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 .
Remarks
This office action fully acknowledges Applicant’s remarks and amendments filed on 16 January 2026.
Claims 27-30 and 34-49 are pending.
Claims 1-26 and 31-33 are cancelled.
No claims are withdrawn.
Claim 49 is newly added.
Claim Interpretation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Such claim limitations are:
“a sample storage unit configured to store vessels” as in Claims 27 and 43.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
“a sample wheel” as in para. [0036] of Applicant’s instant pre-grant publication (US 2022/0326271 A1) and as seen through Applicant’s instant drawings Fig. 1…and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 27, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Hamazumi et al. (US 2009/0148345 A1), referred to herein as “Hamazumi”, in view of Lee et al. (EP 1,648,608 B1), hereinafter “Lee”, and Wilson (US 2009/0035866 A1), hereinafter “Wilson”.
Regarding Claim 27, Hamazumi teaches a method of performing automated sample dilution onboard an immunoassay diagnostic system (Figs. 2-5 and 15 show method steps for the automated chemical analyzer apparatus shown in Fig. 1.),
the method comprising: providing the immunoassay system (Fig. 1 shows the automated analyzer apparatus. Further, [0016] states analyses may include immunoanalysis.), including:
a sample storage unit configured to store vessels (Fig. 1 and [0051]: “reaction disk 11”);
a sample pipetting device configured to pipet patient samples into vessels; (Fig. 1 and [0051]: “sampling probe 3”);
a reagent pipetting device aligned with a carriage unit and configured to pipet a diluent into vessels (Fig. 1 and [0050]: “diluent-dispensing probe 6” – Fig. 1 further shows the probe 6 as being next to/aligned with the carousel 4.); and
a computer configured to automate at least one of the following method steps (Fig. 1 and [0050-0056], for example: “control unit 22” – [0002]: “The present invention relates to automated analyzers”):
pipetting, with the sample pipetting device, a first amount of patient sample from a primary vessel in a sample rack at a sample presentation unit of the immunoassay system (Fig. 1 and [0051]: “sample rack 1”); to a sample vessel at the sample storage unit ([0051]: “A biological sample is first dispensed into the sample vessels 2...” – see further below regarding the amended “held in” recitation”);
making a first patient sample dilution by:
pipetting, with the sample pipetting device, a second amount of patient sample from the sample vessel to a first dilution vessel in a vessel holder of the carriage unit ([0051]: “The biological sample is then dispensed [from sample vessels 2] into one of the dilution vessels 5 on the dilution disk 4 by the sampling probe 3.”); and
pipetting, with the reagent pipetting device, a first amount of diluent to the first dilution vessel at the carriage unit ([0054]: “During each cycle A [Figs. 2 and 3], the following steps are concurrently performed on dilution vessels 5 placed on the dilution disk 4: sampling an original sample into a dilution vessel; dispensing a diluent into a dilution vessel; stirring a sample and diluent in a dilution vessel; and rinsing a dilution vessel.” – Fig. 1 shows diluent-dispensing probe 6.); and
storing the first dilution vessel, containing the first patient sample, in the sample storage unit (Fig. 1 shows that the dilution vessels 12 are stored at the dilution disk 11 (sample storage unit). -- [0066]: “…the remaining sample in dilution vessel # 1 that has completed re-sampling is kept in that vessel until it is determined whether the sample needs to be re-analyzed or not.”), as in Claim 27.
Further regarding Claim 27, Hamazumi does not specifically teach the method discussed above further comprising pipetting, with the sample pipetting device, a first amount of patient sample from a primary vessel in a sample rack at a sample presentation unit of the immunoassay system to a sample vessel held in the sample storage unit; pipetting, with the sample pipetting device, a second amount of patient sample from the sample vessel to a first dilution vessel, as in Claim 27.
