DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
Four documents listed on IDS June 1, 2023 have not been considered due to poor image quality: Casadei et al., Crepcos et al., Malini et al., and Karakas et al.
Election/Restrictions
Applicant’s election without traverse of claims 1-11 and 18-20 in the reply filed on 12 January 2026 is acknowledged.
Claims 1-11 and 18-20 are examined herein.
Claim Objections
Claims 1, 8, and 18-20 are objected to because:
Claim 1 recites “the method comprising”, should be “the method comprising:”.
Claim 1 contains abbreviations OA and HA. These should be completely spelled out in its first occurrence.
Claims 8 and 18-20 recite “the sample is a blood sample selected from the group consisting of serum, plasma, and whole blood”. A blood sample cannot be selected from serum or plasma, because serum and plasma are not blood, there are blood derivatives.
Claims 18-19 recite “binding between (x) FT”. The “(x)” does not follow the designation schemes of claims 18-19. Also, both claims recite “(y)(i)” in two different meanings: “(y)(i) binding between TT” and “(y)(i) binding between SHBG”.
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 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 “an QA-value reflecting the length of the female's menstrual cycle”. There is insufficient antecedent basis for “the length”. It is also unclear the length of which cycle from the entire life of the female is included in the data set.
Claim 10 recites “wherein the method further includes determining one or more values of the data set provided in step a).” Claim 1 recites providing a data set with the OA, HA, and AMH-values, wherein the data values are already determined, so claim 1 does not recite any values being determined. The OA, HA, and AMH-values are used to calculate the combined value in step b). Claim 10 recites further includes determining one or more values of the data set provided in step a), but since no values are determined in claim 1, there is nothing to determine in claim 10. The claim is indefinite because it is unclear what other values are claimed and need to be determined.
Claim 11 recites “wherein the amount or concentration of one or more of the hormone(s) in the female's sample is measured by an immunoassay and/or mass spectrometry”. The claim is indefinite because it is unclear what other hormone(s) are claimed.
Claims 2-9 are rejected because they depend from rejected claim 1.
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 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring correlation, without significantly more.
Claim 1 recites a method of assessing a female's risk of having polycystic ovary syndrome.
The claim recites at least one step of assessing the patient’s risk for a medical condition. Thus, the claim is a process, which is a statutory category of invention.
The claim recites establishing a relationship between certain physiological and biomarker data and female's risk of having polycystic ovary syndrome. This relationship is categorized as a naturally occurring correlation, and therefore it is a judicial exception.
The claim recites a step of providing a data set, processing the data set, comparing the combined value, and indication of the risk via an indication unit. These additional steps are an insignificant extra-solution activity that amounts to mere data gathering necessary to apply the judicial exception.
Additionally, the broadest reasonable interpretation of processing the data set limitation requires a mathematical calculation. Hence, the limitation recites a “mathematical calculation” and so falls into the “mathematical concepts” grouping of abstract ideas.
The limitation of comparing the combined value requires comparing a female’s score against a reference population. The limitation falls into the “mental process” grouping of abstract ideas because the comparing can be practically performed in the human mind.
The final limitation of the claim is indicating the female's risk of having PCOS via an indication unit. Based on the plain meaning of the words “indicating” and “indication unit”, the broadest reasonable interpretation of this limitation is showing calculation results on a calculator display. Therefore, indicating the female's risk of having PCOS via an indication unit is part of a mathematical calculation discussed above.
The claim does not recite any additional steps that would make the claim as a whole to integrate the recited judicial exception into a practical application of the exception. There are no additional elements recited in the claim adding to inventive concepts of the claim, such as a treatment procedure or a medication.
