The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Arai (US 2013/0224768) in view of Inana (US 2011/0072885) and Wada (US 2018/0292398). With respect to claim 1, Arai teaches an immunochromatographic assay apparatus (1) comprising: a loading part (loading unit 14) in which a cartridge (cartridge 20) including a carrier (insoluble carrier 21) and a second reagent holding part (a sensitizing solution pot 28) is attachably and detachably loaded, the carrier having at least three regions of a spotting region (the section of the insoluble carrier 21 adjacent/below a solution injection hole 23) on which a sample is spotted (see at least figure 5 and its associated discussion in paragraph [0105]), an assay region in which a color development state changes depending on whether the sample is positive or negative (see at least figure 2 and observation window 24 provided to observe assay sites - test lines A, B and control line C - of the insoluble carrier 21), and a color development region in which a color development state changes by reaction with a first reagent (see at least figure 2 and observation window 24 provided to observe assay sites - test lines A, B and control line C - of the insoluble carrier 21), and the second reagent holding part holding a second reagent to be developed in the assay region after the first reagent has been developed in the color development region (a sensitizing solution pot 28 in combination with the description of figures 6-7 in paragraphs [0118]-[0119]); a detection unit (first measurement unit 40) that detects a color development state in the color development region; a second reagent supply mechanism (pressure unit 34)for starting a supply of the second reagent from the second reagent holding part to the carrier; and a processor (control unit 80) configured to discriminate the presence or absence of an analyte, based on a change in the color development state of assay region. Arai does not teach that the processor is configured to discriminate, based on a change in the color development state of the color development region, presence or absence of the change in the color development state of the color development region and operate the second reagent supply mechanism. Arai also does not teach a cartridge in which the various components are arranged as described with respect to instant figures 3-4.
The chromatographic measurement apparatus described by Inana is generally similar to that described by Arai in that Figure 1 of both publications is substantially similar to each other. In addition the elements of first measurement unit 40 are substantially similar. Moreover, the insoluble carrier 21 shown in figure 3C has two test lines (A and B) and a control line C that are substantially similar to that taught by Arai. Particularly relevant to the difference between Arai and instant claim 1 are figures 5A-5E with their associated discussion in at least paragraphs [0115]-[0127] teaching that the determination of necessity of amplification and the determination of validity are carried out based on the color development state of the testing area. Figures 5A to 5E are conceptual diagrams showing examples of the color development state of the testing area during a test after the sample solution is injected into the device 20 and the device 20 is loaded in the measurement apparatus 1. As shown in the drawings, the test process mainly includes a step before the amplification, a step of the determination of necessity of amplification, a step after the amplification and a step of the determination of validity. In these drawings, "A" indicates a test line (A line) for testing a test article A, "B" indicates a test line (B line) for testing a test article B, which is different from the test article A, and "C" indicates a control line (C line) for indicating the end of the test (i.e., that the label substance has reached the C line). The insoluble carrier in these examples uses, as the label substance, gold colloid which has appropriately been treated. Therefore, the A line and the B line turn red when the test articles A and B are tested, and the C line turns red when the test ends regardless of the presence or absence of the test article. In the following description, it is assumed that the "predetermined value", which is a criterion for the determination of necessity of amplification and the determination of validity, is set to a "predetermined value indicating a visually observable level", and the determinations are carried out depending on whether or not the color development state on each line is visually observable. During the test, the amplification step is carried out only when it is determined to be necessary to amplify the color development state in the determination of necessity of amplification. Examples of the cases where it is determined to be necessary to amplify the color development state are shown in figures 5A and 5B. STEP 1 of cases 1 to 6 in figure 5A shows states of the testing area when a predetermined time (10 minutes) has elapsed after the device 20 was loaded. When 10 minutes have elapsed after the device 20 was loaded, the determination of necessity of amplification is carried out in STEP 2. In the stage of 10 minutes after, none of the color development states of the test lines of the cases 1 to 6 have reached the predetermined value indicating a visually observable level. Therefore, the "amplification necessary" determination is made in the determination of necessity of amplification for all the cases. This may be the case when, although each test line has developed color, the optical density of the developed color has not reached the predetermined value indicating the visually observable level, and the developed color may possibly be visually observable by amplifying the color development state. STEP 3 shows the color development states of the testing area of these cases after the amplification. In STEP 4, the determination of validity is carried out based on the color development state after the amplification. It can be seen from the states in STEP 3 that the A line has developed color for the case 4, the B line has developed color for the case 5, and the A line and the B line have developed color for the case 6. Therefore, the "valid" determination is made in the determination of validity for the cases 4 to 6, and test results "A positive" for the case 4, "B positive" for the case 5, and "A and B positive" for the case 6 are obtained. For the cases 2 and 3, only the C line has developed color after the amplification, and therefore, the "valid" determination is made in the determination of validity, and a test result "negative" is obtained for each case. For the case 1, none of the lines (in particular, the C line) have developed color even after the amplification, and therefore the "error" determination is made