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 .2. This action is in response to the amendment filed on 05 November 2025. Applicant's arguments and amendments to the claims have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
In particular, the previous objection to the specification and the objection to the drawings have been obviated by the filing of the Petition to Accept Color Drawings, which was granted in the reply of 04 December 2025.
Claim Status
3. Claims 13, 28-30, 57, 65 and 73 are pending.
Claims 29, 30, 57 and 65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 13, 28 and 73 read on the elected invention and have been examined herein to the extent that the claims read on the elected species of the 39 biomarkers of PTGS2, CD3E, CYBB, THBS1, CAV1, NEDD9, F3, SERPINE1, PRDM1, HIF1A, TIPARP, FOS, CDKN1A, AREG, LYN, NDRG1, AQP3, UGT1A6, SLC7A5, EGR1, GHR, IRF8, CYP1B1, PNPLA7, PDE2A, IL6, SLC10A1, AHR, LEPR, FPR2, DKK3, FAT1, GNA13, TGM1, NOS3, HMOX1, CD36, SERPINB2 and FBXO32. Claims 29, 30 and 57 encompass non-elected species of alternative combinations and subcombinations of biomarkers. Each of the claims encompasses non-elected species of biological states, and functional outcomes, and claim 27 encompasses non-elected AHR signaling modulators. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
Election/Restrictions
4. In the reply of 28 February 2026, Applicant elected traverse of Group I, methods for determining an aryl hydrocarbon receptor (AHR) activation signature for a condition, and the species of PTGS2, CD3E, CYBB, THBS1, CAV1, NEDD9, F3, SERPINE1, PRDM1, HIF1A, TIPARP, FOS, CDKN1A, AREG, LYN, NDRG1, AQP3, UGT1A6, SLC7A5, EGR1, GHR, IRF8, CYP1B1, PNPLA7, PDE2A, IL6, SLC10A1, AHR, LEPR, FPR2, DKK3, FAT1, GNA13, TGM1, NOS3, HMOX1, CD36, SERPINB2 and FBXO32
as the particular combination of biomarkers, RNA expression as the species of a biological state, immune modulation as the species of a functional outcome, cancer as the species of a condition, and 2-heteroaryl-3-oxo-2,3- dihydropyridazine-4-carboxamide as the species of an AHR signaling modulator.
In the reply of 05 November 2025, Applicant states: “Applicant submits that claims 57 and 65 have been amended to depend from
independent claim 13. Therefore, Applicant respectfully submits to consider rejoinder of claims 57 and 65 as these claims recite different aspects of the same invention as recited in independent claim 13. Favorable consideration of the rejoinder of claims 57 and 65 as presented herein is therefore respectfully requested.”
These arguments have been fully considered but are not persuasive. Applicant amended claim 57 to recite in the preamble of the claim “A processor to perform the method of claim 13.” However, this constitutes only an intended use of the processor. The body of the claim does not recite a processor that performs each of the method steps of claim 13. Similarly, claim 65 was amended to recite “A computer-readable storage device for the method of claim 13.” This again is only an intended use limitation. Claim 65 does not recite instructions for performing each of the method steps of claim 13. In particular, the claimed processor and computer-readable storage device do not perform or contain the instructions to perform, respectively, each of the steps of claim 13 of obtaining a tissue sample from a human subject, determining in the tissue sample obtained from the human subject the biological state of 10% of the AHR biomarkers listed in claim 13, performing clustering of the AHR biomarkers based on the determined biological state of each AHR biomarker; determining the AHR activation state of the tissue sample based on the clustering, wherein the AHR activation state comprises an increase in AHR signaling, and based on the determined activation state of the tissue sample, administering an AHR signaling modulator that is a small molecule to the human subject. Thus, the processor of claim 57 and the computer readable device of claim 65 do not share the special technical features of claim 13. Further, the linking technical feature of assaying for the expression level of biomarkers selected from the list at step b) of claim 13 was known in the prior art and thereby is not a special technical feature linking the claimed inventions, as discussed in the restriction requirement of 29 November 2024. Additionally, set forth in the Office action of 05 May 2025, Michaelson teaches a method in which the expression level of each of the biomarkers of PTGS2, CD3E, CYBB, THBS1, CAV1, NEDD9, F3, SERPINE1, PRDM1, HIF1A, TIPARP, FOS, CDKN1A, AREG, LYN, NDRG1, AQP3, UGT1A6, SLC7A5, EGR1, GHR, IRF8, CYP1B1, PNPLA7, PDE2A, IL6, SLC10A1, AHR, LEPR, FPR2, DKK3, FAT1, GNA13, TGM1, NOS3, HMOX1, CD36, SERPINB2 and FBXO32 were determined in tissue samples from a subject.
