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
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Claim Objections
Claim 1 is objected to because of the following informality: in line 1, “end point Pe” should read “end point (Pe)”. Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [007], line 2: “followings” should read “following”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-14 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites the limitation “indicator S representing the form of T(X)”, where T(X) is the time needed to reach X% coagulation, and ‘indicator S’ is a mathematical relationship between a plurality of T(X) values; it is unclear what “the form of T(X)” is, so the scope of this claim is undefined. In the interest of compact prosecution, Examiner interprets “indicator S representing the form of T(X)” to mean “indicator S representing T(X)”. Claim 3 remedies this issue by defining Indicator S as being “an indicator representing a relative value of T(X) or a change rate of T(X)”.
Claims 3-14 are rejected due to their dependence on claim 2.
Claim 17 recites the limitation “the method according to claim 1”, but claim 1 is drawn to a method, not an apparatus. Therefore, the boundaries of the claim are unclear. In the interest of compact prosecution, Examiner interprets claim 17 to positively recite all of the elements of claim 1 as being included in the claimed apparatus.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-15 and 17 are rejected under 35 USC 101 because the claimed invention is directed to an abstract idea without significantly more. The claims will be analyzed below according to MPEP 2106.
Inquiry 1: Is the claim directed to a statutory category of invention (process, machine, manufacture, or composition of matter)?
Yes, claim 1 and its dependent claims are directed to a process.
Inquiry 2A Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, claim 1 recites “detecting a coagulation reaction end point Pe”, “calculating T(X)”, and “estimating a cause of coagulation time”. Each of these differentiating steps represent a mental process that can be performed with the human mind and/or with a pen and paper, and are therefore abstract ideas. See MPEP 2106.04(a)(2)(III).
Inquiry 2A Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No, claims 1-15 and 17 do not integrate the judicial exceptions into a practical application.
Claim 1 does not integrate the judicial exception into a practical application; the claim is entirely made up of judicial exceptions.
Regarding Claims 2, 4-7, 10-12, 15, these claims recite additional judicial exceptions and therefore do not integrate claim 1’s judicial exceptions into a practical application; claim 2 recites “calculating” and “estimating”; claim 4 recites the additional limitations of “estimating”, “comparing”, and “determined based on”; claims 5-7 and 10-12 recite “estimating” and “determined based on”; claim 15 recites “calculating”. See MPEP 2106.04(a).
Regarding Claims 3, 8, 9, 13, and 14, each of these claims generally apply the exception through instruction. See MPEP 2106.05(f).
Inquiry 2B: Does the claim recite additional limitations that amount to significantly more than the judicial exception?
No, claims 1-15 and 17 do not amount to significantly more than the judicial exceptions.
Regarding Claim 1, the claim is entirely drawn to judicial exceptions and therefore do not amount to significantly more than judicial exceptions. See MPEP 2106.04(a).
Regarding Claims 2, 4-7, 10-12, 15, these claims recite additional judicial exceptions and therefore do not amount to significantly more than judicial exceptions; claim 2 recites “calculating” and “estimating”; claim 4 recites the additional limitations of “estimating”, “comparing”, and “determined based on”; claims 5-7 and 10-12 recite “estimating” and “determined based on”; claim 15 recites “calculating”. See MPEP 2106.04(a).
Regarding Claims 3, 8, 9, 13-14, and 17, each of these claims generally apply the exception through instruction and therefore do not amount to significantly more than the judicial exceptions. See MPEP 2106.05(f). Furthermore, the elements of claims 1-4, 6-7, 11-12, 14-15, and 17 are well-known, routine, and conventional in the arts; regarding claims 1-3, 14, 15, and 17, Shima et al. (US20180031539A1v) teaches a method of evaluating the severity of hemophilia in subjects with reduced FVIII activity (paragraph [62]) by collecting the coagulation curve of a blood sample (paragraph [8]), calculating an indicator to represent the change rate of coagulation rate (paragraph [56]), and calculating coagulation time (paragraph [62]), using an apparatus (paragraph [9]); regarding claims 4, 6, 7, 11, and 12, Akatsuchi (US20200103421A1) teaches a method of using reference values derived from subjects with conditions that cause prolonged coagulation times, including heparin and lupus anticoagulants, to evaluate the coagulation characteristics of a blood sample (paragraph [63]). See MPEP 2106.05(d).
