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 .
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0005], line 2: “the like of blood” should read “the lack of blood”
Paragraph [51], line 6: “enzyme-lined immunoassay (ELISA)” should read “enzyme-linked immunosorbent assay (ELISA)”.
Appropriate correction is required.
Claim Objections
Claim 11 objected to because of the following informalities: “performed by highly” should read “performed by a highly”. Appropriate correction is required.
Information Disclosure Statement
The information disclosure statement filed 12/20/2023 (starts with the heading “Statement of Relevance”) fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the format requirements of 37 CFR 1.98(a)(1) are not met; for example, there is no column that provides a space next to each document for the examiner’s initials. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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 1-11 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 1 recites only a measuring step. It is unclear to the Examiner how an evaluation is be determined for the disease if only a measuring step occurs. Is this determination meant to happen in the mind or on paper by comparing a known value in the art with what is ‘measured’. Is an observer meant to look at the number and then decided in their mind what this risk is? Examiner requests additional details or clarification to be added to the body of claim 1 to delineate the relationship between this measurement and the evaluation.
Claims 2-11 depend directly or indirectly from Claim 1 and are also rejected under 112(b) as being indefinite.
Claim 10 recites the limitation "in the providing step" in line 5. Claim 10 also recites the limitation “the sample” in line 4. There is insufficient antecedent basis for these limitations in the claim.
Claim 11 recites the limitation "the step of determining" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 11, the phrase "such as" in line 3 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The term “highly sensitive” in claim 11 is a relative term which renders the claim indefinite. The term “highly sensitive” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the scope of the “immunoassay” is indefinite.
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 2-6 and 8-9 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 2-6 and 8-9 are all directed to a process.
Inquiry 2A Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, claim 2 recites “determining the concentration” and “correlating… concentration”; claim 3 recites “evaluating”; claim 5 recites “determining concentration”, “determining platelet counts”, “dividing”, and “correlating”; claim 8 recites “determining the concentration”, “determining a… marker”, “dividing”, and “correlating”. Each of these steps represent a mental process that can be performed with the human mind and/or with a pen and paper. 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 2-6 and 8-9 do not integrate the judicial exception into a practical application.
Claim 2 ends with the “correlating” step, and the steps prior to this judicial exception amounts to the insignificant extra-solution activity of mere data gathering. See MPEP 2106.05(g). Claim 3 ends with the “evaluating” step, so the exception is not integrated into a practical application. Regarding claim 4, the additional limitations read as mere instructions to generally apply the judicial exception. See MPEP 2106.05(f).
Regarding claim 5, nothing happens after the judicial exception of “correlating”, so it is not integrated into a practical application; the steps prior to the exception amount to the insignificant extra-solution activity of mere data gathering. See MPEP 2106.05(g). Regarding claim 6, the additional limitations read as mere instructions to generally apply the judicial exception. See MPEP 2106.05(f).
Regarding claim 8, nothing happens after the judicial exception of “correlating”, so it is not integrated into a practical application; the steps prior to the exception amount to, at best, the insignificant extra-solution activity of mere data gathering. See MPEP 2106.05(g). Regarding claim 9, the additional limitation reads as mere instruction to generally apply the judicial exception. See MPEP 2106.05(f).
Inquiry 2B: Does the claim recite additional limitations that amount to significantly more than the judicial exception?
No, claims 2-6 and 8-9 do not amount to significantly more than the judicial exception.
Claim 2 ends with the “correlating” step, and the steps prior to this judicial exception are either judicial exceptions themselves (see Inquiry 2a Prong 1) or amount to the insignificant extra-solution activity of mere data gathering. See MPEP 2106.05(g). Claim 3 introduces an “evaluating” step, but since this is also a judicial exception the claim does not amount to significantly more than the exception. Regarding claim 4, the additional limitations read as mere instructions to generally apply the judicial exception, which does not amount to significantly more than the judicial exceptions. See MPEP 2106.05(f).
Regarding claim 5, nothing happens after the judicial exception of “correlating”, and the steps prior to the exception amount to the insignificant extra-solution activity of mere data gathering, which does not amount to significantly more than the judicial exception. See MPEP 2106.05(g). Regarding claim 6, the additional limitations read as mere instructions to generally apply the judicial exception, which does not amount to significantly more than the judicial exception. See MPEP 2106.05(f).
