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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/27/24 and 10/24/25 is being considered by the examiner.
Claim Status
Claims 1-16 and 18 are pending and are examined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 15, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lapic (“The missing slope: paradoxical shortening of activated partial thromboplastin time in a patient on unfractionated heparin therapy.” Biochem Med. 31(2): 2021).
Regarding Claim 1, Lapic teaches a method for detecting an anomaly in a blood coagulation reaction (activated partial thromboplastin time (aPTT), comprising:
1) detecting a coagulation reaction end point Pe in a coagulation reaction curve of a subject blood specimen (Fig. 1, aPTT clotting curve, see end point of reaction);
2) calculating T(X), wherein T(X) represents a measurement point or time at which the coagulation reaction curve reaches X% of Pe and X denotes a variable larger than 0 and equal to or smaller than 100 (see Fig. 1); and
3) detecting the anomaly in the blood coagulation reaction of the subject blood specimen based on T(X) (clot formation).
Regarding Claim 15, Lapic teaches the method according to claim 1, further comprising calculating a coagulation time of the subject blood specimen (See section case report, see page 2, activated partial thromboplastin time was requested as part of routine monitoring. A blood sample was drawn.).
Regarding Claim 16, The method according to claim 1, wherein the detection of Pe is performed in parallel to acquisition of the coagulation reaction curve of the subject blood specimen, and the acquisition of the coagulation reaction curve is ended once Pe is detected (see Fig. 1).
Regarding Claim 18, Lapic teaches an apparatus for implementing the method according to claim 1 (coagulometer. See Abstract and Fig. 2).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 2-14 are rejected under 35 U.S.C. 103 as being unpatentable over Lapic (“The missing slope: paradoxical shortening of activated partial thromboplastin time in a patient on unfractionated heparin therapy.” Biochem Med. 31(2): 2021), in view of Shimonishi (“A Novel Assessment of Factor VIII Activity by Template Matching Utilizing Weighted Average Parameters from Comprehensive Clot Waveform Analysis.” Thromb Haemost. 121:164-173. 2021).
Regarding Claim 2, Lapic teaches the method according to claim 1.
Lapic is silent to 3) comprises calculating an index R based on T(X) and detecting presence or absence of the anomaly in the blood coagulation reaction of the subject blood specimen based on the index R.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of 3) c omprises calculating an index R based on T(X) and detecting presence or absence of the anomaly in the blood coagulation reaction of the subject blood specimen based on the index R, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 3, Lapic teaches the method according to claim 2.
Lapic is silent to the index R is at least one selected from the group consisting of a ratio of T(X) in a given range of X, a rate of change of T(X) in a given range of X, and a coefficient of variation of T(X) in a given range of X.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the index R is at least one selected from the group consisting of a ratio of T(X) in a given range of X, a rate of change of T(X) in a given range of X, and a coefficient of variation of T(X) in a given range of X, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 4, Lapic teaches the method according to claim 3.
Lapic is silent to the ratio of T(X) in the given range of X is [T(Xi)/T(X2)]; the rate of change of T(X) in the given range of X is [(T(X3) - T(X5))/T(X4)]; and the coefficient of variation of T(X) in the given range of X is a coefficient of variation of T(X) in a range from X6 to X7.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of ratio of T(X) in the given range of X is [T(Xi)/T(X2)]; the rate of change of T(X) in the given range of X is [(T(X3) - T(X5))/T(X4)]; and the coefficient of variation of T(X) in the given range of X is a coefficient of variation of T(X) in a range from X6 to X7, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 5, Lapic teaches the method according to claim 2.
Lapic is silent to detecting presence or absence of the anomaly in the blood coagulation reaction of the subject blood specimen by comparing the index R with a given threshold.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of detecting presence or absence of the anomaly in the blood coagulation reaction of the subject blood specimen by comparing the index R with a given threshold, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 6, Lapic teaches the method according to claim 5.
Lapic is silent to the threshold is determined based on the index R acquired from a group of specimens.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the threshold is determined based on the index R acquired from a group of specimens, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 7, Lapic teaches the method according to claim 5.
Lapic is silent to the anomaly in the blood coagulation reaction of the subject blood specimen is detected when: the threshold is equal to or larger than "mean + 2 x standard deviation" of index R acquired from a group of normal specimens, and the index R of the subject blood specimen is equal to or larger than the threshold, or the threshold is equal to or smaller than "mean - 2 x standard deviation" of index R acquired from a group of normal specimens, and the index R of the subject blood specimen is equal to or smaller than the threshold.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the anomaly in the blood coagulation reaction of the subject blood specimen is detected when: the threshold is equal to or larger than "mean + 2 x standard deviation" of index R acquired from a group of normal specimens, and the index R of the subject blood specimen is equal to or larger than the threshold, or the threshold is equal to or smaller than "mean - 2 x standard deviation" of index R acquired from a group of normal specimens, and the index R of the subject blood specimen is equal to or smaller than the threshold, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 8, Lapic teaches the method according to claim 1.
Lapic is silent to 3) comprises calculating indexes R1 and R2 based on T(X) and detecting a type of the anomaly in the blood coagulation reaction of the subject blood specimen based on the indexes Ri and R2.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of 3) comprises calculating indexes R1 and R2 based on T(X) and detecting a type of the anomaly in the blood coagulation reaction of the subject blood specimen based on the indexes Ri and R2, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 9, Lapic teaches the method according to claim 8.
