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 . 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 12/17/2025 has been entered.
Priority
The instant application is a 371 of PCT/US21/12892 filed on 01/11/2021, which claims domestic priority to US provisional application no. 62/959,914 filed on 01/11/2020.
Status of the Claims
The claim amendments and remarks filed on 12/17/2025 is acknowledged. Claim 25 is amended. Claims 1-24, 26, and 31-41 are cancelled. Claims 50-55 are newly added.
Accordingly, claims 25, 27-30, and 42-55 are pending and being examined on the merits herein.
Withdrawn Rejections
The 35 USC 103 rejections over US’406 in view of Clapper for claims 25-28 and 43-47, over US’406 in view of Clapper and Anonymous for claims 29-30, and over US’406 in view of Clapper and Ha for claims 48-49 are withdrawn in view of the removal the CYP1B1 or dual CYP1A1/CYP1B1 inhibitor recited in instant claim 25, which has changed the scope of the claims.
The nonstatutory double patenting rejections over US Pat. No. 9,101,603 in view of Clapper and US’406 for claims 25-26 and 43-47, over US Pat. No. 9,101,603 in view of Clapper, US’406, and Anonymous for claims 25 and 29-30, and over US Pat. No. 9,101,603 in view of Clapper, US’406, and Ha for claims 25 and 48-49 are withdrawn in view of the removal of the CYP1B1 or dual CYP1A1/CYP1B1 inhibitor recited in instant claim 25, which has changed the scope of the claims.
The following grounds of rejections are new as necessitated by Applicant’s amendment to the
claims.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 25, 27-30, and 42-53 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 25 and 52 recites “A method of treating a human having a high risk of developing a lung cancer event but who does not yet have lung cancer … wherein the lung cancer event is … having a lung cancer recurrence”
Claims 25 and 52 are indefinite because it is unclear if the recited patient is someone who must have never had lung cancer before or someone who does not currently have lung cancer.
Furthermore, if the patient is interpreted as never having lung cancer before, then claims 25 and 52 are also indefinite because it is not possible for the patient to be at risk of developing a lung cancer recurrence, since a lung cancer recurrence means the patient previously had lung cancer.
For purposes of examination, claims 25 and 52 are being interpreted as a patient having a high risk of developing a lung cancer recurrence but who does not currently have lung cancer.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 25, 27-28, 42-44, 46-47, 50-51, and 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023) in view of Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025).
Peng discloses a study to assess the ability of the human lung to metabolize estrogen and to determine if metabolism is altered either during lung tumorigenesis or by tobacco smoke, sex, or race/ethnicity (see last paragraph of Introduction section, left column page 2). Peng discloses that smoking tobacco continues to be a primary risk factor for lung cancer development, however the etiology of lung tumors that arise in never-smokers is much less clear (see left column page 1). Peng discloses that the percentage of never-smokers among women with lung cancer is much higher in Asia (60–80%) than in the US (15%) or Europe (20%) (see left column page 1), and that recent studies suggest that estrogen and progesterone play an important role in lung carcinogenesis (see right column page 1). Peng discloses that high levels of 4-OHEs, an estrogen metabolite, and less 2-hydroxylation (2-OHEs) of parent estrogens confer a higher risk of breast cancer, and that estrogen was also extensively metabolized in mouse lung to form 2-OHEs, 4-OHEs, and 2-OMEs (see left column page 2). Therefore, Peng suggests that elevated 4-hydroxlyation of estrogen (4-OHEs) in lung tumors, smokers, and Chinese American women may be associated with lung cancer and a target for preventive intervention / treatment of lung cancer (see left column page 2).