Regarding claim 8, nothing happens after the judicial exception of “correlating”, so it is not integrated into a practical application and the steps prior to the exception amount to the insignificant extra-solution activity of mere data gathering, which does not amount to significantly more than the judicial exception. See MPEP 2106.05(g). Regarding claim 9, the additional limitation reads as mere instruction to generally apply the judicial exception, which does not amount to significantly more than the judicial exception. See MPEP 2106.05(f).
Furthermore, the elements of claims 2-6 and 8-9 are well-understood routine and conventional in the arts: Yukio et al. (JP2014070942A) teaches a method of evaluating patients with or suspected of having a hemostatic disease, including transient ischemic attack, by measuring CLEC2 and other blood markers and comparing the measured levels to each other in both healthy and diseased subjects; Gitz et al (Non-Patent Literature, Blood, Vol. 124, no. 14, 2 October 2014, pgs. 2262-2270) teaches a method of measuring CLEC2 concentration and platelet count as well as determining a ratio of CLEC2/platelets to determine the presence or absence of disease; Xu et al. (Non-Patent Literature, BioMed Research International, Vol. 2021, 18 January 2021, pgs. 1-6) teaches a method of measuring D-dimer and comparing it to platelet markers to determine disease states of patients. 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) 1-3, 7, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yukio et al. (JP2014070942A). Note that citations in this office action to Yukio are made using the provided English version (Non-Patent Literature, Machine Translation of JP2014070942A).
Regarding claim 1, Yukio teaches a method for evaluating a risk of acute cerebral vascular disease (Pg. 6 paragraph 3) (suitably used for testing… cerebrovascular disease), said method comprising:
measuring a concentration of soluble CLEC2 in blood collected from a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease (Pg. 6 paragraph 3) (The method for measuring soluble CLEC-2 of the present invention is also suitably used for testing… cerebrovascular disease).
Regarding claim 2, Yukio teaches the method according to claim 1, as rejected above, for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said method comprising:
providing a blood sample derived from the patient (pg. 18 paragraph 2) (plasma was used as a measurement sample);
determining the concentration of soluble CLEC2 in the sample (pg. 19 paragraph 5) (soluble CLEC-2… detected by Western blotting); and
correlating the soluble CLEC2 concentration with a presence or absence of acute cerebral vascular disease in the patient, likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non-cardiogenic (pg. 22 paragraph 2) (plasma levels of patients with acute coronary syndrome had higher levels of soluble CLEC-2 than in the non-stenotic group)
Regarding claim 3, Yukio teaches the method according to claim 2, as rejected above, for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said step of correlating the soluble CLEC2 concentration with a presence or absence of acute cerebral vascular disease in the patient, likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non- cardiogenic comprising:
evaluating whether the patient is at risk based on a change in the soluble CLEC2 concentration (pg. 22 paragraph 2) (plasma levels of patients with acute coronary syndrome had higher levels of soluble CLEC-2 than in the non-stenotic group).
Regarding claim 7, Yukio teaches the method of claim 1 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, wherein a material to judge whether the acute cerebral vascular disease is cardiogenic or non-cardiogenic is provided (Pg. 18 paragraph 2) (A sandwich ELISA system was constructed using mouse anti-human CLEC-2 antibody).
Regarding claim 11, Yukio teaches the method of claim 1, wherein the step of determining the concentration of the soluble CLEC2 is performed by highly sensitive immunoassay, such as chemiluminescence immunoassay, electrochemiluminescence immunoassay, or fluorescence immunoassay (Pg. 18 paragraph 2) (A sandwich ELISA system was constructed using mouse anti-human CLEC-2 antibody).
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 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yukio et al. (JP2014070942A).
Regarding claim 4, Yukio teaches the method of claim 2 as rejected above. Yukio teaches a method of testing for transient ischemic attack based on CLEC2 concentration (Pg. 6 Paragraph 3) (The method for measuring soluble CLEC-2 of the present invention is also suitably used for testing… transient ischemic attack).
Yukio does not explicitly disclose a cutoff value of the soluble CLEC2 concentration being 66-148 pg/mL.