Lapic is silent to the index R1 is a rate of change of T(X) in a first given range of X, and the index R2 is a rate of change of T(X) in a second given range of X or a coefficient of variation of T(X) in a given range of X.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the index R1 is a rate of change of T(X) in a first given range of X, and the index R2 is a rate of change of T(X) in a second given range of X or a coefficient of variation of T(X) in a given range of X, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 10, Lapic teaches the method according to claim 9.
Lapic is silent to the rate of change of T(X) in the first given range of X is [(T(Xi) - T(X3))/T(X2)]; the rate of change of T(X) in the second given range of X is [(T(X4) - T(X6))/T(Xs)]; and the coefficient of variation of T(X) in the given range of X is a coefficient of variation of T(X) in a range from X7 to Xs.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the rate of change of T(X) in the first given range of X is [(T(Xi) - T(X3))/T(X2)]; the rate of change of T(X) in the second given range of X is [(T(X4) - T(X6))/T(Xs)]; and the coefficient of variation of T(X) in the given range of X is a coefficient of variation of T(X) in a range from X7 to Xs, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 11, Lapic teaches the method according to claim 9.
Lapic is silent to comparing R1 with a threshold Th1 and comparing R2 with a threshold Th2, and detecting the type of the anomaly in the blood coagulation reaction of the subject blood specimen based on whether or not R1 and R2 had reached the respective thresholds, wherein R1 is the rate of change of T(X) in the first given range of X and R2 is the rate of change of T(X) in the second given range of X.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of comparing R1 with a threshold Th1 and comparing R2 with a threshold Th2, and detecting the type of the anomaly in the blood coagulation reaction of the subject blood specimen based on whether or not R1 and R2 had reached the respective thresholds, wherein R1 is the rate of change of T(X) in the first given range of X and R2 is the rate of change of T(X) in the second given range of X, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 12, Lapic teaches the method according to claim 9.
Lapic is silent to comparing R1 with a threshold Thi and, when R1 had reached Thl, detecting that the subject blood specimen has the anomaly in the blood coagulation reaction, comparing R2 of the subject blood specimen having been detected to have the anomaly in the blood coagulation reaction with thresholds Th2 and Th3, and detecting the type of the anomaly in the blood coagulation reaction of the subject blood specimen based on whether or not R2 had respectively reached Th2 and Th3, wherein R1 is the rate of change of T(X) in the first given range of X and R2 is the coefficient of variation of T(X) in the given range of X.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of comparing R1 with a threshold Thi and, when R1 had reached Thl, detecting that the subject blood specimen has the anomaly in the blood coagulation reaction, comparing R2 of the subject blood specimen having been detected to have the anomaly in the blood coagulation reaction with thresholds Th2 and Th3, and detecting the type of the anomaly in the blood coagulation reaction of the subject blood specimen based on whether or not R2 had respectively reached Th2 and Th3, wherein R1 is the rate of change of T(X) in the first given range of X and R2 is the coefficient of variation of T(X) in the given range of X, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 13, Lapic teaches the method according to claim 11.
Lapic is silent to the threshold Th1 is determined based on the index R1 acquired from a group of specimens and the threshold Th2 is determined based on the index R2 acquired from the group of specimens.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of the threshold Th1 is determined based on the index R1 acquired from a group of specimens and the threshold Th2 is determined based on the index R2 acquired from the group of specimens, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Regarding Claim 14, Lapic teaches the method according to claim 12.
Lapic is silent to the threshold Th1 is determined based on the index R1 acquired from a group of specimens and the thresholds Th2 and Th3 are determined based on the index R2 acquired from the group of specimens.
Shimonishi teaches in the related art of Fig. 3 Analysis utilizing weighted averages of activated partial thromboplastin time (aPTT)-based modified clot waveforms. (A) The peak height of the waveform was regarded as 100%, and the baseline was drawn at X% of the peak height. The contact point between the waveform and the baseline was defined as t1andt2, and the width of the baseline is defined as “Bx”(t2 t1). The weighted average of the area surrounded by the waveform and baseline (red circle) was calculated using the equation described in the “Methods” section. The time and velocity of weighted averages were defined as “Twx” and “Vwx.” (B) Changes in position of weighted averages infactor(F)VIII-deficient plasma. The blue and black circles indicate the weighted averages at the baseline 10 and 50%, respectively. The time and velocity of weighted averages at baselines 10 and 50% are defined as “Tw10 and Tw50” and “Vw10 and Vw50,” respectively. (C) Shifts in positions of weighted averages in aPTT-prolonged plasma samples (FV-, FVIII-, FIX, FX-, FXI-, and FXII-def, lupus anticoagulant [LA]-positive, and heparin-treated). The red points show the shift of weighted averages after setting the baseline (% of height).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the threshold Th1 is determined based on the index R1 acquired from a group of specimens and the thresholds Th2 and Th3 are determined based on the index R2 acquired from the group of specimens, as taught by Shimshoni, to the method of Lapic, to allow for evaluating comprehensive dynamics of fibrin clot formation, as taught by Shimonishi, in the Abstract.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
Prosecution Insights