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 .
The Amendments and Remarks filed 2/2/26 in response to the Office Action of 10/2/25 are acknowledged and have been entered.
Claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71,73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are pending.
Claims 1, 37, 38, 48, and 88 have been amended by Applicant.
Claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71,73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections Withdrawn
The rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn.
The rejection of claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71,73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, and 98 under 35 U.S.C. 101 is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claims 1, 2, 37-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are rejected under 35 U.S.C. 103(a) as being unpatentable over Hanash et al (WO 2018/148600 A1; 8/16/18) in view of Christians et al (The Oncologist, 2014, 19: 266-274).
Hanash et al teaches a method of determining the risk of a subject for harboring lung cancer comprising measuring the levels of markers CEA, CA125, CYFRA21-1, and Pro-SFTPB, or reporter molecules bound thereto in a biological subject obtained from a subject ([0040]-[0041], in particular). Hanash et al further teaches said method wherein the marker diacetylspermine (DAS) is also measured ([0010], in particular). Hanash et al further teaches said method wherein combined level of a panel comprising the markers CEA, CA125, CYFRA21-1, and Pro-SFTPB classifies the subject as being at risk for harboring lung cancer when the combined level is elevated in the subject relative to a healthy subject that does not have lung cancer ([0033], in particular). Hanash et al further teaches said method wherein concentrations of the markers are measured/determined in a blood, plasma, or serum sample and at substantial the same time and compared to the prediction of a statistical model ([0046], in particular). Hanash et al further teaches said method wherein an alternate diagnostic test for that is an assay is administered for a subject assigned as having lung cancer ([0028], in particular). Hanash et al further teaches said method wherein the lung cancer is diagnosed at or before the borderline resectable stage, or at the resectable stage ([0033], in particular). Hanash et al further teaches said method wherein the amounts of the markers are detected using a solid bead ([0028], in particular). Hanash et al further teaches said method wherein the reporter molecules provide a detectable signal detectable by UV-visible spectroscopy ([0046], in particular). Hanash et al further teaches said method wherein the method further comprises comparing the amount of the markers with a cut-off value comprising an AUC (95% CI) of at least 0.83 ([0047], in particular). Hanash et al further teaches said method wherein a sample is obtained, the panel is measured, amounts of the biomarkers are determined, biomarker scores are summed to obtain a composite score for each subject, quantifying an increased risk for the presence of lung cancer for the subject as a risk score, wherein the composite score is matched to a risk category of a grouping of stratified subject populations, wherein each risk category comprises a multiplier indicating increased likelihood of having the lung cancer correlated to a range of composite scores as compared to use of a single threshold value, wherein the multiplier is determined from positive predictive scores of retrospective samples; and administering a computerized tomography (CT) scan or other imagine modality to the subject with a quantified increased risk for the presence of lung cancer based on both biomarker levels and imaging results ([0072], in particular). Hanash et al further teaches said method wherein a subject identified as having risk of lung cancer is administered chemotherapy, radiation, and surgery of instant claim 98 ([0033], in particular). Hanash et al further teaches said method wherein the subject is human ([0067], in particular).
Hanash et al does not specifically teach the method of determining risk of the subject for harboring lung cancer is performed with a subject having indeterminate pulmonary nodules wherein a sample is collected prior to diagnosis of lung cancer and/or wherein the method has sensitives/specificities and/or AUC as compared to a control recited by claim 85. However, these deficiencies are made up in the teachings of Christians et al.
