample solution is in the capillary (sample 4a is introduced to the capillaries 3a [para. 0057]), detecting the one or more biological molecules (DNA fragments contained in the sample 4a can be distinguished by labeling a primer or a terminator with a fluorescent substance such as, for example, a dye. The labeled DNA fragments can be detected utilizing a suitable optical system. A Charge Coupled Device [CCD] or photodiode can be provided for receiving the light K then emitted by the fluorescent dyes [para. 0031]. a sample containing DNA fragments can be subjected to electrophoresis, and fluorescence from the sample can be detected in the course of electrophoresis, whereby DNA base sequencing can be carried out for determining the base sequence [para. 0058]); and
performing an action to indicate a quality issue for the capillary electrophoresis run (the controller 150 can monitor the speed of the pump piston 102 to detect a leak condition. The controller 150 determines that the pump piston movement exceeds a predetermined threshold, the controller 150 can stop the pump piston 102 and report an error or leak condition to alert an operator to take corrective action [para. 0044]).
Goudberg further teaches a single capillary or multi-capillary array 3 including plural capillaries 3a installed in a container portion CS of a temperature regulated chamber 5 [para. 0022] and the capillary electrophoresis system A can separately control the temperature of different components or regions of the capillary electrophoresis system A [para. 0028].
Goudberg is silent to the following limitations: (1) performing an analysis on at least a portion of the first set of values, wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold; (2) measuring at least one parameter indicative of a sensed value of pressure, temperature, or an optical signal over time during the detecting step by a second plurality of sensors to obtain a second set of values of pressure, temperature, or the optical signal; (3) performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold; and (4) in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, performing the action to indicate a quality issue for the capillary electrophoresis run.
Kaplit teaches a method for determining the quality of the aspirated sample liquid 14, such as the presence or absence of air bubbles, based on an analysis of a pressure profile generated during the aspiration process, wherein the analysis comprises determining a best fit line (i.e., a linear regression line [para. 0045]) for the portion of the pressure values, determining residuals by determining, for each pressure value of the portion of the pressure values, a distance between each pressure value and the best fit line (y is the actual measured pressure value, y′ is the pressure calculated by the linear regression formula, and y-y′ is the residual [para. 0046]), and evaluating the residuals against a threshold standard deviation ([paras. 0046-0047] details the standard deviation of the estimated residuals); and determining the quality of the aspirated sample liquid 14 based on the analysis (It has been discovered that if the standard deviation of the residuals (y-y′) is greater than a predetermined value, then either a clot within the liquid sample 14 blocked the distal orifice 40 after the start of aspirate into pipette 12 or there was insufficient sample to aspirate the desired volume [para. 0047]; if the standard deviation of the residuals is less than a predetermined value, then the aspiration process is free of undesirable events [para. 0012]). “the standard deviation” in Kaplit corresponds to “noise in the pressure values” in view of [para. 0179] of the specification of this instant application.
Goudberg and Kaplit are considered analogous art to the claimed invention because they are in the same field of quality control of liquid sample introduced into capillaries/pipes/pipettes under a pressure. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the method of detecting the presence of air bubbles in a capillary based on the speed of the pump piston (which is correlated to pressure value) in Goudberg with the method of performing an analysis on at least a portion of the first set of values (pressure values), wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold (performing an analysis of the pressure values to determine if a standard deviation of the pressure values exceeds a threshold), as taught by Kaplit, since the method of Kaplit is capable of ascertaining the overall quality and integrity of the amount of liquid which has been transferred [para. 0012 in Kaplit ], and could be applied to the fluid dispensing process to determine success of the dispense operation [para. 0051 in Kaplit]. Furthermore, applying a known technique (detecting the presence of bubbles in a capillary based on the standard deviation of the pressure values, as taught by Kaplit) to a known method (method of detecting the presence of air bubbles in a capillary in Goudberg) ready for improvement to yield predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(D)).
Given the teachings of Goudberg regarding determining whether a capillary electrophoresis run for a sample should proceed based on whether the speed of the pump piston exceeds the predetermined threshold speed [para. 0044], which detects the presence/absence of bubble condition, and the teachings of Goudberg as modified by Kaplit above regarding the determination of the undesirable events including air bubbles based on the analysis of the pressure values to determine whether the first noise metric in the pressure values (i.e., standard deviation of the pressure values) exceeds a first predetermined value, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method in modified Goudberg to determine whether a capillary electrophoresis run for a sample should proceed in response to the first noise metric exceeding the first pre-determined threshold (determine whether a capillary electrophoresis run for a sample should proceed based on whether noise in the pressure values [i.e., standard deviation of the pressure values] exceeds a first predetermined value), since it would ascertain the overall quality and integrity of the amount of liquid which has been loaded [para. 0012 in Kaplit ]. Examiner notes that the above modified method in modified Goudberg is the same as that in the instant application such as “If the pressure parameters do not meet requirements (e.g., standard deviation too high and/or pressure below minimum requirement during period of interest) then step 1535 performs a corrective action. If parameter values at step 1535 are acceptable, then step 1598 proceeds with the sample run” ([para. 0179] in specification of the PGpub of this instant application).
