DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Claims 1-6 are currently pending and under exam herein.
Claims 1-6 are rejected.
Claims 1-6 are objected to.
Priority
3. This application is a U.S. National Stage Application under 35 U.S.C. § 371 of International Application No. PCT/TR2020/051103 which was filed on 13 November 2020. Claimed foreign priority to Turkish Application No. 2020/16430 filed 14 October 2020 is recognized. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. In this action, all claims are examined as though they had an effective filing date of 14 October 2020. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
Information Disclosure Statement
4. The information disclosure statement submitted on 13 April 2023 has been considered by the examiner. Note that the significance of the foreign reference JP208536846A is provided in the specification p. 2, lines 9-16.
Drawings
5. The drawing submitted 13 April 2023 are accepted by the examiner.
Specification
6. The specification is objected to because there is inconsistency of abbreviations used between the specification disclosure and the claimed subject matter. As set forth in the MPEP section 2173.03, correspondence between the specification and claims is required by 37 CFR 1.75(d)(1), which provides that claim terms must find clear support or antecedent basis in the specification so that the meaning of the terms may be ascertainable by reference to the specification. The specific inconsistencies are listed below:
The claims and the specification denote ‘analytical variation’ as CVA and CVA, respectively.
The claims and the specification denote ‘biological variation’ as CVt and CVI, respectively.
The claims and the specification denote ‘personal reference ranges’ as koRA and kӧRA, respectively.
The specification is further objected to because it contains a graph at the top of p. 6. As set forth in the MPEP section 608.01(VI), the written portion of the specification must not contain drawings or flow diagrams.
Appropriate correction is required.
Claim Objections
7. Claims 1-6 are objected to because of the following informalities:
Claim 1, line 4, recites “a predetermined number (n)”, which grammatically incorrect. A possible correction is to change the phrase to “a predetermined number of times”.
Claim 1 lines 7 and 8 recite performing analyses on “the test”, but it is grammatically incorrect. One possible correction is to perform the operations on the “test results” as indicated in the analysis limitation on line 6 instead of on “the test”.
Claim 2 recites “in that sample is taken” , which is grammatically incorrect. A possible correction is to change the phrase to: “in that a sample is taken”.
Claim 2 recites ‘characterized in that sample is taken form person/persons”, which is grammatically incorrect. A possible correction is to change the phrase to: ‘characterized in that a sample is taken form person/persons”.
Claim 3 recites “characterized in that sum of the measurement results are divided”, which is grammatically incorrect. A possible correction is to change the phrase to: “characterized in that a sum of the measurement results are divided”.
Claims 5 and 6 have a spelling error in the term homeostatic. In both claims “homoestatic set point” should be corrected to “homeostatic set point”.
Claim 6 recites “total variation around homoestatic set point”, which is grammatically incorrect. One possible correction is to correct it to “total variation around the homeostatic set point”.
Claims 2-6 contain a semicolon after: “The method according to claim 1”, which should be corrected to a comma.
Appropriate correction is required.
Claim Interpretation
8. Claim 1 recites the contingent limitation “in the event that the obtained result is in percentages, converting it into the concentration value of the test and then adding and subtracting it to/from the arithmetic mean of the test”, which is only performed conditionally. As set forth in the MPEP (section 2111.04(II)), the broadest reasonable interpretation of a method claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition precedent is not met.
Claim 1 recites “for a test to be calculated in terms of personal reference range”, which is not an essential structure or step. Therefore, this phrase is interpreted as a non-limiting intended use phrase.
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.
The claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
9. Claims 1-6 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.
Regarding claim 1, line 4, the phrase “greater than n equal to three” is unclear. A possible correction is to change the phrase to “wherein n is greater than three”.
Regarding claim 1, line 4, the phrase “greater than n equal to three” is in parentheses, which calls into question whether it is an actual limitation of the claim or not.
In claim 1, line 5, the term “healthy” is a relative term which renders the claim indefinite. The term “healthy” 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. Possible replacement terms include more objective terms like “non-diseased” or “having biomarker values within a reference range”.
Regarding claim 1, line 14, the term “desired percentage of probability” is a relative term, which is non-specific. A person of ordinary skill in the art would not have reasonable certainty about the scope of the invention. A possible correction is to include a percentage or range of percentages.