Peng examined the estrogen metabolites including 4-OHE1, 4-OHE2, 2-OHE1, and 2-OHE2 of bronchoalveolar cells isolated from normal and tumor tissue from various NSCLC patients (11 women, 5 men; 12 smokers and 4 never-smokers) (see left column page 2 and Table 1 on page 4). Peng found that among women, 4-hydroxylation (4-OHE1 and 4-OHE2 levels, the percentage of 4-OHEs and the ratio of 4-OHEs/2-OHEs) in normal lung tissue was increased significantly in normal lung tissue from current vs. never-smoking women (see Table 2 on page 5 and right column page 4 through left column page 5). Peng teaches that tobacco smoke induces a shift in estrogen metabolism towards a harmful pathway, which could contribute to lung carcinogenesis specifically in women (see left column page 7 through right column page 7). Peng further demonstrates in Figure 3B on page 7 that smoke exposure also elevated 4-hydroxlation in both lung tissue and matching urinary samples. Peng discloses that even though the urinary sample did not achieve significance, this was likely due to small sample size and cited to another study that also suggests that smoking induced an increase in 4-hydroxlyation of estrogen in the lung and present in urine samples (see right column page 7).
Peng also demonstrates in Figure 4 on page 8 that the ratio of 4-OHEs to 2-OHEs in urinary samples of healthy Chinese American never smoker women was higher than Caucasian American never-smoker women. Peng discloses that racial/ethnic differences in estrogen metabolism could result from race/ethnic group-specific polymorphisms in estrogen metabolizing genes as well as environmental exposures due to varying life styles (i.e. soy (phytoestrogen) intake and exposure to cooking oil fumes and/or secondhand smoke (see left column page 8).
Peng concludes that their data demonstrates a higher proportion of 4-OHEs and a shift from 2-hydrolxation to 4-hydroxlyation (higher 4-OHEs/2-OHEs ratio) in lung tumors (vs. paired normal tissue) and in urine sample from populations at higher risk for lung cancer, including current-smokers (vs never-smokers) and never-smoking Chinse American women (vs. Caucasian women) (see right column third paragraph page 8). Peng concludes that therapeutic interventions that inhibit production of 4-OHEs generation could confer protection from genotoxicity, and that establishment of a link between the causal effects of 4-OHEs and lung cancer will provide strong rationale for targeting the enzyme(s) responsible for their synthesis, a novel strategy for the prevention of this disease (see right column third paragraph page 8).
Even though Peng suggests treatment of a human having a higher risk of developing a lung cancer based on higher 4-OHEs to 2-OHEs ratios by therapeutic interventions that inhibit estrogen metabolite (4-OHEs) production, Peng does not disclose the administration of a therapeutic agent that inhibits estrogen production.
Weinberg discloses the use of aromatase inhibitors in human lung cancer therapy (see Abstract). Weinberg discloses that estrogen and estrogen receptors may have a role in lung cancer progression, and that this pathway may be promoted by tumor expression and the activity of aromatase, an estrogen synthase (see Abstract). Weinberg discloses that in view of the recent surge in female death rates from lung cancer, the potential role of both exogenous and endogenous estrogens in lung cancer development, especially adenocarcinoma in women, requires further investigation, and that estrogens contribute to differentiation and maturation in normal lung and also stimulate growth and progression of lung tumors (see left column page 11287). Weinberg discloses that aromatase, a cytochrome P450 enzyme complex, mediates synthesis of estrogens in lung tissues, and local production of estrogens in women and men could affect lung tumor progression in ER-expressing malignancies (see left column through right column page 11287).
Weinberg teaches that the majority of the lung tumors in their study was adenocarcinomas with the most common histologic type of lung cancer in young persons, women of all ages, and never smokers of both sexes (see left column through right column page 11291).
Weinberg demonstrates in Figure 1 on page 11288 and Figures 2-3 on page 11289 that aromatase was detected in NSCLC tumor specimens from the clinic and that significant activity of aromatase occurred in human NSCLC tumors, with enhanced levels in tumor cells compared with that in nearby normal cells. Weinberg demonstrates in Figure 4 on page 11290 that the aromatase inhibitor, anastrozole, blocks growth of lung tumor cells in vitro and human lung tumor xenografts in nude mice in vivo. Weinberg teaches that therapeutic targeting of lung cancer to block specific receptor pathways, such as estrogen signaling, may provide new options for patients afflicted with lung malignancies (see right column page 11291).