The combined value of step (b) is recited at a high level of generality and constitutes a well-understood, routine, and conventional activity known in the prior art:
Khuraseva et al. (RU 2629720) teach a similar approach of using analogous OA-, HA-, and AMH-parameters for predicting risk levels of polycystic ovary syndrome ([0002]). Specifically, an OA-value reflecting the length of the female's menstrual cycle and/or the number of the female's menstrual cycles per year as menstrual cycle disorders such as oligo-/amenorrhea for more than 1.5-2 years after menarche having a diagnostic coefficient of 3 points ([0024]) and an anovulatory cycle 2 years after menarche having a diagnostic coefficient of 3 points ([0025]); an HA-value reflecting the female's androgen status as increased levels of total testosterone ([0044]) and androstenedione level above normal ([0045]) (both testosterone and androstenedione are androgens); and an AMH-value corresponding to the amount or concentration of anti-Mullerian hormone (AMH) as an increase in the AMH level above the age norm ([0048]). Chajka et al. (RU 2134061) teach calculating from individual biomarker values a combined value of risk for developing PCOS using the formula: y = 0.02012•p1 + 040292•In(t) + 0.07243•p - 1.12114•p(tm) -0.04008•b + 0.07146•gir + 0.07565•yami + 3.74045 ([0005]).
Claims dependent from claim 1:
Claim 2 recites providing additional value of weight to the data set of claim 1 without any additional steps. The limitation of weight is a well-understood, routine, and conventional activity known in the prior art: Khuraseva teaches current body weight as one of the indicators in predicting the degree of risk of developing PCOS ([0027]).
Claim 3 recites the HA-value corresponds to the amount or concentration of free testosterone (FT) in a sample obtained from the female. This limitation is recited at a high level of generality because it does not recite a specific method for determining free testosterone concentration and constitutes a well-understood, routine, and conventional activity known in the prior art: Karakas (Clin Chim Acta. 2017 Aug; 471:248-253) teaches that it is very important not to rely on total testosterone concentrations for PCOS diagnosis but to order a panel which includes total testosterone, SHBG, bioavailable and free-testosterone measurements (pg. 250, col. 1, par. 1).
Claim 4 recites the combined value is a weighted combined value obtained by weighted calculation of the values. The limitation recites a “mathematical calculation” and so falls into the “mathematical concepts” grouping of abstract ideas. Using weighted combined value is a well-understood, routine, and conventional activity known in the prior art: Chajka teaches calculating from individual biomarker values a combined value of risk for developing PCOS using the formula: y = 0.02012•p1 + 040292•In(t) + 0.07243•p - 1.12114•p(tm) -0.04008•b + 0.07146•gir + 0.07565•yami + 3.74045 ([0005]).
Claim 5 recites assigning a risk factor based on the combined value and threshold values. The limitation is a step of comparing the combined value to the three threshold values. The limitation falls into the “mental process” grouping of abstract ideas because the comparing can be practically performed in the human mind. Additionally, the three threshold values are not recited in the claim. The assigning step is a well-understood, routine, and conventional activity known in the prior art: Chajka teaches “if the y value is 0.5, the girl is considered healthy; 0.5 < y < 1.0 - the girl is at risk for developing PCOS; 1.0 < y< 2.0 - mild PCOS is diagnosed; 2.0 < y < 3.0 - moderate PCOS; y > 3.0 - severe PCOS” ([0005]).
Claim 6 recites retrieved from a database one or more values of the reference population and/or the combined value of the reference population. Retrieving values from a database is a well-understood, routine, and conventional activity known in any analytical art – the reference values have to be stored in one form or another and retrieved for comparison or calculation purposes.
Claim 7 recites the data set of step a) further includes a PHE-value reflecting one or more phenotypical characteristics known to be indicative of PCOS, wherein an increased PHE-value relative to the PRE-value of a healthy reference population indicates the presence of one or more phenotypical characteristics known to be indicative of PCOS is reflected by an increased PHE-value, and wherein the phenotypical characteristic is polycystic ovarian morphology (PCOM) and/or hyperandrogenemia. Using hyperandrogenemia as an indicator in predicting the degree of risk of developing PCOS is a well-understood, routine, and conventional activity known in the prior art: Khuraseva teaches ovarian volume of more than 10 cm3 as one of the indicators in predicting the degree of risk of developing PCOS ([0051]).
