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 .
Status of Claims
Currently, claims 1-21 are pending in the instant application. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are reiterated. They constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 101
Claims 1-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites methods of selectively treating or selectively recommending treatment for polycystic kidney disease (PKD) by determining at least one missense or loss of function mutation in the PKD1 gene of the patient. However, this recitation is a natural correlation between mutations in PKD1 and PKD. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed methods also recite steps such as “determining if the patient has a … mutation”, reviewing an electronic health record (EHR), and “obtaining results”, which are abstract ideas because they encompass reading a report and making conclusions and determination which can occur entirely within the mind. It is therefore determined that the claims recite judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps “obtaining or having obtained” a biological sample, and “performing or having performed sequencing on the biological sample”, however these steps do not integrate the JE into a practical application because they are mere data gathering steps to use the correlation and do not add meaningful limitations to the method. Likewise, steps of obtaining results of blood pressure and biomarker determinations, including by accessing an EHR are also data gathering steps. Although the claims recite “treating” in the preamble, the only positive active steps recited in the claims are directed to “triggering a PKD intervention”, “prescribing” specific pharmaceuticals or “implementing” a protein reduced diet, or generating a report recommending criteria for triggering a PKD intervention or not. However, these elements/steps are considered nothing more than instructions to apply the natural correlation because no actual treatment administration is required. The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294. Elements such as “triggering”, prescribing”, “implementing”, and generating a report do not actual require any treatment administration actually take place. This is also literally the case for the recitation of “refraining from triggering a PKD intervention” which requires that the practitioner do nothing. (See MPEP 2106.04(d)(2) for analysis of particular treatments/prophylaxis in Step 2A Prong 2).
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the recitation of “obtaining or having obtained” a biological sample, is considered insignificant post solution activity. The steps of “performing or having performed sequencing on the biological sample” do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Furthermore, the general acts of prescribing, generating reports, and implementing dietary changes are well known and used in the field of clinical medicine. Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore, these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection. The response asserts that under step 2A prong one, the claims are not directed to judicial exceptions. This argument has been thoroughly reviewed but was not found persuasive because as already set forth in the previous office action, Step 2A prong one is analyzed to determine if it recites JE’s. In the instant situation, the correlation between being prone to kidney cysts based on the presence of a qualifying variant in the PKD1 gene is a recitation of the natural correlation between the presence of the PKD1 variants and kidney cysts. Additionally, with regard to the recitation of abstract, mental steps, the claims do not require sequencing, the claims specifically recite having performed sequencing to determine if the patient has a qualifying mutation. This step encompasses reading a report of the results of a sequencing method, which is an abstract mental step since the reading of the report occurs within the mind of the practitioner. With regard to step 2A prong 2, the response asserts that the features of the claims provide additional elements that integrate the JEs into practical application and cites Ex Part Janevski et al, a decision by the Patent Trial and Appeal Board. This argument has been thoroughly reviewed but was not found persuasive because the legal basis for rejecting claims under 35 USC 101 is set forth in the MPEP (MPEP 2106) as well as precedential case law as cited in the instant office action. The arguments that the claims dynamically alter treatment pathways by combining carrier status of a PKD1 variant with clinical thresholds. The response asserts that the claims recite a specific improvement over prior art systems by allowing users to meaningfully process and compare patient biological information to direct targeted care. This argument has been thoroughly reviewed but was not found persuasive because the claim recites that in one embodiment “if the patient does not have a qualifying mutation”, the practitioner do nothing. There is no treatment step in this situation. The claim literally recites “refraining from triggering the PKD intervention” which encompasses that the practitioner do nothing. There is no active step of administering any sort of treatment in this situation. Therefore, a literal reading of this embodiment of the claims requires the active steps of obtaining a sample (or having obtained a sample), performing (or having performed) sequencing to determine “if” the patient has a qualifying PKD1 variant, obtaining results of a blood pressure test, and doing nothing else if a) the blood pressure test does not indicate hypertension, OR b) if it does indicate hypertension but the patient does not have a qualifying PKD1 variant. Furthermore, with regard to the embodiment to “triggering” a PKD intervention, this encompasses writing a prescription (see dependent claim 4 for example) or generating a report “recommending” the PKD intervention (dependent claim 7) which does not actually require any treatment take place. See MPEP 2106.04(d)(2) for analysis of particular treatments/prophylaxis in Step 2A Prong 2. In this situation, the MPEP explicitly states:
Examiners should keep in mind that in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of such a limitation is a step of "administering amazonic acid to a patient" or a step of "administering a course of plasmapheresis to a patient." If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. For example, a step of "prescribing a topical steroid to a patient with eczema" is not a positive limitation because it does not require that the steroid actually be used by or on the patient, and a recitation that a claimed product is a "pharmaceutical composition" or that a "feed dispenser is operable to dispense a mineral supplement" are not affirmative limitations because they are merely indicating how the claimed invention might be used.