However, Lee teaches a respective automatic analyzer method comprising a pipetting arm 44 which access a sample rack 42 holding primary sample specimen tubes 40 at a sample presentation unit 36, wherein the sampling arm 44 obtains a sample aliquot from a respective tube 40 and stores said aliquot within a storage/environmental chamber 38 for future use (Fig. 1 and [0016-0017]), in addition to storing aliquots within the aliquot vessel arrays 52 of the array transport system 50 for nearer-term use after storage. Thereafter, a second amount of the sample is pipetted from the storage module 38/50 to cuvettes of the cuvette carousel 16 for analysis. Therein, this arrangement provides for longer-term safety and efficacy assessments, allowing for the retesting of samples if needed, ensuring the accuracy of results, and maintaining quality control standards.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method and device of Hamazumi further comprising pipetting, with the sample pipetting device, a first amount of patient sample from a primary vessel in a sample rack at a sample presentation unit of the immunoassay system to a sample vessel held in the sample storage unit; pipetting, with the sample pipetting device, a second amount of patient sample from the sample vessel to a first dilution vessel, such as suggested by Lee, so as to provide longer-term safety and efficacy assessments, allowing for the retesting of samples if needed, ensuring the accuracy of results, and maintaining quality control standards. Therein, one skilled in the art would merely rearrange the respective orientation of probes and carousels such that the sampling probe reaches both the samples presented at the sample presentation unit, and the storage unit for storing sample aliquots.
Further regarding Claim 27, Hamazumi does not specifically teach the method discussed above wherein the first dilution vessel is stored in the sample storage unit, as in Claim 27. However, Wilson teaches a respective automated analyzer and method wherein sample-containing vessels are physically moved from other areas of the device to the sample storage unit via a gantry and gripper assembly, as well as removes said vessels from the storage unit for further analysis ([0054]). Therein, this arrangement provides to further enhance safety and efficacy by retaining patient samples for future analysis and storing said samples to retain their properties and prevent degradation.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device and method of Hamazumi wherein the first dilution vessel is stored in the sample storage unit, such as suggested by Wilson, so as to further enhance safety and efficacy by retaining patient samples for future analysis and storing said samples to retain their properties and prevent degradation.
Regarding Claim 34, the prior art meets the limitations of Claim 27 as discussed above. Further, Hamazumi teaches the method discussed above comprising pipetting a first amount of the first patient sample dilution from the first dilution vessel 5 to a second reaction vessel 12 at the carriage unit with the sample pipetting device ([0051] teaches “After diluted, the sample [held in dilution vessel 5] is moved to the re-sampling position 8, where it is sampled again into one of the reaction vessels 12 on the reaction disk 11 by the re-sampling probe 10.” As the dilution vessel moves near the carriage unit to accept a transfer from a vessel held at the carriage unit, it is said to be at the carriage unit.), as in Claim 34.
Regarding Claim 38, the prior art meets the limitations of Claim 37 as discussed above. Further, Hamazumi teaches the method discussed above further comprising storing the second dilution vessel 12 at the sample storage unit 11 (Fig. 1 shows second dilution vessels/reaction vessels 12 stored at the reaction disk 11.), as in Claim 38.
Claims 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hamazumi in view of Lee and Wilson, as applied to Claims 27, 34, and 38 above, and in further view of Yamamoto et al. (US 2019/0219605 A1), hereinafter “Yamamoto”.
Regarding Claim 28, the prior art meets the limitations of Claim 27 as discussed above. Further, Hamazumi teaches the method discussed above wherein:
the sample storage unit includes a sample wheel (Fig. 1 shows the dilution disk 4 and reaction disk 11 (the sample storage unit) as a wheel/carousel structure.);
and the sample pipetting device includes a sample aliquot pipetting unit (Fig. 1 shows the sampling probe 3 (the sample pipetting device) as connected to sampling mechanism 19 (sample aliquot pipetting unit).), as in Claim 28.
Further regarding Claim 28, Hamazumi does not specifically teach the method discussed above wherein the method further comprises cooling the sample storage unit, as in Claim 28.