Regarding claim 1, line 16, the phrase “adding and subtracting it to/from the arithmetic mean of the test” is indefinite because it is unclear if the adding step provides the upper or lower limit and it is similarly unclear if the subtracting step provides the upper or lower limit. A possible correction is to recite the operation for the upper and lower limits separately and include the term “respectively” for clarity.
Regarding claim 2, it is unclear if the limitation directed to “sample is taken” is a step of the invention or if it is merely describing the persons for whom the test is aimed. For purposes of examination and with broadest reasonable interpretation, this limitation will not be considered to be a necessary step of the invention.
Regarding claim 2, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 3 refers to “the sum of the measurement results”, but it is unclear to which “sum” the limitation is referring as two different addition steps were performed in claim 1 (on lines 11 and 16). For the purposes of review and with broadest reasonable interpretation, the “sum of the measurement results” will refer to the result of either of the addition steps.
Claim 3 further limits claim 1 by reciting “that sum of the measurement results are divided by the number of measurements by using the test results in order to calculate personal reference ranges at first”. This limitation is unclear because it is unclear to what “at first” refers to (i.e. what step does this limitation precede). For the purposes of examination, this limitation will be interpreted to happen before calculating the upper and lower limits of the personal reference ranges. That is, the claim will be interpreted to mean the method of claim 1, further comprising calculating the personal reference range before determining upper and lower limits of the personal reference range by a method that includes dividing the sum of the measurement values by the number of measurements taken.
Claim 6 further limits claim 1 and claims that the limitation is performed “at first”. This limitation is unclear because it is unclear to what “at first” is relative to (i.e. what step does this limitation precede). For the purposes of examination, this limitation will be interpreted to happen before calculating the upper and lower limits of the personal reference ranges.
Claims 1, 3, 5, and 6 recite terms that have insufficient antecedent basis in the respective claims as indicated below:
Claim 1 recites “the related test” on lines 4 and 5, but “a related test” was not introduced previously. A possible correction is to instead use the term “the test” as “a test” has been introduced.
Claim 3 refers to “the measurement results”, but the term “measurement results” as not been introduced in the preceding claim family. A possible correction is to change “the measurement results” to “the measurement values”, which have been introduced in claim 1.
Claims 5 and 6 refer to “the total variation around the homeostatic set point”, however this term is not introduced previously in the preceding claim family. For the purposes of examination, claims 5 and 6 will be considered to depend from claim 4 because claim 4 references a determining “total variation around the homeostatic set point”.
Claim 4 refers to “total variation around the homeostatic set point”, but “a homeostatic set point” has not been introduced previously in the preceding claim family. For the purposes of examination, claim 4 will be considered to refer to “a homeostatic set point”.
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.
10. Claims 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 recites: calculating the arithmetic mean of the test results
Claim 1 recites: calculating the analytical variation (CVA) value of the test
Claim 1 recites: taking the intra-individual biological variation (CVt) value of the test
Claim 1 recites: determining upper and lower limits of personal reference ranges of the related test by using analytical variation (CVA), biological variation (CVt) and number of measurement (n)
Claim 1 recites: squaring and then adding analytical variation (CVA) and biological variation (CVt) values and multiplying the obtained value by one more than (n+1) the number of measurement and dividing it by the number of measurement (n)
Claim 1 recites: taking the square root of the obtained value and multiplying the result by a coefficient associated with a desired percentage of probability and in the event that the obtained result is in percentages, converting it into the concentration value of the test and then adding and subtracting it to/from the arithmetic mean of the test.
Claim 3 recites: the method according to claim 1; characterized in that sum of the measurement results are divided by the number of measurements by using the test results in order to calculate personal reference ranges at first.
Claim 4 recites: The method according to claim 1; characterized in that after analytical variation (CVA) and biological variation (CVt) values are obtained, total variation around the homeostatic set point is determined by using the said values and the number of measurements (n).
Claim 5 recites: The method according to claim 1; characterized in that in order to calculate the total variation (TV) around the homoestatic set point: analytical and biological variations (CVA, CVt) of the test are squared and then added; these values added are multiplied by one more than (n+1) the number of measurement and divided by the number of measurement (n); then the square root of the obtained value is taken; and lastly the obtained result is multiplied by a z value at first.
