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 .
Priority
This application is a U.S. National Stage (371) application of PCT/EP2019/076977 filed on 10/04/2019 which claims priority to Foreign Application No. EP18198714.0 filed on 10/04/2018.
Claim Status
Claims 1 and 18 are currently amended and the Applicant notes that no new matter is added. Claims 2-17 and 19-21 are previously presented. Claim 22 is new and the Applicant notes that no new matter is added.
Thus, claims 1-22 are pending and are under examination.
Withdrawn Rejections
The previous rejections of claims 1-21 under 35 U.S.C. 112(a), regarding written description are withdrawn in light of the Applicant’s arguments of 12/16/2025 and amendments to claims.
The previous rejections of claims 1-20 under 35 U.S.C. 112(a), regarding enablement requirement, is withdrawn in light of the Applicant’s arguments of 12/16/2025 and amendments to claims.
Maintained Rejections
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.
Claim 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is for a process or a method that is directed to at least one judicial exception without significantly more. The claims recite a mere collection of information in the form of data from which the applicant or doctor may draw an inference in light of the correlations. Such an inference is not sufficient to transform natural correlations into a patentable application.
The judicial exceptions are not integrated into a practical application because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The claims recite several judicial exceptions, i.e., a mental process (differentially treating a bipolar disorder and a major depressive disorder in a human patient), a mathematical equation (mathematical calculation with a probability equation) and a law of nature (the correlation of selected biomarkers with bipolar disorder or with major depressive disorder). These judicial exceptions are not integrated into a practical application because the additional limitations of the claims amount to insignificant extra-solution activity. The claims do not include additional elements that are sufficient to significantly amount to any added inventive concept to the judicial exceptions as recognized by the court decisions listed in MPEP § 2106.05(d). Furthermore, the treatment step of claims 1 and 18 is conditional, and thus it does not integrate the claims into a practical application.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?)
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03.
Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is directed to a process, which is one of the statutory categories of invention as the claim recites “A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype; (b) administering a treatment to the patient having a non-responder phenotype.” (Step 1: YES).
Similar to Example 43 of “2019 PEG”, claims 1, 13, 14 and 18 of the instant application are also directed to a statutory class of a method as claim 1 recites “An in vitro or ex vivo method for differentially treating a bipolar disorder and a major depressive disorder in a plurality of human patients in a need thereof presenting depressive symptoms and not subject …, the method comprising, for each patient of the plurality: determining, from a biological sample of the patient, the abundance of at least one of the following cytokines: …; selectively diagnosing a bipolar disorder or a major depressive disorder from the determination of the abundance of the at least one of the following cytokines: …; and providing a selective treatment including antidepressants without additional …, or not providing the selective treatment including antidepressants without additional …”, claim 13 recites “The method of claim 12, wherein the probability p is calculated using the following equation: …”, claim 14 recites “The method of claim 12, wherein the probability p is calculated using the following equation: …” and claim 18 recites “A method of performing differential treatment of a bipolar disorder or a major depressive disorder in a plurality of human patients in a need thereof presenting depressive symptoms and not subject …, the method comprising, for each patient of the plurality: relying on at least one of the following cytokines: … as biomarkers to selectively diagnose a bipolar disorder or a major depressive disorder, and - providing a selective treatment including antidepressants without additional …, or - not providing the selected treatment including antidepressants without additional …”.
Thus, similar to claim 1 of example 43 of “2019 PEG” that teaches a treatment method by measuring C11 and C13 levels to calculate the ratio of C11 to C13 for identifying a non-responder in a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3), claims 1, 13, 14 and 18 of the instant application are also directed to a method for differentially treating a bipolar disorder and a major depressive disorder in a plurality of human patients by measuring selected cytokines to reach a selective diagnosis and treatment of major depressive disorder or bipolar disorder (Step 1: YES).
Step 2A, Prong 1: Does the claim recite an abstract idea, law of nature or natural phenomenon?)