However, Yamamoto teaches a commensurate receptacle carrier unit and automated analyzer comprising a turntable 103 (for holding reagent receptacles 24) contained within a cool box 100 and wherein a cooling portion 105 cools the inner space of the cool box and the elements contained within (Fig. 2, Fig. 5, and [0010]). Yamamoto teaches the advantage of keeping the turntable and reagent receptacles held therein as “to prevent deterioration of the liquids such as reagents and analytes” ([0003]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the dilution disk (sample storage unit) of Hamazumi with the cooling assembly taught by Yamamoto to prevent deterioration of the liquids such as reagents and analytes, thereby reducing experimental error due to degraded samples/reagents.
Regarding Claim 29, the prior art meets the limitations of Claim 28 as discussed above. Further, Hamazumi teaches the method discussed above comprising pipetting a third amount of patient sample from the sample vessel to a first reaction vessel, at the carriage unit, with the sample pipetting device (Given that Hamazumi teaches “a reaction vessel” as a vessel where “a sample is reacted with a reagent” (Cl. 1), and that diluent dispensing arm 6 accesses reagent bottles 14 to add reagent to dilution vessels 5, the dilution vessels 5 are considered reaction vessels when a reagent is dispensed thereto. Thus, a third amount of patient sample on the second cycle A is dispensed into a reaction vessel 5 when the diluent is a reagent and/or the vessel requires incubation as part of the pretreatment before re-sampling ([0075]). -- Fig. 1 shows the sample vessels 2, held by sample rack 1, are at/near a carriage unit 4 (As the carriage unit holds sample vessels and moves within the device, the carriage unit is thus said to move the sample vessel from place to place within the system.),
wherein the sample aliquot pipetting unit pipettes the first amount of patient sample from the primary vessel to the sample vessel (Fig. 1 and [0050]: Sampling mechanism 19 is shown as connected to sampling probe 3, which pipettes sample from the sample vessels 2 to the dilution vessels 5.),
and wherein the sample pipetting device includes a sample pipetting unit (The sampling mechanism 19 is considered the sample pipetting unit as said unit may pipette an aliquot or a full sample depending on the sample volume.), as in Claim 29.
Regarding Claim 30, the prior art meets the limitations of Claim 29 as discussed above. Further, Hamazumi teaches the method discussed above wherein pipetting the third amount of patient sample from the sample vessel to the first reaction vessel with the sample pipetting device occurs before pipetting the second amount of patient sample from the sample vessel to the first dilution vessel with the sample pipetting device (Fig. 2 shows that re-sampling of a sampled, diluted, and stirred sample (first cycle A and first cycle B) occur before initial sampling of a second amount of sample (second cycle A).), as in Claim 30.
Claims 35-37 and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Hamazumi in view of Lee and Wilson, as applied to Claims 27, 34, and 38 above, and in further view of Whitney et al. (US 2003/0204331 A1), referred to herein as “Whitney.”
Regarding Claim 35, the prior art meets the limitations of Claim 27 as discussed above. Further, Hamazumi does not teach the method discussed above comprising testing the first amount of the first patient sample dilution in the second reaction vessel and, if a response is non-linear, making a second patient sample dilution by pipetting a second amount of the first patient sample dilution from the first dilution vessel to a second dilution vessel with the sample pipetting device, as in Claim 35.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2). Therefore, a second dilution of Whitney comprises pipetting a second amount of the first patient sample dilution from the first dilution vessel to a second dilution vessel with the sample pipetting device, as in Claim 35. Further, Whitney discusses optimization of the number of dilution steps based on a measured concentration of the sample as determined by a user or algorithm so as to achieve a desired final concentration ([0028]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution and measurement steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample.
Additionally, as the dilution vessel moves near the carriage unit to accept a transfer from a vessel held at the carriage unit, it is said to be at the carriage unit.