Modified Goudberg is silent to the following limitations: (2) measuring at least one parameter indicative of a sensed value of pressure, temperature, or an optical signal over time during the detecting step by a second plurality of sensors to obtain a second set of values of pressure, temperature, or the optical signal; (3) performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold; and (4) in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, performing the action to indicate a quality issue for the capillary electrophoresis run.
Majlof teaches a capillary electrophoresis device (title) comprising multiple temperature sensors (32, 34, 36, 38, 40, and 42 in Fig.2) in thermal contact with the different sections of the electrophoresis capillary (a bundle of 8 capillaries having entering end 54 and exiting end 56 in Fig.2) for measuring temperature data of the different sections of the electrophoresis capillary during capillary electrophoresis [para. 0010, 0074, Fig.2], and the temperature data from discrete temperature sensors are then used by the temperature controller 220 to control temperature of the individual electrical paths using any of a variety of control algorithms to achieve a uniform temperature along the path of the capillaries with a thermal uniformity of 2 oC peak to peak over the entire length of the capillaries [para. 0120, 0130].
Gomi teaches a capillary electrophoresis device (title), and further teaches during the electrophoresis, the electric current is passed through the separation medium in the capillary, and heat is generated from the inside of the capillary. The temperature of the capillary fluctuates by the heat generated from the inside of the capillary, which possibly deteriorates result of analysis. Therefore, the temperature control unit is provided in the capillary to keep the capillary at a constant temperature [para. 0117]. Figs. 11B-D show the temperature fluctuation as a function of time. When a standard deviation is 0.06° C in the temperatures of the first and second temperature control units 1101 and 1102, the standard deviation becomes 0.09° C in the boundary portion 1103. This shows that the temperature is unstable in the boundary portion between the two temperature control units compared with the temperature control units [para. 0120-0121].
Modified Goudberg, Majlof, and Gomi are considered analogous art to the claimed invention because they are in the same field of capillary electrophoresis. Given the teachings of Majlof regarding multiple temperature sensors to measure temperature data of different sections of the electrophoresis capillary for controlling temperature along the path of the capillary; and the teachings of Gomi regarding temperature of the capillary fluctuates by the heat generated from the inside of the capillary, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modified the method and apparatus in modified Goudberg by: (1) providing multiple temperature sensors in thermal contact with different sections of the capillary; (2) measuring temperatures of the different sections of the capillary during capillary electrophoresis; and (3) performing an analysis on the temperature data, wherein the analysis comprises whether a second noise metric (i.e., standard deviation and/or peak to peak of the temperature variation) of the temperature data exceeds a second pre-determine threshold (i.e., 2 oC peak to peak) such that the temperature controller controls the temperature to achieve a thermal uniformity of 2° C peak to peak over the entire length of the capillary, as taught by combined Majlof and Gomi, since it would allow to measure temperatures over the length of the capillary, which would fluctuate by the heat generated from the inside of the capillary and would deteriorate result of analysis, and accordingly provide temperature data to the temperature controller to control the temperature such that a uniform temperature along the path of the capillary would be achieved [para. 0130 in Majlof; 0117 in Gomi ].
With the above modification, modified Goudberg teaches the following limitations: (2) measuring at least one parameter indicative of a sensed value of pressure, temperature, or an optical signal over time during the detecting step by a second plurality of sensors to obtain a second set of values of pressure, temperature, or the optical signal (measuring at least one parameter indicative of a sensed value of temperature over time during the detecting step by a second plurality of sensors [multiple temperature sensors] to obtain a second set of values of temperature); and (3) performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold (the temperature controller uses the temperature data collected by the multiple temperature sensors to control the temperature using a PID type control algorithm to achieve a thermal uniformity of 2 oC peak to peak over the entire length of the capillary [para. 0130 in Majlof]).
Modified Goudberg is silent to the following limitation: (4) in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, performing the action to indicate a quality issue for the capillary electrophoresis run.
Altria teaches improved performance in capillary electrophoresis using internal standards (title), and Table 2 shows several operating effects that can lead to variable peak areas in CE, and the parameters include both temperature variation and pressure variation (see Table 2). Altria further teaches various factors affecting injection volume, and one of them is due to unstable pressure (If the injection pressure varies during the injection, then a variable volume will be injected. Many instruments have a pressure monitor facility, which has a feedback mechanism to automatically compensate for this problem to some extent. The problem is greatest with short injection times [Section of Injection process control in Col. 2 on page 3]). The sample solution viscosity is affected by the temperature. It is essential to maintain a constant temperature for both sample/calibration solutions and the electrolyte in the capillary and vials (the first paragraph in Viscosity in Col. 3 on page 2). Temperature control is essential to obtain consistent viscosities. The mobility of the compound is directly related to temperature, with a 2% change occurring per 1 oC change in temperature (see Temperature Control in Col. 1 on page 3). Thus, Altria teaches both pressure variation and temperature variation affect imprecision of capillary electrophoresis.