Non-Compliant Amendment
5. The status identifiers used for claims 29, 30, 57 and 65 are not correct as these claims are directed to non-elected subject matter and should be accompanied by the status identifier of “(Withdrawn)” or “(Withdrawn – Currently amended), as appropriate.
As set forth in MPEP 714, “For any amendment being filed in response to a restriction or election of species requirement and any subsequent amendment, any claims which are non-elected must have the status identifier (withdrawn). Any non-elected claims which are being amended must have either the status identifier (withdrawn) or (withdrawn – currently amended) and the text of the non-elected claims must be presented with markings to indicate the changes. Any non-elected claims that are being canceled must have the status identifier (canceled).”
MPEP provides the following list of acceptable alternative status identifiers:
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435
908
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Greyscale
Use of the correct status identifiers is required in future responses.
Maintained / Modified Claim Rejections - 35 USC § 101
6. 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 13, 28 and 73 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between a “biological state” of AHR biomarkers (expression with respect to the elected species) and the condition of cancer. As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
2) Certain methods of organizing human activity…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
The claims require performing the step of “determining” the AHR activation state of a sample based on clustering. Neither the specification nor the claims set forth a limiting definition for "determining" and the claims do not set forth how “determining” is accomplished. The broadest reasonable interpretation of the determining step is that this step may be accomplished by reading information in a report regarding the results of clustering to thereby draw a conclusion regarding the AHR activation state of the sample. Such “determining” thereby encompasses processes that may be performed mentally and thus is an abstract idea.
The claims further require performing a step of clustering biomarkers based on their biological state, including their expression level. Neither the specification nor the claims set forth a limiting definition for "clustering" and the claims do not set forth how “clustering” is accomplished. The broadest reasonable interpretation of the “clustering” step is that this step may be accomplished mentally by grouping the results pertaining to the biological state of the biomarkers. Thereby, the clustering step is an abstract idea.
To any extent that the clustering step is intended to require the use of an algorithm or software or a generic computer, as broadly recited the step would also be an abstract idea. The use of a generic computer or software program to implement an abstract idea does not itself impart patent eligibility.
As stated in MPEP 2106.04(a)(2) III “The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation” and that “Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer.”
Herein, the use of a generic computer to apply a generic algorithm to group and classify biological states / gene expression levels does not constitute something more than an abstract idea.
Also the clustering step constitutes the judicial exception of a mathematical concept of the formula that is used to classify the . See MPEP 2106.04(a)(2):
“A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the “mathematical concepts” grouping. A mathematical calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. There is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word “calculating” in order to be considered a mathematical calculation. For example, a step of “determining” a variable or number using mathematical methods or “performing” a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation.”
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The additionally recited steps of obtaining a sample from a subject and determining the “biological state” of biomarkers are part of the data gathering process necessary to observe the judicial exception. These steps do not practically apply the judicial exception.
The claims as amended now recite:
“(d) determining the AHR activation state of biological sample based on the clustering, wherein the AHR activation state comprises an increase in AHR signaling, wherein the AHR activation signature comprises at least 10% of the AHR biomarkers according to Table 1 the list of step (b); and (e) based on the determining step (d), administering an AHR signaling modulator to the subject, wherein an effective amount of the AHR signaling modulator is about 0.01 mg/kg to 100 mg/kg and the AHR signaling modulator is a small molecule compound.”
This step encompasses determining the AHR activation state of the sample, wherein the AHR activation state is defined as an increase in AHR signaling and then administering a small molecule compound that increases or decreases (i.e., modulates) AHR signaling. The claims do not require determining that the tissue sample has an increase in AHR signaling. Rather, the claims define the AHR activation state as an increase in AHR signaling. Since the claims encompass detecting the presence or absence of an increase in AHR signaling and then administering a small molecule compound that increases or decreases AHR signaling (claims 13 and 73) or one of the compounds of claim 28, the administering step is not a practical application of the recited judicial exceptions since the administering step occurs irregardless of whether the tissue sample shows an increase in AHR signaling.
Additionally, the administering step recited in claims 27 and 75 is recited at a high degree of generality, in which any human subject with or without an increase in AHR signaling is administered any small molecule that modulates in any manner AHR signaling. Such broad general treatments of any condition in subjects having or not having AHR activation does not constitute a practical application of the judicial exception. Rather, this is merely an “apply it” limitation.
Regarding specific treatments, see MPEP 2106.04(d)(2):
When determining whether a claim applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, the following factors are relevant.