Regarding Claim 36, the prior art meets the limitations of Claim 35 as discussed above. Further, Hamazumi does not teach the method discussed above wherein making the second patient sample dilution further comprises pipetting a second amount of diluent to the second dilution vessel with the reagent pipetting device, as in Claim 36.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2).
Therefore, a second dilution of Whitney comprises pipetting a second amount of diluent to the second dilution vessel with the reagent pipetting device, as in Claim 36.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample.
Regarding Claim 37, the prior art meets the limitations of Claim 27 as discussed above. Further, Hamazumi does not teach the method discussed above comprising a second patient sample dilution by: pipetting, with the sample pipetting device, a first amount of the first patient sample dilution from the first dilution vessel to a second dilution vessel at the carriage unit; and pipetting, with the reagent pipetting device, a second amount of diluent to the second dilution vessel, as in Claim 37.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2).
Therefore, a second dilution of Whitney comprises pipetting a second amount of the first patient sample dilution from the first dilution vessel to a second dilution vessel with the sample pipetting device; and pipetting a second amount of diluent to the second dilution vessel with the reagent pipetting device, as in Claim 37.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample.
Regarding Claim 39, the prior art meets the limitations of Claim 37 as discussed above. Further, Hamazumi does not teach the method discussed above further comprising pipetting a first amount of the second patient sample dilution from the second dilution vessel to a third reaction vessel with the sample pipetting device, as in Claim 39.
However, Whitney teaches sampling of diluted samples into reaction vessels at any point in the dilution pathway ([0046]: “a detection assay can be performed at any one or more points or stages in the dilution pathway”). Whitney Fig. 5 illustrates this with a microtiter plate wherein all of the serial dilutions are transferred to a reaction plate (the reaction vessel) containing reagents for PCR.
Therefore, Whitney teaches pipetting a first amount of the second patient sample dilution from the second dilution vessel to a third reaction vessel, as in Claim 39.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method perform analysis on each of the diluted samples.
Additionally, as the dilution vessel moves near the carriage unit to accept a transfer from a vessel held at the carriage unit, it is said to be at the carriage unit.
Regarding Claim 40, the prior art meets the limitations of Claim 39 as discussed above. Further, Hamazumi does not teach the method discussed above further comprising testing the first amount of the second patient sample dilution in the third reaction vessel and, if a response is non-linear, making a third patient sample dilution by pipetting a second amount of the second patient sample dilution from the second dilution vessel to a third dilution vessel with the sample pipetting device, as in Claim 40.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2). Therefore, a third dilution of Whitney comprises pipetting a second amount of the
second patient sample dilution from the second dilution vessel to a third dilution vessel with the sample pipetting device, as in Claim 40. Further, Whitney discusses optimization of the number of dilution steps based on a measured concentration of the sample as determined by a user or algorithm so as to achieve a desired final concentration ([0028]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample.
Additionally, as the dilution vessel moves near the carriage unit to accept a transfer from a vessel held at the carriage unit, it is said to be at the carriage unit.
Regarding Claim 41, the prior art meets the limitations of Claim 40 as discussed above. Further, Hamazumi does not teach the method discussed above wherein making the third patient sample dilution further comprises pipetting a third amount of diluent to the third dilution vessel with the reagent pipetting device, as in Claim 41.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2).
Therefore, a third dilution of Whitney comprises pipetting a third amount of diluent to the third dilution vessel with the reagent pipetting device, as in Claim 40.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample.
Regarding Claim 42, the prior art meets the limitations of Claim 37 as discussed above. Further, Hamazumi teaches storing the third dilution vessel at the sample storage unit (Fig. 15).
Hamazumi does not teach making a third patient sample dilution by: pipetting, with the sample pipetting device, a first amount of the second patient sample dilution from the second dilution vessel to a third dilution vessel; pipetting, with the reagent pipetting device, a third amount of diluent to the third dilution vessel with the reagent pipetting device; and pipetting, with the sample pipetting device, a first amount of the third patient sample dilution from the third dilution vessel to a fourth reaction vessel with the sample pipetting device, as in Claim 42.
