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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claims 24-29, 34, 36, 39-42 and 44 are objected to because of the following informalities: On line 51 of claim 24, the phrase “the first light-absorption profile” should be changed to –the first light absorbance profile—so as to recite the same terminology as recited earlier in the claim. On line 53 of claim 24, the phrase “the second light-absorption profile” should be changed to –the second light-absorbance profile-- so as to recite the same terminology as recited earlier in the claim. At the end of line 30 in claim 40, the word –and—should be inserted because the following step of obtaining the first and second pairs of parameters is the last step of the method performed by the controller. On line 39 of claim 40, the phrase “the third light-absorption profile” should be changed to –the third light absorbance profile—so as to recite the same terminology as recited earlier in the claim. On line 41 of claim 40, the phrase “the fourth light-absorption profile” should be changed to –the fourth light-absorbance profile-- so as to recite the same terminology as recited earlier in the claim. On line 43 of claim 40, the phrase “between the parameters in the selected one pair comprises” should be changed to -- between the parameters in the selected at least one pair comprises—so as to recite the same terminology as recited in independent claim 24. On line 52 of claim 40, the phrase “calculated arithmetic relationship relative to a predetermined value” should be changed to -- calculated arithmetic relationship relative to at least one predetermined value-- so as to recite the same terminology as recited in independent claim 24. On line 11 of claim 44, the phrase “and dispense the calcium solution in the second” should be changed to –and dispensing the calcium solution in the second—so as to make proper sense. On line 31 of claim 44, , the phrase “the first light-absorption profile” should be changed to –the first light absorbance profile—so as to recite the same terminology as recited earlier in the claim. On line 33 of claim 44, the phrase “the second light-absorption profile” should be changed to –the second light-absorbance profile-- so as to recite the same terminology as recited earlier in the claim Appropriate correction is required.
Inventorship
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 24-29, 39-42 and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ieko et al (US 2017/0350907) in view of Barco et al (article from the Journal of Thrombosis and Haemostasis, vol. 18, no. 7, July 2020. [ages 1598-1617 submitted in the IDS filed on March 6, 2023).
With regards to claims 24 and 44, Ieko et al teach of a method and an analysis system for analyzing a cause of prolonged coagulation time in a blood sample. The analysis system 10 comprises a sample preparator 50 including a sample dispenser having a first arm (sample dispensing arm 17) and a first pipette 17a attached to the first arm 17, wherein the sample dispenser is configured to dispense a quantity of a blood sample into each of a first and a second cuvette 104 located on a cuvette table 13 (see Figure 3 in Ieko et al), and a reagent dispenser including a second arm 18 (reagent dispensing arm 18) and a second pipette 18a attached to the second arm 18, wherein the reagent dispenser is configured to dispense a reagent used in a blood coagulation assay, such as an activated partial thromboplastin time (APTT) measurement reagent and a calcium solution in each of the first and second cuvettes 104 (see paragraphs 0051, 0084-0090 and 0145 in Ieko et al). The analysis system further comprises a light applicator 27 configured to apply light to the first and second cuvettes 104, a detector 22 configured to detect the light through the first and second cuvettes 104 (see paragraphs 0091-0092 in Ieko et al), and a controller 200 operably connected with the sample preparator 50, the light applicator 27 and the detector 22 (see paragraph 0099 in Ieko et al). The controller is programmed to control the sample preparator 50 to dispense a quantity of a blood sample from a single patient and an APTT reagent into a first cuvette 104 on the cuvette table 13, wherein the blood sample from a single patient comprises “the blood specimen of a subject” in paragraphs 0047-0048 of Ieko et al and the “test plasma” in paragraphs 0145-0146 of Ieko et al, and dispense a quantity of a calcium solution into the first cuvette immediately after dispensing the quantity of the blood sample and the APTT reagent in the first cuvette in order to obtain an immediate coagulation time of the blood sample (see Example 1, paragraphs 0144-0146 in Ieko et al where an immediate coagulation reaction of a test plasma, a normal plasma and a mixed plasma is measured by adding APTT and a calcium chloride solution to the samples). The controller is also programmed to dispense a quantity of