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.
Claim(s) 1-4, 15, 17 and is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kawabe et al. (WO 2020101025 A1, as cited in the IDS submitted on 09/01/2023). Note that citations to Kawabe et al. in this office action are drawn to the English equivalent version that is provided (US20210333295A1).
Regarding claim 1, Kawabe teaches a method for estimating a cause of coagulation time prolongation (paragraph [280]) (examined is… a blood specimen derived from a subject… required to be examined for abnormalities caused by a coagulation factor), comprising:
1) detecting a coagulation reaction end point Pe in a coagulation reaction curve of a subject blood specimen having a prolonged coagulation time (paragraph [313]) (defined as the coagulation end determination point Te);
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 is a variable of greater than 0 and equal to or less than 100 (paragraph [313]) (time corresponding to the amount of scattered light of 50% is defined as coagulation time T50); and
3) estimating a cause of coagulation time prolongation of the subject blood specimen based on a form of T(X) (paragraph [369]) (identifying a cause of prolongation of coagulation time based on a ratio or a difference between the first parameter and the second parameter).
Regarding claim 2, Kawabe teaches the method according to claim 1 as rejected above, wherein the 3) comprises calculating an indicator S representing the form of T(X) and estimating a cause of coagulation time prolongation of the subject blood specimen based on a value of the indicator S (paragraph [444]) (correction was performed such that a maximum height of the coagulation reaction curve… was 100 to obtain a corrected coagulation reaction curve).
Regarding claim 3, Kawabe teaches the method according to claim 2 as rejected above, wherein the indicator S is an indicator representing a relative value of T(X) or a change rate of T(X) (paragraph 444) (correction was performed such that a maximum height of the coagulation reaction curve… was 100 to obtain a corrected coagulation reaction curve).
Regarding claim 4, Kawabe teaches the method of claim 3 as rejected above, wherein the 3) further comprises estimating a cause of coagulation time prolongation of the subject blood specimen by comparing the indicator S with a reference value, and the reference value is determined based on an indicator S calculated from a blood specimen group in which the cause of coagulation time prolongation is known (paragraph [627]) (the data (LA) of “equal volume mixed plasma of a LA-positive plasma and a normal plasma”… it can be identified whether a specimen of a subject is LA-positive or factor VIII inhibitor-positive by setting a threshold between both distributions).
Regarding claim 15, Kawabe teaches the method according to claim 1 as rejected above, further comprising calculating coagulation time of the subject blood specimen (paragraph [313]) (reaction elapsed time corresponding to the amount of scattered light of 50% is defined as coagulation time T50).
Regarding claim 17, Kawabe teaches an apparatus for performing the method according to claim 1 (paragraph [396]) (analyses described above… can be performed automatically by an automatic analysis apparatus).
Claim(s) 1-3, 15, and 17 and is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shima et al. (US20180031539A1).
Regarding claim 1, Shima teaches a method for estimating a cause of coagulation time prolongation (paragraph [8]) (a method for determining severity of hemophilia), comprising:
1) detecting a coagulation reaction end point Pe in a coagulation reaction curve of a subject blood specimen having a prolonged coagulation time (paragraph [8] and [47]) (coagulating a blood specimen to acquire a coagulation waveform… point c is the endpoint of coagulation);
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 is a variable of greater than 0 and equal to or less than 100 (paragraph [47]) (In the coagulation waveform… point c is the endpoint of coagulation); and
3) estimating a cause of coagulation time prolongation of the subject blood specimen based on a form of T(X) (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Regarding claim 2, Shima teaches the method according to claim 1 as rejected above, wherein the 3) comprises calculating an indicator S representing the form of T(X) and estimating a cause of coagulation time prolongation of the subject blood specimen based on a value of the indicator S (paragraph [56]) (the average change rate of the coagulation rate is preferably calculated using the maximum coagulation rate (|min1|)).
