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 .
Status of the Claims
Claims 1-29 are pending and before the Examiner.
Priority
The following continuity data is acknowledged in the present application file:
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09 September 2025 has been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered 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.
Claim 5 is 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.
Claim 5 recites the limitation “said initial 4 weeks of treatment”, which lacks antecedent basis as it is not recited in claim 1. (*Note: For examination purposes claim 5 will be treated as if dependent on claim 4, which recites the 4 weeks of treatment, to speed up prosecution).
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 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 1-29 are rejected under 35 U.S.C. 103 as being obvious over WO 2018153513 (‘513; Publication Date: 30 August 2018, IDS) in view of US Patent No. 11174247 (‘247; Publication Date: 16 November 2021) and in view of Gradman et al. (J Clin Hypertens (Greenwich) 2011, 3, 3; Publication Date: 03 March 2011).
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Regarding claims 1-3, 16-17, 19-21, and 24-25, reference ‘513 discloses a method of treating difficult to treat/resistant hypertension by administering a pharmaceutical composition containing aprocitentan in combination with standard background therapy comprising at least three other antihypertensive drugs selected from an angiotensin receptor blocker (especially valsartan) and/or a calcium channel blocker (especially amlodipine), and preferably a thiazide-like diuretic (especially hydrochlorothiazide or chlorthalidone) [line 5-8, page 2]. It further discloses Example K, where aprocitentan is used in combination with EXFORGE HCT (a fixed dose combination of valsartan; an angiotensin receptor blocker/ amlodipine; a calcium channel blocker/ hydrochlorothiazide, a diuretic) in spontaneously hypertensive rats [line 15-20, page 37] and results showed Aprocitentan reduced blood pressure when added on top of EXFORGE HCT [Fig. 19, page 51]. The reference does not disclose wherein the method comprises administering to the human subject a pharmaceutical composition comprising a clinically proven effective amount of aprocitentan.
Reference ‘247 discloses the use of aprocitentan in combination with further active ingredients including angiotensin receptor blocker, a calcium blocker, and a diuretic for the treatment of endothelin related diseases (e.g., resistant hypertension) [line 10-15, page 18]. It further discloses the method comprises administering to a subject (preferably a human subject) in thereof an effective amount of aprocitentan in combination with said active ingredients (line 28-30, page 21). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to administer the combination therapy of ‘513 to human subjects as taught by ‘247 with reasonable expectation of success because ‘513 demonstrates that the combination therapy is effective in treating hypertension in an animal model, and ‘247 discloses the administration of the same therapy to humans for the same therapeutic purpose. Accordingly, a person of ordinary skill in the art would have been motivated to apply the known combination therapy to human subjects to obtain its known therapeutic benefits in treating resistant hypertension.
Regarding claims 12-15, 22-23, and 28-29, reference ‘513 discloses that aprocitentan or a pharmaceutically acceptable salt thereof is comprised in a pharmaceutical unit dosage form suitable for the oral administration of 2.5 to 100 mg (in particular 5 or 10 to 50 mg, notably 12.5 mg, 25 mg or 50 mg, especially 12.5 mg or 25 mg) per day of aprocitentan [line 8-10, page 10].
Regarding claim 18, Gradman et al. discloses that combination therapy involving angiotensin receptor blockers, calcium channel blockers, or diuretics, a beta blocker is often added for the treatment of hypertension to achieve additional blood pressure control [page 3-5, Table1]. Therefore, it would have been obvious to try to modify the antihypertensive regimen of ‘513 and ‘247 by adding a beta blocker to have additional blood pressure reduction and improved control of hypertension.
Regarding claims 4-11 and 26-27, the references do not disclose data of the mean reduction from baseline blood pressure (systolic and diastolic) in a human subject with resistant hypertension after 4 to 32 weeks of treatment compared to the placebo. However, the instantly claimed data reflects the result of administering the combination therapy already disclosed by the references, therefore, it does not overcome the prima facie case of obviousness. Therefore, considering the teachings of ‘513, ‘247 and, Gradman it would have been obvious to
combine these methods through routine optimization (such as dosage, concentration, or relative proportion of the combination agents) to achieve the instantly claimed mean reduction from baseline blood pressure (systolic and diastolic) data. Accordingly, one of ordinary skill in the art would have been motivated to evaluate the therapeutic response and determine whether the combination therapy produces the desired result when administered to human subjects.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
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 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 10-11, 13-14, and 16 of copending Application No. 18868772 in view of Karagianni et al. (Pharmaceutics 2018, 10, 18; Publication Date: 02 January 2018).
The co-pending application discloses the use of the crystalline form of aprocitentan for the treatment of hypertension (e.g., resistant hypertension), but it does not disclose the amorphous form (non-crystalline) of aprocitentan. Karagianni et al. discloses that for pharmaceutical materials, amorphicity offers advantages, since amorphous solids have higher solubility and dissolution rates [page 2]. Therefore, it would have been obvious to a person of ordinary skills in the art to make and use the non-crystalline form of aprocitentan as claimed for the treatment of resistant hypertension with reasonable expectation of success because of the improved solubility and dissolution. Accordingly, the artisan would have reasonably expected the non-crystalline form to remain therapeutically effective since it contains the same pharmaceutical active component.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 12-16, and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-26, 43-44, and 46-47 of U.S. Patent No. 11174247, IDS.
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent discloses a method for the treatment of hypertension (e.g., resistant hypertension) comprising the administration of a pharmaceutically effective amount of aprocitentan, or of a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein aprocitentan is administered in combination with a pharmaceutically effective amount of an angiotensin receptor blocker, calcium channel blocker, and a diuretic or a pharmaceutically acceptable salt thereof, which reads on the method of the instant application.
The limitation specifying the human subject in the instant claims does not render the claimed invention patentably distinct from the method disclosed by the reference. This is because the reference claims encompass the administration of the instantly claimed combination therapy to humans. Accordingly, the claimed subject matter would have been an obvious variation of the subject matter defined in the reference claims.
Claims 1-2, 13, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5, 7, 20, and 23 of U.S. Patent No. 11787782; IDS in view of Karagianni et al. (Pharmaceutics 2018, 10, 18; Publication Date: 02 January 2018).
The reference patent discloses a method for the treatment of hypertension (e.g., resistant hypertension) comprising the administration of a pharmaceutically effective amount of aprocitentan, or of a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein aprocitentan is administered in combination with a pharmaceutically effective amount of an angiotensin converting enzyme inhibitor or a pharmaceutically acceptable salt thereof; and wherein the aprocitentan is in crystalline Form A.
The limitation specifying the human subject in the instant claims does not render the claimed invention patentably distinct from the method disclosed by the reference patent. This is because the reference claims encompass the administration of the instantly claimed combination therapy to humans. Accordingly, the claimed subject matter would have been an obvious variation of the subject matter defined in the reference claims.
In addition, the patent does not disclose the amorphous form (non-crystalline) of aprocitentan. Karagianni et al. discloses that for pharmaceutical materials, amorphicity offers advantages, since amorphous solids have higher solubility and dissolution rates [page 2]. Therefore, it would have been obvious to a person of ordinary skills in the art to make and use the non-crystalline form of aprocitentan as claimed for the treatment of resistant hypertension with reasonable expectation of success because of the improved solubility and dissolution. Accordingly, the artisan would have reasonably expected the non-crystalline form to remain therapeutically effective since it contains the same pharmaceutical active component.
Conclusion
Claims 1-29 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARINE P SEUDIEU SEUDIEU whose telephone number is (571)272-0459. The examiner can normally be reached Mon-Fri 8 AM - 4 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.S./Examiner, Art Unit 1626
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
