DETAILED ACTION
Applicant’s response, filed 22 July 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
References to Applicant’s specification are made with respect to the published version.
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
Claims 1-2 are cancelled.
Claims 4-18 are newly added.
Claims 3-18 are pending.
Claims 3-18 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application, U.S. Provisional App. No. 63/033,192 filed 01 June 2020 and PCT/US21/35251 filed 01 June 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Accordingly, the effective filing date of the claimed invention is 01 June 2020.
Drawings
The objection to the drawings in the previous Office action has been withdrawn in view of the replacement drawings filed 22 July 2026.
The drawings filed 22 July 2026 are accepted.
Specification
The objection to the specification in the previous Office action has been withdrawn in view of the amendments to the specification filed 22 July 2026.
Claim Objections
The objection to claims 2-3 in the previous Office action has been withdrawn in view of the claim amendments and cancellations received 22 July 2026.
Claim Interpretation
Claims 6-9 recite “about” with respect to the time interval. Applicant’s specification at para. [0037] defines the term “about” to refer to an amount that is approximately, nearly, almost, or in the vicinity of being equal to or is equal to a stated amount, e.g., the state amount plus/minus about 5%, about 4%, about 3%, about 2% or about 1%. Therefore “about” is interpreted to mean plus/minus 5%.
Claim 16 recites “wherein the trained machine learning software is selected based on the gender of the human subject”. The limitation regarding how the machine learning software is selected is interpreted as a product by process limitation that defines the process in which the machine learning software was previously selected. However, the claims do not recite a step of selecting the trained machine learning software based on the gender of the human subject. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. See MPEP 2113 I.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-2 under 35 U.S.C. 112(b) in the previous Office action has been withdrawn in view of the cancellation of these claims received 22 July 2026.
The rejection of claim 3 under 35 U.S.C. 112(b) in the previous Office action has been withdrawn in view of claim amendments received 22 July 2026.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 11-12 and 14-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection is newly recited and necessitated by claim amendment.
Claims 11-12 are indefinite for recitation of “…wherein…the at least two markers are selected from AFP, CEA, CA19-9, CYFRA21-1, SCC, and PSA” and “…wherein…the at least two markers are selected from AFP, CEA, CA19-9, CYFRA21-1, SCC, CA125, and CA15-3”, respectively. However, claim 3, from which claim 3 depends recites “at least two markers in the sample, wherein said markers are selected from the group consisting of CEA, AFP, CA125, CA15-3, CA19-9, Cyfra, and PSA”. The list of markers recited in claims 11-12 includes markers that were not recited in the closed set of markers recited in claim 3, including “SCC” and “CYFRA21-1”. As a result, it is not clear if the set of markers is closed to unrecited elements or open to unrecited elements. If Applicant intends for the limitation to be open to unrecited elements, then the Markush group is indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022). See MPEP 2173.05(h).
Claim 14, and claim(s) dependent therefrom, are indefinite for recitation of “The method of claim 3, wherein the cancer likelihood score is a probability value and a threshold is set to separate human subjects into a low or non-risk category from an increased risk category”. Examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: (B) "wherein" clauses. See MPEP 2111.04. In the instant case, it is not clear if the wherein clause pertaining to a “a threshold is set to separate...” is merely expressing an intended result or use of the probability value, or if the claims intend to further require a step of setting a threshold for separating. Claim 15 recites “…wherein the increased risk category is further subdivided into…”, which is indefinite for the same reasons applied to claim 14 above regarding the limiting effect of the wherein clause being unclear. Furthermore, even if claim 14 required a step of setting the threshold, the limitation “to separate…from an increased risk category” is merely an intended use of the threshold; as a result, it is similarly unclear if the wherein clause of claim 15 is merely an intended use of the probability value or threshold, or if the claim intends to require a step of subdividing. Clarification is requested via claim amendment. For purpose of examination, the wherein clause pertaining to “a threshold is set” is interpreted as an intended use of the probability value. See MPEP 2111.04 I. stating a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. If Applicant intends to require a step of setting a threshold, claim 14 should recite “The method of claim 14, wherein the cancer likelihood score is a probability value and further comprising setting a threshold to separate…”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11-12 and 15 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This rejection is newly recited and necessitated by claim amendment.