It would have been prima facie obvious before the effective filing date of the claimed invention to have administered to the patient populations of Peng at risk of developing NSCLC such as never-smoking or smoking women based on elevated 4-OHEs / 2-OHEs ratios from urine samples the aromatase inhibitor, anastrozole, as disclosed in Weinberg to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because both Peng and Weinberg teach that estrogen plays an important role in lung carcinogenesis, Peng suggests inhibiting the production of estrogen metabolites such as 4-OHEs as a therapeutic method to treat lung cancers, and Weinberg further demonstrates the effective use of anastrozole to treat lung cancers by inhibiting aromatase, an estrogen synthase. Therefore, an ordinary skilled artisan could have predictably administrated this compound of Weinberg to the patient populations of Peng with a reasonable expectation of success.
In regards to instant claim 27, as currently written, neither instant claims 27 nor 25 on which it depends require that the therapeutic agent be one that induces or restores COMT. Therefore, the combined teachings of Peng and Weinberg described above, which teaches administering an alternative therapeutic agent that inhibits estrogen production, meets the limitation of instant claim 27.
Claim(s) 29-30, 45, and 48-49 are rejected under 35 U.S.C. 103 as being unpatentable over Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023) in view of Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025), as applied to claim 25 above, and further in view of Kazmi et al. (Lung Cancer Manag., 2012 in PTO-892).
The combined teachings of Peng and Weinberg are as described above and teach the method of instant claim 25 as discussed above. Furthermore, Peng teaches that given the genotoxicity of 4-OHEs and the high frequency of acquired EGFR mutations in Asian women with lung cancer, it will be important to determine if 4-OHEs accelerate the rate of EGFR mutation.
The combined references, however, do not teach further administering to the human a tyrosine kinase inhibitor such as geftinib, further administering one of the limitations recited in instant claim 45 such as chemotherapy, and a human that has an estrogen-induced mutation in cancer drive genes such as EGFR.
Kazmi teaches the role of estrogen, progesterone, and aromatase in human non-small cell lung cancer (NSCLC) (see Abstract). Kazmi teaches that lung cancer is a leading cause of cancer-related deaths, and that patients have few effective therapeutic options and survival rates remain low (see Abstract). Kazmi teaches that hormones estrogen and progesterone play a key role in the progression of NSCLC, and that the aromatase enzyme, a key step in estrogen biosynthesis, elicits higher levels of estrogen in lung tumors as well as in metastases compared with nonmalignant tissues, thus could be a key biomarker for the treatment of NSCLC (see Abstract). Kazmi teaches that combination therapies that include estrogen receptor down regulators and aromatase inhibitors are currently being assessed in clinical trials among patients with advanced NSCLC (see Abstract). Kazmi teaches that tobacco smoking is a leading cause of lung cancer worldwide (second paragraph page 2). However, Kazmi teaches certain lung cancer types such adenocarcinoma have a weak relationship with tobacco use and was found to be more associated with nonsmokers, suggesting that other factors including EGFR mutations and EML4-ALK fusion gene may be involved in the etiology of this major subtype of NSCLC (second paragraph page 2).
Kazmi teaches that there is emerging evidence between possible interactions with sex steroid hormones and EGFR signaling in lung cancer (see first paragraph page 8). Kazmi teaches that activation of EGFR is observed when estrogen is depleted in the medium of NSCLC cells, and that activation of EGFR appears to promote increased levels of aromatase activity in lung tumors, leading to higher intratumoral levels of estrogen (see first paragraph page 8). Kazmi teaches that a combination therapy strategy to block both estrogen and EGFR signaling pathways can result in a more favorable anticancer therapy for NSCLC patients. Kazmi points to several studies that indicate so such as a combination therapy with an antiestrogen fulvestrant and the EGFR-TKI geftinib that was well tolerated by NSCLC patients in a recent clinical trial (see first paragraph page 8).