Regarding claim 3, Shima teaches the method according to claim 2 as rejected above, wherein the indicator S is an indicator representing a relative value of T(X) or a change rate of T(X) (paragraph [56]) (the average change rate of the coagulation rate is preferably calculated using the maximum coagulation rate (|min1|)).
Regarding claim 15, Shima teaches the method according to claim 1 as rejected above, further comprising calculating coagulation time of the subject blood specimen (paragraph [62]) (the coagulation time is markedly prolonged in the APTT test in both hemophilia).
Regarding claim 17, Shima teaches an apparatus for performing the method according to claim 1 (paragraph [0009]) (A second aspect of the present invention is to provide a blood specimen analyzer).
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.
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(s) 4-14 are rejected under 35 U.S.C. 103 as being unpatentable over Shima et al. (US20180031539A1) in view of Akatsuchi et al. (US20200103421A1).
Regarding claim 4, Shima teaches the method of claim 3 as rejected above. Shima teaches of using coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima fails to teach wherein the 3) further comprises estimating a cause of coagulation time prolongation of the subject blood specimen by comparing the indicator S with a reference value, and the reference value is determined based on an indicator S calculated from a blood specimen group in which the cause of coagulation time prolongation is known.
In the analogous art of measuring blood coagulation time in subjects, Akatsuchi teaches of comparing a sample to a reference value based on an indicator that is calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this analysis can enable the detection of lupus anticoagulant (paragraph [0003]) (In recent years, the determination of APTT has also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the analysis using rates of coagulation acceleration of Shima to use a reference value as disclosed by Akatsuchi because doing so would enable the detection of lupus anticoagulant with a reasonable expectation of success (see paragraph [8] of Shima and [3], [63] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 5, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima fails to teach wherein the 3) further comprises estimating the subject blood specimen to be heparin positive when the indicator S is less than threshold 1 or when the indicator S is equal to or less than threshold 1, wherein the threshold 1 is a reference value determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to reference value based on an indicator calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used to determine if a subject is heparin or lupus positive based on reference values derived from subjects having heparin or lupus (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to use a reference value derived from patients with lupus to monitor heparin levels as disclosed by Akatsuchi because doing so would enable the monitoring of heparin therapy or the detection of lupus with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 6, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima does not teach wherein the 3) further comprises estimating the subject blood specimen to be lupus anticoagulant positive when the indicator S is equal to or greater than threshold 1 and equal to or less than threshold 2 or when the indicator S is greater than threshold 1 and less than threshold 2, wherein the thresholds 1 and 2 are reference values each determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to two reference values based on an indicator that is calculated from a blood specimen group compose of subjects with diseases, such as those caused by lupus anticoagulant (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used for monitoring heparin therapy and detecting lupus anticoagulant (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to detect lupus anticoagulant using threshold values derived from patients, including those with lupus anticoagulant, as disclosed by Akatsuchi because doing so would enable the monitoring of heparin therapy with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 7, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima does not teach wherein the 3) further comprises estimating the subject blood specimen to be coagulation factor deficiency or coagulation factor inhibitor positive when the indicator S is greater than threshold 2 or when the indicator S is equal to or greater than threshold 2, wherein the threshold 2 is a reference value determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to reference value based on an indicator calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used to determine if a subject is lupus anticoagulant positive based on reference values derived from subjects having lupus (paragraph [3]) (The determination of APTT is used, for example, for…monitoring of heparin therapy… tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to use a reference value derived from patients with known causes of prolonged coagulation, such as lupus anticoagulant, as disclosed by Akatsuchi because doing so would enable the monitoring of heparin therapy and detection of lupus anticoagulant with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 8, modified Shima teaches the method according to claim 10 as rejected above. Shima teaches a method of evaluating the average change rate of the coagulation rate (paragraph [48]) (includes the step of acquiring an average change rate of the coagulation rate from the coagulation waveform). Shima teaches that this change rate can be taken from various points along the coagulation curve ranging from the starting point (0% coagulation) to the end point (100% coagulation) (paragraph [52]) (differentiation of the coagulation waveform include… an average change rate of the coagulation rate… a time until coagulation acceleration becomes a times (0<a<1) the maximum). Shima teaches that this approach enables the discrimination of FVIII activity and hemophilia (paragraph [62]) (factor VIII activity of less than 0.2 IU/dl can be discriminated from hemophilia in which the antibody has appeared).