Claim 8 recites the sample is a blood sample selected from the group consisting of serum, plasma, and whole blood; and claim 9 recites the female is a human. Using serum, plasma, or whole blood samples is well-understood, routine, and conventional activity known in the prior art: Karakas teaches serum levels of AMH (pg. 249, col. 2, par. 2) and polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting young women (Abstract).
Claim 10 recites wherein the method further includes determining one or more values of the data set provided in step a). The claim fails to recite any limitation that is different from those of parent claim 1.
Claim 11 recites the amount or concentration of one or more of the hormone(s) in the female's sample is measured by an immunoassay and/or mass spectrometry. Using mass spectrometry for an analyte measurement is a well-understood, routine, and conventional activity known in the prior art: Karakas teaches “the preferred method for measuring testosterone is liquid chromatography tandem mass spectrometry” (pg. 250, col. 1, par. 1).
Therefore, claims 2-11 are not eligible under 35 U.S.C. 101 for the same reasons as parent claim 1.
For these reasons, claims 1-11 are ineligible under 35 U.S.C. 101.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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.
Claims 1-2 and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Khuraseva et al. (RU 2629720).
Regarding claim 1, Khuraseva teaches a method for predicting risk levels of polycystic ovary syndrome (PCOS) ([0002]) comprising clinical signs corresponding to an OA-value reflecting the length of the female's menstrual cycle and/or the number of the female's menstrual cycles per year as menstrual cycle disorders such as oligo-/amenorrhea ([0024]); and laboratory signs corresponding to an HA-value reflecting the female's androgen status as increased levels of total testosterone ([0044]) and androstenedione level above normal ([0045]) (both testosterone and androstenedione are androgens); and an AMH-value corresponding to the amount or concentration of anti-Mullerian hormone (AMH) as an increase in the AMH level above the age norm ([0048]).
Regarding the limitation of processing the data set by combining values of the data set into one combined value, the reference teaches assigning to each data parameter a value (menstrual cycle disorder - 3 points; increased levels of total testosterone - 2 points; androstenedione level above normal - 2 points; and an increase in the AMH level above the age norm - 1 point) and calculating the sum of the points ([0055]). The total score is compared to a set of reference values to estimate a risk of developing polycystic ovary syndrome: a score of 1-15 indicates a low risk; a score of 16-31 indicates an average risk; and a score of 32-62 corresponds to a high risk of developing polycystic ovary syndrome ([0056]-[0058]).
Khuraseva does not explicitly teach processing the data set with a processing unit and indicating the female's risk of having PCOS via an indication unit. However, Khuraseva teaches that “the sum of the points obtained is calculated” ([0055]). One having ordinary skill in the art would have found it obvious to use a calculator as a processing unit and indicate the final result on the calculator display (the indication unit) because calculators are widely used for calculations and they improve accuracy of the results.
Regarding claim 2, Khuraseva teaches including current body weight of a patient in the calculation of the total score ([0027]).
Regarding claim 5, Khuraseva teaches that the total score is compared to a set of reference values to estimate a risk of developing polycystic ovary syndrome: a score of 1-15 indicates a low risk; a score of 16-31 indicates an average risk; and a score of 32-62 corresponds to a high risk of developing polycystic ovary syndrome ([0056]-[0058]). Therefore, the score of 32 corresponds to thresholdhigh and the score 16 corresponds to thresholdmoderate of instant invention.
