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, filed 25 April, 2023, is a national stage application of PCT/US2021/056499, filed 25 October, 2021, which claims the benefit of U.S. Provisional Application N° 63/223,719, filed 20 July, 2021, and Provisional Application N° 63/105,745, filed 26 October, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1 June, 2026 is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 1 June, 2026, in the matter of Application N° 18/250,402. Said documents have been entered on the record.
Claims 1-2, 4-6, 8-9, 11, 13-16, 19, 22, 24, 30, 32, and 34-35 are canceled. Claims 37-56 are new. No new matter was introduced.
Thus, Claims 37-56 represent all claims currently under consideration.
Response to Amendments/Arguments
Claims 1-2, 4-6, 8-9, 11, 13-16, 19, 22, 24, 30, 32, and 34-35 have been canceled. Therefore, the rejections of these claims under 35 U.S.C. 112(a), 112(b), and 101 are moot.
Regarding the previous rejections under 35 U.S.C. 103, Applicant argues that Ushirogochi (US Patent 10,029,993 of previous record) does not specifically teach selecting a daily dosage of 25 mg or 50 mg from the disclosed dosage range and, therefore, does not teach that administration of such doses of the known compound for the known therapeutic use would produce the recited biological effects (‘993, Remarks Pgs 13-16). These arguments are not persuasive.
Ushirogochi teaches administration of the same compound for the same therapeutic indication at a therapeutically effective dosage range that encompasses the presently claimed daily doses. The fact that Ushirogochi does not expressly identify the specific values of 25 mg or 50 mg does not negate its teaching of a dosage range that includes those doses. It is well established that where the general conditions of a claim are disclosed in the prior art, it is ordinarily obvious to discover the optimum or workable ranges by routine experimentation.
See MPEP §2144.05 (I) In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) and (II) “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Applicant has not presented persuasive evidence that administration at 25 mg or 50 mg constitutes a critical selection from the disclosed dosage range or that these doses achieve results that are unexpectedly different from those obtainable using the dosage regimen taught by Ushirogochi. Mere selection of a specific value within a disclosed range, absent evidence of criticality or unexpected results, does not render the claimed method nonobvious. See MPEP §2144.05.
Furthermore, because Ushirogochi teaches administration of the same compound for the same therapeutic purpose at dosages encompassing the claimed doses, one of ordinary skill in the art would have reasonably expected the administration of the selected doses to produce the pharmacological effects normally associated with treatment using the known compound (e.g., suppresses aldosterone production in the subject, as in instant Claim 41). The recited biological effects merely describe the natural pharmacological consequences of administering the known compound for its known therapeutic use (e.g., “Cyp11B2 inhibitor showed a plasma aldosterone level-lowering effect…in hypertensive patients” ‘993, Col 2, Lines 3-6), and therefore do not patentably distinguish the claimed method from that taught by the prior art.
See MPEP §2112(I). "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
To the extent Applicant argues that the prior art fails to expressly disclose administration of exactly 25 mg or 50 mg, such argument is unpersuasive because obviousness does not require an express teaching of every individual value encompassed by a disclosed range. Rather, the prior art provides sufficient motivation to administer therapeutically effective amounts of the known compound to treat the known disease, and selection of the presently claimed doses would have been an obvious matter of routine optimization. Absent persuasive evidence demonstrating that administration at 25 mg or 50 mg produces a result that is critical or unexpectedly different from administration within the dosage regimen disclosed by Ushirogochi, the rejections under 35 U.S.C. §103 are maintained.
Applicant has canceled all previous pending claims and replaced them with a new set of claims. The Examiner has fully considered the amendments and corresponding arguments. While the amended claims have been redrafted and include revised claim language, the amendments do not materially alter the scope of the claimed invention with respect to the prior art. Accordingly, the rejections under 35 U.S.C. 103 has been revised to correspond to the amended claims and is maintained because the amendments do not overcome the deficiencies set forth in the previous Office Action.
Claim Rejections - 35 USC § 103 MAINTAINED
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.
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.
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.
Claims 37-56 are rejected under 35 U.S.C. 103 as being unpatentable over Ushirogochi (US Patent 10,029,993, published 24 July, 2018, cited in IDS and of previous record).
Regarding Claim 37-38, Ushirogochi teaches method for preventing or treating various diseases or conditions associated with aldosterone, comprising administering a therapeutically effective amount of a compound of the above formula [I] or a pharmacologically acceptable salt thereof (‘993, Col 6, Lines 35-39), which includes hydrobromide (‘993, Col 39, Line 40), wherein a compound of formula I is Example 48 (‘993, Col 71, Table 5; which is also instant Formula A), which has an excellent inhibitory activity against aldosterone synthetase (Cyp11B2) and therefore, it is useful for preventing or treating various diseases and/or disease states evoked by an increased level of aldosterone and/or overproduction of aldosterone, such as hypertension (‘993, Col 6, Lines 56-61), treatment-resistant hypertension (‘993, Col 38, Lines 61-62.) Furthermore, Ushirogochi teaches in oral administration, the dosage is generally 0.01-100 mg/kg/day, (‘993, Col 40, Lines 3-4.)