Shima does not explicitly teach wherein the indicator S is [T(X1)/T(X2)], wherein X1 > X2, X1= 30 to 85, and X2 = 5 to 20.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the coagulation acceleration equation of Shima to instead be [T(X1)/T(X2)], wherein X1 > X2, X1= 30 to 85, and X2 = 5 to 20, because doing so would enable the discrimination of FVIII activity and hemophilia with a reasonable expectation of success (see paragraph [62]). See MPEP 2143(I)(G).
Regarding claim 9, modified Shima teaches the method according to claim 10 as rejected above. Shima teaches a method of evaluating the average change rate of the coagulation rate (paragraph [48]) (determining the severity of hemophilia includes the step of acquiring an average change rate of the coagulation rate from the coagulation waveform). Shima teaches that this change rate can be taken from various points along the coagulation curve ranging from the starting point to the end point (paragraph [52]) (differentiation of the coagulation waveform include… an average change rate of the coagulation rate… a time until coagulation acceleration becomes a times (0<a<1) the maximum). Shima teaches that this approach enables the discrimination of FVIII activity and hemophilia (paragraph [62]) (factor VIII activity of less than 0.2 IU/dl can be discriminated from hemophilia in which the antibody has appeared).
Shima does not teach wherein the indicator S is [(T(X1) - T(X2))/T(X3)], wherein X1 > X2, X1 = 20 to 80, X2= 5 to 45, and X3 = 5 to 95.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the coagulation acceleration equation of Shima to instead be [(T(X1) - T(X2))/T(X3)], wherein X1 > X2, X1 = 20 to 80, X2= 5 to 45, and X3 = 5 to 95, because doing so would enable the discrimination of FVIII activity and hemophilia with a reasonable expectation of success (see paragraph [62]). See MPEP 2143(I)(G).
Regarding claim 10, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima does not teach wherein the 3) further comprises estimating the subject blood specimen to be heparin positive when the indicator S is greater than threshold 1 or when the indicator S is equal to or greater than threshold 1, wherein the threshold 1 is a reference value determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to reference value based on an indicator calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used to determine if a subject is heparin or lupus positive based on reference values derived from subjects having heparin or lupus (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to use the reference value derived from patients with known causes of prolonged coagulation such as heparin or lupus anticoagulant to detect heparin as disclosed by Akatsuchi because doing so would enable the detection of heparin or lupus with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 11, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima does not teach wherein the 3) further comprises estimating the subject blood specimen to be lupus anticoagulant positive when the indicator S is equal to or less than threshold 1 and equal to or greater than threshold 2 or when the indicator S is less than threshold 1 and greater than threshold 2, wherein the thresholds 1 and 2 are reference values each determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to reference value based on an indicator calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used to determine if a subject is lupus positive based on reference values derived from subjects having lupus, and that this approach can be used for monitoring heparin therapy (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to use the reference value derived from patients with lupus anticoagulant to detect lupus anticoagulant as disclosed by Akatsuchi because doing so would enable the detection of lupus anticoagulant and monitoring of heparin therapy with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 12, Shima teaches the method of claim 3 as rejected above. Shima teaches using rates of coagulation acceleration to evaluate causes of prolonged coagulation (paragraph [8]) (acquiring information regarding the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate).
Shima does not teach wherein the 3) further comprises estimating the subject blood specimen to be coagulation factor deficiency or coagulation factor inhibitor positive when the indicator S is less than threshold 2 or when the indicator S is equal to or less than threshold 2, wherein the threshold 2 is a reference value determined based on indicator S calculated from a blood specimen group including lupus anticoagulant positive.