Claim 1 of example 43 of the “2019 PEG” recites judicial exceptions that are similar to claims 1, 13, 14 and 18 of the instant application. Specifically, and per Step 2A, prong 1, claim 1 of example 43 of the “2019 PEG” recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” and according to broadest reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the ratio of C11 to C13 that can be used to identify whether the patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or greater and thus is not responding, or will not respond, to glucocorticoids). This limitation therefore recites a mathematical calculation. And the grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) of claim 1 of “2019 PEG” falls into the “mathematical concept” grouping of abstract ideas.
Similar to claim 1 of example 43 of the “2019 PEG”, claims 13 and 14 of the instant application also recite a judicial exception of calculating “the probability p” after measuring serum concentration of one of selected cytokines. And according to the equation of claims 13 and 14, an arithmetic calculation of a division is also required to obtain the value of p. This limitation therefore recites a mathematical calculation which falls under an abstract idea as noted above in “2019 PEG”.
In addition, regarding the ratio of C11 to C13 of limitation (a) of claim 1 of “2019 PEG” and the equation of claims 13 and 14, the simple arithmetic calculation (division) can be practically performed in the human mind to calculate a ratio, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, the ratio of limitation (a) of claim 1 of “2019 PEG” and the equation of claims 13 and 14 of the instant application also fall into the “mental process” groupings of abstract ideas.
Also, limitation (a) of claim 1 of “2019 PEG” describes a naturally occurring relationship between the ratio of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a law of nature. Similarly, claims 1, 13 and 14 of the instant application are also calculating a probability and associating such a calculation with the selective diagnosis and treatment of major depressive disorder or bipolar disorder. Thus, claims 1, 13 and 14 of the instant application also describes a naturally occurring relationship between the probability of having major depressive disorder and selective treatment, and thus is considered to recite a law of nature.
Similar to claim 1 of example 43 of “2019 PEG” , claims 1, 13, 14 and 18 of the instant application also recite a judicial exception of abstract idea of a mental process (differentially treating a bipolar disorder and/or a major depressive disorder in a plurality of human patients) as claim 1 recites “An in vitro or ex vivo method for differentially treating a bipolar disorder and a major depressive disorder in a plurality of human patients” and claim 18 recites “A method of performing differential treatment of a bipolar disorder or a major depressive disorder”.
Furthermore, and similar to claim 1 of example 43 of “2019 PEG” which is also directed to a law of nature that describes a naturally occurring relationship between the ratio of C11 to C13 and the non-responder phenotype, claims 1, 13, 14 and 18 of the instant application also recite a judicial exception of a law of nature (the correlation of selected biomarkers with bipolar disorder or with major depressive disorder) as claim 1 recites “selectively diagnosing a bipolar disorder or a major depressive disorder from the determination of the abundance of the at least one of the following cytokines: TNF-α, IFN-γ, IL-6, IL-10, IL-12p40, IL-15, IL-16, IL-17A, IL-27” which is in essence a correlation between the between these cytokines and bipolar disorder and major depressive disorder and claim 18 recites “relying on at least one of the following cytokines: TNF-α, IFN-γ, IL-6, IL-10, IL-12p40, IL-15, IL-16, IL-17 A, IL-27 as biomarkers to selectively diagnose a bipolar disorder or a major depressive disorder”. Claims 13 and 14 of the instant application recites a judicial exception of a mathematical equation (mathematical calculation with a probability equation) as claim 13 recites “The method of claim 12, wherein the probability p is calculated using the following equation: …” and claim 14 recites “The method of claim 12, wherein the probability p is calculated using the following equation: …”. Therefore, claims 1, 13-14 and 18 recite a judicial exception of a law of nature as in claim 1 of example 43 of “2019 PEG”.