Claim 6 recites: the method according to claim 1; characterized in that in order that the values can be converted from percentage into concentration value (kbRA), the concentration limit values of the area (kbRA) are obtained after multiplying the value of arithmetic mean of measurement results (X) by the value of total variation around homoestatic set point and dividing by 100 and then adding and subtracting it to/from the value of arithmetic mean of measurement results (X).
The limitations regarding calculating the arithmetic mean, calculating the analytical variation, taking the intra-individual biological variation, determining upper and lower limits, squaring, multiplying, dividing, taking the square root, multiplying the result by a coefficient, converting a number, adding and subtracting, divided by the number of measurements, determining total variation around the homeostatic set points, multiplying by one more than (n+1), multiplying by a z value, multiplying a value, and dividing by 100 are verbal equivalents that describe a mathematical calculation that is performed as the limitation and are so simple that they could be performed in the human mind or with pen and paper. Therefore, these limitations fall under the "Mathematical concepts" and "Mental processes" groupings of abstract ideas.
As such, claims 1-6 recite an abstract idea (Step 2A, Prong 1: YES).
Step 2A, Prong 2
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception in some other meaningful way. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or insignificant extra-solution activity. Specifically, the claims recite the following additional elements:
Claim 1 recites: for a test to be calculated in terms of personal reference range, conducting the related test for a predetermined number (n) (greater than n equal to three) at different times in a period when s/he is healthy
Claim 1 recites: taking the measurement values of the related test
Claim 2 recites: The method according to claim 1; characterized in that sample is taken from person/persons from whom it is aimed to determine the reference range, on different days and preferably at the same time of the day for n (n > three) times and the measurements obtained in the test results are taken
The limitations for ‘conducting the related test’ and ‘taking the measurement values’ merely serve to gather data that is used an input for the judicial exception. Therefore, these limitations are mere data gathering activities. As set forth in MPEP 2106.05(g), mere data gathering activity has been identified by the courts as insignificant extra-solution activity that does not provide a practical application.
The limitations in claim 2 further limit the time and frequency of the measurement taking of the additional element limitations, but do not integrate the judicial exception into a practical application because they just further limit data gathering activities but don’t change their position as data gathering activities.
The above recited additional elements do not provide a practical application of the recited judicial exception. As such, claims 1-6 are directed to an abstract idea (Step 2A, Prong 2: NO).
Step 2B
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are well-understood, and conventional activity.
As set forth in MPEP section 2106.05(g), the courts have decided that limitations that merely add an insignificant extra-solution activity, do not amount to an inventive concept, particularly when the activities are well-understood and conventional. Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978). As set forth in MPEP section 2106.05(d), the courts have recognized that limitations directed to data gathering that are claimed as insignificant extra-solution activity are routine, well understood and conventional. Mayo Collaborative servs. V. Prometheus Labs., Inc., 566 U.S. at 79, 101 USPQ2d at 1968.
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-6 are not patent eligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
11. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Coskun et al. (Clin Chem Lab Med, 2018, Vol. 56, p. 1309-1318), in view of Guenther (Introduction to Statistical Prediction, McGraw-Hill Book Company, 1977). The italicized text corresponds to the instant claim limitations.
Pertaining to claim 1, Coskun et al. disclose a method for defining biological variation of complete blood count parameters in healthy subjects, and specifically using the approach to determine within subject biological variation. Coskun et al. further discloses data from blood samples drawn from healthy subjects once weekly for 10 weeks (p. 1309, col. 1, para. 1 – col. 2, para. 3; a method used for calculating personal reference ranges (koRA) of medical laboratory tests; characterized by comprising steps of: for a test to be calculated in terms of personal reference range, conducting the related test for a predetermined number (n) (greater than n equal to three) at different times in a period when s/he is healthy and taking the measurement values of the related test).