Yukio teaches that an average CLEC2 concentration of 160.05 pg/mL was indicative of disease (pg. 22 paragraph 2) (The median of each is 160.05 pg / mL in the acutecoronary syndrome (n = 20)). Yukio teaches that the CLEC2 concentration is a result-effective variable; measuring an average CLEC2 concentration of 160.05 pg/mL achieved the desired outcome of indicating the presence of disease. Yukio teaches that this average concentration may be used to differentiate between stenotic and non-stenotic subjects (pg. 22 paragraph 2) (The median of each is 160.05 pg / mL in the acutecoronary syndrome (n = 20) and 61.05 pg / mL in the non-stenotic group(n = 10)).
It would have been obvious for a person having ordinary skill in the art before the
effective filing date of the instant application to try a defined cutoff value of 66-148 pg/mL because the concentration is a result-effective variable that can be lowered through routine optimization to lead to the predictable outcome of differentiating between stenotic and non-stenotic subjects with a reasonable chance of success (see pg. 22 paragraph 2). See MPEP 2144.05(II).
Claim(s) 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yukio et al. (JP2014070942A) in view of Gitz et al. (Non-Patent Literature, Blood, Vol. 124, no. 14, 2 October 2014, pgs. 2262-2270).
Regarding claim 5, Yukio teaches the method of claim 1 as rejected above. Yukio teaches:
(1) providing a blood sample derived from the patient (pg. 18 paragraph 2) (plasma was used as a measurement sample);
(2) determining the concentration of soluble CLEC2 in the sample (pg. 19 paragraph 5) (soluble CLEC-2 contained in the supernatant fraction and CLEC-2 contained in the platelet fraction were detected by Western blotting);
Yukio fails to teach (3) determining platelet counts in the sample, (4) dividing the soluble CLEC2 concentration by the platelet counts, and (5) correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts, with a presence or absence of acute cerebral vascular disease in the patient, the likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non- cardiogenic.
In the analogous art of studying CLEC2 and its effect on platelet activation for cardiovascular and inflammatory diseases, Gitz teaches a method of calculating a ratio of CLEC2 and platelets (pg. 3 in Figure 2 legend) (The number of surface copies of CLEC-2 per platelet was determined). Gitz teaches that the ratio was calculated via extrapolation from the geometric mean fluorescence intensity (MFI), which represents a way of comparing between CLEC2 concentration and platelet count (pg. 3 in Figure 2 legend) (The MFI was determined by flow cytometry and used to quantify surface expression of CLEC-2 by extrapolation from the linear regression line of C). See also annotated Figure 2d:
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Calculating a value of “CLEC-2 receptors per cell” is a means of comparing between the two variables, which will differ depending on how the concentration of CLEC2 or the platelet count is measured and the unit of measurement. Gitz teaches that calculating the ratio of platelets to CREP-2 may be used to establish a threshold value that represents a “healthy” amount of CLEC-2 relative to platelet count (pg. 3 left column paragraph 4) (We used an established flow cytometry assay to determine the level of expression of CLEC-2 in healthy individuals).
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 method of Yukio to measure platelet count, divide the CLEC2 concentration by platelet count, and correlate the resulting value with the presence or absence of acute cerebrovascular disease because doing so would lead to establishing a ‘healthy’ amount of CLEC-2 relative to platelet count with a reasonable chance of success (see pg. 3 left column paragraph 4 of Gitz and pg. 19 paragraph 5 of Yukio).
Regarding claim 6, modified Yukio teaches the method of claim 5 as rejected above. Yukio teaches a method of detecting transient ischemic attack (Pg. 6 Paragraph 3) (The method for measuring soluble CLEC-2 of the present invention is also suitably used for testing… transient ischemic attack). Yukio teaches that CLEC2 concentrations are elevated in patients with acute coronary syndrome when compared with health individuals (pg. 22 paragraph 2) (patients with acute coronary syndrome had higher levels of soluble CLEC-2 than in the non-stenotic group).
Yukio does not explicitly describe a cutoff value of the value obtained by dividing the soluble CLEC2 concentration by the platelet counts is 0.55 to 0.7.
In the analogous art of studying CLEC2 and its effect on platelet activation for cardiovascular and inflammatory diseases, Gitz teaches a method of using flow cytometry to determine a ratio of CLEC2 and platelets (pg. 3 left column paragraph 4) (We used an established flow cytometry assay to determine the level of expression of CLEC-2 in healthy individuals). Gitz teaches that an average indicative ratio of CLEC2 and platelet count was ~2016 ± 239 for healthy individuals (pg. 3 Figure 2 legend) (CLEC-2 copy number was… a mean of 2016 ± 239 (mean 6 standard deviation)). The ratio of CLEC2 and platelet count is a result effective variable because 2016 ± 239 CLEC2/platelet is indicative of an absence of transient ischemic attack; furthermore, the cutoff value of the ratio is dependent on the method of measuring platelet count and CLEC2 concentration as well as the units associated with the two individual values (‘platelet count’ for example may be presented as a number-per-volume or mass-per-volume).