Claims 11-12 recite “…wherein…the at least two markers are selected from AFP, CEA, CA19-9, CYFRA21-1, SCC, and PSA” and “…wherein…the at least two markers are selected from AFP, CEA, CA19-9, CYFRA21-1, SCC, CA125, and CA15-3”, respectively. However, claim 3, from which claim 3 depends recites “at least two markers in the sample, wherein said markers are selected from the group consisting of CEA, AFP, CA125, CA15-3, CA19-9, Cyfra, and PSA”. Therefore, claims 11-12 no longer require the at least two markers are selected from the closed group of CEA, AFP, CA125, CA15-3, CA19-9, Cyfra, and PSA, given “SCC” and “CYFRA21-1” are not in the closed group of claim 3.
Claim 15 recites “wherein the increased risk category is further subdivided into a mild, moderate, and/or high-risk category”. Claim 14, from which claim 15 depends, does not require setting a threshold or separating human subjects, and instead this limitation is interpreted as an intended use of the probability value or threshold as set forth above under 35 U.S.C. 112(b). Therefore, claim 15 fails to further limit the claimed subject matter of claim 14, from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
The rejection of claims 1-2 under 35 U.S.C. 101 in the previous Office action has been withdrawn in view of the cancellation of these claims received 22 July 2026.
Claim Rejections - 35 USC § 102
The rejection of claim 1 under 35 U.S.C. 102(a)(1) as being anticipated by Cohen (2018) in the previous Office action has been withdrawn in view of the cancellation of this claim received 22 July 2026.
Claim Rejections - 35 USC § 103
The rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Hori (2017) in view of Cohen (2018) in the previous Office action has been withdrawn in view of the cancelation of this claim received 22 July 2026.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3-4 and 6-18 are rejected under 35 U.S.C. 103 as being unpatentable over Cohen (2018) in view of Hori (2017). Any newly recited portion is necessitated by claim amendment.
Cited references:
Cohen at al. US 2018/0068083 A1; cited in IDS filed 03 Aug. 2024 (previously cited); and
Hori et al., A Model-Based Personalized Cancer Screening Strategy for Detecting Early-Stage Tumors Using Blood-Borne Biomarkers, 2017, Cancer Res, 77(1), pg. 2570-2584 (previously cited).
Regarding claim 3, Cohen discloses a method for predicting the risk of having cancer using measured biomarkers (Abstract), comprising the following steps:
Cohen discloses a) obtaining a blood sample from a human subject ([0035]; [0063], e.g. human subject).
Cohen discloses b) measuring a panel of at least two biomarkers from the blood, wherein the biomarkers may be any two or more biomarkers selected from: CEA, AFP, CA125, CA15-3, CA19-9, CYFRA, and PSA ([0003]; [0024]).
Cohen discloses c) providing a machine learning classifier ([0025]), wherein the classifier is generated (i.e. trained) using data comprising measured biomarkers and clinical factors of retrospective training patients in addition to a diagnostic indicator of whether the patient has been diagnosed (i.e. individuals previously tested with the marker panel and for which cancer outcomes are known ([0018]; [0062]).
Cohen discloses d) generating a cancer risk score indicating a likelihood of having cancer for the subject ([0024]; [0062]).
Cohen discloses e) using the risk score to recommend a subject for follow-up testing ([0029]; [0035]).
Cohen discloses f) performing serial testing on the markers (i.e. a second blood sample is obtained) ([0024], e.g. biomarkers are from blood; [0030], e.g. serial testing).
Cohen discloses g) determining a biomarker change over time following the serial testing (i.e. markers are re-measured and changes compared between the first and second samples) ([0030]).
Regarding claim 3, Cohen does not disclose the following limitations:
Regarding claim 3, while Cohen uses the likelihood score to recommend follow-up testing, Cohen does not disclose e) using the score to calculate the optimal time interval when at least two markers should be re-measured in a second blood sample from the human subject.
Cohen further does not disclose f) the second blood sample is obtained based on said time interval.