Even if the claim were to recite “administering a PKD intervention”, this is not particular and is instead merely instructions to “apply” the exception in a generic way. The MPEP at 2106.04(d)(2) also explicitly states:
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.
It is additionally noted that the office action cited Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals in analysis of step 2A prong 2. Unlike the claims in Vanda, which required administration of a particular dose of a specific medication depending on genotype (the dose was different depending on the genotype), no such requirement is set forth here. The claims either don’t require any intervention (refraining), or if they do, they are not recited as affirmative limitations because they are merely indicating how the claimed invention might be used.
The response also asserts citations to Flook and Bilski to categorize the claimed invention as insignificant post solution activity is a misapplication of those cases. This argument is not found persuasive because the office action stated “the recitation of ‘obtaining or having obtained’ a biological sample, is considered insignificant post solution activity”. It did not assert that the sequencing step or sequencing requirement was insignificant post solution activity. Arguments that the office action improperly dissects the claims into isolated pieces is also not found persuasive because the office action also considered the claims as a whole. This is evident in the following recitation from the office action: “When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.”. The rejection is maintained.
Claim Rejections - 35 USC § 112
Claims 1-21 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
Relevant to the lack of particular structural limitations in the rejected claims drawn to detecting loss of function mutations in PKD1, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The claims are broadly drawn to methods which require determining if a sample from a patient has a “qualifying” mutation including any loss of function mutation or missense mutation in PKD1.
In the case of the instant claims, the functionality of identifying “qualifying mutations” as well as loss of function mutations in PKD1, let alone those that are “qualifying” or “qualifying” missense mutations is a critical feature of the claimed methods.
The specification teaches that variants which inactivate PKD1 are called loss of function mutations (para 0084). The specification teaches using an Ensembl Variant Effect Predictor tool to determine whether any variant inactivates PKD1. However, this is not a description of what the structure of the variants are but rather a tool that can be used to predict which ones may or may not be within the claimed genus.
The claims encompass a genus of structurally undefined PKD1 mutations which must possess a function which the specification provides no guidance for. As such, the skilled artisan would not be capable of distinguishing between members of the claimed genus of “qualifying” or “loss of function mutations”, from PKD1 missense mutations or other PKD1 mutations which are not “qualifying” or “loss of function”. Although the prior art teaches mutations in the PKD1 gene which are associated with kidney cysts and PKD, these are not representative of the claimed genus because it is not clear from this disclosure, what the structure of other members of the claimed genus would be. While the skilled artisan may be capable of sequencing and identifying mutations, including missense mutations, in the PKD1 gene, or using the Ensemble VEP tool, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615.