the blood sample from the single patient into a second cuvette 104 on the cuvette table 13 and allow incubation of the blood sample in the second cuvette for a waiting time of about 2 hours before dispensing both an APTT reagent and a calcium solution into the second cuvette 104 in order to initiate a coagulation reaction (see Example 1, paragraphs 0144-0146 in Ieko et al where a delayed coagulation reaction of the test plasma, the normal plasma and the mixed plasma is measured by first incubating each of these plasma samples for 2 hours at 37oC followed by measuring coagulation in these incubated plasma samples by adding APTT reagent and a calcium solution). The controller is also programmed to control the light applicator 27 to apply light to the first and second cuvettes 104 that each contain a quantity of the blood sample from the single patient (i.e. the “blood specimen of a subject” in paragraphs 0047-0048 and the “test plasma” in paragraphs 0145-0146 of Ieko et al), the APTT reagent and the calcium solution, obtain a first coagulation waveform representing a first profile of the light detected through the first cuvette 104 for the immediate coagulation plasma samples, obtain a second coagulation waveform representing a second profile of the light detected through the second cuvette 104 for the delayed coagulation plasms samples, obtain a first coagulation time derived from the first coagulation waveform (i.e. equivalent to the “the first coagulation time” described for the single blood specimen of the subject or “test plasma” in paragraphs 0048, 0056 and 0146 of Ieko et al), obtain a second coagulation time derived from the second coagulation waveform (i.e. equivalent to the “the fourth coagulation time” described for the single blood specimen of the subject or “test plasma” in paragraphs 0049, 0056 and 0146 of Ieko et al), calculate an arithmetic relationship between the first coagulation time and the fourth coagulation time, wherein the arithmetic relationship comprises calculating a first quantification index that uses the first coagulation time of the single blood specimen of the subject or “test plasma”, calculating a second quantification index that uses the fourth coagulation time of the single blood specimen of the subject or “test plasma”, and obtaining either a difference or a ratio between the first and second quantification indexes, analyze a cause for a prolonged coagulation time in the single blood specimen of the subject or “test plasma” by comparing the calculated difference or ratio between the first and second quantification indexes with a predetermined threshold value (see paragraphs 0070-0079 and Example 1 in paragraphs 0144-0150 in Ieko et al), and output an analysis result of the cause of the prolonged coagulation time. The analysis system 10 taught by Ieko et al performs the corresponding steps recited in claim 44 for analyzing a cause of prolonged coagulation time in a blood sample. See paragraphs 0041-0044, 0047-0056, 0080-0092, 0099, 0104 and 0144-0146 in Ieko et al.
Ieko et al fail to teach that the controller 200 is programmed to control the sample preparator to dispense a quantity of a blood sample and an APTT reagent into a first cuvette 104, and dispense the calcium solution in the first cuvette 104 a first waiting time after dispensing the quantity of the blood sample and the APTT reagent in the first cuvette 104, and to dispense a quantity of the blood sample and the APTT reagent into the second cuvette 104, and dispense the calcium solution in the second cuvette a second waiting time after dispensing the quantity of the blood sample and the APTT reagent in the second cuvette 104, wherein the second waiting time is set to longer than the first waiting time.
Barco et al teach that coagulation abnormalities in a blood sample leading to a prolonged coagulation time can be differentiated by performing an activated partial thromboplastin time (APTT) coagulation assay of a blood sample, wherein the assay comprises incubating the blood sample with an APTT reagent for different incubation times before addition of a calcium solution to initiate the coagulation reaction. See Figure 2 in Barco et al which depicts the results of different plasma samples representing either a normal, healthy individual having normal blood coagulation or abnormal individuals having a coagulation abnormality (such as a FVIII deficient plasma, heparin therapy plasma, etc.), wherein the plasma samples are incubated with an APTT reagent for different time intervals before addition of a calcium solution to initiate blood coagulation. A coagulation waveform for each of these blood samples is obtained, and a coagulation time can be derived from these coagulation waveforms. As depicted in Figure 2 of Barco et al, each of the blood samples having a prolonged coagulation time as compared to a normal blood sample can be differentiated from the normal sample and from each other. See Figure 2 in Barco et al.