However, Hori discloses a method for developing a personalized cancer screening strategy (Abstract), which comprises determining a number of tumor cells in a patient indicative of tumor presence if the number is greater than 0 and an associated growth rate of the tumor cell population, calculated based on a subject’s biomarker profile determined from a blood sample (pg. 2579, col. 1, para. 4) (pg. 2575, col. 2, para. 3 to pg. 1576, col. 1, para. 1). Hori further discloses using the blood biomarker levels over time to monitor an aggressiveness of a tumor (i.e. a risk score) in terms of the time required for the tumor to become imaging detectable (pg. 2579, col. 2, para. 3; pg. 2580, col. 1, para. 1; Figures 5-6). Hori discloses using the determined aggressiveness to implement alternative patient-specific blood sampling schedules in which additional blood samples may taken more frequently for biomarker measurements (i.e. a risk of cancer is used to identify an optimal time interval for re-measuring biomarkers) (pg. 2582, col. 1, para. 1 to col. 2, para. 1; Supplementary Fig. S1). Hori further discloses that the implementation of patient-specific blood sampling schedules makes it less likely that the blood sampling history will misrepresent true tumor growth (pg. 2582, col. 2, para. 1 to pg. 2583, col. 1, para. 1).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Cohen to have used the cancer likelihood score to determine an optimal time interval when biomarkers should be remeasured, as shown by Hori, discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Cohen and Hori in order to implement patient-specific blood sampling schedules that are less likely to misrepresent true tumor growth, as shown by Hori (pg. 2582, col. 2, para. 1 to pg. 2583, col. 1, para. 1). This modification would have had a reasonable expectation of success because Cohen also determines a risk of cancer using biomarker velocity representing a biomarker change over time ([0030]; [0197]), such that the model for monitoring biomarker levels over time of Hori is applicable to Cohen.
Regarding the dependent claims:
Regarding claim 4, Cohen discloses the cancer is breast cancer ([0026]).
Regarding claims 6-9, Cohen in view of Hori make obvious determining an optimal time interval for when the biomarkers should be remeasured, as applied to claim 3 above. However, Cohen in view of Hori do not explicitly disclose the optimal time interval for re-measuring the panel of markers is about two to four months, about two to size months, about once a month, or about six to 12 months, as respectively recited in claims 6-9.
However, as discussed above, Hori discloses using the blood biomarker levels over time to monitor an aggressiveness of a tumor (i.e. a risk score) in terms of the time required for the tumor to become imaging detectable (pg. 2579, col. 2, para. 3; pg. 2580, col. 1, para. 1; Figures 5-6), and then using the determined aggressiveness to implement alternative patient-specific blood sampling schedules in which additional blood samples may taken more frequently for biomarker measurements when cancer is detected (i.e. a risk of cancer is used to identify an optimal time interval for re-measuring biomarkers) (pg. 2582, col. 1, para. 1 to col. 2, para. 1; pg. 2583, col. 1, para. 2; Supplementary Fig. S1). Hori further discloses it is important to minimize intervention on slow growing tumors that may never pose a threat during a patient’s lifetime (pg. 2570, col. 2, para. 1). Hori further discloses that the implementation of patient-specific blood sampling schedules makes it less likely that the blood sampling history will misrepresent true tumor growth (pg. 2582, col. 2, para. 1 to pg. 2583, col. 1, para. 2).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have re-measured the panel of markers at a time interval of two to four months, about two to size months, about once a month, or about six to 12 months through routine experimentation of the frequency of blood samples within the prior art conditions of increasing or decreasing the frequency of blood samples if a tumor is aggressive or less aggressive, respectively to accurately represent true tumor growth and minimize interventions on slow growing tumors, as shown by Hori (pg. 2570, col. 2, para. 1; pg. 2852, col. 1, para. 1 to pg. 2583, col. 1, para. 1; Supplementary Fig. S1). See MPEP 2144.05 II. A.
Regarding claim 10, Cohen discloses d) providing a notification of a recommendation of diagnostic testing of a radiographic screening when the patient is classified into the category indicative of a likelihood of having cancer ([0022], e.g. risk score provided to the user and notification recommending diagnostic testing), and then obtaining test results from the diagnostic testing to confirm or deny the presence of cancer (i.e. the confirmatory diagnostic test is administered) ([0023]).
Regarding claims 11-12, Cohen discloses b) measuring a panel of at least two biomarkers from the blood, wherein the biomarkers may be any two or more biomarkers selected from: CEA, AFP, CA125, CA15-3, CA19-9, CYFRA, and PSA ([0003]; [0024]), and discloses that the subject is a human subject ([0063]), such that the human subject is inherently either male or female. Accordingly, Cohen discloses measuring CEA, AFP, and CA19-9 in both female and male subjects.