However, Whitney teaches a commensurate automated sample preparation method and device wherein a serial dilution is performed by pipetting an amount of sample to a sample vessel, pipetting an amount of sample from the sample vessel to a dilution vessel, pipetting an amount of diluent to the dilution vessel, and repeating the process of sampling and dilution on the diluted sample as many times as necessary until the desired concentration is achieved ([0032]: “an appropriate dilution scheme can be designed for any application” – See also [0020] and Fig. 2).
Therefore, a third dilution of Whitney comprises pipetting a second amount of the second patient sample dilution from the second dilution vessel to a third dilution vessel with the sample pipetting device; pipetting a third amount of diluent to the third dilution vessel with the reagent pipetting device, as in Claim 40.
Further, Whitney teaches sampling of diluted samples into reaction vessels at any point in the dilution pathway ([0046]: “a detection assay can be performed at any one or more points or stages in the dilution pathway”). Whitney Fig. 5 illustrates this with a microtiter plate containing first, second, and third dilutions, wherein all of the samples are transferred to a reaction plate containing reagents for PCR.
Therefore, Whitney teaches pipetting a first amount of the third patient sample dilution from the third dilution vessel to a fourth reaction vessel with the sample pipetting device, as in Claim 39.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the serial dilution steps taught by Whitney so as to provide a suitable method to achieve a desired target concentration of the sample and perform analysis on each of the diluted samples.
Additionally, as the dilution vessel moves near the carriage unit to accept a transfer from a vessel held at the carriage unit, it is said to be at the carriage unit.
Claims 43-48 are rejected under 35 U.S.C. 103 as being unpatentable over Hamazumi in view of Langhoff et al. (US 2017/0307525 A1), referred to herein as “Langhoff”, Stein et al. (WO 2018/017771 A1), hereinafter “Stein”, and Hegel et al. (US 2016/0161480 A1), hereinafter “Hegel”. Hamazumi has been discussed above.
Regarding Claim 43, Hamazumi teaches a method of performing automated sample dilution onboard an immunoassay diagnostic system (Figs. 2-5 and 15 show method steps for the automated chemical analyzer shown in Fig. 1.), the method comprising: providing the immunoassay system (Fig. 1 shows the automated analyzer apparatus. Further, [0016] states analyses may include immunoanalysis.), including:
a sample pipetting device configured to pipet patient samples into vessels (Fig. 1 and [0051]: “sampling probe 3”);
a reagent pipetting device configured to pipet a diluent into vessels (Fig. 1 and [0050]: “diluent-dispensing probe 6”); and
a computer configured to automate at least one of the following method steps (Fig. 1 and [0051]: “sampling probe 3”):
pipetting, a first amount of patient sample from a primary vessel to a sample vessel and a second amount of patient sample from the sample vessel to a reaction vessel ([0058]),
diluting the sample by: pipetting an amount of sample from the sample vessel to a dilution vessel with the sample pipetting device; and pipetting an amount of diluent to the dilution vessel with the reagent pipetting device (Fig. 2 and Fig. 3), as in Claim 43.
Further regarding Claim 43, Hamazumi does not specifically teach the automated analyzer discussed above wherein the same probe of the automated analyzer which handles a primary sample solution also functions as a serial dilution and reagent pipettor, as in Claim 43.
However, Stein teaches a respective automated analyzer wherein a singular probe 20 (Figs 1 and 2) performs all aspects of sample handling, including performing serial dilutions ([000218]), as well as reagents ([00012]), wherein this arrangement provides for simpler calibration (only need to calibrate one probe instead of two), providing more consistency between runs, reduces inter-probe latency between runs, and allows more flexibility on sample locations within the device while also being capable of holding more samples in a defined space as opposed to along the circumference of a carousel.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the automated analyzer of Hamazumi wherein the same probe of the automated analyzer which handles a primary sample solution also functions as a serial dilution and reagent pipettor, such as suggested by Stein, so as to achieve the benefits of simpler calibration (only need to calibrate one probe instead of two), providing more consistency between runs, reducing inter-probe latency between runs, and allowing more flexibility on sample locations within the device while also being capable of holding more samples in a defined space as opposed to along the circumference of a carousel; and would have a reasonable expectation of success therein.
