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 the Claims
Claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70 are pending. Claims 54, 58, 61, 62, 67, and 68 are amended. Accordingly, claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70 are examined herein.
Priority
The present application, filed 08/18/2025 is an RCE of U.S. Patent Application 18/376,575, filed 10/04/2023, is a divisional of U.S. Patent Application 16/883,468, filed 05/26/2020, which is a continuation of U.S. Patent Application 15/813,418, filed 11/15/2017, now abandoned, which is a divisional of U.S. Patent Application 14/447,691, filed 07/31/2014, now abandoned, which claims benefit of U.S. Provisional Patent Applications 61/945,006 and 61/860,958, filed 02/26/2014 and 08/01/2013 respectively.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 10/21/2025 are acknowledged and have been considered.
Maintained 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.
Applicant amended independent claim 54 in an attempt to overcome the rejection under 35 U.S.C. 101 by adding treatment-related limitations directed to administration of a second treatment regimen if a patient is determined to be non-responsive to a first treatment regimen, or continuation of the first treatment regimen if the patient is determined to be responsive. The rejection under 35 U.S.C. 101 has been reconsidered in view of Applicant’s amendments and arguments. However, for the reason set forth below, the amendments do not overcome the rejection. Accordingly, the rejection under 35 U.S.C. 101 is maintained and updated to address the amended claim language.
Claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception, i.e., a law of nature/natural phenomenon and an abstract idea, without significantly more.
Independent claim 54 is directed to a computer-implemented method for evaluating the efficacy of a treatment regimen in a patient diagnosed with small cell lung cancer (SCLC) and undergoing treatment for SCLC, wherein the treatment is administration of one or more of cisplatin, carboplatin, irinotecan, and etoposide. The claim recites receiving a measurement of a level of a plurality of biomarkers in a test sample from the patient, comparing the measured level of the plurality of biomarkers to a normal control level of the plurality of biomarkers, evaluating from the comparison that the patient is responsive or not responsive to a first treatment regimen, and, based on the evaluating step, either administering a different second treatment regimen if the patient is not responsive, or continuing administration of the first treatment regimen if the patient is responsive.
Step 1: This part of the eligibility analysis evaluates whether the claim falls within a statutory category. MPEP §2106.03. Claim 54 recites a method comprising steps including receiving, comparing, evaluating, and administering or continuing administration of a treatment regimen. Thus, the claim is directed to a process, which is a statutory category of invention (Step 1: YES).
Step 2A, Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP § 2106.04(II), a claim recites a judicial exception when the judicial exception is set forth or described in the claim. Claim 54 recites a natural relationship between measured levels of a plurality of biomarkers selected from MMP-3 and/or Adiponectin in combination with at least one biomarker selected from the group consisting of IP-10, TPO, EPO, sFlt-1, S100A6 and IL-6, and the biological responsiveness or non-responsiveness of a patient diagnosed with SCLC to the first treatment regimen. The relationship between biomarker levels in a patient sample and the patient’s biological response to treatment exists apart from any human action and is therefore a law of nature/natural phenomenon.
Claim 54 also recites an abstract idea in the form of mental processes. In particular, the comparing step and evaluating step, under their broadest reasonable interpretation, encompass observation, comparison, and judgment that could practically be performed in the human mind, but for the recitation that the method is computer-implemented. The claim does not recite any specific algorithm, specialized computer operation, or technological improvement in how the comparison or evaluation is performed. Accordingly, the comparing and evaluating limitations recite an abstract idea falling within the mental processes grouping.
Accordingly, claim 54 recites a judicial exception in the form of a law of nature/natural phenomenon and an abstract idea (Step 2A, Prong One: YES).
Step 2A, Prong Two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. Besides the abstract idea and law of nature, claim 54 recites the additional elements of a computer, receipt of biomarker measurement data, a patient diagnosed with SCLC and undergoing treatment with one or more of cisplatin, carboplatin, irinotecan and etoposide, and the recited clinician-performed alternatives of administering a different second treatment regimen if the patient is not responsive or continuing the first treatment regimen if the patient is responsive.
The use of a computer does not integrate the exception into a practical application because the claim merely uses generic computer implementation to receive, compare, and evaluate information. The claim does not recite any specific improvement in computer functionality, any particular machine, or any specific computational technique that improves another technology or technical field. The claim states nothing more than that generic computer hardware performs functions that constitute the abstract idea and therefore merely instructs application of the abstract idea using generic computer implementation. See MPEP §§ 2106.04(d) and 2106.05(f).
