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 .
Priority
This application is a 371 to PCT/US2020/063534 filed 12/07/2020 which claims priority to application 62/944,804 filed 12/06/2019.
Information Disclosure Statement
The information disclosure statement filed 12/01/2025 has been considered.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10 are rejected under 35 U.S.C. 101 because the claimed invention can be directed to an abstract idea without significantly more. This rejection is modified in view of applicant’s claim amendments. The claims recites the abstract idea and mathematical calculation of applying measured prostate specific antigen (PSA) and androgen-independent prostate cancer stem cell (PcaSC) levels to a prostate cancer dynamic model and calculating a subject-specific PSA and/or PCaSC dynamic threshold. This judicial exception is not integrated into a practical application in the event that the levels are not greater than the threshold, because in this case, intermittent on and off androgen deprivation therapy (IADT) not administered. Furthermore, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1: Does the claim falls within any statutory category? MPEP 2106.03. The claims recites at least one step or act. Thus, the claim is to a process, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong One: Does the claim recites a judicial exception? The recitations in limitation (b) and (c) of the claims has a BRI that requires performing an arithmetic calculation. Thus, limitation (b) and (c) falls into the “mathematical concept” grouping of abstract ideas. In addition, mathematical calculations can be practically performed in the human mind, regardless if there is a use of physical aid which does not negate the mental nature of this limitation. Accordingly, limitation (b) and (c) recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings).
Step 2A Prong Two: Does the claim recite any other additional elements as a whole that integrates the recited judicial exception into a practical application of the exception. The claim additionally recites “wherein when PSA levels and/or PCaSC levels are greater than the subject-specific PSA dynamic threshold and/or a subject-specific PCaSC dynamic threshold then administering to the subject one or more subsequent cycles of intermittent on and off androgen deprivation therapy (IADT).” Although this limitation indicates that a treatment is to be administered, the claims does not provide any information as to how the patient is to be treated when the levels are not greater than the threshold, which is an embodiment of the claim. Accordingly, in this case, the additional elements do not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception (Step 2A: YES).
Step 2B: Does the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element which does not require any particular application when the levels are not greater than the threshold. (Step 2B: NO). The claim is not eligible.
Claims 2-10 also does not recite any additional elements that amount to significantly more or markedly different than the judicial exception.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 1-4 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Haber (US20150168413A1) in view of Bui (Bui et al. Cancer and Metastasis Reviews 17: 391–399, 1999), Collins (Collins et al. Cancer Res 2005; 65: (23). December 1, 2005), and Hirata (Hirata et al. Journal of Theoretical Biology 264 (2010) 517–527). This is a new rejection in view of applicant’s claim amendments.
Regarding claim 1, Haber teaches methods related to determining a ratio of expression levels of PSA/ prostate specific membrane Antigen (PSMA) or determining the expression level of PSMA in circulating tumor cells for diagnosis and/or for the purpose of monitoring treatment efficacy for prostate cancers that are likely hormone resistant [abstract]. Haber teaches a method of treating prostate cancer comprising measuring PSA and PSMA in circulating tumor cells, determining the ratio of prostate specific antigen (PSA) to prostate specific membrane antigen (PSMA) expression and, if the PSA/PSMA expression ratio is increased compared to that of a reference value (i.e., prostate cancer dynamic model), administering to the subject a prostate cancer agent [0007, 0031, 0073, claims 80-81]. Haber teaches that the subject is currently undergoing treatment with a hormone therapy for prostate cancer, or was previously treated with a hormone therapy for prostate cancer [claim 82]. Haber teaches identifying (i.e., calculating) a threshold for detection determined by analysis of healthy donor blood samples, below which a signal is considered a false positive [097, 0284-0286; Fig. 7].
Regarding claim 3, Haber teaches that increased means at least about 10% [0113].
Regarding claim 4, Haber teaches that the PSA levels are measured from cells from a blood sample [0031].
Regarding claim 6, Haber teaches repeating the cycle every 2 weeks, 1, 2, 3, or 4 months [0167].
Regarding claim 7, Haber teaches that the primary treatment is neoadjuvant androgen-deprivation therapy by only teaching that the subject was previously treated with a hormone therapy for prostate cancer, where the hormone therapy is a therapy for the treatment of prostate cancer that deprives a tumor of androgen [103; claim 82].
Haber does not teach measuring androgen-independent PcaSC and applying those levels to a prostate cancer dynamic model. Haber does not teach that the prostate cancer agent is IADT.