Christians et al teaches diagnostic assays are performed on patients with indeterminate pulmonary nodules (left column on page 270, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the method of Hanash et al of determining the risk of a subject for harboring lung cancer wherein the sample is from just any subject prior to diagnosis that is suspected of having lung cancer, including a subject with indeterminate pulmonary nodules, wherein an elevated risk of lung cancer indicates the pulmonary nodules are malignant because the method of Hanash et al determines risk of a subject for harboring lung cancer, subjects with indeterminate pulmonary nodules would be suspected of having lung cancer, and a high risk of lung cancer would indicate pulmonary nodules are malignant lung cancer. Regarding the recited sensitives/specificities and/or AUC as compared to a control recited by claim 85, the method of Hanash et al has those sensitivities/specificities and/or AUC as compared to a control, depending on particular samples used to determine the sensitivities/specificities and depending on particular control. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 2/2/26, Applicant argues Chistian et al is drawn to pancreatic cancer and not lung cancer, Christians et al examines pulmonary nodules in evaluating metastatic cancer from another organ, Christians et al does not teach discriminating between benign nodules and cancer arising from lung cancer, and Christians et al does not suggest that pulmonary nodules be evaluated using biomarkers. Applicant further argues a lack of motivation to combine Hanash et al and Christians et al. Applicant further argues Christians et al teaches away from the claimed method by using CA19-9 as a biomarker to evaluate the status of pancreatic cancer and use visual imaging for pulmonary nodules implies the prior art did not recognize the possibility of a biomarker-based risk assessment method for pulmonary nodules. Applicant further indicates the claims are non-obvious because the claims are directed to a long-felt need to non-invasively monitor and assess risks associated with patients with indeterminate pulmonary nodules that is not currently addressed.
The amendments to the claims and the arguments found in the Reply of 2/2/26 have been carefully considered, but are not deemed persuasive. In regards to the arguments Christians et al is drawn to pancreatic cancer and not lung cancer, Christians et al examines pulmonary nodules in evaluating metastatic cancer from another organ, Christians et al does not teach discriminating between benign nodules and cancer arising from lung cancer, and Christians et al does not suggest that pulmonary nodules be evaluated using biomarkers, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The examiner agrees Christians is drawn to pancreatic cancer patients that have indeterminate pulmonary nodules, Christians et al examines pulmonary nodules in evaluating metastatic cancer from another organ, and Christians et al does not teach discriminating between benign nodules and cancer arising from lung cancer. Christians et al is cited that patients can have indeterminate pulmonary nodules. Sometimes those pulmonary nodules happen to be due to metastasis of a cancer other than lung cancer. The claims do not recite evaluating pulmonary nodules using biomarkers. The combined method is drawn to a method of determining the risk of a subject for harboring lung cancer wherein the sample is from just any subject prior to diagnosis that is suspected of having lung cancer, including a subject with indeterminate pulmonary nodules (which are “indeterminate”). Such indeterminate pulmonary nodules can be due to metastatic pancreatic cancer, as what appears to be the case in Christians et al. Alternatively, they may be benign or malignant from lung cancer.
In regards to the arguments Christians et al teaches away from the claimed method by using CA19-9 as a biomarker to evaluate the status of pancreatic cancer and use visual imaging for pulmonary nodules implies the prior art did not recognize the possibility of a biomarker-based risk assessment method for pulmonary nodules and that the claims are non-obvious because the claims are directed to a long-felt need to non-invasively monitor and assess risks associated with patients with indeterminate pulmonary nodules that is not currently addressed, the examiner disagrees. Christians in no way teaches against the claimed method. Further, the prior art does teach using biomarkers (including CEA and CYFRA21-1) to differentiate benign from malignant indeterminate pulmonary nodules (see “pulmonary node classifier” discussed in the abstract and first full paragraph at left column on page 2 of Birse et al (Clin Proteom, 2017, 14(25): 1-9; 2/2/26 IDS); see nodule model discussed at Abstract and Patient Selection at right column on page 263 of Yang et al (Cancer, 2018, 124(2): 262-270)).
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 36-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hanash et al (WO 2018/148600 A1; 8/16/18) in view of Christians et al (The Oncologist, 2014, 19: 266-274) as applied to claims 1, 2, 37-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 above, and further in view of Zhang et al (Oncology Letters, 2017, 13: 669-676), Sanfiorenzo et al (PLOS ONE, 2013, 8(1)(e54596):1-8), Etzioni et al (Nature Reviews, 2003, 3: internet pages 1-10), and Mercer (Immunol Ser, 1990, 53: 39-54).
Teachings of Hanash et al and Christians et al are discussed above.
Hanash et al and Christians et al do not specifically teach measuring levels of miR-320, miR-210, and miR-21. However, these deficiencies are made up in the teachings of Zhang et al, Sanfiorenzo et al, Etzioni et al, and Mercer.
Zhang et al teaches miR-21 levels are increased and miR-210 levels are reduced in plasma samples from patients with NSCLC as compared to controls (Table III, in particular).