In the analogous art of measuring blood coagulation time to detect lupus anticoagulant, Akatsuchi teaches of comparing a sample to a threshold value based on an indicator calculated from a blood specimen group in which the cause of prolonged coagulation time is known (paragraph [63]) (value can be defined by accumulation of APTT data for healthy people and patients with various diseases… APTT ratio can be determined from… range of not less than 1.2 and not more than 1.5). Akatsuchi teaches that this approach can be used to monitor heparin therapy or detect lupus anticoagulant (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify Shima’s analysis using rates of coagulation acceleration to use a threshold value derived from patients with lupus anticoagulant as disclosed by Akatsuchi because doing so would enable the detection of lupus anticoagulant and monitoring of heparin therapy with a reasonable expectation of success (see [8] of Shima and [63] and [3]] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 13, modified Shima teaches the method according to claim 10 as rejected above. Shima teaches a method of evaluating the average change rate of the coagulation rate (paragraph [48]) (determining the severity of hemophilia includes the step of acquiring an average change rate of the coagulation rate from the coagulation waveform). Shima teaches that this change rate can be taken from various points along the coagulation curve ranging from the starting point (0% coagulation) to the end point (100% coagulation) (paragraph [52]) (differentiation of the coagulation waveform include… an average change rate of the coagulation rate… a time until coagulation acceleration becomes a times (0<a<1) the maximum). Shima teaches that this approach enables the discrimination of FVIII activity and hemophilia (paragraph [62]) (factor VIII activity of less than 0.2 IU/dl can be discriminated from hemophilia in which the antibody has appeared).
Shima does not teach wherein the indicator S is [T(X1)/T(X2)], wherein X1< X2, X1 = 5 to 20, and X2 = 30 to 85.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the instant application to modify the coagulation acceleration equation of Shima to instead be [T(X1)/T(X2)], wherein X1< X2, X1 = 5 to 20, and X2 = 30 to 85, because doing so would enable the discrimination of FVIII activity and hemophilia with a reasonable expectation of success (see paragraph [62]). See MPEP 2143(I)(G).
Regarding claim 14, modified Shima teaches the method according to claim 7 as rejected above. Shima teaches wherein the coagulation factor deficiency refers to an FVIII activity value of less than 1% (paragraph [111]) (10 specimens (Severe Haemophilia A; factor VIII activity <1.0 IU/dl)). Claim 14 is rejected under 35 USC 103 by virtue of its dependency on claim 7.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-3, 8, 9, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 10, and 18 of copending Application No. 18/548,614 in view of Shima (US20180031539A1) further in view of Akatsuchi (US20200103421A1).
Instant Application 18/548,614
Reference Application 18/687,063
Bold text = points where the reference application does not anticipate the instant application.
Claim 1: A method for estimating a cause of coagulation time prolongation, comprising:
1) detecting a coagulation reaction end point Pe in a coagulation reaction curve of a subject blood specimen having a prolonged coagulation time;
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 is a variable of greater than 0 and equal to or less than 100; and
3) estimating a cause of coagulation time prolongation of the subject blood specimen based on a form of T(X).
Claim 1: A method for detecting an anomaly in a blood coagulation reaction, comprising:
1) detecting a coagulation reaction end point Pe in a coagulation reaction curve of a subject blood specimen;
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; and
3) detecting the anomaly in the blood coagulation reaction of the subject blood specimen based on T(X).
Claim 2: The method according to claim 1, wherein the 3) comprises calculating an indicator S representing the form of T(X) and estimating a cause of coagulation time prolongation of the subject blood specimen based on a value of the indicator S.
Claim 2: The method according to claim 1, wherein 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.
Claim 3: The method according to claim 2, wherein the indicator S is an indicator representing a relative value of T(X) or a change rate of T(X).
Claim 3: The method according to claim 2, wherein 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.
Claim 8: The method according to claim 5, wherein the indicator S is [T(X1)/T(X2)], wherein X1 > X2, X1= 30 to 85, and X2 = 5 to 20.
Claim 4: The method according to claim 3, wherein: the ratio of T(X) in the given range of X is [T(X1)/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.
Claim 9: The method according to claim 5 wherein the indicator S is [(T(X1) - T(X2))/T(X3)], wherein X1 > X2, X1 = 20 to 80, X2= 5 to 45, and X3 = 5 to 95.