Kazmi also teaches that chemotherapeutics such as platinum-based and taxane-based agents to treat lung cancer may be suppressed by estradiol, which acts as a tumor survival factor (see first paragraph under Conclusions on page 8). Kazmi teaches that combination therapies with exemestane (an irreversible aromatase inhibitor) and cisplatin (standard chemotherapeutic agent in NSCLC) resulted in markedly increased antitumor activity in lung cancer xenograft studies in vivo, and that clinical trials are underway to initially investigate the utility of aromatase inhibitors combined with a platinum-based chemotherapy regimen for treating lung cancer (see first paragraph under Conclusions page 8).
It would have been prima facie obvious before the effective filing date of the claimed invention to have further administered to the patient population of the combined teachings of Peng and Weinberg as described above the geftinib of Kazmi and/or in combination with a chemotherapy such as cisplatin as disclosed in Kazmi to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because the combined teachings of Peng and Weinberg provide guidance of using aromatase inhibitors for treating the patient populations in Peng, and Kazmi provides guidance that aromatase inhibitors in combination with either geftinib or cisplatin is effective for treating the same NSCLC patient. Therefore, an ordinary skilled artisan could have predictably tried these combinations for the same patient populations described in the combined teachings of Peng and Weinberg described above with a reasonable expectation of success.
In regards to instant claims 48-49, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the patient population described in the combined teachings of Peng, Weinberg, and Kazmi described above to also have an EGFR mutation as suggested by Peng and Kazmi to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Peng provides guidance that EGFR mutations are common in Asian women with lung cancer and further contemplating the link between 4-OHEs and EGFR mutation, and Kazmi also suggests EGFR mutation as a major factor in the etiology of certain lung cancer such as adenocarcinoma and further establishes a link between estrogen and EGFR mutations in lung cancer patients with geftinib being effective for treating this patient population. Therefore, an ordinary skill artisan could have predictably considered treating patients who additionally have EGFR mutations with a reasonable expectation of success.
Claim(s) 52 is rejected under 35 U.S.C. 103 as being unpatentable over Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023) in view of Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025), as applied to claim 25 above, and further in view of Kazmi et al. (Lung Cancer Manag., 2012 in PTO-892) and Rodriguez-Lara et al. (J Thorac Dis., 2018 in PTO-892)
The combined teachings of Peng and Weinberg are as described above and teach the method of instant claim 25 as discussed above.
The combined references, however, do not teach wherein the cancer event is lung cancer recurrence.
The teachings of Kazmi are as described above
Rodriguez-Lara teaches the role of estrogen signaling in the pathogenesis of NSCLC (see Abstract). Rodriguez-Lara teaches that estrogen induces expression of pro-inflammatory proteins and ligands that promote tumor evasion, suggesting that estrogen might modify the microenvironment and anti-tumor immune response (see Abstract). Rodriguez-Lara teaches that an interaction between the epidermal growth factor receptor (EGFR) pathway and estrogen signaling in lung adenocarcinoma, therefore combined treatment based on tyrosine kinase inhibitors (TKIs) and antiestrogen therapy is beginning to be evaluated (see Abstract).