Based upon a combination of Ieko et al and Barco et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method taught by Ieko et al for analyzing a cause of prolonged coagulation time in a blood sample by programming the controller 200 in the analysis system 10 to dispense a quantity of a blood sample from a single patient and an APTT reagent into a first cuvette 104, and dispense the calcium solution in the first cuvette 104 a first waiting time after dispensing the quantity of the blood sample and the APTT reagent in the first cuvette 104, and to dispense a quantity of the blood sample from the single patient and the APTT reagent into the second cuvette 104, and dispense the calcium solution in the second cuvette a second waiting time after dispensing the quantity of the blood sample and the APTT reagent in the second cuvette 104, wherein the second waiting time is set to longer than the first waiting time, because Barco et al teach that coagulation abnormalities in a blood sample leading to a prolonged coagulation time can be differentiated by incubating the blood sample with an APTT reagent for different incubation times before addition of a calcium solution to initiate the coagulation reaction, which is equivalent in operation to the analysis of the immediate and delayed coagulation times of the blood samples taught by Ieko et al in order to determine a cause of prolonged coagulation times.
With regards to claim 25, Ieko et al teach that the analysis system further comprises a heater 24 to incubate the quantity of the blood sample in the first and second cuvettes 104, wherein the controller is operably connected to the heater and programmed to control the heater 24 to maintain the quantity of the blood sample in the first cuvette to a predetermined temperature (37oC) during the immediate coagulation reaction (i.e. the first waiting time) and during the delayed coagulation reaction (i.e. the second waiting time). See paragraphs 0089 and 0103 in Ieko et al.
With regards to claims 26-29, the combination of Ieko et al and Barco et al fails to teach of the same specific first and second waiting times for incubating the quantities of the blood samples mixed with an APTT reagent prior to adding a calcium solution to initiate coagulation as recited in these claims. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to adjust the first and second waiting times for incubating the quantities of the blood samples mixed with an APTT reagent prior to adding a calcium solution to initiate coagulation in the combination of the teachings of Ieko et al and Barco et al because as taught by Barco et al, different incubation times of a blood sample with an APTT reagent prior to addition of a calcium solution produces different coagulation waveforms and coagulation times of blood samples having different abnormalities, thus allowing different blood coagulation abnormalities to be distinguished from one another by incubating blood samples with an APTT reagent for different waiting times prior to calcium addition.
With regards to claim 39, Ieko et al teach that the controller is programmed to obtain an analysis result of the cause for prolonged coagulation time of the blood sample obtained from the single patient based on calculating an arithmetic relationship between the first quantification index involving the first coagulation time of the blood sample and the second quantification index involving the fourth coagulation time of the blood sample (i.e. either a difference or a ratio between the first and second quantification indexes), comparing a result of the calculation to a predetermined threshold value, and reporting a result of the comparison as a cause of prolonged coagulation. See paragraphs 0056-0076 in Ieko et al, especially paragraphs 0070 where it states “The present inventors have found that the values of ratio and difference based on the immediate coagulation time and the delayed coagulation time enables differentiation between the coagulation factor inhibitor and other causes of prolongation”, and paragraph 0071 where it states “Specifically, the value of the ratio or difference or the value by combining them is compared with the first threshold value, and based on the comparison result, the information on whether a blood specimen of a subject is suspected of being a specimen containing a coagulation factor inhibitor or suspected of being a specimen having a cause of prolongation other than the coagulation factor inhibitor is acquired”. Also, see paragraph 0133 in Ieko et al.