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 calculation of a CLEC2/platelet ratio as disclosed by modified Yukio to include a cutoff value of 0.55-0.7 because doing so would lead to establishing a ‘healthy’ amount of CLEC2 relative to platelet count with a reasonable chance of success (see pg. 3 left column paragraph 4 of Gitz and pg. 19 paragraph 5 of Yukio).
Claim(s) 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yukio et al. (JP2014070942A) in view of Xu et al. (Non-Patent Literature, BioMed Research International, Vol. 2021, 18 January 2021, pgs. 1-6).
Regarding claim 8, Yukio teaches the method of claim 1 as rejected above. Yukio teaches:
(1) providing a blood sample derived from the patient (pg. 18 paragraph 2) (plasma was used as a measurement sample);
(2) determining the concentration of soluble CLEC2 in the sample (pg. 19 paragraph 5) (soluble CLEC-2 contained in the supernatant fraction and CLEC-2 contained in the platelet fraction were detected by Western blotting).
(3) determining a coagulation-fibrinolysis marker the sample (pg. 21 paragraph 5) (PF4 [platelet factor 4] amount: CTAD; 6.5, SERUM; 174.5, EDTA; 137.5, Citrate; 84.5 (ng /mL)).
Yukio does not teach (4) dividing the soluble CLEC2 concentration by the coagulation-fibrinolysis marker nor (5) correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts, with a presence or absence of acute cerebral vascular.
In the analogous art of using D-dimer and P-selectin to judge the severity of acute cerebral infarction, Xu teaches of measuring D-dimer and P-selectin concentrations and mathematically comparing them to each other to prognose acute cerebral infarction (pg. 3 left column paragraph 6) (The AUC of D-dimer and CD62p alone in predicting poor prognosis of acute cerebral infarction were 0.712 and 0.848 (P < 0:05), respectively. The combined detection of the two to predict the poor prognosis of acute cerebral infarction AUC was 0.859). See also table 2 and table 3 below, which show the measurements and mathematical comparisons:
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Xu teaches that these comparisons may be used to monitor the progress/effectiveness of thrombolysis in real time (pg. 5 left column paragraph 2) (D-dimer and CD62p can be dynamically monitored during clinical thrombolysis to evaluate whether thrombus fusion is possible).
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 CLEC2 analysis method of Yukio to measure a concentration of D-dimer, divide the CLEC2 concentration by the concentration of D-dimer, and correlate the resulting value with a presence or absence of acute cerebral vascular disease as disclosed by Xu because it can allow for monitoring of thrombolysis efficacy with a reasonable chance of success (see tables 2-3 and pg. 5 left column paragraph 2 of Xu).
Regarding claim 9, modified Yukio teaches the method of claim 8 as rejected above. Yukio teaches of measuring the coagulation-fibrinolysis marker PF4 (pg. 21 paragraph 5) (PF4 [platelet factor 4] amount: CTAD; 6.5, SERUM; 174.5, EDTA; 137.5, Citrate; 84.5 (ng /mL)).
Yukio fails to teach wherein the coagulation-fibrinolysis marker is D-dimer.
In the analogous art of using D-dimer and P-selectin to judge the severity of acute cerebral infarction, Xu teaches of measuring levels of D-dimer for prognostic/diagnostic purposes. See modified table 2 below:
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Xu teaches that comparisons that include D-dimer may be used to monitor the progress/effectiveness of thrombolysis in real time (pg. 5 left column paragraph 2) (D-dimer and CD62p can be dynamically monitored during clinical thrombolysis to evaluate whether thrombus fusion is possible).
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 CLEC2 and PF4 analysis method of Yukio to measure a concentration of D-dimer as disclosed by Xu because it can allow for monitoring of thrombolysis efficacy with a reasonable chance of success (see tables 2-3 and pg. 5 left column paragraph 2 of Xu). See MPEP 2144.05(II).
