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 .
Non-Final Rejection
The Status of Claims:
Claims 1-18 are pending.
Claims 1-18 are rejected.
DETAILED ACTION
1. Claims 1-18 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/JP22/08383 02/28/2022, which has a priority date of 63222323 07/15/2021 and PCT/JP22/08383 has a priority date of 63154426 02/26/2021.
Drawings
3. None.
IDS
4. The IDS filed on 10/06/25, 06/03/25, 01/06/25, 12/03/24, 7/09/24 were reviewed
by the examiner.
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 1-18 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.
In claim 1 , the limitations “ proven prostate cancer”, “an amount and for a period of time clinically proven effective” are recited. These can be vague and indefinite because the claim appears to indicate that tha treatment was already known and the claim has already acknowledged that enzalutamide monotherapy was administered in an amount and period proven effective prior to the current invention. How can it be ‘ proven effective” ? It seems that the claim could benefit from some clarification of the language chosen. The examiner recommends to remove the 'proven effective' from the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 5, 8, 13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by Averback (US 2021/030842 A1)
Averback discloses a method of reducing a low grade univocal prostate cancer progression by using a composition comprising at !east one pharmaceutically active ingredient such as fexapotide triflutate, and Xtandi (enzalutamide) capable of inducing necrosis of the !ow grade, !ow risk, localized prostate cancer tumor in mammals having low grade or at low risk of prostate cancer( i.e., Gleason Score ≤6) (see page 2 , a paragraph#0015). The method includes administering a therapeutically effective amount of the composition to a single cancerous foci (unifoca! tumor) in the prostate of the mammal, and reducing treatment side hemi-prostate Gleason grade increase by an amount of from about 15'% to about 100%, when compared to active surveillance, when measured at !east 18 months after treatment (see page 2 , paragrphs#0014-0015; page 7, a paragraph#0046 and page 13, claims 11-12). These are identical with the claims.
Also, it teaches that the composition delays PSA progression by six months relative to PSA progression of patients in the control population (GL, F-IV, 4.10: "result to be achieved"). Therefore, these are identical with the claims.
6. Claim(s) 1, 2, 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by Moyad et al( Research and Reports in Urology 2014:6 , p.71–77).
Moyad et al discloses the potential application of enzalutamide, a second-generation androgen-receptor inhibitor, as a short-term treatment for patients with intermediate-risk prostate cancer undergoing active surveillance (AS) to mitigate the risk of disease progression. A follow-up biopsy in a patient revealed Gleason scores of 3+4=7 (10%) and 3+3=6 (50% Gleason score) from left lateral midgiand, along with 3+3=6 (15%, Gleason score) in another region. Additionally, it discloses a patient with intermediate-risk prostate cancer and rising PSA levels who was treated with enzalutarnide (80-120 mg/day) for six months. The treatment led to a marked reduction in tumor size, undetectable PSA levels, and only mild side effects, including hot flashes and reduced libido. After discontinuing enza!utamide, the patient remained stable under ongoing monitoring (see page 71, abstract; pages 72-73, case report). These are identical with the claims.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
7. Claims 1-14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over NCT02799745 (ClinicalTrials.gov archive [online], 2020.11.27, [retrieved on 2022-04-04], Retrieved from the Internet: <URL: https://www.clinicaltrials.gov/ct2/ history/NCT027997 45? A=46&B=46&C=merged#StudyPageTop>) in view of Averback (US 2021/030842 A1).
1. (original) A method of reducing the risk of prostate cancer progression in a patient with a histologically proven prostate cancer characterized as low or intermediate risk for which no other treatment for prostate cancer is indicated, comprising administering enzalutamide monotherapy to the patient in an amount and for a period of time clinically proven effective in reducing the risk of prostate cancer progression.
2. (original) The method of claim 1, wherein the risk of prostate cancer progression in the patient is reduced relative to a control population of patients under surveillance, wherein patients in the control population have histologically proven prostate cancers characterized as low or intermediate risk for which no other treatment for prostate cancer is indicated, and wherein patients in the control population do not receive a therapy for prostate cancer.
3. (original) The method of claim 1, wherein the life expectancy of the patient and the life expectancies of patients in the control population is > 5 years.
4. (original) The method of claim 1, wherein the life expectancy of the patient and the life expectancies of patients in the control population is
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5 years.
5. (original) The method of claim 1, wherein the prostate cancer of the patient and the prostate cancers of the control population are characterized as low risk.
6. (original) The method of claim 5, wherein low risk is defined by one or more of a stage identification of Tic-T2a, prostate-specific antigen (PSA) level <10 ng/mL, a Gleason score of <6, and an Eastern Cooperative Oncology Group (ECOG) status of <2.
7. (original) The method of claim 1, wherein the prostate cancer of the patient and the prostate cancers of the control population are characterized as intermediate risk.
8. (original) The method of claim 7, wherein intermediate risk is defined by one or more of a stage identification of T2b-T2c, a PSA level < 20 ng/mL, a Gleason score of <7 (3+4 pattern), and an ECOG status <2.
9. (currently amended) The method of claim1,wherein the prostate cancer progression comprises pathological prostate cancer progression.
10. (original) The method of claim 9 wherein the pathological prostate cancer progression comprises an increase in primary or secondary Gleason pattern by >1 or a >15% increase in cancer positive cores.
11. (currently amended) The method of claim 1, wherein the prostate cancer progression comprises therapeutic prostate cancer progression.
12. (original) The method of claim 11, wherein the therapeutic prostate cancer progression comprises the earliest occurrence of a further therapy for prostate cancer.