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….
b. Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)
The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition). The claim also recites "treating a patient having a blood glucose level over 250 mg/dl with insulin". Insulin acts to lower blood glucose levels, and administering insulin to a patient will reduce the patient’s blood glucose level, thereby lowering the risk that the patient will develop ketoacidosis. Thus, in the context of this claim, the administration step is significantly related to the recited correlation between high blood glucose levels and the risk of ketoacidosis. Because insulin is also a "particular" treatment, this administration step integrates the law of nature into a practical application. Alternatively, consider a claim that recites the same law of nature and also recites "treating a patient having a blood glucose level over 250 mg/dl with aspirin." Aspirin is not known in the art as a treatment for ketoacidosis or diabetes, although some patients with diabetes may be on aspirin therapy for other medical reasons (e.g., to control pain or inflammation, or to prevent blood clots). In the context of this claim and the recited correlation between high blood glucose levels and the risk of ketoacidosis, administration of aspirin has at best a nominal connection to the law of nature, because aspirin does not treat or prevent ketoacidosis. This step therefore does not apply or use the exception in any meaningful way. Thus, this step of administering aspirin does not integrate the law of nature into a practical application.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The additionally recited steps of obtaining a sample from a subject and determining the biological state, and particularly the expression level, of biomarkers were well-known, routine and conventional in the prior art. This finding is evidenced by the teachings in the specification. See, for example, para [0069] which states “In some embodiments, RNA expression of a biomarker is detected by methods known in the art including, but not limited to, qPCR, RT-qPCR, RNA-Seq, and in-situ hybridization.”
See also MPEP 2106.05(d) II which states that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Note that while the claims recite detecting the biological state / expression level of particular genes, the identity of the genes is part of the judicial exception and not something in addition to the recited judicial exceptions. The claims do not require using a particular non-conventional reagent, such as a particular, non-conventional probe or primer consisting of or comprising a specific nucleotide sequence so as to add something ‘significantly more’ to the recited judicial exceptions.
To any extent that the step of clustering is intended to encompass using a generic computer, MPEP 2106.05(a) states that ”Limitations that the courts have found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include: i. Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, e.g., a limitation indicating that a particular function such as creating and maintaining electronic records is performed by a computer, as discussed in Alice Corp., 134 S. Ct. at 2360, 110 USPQ2d at 1984 (see MPEP § 2106.05(f))”
In Mayo v. Prometheus, the Supreme Court stated: "[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."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.Response to Remarks:
The response states:
“Independent claim 13 has been amended to recite "wherein the AHR activation state comprises an increase in AHR signaling" and "based on the determining step (d), administering an AHR signaling modulator to the subject, wherein an effective amount of the AHR signaling modulator is about 0.01 mg/kg to 100 mg/kg and the AHR signaling modulator is a small molecule compound" as suggested by the Examiner in the Interview.”
However, the examiner did not suggest the language set forth in amended claim 13 in the interview. Rather, the examiner suggested amending claim 13 to recite a step of determining that the biological sample has an increase in AHR signaling and to recite a step of administering one of the specific AHR signaling modulators listed in claim 28 to the biological sample determined to have the increase in AHR signaling. In contrast, Applicant amended claim 13 to recite a limitation that merely defines an AHR activation state as comprising an increase in AHR signaling and to include a step of administering to the subject any small molecule compound that modulates (increases or decreases) AHR signaling in the wide dosage range of 0.01 mg/kg to 100 mg/kg.
The response argues:
“the currently amended claims include a step of administering an AHR signaling modulator to the subject and are therefore directed to patentable subject matter. The currently amended claims are directed to a specific AHR activation state comprising an increase in AHR signaling, a specific treatment regimen (about 0.01 mg/kg to 100 mg/kg) using a specific type of AHR signaling modulator (a small molecule compound) for a specific AHR- related disease or condition (cancer) and thus are patent eligible consistent with Vanda Pharmaceuticals, Inc. v. West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018).”
These arguments have also been fully considered but are not persuasive. The fact pattern herein is distinct from that in the Vanda decision. The claims in the Vanda decision required administering 12mg/day or less of iloperidone to subjects having a CYP2D6 poor metabolizer genotype and administering more than 12mg/day, up to 24mg/day, of iloperidone to subjects that do not have a CYP2D6 poor metabolizer genotype. Thereby, the two groups of patients were clearly treated in different manners based on the determined CYP2D6 genotype. In contrast, in the present claims the subjects are treated in the same manner irregardless of whether the sample is determined to have an increase in AHR signaling. As argued by Applicant, claim 13 was amended to recite “"wherein the AHR activation state comprises an increase in AHR signaling." This limitation only defines what constitutes the AHR activation state. The claims do not require that it is determined that the sample does in fact have an increase in AHR signaling. The claims thereby include methods wherein an increase in signaling is or is not determined to be present in the sample and the subject is administered a small molecule compound that modulates AHR signaling by either increasing or decreasing AHR signaling. Thus, the subjects having an increase in AHR signaling are treated in the same manner as the subjects that do not have an increase in AHR signaling. As broadly recited, the administering step does not integrate the judicial exception into a practical application.