in the determination of validity, assuming that the test has not been normally completed due to some errors. STEP 1 of cases 7 to 12 in figure 5B also shows states of the testing area when a predetermined time (10 minutes) has elapsed after the device 20 was loaded. Similarly to the above-described cases shown in figure 5A, when 10 minutes have elapsed after the device 20 was loaded, the determination of necessity of amplification is carried out in STEP 2. In the stage of 10 minutes after, the color development state of at least one of the test lines has reached the predetermined value indicating the visually observable level in each of the cases 7 to 12, and the rest of the test lines and the C line have not reached the predetermined value indicating the visually observable level. Therefore, the "amplification necessary" determination is made in the determination of necessity of amplification for all the cases. This is because that the developed color may possibly be visually observable by amplifying the color development state. STEP 3 shows the color development states of the testing area of these cases after the amplification. In STEP 4, the determination of validity is carried out based on the color development state after the amplification. Based on the states in STEP 3, the "valid" determination is made in the determination of validity for the cases 7 to 9, and test results "A positive" for the case 7, "B positive" for the case 8, and "A and B positive" for the case 9 are obtained. In contrast, for each of the cases 10 to 12, the C line in STEP 3 has not developed color and this indicates that the test has not been normally completed. Therefore, the "error" determination is made in the determination of validity. Figure 5C shows cases where it was determined to be unnecessary to amplify the color development state. In cases 13, 14, 16 and 17, in the second operation mode, the determination of necessity of amplification is carried out only for a specified test line among the two or more test lines. For the cases 13 and 16, the A line is specified, and the A line and the C line have developed color of the visually observable level after the predetermined time (5 or 10 minutes) has elapsed. For the cases 14 and 17, the B line is specified, and the B line and the C line have developed color of the visually observable level after the predetermined time (5 or 10 minutes) has elapsed. Therefore, for these cases, the "amplification unnecessary" determination is made in the determination of necessity of amplification regardless of the color development state of the other test line. For the cases 15 and 18 in figure 5C, all the test lines and the C line have developed color of the visually observable level after or before the predetermined time (5 or 10 minutes) has elapsed. Therefore, for these cases, the "amplification unnecessary" determination is made in the determination of necessity of amplification (the first operation mode). It should be noted that, as shown in cases 16 to 18, if the color development state has already reached the level at which the purpose of the test is achieved before the predetermined time (10 minutes in this example) has elapsed, the determination of necessity of amplification may be carried out as appropriate before the predetermined timing to carry out the determination of necessity of amplification in order to reduce the test time. In this manner, when the purpose of the test can be achieved without amplifying the color development state of the testing area, the "amplification unnecessary" determination is made as appropriate in the determination of necessity of amplification, thereby reducing the test time and use of the amplifying solution comparing to the case where the amplification step is always carried out. The timing for carrying out the determination of validity according to the invention is not limited to when the final test result is obtained. For example, the determination of validity may be carried out immediately after the device 20 is loaded in the measurement apparatus 1. In this case, whether or not the test is normally progressing can be determined in the early stage of the test. Figure 5D shows cases 19 to 22 of states of the testing area immediately after the device 20 was loaded in the measurement apparatus 1. In these cases, the C line has already developed color immediately after the device 20 was loaded. In these cases, it is impossible to identify the time elapsed after the sample solution was put on the device 20 and before the device 20 was loaded. Therefore, the "error" determination is made in the determination of validity, assuming that the test result is not reliable. Figure 5E also shows cases 23 to 27 of states of the testing area immediately after the device 20 was loaded in the measurement apparatus 1. In the cases 23 to 27, although the amplification of the color development state is not carried out, the chromaticity of the color development state of each line is at the same level as that after the amplification. In this case, it is possible that a once-used device is used again. Therefore, the "error" determination is made in the determination of validity, assuming that the test result is not reliable. Information of reference chromaticity before and after the amplification may be set by the user in advance, or may be automatically set by the measurement apparatus 1 based on the information about the sample and the reagent used in the test, which is obtained from the information display area 25 of the device 20. Also relevant id the description of figures 7-8 in which the information obtained by the image sensor(s) of the first measurement unit 40 and/or the second measurement unit 50 is displayed in real-time on the screen displaying unit 11. With respect to this embodiment, paragraph [0149] teaches that a user can make real-time observation of the interior of the measurement apparatus 2. Thus, the user can learn the state of progress of the reaction easily, and can determine the end of the test easily. For example, when a developed color is observed after a shorter time than the reaction completion time that is determined depending on the reagent, the user can determine the end of the test at that point of time, and thus efficiency of the test can be increased. Also of importance relative to the instant claims are paragraphs [0007]-[0008] describing a prior apparatus that is described as a simple automation of the conventional method practiced by the user using a visual test kit (that is, in principle, determination of the test result is carried out when a reaction completion time determined for each reagent has elapsed; however, if it can be seen through visual observation that the reaction has apparently completed, the test result is determined before the reaction completion time elapses).