The measurement of biomarker levels is data-gathering activity. The claim does not recite any particular unconventional measurement technique or any specific technical improvement in biomarker detection. The recited measurement is used merely to obtain data needed to apply the biomarker/treatment-response relationship. Such data-gathering activity is insignificant extra-solution activity and does not integrate the judicial exception into a practical application. See MPEP § 2106.05(g); Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012); In re Grams, 888 F.2d 835 (Fed. Cir. 1989).
Applicant amended claim 54 to recite that, based on the evaluating step, one of two alternatives is performed by a clinician: (d) a second treatment regimen is administered if the patient is not responsive to the first treatment regimen, wherein the second treatment regimen is different from the first treatment regimen and is administration of one or more of cisplatin, carboplatin, irinotecan and etoposide; or (e) the first treatment regimen continues to be administered if the patient is responsive to the first treatment regimen. However, these amendments do not integrate the judicial exception into a practical application for the full scope of claim 54.
With respect to the responsive-patient alternative, the claim merely requires continuing administration of the same first treatment regimen that the patient was already receiving. Thus, for a patient determined to be responsive, the claim does not require changing, selecting, adjusting, modifying, or otherwise applying a new treatment based on the biomarker evaluation. Instead, the claim informs the clinician of the result of the biomarker comparison and continues the pre-existing treatment regimen. Merely continuing the status quo after informing a clinician of a natural correlation does not meaningfully limit the judicial exception or apply it in a manner that imposes a practical application.
With respect to the non-responsive-patient alternative, the claim recites administering a different second treatment regimen if the patient is not responsive. However, claim 54 is drafted in the alternative, requiring that one of limitations (d) or (e) is performed. Since the claim encompasses the responsive-patient alternative in which no treatment is changed or selected based on the biomarker evaluation, the claim as a whole remains directed to the judicial exception.
Moreover, even in the non-responsive-patient alternative, although the claim identifies known SCLC chemotherapy agents, i.e., cisplatin, carboplatin, irinotecan and etoposide, the claim does not recite any particular dosage, schedule, route of administration, treatment protocol, or specific therapeutic adjustment dictated by any particular biomarker level or combination of biomarker levels. Nor does the claim require that a particular biomarker result lead to administration of a particular drug, drug combination, dosage, or treatment modification. Instead, once a patient is determined to be non-responsive, the claim broadly permits administration of a different regimen comprising one or more known SCLC chemotherapy agents without specifying how the biomarker evaluation dictates the treatment selected. Thus, the claim does not require a particular treatment application tied to the recited biomarker values, but instead broadly instructs a clinician to use the biomarker evaluation when deciding whether to continue therapy or administer a different regimen selected from the known list of SCLC chemotherapy agents. The treatment limitation is therefore recited at a high level of generality and does not meaningfully limit the judicial exception by applying it through a specific biomarker-directed treatment protocol.
Accordingly, claim 54 does not integrate the recited judicial exception into a practical application and is therefore directed to the judicial exception (Step 2A, Prong Two: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited judicial exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP § 2106.05. Claim 54 does not recite significantly more than the judicial exception. The additional elements, individually and in combination, amount to no more than generic computer implementation, routine receipt and analysis of biomarker data, routine biomarker measurement, and broadly recited administration or continuation of known SCLC chemotherapy agents. These elements do not provide an inventive concept sufficient to transform the judicial exception into patent-eligible subject matter.
Computer-implemented methods for analyzing biomarker information and evaluating disease or treatment efficacy were well-understood, routine, and conventional. See, e.g., Colpitts et al., US 2007/0178504 A1, published 08/02/2007; Yamka et al., US 2011/0183006 A1, published 07/28/2011; Gold et al., US 2010/0070191 A1, published 03/18/2010; and Wilcox et al., US 2013/0116150 A1, published 05/09/2013. These references teach computer-implemented analysis of biomarker information, comparison of biomarker data, and evaluation of disease status or treatment efficacy using biomarker measurements. Biomarker measurement and comparison to control values were also well-understood, routine, and conventional in the diagnostic and treatment-monitoring arts. The recited chemotherapy agents, cisplatin, carboplatin, irinotecan and etoposide, were known SCLC treatment agents. See, e.g., Kalemkerian et al. Small Cell Lung Cancer: Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, Vol. 11, No. 1, January 2013). The claim does not recite a new drug, a new dosing regimen, a new administration technique, a new laboratory technique, or a technological improvement in biomarker measurement or computer analysis.