Given the teachings of Goudberg regarding the controller determines that the pump piston movement (which is correlated to pressure value) exceeds a predetermined threshold, and the controller can stop the pump piston and report an error or leak condition to alert an operator to take corrective action [para. 0044]; the teachings of Goudberg as modified by Kaplit above regarding determining whether a capillary electrophoresis run for a sample should proceed in response to the first noise metric exceeding the first pre-determined threshold (determine whether a capillary electrophoresis run for a sample should proceed based on whether noise in the pressure values [i.e., standard deviation of the pressure values] exceeds a predetermined value); the teachings of Gomi regarding temperature of the capillary fluctuates by the heat generated from the inside of the capillary, which possibly deteriorates result of analysis; and the teachings of Altria regarding both pressure variation and temperature variation affect imprecision of capillary electrophoresis, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modified the method in modified Goudberg by providing the step of in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold (when the pressure variation or the temperature variation exceeding the respective first/second pre-determined thresholds), performing an action to indicate a quality issue for the capillary electrophoresis run such as stop the pump and/or report an error to alert an operator to take corrective action when it is determined that a capillary electrophoresis run for a sample should not proceed in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, since an unstable injection pressure leads to a variable injection volume and undesired variable peak areas in CE (the 2nd paragraph in Col. 1 on page 1 in Altria), and the mobility of the compound is directly related to temperature, with a 2% change occurring per 1 oC in temperature leading to undesired variable peak areas in CE (the 2nd paragraph in Col. 3 on page 1 and Temperature Control in Col. 1 on page 3 in Altria).
Regarding claim 79, modified Goudberg teaches the method of claim 75, wherein measuring the at least one parameter indicative of the sensed value of pressure over time during the polymer loading and measuring the at least one parameter indicative of the sensed value of pressure, temperature, or the optical signal during the detection step comprises measuring the respective at least one parameter at a plurality of discrete times (Goudberg teaches as polymer is pushed into the capillaries, the pressure in the polymer flow path will be reduced and the stepper motor 160 can start again until the pressure reaches 1000 psi, at which point the stepper motor 160 stalls. This process can be completed until the capillary fill operation is complete [para. 0043]; thus pressure is measured at a plurality of discrete times during the polymer loading. During the detecting step, Majlof teaches the temperature data is measured at a plurality of discrete times for the temperature controller to control the temperature [para. 0130], and Gomi also teaches the temperature data is measured at a plurality of discrete times and Figs. 11B-D show the measured temperature as a function of time).
Regarding claim 97, modified Goudberg teaches the method of claim 75, wherein the action comprises one or more of: setting a flag; sending a warning signal; sending a service call signal; closing a valve between a reservoir of the polymer solution and a pump used to apply the pressure; or discontinuing transferring (stop the pump and/or report an error to alert an operator to take corrective action [para. 0044 in Goudberg]. Thus, Goudberg teaches the action performed including setting a flag [report an error]; sending a warning signal [sending an error to alert]; sending a service call signal [report an error to alert an operator to take corrective action]; closing a valve between a reservoir of polymer solution and a pump used to apply the pressure [stop the pump]; or discontinuing transferring [stop the pump]).
Regarding claims 98-99 and 101-103, modified Goudberg teaches the method of claim 97, and further teaches:
wherein the action performed is sending the warning signal, of instant claim 98 (sending an error to alert [para. 0044 in Goudberg]);
wherein the action performed is sending the service call signal, of instant claim 99 (report an error to alert an operator to take corrective action [para. 0044 in Goudberg]);
wherein the action performed is closing the valve between the reservoir of the polymer solution and the pump used to apply the pressure, of instant claim 101 (stop the pump piston [para. 0044 in Goudberg]);
wherein the action performed is discontinuing the transferring, of instant claim 102 (stop the pump piston [para. 0044 in Goudberg]); and
wherein the action performed is setting the flag, of instant claim 103 (report an error [para. 0044 in Goudberg]).
Claims 78 and 80-81 are rejected under 35 U.S.C. 103 as being unpatentable over Goudberg, Kaplit , Majlof, Gomi, and Altria, as applied to claim 75 above, and further in view of DeSimas et al. (US20180052138A1).
Regarding claim 78, modified Goudberg teaches the method of claim 75, and is silent to while detecting the one or more biological molecules, measuring current in the capillary in which the one or more biological molecules are being moved by the current over time to determine a current trace; performing an analysis on the current trace; and performing an action based on the analysis on the current trace.