Sanfiorenzo et al teaches miR-320-3p (a “miR-320”) levels are increased in plasma samples from patients with NSCLC as compared to controls (left column on page 3, in particular).
Etzioni et al teaches motivation for early detection of tumor markers in order to detect tumors before they spread and become incurable (page 1 and Table 1, in particular). Etzioni et al further teaches that the power of combining multiple tumor markers for diagnosis to improve specificity and sensitivity has been known in the art (Box 2, in particular). Mercer teaches that the use of multiple markers to create a panel of tumor markers for diagnosis in order to improve sensitivity and specificity is known (page 39, in particular). Mercer teaches the use of multiple markers for cancer diagnosis is known and provides significant gains in sensitivity for diagnosis (page 43, in particular). Therefore, methods using multiple markers gain the advantages of early diagnosis, increased sensitivity and increased specificity of diagnosis.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Hanash et al and Christians et al wherein the markers of Zhang et al and Sanfiorenzo et al (miR-21, miR-210, and miR-320-3p) are measured alongside the markers of the combined method because levels of all the markers are indicative of lung cancer and such a combination is merely a "predictable use of prior art elements according to their established functions." KSR, 550 U.S. at 417. Further, in a non-precedential decision involving analogous claims that the BPAI found obvious, the BPAI stated that “…the ordinary artisan would have been motivated to test multiple proteins in order to confirm the diagnosis based on a single protein. Such a combination is merely a “predictable use of prior art elements according to their established functions.”…” (see page 14 of Appeal No 2012008274). Further, in another non-precedential decision involving analogous claims that the BPAI found obvious, the BPAI acknowledges Mercer teaches that “the use of multiple markers for cancer diagnosis provides significant gains in sensitivity for diagnosis” provides a reason to have use a combination of known markers and that Mercer teaches it was known in the art that utilizing more than one marker for diagnostic detection increases sensitivity (see Appeal 2018-008269). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 2/2/26, Applicant repeats arguments addressed above.
Claim Rejections - 35 USC § 101
Claim 100 remains rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) (i.e., a law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. The rationale for this determination is explained below:
Claim 100 is directed to natural phenomenon because the claims recite natural phenomenon (“Step 2A prong one”) and the judicial exception(s) is/are not integrated into a practical application (“Step 2A prong two”). The “natural phenomenon” is: levels of recited markers in a biological sample from a subject are indicative of lung cancer risk. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception(s). A claim that focuses on judicial exception(s) can be shown to recite something “significantly more” than the judicial exception(s) by reciting a meaningful limitation beyond the judicial exceptions. However, in the instant case, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (when considered both individually and as an ordered combination) are limited to well-understood, routine and conventional steps of obtaining a biological sample from a subject and detecting known markers by conventional methods in the sample and administering “a treatment for lung cancer” to a subject with lung cancer (“Step 2B”). It is noted claim 100 recites a treatment step; however, the treatment step is generic and does not require any particular treatment and is equivalent to an “apply it” step (see MPEP 2106.04(d)(2)). Therefore, the treatment step of claim 100 does not integrate the judicial exception(s) into a practical application. MPEP 2106.04(d)(2) indicates a claim reciting a judicial exception is not directed to a judicial exception if it also recites additional elements(s) demonstrating the claim as a whole integrates the exception into a practical application by using recited judicial exceptions to effect a particular treatment or prophylaxis that has more than a nominal or insignificant relationship to the exception(s) (see aspirin example under “Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)” at MPEP 2106.04(d)(2)). In the instant situation, there is not more than a “nominal or insignificant relationship” between levels of recited markers in a biological sample from a subject are indicative of lung cancer risk (judicial exception) and the step of administering just any treatment for lung cancer.
Well-understood, routine and conventional limitations are not meaningful limitations and are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see Part I.B.1 of the interim Guidance).