Accordingly, claim 54, considered as a whole, does not amount to significantly more than the recited judicial exception. Claim 54 is not patent eligible.
With regard to claims 55 and 57, as admitted by Applicant at page 15 of the specification, the use of an assay chamber, such as a well of an assay plate, for conducting diagnostic tests is simply appending well-understood, routine, conventional activity previously known to the industry, specified at a high level of generality, to the judicial exception. Claims 55 and 57 are not eligible.
With regard to claim 58, as admitted by Applicant at pages 14-15 of the specification, conducting a multiplexed assay measurement of a plurality of biomarkers in a test sample, wherein the multiplexed assay measurement is conducted using one reaction volume comprising the test sample is simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. Claim 58 is not eligible.
With regard to claims 61 and 66, as admitted by Applicant at pages 15-16 of the specification, the use of at least four discrete binding domains, which are in the form of a spot pattern, such as commercially available MULTI-SPOT®, is simply appending well-understood, routine, conventional activity previously known to the industry, specified at a high level of generality, to the judicial exception. Claims 61 and 66 are not eligible.
With regard to claims 62 and 64, the courts have recognized determining the level of a biomarker in blood by any means as well-understood, routine, and conventional activity in the life science arts when claimed in a merely generic manner or as insignificant extra-solution activity. See Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79 (2012); Cleveland Clinic Found. v. True Health Diagnostics LLC, 859 F.3d 1352, 1362 (Fed. Cir. 2017). Claims 62 and 64 are not eligible.
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With regard to claims 67 and 68, using calibrator proteins in immunoassays is well-understood, routine, and conventional activity in the life science arts.
Claims 67 and 68 are not eligible.
With regard to claim 70, the recited treatment-regimen modifications, including increasing or decreasing dosage, frequency, or route of administration, adding an additional therapeutic or palliative agent, or eliminating one or more therapeutic or palliative agents, are recited at a high level of generality and do not require any specific treatment adjustment based on any particular biomarker level or biomarker combination. Although claim 70 identifies categories of treatment modifications, it does not require that any particular biomarker result lead to any particular treatment modification. Rather, the claim broadly encompasses numerous possible treatment adjustments without specifying how the biomarker evaluation dictates the treatment selected. These limitations therefore do not integrate the judicial exception into a practical application and do not amount to significantly more than the judicial exception.
Accordingly, claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70 are rejected under 35 U.S.C. § 101.
Response to Arguments
Applicant’s arguments filed 02/20/2026 have been fully considered but are not persuasive except to the extent that the rejection under 35 U.S.C. §112(b) is withdrawn.
Applicant’s arguments and amendments with respect to the rejection of claims 61, 62, 67, and 68 under 35 U.S.C. §112(b), have been fully considered and are persuasive. Applicant amended claim 61 to replace “human analytes” with “at least four biomarkers from said plurality of biomarkers,” amended claim 62 to replace “said human analytes” with “at least four biomarkers from said plurality of biomarkers,” amended claim 67 to recite “a lyophilized blend of calibrator proteins,” and amended claim 68 to depend from claim 62. Accordingly, the rejection of claims 61, 62, 67, and 68 under 35 U.S.C. §112(b) is withdrawn.
Applicant’s remarks regarding the corrected Application Data Sheet have been considered. The Examiner acknowledges Applicant’s statement that a corrected ADS was submitted to address the priority issue identified in the prior Office Action.
Applicant’s remarks regarding the listing of claims 90-97 and the prior omission of claims 84-89 from the restriction/election requirement have also been considered. Applicant asserts that claims 54-97 were originally pending and the claims 90-97 would have been part of Group III. However, upon review of the record, claims 90-97 are not found in the file wrapper of the instant application. The Preliminary Amendment filed 10/04/2023 includes claims 84-89 (below) as Applicant Remarks, but does not include claims 90-97. Accordingly, the record is clarified to indicate that examination remains limited to elected claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70. No rejection is made on this basis.
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With respect to the obviousness-type double patenting rejections, Applicant notes that the rejections were obviated by the terminal disclaimer filed and approved August 18, 2025. This matter was previously addressed in the prior Office Action, which withdrew the nonstatutory double patenting rejection over U.S. Patent No. 11,802,877 and the provisional nonstatutory double patenting rejection over copending Application No. 18/538,543 in view of the approved terminal disclaimer. No double patenting rejection is maintained in the present Office Action.