In the patent publication Wada teaches an immunochromatographic kit. Figures 1-3 of Wada are substantially similar to instant figures 2-4 so that the Wada immunochromatographic kit shown and described in figures 1-3 of Wada appears to be substantially similar to the cartridge shown in and described with respect to instant figures 2-4. Of relevance in the structure of the Wada immunochromatographic kit is the first pot 40 and a second pot 45 which respectively include a first amplification liquid 41 and a second amplification liquid 46, in order to amplify a detection signal in the inspection region. Paragraph [0037] teaches that there is an inspection region L1, a confirmation region L2, and an amplification label region L3, which can be visually checked. Paragraph [0041] describing figure 3, teaches that the insoluble carrier 2 sequentially has the inspection region L1 including a second substance being bonded to the test substance, the confirmation region L2 including a substance bondable to the first substance, and the amplification label region L3 including a substance being reacted with the second amplification liquid from the label-holding pad 3 side between the label-holding pad 3 and the absorption pad 6. Paragraph [0050] teaches that the first amplification liquid 41 is added dropwise to the upper portion of the insoluble carrier 2 in a manner that it will be supplied to the inspection region L1, the confirmation region L2, and the amplification label region L3 on the insoluble carrier. Paragraph [0059] teaches that a liquid-sending pad 4 is immersed into the second amplification liquid 46 in the second pot 45, and the second amplification liquid 46 can permeate through the liquid-sending pad 4 by capillarity so as to be supplied to the insoluble carrier 2. Paragraph [0077] teaches that the amplification label region L3 is a region which includes a substance being reacted with the second amplification liquid 46, is reacted with the second amplification liquid 46 and thus produces or changes color, thereby indicating the spread of the second amplification liquid 46 to the region, and serves as an index of timing for the dropwise addition of the first amplification liquid 41. For example, in a case in which a mixed aqueous solution of an aqueous solution of iron nitrate and citric acid (038-06925 manufactured by Wako Pure Chemical Industries, Ltd.) is used as the second amplification liquid 46, an aspect in which the amplification label region L3 is constituted of coloring reagent immobilization lines in which bromocresol green (manufactured by Wako Pure Chemical Industries, Ltd.) is linearly immobilized is preferred. In this case, in a case where the second amplification liquid 46 arrives at the amplification label region L3, the color of the region L3 changes from green to orange. This color change can be considered as an index indicating that the inspection region L1 and the confirmation region L2 are sufficiently wetted with the second amplification liquid 46. Starting a paragraph [0094], the method is explained. In paragraph [0096] a specimen liquid is added dropwise onto the label-holding pad 3 from the hole 16 for dropwise addition of specimen liquid. In a case in which the test substance is included in the specimen liquid, the test substance and the first substance are bonded to each other in the label-holding pad 3, whereby a complex body of the test substance and the label substance is formed through the first substance, and the complex body is spread toward the absorption pad 6 side together with the specimen liquid due to the suctioning force of the absorption pad 6 and capillarity. At the same time as or after the dropwise addition of the specimen liquid, the second protrusive deforming portion 14 is pressed down, the liquid-sending pad 4 is displaced, the sheet member 48 of the second pot 45 is torn up, the second amplification liquid 46 penetrates through the liquid-sending pad 4, and therefore the second amplification liquid 46 is sent to the insoluble carrier 2. Meanwhile, a timing of pressing down the second protrusive deforming portion 14 is preferably within 30 seconds or shorter from the dropwise addition of the specimen liquid and a timing immediately after the dropwise addition of the specimen liquid is particularly preferable. Paragraph [0097] describes the arrival and trapping of the complex body at the inspection region L1 and the arrival and bonding of other substances at the confirmation region L2. Paragraph [0098] teaches that the second amplification liquid 46 arrives at the amplification label region L3 via the inspection region L1 and the confirmation region L2. At this time, the amplification label region L3 discolors, whereby it is possible to visually recognize the arrival of the second amplification liquid 46 at the amplification label region L3. After the discoloration of the amplification label region L3 is confirmed, the first protrusive deforming portion 12 is pressed down and the first amplification liquid 41 is supplied to the insoluble carrier 2. Paragraph [0099] teaches that after supplying the first amplification liquid 41 to the insoluble carrier 2, a period of time is allowed to pass until the completion of the reaction, and the discoloration in the inspection region L1 and the confirmation region L2 is confirmed through the observation window 18. The presence or absence of the test substance and the concentration thereof can be confirmed from the discoloration of the inspection region L1, and whether or not inspection for measuring the test substance succeeded can be confirmed from the discoloration of the confirmation region L2. Discoloration in the inspection region L1 and the confirmation region L2 is caused by amplifying the signals of the label, and highly sensitive inspection can be carried out.