Bui teaches that although the majority of patients with advanced prostate cancer disease respond initially to androgen ablation therapy (i.e., IADT), most go on to develop androgen-independent tumors that are inevitably fatal [abstract]. Bui teaches that the study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer [abstract]. According to this model, Bui teaches that the overexpression of basal cell genes by androgen-independent tumors may reflect the expansion of a preexisting basal-like cancer stem cell [pg. 395, col., 1, para 3 – col. 2, para 1; Fig. 1]. Bui teaches that this cancer stem cell partially retains its ability to differentiate in response to androgen, leading to the expression of secretory cell genes such as PSA [pg. 395, col., 1, para 3 – col. 2, para 1; Fig. 1]. Bui teaches that hormone ablation leads to the regression of terminally differentiated androgen-dependent cells and to the selection and/or adaptation of self-renewing androgen-independent stem cells which express a basal-like phenotype [pg. 395, col., 1, para 3 – col. 2, para 1; Fig. 1].
Collins teach that although the existing therapies for prostate cancer eradicates the bulk of cells within a tumor, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies [abstract]. Collins teach that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor, and report the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal [abstract]. Collins teach that the identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell [abstract].
Hirata teaches a mathematical model that quantitatively reproduces the dynamics of the serum prostate specific antigen (PSA) level under intermittent androgen suppression (IAS) for prostate cancer. Hirata teaches that if the serum PSA level decreases to a value below 4.0ng/ml, IAS therapy is interrupted and no further treatment is given until the PSA level recovers to approximately 10ng/ml when patients are restarted on treatment [pg. 518, col. 1, para 2; Fig. 1].
Regarding claim 2, Hirata teaches that treatment IADT is stopped when 50% of pre-treatment levels by teaching that when the PSA levels are 10ng/ml IADT is administered and is stopped at 4ng/ml [pg. 518, col. 1, para 2; Fig. 1].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to have also measured androgen-independent PcaSC in the model of Haber, and applied those levels to a prostate cancer dynamic model that additionally identifies a subject-specific PCaSC dynamic threshold and administer IADT, as taught by the model of Hirata, when both the PSA levels and/or PCaSC are above their respective thresholds. One of ordinary skill would be motivated to make the modification for the advantage of developing a therapy targeted to both the PCa cells and the self-renewing androgen-independent stem cells as taught by Bui and Collins. One of ordinary skill would have a reasonable expectation of success since Bui teaches that hormone ablation leads to the regression of terminally differentiated androgen-dependent cells and selection and/or adaptation of self-renewing androgen-independent stem cells which are responsible for maintaining the prostate cancer as taught by Collins.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Haber (US20150168413A1) in view of Bui (Bui et al. Cancer and Metastasis Reviews 17: 391–399, 1999), Collins (Collins et al. Cancer Res 2005; 65: (23). December 1, 2005), and Hirata (Hirata et al. Journal of Theoretical Biology 264 (2010) 517–527) as applied to claim 1, and further in view of Lee (Lee et al. Journal of Molecular Cell Biology (2013), 5, 14–26). This is a new rejection in view of applicant’s claim amendments.
The teachings of Haber, Bui, Collins, and Hirata are discussed above as applied to claims 1, and similarly apply to claim 5. Haber, Bui, Collins, and Hirata fails to do not teach further measuring androgen dependent non-stem prostate cancer cell (PcaC) levels and applying the measured values to a prostate cancer dynamic model before calculating the subject-specific PCaC dynamic threshold.
Lee teaches that ADT might result in an undesired expansion of PCa stem/progenitor cell population and that targeting PCa non-stem/progenitor cells with AR degradation enhancer and targeting PCa stem/progenitor cells with 5-azathioprine and y-tocotrienol resulted in a significant suppression of the tumors at the castration resistant stage [abstract]. Lee teaches that a combinational therapy that simultaneously targets both stem/progenitor and non-stem/progenitor cells will lead to better therapeutic efficacy and may become a new therapy to battle the PCa before and after castration resistant stages [abstract].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to further measure androgen dependent non-stem prostate cancer cell (PcaC) levels and apply the measured values to a prostate cancer dynamic model before calculating the subject-specific PCaC dynamic threshold in the model as taught and suggested by Haber, Bui, Collins, and Hirata. One of ordinary skill would be motivated to make the modification for the advantage of additionally adding an AR degradation enhancer to the treatment step providing for a combinational therapy that simultaneously targets both stem/progenitor and non-stem/progenitor cells for better therapeutic efficacy.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Haber (US20150168413A1) in view of Bui (Bui et al. Cancer and Metastasis Reviews 17: 391–399, 1999), Collins (Collins et al. Cancer Res 2005; 65: (23). December 1, 2005), and Hirata (Hirata et al. Journal of Theoretical Biology 264 (2010) 517–527) as applied to claim 1, and further in view of Portz (Portz et al. AIP ADVANCES 2, 011002 (2012)). This is a new rejection in view of applicant’s claim amendments.