And further, regarding Claims 47-48, Ushirogochi additionally teaches treating hypertension, including aldosterone-associated hypertension, using the same compound. A subject having systolic blood pressure >130 mmHg and diastolic pressure >90 mmHg is, by definition, hypertensive, and evaluating plasma renin activity and aldosterone levels to identify aldosterone-driven or low-renin hypertension is routine clinical practice. Selection of an appropriate patient subgroup for a known treatment is considered obvious absent evidence of unexpected results.
Regarding Claims 39 and 49, Ushirogochi teaches the compound can be used in combination with one or more other medicaments including one more medicaments selected from the group consisting of an antihypertensive drug such as an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium antagonist, a B-blocker, an A/B-blockers; (2) a diuretic, etc. (‘993, Col 40, Lines 7-16.) Because Ushirogochi teaches administering the compound Example 48 in combination with other antihypertensive agents and expressly discloses use in treatment-resistant hypertension (‘993, Col 38, Lines 61-62), it would have been obvious to treat subjects who are taking or have taken additional antihypertensive medications.
Regarding Claims 40 and 50, the limitation requiring that administration of the compound of Formula A “does not inhibit the activity of 11B-hydroxylase as demonstrated by a lack of a clinically meaningful reduction in cortisol production in an ACTH (Cortrosyn) Stimulation test” represents a biological result of administering the same selective CYP11B2 inhibitor disclosed by Ushirogochi. The prior art teaches the identical compound for treating hypertension via CYP11B inhibition. A compound’s inherent biological properties, including its selectivity profile and the resulting endocrine response, necessarily flow from administration of that compound. “The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)”, see MPEP §2112(I). The claimed functional outcome is an inherent property of the known compound when used as taught in the prior art.
Similarly, regarding Claims 41-44 and 51-54, Ushirogochi teaches administering the same Cyp11B2 hydroxylase inhibitor (instant Formula A) to treat hypertension by selectively inhibiting aldosterone synthase. The pharmacodynamic outcomes recited – including suppression of aldosterone production, increases in serum potassium and plasma renin activity, lack of cortisol suppression, and absence of 11-DOC and 11-deoxycortisol accumulation – are inherent or predictable consequences of administering a selective Cyp11B2 inhibitor. These physiological effects necessarily flow from the enzyme selectivity and mechanism of action disclosed in the prior art, even if the art did not explicitly measure them. See MPEP §2112.
Regarding Claims 45-46 and 55-56, Ushirogochi teaches administration of the identical CYP11B2 inhibitor for treatment of hypertension. Because the purpose of administering the inhibitor is to lower blood pressure, one of ordinary skill in the art would have reasonably expected administration of the taught therapeutically effective dose to reduce ambulatory systolic blood pressure. The recited reduction of between 5 and 15 mmHg merely quantifies an expected clinical outcome of the known treatment and does not patentably distinguish the claimed method absent evidence that the recited magnitude of blood pressure reduction is critical or unexpectedly achieved.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to administer Example 48 (instant Formula A) to treat hypertensive patients meeting the recited physiological characteristics, and to identify such patients using routine clinical measurements, as taught or suggested by Ushirogochi.
Ushirogochi discloses treating hypertension, including aldosterone-associated forms, with the same compound via Cyp11B2 inhibition. Subjects exhibiting elevated systolic and/or diastolic blood pressure, low plasma renin activity, and elevated aldosterone levels represent an art-recognized subtype of aldosterone-driven hypertension. Measurement of blood pressure, plasma renin activity, and plasma aldosterone levels constitutes routine clinical evaluation for characterizing hypertensive patients and selecting candidates for aldosterone-targeted therapy. Identifying and treating this patient subgroup is therefore an obvious selection of appropriate subjects for the known therapeutic method. In re Woodruff.
Administration of a selective Cyp11B2 inhibitor inherently and predictable results in the pharmacodynamic outcomes recited in the dependent claims, including suppression of aldosterone production, increases in serum potassium and plasma renin activity, and lack of cortisol suppression of 11-DOC/11-deoxycortisol accumulation. These effects are natural consequences of inhibiting aldosterone synthase while sparing Cyp11B2, and thus constitute expected results of administering the same compound disclosed by Ushirogochi. In re Best; In re Papesch.
Furthermore, the dose amounts, dose ranges, and dosing frequencies (once daily or twice daily oral administration) fall within, or are routine optimizations of, the oral dosing ranges taught by Ushirogochi (e.g., 0.01-100 mg/kg/day.) Adjusting dose and schedule to achieve the desired endocrine and blood-pressure effects represents routine optimization of known parameters with predictable results. In re Aller.
Accordingly, the claimed methods of identifying hypertensive subjects and/or treating those subjects with Example 48 (instant Formula A) represent nothing more than the obvious application of known diagnostic practices and routine clinical optimization applied to a known compound for a known therapeutic indication.
Conclusion
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.
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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