Secondly, in contrast to the claims in Vanda, present claims 13 and 73 do not recite administering a specific compound. Reciting the 1,000 fold range of dosages that are to be administered to the subject does not equate to reciting a specific compound. Also, reciting that the compound is a small molecule compound only defines the class of compounds but does not ensure that the claims are limited to administering a specific compound. Rather, claims 13 and 73 encompass administering any small molecule compound that directly or indirectly increases or decreases (i.e., modulates) AHR signaling by targeting any unspecified molecule or pathway. This type of administering step is not specific and does not integrate the judicial exception into a practical application.
Maintained Claim Rejections - 35 USC § 112(a) - Enablement
7. Claims 13, 28 and 73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
This rejection was previously presented in the Office action of 05 May 2025 and is maintained for the reasons set forth therein.Response to Remarks:
It is first acknowledged that Applicant has amended claim 13 to recite that the subject is a human subject, that the AHR activation signature “is specific for” cancer and the “AHR activation state comprises an increase in AHR signaling.”
The response argues:
“Applicant respectfully disagrees with the Examiner to limit the biological state to RNA expression. Applicant submits that the specification as filed discloses that in a specific embodiment, the first AHR activation signature is based on RNA expression, and the second AHR activation signature is based on protein analysis. Alternative AHR signatures are useful for use on samples where, e.g., RNA amount or quality is not good enough for RNA expression analyses (e.g., paraffin-embedded samples, frozen samples). Alternative AHR signatures may also lead to development of other diagnostic techniques (e.g., a protein-based assay looking at the alternative AHR signature of a condition based on proteomics). An alternative AHR signature is determined based on a second biological state which includes, but is not limited to, one of mutation state, methylation state, copy number, protein expression, metabolite abundance, and enzyme activity. See paragraphs [0079] - [0080] of the specification as filed. Examples 4 and 9-10 of the instant application discloses use of alternative (secondary) AHR activation signatures based on proteomics data. Applicant respectfully submits that the phrase "at least 10% of the AHR biomarkers according to the list of step (b)" as recited in the currently amended independent claim 13, clearly demonstrates any combination of at least 16-17 genes of the 166 genes as recited in the list of step (b) of claim 13.”
These arguments have been fully considered but are not persuasive. While the specification provides literal basis for the concept that an AHR biological state could be determined by assaying for a “mutation state, methylation state, copy number, protein expression, metabolite abundance, and enzyme activity,” the specification provides no evidence to support the contention that a representative number of these different types of biological states can be determined for 10% of the biomarkers of table 1 (or each of the elected 39 biomarkers) as “specific for cancer,” as indicative of an increase in AHR signaling and as indicative of the need to administer to a subject a small molecule compound that increases or decreases AHR signaling. For instance, the specification is silent as to particular mutations present in each of the genes or the 39 genes or 10% of the genes listed in Table 1 (claim 13) which should be assayed for to establish the biological state of the tissue sample. Similarly, the specification is silent as to particular copy number changes of these genes or metabolites associated with the genes, that are “specific for cancer” and indicative of an increase in AHR signaling. The specification does not provide sufficient guidance to enable the broadly claimed methods wherein any biological state of the biomarkers is determined as indicative of the AHR activation state of an increase in AHR signaling in the sample without undue experimentation.
Secondly, while the specification teaches that databases were analyzed for expression levels of the genes of Table 1 in 32 types of cancer, the specification does not teach that an increase or decrease in the RNA or protein level of 10% of any of the biomarkers from Table 1 or each of the biomarker in claim 73 is “specific for cancer” per se and can be used to determine that a tissue sample has an increase in AHR signaling, as indicative that a subject should be treated with a small molecule compound that either increases or decreases AHR signaling. Note that the specification teaches genes from Table 1 whose mRNA levels are correlated with the 32 different cancer types (see Examples 3 and 6 and Table 2). Subgroups of differentially expressed genes are also provided in Table 4 (see Example 8 beginning at para [0171]; see also figure 23). However, the specification does not teach that the elected subcombination of 39 biomarkers are correlated with the “specific condition” of cancer per se. The specification does not establish, for example, that the mRNA levels of the 39 biomarkers were found to be diagnostic of cancer per se and if you cluster them or classify them based on any biological state, then the result will indicate that the tissue sample has an increase or no increase in AHR signaling and the tissue or subject from which the tissue is obtained should be treated with a small molecule that increases or decreases AHR signaling. Regarding “proteomics data,” Table 5 lists “the different RPPA features that could be used to call AHR activation for the 32 TCGA cancers divided among the different AHR subgroups for each cancer entity defined by consensus K means clustering.” However, the specification does not appear to teach that the elected subcombination of 39 biomarkers have the biological state of protein levels that are correlated with one of the 32 types of cancer. Nor does the specification teach that a representative number of 16 or 17 of the biomarkers from Table 1 have an expression level that is specific for cancer per se and indicative of an increase or no increase in AHR signaling.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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, Wu-Cheng (Winston) Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682