The teachings of Haber, Bui, Collins, and Hirata are discussed above as applied to claims 1, and similarly apply to claims 8-9. While Haber teaches the subject was previously treated with a hormone therapy for prostate cancer, where the hormone therapy is a therapy for the treatment of prostate cancer that deprives a tumor of androgen [103; claim 82], Haber, Bui, Collins, and Hirata fails to explicitly disclose wherein the method is performed after the patient begins IADT.
Portz teaches that prostate cancer is commonly treated by a form of hormone therapy called androgen suppression (i.e., IADT) [abstract]. Portz teaches that this form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form [abstract]. Portz teaches that intermittent androgen suppression aims to alleviate some of these adverse effects by cycling the patient on and off treatment [abstract]. Portz teaches that clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods [abstract].
Regarding claim 9, Haber teaches that the methods for treating a prostate cancer can further include the use of one or more additional anti-cancer or chemotherapeutic agents such as docetaxel.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to have modified the model as taught and suggested by Haber, Bui, Collins, and Hirata where the method is performed after the patient begins IADT versus continuous ADT. One of ordinary skill would be motivated to make the modification for the advantage alleviating some of these adverse effects of continuous ADT and increasing quality of life for patients during off-treatment periods as taught by Portz.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Haber (US20150168413A1) in view of Bui (Bui et al. Cancer and Metastasis Reviews 17: 391–399, 1999), Collins (Collins et al. Cancer Res 2005; 65: (23). December 1, 2005), Hirata (Hirata et al. Journal of Theoretical Biology 264 (2010) 517–527), and Portz (Portz et al. AIP ADVANCES 2, 011002 (2012)) as applied to claims 1 and 8-9, and further in view of Gao (WO2015065919A1). This is a new rejection in view of applicant’s claim amendments.
The teachings of Haber, Bui, Collins, Hirata, and Potrz are discussed above as applied to claims 1 and 8-9, and similarly apply to claim 10. Haber, Bui, Collins, Hirata, Portz fails to explicitly disclose calculating docetaxel or AA cytotoxicity and adjusting dosage and timing of docetaxel or AA.
Gao teaches compositions and methods for treating prostate cancer [abstract] by enhancing the therapeutic effects of docetaxel and reducing prostate cancer cell resistance to docetaxel [0014-0015]. Gao teaches that “optimum dosages, toxicity, and therapeutic efficacy of the compositions of the present invention may vary depending on the relative potency of the administered composition and can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, for example, by determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio, LD50/ED50. Agents that exhibit large therapeutic indices are preferred. While agents that exhibit toxic side effects can be used, care should be taken to design a delivery system that targets such agents to the site of affected tissue to minimize potential damage to normal cells and, thereby, reduce side effects.” [0231]. Gao teaches the importance of administering to a patient a therapeutically effective dose to prevent, treat, or control prostate cancer [0229]. Gao also teaches that compositions described herein may be administered in different amounts and at different times where certain factors may influence the dosage and timing required to effectively treat a subject [0236].
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method as taught and suggested by Haber, Bui, Collins, Hirata, and Potrz to include adjusting the therapeutic dosage and timing of docetaxel as taught by Gao for the purpose of determining the therapeutically effective dose of docetaxel to prevent, treat, or control prostate cancer.
Response to Arguments
Applicant’s arguments with respect to claims 1-10 under 35 U.S.C. 101 have been considered but are moot because the arguments are directed to the newly amended claims. Furthermore, in the newly amended claims, the judicial exception is only integrated into a practical application when the PSA levels and Androgen-Independent PCa Stem Cells (PCaSC) levels are higher than threshold values calculated according to the inventive prostate cancer dynamic model. The judicial exception is not integrated into a practical application when the levels are the same or lower. Therefore, since the method encompasses all three embodiments, the claim as a whole is not eligible.
Applicant’s arguments and declaration under 37 C.F.R. § 1.130 filed 12/01/2025, with respect to the rejection(s) of claims 1-10 under 35 USC§ 102 and 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Haber, Bui, Collins, Hirata, Lee, and Portz.
Conclusion
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637