13. (original) The method of claim 12, wherein the further therapy is selected from the group consisting of androgen deprivation therapy, prostatectomy, radiation, focal therapy, and systemic therapy.
14. (currently amended) The method of claim 1,wherein the period of time is one year.
17. (currently amended) The method of claim 1,wherein the enzalutamide monotherapy is administered at a daily dose of 160 mg.
Determination of the scope and content of the prior art
NCT02799745 discloses a study that compares the time to prostate cancer progression (pathological or therapeutic progression) as in claim 9 & 11-12 between patients treated with enzalutamide as in claim 1 versus patients undergoing active surveillance.
The study evaluates the efficacy and safety of enzalutamide for extension of time to prostate cancer progression (pathological or therapeutic) in patients with clinically localized, histologically proven prostate cancer that is categorized as low risk as in claim 5 or intermediate risk as in claims 2 & 7 and who are under Active Surveillance (AS) (see page 6, Study Description).
Regarding the participant group, participants received 160-milligrams (mg) enzalutamide administered as four 40-mg capsules, orally once daily as in claim 17 for 1 year of treatment period as in claim 14 . Following the 1-year treatment period, all participants were followed for 1 additional year (see page 8, Design Details).
Also, it discloses the following description:
- Prostate cancer categorized as low risk is defined as Tlc-T2a, PSA<l0, GS less than or equal to 6, ECOG status less than or equal to 2 as in claim 3 and estimated life expectancy >5 years as in claim 6 or intermediate risk is defined as T2b-T2c, PSA<20, GS less than or equal to 7 (3+4 pattern) as in claim 10, ECOG status less than or equal to 2 as in claim 8 and estimated life expectancy > 5 years (see page 11, Eligibility).
- Secondary outcome measures include incidence of negative biopsies for cancer at 1 year, and time to PSA (Prostate Specific Antigen) progression (see page 8, Outcome Measures).
The current invention, however, differs from the prior art in that the further therapy selected from the group consisting of focal therapy is unspecified in the prior art.
Averback discloses a method of reducing a low grade univocal prostate cancer progression by using a composition comprising at !east one pharmaceutically active ingredient such as fexapotide triflutate, or Xtandi (enzalutamide) capable of inducing necrosis of the !ow grade, !ow risk, localized prostate cancer tumor in mammals having low grade or at low risk of prostate cancer( i.e., Gleason Score ≤6) (see page 2 , a paragraph#0015). The method includes administering a therapeutically effective amount of the composition to a single cancerous foci (unifoca! tumor) in the prostate of the mammal, and reducing treatment side hemi-prostate Gleason grade increase by an amount of from about 15'% to about 100%, when compared to active surveillance, when measured at !east 18 months after treatment (see page 2 , paragrphs#0014-0015; page 7, a paragraph#0046 and page 13, claims 11-12).
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied NCT02799745 prior art is that the applied art does not expressly teach the claimed further therapy selected from the group consisting of focal therapy. The deficiency of the NCT02799745 is cured by the Averback.
The difference between the instant application and the applied Averback art is that the Averback does not expressly teach the claimed life expectancy of the patient and the life expectancies of patients in the control population being
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5 years or >5 years, a stage identification of Tic-T2a, prostate-specific antigen (PSA) level <10 or 20 ng/mL and pathological prostate cancer progression, the period of time being one year and a daily dose of 160 mg. The deficiencies of the Averback are cured by NCT02799745.
Resolving the level of ordinary skill in the pertinent art.
Regarding the Claim 13 , with respect to the lack of disclosing the claimed further therapy selected from focal therapy, the Averback does teach the use of fexapotide triflutate as a focal therapy for reducing prostate cancer progression (see page 12 , claim 1) as well as enzalutamide (see page 4 , a paragraph#0023). Also, NCT02799745 does disclose the prostate cancer progression for patients being treated with enzalutamide in the study.
From the above, it is clear that both prior art are closely interrelated to each other with the reduction of prostate cancer progression. So, it would have been obvious to the skilled artisan in the art to be motivated to incorporate the teaching of the Averback’s fexapotide triflutate as for a focal therapy into the the NCT02799745 study in order to enhance the method of reducing the risk of prostate cancer progression. This is because the skilled artisan in the art would expect the combined prior art method to be feasible and successful as guidance in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
NCT02799745 expressly discloses the efficacy and safety of enzalutamide for treating prostate cancer progression pathologically and therapeutically in patients with clinically localized, histologically proven prostate cancer. Similarly, Averback does teach the method of reducing a low grade univocal prostate cancer progression by using a composition comprising fexapotide triflutate, and/or Xtandi (enzalutamide) capable of inducing necrosis of the !ow grade, !ow risk, localized prostate cancer tumor in mammals having low grade or at low risk of prostate cancer.
Both prior art are closely interrelated to each other with the reduction of prostate cancer progression using enzalutamide or fexapotide triflutate, and/or Xtandi (enzalutamide). Averback does give a guidance that there is a need to reduce the need for invasive surgical intervention intervention, even after treatment with an effective composition (see page 1 a pargraph#0003)..
So, it would have been obvious to the skilled artisan in the art to be motivated to incorporate the teaching of the Averback’s fexapotide triflutate as for a focal therapy into the NCT02799745 study in order to promote the method of reducing the risk of prostate cancer progression more effectively. This is because the skilled artisan in the art would expect the combined prior art method to be feasible and successful as guidance in the prior art.
Conclusion
Claims 1-18 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 1/22/2026