Rodriguez-Lara teaches that in a phase I clinical trial, gefitinib (EGFR-TKI) and fulvestrant (antiestrogen) co-treatment showed a good safety profile and significant anti-tumor activity in female patients with advanced or recurrent (stage IV) NSCLC, regardless of the prior lines of therapy they had received (see second paragraph right column page 490). Rodriguez-Lara teaches combined gefitinib and fulvestrant treatment causes a significant decrease in the proliferation of T790 NSCLC cells, compared with separated treatments and that a functional interaction between ERs and EGFR signaling pathways in a gefitinib-resistant cell line was observed. Therefore, this type of combined therapy strategies could be used in lung tumors with acquired resistance mutations.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further modified the combined teachings of Peng and Weinberg described above by identifying and treating patients at risk of having a recurrent cancer with EGFR mutation as disclosed in Kazmi and Rodriguez-Lara to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Kazmi establishes a link between estrogen and EGFR mutations in lung cancer patients with geftinib being effective for treating this patient population, and Rodriguez-Lara also establishes the same link and treatment being effective for a patient with recurrent NSCLC. Therefore, an ordinary skill artisan could have predictably considered treating recurrent lung cancer patients with a reasonable expectation of success.
Response to Arguments
Applicant’s arguments filed on 12/17/2025 have been fully considered in so far as they apply to
the rejections of the instant office action, but were not persuasive.
Applicant presents several arguments for the previous rejections over US’406 in view of Clapper for claims 25-28 and 43-47, over US’406 in view of Clapper and Anonymous for claims 29-30, and over US’406 in view of Clapper and Ha for claims 48-49. However, the new rejections do not cite any of these references, rendering Applicant’s arguments moot.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25, 27-28, 42-44, 46-47, 50-51, and 53-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,101,603 (‘603) in view of Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023) and Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025).
Claim 1 of ‘603 recites a method for reducing the risk of motility of premalignant cells of the lung, comprising a. isolating cells of the lung from a human subject; b. determining whether the cells are premalignant; c. if the isolated cells are premalignant, determining whether the level of mRNA encoding the cytochrome P450 1B1 (CYP1B1) protein or whether the level of the CYP1B1 protein is elevated in the isolated cells; d. if the level of mRNA encoding the CYP1B1 protein is elevated in the isolated cells, or if the level of CYP1B1 protein is elevated in the isolated cells, administering to the subject a flavonoid selected from the group consisting of hesperidin, hesperetin, diosmetin, diosmin, eriodictyol, and homoeriodictyol in an amount effective to inhibit the motility-promoting activity of CYP1B1 protein in premalignant cells of the lung in the subject, thereby reducing the risk that the premalignant cells will become motile. Claim 2 of ‘603 recites wherein the subject has smoked tobacco. Claim 4 of ‘603 recites wherein the premalignant cells of the lung are capable of transforming into a non-small cell lung cancer cell, a small cell lung cancer cell, a squamous cell carcinoma of the lung, an adenocarcinoma cell, an adenoma cell, or a bronchioalveolar carcinoma cell.
The difference between the claims of ‘603 and the claimed invention is that the claims of ‘603 do not recite treating a human that has a higher ratio of 4-OHEs to 2-OHEs compared to the same ratios from a cancer-free subject as well as administering an agent that inhibits estrogen production such as anastrozole.
The independent teachings of Peng and Weinberg are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the treatment method as recited in the claims of ‘603 for treating the patient populations of Peng at risk of developing NSCLC such as never-smoking or smoking women based on elevated 4-OHEs / 2-OHEs ratios from urine samples and further substituted the agent recited in the claims of ‘603 with the aromatase inhibitor, anastrozole, as disclosed in Weinberg to arrive at the claimed invention to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because the claims of ‘603 recite a method of treating a smoker patient who is at risk of developing NSCLC, and Peng also suggests treatment of a human having a higher risk of developing a lung cancer with both Peng and Weinberg providing further guidance that estrogen plays an important role in lung carcinogenesis. Furthermore, Peng suggests inhibiting the production of estrogen metabolites such as 4-OHEs as a therapeutic method to treat lung cancers, and Weinberg further demonstrates the effective use of anastrozole to treat lung cancers by inhibiting aromatase, an estrogen synthase. Therefore, an ordinary skilled artisan could have predictably considered treating the patient population of Peng and could have administrated the compound of Weinberg with a reasonable expectation of success.