Regarding claim 6, Khuraseva teaches that the total score is compared to a set of reference values to estimate a risk of developing polycystic ovary syndrome: a score of 1-15 indicates a low risk; a score of 16-31 indicates an average risk; and a score of 32-62 corresponds to a high risk of developing polycystic ovary syndrome ([0056]-[0058]). Khuraseva does not explicitly teach that the reference values are retrieved from a database. However, the score values indicating the ranges of the risk categories must be stored in an electronic or printed form to prevent their loss (the database of instant invention) and retrieved from the database when actual patient’s data are analyzed. One having ordinary skill in the art would have found it obvious to store the score values in an electronic or printed form to preserve them for future use and retrieve them from this storage when needed. It is a common practice of dealing with any reference data.
Regarding claim 7, Khuraseva teaches ovarian volume of more than 10 cm3 as one of the indicators in predicting the degree of risk of developing PCOS ([0051]). Ovarian volume of more than 10 cm3 is a characteristic of polycystic ovarian morphology.
Regarding claim 8, Khuraseva teaches determining the level of hormones in the blood ([0004]), meeting the limitation of claim 8 reciting whole blood.
Regarding claim 9, Khuraseva teaches diagnosing PCOS in adolescent girls ([0004]), meeting the limitation of claim 9 reciting the female is human.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Khuraseva as applied to claim 1 above, in view of Karakas (Clin Chim Acta. 2017 Aug; 471:248-253).
The teachings of Khuraseva have been set forth above.
Khuraseva teaches total testosterone as a biomarker of PCOS, but does not specifically teach the HA-value corresponds to the amount or concentration of free testosterone.
Regarding claim 3, Karakas teaches new biomarkers for diagnosis and management of polycystic ovary syndrome (Title). Karakas also teaches measuring free testosterone as a biomarker of PCOS. Specifically, the reference teaches that insulin resistance or use of contraceptives can elevate total testosterone and “it is very important not to rely on total testosterone concentrations for PCOS diagnosis but to order a panel which includes total testosterone, SHBG, bioavailable and free-testosterone measurements” (pg. 250, col. 1, par. 1).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Khuraseva, by employing free-testosterone measurements as taught by Karakas, in order to provide a more reliable method for diagnosis of polycystic ovary syndrome (Karakas, pg. 250, col. 1, par. 1). One having ordinary skill in the art would have been motivated to make such a change because more reliable method for diagnosis leads to better healthcare. The use of such combination would have been desirable to those of ordinary skill in the art for the reasons mentioned above.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Khuraseva and Karakas as similarly drawn to detection of an androgen level in female samples and total testosterone assay results of Khuraseva is replaced by free-testosterone assay results of Karakas.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Khuraseva as applied to claim 1 above, in view of Chajka et al. (RU 2134061).
The teachings of Khuraseva have been set forth above.
Regarding claim 4, Khuraseva teaches combining values of the data set into one combined value based on points assigned to each data parameter, but does not explicitly teach the combined value is a weighted combined value obtained by weighted calculation of the values.
Regarding claim 4, Chajka teaches a method for diagnosis of polycystic ovary syndrome in adolescent girls (Title). Chajka also teaches the combined value is a weighted combined value obtained by weighted calculation of the values.
Specifically, Chajka teaches calculating the risk for developing PCOS from individual biomarker values using the formula: y = 0.02012•p1 + 040292•In(t) + 0.07243•p - 1.12114•p(tm) -0.04008•b + 0.07146•gir + 0.07565•yami + 3.74045 ([0005]), wherein the coefficients for each biomarker concentration are weights of the biomarker contribution to the total combined value of the risk.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Khuraseva, by replacing approximate weight points for each biomarker with more precise weights as taught by Chajka, as an obvious matter of simple substitution of one known element for another to obtain predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because an approximate calculation scheme of Khuraseva is replaced by more precise calculation scheme of Chajka without changing the principle of the calculation.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Khuraseva as applied to claim 1 above, in view of Casadei et al. (Arch Gynecol Obstet. 2018 Jul;298(1):207-215).
The teachings of Khuraseva have been set forth above.
Khuraseva does not specifically teach the hormone in the female's sample is measured by an immunoassay and/or mass spectrometry.
