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 .
Claims and Previous Objection/Rejections Status
Claims 30-42 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Response to Arguments
Applicant's arguments filed 12/22/25 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 30-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jalomӓki et al. (US
2025/0121103A1) in view of von Eyben et al. (Biomedicines 2021, 9, 1042; see pgs 1-18) as stated in the office action mailed 9/24/25.
Applicant asserts that Jalomӓki distinguishes between radiographic progression-free survival (rPFS) and overall survival (OS). Jalomӓki states that a target hazard ratio (HR) under the alternative hypothesis of 0.60 for rPFS is reasonably expected (i.e., ~40% risk reduction relative to control), and an HR of 0.70 for OS is reasonably expected (i.e., ~30% risk reduction). A composite endpoint of "radiographic progression or death" must be evaluated in view of both components in order to meaningfully compare Jalomӓki to the instant claims. Logically, combining an expected ~40% reduction in radiographic progression with an expected ~30% reduction in death would yield a composite effect size between those values-not the 50% ("at least 50%") reduction required by the instant claims.
The Examiner asserts that the rPFS of Jalomӓki correlates to OS and is a surrogate for OS but the
HR for rPFS and HR for OS are not combinable into a single HR.
The reference of Jalomӓki teaches that a target HR under the alternative hypothesis of 0.6 is reasonable to expect for the Phase 3 study and therefore the HR of 0.6 is expected but is not definite.
The method of Jalomӓki comprises administration of 7.4 GBq ± 10% of 177Lu-PSMA RLT (e.g. 177Lu-PSMA I&T and 177Lu-PSMA-617) to taxane-naive subjects in a six week treatment cycle of single dose injections wherein the subjects had previous ARAT therapy.
The primary objective of the study is to prospectively assess the efficacy of 177Lu-PSMA I&T on the improvement of radiographic progression free survival (rPFS) compared to standard of care hormone therapy. Therefore, Jalomӓki envisioned the examination of risk reduction of rPFS versus standard of care ARAT therapy.
The method of reducing the risk of radiographic progression of the instant claims comprises administration of 7.4 GBq ± 10% of 177Lu-PSMA RLT (e.g. 177Lu-PSMA I&T and 177Lu-PSMA-617) to taxane-
naive subjects in a six week treatment cycle of single dose injections wherein the subjects had previous
ARAT therapy.
The reference of Jalomӓki and the instant invention teach the same compounds 177Lu-PSMA I&T and 177Lu-PSMA-617 that are analogously used for determining the risk reduction of rPFS. The instant claims do not include any different method steps, any different conditions or any different techniques over the prior art.
Therefore, the 177Lu-PSMA I&T or 177Lu-PSMA-617 of Jalomӓki in taxane-naïve subjects have the same properties and are capable of the same functions, such as being characterized by an at least 50% reduction of risk of radiographic progression or death as compared to continued ARPI therapy.
Applicant asserts that the Office's reliance on von Eyben's reported improvements to rPFS to "optimize" Jalomӓki is inapposite because the control arms differ. Von Eyben quantifies rPFS and OS improvements relative to a taxane (e.g., cabazitaxel) control, whereas Jalomӓki's comparator is standard-of-care hormone therapy (abiraterone or enzalutamide). Hazard ratios are comparisons over time between a treatment and a specified control; substituting a different control arm fundamentally changes the measured effect and does not support an inference that Jalomӓki's expected HRs can be optimized by 5-10% to even approach a composite 50% risk reduction against continued ARPI. Cross-study "optimization" between different comparators is methodologically unsound and cannot bridge the gap, even partially (noting that a 10% improvement of Jalomӓki still falls short of the claimed risk reduction) between the endpoint of Jalomӓki and the claimed endpoint.
The reference of von Eyben was not used to teach that the HR of the taxane control is a direct comparison of the HR of the ARAT control of Jalomӓki or merely a 10% improvement of Jalomӓki reduction in risk of rPFS.
The reference of von Eyben was used to teach that the treatment of patients having mCRPC
with prostate-specific membrane (PSMA)-based radioligand therapy (RLT) resulted in a 1.1 times higher six-month rate of median radiographic progression free survival. Therefore, patients see more than a 1.1
times improvement.
The reference of Jalomӓki teaches that stated above and does not limit the risk reduction of
rPFS to 40% but estimates that the risk reduction of rPFS will be at least 40%.
It would have been predictable to one of ordinary skill in the art that the RLT method (e.g. 177Lu-PSMA I&T or 177Lu-PSMA-617) advantageously provides a greater than 40% risk reduction of rPFS with a reasonable expectation of success, such as at least 50%, at least 55% or at least 57% as Jalomӓki teaches that the 40% (HR 0.6) reduced risk of rPFS is reasonable to expect but does not limit the HR to 0.6 and von Eyben teaches that the RLT method significantly improves the median rPFS by 1.1 times in patients with mCRPC.
Also, the reference of Jalomӓki and the instant invention teach the same compounds 177Lu-PSMA I&T and 177Lu-PSMA-617 that are analogously used for determining the risk reduction of rPFS. The instant claims do not include any different method steps, any different conditions or any different techniques over the prior art.
Further, the reduced risk as claimed would be expected to occur as this is a property of the combination treatment that is an obvious combination of the cited prior art.
Therefore, the 177Lu-PSMA I&T or 177Lu-PSMA-617 of Jalomӓki in taxane-naïve subjects have the same properties and are capable of the same functions, such as being characterized by an at least 50% reduction of risk of radiographic progression or death as compared to continued ARPI therapy.
Claim(s) 30-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sartor et al. (J. Clin. Oncol. 40(6), suppl February 2022, TPS211) in view of von Eyben et al. (Biomedicines 2021, 9, 1042; see pgs 1-18) and in further view of Jalomӓki et al. (US 2025/0121103A1) as stated in the office action mailed 9/24/25.
Applicant asserts that the Office cites Sartor et al. ("Sartor"), which describes the PSMAfore phase 3 trial (the same trial underlying the instant application), and combines it with von Eyben and Jalomӓki. Sartor discloses that the planned sample size provided 95% power to detect an HR of 0.56 for rPFS-reflecting the effect size considered plausible at the time of planning, i.e., before the study was performed. However, the observed treatment effect was substantially greater: the trial demonstrated a statistically significant benefit with an HR of approximately 0.41. The observed HR corresponds to -59% risk reduction, materially exceeding the powered assumption (-44% risk reduction). This magnitude of improvement-roughly 34% greater risk reduction than assumed-constitutes evidence of unexpected results.
The prior art reference of Sartor observed a -59% risk reduction for the treatment of patients having mCRPC with 177Lu-PSMA-617 that is roughly 34% greater risk reduction than assumed and therefore, the result is not unexpected.
The Applicant concedes in the Remarks filed 12/22/25 that the method of Sartor and the method of the instant claims are identical and therefore, use the same compound 177Lu-PSMA-617 analogously for determining the risk reduction of rPFS, do not include any different method steps, any different conditions or any different techniques.
Therefore, the 177Lu-PSMA-617 in taxane-naïve subjects has the same properties and is capable of the same functions, such as being characterized by an at least 50% reduction of risk of radiographic progression or death as compared to continued ARPI therapy.
The reference of von Eyben was used to teach that stated above.
Therefore, it would have been predictable to one of ordinary skill in the art that the references of Sartor and von Eyben both teach of a greater risk reduction for radiographic progression using the 177Lu-PSMA-617 RLT method in patients with mCRPC regardless of the control with a reasonable expectation of success.
Conclusion
No claims are allowed at this time.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618