Regarding claim 1, Coskun et al. discloses calculating the mean, within-subject biological variation (CVI) and the analytical variation (CVA) for nine erythrocyte- or reticulocyte-related parameters and ten leukocyte- and platelet-related parameters. Coskun et al. further discloses calculating the coefficients of variation (CVs) by using CV-analysis of variance (ANOVA) (p. 1311, col. 1, para. 5 – col. 2, para. 3; Table 1; Table 2 calculating the arithmetic mean of the test results; calculating the analytical variation (CVA) value of the test; taking the intra-individual biological variation (CVt) value of the test).
Regarding Claim 1, the limitations directed to determining a personal reference range are the verbal equivalent of equation 1 on p. 5, lines 12-14 of the instant specification. Coskun et al. teaches the calculation of reference change value (RCV) for an analyte measured over time for an individual, including the steps of squaring and then adding analytical variation and biological variation, taking the square root of the obtained value and multiplying the results by a coefficient (see Fig. 1 of this office action)
PNG
media_image1.png
50
261
media_image1.png
Greyscale
Figure 1. Equation 4 of Coskun et al. to calculate reference change value (RCV) for an individual based on analytical variation (CVA) and within subject biological variation (CVI) and a Z score for desired confidence level (Z).
(p. 1311, col. 2, Equation 4; Table 3; p. 1317, col. 1, para. 4; squaring and then adding analytical variation (CVA) and biological variation (CVt) values; taking the square root of the obtained value and multiplying the result by a coefficient associated with a desired percentage of probability).
Regarding claim 1, Coskun et al. is silent to the limitations of: determining upper and lower limits of personal reference ranges of the related test by using analytical variation (CVA), biological variation (CVt) and number of measurement (n); and multiplying the obtained value by one more than (n+1) the number of measurement and dividing it by the number of measurement (n) (in the context of the equation described above (i.e. subsequently taking the square root)). However, these limitations were known in the art at the time of the effective filing date of the invention as taught by Guenther.
Regarding claim 1, Guenther taught calculating a prediction interval describing the predicted range of values for normally distributed data with unknown mean and known variance with the same structure as the RCV equation taught by Coskun et al (see Fig. 2 of this office action). Note that in the Guenther equation, the variance term (σ) corresponds to the term containing CVA and CVI of Fig. 1 of this office action). Guenther further discloses calculating the upper and lower limits of the prediction interval as shown in the equation (see Figure 2 of this office action). Note that the Guenther equation in Fig. 2 and the Coskun et al. equation of Fig. 1 are structurally similar (with a variance term, a z score term and a term representing the sample number), but the equation in Fig. 2 differs from the RCV equation in Fig. 1 in that the sample number term, sqrt 2, is replaced with ‘sqrt (1+1/n)’, wherein n is the number of samples collected. This is due to changing the equation from the specific case of having one previous measurement (Fig. 1), to having n previous measurements (Fig. 2). Additionally note that term (sqrt (1+1/n)) is the mathematical equivalent of the term (sqrt of (n+1)/n) recited in claim 1 of the instant application.
PNG
media_image2.png
125
657
media_image2.png
Greyscale
Figure 2 Equation from Guenther citation showing calculation of a prediction interval of a future observation with similar corresponding to the term sqrt (n+1)/n. x̄ is the point estimator of a new observation given a known variance and unknown mean.
(Guenther, p. 241, para. 1 – p. 242, para. 4; determining upper and lower limits of personal reference ranges of the related test by using analytical variation (CVA), biological variation (CVt) and number of measurement (n); and multiplying the obtained value by one more than (n+1) the number of measurement and dividing it by the number of measurement (n).
Regarding claim 1, the limitation “in the event that the obtained result is in percentages, converting it into the concentration value of the test and then adding and subtracting it to/from the arithmetic mean of the test” is a contingent limitation and thus was not considered a required step of the invention (see MPEP 2111.04(II)).
Pertaining to claim 2, Coskun et al. teaches that samples were drawn from all subjects once weekly for 10 consecutive weeks from February to May 2016. Coskun et al. further discloses that samples were collected on defined days (Tuesday–Thursday) at the same time (8.30–10.30 a.m.) (p. 1311, col. 1, para. 2; the method according to claim 1; characterized in that sample is taken from person/persons from whom it is aimed to determine the reference range, on different days and preferably at the same time of the day for n (n > three) times and the measurements obtained in the test results are taken).