MPEP 2106.05(d)(II) provides a non-limiting list of laboratory techniques recognized by courts as well-understood, routine, conventional activity. These techniques include:
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);
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Here, the claim does not contain any significant additional elements or steps beyond the observation of judicial exception(s) present when performing routine and conventional methods. Further, the active method steps are conventional and routine in the art for the reasons stated above and the claim does not amount to significantly more than the judicial exception(s). Further, just as methods comprising detecting paternal DNA sequences in particular samples by PCR was identified in Ariosa v. Sequenom as "well-known, routine, and conventional" (see first paragraph on page 13 of Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015)) even though the prior art did not demonstrate detecting said paternal DNA sequences in said particular samples by PCR, the methods encompassed by the instant claims are well-known, routine, and conventional. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of detecting expression and administering just any treatment) are routinely performed in the art to obtain data regarding expression and treat subjects. Moreover, “[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility…." Ariosa Diagnostics, Inc., v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015), cert. denied, No. 15-1182, 2016 WL 1117246 (U.S. June 27, 2016). Further, “Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2117 (2013). The claim does not recite something “significantly more” than the judicial exception(s); rather, the claim “simply informs” the natural phenomenon to one performing routine active method steps and does not amount to significantly more than the judicial exception(s).
Response to Arguments
In the Reply of 2/2/26, Applicant indicates claim 100 should be patent eligible because the claim recites both a diagnosis and treatment step.
The amendments to the claims and the arguments found in the Reply of 2/2/26 have been carefully considered, but are not deemed persuasive. It is acknowledged claim 100 recites a treatment step; however, the treatment step is generic and does not require any particular treatment and is equivalent to an “apply it” step (see MPEP 2106.04(d)(2)). Therefore, the treatment step of claim 100 does not integrate the judicial exception(s) into a practical application. MPEP 2106.04(d)(2) indicates a claim reciting a judicial exception is not directed to a judicial exception if it also recites additional elements(s) demonstrating the claim as a whole integrates the exception into a practical application by using recited judicial exceptions to effect a particular treatment or prophylaxis that has more than a nominal or insignificant relationship to the exception(s) (see aspirin example under “Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)” at MPEP 2106.04(d)(2)). In the instant situation, there is not more than a “nominal or insignificant relationship” between levels of recited markers in a biological sample from a subject are indicative of lung cancer risk (judicial exception) and the step of administering just any treatment for lung cancer. Further, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements (common methods of detecting expression and administering just any treatment) are routinely performed in the art to obtain data regarding expression and treat subjects.
Double Patenting
Claims 1, 2, 37-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12405274 B2 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274). The patent claims do not specifically recite the method of treating determining risk of the subject for harboring lung cancer is performed with a subject having indeterminate pulmonary nodules wherein a sample is collected prior to diagnosis of lung cancer and/or wherein the method has sensitives/specificities and/or AUC as compared to a control recited by claim 85. However, these deficiencies are made up in the teachings of Hanash et al and Christians et al.
Teachings of Hanash et al and Christians et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the patented method comprising the method of Hanash et al of determining the risk of a subject for harboring lung cancer wherein the sample is from just any subject prior to diagnosis that is suspected of having lung cancer, including a subject with indeterminate pulmonary nodules, wherein an elevated risk of lung cancer indicates the pulmonary nodules are malignant because the method of Hanash et al determines risk of a subject for harboring lung cancer, subjects with indeterminate pulmonary nodules would be suspected of having lung cancer, an a high risk of lung cancer would indicate pulmonary nodules are malignant and not benign. Regarding the recited sensitives/specificities and/or AUC as compared to a control recited by claim 85, such a method has those sensitivities/specificities and/or AUC as compared to a control, depending on particular samples used to determine the sensitivities/specificities and depending on particular control.
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Double Patenting
Claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12405274 B2 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274), as applied above, and in further view of Zhang et al (Oncology Letters, 2017, 13: 669-676), Sanfiorenzo et al (PLOS ONE, 2013, 8(1)(e54596):1-8), Etzioni et al (Nature Reviews, 2003, 3: internet pages 1-10), and Mercer (Immunol Ser, 1990, 53: 39-54).
Obvious methods of the patent claims in combination with Hanash et al and Christians et al are discussed above.
The patent claims, Hanash et al, and Christians et al do not specifically teach measuring levels of miR-320, miR-210, and miR-21. However, these deficiencies are made up in the teachings of Zhang et al, Sanfiorenzo et al, Etzioni et al, and Mercer.
Zhang et al teaches miR-21 levels are increased and miR-210 levels are reduced in plasma samples from patients with NSCLC as compared to controls (Table III, in particular).