Claim 17: An apparatus for performing the method according to claim 1.
Claim 18: An apparatus for implementing the method according to claim 1.
Regarding claim 1 of the instant application: As mapped above, claim 1 of Copending Application No. 18/687,063 teaches the limitations of claim 1 of the instant application except for “estimating a cause of coagulation time prolongation” and “having a prolonged coagulation time”. Claim 1 of Copending Application No. 18/687,063 instead recites “detecting an anomaly in a blood coagulation reaction”.
Shima teaches the limitations of claim 1 as rejected under 35 USC 102 above (see section No. 4 of this office action). Shima teaches that estimating a cause of prolonged coagulation time can differentiate between low FVIII activity and hemophilia in a subject (paragraph [62]) (factor VIII activity of less than 0.2 IU/dl can be discriminated from hemophilia).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detection of an anomaly in a blood coagulation reaction of Copending Application No. 18/687,063 to estimate a cause of coagulation time prolongation in a sample having a prolonged coagulation time as disclosed by Shima because it can lead to the differentiation of low FVIII activity and hemophilia with a reasonable expectation of success (see paragraph [62] of Shima). See MPEP 2143(I)(G).
Regarding claim 2 of the instant application: Claim 2 of Copending Application No. 18/687,063 teaches the limitations of claim 2 except for “estimating a cause of coagulation time prolongation”. Claim 2 of Copending Application No. 18/687,063 instead recites “detecting presence or absence of the anomaly in the blood coagulation reaction.”
Shima teaches the limitations of claim 2 as rejected above under 35 USC 102 (see section No. 4 of this office action). Shima teaches that estimating a cause of coagulation time prolongation can differentiate between low FVIII activity and hemophilia in a subject (paragraph [62]) (factor VIII activity of less than 0.2 IU/dl can be discriminated from hemophilia).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detection of an anomaly in a blood coagulation reaction of Copending Application No. 18/687,063 to estimate a cause of coagulation time prolongation as disclosed by Shima because it would lead to differentiating between low FVIII activity and hemophilia with a reasonable expectation of success (see paragraph [62] of Shima). See MPEP 2143(I)(G).
Regarding claim 3 of the instant application: claim 3 of Copending Application No. 18/687,063 teaches the additional limitations of claim 3. Both applications recite “the method according to claim 2”, which is obvious in view of Shima as rejected above.
Regarding claims 8 and 9 of the instant application: claim 4 of Copending Application No. 18/687,063 teaches all of the limitations of claims 8 and 9 except for “the method according to claim 5”. Claim 4 of Copending Application No. 18/687,063 instead recites “the method according to claim 3.”
Regarding the method of claim 5, modified Shima teaches the method of claim 5 as rejected above under 35 USC 103 (see Section No. 5 of this office action). Akatsuchi teaches that estimating the subject to be heparin positive based on a threshold value derived from subjects with lupus anticoagulant can enable the monitoring of heparin therapy (paragraph [3]) (The determination of APTT is used, for example, for… monitoring of heparin therapy… also been applied to screening tests for lupus anticoagulant (LA)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of claim 3 of Copending Application No. 18/687,063 with the method of claim 5 as disclosed by Akatsuchi because doing so would enable the detection of lupus anticoagulant and the monitoring of heparin therapy with a reasonable expectation of success (see [8] of Shima and [63] and [3] of Akatsuchi). See MPEP 2143(I)(G).
Regarding claim 17 of the instant application: claim 18 of Copending Application No. 18/687,063 teaches all of the limitations of claim 17. Both applications recite “the method according to claim 1”, which is obvious in view of Shima as rejected above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. Kawabe et al. (WO2020158948A1, paragraph numbers cited using the English translation: US20220146537A1) teaches a method of analyzing blood coagulation characteristics to detect FVIII activity of less than 1% (paragraph [241]) (FVIII activity level of a test specimen was classified into 4 stages (FVIII activities: <1%, 1 to 5%, 5 to 40%, and Other)).
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/H.D.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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