Thus, considering the breadth of the PKD1 mutations required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Response to Arguments
The response traverses the rejection. The response traverses that the office action is incorrect in asserting that the claimed mutations are undefined because variants are inherently defined by deviation from a known, structurally defined wild type reference sequence. The response asserts that since the coordinates of PKD1 are known, one can easily envision variants. The response also asserts that the terms “loss of function” variants are improperly characterized as purely functional descriptions. These arguments have been thoroughly reviewed but were not found persuasive because the functionality of identifying “qualifying mutations” as well as loss of function mutations in PKD1, let alone those that are “qualifying” or “qualifying” missense mutations is a critical feature of the claimed methods. The skilled artisan would not expect that ALL PKD1 variants are loss of function variants or “qualifying” variants because it is well known in the art that variants can occur within genes which do not alter the function of the encoded protein such that they would be characterized as “loss of function” variants. While the specification provides a list of possible categories of variants that may result in loss of function (eg nonsense, insertions, deletions, missense mutations), this is not a description of the specific PKD1 nonsense, missense, insertions, etc mutations that would result in a “qualifying” or “loss of function” mutation. It is merely a listing of general categories which the undisclosed mutations may fall into. The claims require the identification of a genus of structurally undefined PKD1 mutations which must possess a function. The specification does not provide guidance as to distinguishing between members of the claimed genus of “qualifying” or “loss of function mutations”, from PKD1 missense mutations or other PKD1 mutations which are not “qualifying” or “loss of function”. Although the prior art teaches mutations in the PKD1 gene which are associated with kidney cysts and PKD, these are not representative of the claimed genus because it is not clear from this disclosure, what the structure of other members of the claimed genus would be. This is also true of the limited number of variants listed in the specification. While the skilled artisan may be capable of sequencing and identifying mutations, including missense mutations, in the PKD1 gene, or using the Ensemble VEP tool, these mutations are not necessarily “qualifying” or “loss of function” variants and the specification does not provide guidance as to how to distinguish which, for example, missense variants are “qualifying” or “loss of function” variants from those that are not. While a limited number of variants are listed in the specification, they are not representative of the claimed genus because the specification does not provide guidance as to how to deduce the structure of the undisclosed variants and the functional consequence to the resulting protein so that the skilled artisan would be able to then distinguish the claimed genus of functionally associated variants from those that are not functionally associated. For this reason, the arguments that the specification provides a representative number of species is not found persuasive. The arguments regarding the office action’s citation of case law is not found persuasive because the instant claims are directed to a situation where a genus of variants with a particular function are critical to the claimed invention, when only a limited number of species have been disclosed. The rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 1, 4-8, 10, 12-15, and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Allerson (Allerson et al; US 2020/0392503) in view of Audrézet (Audrézet et al; Human Mutation, 2012; vol 33; pages 1239-1250).
Allerson teaches methods of treating polycystic kidney disease in patients by selecting patients using clinical, histophathologic, and/or genetic criteria. With regard to claims 1, 8, 18, and 21, Allerson specifically teaches (see pages 40-43, claims 69-93 of Allerson) methods which comprise selecting patients using clinical, histopathologic, and/or genetic criteria. Allerson teaches genetic criteria include detecting mutations in the PKD1 gene (para 0230) and clinical criteria include measuring blood pressure (hypertension, see claims 69-93 of Allerson) eGFR, creatinine, and urea (see para 0244-0247, claims 69-93 of Allerson). Allerson teaches treating patients for PKD (“triggering a PKD intervention). With regard to claims 6, 7, 12, and18, although Allerson does not teach to generate a report recommending criteria for PKD intervention, Allerson does teach analysis of both hypertension as well as confirming PKD because Allerson teaches treating patients who have PKD. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have generated a report, such as writing recommendations or prescribing therapeutics for the obvious benefit of informing the patient and other caregivers of treatment necessity. With regard to the sequence of obtaining particular information, such as genetic information, biomarker information, blood pressure information, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have optimized the order of data gathering for the purpose of providing accurate diagnosis and treatment (eg manage hypertension- see para 0355). Allerson does not specifically teach detecting PKD1 mutations which are, for example, missense mutations, however Audrézet teaches identifying a number of PKD1 missense mutations which are considered pathogenic (see whole document, tables 3 and 4). Since these mutations are taught to be pathogenic, they are taken as necessarily being “qualifying” and “loss of function” mutations. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have detected qualifying missense mutations in PKD1, such as those taught by Audrézet, because Audrézet teaches that certain missense mutations are associated with PKD pathology.