Sanfiorenzo et al teaches miR-320-3p (a “miR-320”) levels are increased in plasma samples from patients with NSCLC as compared to controls (left column on page 3, in particular).
Etzioni et al teaches motivation for early detection of tumor markers in order to detect tumors before they spread and become incurable (page 1 and Table 1, in particular). Etzioni et al further teaches that the power of combining multiple tumor markers for diagnosis to improve specificity and sensitivity has been known in the art (Box 2, in particular). Mercer teaches that the use of multiple markers to create a panel of tumor markers for diagnosis in order to improve sensitivity and specificity is known (page 39, in particular). Mercer teaches the use of multiple markers for cancer diagnosis is known and provides significant gains in sensitivity for diagnosis (page 43, in particular). Therefore, methods using multiple markers gain the advantages of early diagnosis, increased sensitivity and increased specificity of diagnosis.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of the patent claims, Hanash et al, and Christians et al wherein the markers of Zhang et al and Sanfiorenzo et al (miR-21, miR-210, and miR-320-3p) are measured alongside the markers of the combined method because levels of all the markers are indicative of lung cancer and such a combination is merely a "predictable use of prior art elements according to their established functions."
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Double Patenting
Claims 1, 2, 37-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 237-257 of copending Application No. 16/484177 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274). The ‘177 claims do not specifically recite the method of treating determining risk of the subject for harboring lung cancer is performed with a subject having indeterminate pulmonary nodules wherein a sample is collected prior to diagnosis of lung cancer and/or wherein the method has sensitives/specificities and/or AUC as compared to a control recited by claim 85. However, these deficiencies are made up in the teachings of Hanash et al and Christians et al.
Teachings of Hanash et al and Christians et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the ‘177 method comprising the method of Hanash et al of determining the risk of a subject for harboring lung cancer wherein the sample is from just any subject prior to diagnosis that is suspected of having lung cancer, including a subject with indeterminate pulmonary nodules, wherein an elevated risk of lung cancer indicates the pulmonary nodules are malignant because the method of Hanash et al determines risk of a subject for harboring lung cancer, subjects with indeterminate pulmonary nodules would be suspected of having lung cancer, an a high risk of lung cancer would indicate pulmonary nodules are malignant and not benign. Regarding the recited sensitives/specificities and/or AUC as compared to a control recited by claim 85, such a method has those sensitivities/specificities and/or AUC as compared to a control, depending on particular samples used to determine the sensitivities/specificities and depending on particular control.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Double Patenting
Claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 237-257 of copending Application No. 16/484177 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274), as applied above, and in further view of Zhang et al (Oncology Letters, 2017, 13: 669-676), Sanfiorenzo et al (PLOS ONE, 2013, 8(1)(e54596):1-8), Etzioni et al (Nature Reviews, 2003, 3: internet pages 1-10), and Mercer (Immunol Ser, 1990, 53: 39-54).
Obvious methods of the ’177 claims in combination with Hanash et al and Christians et al are discussed above.
The ’177 claims, Hanash et al, and Christians et al do not specifically teach measuring levels of miR-320, miR-210, and miR-21. However, these deficiencies are made up in the teachings of Zhang et al, Sanfiorenzo et al, Etzioni et al, and Mercer.
Zhang et al teaches miR-21 levels are increased and miR-210 levels are reduced in plasma samples from patients with NSCLC as compared to controls (Table III, in particular).
Sanfiorenzo et al teaches miR-320-3p (a “miR-320”) levels are increased in plasma samples from patients with NSCLC as compared to controls (left column on page 3, in particular).
Etzioni et al teaches motivation for early detection of tumor markers in order to detect tumors before they spread and become incurable (page 1 and Table 1, in particular). Etzioni et al further teaches that the power of combining multiple tumor markers for diagnosis to improve specificity and sensitivity has been known in the art (Box 2, in particular). Mercer teaches that the use of multiple markers to create a panel of tumor markers for diagnosis in order to improve sensitivity and specificity is known (page 39, in particular). Mercer teaches the use of multiple markers for cancer diagnosis is known and provides significant gains in sensitivity for diagnosis (page 43, in particular). Therefore, methods using multiple markers gain the advantages of early diagnosis, increased sensitivity and increased specificity of diagnosis.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of the ’177 claims, Hanash et al, and Christians et al wherein the markers of Zhang et al and Sanfiorenzo et al (miR-21, miR-210, and miR-320-3p) are measured alongside the markers of the combined method because levels of all the markers are indicative of lung cancer and such a combination is merely a "predictable use of prior art elements according to their established functions."