Pertaining to claim 3, the limitation “in order to calculate personal reference ranges at first” is not an essential structure or step. Therefore, this phrase is interpreted as a non-limiting intended use phrase. The limitation for dividing measurement results by the number of measurements describes calculating a mean value. Coskun et al. teaches calculating mean values for 10 erythrocyte- and reticulocyte-related parameters (p. 1313, Table 1; The method according to claim 1; characterized in that sum of the measurement results are divided by the number of measurements by using the test results in order to calculate personal reference ranges at first).
Regarding claim 4, Coskun et al. teaches that the reference change value (RCV) (shown in Fig. 2 of this office action) is an estimate of the homeostatic set point (HSP) with some deviation from the true homeostatic set point (from 5%-20%) in cases where a high enough number of samples are analyzed. Coskun et al. further discloses an equation used for determining sufficient sample number for RCV to approximate HSP (Fig. 3 of this office action). Coskun et al. further discloses that for many of the measurements of the study, there were a sufficient number of samples to estimate HSP with good accuracy (e.g., the result of a single measurement of a single sample was sufficient to predict HSP within 10%). Coskun et al. discloses that using the RCV equation disclosed in Fig. 1 of this office action, their study had a sufficient number of samples to predict HSP from RCV for the analytes in Table III of Coskun et al. within at least 20% of the true value (p. 1311, col. 2, para. 4, Equation 5; Table 3; p. 1317, col. 1, para. 2; the method according to claim 1; characterized in that after analytical variation (CVA) and biological variation (CVt) values are obtained, total variation around the homeostatic set point is determined by using the said values and the number of measurements (n)).
PNG
media_image3.png
48
263
media_image3.png
Greyscale
Fig. 3, Eq. 5 of Coskun et al. showing calculation of number of samples required to for RCV to estimate HSP. NHSP, number of samples required; HSP, homeostatic set point; CVA, analytical CV; CVI, intra-sample biological CV; D, allowable % deviation from true HSP)
Pertaining to claim 5, this limitation is the verbal equivalent of equation 1 on p. 5, lines 12-14 of the instant specification. Coskun et al. teaches the calculation of reference change value (RCV) for an analyte measured over time for an individual, including the steps of squaring and then adding analytical variation and biological variation, taking the square root of the obtained value and multiplying the results by a coefficient (see Fig. 1 of this office action) (p. 1311, col. 2, Equation 4; Table 3; p. 1317, col. 1, para. 4; analytical and biological variations (CVA, CVt) of the test are squared and then added; then the square root of the obtained value is taken; and lastly the obtained result is multiplied by a z value at first).
Regarding claim 5, Coskun et al. is silent to the limitations of: these values added are multiplied by one more than (n+1) the number of measurement and divided by the number of measurement (n). Note that in the context of the whole claim, this limitation also includes taking the square root of (n+1)/n. However, these limitations were known in the art at the time of the effective filing date of the invention as taught by Guenther.
Regarding claim 5, Guenther taught calculating a prediction interval describing the predicted range of values for normally distributed data with unknown mean and known variance with the same structure as the RCV equation taught by Coskun et al. (see Figs. 1 and 2 of this office action). Both equations have three terms, a variance term, a z score term and a term corresponding to sample number). In the Guenther equation (Fig. 2), the variance term (σ) corresponds to the term that includes CVA and CVI in Fig. 1. Note that the Guenther equation in Fig. 2 of this office action and the Coskun et al equation of Fig. 1 of this office action are structurally similar, but the equation in Fig. 2 differs from the RCV equation in Fig. 1 in that the ‘sqrt 2’ term is replaced with ‘sqrt (1+1/n)’, wherein n is the number of samples collected, to enable accounting for the number of previous measurements. Additionally note that term (sqrt (1+1/n)) is the mathematical equivalent of the term (sqrt of (n+1)/n) recited in claim 5 of the instant application (Guenther, p. 241, para. 1 – p. 242, para. 4; these values added are multiplied by one more than (n+1) the number of measurement and divided by the number of measurement (n) (in the context of the limitation, which includes taking the square root).