In regards to instant claim 27, as currently written, neither instant claims 27 nor 25 on which it depends require that the therapeutic agent be one that induces ore restores COMT. Therefore, the combined teachings of Peng and Weinberg described above, which teaches administering an alternative therapeutic agent that inhibits estrogen production, meets the limitation of instant claim 27.
Claims 25, 29-30, 45, and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,101,603 (‘603) in view of Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023), Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025), and Kazmi et al. (Lung Cancer Manag., 2012 in PTO-892).
Claim 25 is prima facie obvious in view of the combination of the claims of ‘603, Peng, and Weinberg as described above.
The combination, however, does not recite further administering to the human a tyrosine kinase inhibitor such as gefitinib.
The teachings of Kazmi are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further administered to the patient population as recited by the combination of the claims of ‘603, Peng, and Weinberg as described above the geftinib of Kazmi and/or in combination with a chemotherapy such as cisplatin as disclosed in Kazmi to arrive at the claimed invention to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because the combination of the claims of ‘603, Peng, and Weinberg as described above provide guidance of using aromatase inhibitors for treating the patient populations in Peng, and Kazmi provides guidance that aromatase inhibitors in combination with either geftinib or cisplatin is effective for treating the same NSCLC patient. Therefore, an ordinary skilled artisan could have predictably tried these combinations for the same patient populations recited for the combination of the claims of ‘603, Peng, and Weinberg as described above with a reasonable expectation of success.
In regards to instant claims 48-49, it would have also been prima facie obvious before the effective filing date of the claimed invention to have modified the patient population as recited by the combination of the claims of ‘603, Peng, and Weinberg as described above to also have an EGFR mutation as suggested by Peng and taught by Kazmi to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Peng provides guidance that EGFR mutations are common in Asian women with lung cancer and further contemplating the link between 4-OHEs and EGFR mutation, and Kazmi also suggests EGFR mutation as a major factor in the etiology of certain lung cancer such as adenocarcinoma and further establishes a link between estrogen and EGFR mutations in lung cancer patients with geftinib being effective for treating this patient population. Therefore, an ordinary skill artisan could have predictably considered treating patients who additionally have EGFR mutations with a reasonable expectation of success.
Claims 25 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,101,603 (‘603) in view of Peng et al. (Oncotarget, 2017 in IDS filed 04/11/2023), Weinberg et al. (Cancer Research, 2005 in PTO-892 dated 01/13/2025), Kazmi et al. (Lung Cancer Manag., 2012 in PTO-892) and Rodriguez-Lara et al. (J Thorac Dis., 2018 in PTO-892)
Claim 25 is prima facie obvious in view of the combination of the claims of ‘603, Peng, and Weinberg as described above.
The combination, however, does not recite wherein the cancer event is lung cancer recurrence.
The independent teachings of Kazmi and Rodriguez-Lara are as described above.
It would have been prim facie obvious before the effective filing date of the claimed invention to have further modified the combination of the claims of ‘603, Peng, and Weinberg as described above by identifying and treating patients at risk of having a recurrent cancer with EGFR mutation as disclosed in Kazmi and Rodriguez-Lara to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Kazmi establishes a link between estrogen and EGFR mutations in lung cancer patients with geftinib being effective for treating this patient population, and Rodriguez-Lara also establishes the same link and treatment being effective for a patient with recurrent NSCLC. Therefore, an ordinary skill artisan could have predictably considered treating recurrent lung cancer patients with a reasonable expectation of success.
Response to Arguments
Applicant’s arguments filed on 12/17/2025 have been fully considered in so far as they apply to
the rejections of the instant office action, but were not persuasive.
Applicant requests that the nonstatutory double patenting rejections over ‘603 to be held in abeyance until allowable subject matter is found.
Since allowable subject matter has not been found, the nonstatutory double patenting rejections over ‘603 is maintained.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693