DETAILED ACTION
This office action is in response to applicant’s filing dated April 20, 2026.
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 .
Status of Claims
Claims 1-13, 22, 25-27, and 30-32 are pending in the instant application. Acknowledgement is made of Applicant's remarks filed April 20, 2026. Claims 14-21, 23, 24, 28, and 29 were previously canceled.
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a method of treating hypertension in a human having a mean seated blood pressure of ≥130/80 mmHg, comprising administering 0.1 to 10 mg/day of (R)-Compound 1 to the human in the reply filed on April 20, 2026 is acknowledged.
Claims 30-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 20, 2026.
Applicant’s election without traverse of a diuretic as the hypertension regimen species in the reply filed on April 20, 2026 is acknowledged.
Claims 1-13, 22, 25-27 are presently under examination as they relate to the elected species: diuretic.
Priority
The present application is a 371 of PCT/US2022/073148 filed on June 24, 2022, which claims benefit of US Provisional Application Nos. 63/214,521 and 63/290,364 filed on June 24, 2021 and December 16, 2021, respectively.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on April 4, 2024; February 12, 2025; and June 6, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on December 13, 2023.
The drawings are objected to because:
Figures 1-12, 15, and 18 are blurry and pixelated. The axis labels of each graph are difficult to read.
Figure 13 and the graphs of Figure 18 contain text at the bottom right of the figure that is not visible and the legend is blurry.
Figures 14, 16 and 17, the legend are blurry and difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 3 is objected to because of the following informalities:
Claim 3 recites the phrase “wherein the stable hypertensive regimen comprising ≥3 antihypertensive agents.” This phrase is grammatically incorrect and should be written “wherein the stable hypertensive regimen comprises ≥3 antihypertensive agents.
Appropriate correction is required.
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.
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 1, 5-13, 22, and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Aebi et al (WO 2013/041591 A1, cited in a previous Office Action) in view of Mayo Clinic (https://www.mayoclinic.org/tests-procedures/blood-pressure-test/about/pac-20393098, Internet Archive Wayback Machine Date, July 28, 2018, obtained from the internet February 11, 2026).
Regarding claims 1 and 27, Aebi teaches a method for the treatment of hypertension comprising administering an effective amount of a compound (claim 49) wherein the compound is (+)-(R)-N-(4-(1-Methyl-2-oxo-1, 2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide or pharmaceutically acceptable salts thereof (claim 52). Aebi teaches (+)-(R)-N-(4-(1-Methyl-2-oxo-1, 2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide is Example 3 and has the structure:
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Thus, (+)-(R)-N-(4-(1-Methyl-2-oxo-1, 2,3,4-tetrahydroquinolin-6-yl)-5,6,7,8-tetrahydroisoquinolin-8-yl)propionamide is (R)-Compound 1.
Aebi does not explicitly teach treating hypertension in a human having a mean seated blood pressure of ≥130/80 mmHg.
However, Aebi does teach Example 3 has EC50 in human CYP11B2 of 0.014 µM and EC50 in human CYP11B1 of µM.
Moreover, Mayo Clinic teaches having a blood pressure test is often a routine part of a medical appointment; the test may be performed by a nurse or technician; and the test is performed best while you are seated in a chair in the examining room (page 2, 6th paragraph). Mayo Clinic teaches there are four blood pressure categories; Stage 1 high blood pressure (hypertension) is categorized by top number (systolic) in mm Hg of 130-139 or bottom number (diastolic) in mm Hg of 80-89 and Stage 2 high blood pressure (hypertension) is categorized by top number (systolic) in mm Hg of 140 or more or bottom number (diastolic) in mm Hg of 90 or more.
As such, since Aebi teaches a method of treating hypertension comprising administering an effective amount of (R)-Compound 1, and since Mayo Clinic teaches that humans having a blood pressure of greater than 130 / 80 are categorized as subjects having hypertension, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of treating hypertension taught by Aebi to treat a having a mean seated blood pressure of ≥130/80 mmHg with an expectation of success, since the prior art establishes that (R)-Compound 1 is useful for treating hypertension generically and is effective in human cells and blood pressure of ≥130/80 mmHg is utilized to determine if a subject is suffering from hypertension.
Regarding the claimed amounts of (R)-Compound 1, Aebi does not explicitly teach administering 0.1 to 10 mg/day of (R)-Compound 1 (instant claim 1), about 0.5 mg/day of (R)-Compound 1 (instant claim 11), about 1 mg/day of (R)-Compound 1 (instant claim 12), about 2 mg/day of (R)-Compound 1 (instant claim 13) in a single dose (instant claim 22). However, Aebi teaches the dosage can vary in wide limits and will, of course, be fitted to the individual requirements in each particular case; in general, in the case of oral administration a daily dosage of about 0.1 mg to 20 mg per kg body weight, preferably about 0.5 mg to 4 mg per kg body weight (e.g. about 300 mg per person), divided into preferably 1-3 individual doses, which can consist, for example, of the same amounts, should be appropriate (page 60, lines 11-15). Assuming the weight of an average adult is about 60 kg, an amount of 0.1 mg-20 mg would be equivalent to 6 mg – 1200 mg. Assuming the weight of an average human adult is about 60 kg, an amount of 0.1 mg-20 mg would be equivalent to 6 mg – 1200 mg. A human adult reads on a human at least 18 years of age (instant claim 26).