Further regarding Claim 43, Hamazumi does not teach testing the second amount of patient sample with the immunoassay system; to determine, based on the testing, if a hook effect or a prozone effect is present in the second amount of patient sample; and diluting or further diluting the patient sample, based on the determining, to make a first patient sample dilution, by: pipetting, with the sample pipetting device, ana third amount of patient sample from the sample vessel to a dilution vessel and pipetting, with the reagent pipetting device, an amount of the diluent to the dilution vessel, as in Claim 43.
However, Langhoff teaches an apparatus for optical inspection of small volumes of liquid wherein the apparatus determines the turbidity of a sample (the pre-determined characteristic) and, based on the turbidity value determined, automatically dilutes the sample as many times as necessary until the desired turbidity value is obtained ([0058]). This optical monitoring allows for precise control over the dilution process, providing consistency across multiple samples, and reducing error related to over- or under-dilution of the samples.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the optical dilution monitoring taught by Langhoff to allow for precise control over the dilution process, providing consistency across multiple samples, and reducing error related to over- or under-dilution of the samples.
Further regarding Claim 43, regarding the hook effect and the prozone effect, Hegel teaches that most modern automated analyzers are equipped with the capability to recognize this effect ([0005]: “Most modern automated analyzers used in clinical chemistry have built in methods for recognizing the prozone effect in the measured samples. In case that a sample shows a prozone effect, the sample measurement is flagged by the analyzer. For such flagged measurements, a re-measurement of the sample after a dilution is recommended or even performed automatically by the analyzer, depending on the instrument setting.”), wherein this arrangement reduces the number of false negative test results.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the analyzer of Hamazumi so as to include checking for hook/prozone effect, such as suggested by Hegel, so as to reduce the frequency of false negative test results; and would have a reasonable expectation of success therein.
Regarding Claim 44, the prior art meets the limitations of Claim 43 as discussed above. Further, Hamazumi does not teach the method discussed above wherein the hook effect or the prozone effect is present in the second amount of patient sample is determined by a measurement by a light measurement device.
However, Hegel teaches a respective automated analyzer, discussed above regarding Claim 43, wherein determination of the hook/prozone effect is made using light measurement ([0062]: “the optical signal for the specific analyte in the sample to be determined is measured simultaneously at the wavelength used for the determination of the analyte and at least at an additional specific wavelength used for the detection of the prozone effect over the complete reaction time”).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious that when modifying the analyzer of Hamazumi with the hook/prozone check process of Hegel, to implement the process using light measurement, as taught by Hegel, so as to provide a sufficient measurement arrangement for determining the hook/prozone effect; and would have a reasonable expectation of success therein.
Regarding Claim 45, the prior art meets the limitations of Claim 44 as discussed above. Further, Hamazumi does not teach the hook effect or the prozone effect is present in the second amount of patient sample is indicated if output from the light measurement device is proportionate to a dilution ratio of the patient sample.
However, Hegel teaches a respective automated analyzer, discussed above regarding Claim 43, wherein determination of the hook/prozone effect is made using light measurement of scattering, wherein scattering is a characteristic proportionate to the dilution ratio/concentration of the sample.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious that when modifying the analyzer of Hamazumi with the hook/prozone check process of Hegel, to implement the process using light scattering, such as suggested by Hegel, so as to provide a sufficient measurement process, wherein light scattering is proportional to the concentration/dilution ratio of a sample; and would have a reasonable expectation of success therein.
Regarding Claim 46, the prior art meets the limitations of Claim 45 as discussed above. Further, Hamazumi does not teach further diluting the sample if the output from the light measurement device is not proportionate to the dilution ratio of the sample.