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Double Patenting
Claims 1, 2, 37-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 1-8, 10, 13, 16, 24-30, 46, 47, and 49 of copending Application No. 19/206866 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274). The ‘177 claims do not specifically recite the method of treating determining risk of the subject for harboring lung cancer is performed with a subject having indeterminate pulmonary nodules wherein a sample is collected prior to diagnosis of lung cancer and/or wherein the method has sensitives/specificities and/or AUC as compared to a control recited by claim 85. However, these deficiencies are made up in the teachings of Hanash et al and Christians et al.
Teachings of Hanash et al and Christians et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the ‘177 method comprising the method of Hanash et al of determining the risk of a subject for harboring lung cancer wherein the sample is from just any subject prior to diagnosis that is suspected of having lung cancer, including a subject with indeterminate pulmonary nodules, wherein an elevated risk of lung cancer indicates the pulmonary nodules are malignant because the method of Hanash et al determines risk of a subject for harboring lung cancer, subjects with indeterminate pulmonary nodules would be suspected of having lung cancer, an a high risk of lung cancer would indicate pulmonary nodules are malignant and not benign. Regarding the recited sensitives/specificities and/or AUC as compared to a control recited by claim 85, such a method has those sensitivities/specificities and/or AUC as compared to a control, depending on particular samples used to determine the sensitivities/specificities and depending on particular control.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Double Patenting
Claims 1, 2, 36-41, 48, 50, 53, 56, 64, 71, 73, 75, 76, 78, 81, 85, 88-90, 92, 94, 95, 98, and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 1-8, 10, 13, 16, 24-30, 46, 47, and 49 of copending Application No. 19/206866 in view of Hanash et al (WO 2018/148600 A1; 8/16/18) and Christians et al (The Oncologist, 2014, 19: 266-274), as applied above, and in further view of Zhang et al (Oncology Letters, 2017, 13: 669-676), Sanfiorenzo et al (PLOS ONE, 2013, 8(1)(e54596):1-8), Etzioni et al (Nature Reviews, 2003, 3: internet pages 1-10), and Mercer (Immunol Ser, 1990, 53: 39-54).
Obvious methods of the ’177 claims in combination with Hanash et al and Christians et al are discussed above.
The ’177 claims, Hanash et al, and Christians et al do not specifically teach measuring levels of miR-320, miR-210, and miR-21. However, these deficiencies are made up in the teachings of Zhang et al, Sanfiorenzo et al, Etzioni et al, and Mercer.
Zhang et al teaches miR-21 levels are increased and miR-210 levels are reduced in plasma samples from patients with NSCLC as compared to controls (Table III, in particular).
Sanfiorenzo et al teaches miR-320-3p (a “miR-320”) levels are increased in plasma samples from patients with NSCLC as compared to controls (left column on page 3, in particular).
Etzioni et al teaches motivation for early detection of tumor markers in order to detect tumors before they spread and become incurable (page 1 and Table 1, in particular). Etzioni et al further teaches that the power of combining multiple tumor markers for diagnosis to improve specificity and sensitivity has been known in the art (Box 2, in particular). Mercer teaches that the use of multiple markers to create a panel of tumor markers for diagnosis in order to improve sensitivity and specificity is known (page 39, in particular). Mercer teaches the use of multiple markers for cancer diagnosis is known and provides significant gains in sensitivity for diagnosis (page 43, in particular). Therefore, methods using multiple markers gain the advantages of early diagnosis, increased sensitivity and increased specificity of diagnosis.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of the ’177 claims, Hanash et al, and Christians et al wherein the markers of Zhang et al and Sanfiorenzo et al (miR-21, miR-210, and miR-320-3p) are measured alongside the markers of the combined method because levels of all the markers are indicative of lung cancer and such a combination is merely a "predictable use of prior art elements according to their established functions."
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 2/2/26, Applicant repeat arguments addressed above.
Conclusion
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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/SEAN E AEDER/Primary Examiner, Art Unit 1642