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yukio et al. (JP2014070942A) in view of Christensen et al. (Non-Patent Literature, Cerebrovascular Disease, Vol. 18, No. 3, 14 September 2004, pgs. 214-219).
Regarding claim 10, Yukio teaches the method of claim 1 as rejected above. Yukio teaches of collecting blood samples from patients with acute coronary syndrome (pg. 22 first paragraph) (blood collected from 20 patients with acute coronary syndrome).
Yukio does not teach where in the sample derived from the patient is collected from the patient within 48 hours after the onset of symptoms of acute cerebral vascular disease.
In the analogous art of diagnosing and treating patients with infarctions, Christensen teaches of collecting a blood sample from patients within 9 hours of stroke onset (abstract) (WBC test material was obtained within 9 h of stroke onset). Christensen teaches that measuring blood characteristics within the first 24 hours can determine the severity of the stroke that has taken place (pg. 218 left column paragraph 2) (CRP and WBC relate to stroke severity in such a way that increasing levels within the first 24 h were found in patients with severe stroke but not in patients with mild to moderate stroke).
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 blood collection method of Yukio to collect blood samples within 48 hours as disclosed by Christensen because it would lead to determining the severity of the stroke with a reasonable chance of success (see pg. 218 left column paragraph 2 of Christensen and pg. 22 first paragraph of Yukio).
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6 and 11 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8 of copending Application No. 18/565,258 in view of Yukio (JP2014070942A). See below for claim mapping:
Instant Application 18/565,207
Reference Application 18/565,258
Claim 1: A method for evaluating a risk of acute cerebral vascular disease, said method comprising: measuring a concentration of soluble CLEC2 in blood collected from a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease.
Claim 1: A method for evaluating a risk of hemorrhagic stroke, said method comprising: measuring a concentration of soluble CLEC2 in blood collected from a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke.
Claim 2: The method according to claim 1 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said method comprising:
(1) providing a blood sample derived from the patient;
(2) determining the concentration of soluble CLEC2 in the sample; and
(3) correlating the soluble CLEC2 concentration with a presence or absence of acute cerebral vascular disease in the patient, likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non-cardiogenic.
Claim 2: The method according to claim 1 for evaluating the risk of hemorrhagic stroke in a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke, said method comprising:
(1) providing a blood sample derived from the patient;
(2) determining the concentration of soluble CLEC2 in the sample; and
(3) correlating the soluble CLEC2 concentration with the presence or absence of hemorrhagic stroke in the patient, or likelihood of outcome.
Claim 3: The method according to claim 2 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said step of correlating the soluble CLEC2 concentration with a presence or absence of acute cerebral vascular disease in the patient, likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non- cardiogenic comprising:
evaluating whether the patient is at risk based on a change in the soluble CLEC2 concentration.
Claim 3: The method according to claim 2 for evaluating the risk of hemorrhagic stroke in a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke, said step of correlating the soluble CLEC2 concentration with a presence or absence of hemorrhagic stroke in the patient, or likelihood of outcome comprising:
evaluating whether the patient is at risk based on a change in the soluble CLEC2 concentration.
Claim 4: The method according to claim 2 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, wherein the acute cerebral vascular disease is transient ischemic attack, and wherein, in the step of correlating the soluble CLEC2 concentration with the transient ischemic attack, a cutoff value of the soluble CLEC2 concentration is 66 to 148 pg/mL.
Claim 4: The method according to claim 2 for evaluating the risk of hemorrhagic stroke in a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke, wherein, in the step of correlating the soluble CLEC2 concentration with hemorrhagic stroke, its threshold is 137 pg/mL.
Claim 5: The method according to claim 1 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said method comprising:
(1) providing a blood sample derived from the patient;
(2) determining the concentration of soluble CLEC2 in the sample;
(3) determining platelet counts in the sample;
(4) dividing the soluble CLEC2 concentration by the platelet counts; and
(5) correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts, with a presence or absence of acute cerebral vascular disease in the patient, the likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non- cardiogenic.
Claim 5: The method according to claim 1 for evaluating the risk of hemorrhagic stroke in a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke, said method comprising:
(1) providing a blood sample derived from the patient;
(2) determining the concentration of soluble CLEC2 in the sample;
(3) determining platelet counts in the sample;
(4) dividing the soluble CLEC2 concentration by the platelet counts; and
(5) correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts, with a presence or absence of hemorrhagic stroke in the patient.