However, Langhoff teaches further diluting the sample if the output from the light measurement device is not proportionate to the dilution ratio of the sample ([0058]: “The apparatus described herein measures the initial turbidity of the test sample and the McFarland value is recorded. The sample suspension is further diluted by adding additional suspension fluid if the initial turbidity readings are too high.”). This allows the desired turbidity value to be obtained, allowing for precise control over the dilution process, providing consistency across multiple samples, and reducing error related to over- or under-dilution of the samples.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method taught by Hamazumi with the automated dilution process taught by Langhoff to allow for precise control over the dilution process, providing consistency across multiple samples, and reducing error related to over- or under-dilution of the samples.
Regarding Claim 47, the prior art meets the limitations of Claim 43 as discussed above. Further, Hamazumi does not specifically teach the method discussed above further comprising testing the diluted sample; determining if the hook effect or the prozone effect is present in the first patient sample dilution; and further diluting and testing the first patient sample dilution into a diluted sample until the hook effect or the prozone effect is not present in the diluted sample, as in Claim 47.
However, Hegel teaches a respective automated analyzer wherein dilution of the sample is repeated until a prozone effect is not detected, wherein only then is a result reported ([0072-0075] and [0102-0111]), wherein this process provides for a reportable result from a patient sample even if initial dilution is unsuccessful.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Hamazumi wherein the sample is re-diluted until a prozone effect is not detected, such as suggested by Hegel, so as to provide a reportable result from a patient sample even when initial dilution is unsuccessful, and would have a reasonable expectation of success therein.
Regarding Claim 48, the prior art meets the limitations of Claim 43 as discussed above. Further, similarly as above regarding Claim 47, Hamazumi does not specifically teach the method discussed above further comprising iteratively testing and diluting the patient sample until the testing indicates a hook effect or a prozone effect is not present in the patient sample, as in Claim 48.
However, Hegel teaches a respective automated analyzer wherein dilution of the sample is repeated until a prozone effect is not detected, wherein only then is a result reported ([0072-0075] and [0102-0111]), wherein this process provides for a reportable result from a patient sample even if initial dilution is unsuccessful.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Hamazumi wherein the sample is iteratively tested and re-diluted until a prozone effect is not detected, such as suggested by Hegel, so as to provide a reportable result from a patient sample even when initial dilution is unsuccessful, and would have a reasonable expectation of success therein.
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Hamazumi in view of Lee and Wilson, as applied to Claims 27, 34, and 38 above, and in further view of Kodama et al. (US PAT 6,599,749 B1), hereinafter “Kodama”.
Regarding Claim 49, the prior art meets the limitations of Claim 27 as discussed above. Further, Hamazumi teaches the method discussed above further comprising the step of: moving vessels within the immunoassay system with the carriage unit 4 ([0077]), as in Claim 49.
Further regarding Claim 49, Hamazumi does not specifically teach the method discussed above comprising transporting vessels with the sample presentation unit, as in Claim 49.
However, Kodama teaches a respective automated analyzer wherein one or more racks containing samples (Fig. 11) are fed into the automated analyzer via a conveyance line/belt (Fig. 2) as discussed in col. 1, line 8. Therein, this arrangement allows additional patient samples to be queued to the analyzer, reducing downtime, increasing throughput.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device and method of Hamazumi for transporting vessels with the sample presentation unit, such as suggested by Kodama, so as to increase throughput of the analyzer; and would have a reasonable expectation of success therein.
Response to Arguments
35 USC 103 – Claim 27
Applicant’s arguments are on the alleged grounds that Hamazumi lacks the claimed “sample pipetting device” as the sampling probe 3 of Hamazumi is not able to pipet from the sample rack 1 to the reaction disk 11 as in the Claim 27 amendments requiring the sample vessel being “held in” the sample storage unit and not merely “at” the sample storage unit as previously recited.