Similarly, Aebi does not teach 4 weeks of treatment (instant claims 5, 7, and 9) or 12 weeks of treatment (instant claims 6, 8, and 10). However, Aebi does teach administering a CYP11B2 inhibitor, FAD286, for 4 weeks (page 7, line 11); the CYP11B2 inhibitor FAD286 improved blood pressure (page 7, lines 14-15).
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amount of (R)-Compound 1 and the treatment regimen taught by Aebi as a starting point for optimizing the amount and treatment regimen of (R)-Compound 1 utilized to treat hypertension since Aebi teaches (R)-Compound 1 is useful for treating hypertension and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding claims 5-10 and 25, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). In the instant case, the wherein clause is directed to the intended result (i.e. mean decrease in baseline in systolic blood pressure (instant claims 5 and 6), mean decrease in baseline in seated diastolic blood pressure (instant claims 7 and 8), seated blood pressure of [Symbol font/0x3C]130/80 mmHg (instant claims 9 and 10), or does not result in a clinically significant adverse even in the human (instant claim 25) of the process step positively recited (i.e. administering (R)-Compound 1 to a subject suffering from hypertension).
Taken together, all this would result in the practice of the method of claims 1, 5-13, 22, and 25-27 with a reasonable expectation of success.
Claims 2-4 are rejected under 35 U.S.C. 103 as being unpatentable over Aebi et al (WO 2013/041591 A1, cited in a previous Office Action) in view of Mayo Clinic (https://www.mayoclinic.org/tests-procedures/blood-pressure-test/about/pac-20393098, Internet Archive Wayback Machine Date, July 28, 2018, obtained from the internet February 11, 2026) as applied to claims 1, 5-13, 22, and 25-27 above, and further in view of Egan (Ethn Dis, 2015; 25(4):495-8).
Aebi teaches all the limitations of instant claims 2 and 3 (see above 103), except the human is on a stable background of hypertensive regimen prior to the administration of the (R)-Compound 1 (instant claim 2) or the table background of hypertensive regimen comprising ≥3 antihypertensive agents (instant claim 3). However, Aebi does teach in a particular embodiment, the cardiovascular condition is treatment-resistant hypertension.
Moreover, Egan teaches treatment resistant hypertension (TRH) has been defined as BP above goal on ≥ or controlled to goal on ≥ 4 BP medications (page 495, center, 1st paragraph).
As such, since Aebi and Mayo Clinic teach a method of treating hypertension comprising administering an effective amount of (R)-Compound 1 to human having a blood pressure of greater than 130 / 80 and that (R)-Compound 1 is useful for treating treatment resistant hypertension, and since Egan teaches that treatment resistant hypertension (TRH) has been defined as BP above goal on ≥ or controlled to goal on ≥ 4 BP medications, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the method of treating hypertension taught by Aebi and Mayo Clinic to treat a human subject on a stable background of hypertensive regimen comprising ≥3 antihypertensive agents with an expectation of success, since the prior art establishes that (R)-Compound 1 is useful for treating treatment resistant hypertension generically and treatment resistant hypertension (TRH) has been defined as BP above goal on ≥ or controlled to goal on ≥ 4 BP medications.
Taken together, all this would result in the practice of the method of claims 2 and 3 with a reasonable expectation of success.
Regarding claim 4, Egan teaches treatment resistant hypertension (TRH) has been defined as BP above goal on ≥3 or controlled to goal on ≥4 BP medications prescribed at op-timal doses and preferably includ-ing a diuretic (page 495, center, 1st paragraph); prescribing ≥3 different antihypertensive medication classes, e.g., thiazide-type diuretic, renin-angiotensin blocker and calcium antagonist at ≥50% of maximum recommended doses reasonably defines optimal therapy (page 495, left); and intensifying diuretic therapy, e.g., adding an aldosterone antagonist, is effec-tive for many TRH patients who are volume expanded (page 495, left).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to utilize the method of treating treatment resistant hypertension comprising administering an effective amount of (R)-Compound 1 to human having a blood pressure of greater than 130 / 80 and that (R)-Compound 1 and on a stable background of hypertensive regimen comprising ≥3 antihypertensive agents wherein one of the antihypertensive agents is a diuretic in view of the teachings of Egan, since the prior art teaches optimum hypertension treatments include a diuretic and intensifying diuretic therapy by adding an aldosterone antagonist is effective for many treatment resistant hypertension patients.
Taken together, all this would result in the practice of the method of claims 2 and 3 with a reasonable expectation of success.
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 1-13, 22, and 25-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 9, 11, 13, 17-20, 24, 25, 27, 28, 30-33, 35, and 37 of copending Application No. 19/100,134 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to a method of treating hypertension in a human having a mean seated blood pressure of30/80 mmHg, comprising administering 0.1 to 10 mg/day of (R)-Compound 1 to the human wherein the human is on a stable background hypertensive regimen prior to the administration of the (R)-Compound 1 wherein the stable background hypertensive regimen comprises ≥3 antihypertensive agents.
The copending claims are directed to a method of treating uncontrolled or treatment-resistant hypertension in a human in need of treatment thereof, comprising administering during a treatment period, 1 mg/day or 2 mg/day of (R)-Compound 1 to the human:(R)-Compound wherein the human is on a stable background anti-hypertensive regimen prior to the administration and during the treatment period wherein the stable background hypertensive regimen comprises ≥3 antihypertensive agents.
Thus, the method of the copending claims would anticipate the instantly claimed method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-13, 22, and 25-27 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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