DeSimas teaches a method of capillary electrophoresis for analytes such as nucleic acids (abstract) wherein the analytes can have an appropriate fluorescent dye label attached to the analyte such that the fluorescent dye can be detected in an electrophoresis apparatus [para. 0049]. DeSimas further teaches:
while detecting the one or more biological molecules, measuring current in the capillary in which the one or more biological molecules are being moved by the current over time to determine a current trace (measuring electrical current in a separation channel [paras. 0058-0060]; Fig.6);
performing an analysis on the current trace (making use of measured current in a separation channel in the processing of data collected during an electrophoretic run [para. 0058]; processing the collected signal data via a method that employs the measured current as a variable [para. 0058]; Fig.6; the processing station can be interfaced for communication with an electrophoresis apparatus. Such a processing station can comprise, for example, a central processing unit [CPU] and digital memory. The CPU can execute instructions in the memory for collecting and processing digital data. The peak analysis program can run simultaneously with the data collection program [paras. 0053-0054]); and
performing an action based on the analysis on the current trace (the processing can comprise, for example, correcting for problematic issues, e.g., one or more errors, in the data during peak detection [para. 0058]; the peak analysis program can run simultaneously with the data collection program [paras. 0053-0054]).
Modified Goudberg and DeSimas are considered analogous art to the claimed invention because they are in the same field of capillary electrophoresis. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method and apparatus in modified Goudberg by including the following steps: while detecting the one or more biological molecules, measuring current in the capillary in which the one or more biological molecules are being moved by the current over time to determine a current trace; performing an analysis on the current trace; and performing an action based on the analysis on the current trace, as taught by DeSimas, since the electrical current data would allow to correct problematic issues, e.g., one or more errors, in the data during peak detection ([para. 0058] in DeSimas).
Regarding claim 80, modified Goudberg teaches the method of claim 78, wherein measuring current over time comprises measuring current at a plurality of discrete times (Modified Goudberg teaches while detecting the one or more biological molecules, measuring current in the capillary over time to determine a current trace, as outlined in the rejection of claim 78 above; Fig.6 shows electrical current sum at a plurality of discrete times [para. 0093-0094] in DeSimas).
Regarding claim 81, modified Goudberg teaches the method of claim 78, and Goudberg does not explicitly teach wherein the analysis comprises determining a noise metric corresponding to signal noise in the current trace and further wherein performing the action based on the analysis comprises performing the action based on a value of the noise metric.
DeSimas further teaches the movement of the particles can be affected by many factors only partially, or not related to the properties of the target particles to be measured. Electric current created during electrophoresis can be used to effect that correction. The electric current measures the amount of charge flowing through the conduit (capillary for example for capillary electrophoresis). Accordingly, the electric current data can be employed to estimate how much charge went through from the beginning of the process to every subsequent time point of the process [para. 0060]. DeSimas teaches determining a noise metric corresponding to signal noise in the current trace (such as determining the difference between the migration time 113 from the raw sample and the migration time 114 from a reference model 112 as shown in Fig.6 [para. 0067]) and further performing an action based on a value of the noise metric (this conversion from the raw sample time 113 into a normalized time based on the reference ladder 114 can be used to align each subsequent injection [separation] electrophoretic data, where each unknown sample can be transformed from the original raw migration time to a common scale of the same units. Fig.7 is a flow diagram showing the overall process of the using RFU data 115, current 116, and optionally, voltage 117 as inputs into the pre-alignment process to give aligned electropherogram data in the native migration time scale [seconds for example] [para. 0067]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Goudberg by adding the step of determination of a noise metric corresponding to signal noise in the current trace to the analysis on the current trace and further performing an action based on a value of the noise metric, as taught by DeSimas, since it would provide aligned electropherogram data and correction for problematic issues, e.g., one or more errors, in the data during peak detection ([paras. 0058, 0067] in DeSimas). Furthermore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Goudberg by including the action based on a value of the noise metric as a part of the action based on the analysis on the current trace such that performing the action based on the analysis comprises performing the action based on a value of the noise metric, since it would increase the yield of useful results in automated peak detection ([para. 0005] in DeSimas).
Claim 100 is rejected under 35 U.S.C. 103 as being unpatentable over Goudberg, Kaplit, Majlof, Gomi and Altria, as applied to claim 97 above, and further in view of Life Technologies Corporation, Applied Biosystems 3500/3500xL Genetic Analyzer User Guide, 2010 (hereinafter “Life Technologies”).
Regarding claim 100, modified Goudberg teaches the method of claim 97, and does not teach wherein the action performed is sending the check cartridge signal.
Life Technologies teaches a user guide for analyzer for performing capillary electrophoresis and integrated software for instrument control, data collection, quality control and basecalling or sizing of sample (page 1). When error messages are received such as leak detected during polymer delivery or leak detected during bubble compression and the run aborts, there are few suggested actions including checking for evidence of leaks, checking the buff-pin valve, or run the fill array with refresh polymer wizard or run change polymer type wizard (page 308).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method in modified Goudberg to include sending a check cartridge signal, as taught by Life Technologies, since it would facilitate curing the causes of an error aborting the run (page 308 in Life Technologies).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 9-17, filed 1/2/2026, with respect to the 35 U.S.C. § 101 and 35 U.S.C. § 103 rejections have been fully considered and are not persuasive.