With regard to claims 4, 10, and 20, Allerson teaches administering therapeutic compounds including ACE inhibitors, diuretics, etc (see para 0402-0420).
With regard to claims 14, 15, and 17 Allerson teaches eGFR, urea, and creatine measurement (see para 0244-0247), including optimizing ranges for indication of kidney function. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). One skilled in the art would have known to use standards to establish thresholds for distinguishing normal from abnormal values. Thus, the recited threshold values of the claims would be arrived at by routine experimentation by one of ordinary skill in this art.
Claims 2, 3, 5, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Allerson in view of Audrézet as applied to claims 1, 4-8, 10, 12-15, and 17-21 above, and further in view of Vos (Vos et al; BMC Health Services Research, vol 20, pages 1-11; 2020).
The teachings of Allerson in view of Audrézet are set forth above. Allerson and Audrézet do not teach reviewing or storing information in an electronic health record (EHR), however Vos teaches the usefulness and benefits of storing information in an EHR (see table 2), as well as identifying constraints for its improvement (see whole document). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have stored and retrieved information regarding PKD therapy taught by Allerson and Audrézet for the benefits taught by Vos. Allerson, Audrézet, and Vos do not teach the hypertension thresholds set forth in the claim 3, however it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). One skilled in the art would have known to use standards to establish thresholds for distinguishing normal from abnormal values. Thus, the recited threshold values of the claims would be arrived at by routine experimentation by one of ordinary skill in this art.
Claims 16 and 21 (directed to cystatin C) is rejected under 35 U.S.C. 103 as being unpatentable over Allerson in view of Audrézet as applied to claims 1, 4-8, 10, 12-15, and 17-21 above, and further in view of Sans (Sans et al; PLoS ONE 12(3) e.0174583; pages 1-7; 2017).
The teachings of Allerson in view of Audrézet are set forth above. Allerson and Audrézet do not teach measuring cystatin C, however Sans teaches that Cystatin C measurement is useful and may be an improvement over creatinine for inclusion in eGFR equations. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have included biomarker measure of cystatin C because Sans teaches it may be an improvement for eGFR equations. Although Allerson, Audrézet, and Sans do not teach the threshold value taught in the claim, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). One skilled in the art would have known to use standards to establish thresholds for distinguishing normal from abnormal values. Thus, the recited threshold values of the claims would be arrived at by routine experimentation by one of ordinary skill in this art.
Response to Arguments
The response traverses the rejections. The response asserts that claims 1 and 8 require a conditional bifurcation of medical treatment based on genetic status. This argument has been thoroughly reviewed but was not found persuasive because the claims recite different conditional limitations which is clearly evident from the multiple recitations of the term “if”. There is no requirement that the multiple possible embodiments which result from these conditional limitations must be met when “analyzing a sample”. In other words, the claims does not require that a patient being analyzed has a test result that indicates hypertension AND does not indicate hypertension, or that the patient has a qualifying PKD1 variant AND does not have a qualifying PKD1 variant. This appears to be a fallacy in logic because either a patient has hypertension or they do not. Likewise, the patient either does or does not have a qualifying PKD1 variant. The response also asserts that the rejection of specific clinical thresholds is a misapplication because the claims define highly specific clinical decision-making thresholds used to trigger medical interventions tied to a genetic variant and disease onset. This argument has been thoroughly reviewed but was not found persuasive. It is not clear if the response is asserting that the clinical thresholds were not known before or if they change depending on which PKD1 variant is found in the sample. For these reasons and the reasons already made of record, the rejections are maintained.
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.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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