With respect to the rejection under 35 U.S.C. §101, Applicant argues that amended claim 54 is patent eligible because the claim now recites affirmative treatment steps and is allegedly directed to a method of treatment that applies a natural relationship rather than being directed to the natural relationship itself. Applicant further argues that, under the June 7, 2018 Vanda memorandum and MPEP §2106.04(d)(2), whether the recited treatments are routine or conventional is not considered when the claims are directed to a method of treatment. These arguments are not persuasive.
Amended claim 54 still recites a judicial exception. The claim recites a relationship between measured levels of a plurality of biomarkers selected from MMP-3 and/or Adiponectin in combination with at least one biomarker selected from IP-10, TPO, EPO, sFlt-1, S100A6 and IL-6, and responsiveness or non-responsiveness of a patient diagnosed with SCLC to a treatment regimen. The claim also recites comparing the measured biomarker levels with normal control levels and evaluating whether the patient is responsive or not responsive. These comparing and evaluating steps are mental processes and may be performed by observation, comparison, and judgment, but for the recitation of generic computer implementation.
Applicant’s amendment does not integrate the judicial exception into a practical application for the full scope of the claim. Although amended claim 54 now recites that a different second treatment regimen is administered if the patient is not responsive to the first treatment regimen, the claim also recites an alternative in which, if the patient is responsive, the first treatment regimen merely continues to be administered. In that responsive-patient alternative, the claim does not require changing, selecting, adjusting, modifying, or otherwise applying a new treatment based on the biomarker evaluation. Rather, the claim merely informs the clinician of the result of the biomarker comparison and continues the treatment regimen that the patient was already receiving.
Thus, unlike a claim that requires a specific treatment action based on the result of the analysis, amended claim 54 still encompasses an alternative in which the judicial exception is used only to evaluate or inform the clinician that the patient is responsive, followed by continuation of the status quo. Merely continuing a pre-existing treatment regimen after receiving information from the biomarker comparison does not meaningfully limit the judicial exception or apply it in a manner that imposes a practical application.
Applicant’s reliance on Vanda is not persuasive. The eligibility rationale in Vanda applies where the claim as a whole is directed to a method of treatment that applies the discovered relationship by requiring a particular treatment step based on the result. Here, claim 54 is drafted in the alternative, requiring that “one of (d) or (e)” is performed. Because the claim encompasses the responsive-patient alternative in which no treatment is changed, selected, or adjusted based on the biomarker evaluation, the full scope of the claim is not limited to a practical treatment application.
Applicant also relies on data from the Examples, including testing serum samples from heavy smokers, NSCLC patients, SCLC patients, and healthy controls using MSD multiplex panels, and argues that certain biomarker panels were clinically useful. This argument is not persuasive because the cited data may show diagnostic or classification utility, but it does not alter the eligibility analysis. The rejection under §101 is not based on a finding that the biomarkers lack utility. Rather, the rejection is based on the fact that the claims recite a natural relationship and mental-process steps, and the additional elements do not integrate the judicial exception into a practical application or amount to significantly more. The presence of useful or clinically relevant biomarker correlations does not, by itself, render a claim patent eligible.
Applicant further argues that the claimed administration of cisplatin, carboplatin, irinotecan, and etoposide can be patent eligible even if those treatments are known. This argument is not persuasive because the rejection does not rest solely on the conventionality of the drugs. Rather, the claim, as a whole, does not require a specific treatment adjustment tied to particular biomarker values or a particular biomarker-defined clinical state across its full scope. In the responsive-patient branch, the claim merely continues the same treatment already being administered. In the non-responsive-patient branch, the claim broadly recites administration of one or more of the known SCLC chemotherapy agents without specifying dosage, timing, route, schedule, or a specific therapeutic adjustment dictated by the recited biomarker levels.
Applicant’s arguments do not address the fundamental deficiency identified in the updated rejection. As explained above, the claims do not require that any particular biomarker level or combination of biomarker levels result in any particular treatment selection, dosage adjustment, treatment modification, or therapeutic protocol. Rather, the claims broadly encompass continuing therapy or selecting a different treatment regimen without requiring a specific biomarker-directed treatment application across the full scope of the claims. Accordingly, the claims do not integrate the recited judicial exception into a practical application.
Accordingly, Applicant’s amendments and arguments do not overcome the rejection under 35 U.S.C. §101. The rejection of claims 54, 55, 57, 58, 61, 62, 64, 66-68, and 70 under 35 U.S.C. §101 is maintained.
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.
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 17, 2026
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