Applicant’s Argument #1:
Regarding step 2A prong one of the 101 rejection for claim 75, Applicant argues at pages 9-10 that claim 75 requires measuring at least one parameter indicative of a sensed value of pressure, temperature, or an optical signal over time during polymer loading using a plurality of first sensors of a capillary electrophoresis instrument; measuring at least one parameter indicative of pressure, temperature, or an optical signal over time during a detecting step using a plurality of second sensors; performing analyses on the respective measured data sets to determine whether first and second noise metrics exceed corresponding pre-determined thresholds; and in response, performing an action to indicate a quality issue for the capillary electrophoresis run. These steps are not abstract mental processes. The claimed "noise metrics" are derived from time varying physical measurements generated by plural sensors during specific operational phases of a capillary electrophoresis instrument. A human mind cannot perform these steps absent the claimed sensors, instrumentation, and physical electrophoresis process. Under USPTO guidance and Federal Circuit precedent, claims that require physical sensing and generation of real-world data are not properly categorized as mental processes merely because the data are later analyzed.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are not persuasive. As outlined in the Step 2A analysis, ”performing an analysis on at least a portion of the first set of values, wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold”, “performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold”; and “in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold” are abstract ideas. Each of the analysis steps is a determination step that can be performed as mental process and comparing the first/second noise metrics to the first/second pre-determined thresholds is also a mental process of comparing.
The measuring steps are not categorized as metal processes, but they are performed to gather data that is then used in the abstract idea of analysis/determining, as outlined in the step 2A-prong-2 analysis. Note that data gathering to be used in the abstract idea is insignificant extra-solution activity, and is not a particular practical application (See MPEP 2106.05(g)).
Applicant’s Argument #2:
Regarding 101 rejection for claim 75, Applicant argues at page 10 that claim 75 is directed to a method of quality control for a capillary electrophoresis run, not to a disembodied data analysis. Accordingly, claim 75 is not directed to an abstract idea at Step 2A, Prong One.
Examiner’s Response #2:
Applicant’s arguments have been fully considered, but are not persuasive since claim 75 recites the abstract ideas of ”performing an analysis on at least a portion of the first set of values, wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold”, “performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold”; and “in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold”. Each of the analysis steps is a determination step that can be performed as mental process and comparing the first/second noise metrics to the first/second pre-determined thresholds is also a mental process of comparing.
Applicant’s Argument #3:
Regarding 101 rejection for claim 75, applicant argues in II.A at pages 10-11 that
the action is performed in the context of an ongoing capillary electrophoresis run; the action is triggered by sensor noise behavior observed during polymer loading and/or detection, not by abstract numerical manipulation; and the action functions as part of a quality-control workflow that determines whether the run acceptable or compromised. Thus, the action is not merely "outputting information," but is part of a closed-loop operational scheme that directly relates to the integrity of the electrophoresis process. Courts have consistently held that claims which apply calculations to control or assess a physical process in real time integrate any abstract idea into a practical application.
Examiner’s Response #3:
It is noted that the features upon which applicant relies (i.e., apply calculations to control or assess a physical process in real time) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Performing any action to indicate a quality issue is not particular and is therefore not a particular practical application, and at best could be considered generally linking the abstract idea to the field of endeavor. As evidenced by the specification and claim 97, the actions can include setting a flag or sending a warning (or any signal). Therefore, providing an output/signal does not integrate the exception into a practical application because outputting the determined information is insignificant post-solution activity, similar to the alarm in Parker v. Flook. See MPEP 2106.04(d) and 2106.05(g).
Applicant’s Argument #4:
Regarding 101 rejection for claim 75, applicant argues in II.B at page 11 that
claim 75 improves capillary electrophoresis technology by enabling early identification of problematic runs based on noise behavior in sensor signals during defined operational phases. This is a technical improvement to how electrophoresis runs are monitored and assessed, not an abstract informational task.
Examiner’s Response #4:
The arguments are unpersuasive because each of the analysis steps recited in claim 75 is a determination step that can be performed as mental process and comparing the first/second noise metrics to the first/second pre-determined thresholds is also a mental process of comparing. The measuring steps are performed to gather data that is then used in the abstract idea of analysis/determining. Performing an action to indicate a quality issue is insignificant post-solution activity. Thus, claim 75 is an abstract information task.
Applicant’s Argument #5:
Regarding step 2B of the 101 rejection for claim 75, applicant argues in III.A at pages 11-12 that the Office Action does not establish that it was conventional to: collect time-varying sensor data during polymer loading and detection using separate pluralities of sensors, and evaluate noise metrics of those phase-specific data sets to determine run quality and trigger responsive action.
Examiner’s Response #5:
Applicant’s arguments have been fully considered, but are not persuasive. Firstly, collecting time-varying sensor data during polymer loading and detection using separate pluralities of sensors is to gather data that is then used in the abstract idea of analysis/determining. Note that data gathering to be used in the abstract idea is insignificant extra-solution activity, and is not a particular practical application (See MPEP 2106.05(g)). Secondly, as outlined in the prior art rejection for claim 75, the prior art teaches collecting time-varying sensor data during polymer loading and detection using separate pluralities of sensors. Thirdly, evaluating noise metrics of those phase-specific data set to determine run quality and trigger a response action is an abstract idea and can be performed as mental process.