Applicant’s arguments are not persuasive because this alleged deficiency in Hamazumi is cured by obvious combination with the prior art of Lee, newly added herein as necessitated by Applicant’s “held in” amendment, wherein Lee teaches a sample pipetting arm accessing both primary sample vessels at a sample presentation unit, and pipetting using said pipetting arm aliquots of the primary sample to a storage area to retain the samples for future use, thereby providing added safety and efficacy as discussed above in the body of the action.
Applicant further alleges one skilled in the art would not find it obvious to provide the sampling probe 3 of Hamazumi as transferring primary patient sample directly to the reaction disk 11 as the reaction disk 11 is provided for re-sampling of a diluted sample. However, in view of Lee, one skilled in the art would find it obvious to provide a primary undiluted sample to the respective disk of Hamazumi so as to store the sample for future use, as discussed above. Such a process would not undermine the functionality of Hamazumi which is fully capable of performing transfer operations between disks on both diluted and undiluted samples and would not require a materially different mode of operation.
Applicant further alleges that there is no sample vessel in Hamazumi which both receives patient sample pipetted from the sample rack in a sample storage unit and also has sample pipetted from it to a vessel of the carriage unit.
Applicant’s arguments are not persuasive because, similarly as above as necessitated by Applicant’s amendment specifying the vessel is “held in” the storage unit, Lee provides for pipetting sample from the vessels held in the sample storage areas to analysis cuvettes of the device receiving diluent/reagent, wherein this arrangement provides an alternate path for transferring the sample to the dilution cuvette, similarly as in the re-sampling procedure of Hamazumi.
Applicant further alleges that Hamazumi lacks the claimed first dilution vessel which receives patient sample from the sample storage unit transferred to the carriage unit, and which is then stored in the sample storage unit.
Applicant’s arguments are not persuasive because this alleged deficiency in Hamazumi is cured by obvious combination with Wilson, newly added herein as necessitated by Applicant’s amendments requiring the first dilution vessel be stored “in” the sample storage unit, which teaches physically moving the actual sample-containing vessels from analysis locations of the device to and from a storage area of the device using a robotic gripper assembly, thereby providing to further enhance the safety and efficacy of the device by retaining patient samples for future testing/re-testing.
Thus, Examiner sets forth the rejection of Claims 27-30, 34-42, and 49 as unpatentable under 35 USC 103 over Hamazumi in view of at least Lee and Wilson, as discussed above in the body of the action and as necessitated by Applicant’s amendments more particularly reciting the specific holding locations of the vessels of the method.
35 USC 103 – Claim 43
Applicant’s arguments are on the alleged grounds that modification of Hamazumi in view of Stein such that a single probe performs all aspects of sample handling would render the device of Hamazumi inadequate for its intended purpose as a single probe would allegedly add a chokepoint in the simultaneous pre-treatment and re-sampling operations.
Applicant’s arguments are not persuasive because the simultaneous pretreatment and sampling operations of Hamazumi are fully capable of being performed by a single probe given that pretreatment sometimes includes an incubation time ([0075]) allowing the probe to perform other operations during the incubation, and that the single probe mounted on an x/y gantry is capable of moving to perform other operations at the same time as pretreatment. Further it is noted that the prior office action states “the same probe of the automated analyzer which handles a primary sample solution also functions as a serial dilution and reagent pipettor”, not specifically stating that the device of Hamazumi be limited to a single probe as in Stein. As such, the re-sampling probe would remain present in Hamazumi, further allowing the simultaneous pretreatment and re-sampling processes to take place.
Thus, Examiner maintains the rejection of Claims 43-48 under 35 USC 103 as unpatentable over Hamazumi in view of Langhoff, Stein, and Hegel as discussed above in the body of the action.
New Claim 49
Claim 49 is newly added herein and rejected under 35 USC 103 as unpatentable over Hamazumi in view of Lee, Wilson, and Kodama as discussed above in the body of the action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/B.J.K./Examiner, Art Unit 1798
/NEIL N TURK/Primary Examiner, Art Unit 1798