With respect to claim 1, it would have been obvious to one of ordinary skill in the art to modify the Arai device with a processing capability as taught by Inana to both determine if amplification is needed and/or end a waiting period once a predetermined level of signal has been reached in the analysis region prior to a defined waiting period because of the efficiency gained as taught by Inana. Additionally, it would have been obvious to one of ordinary skill in the art at the time the application was filed to handle an immunochromatographic kit/cartridge as taught by Wada because of the ability to automatically perform the release of amplification fluids as taught by Arai, the ability of the L3 region to be used as an index of timing for the dropwise addition of the first amplification liquid as taught by Wada and the ability of one of ordinary skill in the art to operate an analysis instrument and/or provide automation in the same manner as a conventional method practiced by a user using a visual test kit as taught by Inana for a prior art device.
With respect to claim 2, Arai teaches that at least the second reagent among the first reagent and the second reagent is an amplifying liquid that amplifies color development in the assay region. With respect to claim 3, Wada teaches that the first reagent and the second reagent are amplifying liquids that amplify color development in the assay region by reacting with each other so that modification of Arai with the teachings of Wada would meet the requirement of claim 3 for the reasons given above for claim 1. With respect to claim 4, Inana and Wada teach the discrimination of the presence or absence of a color change in a color development state after a lapse of a preset time so that modification of Arai with the teachings of Inana and Wada would meet the requirement of claim 4 for the reasons given above for claim 1. With respect to claim 5, Inana teaches the discrimination an error based absence of a color change after a lapse of a preset time so that modification of Arai with the teachings of Inana would meet the requirement of claim 5 for the reasons given above for claim 1. With respect to claim 6, the all three applied references have first, second and third areas for color detection and Arai teaches a camera having plural photodiodes so that the plurality of detectors language is met. Wada teaches first, second and third areas for color detection consistent with that being claimed so that modification of Arai with the teachings of Wada would meet the requirement of claim 6 for the reasons given above for claim 1. With respect to claim 7, Inana teaches the operation of a reagent supply mechanism for amplification reagent based on the absence and/or presence of a color change in certain areas of the device so that modification of Arai with the teachings of Inana would meet the requirement of claim 7 for the reasons given above for claim 1. With respect to claim 8, Inana teaches the discrimination an error based absence of a color change after a lapse of a preset time so that modification of Arai with the teachings of Inana would meet the requirement of claim 8 for the reasons given above for claim 1. With respect to claims 9-13, Arai teaches a cartridge that has reagent holding parts and means to cause the release of those reagents under different conditions. Wada also teaches a cartridge with reagent holding parts and structures to release those reagents. Inana and Wada teach alternative conditions under which release of reagents occur that cover the claimed conditions so that modification of Arai with the teachings of Inana and Wada would meet the requirements of claims 9-13 for the reasons given above for claim 1.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The additionally cited art is directed toward chromatographic assay devices and detection/reader devices.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Arlen Soderquist whose telephone number is (571)272-1265. The examiner can normally be reached 1st week Monday-Thursday, 2nd week Monday-Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571)272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARLEN SODERQUIST/ Primary Examiner, Art Unit 1797
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