Applicant’s Argument #6:
Regarding step 2B of the 101 rejection for claim 75, applicant argues in III.B at page 12 that the inventive concept resides in the ordered combination of: 1. Phase-specific sensing during polymer loading and detection, 2. Noise-metric evaluation of those sensor signals, and 3. Using the results to identify a quality issue for the electrophoresis run. Even if individual components were known in isolation, their claimed arrangement reflects a nonconventional approach to electrophoresis quality control, consistent with Bascom (Bascom Global Internet Serv., Inc v. AT&T Mobility LLC, 27 F.3d 1341 (Fed. Cir. 2016)).
Examiner’s Response #6:
Applicant’s arguments have been fully considered, but are not persuasive. Firstly, phase-specific sensing during polymer loading and detection is to gather data that is then used in the abstract idea of analysis/determining. Note that data gathering to be used in the abstract idea is insignificant extra-solution activity, and is not a particular practical application (See MPEP 2106.05(g)). Secondly, as outlined in the prior art rejection for claim 75, the prior art teaches phase-specific sensing during polymer loading and detection. Thirdly, noise-metric evaluation of those sensor signals and using the results to identify a quality issue for electrophoresis run is an abstract idea and can be performed as mental process.
Applicant’s Argument #7:
Regarding dependent claims 78-81 and 97-103 of the 101 rejection, applicant argues in IV at page 12 that several dependent claims add further technical limitations, including: Measurement at plural discrete times, Particular forms of sensor-derived signals, and Specific responsive actions taken within the electrophoresis workflow. These additional limitations further reinforce that the claims are directed to and integrated into a practical laboratory instrument process and, at minimum, must be analyzed separately for eligibility.
Examiner’s Response #7:
Applicant’s arguments have been fully considered, but are not persuasive based on the 101 rejections for claim 78-81 and 97-103. Note that measurement at plural discrete times and particular forms of sensor-derived signals are to gather data that is then used in the abstract idea of analysis/determining. Most of the responsive actions recited in claims 97-100 and 103 are just a flag/warning/signal. Under step 2A prong 2, sending a warning/signal does not integrate the exception into a practical application because displaying is insignificant post-solution activity, similar to the alarm in Parker v. Flook. See MPEP 2106.04(d) and 2106.05(g). Claims 101 and 102 recite closing the valve or discontinuing the transferring, which are not very particular and amount to just discontinue/stop the polymer loading and sample transferring.
Applicant’s Argument #8:
Regarding the 103 rejection for claim 75, applicant argues at II on page 13 that
none of these references-alone or in any combination-identify the technical problem addressed by Applicant, namely: determining capillary electrophoresis run quality by evaluating noise behavior of sensor signals collected during distinct operational phases, including polymer loading and detection. Absent recognition of this problem, a person of ordinary skill in the art would have no reason to assemble the cited references in the manner proposed. The Examiner's rationale therefore reflects hindsight reconstruction rather than a teaching or suggestion found in the art.
Examiner’s Response #8:
Applicant’s arguments have been considered but are not persuasive. As outlined in the 103 rejection of claim 75 above, the combined prior art does teach “in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, performing an action to indicate a quality issue for the capillary electrophoresis run”. Note that Goudberg teaches the controller determines that the pump piston movement (which is correlated to pressure value) exceeds a predetermined threshold, and the controller can stop the pump piston and report an error or leak condition to alert an operator to take corrective action [para. 0044]. As evidenced by instant claim 97, “stop the pump piston and report an error or leak condition to alert an operator to take corrective action” is an action to indicate the quality issue. Goudberg as modified by Kaplit teaches determining whether a capillary electrophoresis run for a sample should proceed in response to the first noise metric exceeding the first pre-determined threshold (determine whether a capillary electrophoresis run for a sample should proceed based on whether noise in the pressure values [i.e., standard deviation of the pressure values] exceeds a predetermined value). Goudberg as modified by Kaplit, Gomi and Altria teaches
the step of in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold (when the pressure variation or the temperature variation exceeding the respective first/second pre-determined thresholds), performing an action to indicate a quality issue for the capillary electrophoresis run such as stop the pump and/or report an error to alert an operator to take corrective action when it is determined that a capillary electrophoresis run for a sample should not proceed in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, since an unstable injection pressure leads to a variable injection volume and undesired variable peak areas in CE (the 2nd paragraph in Col. 1 on page 1 in Altria), and the mobility of the compound is directly related to temperature, with a 2% change occurring per 1 oC in temperature leading to undesired variable peak areas in CE (the 2nd paragraph in Col. 3 on page 1 and Temperature Control in Col. 1 on page 3 in Altria).