Regarding claims 13-14¸ Cohen discloses the cancer risk score indicating a likelihood of having cancer comprises a probability value ([0463]; [0465]; FIG. 20)
Regarding claim 15, the claim fails to further limit the subject matter of claim 14, from which it depends, and therefore is rejected for the same reasons discussed above for claim 14.
Regarding claim 16¸ the process in which the trained machine learning software was previously selected is a product by process limitation, and the machine learning classifier of Cohen is the same as in the claims, as applied to claim 1 above. Therefore, Cohen discloses this limitation. Regardless, Cohen discloses the machine learning classifier is generated (i.e. selected) using data comprising measured biomarkers and clinical factors of retrospective training patients in addition to a diagnostic indicator of whether the patient has been diagnosed (i.e. individuals previously tested with the marker panel and for which cancer outcomes are known ([0018]; [0025]; [0062]). Cohen discloses the clinical factors include the gender of the patients ([0024]; [0202]), such that the trained machine learning model was selected based on the gender of the human subject.
Regarding claim 17, Cohen discloses d) providing a notification of a recommendation of diagnostic testing of a radiographic screening when the patient is classified into the category indicative of a likelihood of having cancer ([0022], e.g. risk score provided to the user and notification recommending diagnostic testing), and then obtaining test results from the diagnostic testing to confirm or deny the presence of cancer (i.e. confirmatory cancer diagnostic) ([0023]).
Regarding claim 18, Cohen discloses the confirmatory cancer diagnostic is radiographic screening ([0022]-[0023])
Therefore, the invention is prima facie obvious.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Cohen in view of Hori, as applied to claim 3 above, and further in view of Ramaswamy (2001). This rejection is newly recited and necessitated by claim amendment.
Cited reference: Ramaswamy et al., Multiclass cancer diagnosis using tumor gene expression signatures, 2001, PNAS, 98(26) pg. 15149-15154 (newly cited).
Regarding claim 5, Cohen in view of Hori disclose the method of claim 3, as applied above.
Further regarding claim 5, Cohen in view of Hori, as applied to claim 3 above, do not disclose identifying three possible organ systems for origin of the cancer.
However, Ramaswamy discloses a method for multiclass cancer diagnosis for classifying a cancer according to its tissue of origin (Abstract), which comprises inputting gene expression data of genes into a multiclass classification model, which then outputs a confidence score for each of 14 different cancer types indicating possible tumor of origins for the cancer, including breast, prostate, lung, ovarian, etc. (i.e. three organ systems) (Fig. 1-2; pg. 15150, col. 2, para. 5). Ramaswamy further discloses that optimal treatment of patients with cancer depends on establishing an accurate cancer diagnosis (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have modified the method of Cohen in view of Hori to have further determined three possible organ systems for origin of the cancer, as shown by Ramaswamy above. One of ordinary skill in the art would have been motivated to combine Cohen in view of Hori with Ramaswamy in order to accurately diagnosis a patient’s cancer, thus facilitating optimal treatment of the patient, as shown by Ramaswamy (Abstract). This modification would have had a reasonable expectation of success because Cohen classifies a likelihood of a patient having cancer, and thus the tumor of origin classification of Ramaswamy is applicable to the method of Cohen.
Therefore, the invention is prima facie obvious.
Response to Arguments
Applicant's arguments filed 22 July 2026 regarding 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant remarks the rejection is traversed because the Cohen reference is disqualifies as prior art under 35 U.S.C. 102(b)(2) because Cohen and the claimed invention were both under an obligation of assignment to 2020 GeneSystems Inc. at the time of the effective filing date of the claimed invention (Applicant’s remarks at pg. 5, para. 9 to pg. 6, para. 3).
This argument is not persuasive because Cohen was published in 2018, greater than one year before the effective filing date of the claimed invention, and therefore qualifies as prior art under 35 U.S.C. 102(a)(1). The exception under 35 U.S.C. 102(b)(2) cited by Applicant states “A disclosure shall not be prior art to a claimed invention under subsection (a)(2) if—…..(C) the subject matter disclosed and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. This exception does not apply to prior art under 35 U.S.C. 102(a)(1), such as Cohen.
Conclusion
No claims are allowed.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAITLYN L MINCHELLA whose telephone number is (571)272-6485. The examiner can normally be reached 7:00 - 4:00 M-Th.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