Regarding claim 11, Casadei teaches “The diagnosis of PCOS in young infertile women according to different diagnostic criteria: the role of serum anti-Mullerian hormone” (Title). Casadei also teaches AMH blood levels were measured using the enzyme immunoassay AMH-EIA (pg. 208, col. 2, par. 2).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Khuraseva, by employing the immunoassay method as taught by Casadei, as an obvious matter of applying a known technique to a known product to yield predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Casadei teaches the immunoassay of AMH and Khuraseva is generic on AMH measurement method.
Claims 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Khuraseva in view of Karakas and Casadei.
Regarding claims 18-20, Khuraseva teaches measuring AMH and total testosterone as biomarkers of PCOS ([0002], 00044], and [0048]), but does not specifically teach measuring free testosterone.
Regarding claims 18-20, Karakas teaches measuring free testosterone as a biomarker of PCOS. Specifically, the reference teaches that insulin resistance or use of contraceptives can elevate total testosterone and “it is very important not to rely on total testosterone concentrations for PCOS diagnosis but to order a panel which includes total testosterone, SHBG, bioavailable and free-testosterone measurements” (pg. 250, col. 1, par. 1).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Khuraseva, by employing free-testosterone measurements as taught by Karakas, in order to provide a more reliable method for diagnosis of polycystic ovary syndrome (Karakas, pg. 250, col. 1, par. 1). One having ordinary skill in the art would have been motivated to make such a change because more reliable method for diagnosis leads to better healthcare. The use of such combination would have been desirable to those of ordinary skill in the art for the reasons mentioned above.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Khuraseva and Karakas as similarly drawn to detection of an androgen level in female samples and total testosterone assay results of Khuraseva is replaced by free-testosterone assay results of Karakas.
Khuraseva and Karakas do not specifically teach the methods of claims 18-19 for detecting AMH and free testosterone using binding agents for AMH and free testosterone; and the method of claim 20 for determining a measurement for the panel of biomarkers in the sample, wherein the panel comprises the biomarkers anti-Mullerian hormone (AMH) and free testosterone.
Regarding claims 18-19, Casadei teaches measuring AMH and free testosterone (FT) levels using immunoassays. Specifically, AMH blood levels were measured using the enzyme immunoassay AMH-EIA and Serum FT levels were tested by RIA (pg. 208, col. 2, par. 2). EIA and RIA are enzyme immunoassay and radio immunoassay methods correspondingly.
Although, Casadei does not explicitly teach contacting the sample with a binding agent for AMH and a binding agent for FT, and detecting the binding between AMH and the AMH binding agent and binding between FT and the FT binding agent, the recited binding events are inherent to immunoassays. During an immunoassay a sample is contacted with an antibody (a binding agent); the antibody binds its target (e.g., AMH) present in the sample; unbound components are washed out; and a complex antibody-AMH is detected (detecting the binding between AMH and the AMH binding agent). Therefore, Casadei meets the claims.
Casadei teaches measuring levels of AMH and FT, therefore the teaching meets both claims: claim 19 reciting detecting the amount or concentration of AMH and FT in the sample and claim 18 reciting detecting whether AMH and FT is present in the sample.
Regarding claim 20, Casadei teaches assays of both AMH and FT, therefore, these biomarkers are a panel. As such, Casadei teaches determining a measurement for the panel of biomarkers in the sample, wherein the panel comprises the biomarkers anti-Mullerian hormone (AMH) and free testosterone as recited in claim 20.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Khuraseva and Karakas, by employing the immunoassay methods for detecting AMH and free testosterone as taught by Casadei, as an obvious matter of applying a known technique to a known products to yield predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because Casadei teaches the immunoassays of AMH and free testosterone and Khuraseva and Karakas are generic on AMH and free testosterone measurement methods.
Subject Matter Free of the Prior Art
Claim 10 is free of the prior art. Please, see 112(b) rejection above for details.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677