In response to applicant's argument that the examiner's rationale reflects hindsight reconstruction rather than a teaching or suggestion found in the art, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, since the office action does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. Furthermore, to examine each claim, Examiner has to read each element recited in the claim.
Applicant’s argument #9
Regarding the 103 rejection of claim 75, applicant argues at III on pages 13-14 that Goudberg does not teach evaluating noise metrics, nor does it disclose comparing noise behavior across different operational phases. Kaplit and DeSimas discuss statistical treatment of signals, but they do not teach phase-specific analysis tied to polymer loading versus detection, or using noise behavior as a run-quality gate. Majlof and Gomi discuss temperature control or sensing, but not the claimed noise-metric-based quality determination, and not in the context of correlating noise behavior across distinct electrophoresis phases. The Examiner's combination therefore fills critical gaps only by relying on Applicant's claim language, not on any teaching or suggestion in the prior art.
Examiner’s response #9
Applicant’s arguments have been fully considered, but are not persuasive. As outlined in the rejection of claim 75 above, Goudberg teaches detecting the presence of air bubbles in a capillary based on the speed of the pump piston (which is correlated to pressure value) and determining whether a capillary electrophoresis run for a sample should proceed based on whether the speed of the pump piston exceeds the predetermined threshold speed [para. 0044], which detects the presence/absence of bubble condition. Kaplit teaches the presence of air bubbles based on the standard deviation of the pressure value (which corresponds to the noise in the pressure value). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the method of detecting the presence of air bubbles in a capillary based on the speed of the pump piston (which is correlated to pressure value) in Goudberg with the method of performing an analysis on at least a portion of the first set of values (pressure values), wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold (performing an analysis of the pressure values to determine if a standard deviation of the pressure values exceeds a threshold), as taught by Kaplit, since the method of Kaplit is capable of ascertaining the overall quality and integrity of the amount of liquid which has been transferred [para. 0012 in Kaplit ], and could be applied to the fluid dispensing process to determine success of the dispense operation [para. 0051 in Kaplit]. Furthermore, applying a known technique (detecting the presence of bubbles in a capillary based on the standard deviation of the pressure values, as taught by Kaplit) to a known method (method of detecting the presence of air bubbles in a capillary in Goudberg) ready for improvement to yield predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(D)).
Furthermore, Given the teachings of Goudberg regarding determining whether a capillary electrophoresis run for a sample should proceed based on whether the speed of the pump piston exceeds the predetermined threshold speed [para. 0044], which detects the presence/absence of bubble condition, and the teachings of Goudberg as modified by Kaplit above regarding the determination of the undesirable events including air bubbles based on the analysis of the pressure values to determine whether the first noise metric in the pressure values (i.e., standard deviation of the pressure values) exceeds a first predetermined value, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method in modified Goudberg to determine whether a capillary electrophoresis run for a sample should proceed in response to the first noise metric exceeding the first pre-determined threshold (determine whether a capillary electrophoresis run for a sample should proceed based on whether noise in the pressure values [i.e., standard deviation of the pressure values] exceeds a first predetermined value), since it would ascertain the overall quality and integrity of the amount of liquid which has been loaded [para. 0012 in Kaplit ]. Thus, Goudberg as modified by Kaplit teaches pressure analysis during the polymer loading and using the noise in the pressure value as a run-quality gate.
Furthermore, Goudberg as modified by Kaplit, Majlof and Gomi teaches measuring at least one parameter indicative of a sensed value of temperature over time during the detecting step, and performing an analysis on at least a portion of the second set of values, wherein the analysis comprises whether a second noise metric of the second set of values exceeds a second pre-determined threshold (the temperature controller uses the temperature data collected by the multiple temperature sensors to control the temperature using a PID type control algorithm to achieve a thermal uniformity of 2 oC peak to peak over the entire length of the capillary [para. 0130 in Majlof]).
Altria teaches wherein Table 2 shows several operating effects that can lead to variable peak areas in CE, and the parameters include both temperature variation and pressure variation (see Table 2). Altria further teaches various factors affecting injection volume, and one of them is due to unstable pressure (If the injection pressure varies during the injection, then a variable volume will be injected. Many instruments have a pressure monitor facility, which has a feedback mechanism to automatically compensate for this problem to some extent. The problem is greatest with short injection times [Section of Injection process control in Col. 2 on page 3]). The sample solution viscosity is affected by the temperature. It is essential to maintain a constant temperature for both sample/calibration solutions and the electrolyte in the capillary and vials (the first paragraph in Viscosity in Col. 3 on page 2). Temperature control is essential to obtain consistent viscosities. The mobility of the compound is directly related to temperature, with a 2% change occurring per 1 oC change in temperature (see Temperature Control in Col. 1 on page 3).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modified the method in modified Goudberg by providing the step of in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold (when the pressure variation or the temperature variation exceeding the respective first/second pre-determined thresholds), performing an action to indicate a quality issue for the capillary electrophoresis run such as stop the pump and/or report an error to alert an operator to take corrective action when it is determined that a capillary electrophoresis run for a sample should not proceed in response to the first noise metric exceeding the first pre-determined threshold or the second noise metric exceeding the second pre-determined threshold, since an unstable injection pressure leads to a variable injection volume and undesired variable peak areas in CE (the 2nd paragraph in Col. 1 on page 1 in Altria), and the mobility of the compound is directly related to temperature, with a 2% change occurring per 1 oC in temperature leading to undesired variable peak areas in CE (the 2nd paragraph in Col. 3 on page 1 and Temperature Control in Col. 1 on page 3 in Altria).