Regarding claim 6, the limitations of claim 6 further limit the contingent limitation of claim 1 and thus was not considered a required step of the invention (see MPEP 2111.04(II)). The method according to claim 1; characterized in that in order that the values can be converted from percentage into concentration value (kbRA), the concentration limit values of the area (kbRA) are obtained after multiplying the value of arithmetic mean of measurement results (X) by the value of total variation around homeostatic set point and dividing by 100 and then adding and subtracting it to/from the value of arithmetic mean of measurement results (X).
An invention would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention if some motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Guenther taught that using ‘1 + 1/n’ in calculating a prediction interval (with upper and lower limits) is useful for predicting the interval of a future observation with unknown mean and known variance. Guenther et al. further taught that the equation is useful in predicting uncertainty of one single new observation by accounting for not only the variation due to estimating the mean, but also accounting for variation of the future observation (which is quite different). Guenther et al. taught that the equation is useful in predicting 95% prediction interval of the future loan amount of a customer given a known amount average and population standard deviation (p. 241, para. 1 – p. 242, para. 4). Therefore, one of ordinary skill in the art would have been motivated to use the sqrt (1 + 1/n) term and the upper and lower limit determination taught by Guenther et al. in the equation taught by Coskun et al., in order to properly account for not only the variation due to estimating the mean, but also accounting for the variation of the future observation to yield more accurate results. Furthermore, one of ordinary skill in the art would predict that the sqrt(1 + 1/n) factor and upper and lower limits calculation taught by Guenther et al. could be readily added to the method of Coskun et al. with a reasonable expectation of success because they both pertain to predicting intervals with known variance and unknown mean. Furthermore, Equation 1 taught by Coskun et al. and Equation 2 taught by Guenther et al. are each well-known and widely used in the fields of reference values and statistics, respectively. The invention is therefore prima facie obvious.
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 and 2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18294241 in view of Coskun et al. (Clin Chem Lab Med, 2018, Vol. 56, p. 1309-1318).
12. Claim 1 of the reference application and the instant application both teach an approach for calculating a personal reference range (koRA) of medical laboratory test for a healthy individual, which is calculated as the arithmetic mean of the test +/- some measure of total variance (TV). The reference application is an obvious variant of the claimed invention. Claim 1 of the reference application teaches all aspects of claim 1 of the instant application except two terms in the equation to calculate TV are different as shown below:
Claim 1 of the reference teaches:
T
V
=
T
a
x
S
D
x
(
n
+
1
)
n
, wherein SD is standard deviation and Ta is a coefficient.
Claim 1 of the instant application teaches
T
V
=
z
x
C
V
A
2
+
C
V
I
2
x
(
n
+
1
)
n
, wherein CVA and CVI are analytical and biological variation, respectively and z is a coefficient.
Claim 2 of the reference application teaches all the limitations of claim 2 of the instant application. The reference application teaches taking >5 measurements, which includes taking >3 measurements.
Therefore, claims 1 and 2 of the reference teache the claims 1 and 2 of the instant application except for the first two terms of the equation (i.e. the constant and measure of variance). However, these terms were known in the art before the effective filing dates as taught by Coskun et al. Coskun et al. teaches the first two terms of the instant claim equation. Specifically, Coskun et al. teaches the calculation of reference change value (RCV) for an analyte measured over time for an individual, include the steps of squaring and then adding analytical variation and biological variation, taking the square root of the obtained value and multiplying the results by a coefficient (see Fig. 1 of this office action) (Coskun et al. p. 1311, col. 2, Equation 4; Table 3; p. 1317, col. 1, para. 4).
It would have been obvious to substitute one known measure of variability for another (i.e. to substitute the variability taught by Coskun et al. for the variability taught in the reference application) because both are recognized methods for defining interval width around and estimated homeostatic setpoint.
This is a provisional nonstatutory double patenting rejection.
E-mail Communications Authorization
13. Per updated USPTO Internet usage policies, Applicant and/or applicant's representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300): "Recognizing that Internet communications are not secure, / hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. / understand that a copy of these communications will be made of record in the application file."
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273- 8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Inquiries
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER J SMITH whose telephone number is (571)272-7801. The examiner can normally be reached Monday-Friday 7:00 AM - 3:00 PM.
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, Olivia Wise can be reached at (571) 272-2249. 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.
/J.J.S./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
Prosecution Insights