With regards to claim 40, Ieko et al teach that the sample dispenser 17 and the reagent dispenser 18 are configured for dispensing a quantity of a blood sample, an APTT reagent and a calcium solution into multiple cuvettes 104 held on a cuvette table 13 at different times in accordance with a program run by the controller 200, wherein some of the blood samples undergo immediate coagulation by adding both APTT and a calcium solution to the blood samples at the same time and some of the blood samples are first incubated for a waiting time prior to adding the APTT reagent and the calcium solution. Multiple coagulation waveforms and multiple coagulation times are obtained for each of the cuvettes 104 by the controller 200, and a cause for prolonged coagulation in some of the blood samples is determined based on each of the measured multiple blood coagulation times. Based upon a combination of Ieko et al and Barco et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method taught by Ieko et al for analyzing a cause of prolonged coagulation time in a blood sample by programming the controller 200 in the analysis system 10 to dispense a quantity of a blood sample and an APTT reagent into multiple cuvettes 104, and dispense the calcium solution in the cuvettes 104 at multiple waiting times after dispensing the quantity of the blood sample and the APTT reagent in the cuvettes 104, wherein certain of the waiting times are set to longer than the other waiting times, because Barco et al teach that coagulation abnormalities in a blood sample leading to a prolonged coagulation time can be differentiated by incubating the blood sample with an APTT reagent for different incubation times before addition of a calcium solution to initiate the coagulation reaction.
With regards to claims 41-42, the combination of Ieko et al and Barco et al fails to teach of the same specific multiple waiting times (i.e. first, second, third and fourth waiting times) for incubating the quantities of the blood samples mixed with an APTT reagent prior to adding a calcium solution to initiate coagulation as recited in these claims. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to adjust the multiple waiting times for incubating the quantities of the blood samples mixed with an APTT reagent prior to adding a calcium solution to initiate coagulation in the combination of the teachings of Ieko et al and Barco et al because as taught by Barco et al, different incubation times of a blood sample with an APTT reagent prior to addition of a calcium solution produces different coagulation waveforms and coagulation times of blood samples having different abnormalities, thus allowing different blood coagulation abnormalities to be distinguished from one another by incubating blood samples with an APTT reagent for different waiting times prior to calcium addition.
Allowable Subject Matter
Claims 34 and 36 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims because the closest prior art to Ieko et al (US 2017/0350907) fails to teach or fairy suggest that a cause of prolonged coagulation in a blood sample from a single patient is determined by directly calculating either a difference or a ratio between a first coagulation time determined for the blood sample after adding a calcium solution to the blood sample and an APTT reagent at a first waiting time and a second coagulation time determined for the blood sample after adding a calcium solution to the blood sample and an APTT reagent at a second waiting time that is longer than the first waiting time. In the method and device taught by Ieko et al, the first coagulation time determined for the blood sample of a single patient (i.e. called the “blood specimen of a subject” in paragraphs 0047-0048 and a “test plasma” in paragraphs 0145-0146 of Ieko et al) at a first incubation time and the fourth coagulation time determined for the blood sample of the single patient at a second incubation time which is longer than the first incubation time (and is equivalent to the second coagulation time recited in instant claims 24 and 44), are used in separate calculations of a first and a second quantification index, which calculations also involve the use of coagulation times of a normal plasma sample and a mixed plasma sample comprising a mixture of the blood sample from the single patient and the normal plasma sample, and then either a difference or a ratio of the first and second quantification indexes is calculated in order to determine a cause of prolonged coagulation in the blood sample from the single patient. Therefore, in the method taught by Ieko et al, a cause for prolonged coagulation in a blood sample from a single patient is not determined by directly calculating a difference or a ratio between the first and fourth coagulation times of the blood sample obtained from the single patient, which are equivalent to the first and second coagulation times recited in the instant claims.
Response to Arguments
Applicant's arguments filed January 26, 2026 have been fully considered but they are not persuasive.
The previous rejections of the claims under 35 USC 112(a) and 35 USC 112(b) made in the last Office action mailed on November 6, 2025 have been withdrawn in view of the amendments made to the claims.