Accordingly, limitation (a) of claim 1 of “2019 PEG” recites three judicial exceptions (an abstract idea that falls within the mathematical concept, a mental process groupings in the “2019 PEG”, and a law of nature); whereas claims 1, 13, 14 and 18 of the instant application also recite four judicial exceptions of an abstract idea that falls within the mathematical concept, a first mental process, a second mental process and a law of nature, and the analysis must therefore proceed to Step 2A Prong Two.
(Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the abstract idea, claim 1 of example 43 of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient having a non-responder phenotype”. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome (the patient’s
phenotype) into account when deciding which treatment to administer, making the limitation’s inclusion in this claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Similarly, claims 1, 13, 14 and 18 of the instant application do not have additional elements that would integrate the judicial exceptions cited above into a practical application. The claims have steps of measuring cytokines and assessing a pathological condition in an individual by comparing values based on the measurements. These steps do not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Although claims 1 and 18 of the instant application have a treatment step, such a step does not integrate the judicial exception into a practical application because the treatment step is conditional as claims 1 and 18 recite “- providing a selective treatment including antidepressants without additional bipolar disorder medication to the patient, when the patient has been diagnosed with major depressive disorder, or - not providing the selective treatment including antidepressants without additional bipolar medication to the patient, when the patient has been diagnosed with bipolar disorder”. Therefore, similar to claim 1 of example 43 of “2019 PEG”, claims 1, 13, 14 and 18 do not integrate the judicial exceptions into a practical application.
(Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?)
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept (Step 2B: NO). The claim is not eligible.
Similarly, claims 1, 13, 14 and 18 of the instant application simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, such as measuring the concentration of a biomarker using a commercially available test (Specification, page 15, second paragraph, “For measuring the abundance of the plurality of the biomarkers in the collected sample of blood according to the invention, various methods, that are well-known from the man skilled in the art, may be used”). Furthermore, the claims themselves are recited at a high level of generality in which any assay can be used as the detection method for claims 1, 13, 14 and 18. Thus, similar to claim 1 of example 43 of “2019 PEG”, claims 1, 13, 14 and 18 do not amounts to significantly more than the recited judicial exceptions.
Therefore, claims 1, 13, 14 and 18 are rejected under 35 USC 101.
Regarding claims 2-7, 15 and 19-20 the claims further select the type of biomarker to measure which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 8, the claim selects the biomarkers to be excluded from measurement and comparison which does not integrate the judicial exceptions into a practical application because they do not amount to more than the judicial exceptions themselves, nor do they amount to significantly more.
Regarding claims 9-10, the claims define the type of specimen which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 11, the claim selects the type of biomarker to measure for comparison which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 12, the claim defines the determination criteria for a patient to be bipolar which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 15, the claim defines the expression units for the measured cytokines which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 16, the claim defines the range of reference values identified for a cytokine which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claim 17, the claim takes into account the type of medication a patient is taking for the probability calculation of a bipolar disorder or major depression which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Regarding claims 19 and 20, the claims define the type of biomarker to measure for diagnosing a bipolar disorder or a major depressive disorder which does not integrate the judicial exceptions into a practical application because it does not amount to more than the judicial exceptions themselves, nor does it amount to significantly more.
Allowable Subject Matter
Claims 21-22 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered but they are not fully persuasive regarding the 101 rejection for the following reasons.
The Applicant still introduced a conditional treatment step as claims 1 and 18 recite “Not providing the selective treatment including antidepressants without additional bipolar medication to the patient, when the patient has been diagnosed with bipolar disorder”. The limitation indicates that the patient would not get selective treatment if they have been diagnosed with bipolar disorder, and thus the judicial exceptions are not integrated into a practical application of treatment in this case.
The Examiner suggests to focus on the selective treatment for major depressive disorder and to remove the conditional step of treatment to overcome the 101 rejection.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OMAR RAMADAN whose telephone number is (571)270-0754. The examiner can normally be reached Monday-Friday 8:30 am - 5:00 pm.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678