Claim 6: The method according to claim 5 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, wherein the acute cerebral vascular disease is transient ischemic attack, and wherein, in the step of correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts with the transient ischemic attack, a cutoff value of the value obtained by dividing the soluble CLEC2 concentration by the platelet counts is 0.55 to 0.7.
Claim 6: The method according to claim 5 for evaluating the risk of hemorrhagic stroke in a patient suspected of having hemorrhagic stroke or a patient diagnosed with hemorrhagic stroke, said method comprising: wherein, in the step of correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts with hemorrhagic stroke, a threshold of the value obtained by dividing the soluble CLEC2 concentration by the platelet counts is 0.7 to 1.0.
Claim 11: The method according to claim 1, wherein the step of determining the concentration of the soluble CLEC2 is performed by highly sensitive immunoassay, such as chemiluminescence immunoassay, electrochemiluminescence immunoassay, or fluorescence immunoassay.
Claim 8: The method according to the method according to claim 1 wherein the step of determining the concentration of the soluble CLEC2 is performed by highly sensitive immunoassay, such as chemiluminescence immunoassay, electrochemiluminescence immunoassay, or fluorescence immunoassay.
As mapped above, claims 1-5 and 11 of the instant application are anticipated by claims 1-6 and 8 of Reference Application No. 18/565,258. Note that claim 1 of the reference application recites a method for evaluating “a risk of hemorrhagic stroke”, which anticipates claim 1 of the instant application’s method for evaluating “a risk of acute cerebral vascular disease” because hemorrhagic stroke is a form of acute cerebral vascular disease.
Regarding claim 6 of the instant application, claim 6 of the reference application recites all of the limitations of claim 6 except for “wherein the acute cerebral vascular disease is transient ischemic attack”. Note that the reference application’s range of 0.7-1.0 reads on the instant application’s range of 0.55-0.7 because the endpoints overlap; for example, if a CLEC2/platelet ratio was found to be 0.7, it would fall under both ranges.
In the analogous art of using CLEC2 and other blood markers to evaluate stroke patients, Yukio teaches a method of detecting a variety of hemostatic diseases, including diseases involving excessive bleeding (such as hemorrhagic strokes) and transient ischemic attack (Pg. 6 Paragraph 3) (The method for measuring soluble CLEC-2 of the present invention is also suitably used for testing hemostatic disease… diseases involving excessive bleeding… transient ischemic attack).
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 correlation of CLEC2/platelet to hemorrhagic stroke as disclosed by reference application 18/565,258 to instead correlate the ratio to transient ischemic attack as disclosed by Yukio because hemorrhagic stroke and transient ischemic attack may be evaluated in the same manner with a reasonable chance of success (see pg. 6 Paragraph 3 of Yukio).
This is a provisional nonstatutory double patenting rejection.
Claim 5 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 12,590,978. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented method of “monitoring a prognosis or treatment progress of a thrombotic hemostatic disease” anticipates the instant application’s “method for evaluating a risk of acute cerebral vascular disease” because thrombotic hemostatic disease is a type of acute cerebral vascular disease. See mapping below:
Instant Application 18/565,207
Reference Patent No. 12,590,978
Claim 5: The method according to claim 1 for evaluating the risk of acute cerebral vascular disease in a patient suspected of having acute cerebral vascular disease or a patient diagnosed with acute cerebral vascular disease, said method comprising:
providing a blood sample derived from the patient;
determining the concentration of soluble CLEC2 in the sample; determining platelet counts in the sample;
dividing the soluble CLEC2 concentration by the platelet counts; and
correlating the value obtained by dividing the soluble CLEC2 concentration by the platelet counts, with a presence or absence of acute cerebral vascular disease in the patient, the likelihood of outcome, or whether the acute cerebral vascular disease is cardiogenic or non- cardiogenic.
Claim 2: The method according to claim 1, further comprising, method for monitoring a prognosis or treatment progress of a thrombotic hemostatic disease in the human subject, wherein monitoring comprises:
obtaining or having obtained one or more additional samples from the human subject;
measuring a concentration of soluble CLEC-2 and a platelet count in the one or more additional samples;
calculating a ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more additional samples; and
comparing the ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more additional samples to the ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more samples.
Conclusion
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/H.D.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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