Applicant argues the rejection of the claims under 35 USC 103 as being obvious over Ieko et al (US 2017/0350907) in view of Barco et al (article from the Journal of Thrombosis and Haemostasis, vol. 18, no. 7, July 2020. [ages 1598-1617 submitted in the IDS filed on March 6, 2023) by first stating that Ieko et al teach of a cross mixing test in which coagulation for each of a blood specimen from a subject, a normal blood specimen and a mixed specimen thereof is analyzed rather than a blood sample from a single patient, as now recited in the instant claims. This argument is not persuasive since Ieko et al teach of analyzing a first and a second coagulation time of different types of blood or plasma specimens incubated under two different predetermined conditions, wherein one of the different types of blood or plasma specimens comprises a “blood specimen of a subject” (see paragraphs 0047-0048 in Ieko et al) or “test plasma” from a subject being LA positive or coagulation factor deficient (see paragraphs 0145-0146 in Ieko et al). The “blood specimen of a subject” or “test plasmas” taught by Ieko et al qualify as a “blood sample from a single patient” since this single type of blood specimen or plasma is analyzed for blood coagulation at two different incubation times and does not contain anything else besides the blood or plasma from the subject. While Ieko et al teach of also analyzing coagulation in a normal blood sample and a mixed sample comprising a mixture of the blood sample from a single patient and the normal blood sample at two different incubation times, Ieko et al also teach of separately determining coagulation times in a “blood specimen of a subject” or “test plasmas” at two different incubation times, which are designated by Ieko et al as a “first coagulation time” under a first incubation condition and a “fourth coagulation time” under a second incubation condition.
Applicant also argues that Ieko et al and Barco et al fail to teach or fairly suggest the limitations of obtaining at least one of the parameters A1 and A1 and/or B1 and B2 now recited in the instant claims, calculating an arithmetic relationship between the parameters in the selected at least one pair, and analyzing the calculated arithmetic relationship relative to at least one predetermined value to determine a suspected cause of prolonged coagulation in the blood sample analyzed. This argument is not persuasive since Ieko et al teach of obtaining a first coagulation time A1 derived from the first coagulation waveform of the “blood specimen of a subject” or a “test plasma”, called the “the first coagulation time” described for the single blood specimen of the subject or “test plasma” in paragraphs 0048, 0056 and 0146 of Ieko et al, obtaining a second coagulation time A2 derived from the second coagulation waveform, called the “the fourth coagulation time” described for the single blood specimen of the subject or “test plasma” in paragraphs 0049, 0056 and 0146 of Ieko et al, calculating an arithmetic relationship between the first coagulation time and the fourth coagulation time, wherein the arithmetic relationship comprises calculating a first quantification index that uses the first coagulation time A1 of the single blood specimen of the subject or “test plasma”, calculating a second quantification index that uses the fourth coagulation time A2 of the single blood specimen of the subject or “test plasma”, obtaining either a difference or a ratio between the first and second quantification indexes, and analyzing a cause for a prolonged coagulation time in the single blood specimen of the subject or “test plasma” by comparing the calculated difference or ratio between the first and second quantification indexes with a predetermined threshold value (see paragraphs 0070-0079 and Example 1 in paragraphs 0144-0150 in Ieko et al). Therefore, the method and device taught by Ieko et al measures a pair of parameters A1 and A2 representing coagulation times of a blood sample of a single patient measured at different incubation times, calculating an arithmetic relationship between the parameters in the selected pair A1 and A2 based on a difference or a ratio between calculated first and second quantification indexes, which quantification indexes include the parameters A1 and A2, and analyzing a cause for a prolonged coagulation time in the single blood specimen of the subject or “test plasma” by comparing the calculated difference or ratio between the first and second quantification indexes with a predetermined threshold value. It is noted that the instant claims do not exclude the use of the measured coagulation times A1 and A2 taught by Ieko et al in calculations of a first and a second quantification index from the “calculated arithmetic relationship”, and independent claims 24 and 44 do not recite that a cause of prolonged coagulation in a blood sample from a single patient is determined by directly calculating either a difference or a ratio between a first coagulation time determined for the blood sample after adding a calcium solution to the blood sample and an APTT reagent at a first waiting time and a second coagulation time determined for the blood sample after adding a calcium solution to the blood sample and an APTT reagent at a second waiting time that is longer than the first waiting time.
For these reasons, Applicant’s arguments are not found persuasive.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 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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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 March 9, 2026