Therefore, the combined prior arts teach phase-specific analysis tied to polymer loading and detection, and use the noise behavior to perform an action to indicate a quality issue for the CE run.
Applicant’s argument #10
Regarding the 103 rejection, applicant argues in IV at pages 14-15 that the Office Action does not explain why a skilled artisan would abandon the prior art's focus on absolute thresholds, bubble detection, or gross fault detection in favor of Applicant's noise-metric-based, phase-specific quality control scheme. Without such an explanation, the rejection lacks the required rational underpinning.
Examiner’s response #10
Applicant’s arguments have been considered, but are not persuasive. Goudberg and Kaplit are considered analogous art to the claimed invention because they are in the same field of quality control of liquid sample introduced into capillaries/pipes/pipettes under a pressure. As explained in the Examiner’s response #9 above, Goudberg teaches determining whether a capillary electrophoresis run for a sample should proceed based on the presence of bubbles, which is detected based on whether the speed of the pump piston exceeds the predetermined threshold speed; and Kaplit teaches the use of the noise in the pressure value to detect the presence of air bubbles. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the method of detecting the presence of air bubbles in a capillary based on the speed of the pump piston (which is correlated to pressure value) in Goudberg with the method of performing an analysis on at least a portion of the first set of values (pressure values), wherein the analysis comprises determining whether a first noise metric of the first set of values exceeds a first pre-determined threshold (performing an analysis of the pressure values to determine if a standard deviation of the pressure values exceeds a threshold), as taught by Kaplit, since the method of Kaplit is capable of ascertaining the overall quality and integrity of the amount of liquid which has been transferred [para. 0012 in Kaplit ], and could be applied to the fluid dispensing process to determine success of the dispense operation [para. 0051 in Kaplit]. Furthermore, applying a known technique (detecting the presence of bubbles in a capillary based on the standard deviation of the pressure values, as taught by Kaplit) to a known method (method of detecting the presence of air bubbles in a capillary in Goudberg) ready for improvement to yield predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(D)).
Furthermore, Given the teachings of Goudberg regarding determining whether a capillary electrophoresis run for a sample should proceed based on the presence of bubbles which is determined based on whether the speed of the pump piston exceeding the predetermined threshold speed [para. 0044], and the teachings of Goudberg as modified by Kaplit above regarding the determination of the undesirable events including air bubbles based on the analysis of the pressure values to determine whether the first noise metric in the pressure values (i.e., standard deviation of the pressure values) exceeds a first predetermined value, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method in modified Goudberg to determine whether a capillary electrophoresis run for a sample should proceed in response to the first noise metric exceeding the first pre-determined threshold (determine whether a capillary electrophoresis run for a sample should proceed based on whether noise in the pressure values [i.e., standard deviation of the pressure values] exceeds a first predetermined value), since it would detect the presence of air bubbles and ascertain the overall quality and integrity of the amount of liquid which has been loaded [para. 0012 in Kaplit ].
Applicant’s argument #11
Regarding 103 rejection of claim 75, applicant argues at V on page 15 that the Office Action does not identify any reference, or combination of references, that discloses or suggests this ordered combination. Instead, the rejection improperly disassembles the claim and reconstructs it using hindsight.
Examiner’s response #11
Applicant’s arguments have been considered, but are not persuasive. As outlined in the rejection of claim 75, the combined prior art teaches the ordered combination recited in claim 75. In response to applicant's argument that the rejection improperly disassembles the claim and reconstructs it using hindsight, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, since the office action does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. Furthermore, to examine each claim, Examiner has to read each element recited in the claim.
Applicant’s argument #12
Regarding 103 rejections of claims 78 and 80-81, applicant argues at pages 15-16 that claims 78 and 80-81 depend directly or indirectly from claim 75. Thus, claims 78 and 80-81 are not obvious over Goudberg, Kaplit, Majlof, Gomi, and Altria for at least the reasons outlined above.
Examiner’s response #12
Claim 75 is still unpatentable over the prior art, as outlined in the rejection of claim 75 above.
Applicant’s argument #13
Regarding 103 rejection of claim 100, applicant argues at page 16 that Claim 100 depends from claim 75. Thus, claim 100 is not obvious over Goudberg, Kaplit, Majlof, Gomi and Altria for at least the reasons outlined above.
Examiner’s response #13
Claim 75 is still unpatentable over the prior art, as outlined in the rejection of claim 75 above.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V 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.
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/SHIZHI QIAN/Examiner, Art Unit 1795