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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3 September 2026 has been entered.
Applicant’s amendment of 3 September 2026, in which claims 30-43 have been cancelled, and new claims 44-53 have been added, is acknowledged.
Claims 44-53 are pending in the instant application.
Claims 44-53 are being examined herein.
Response to arguments of 3 September 2026
In view of Applicant’s amendment of 3 September 2026, all the rejections to claims 30-43 are herein withdrawn. Claims 30-43 have been cancelled.
New rejections are made below, based on Applicant’s amendment of 3 September 2026.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Note: the recitation “less than 30 days” in instant claims 44-53 finds support in the term “within 30 days” (Specification, [0015], [0026]), which is interpreted to be 30 days or less (than 30 days) from the start of the time interval. Similarly, the recitation “less than 90 days” in instant claims 44-53 finds support in the term “within 90 days” (Specification, [0015], [0016], [0026]), which is interpreted to be 90 days or less (than 90 days) from the start of the time interval.
Claims 44-53 are rejected under 35 U.S.C. 103 as being unpatentable over Ong et al. (Lancet 2010, 376, 1476-1484, cited in IDS; Supplementary webappendix, cited in PTO-892 of 4 December 2024).
Ong (Lancet 2010, 376, 1476-1484) teaches a method for treating Ehlers-Danlos syndrome, comprising administering to a patient in need thereof a 100 mg daily dose of celiprolol, and increasing the daily dose to 400 mg according to the following schedule (Figure 1, and page 1477, left column, first paragraph under study design):
celiprolol was started at 100 mg daily dose and was uptitrated by 100 mg steps (titrated to 200 mg/day, 300 mg/day and 400 mg per day) every six months.
Thus, the method taught by Ong teaches that the initial dose of celiprolol (100 mg/day) and the final/maintenance/maximum therapeutic dose of celiprolol (400 mg/day) are same as in the instant claims; and the daily dose is uptitrated in steps of 100 mg increments as in the instant claims.
The method taught by Ong teaches a celiprolol dose escalation as follows:
100 mg/day for 6 months; 200 mg/day for 6 months; 300 mg/day for 6 months; 400 mg/day until the 5-year intervention point is reached, which is consistent with three dose increases in increments of 100 mg/day within the treatment regimen, as in the instant claims.
Ong teaches (Supplementary material webappendix, page 9, attached) patients suffering from Ehlers-Danlos treated with both celiprolol and blockers of the renin angiotensin system, namely ACEi and/or ARB, which are cardiovascular drugs of instant claims 50, 52, 53. Ong teaches (Ong page 1481, left column, first paragraph) that said blockers of the renin angiotensin system did not change the effect of celiprolol in these patients.
Ong also teaches (page 1478, right column, last paragraph, also Figure 1) that patients treated with beta blockers (which are cardiovascular drugs of instant claims 50, 51) for arterial dissection or rupture or another cardiovascular indication were included in the cohort of patients suffering from Ehlers-Danlos treated with celiprolol.
Ong does not teach the method, where the celiprolol was started at 100 mg daily dose and was uptitrated by 100 mg steps (titrated to 200 mg/day, 300 mg/day and 400 mg per day) every less than 30 days, to arrive at a dose of 400 mg/day in less than 90 days, as in the instant claims.
It would have been obvious to a person of ordinary skill in the art to use the teachings of Ong to arrive at the instantly claimed dosing schedule of celiprolol used in a method of treating Ehlers-Danlos syndrome in a patient in need thereof. The person of ordinary skill in the art would have explored a celiprolol dosing regimen encompassing dose escalation based on patient monitoring, starting from the initial 100 mg celiprolol (commercially available celiprolol is hydrochloride salt, thus 100 mg celiprolol in Ong is actually 100 mg celiprolol hydrochloride salt) daily taught by Ong, the daily dose being uptitrated in 100 mg increments, as in Ong, to the 400 mg daily taught by Ong, and would have varied the dose escalation period, so that the maximum therapeutic dose of 400 mg taught by Ong is reached faster (in less than 90 days), with the expectation of achieving therapeutic effect.
With respect to duration and frequency of treatment, it is typical for skilled clinicians to monitor subjects in order to determine when the treatment is providing therapeutic benefit, and to determine whether to increase or maintain/decrease dosage, increase or maintain/decrease administration frequency, discontinue treatment, resume treatment or make other alteration to treatment regimen. In this case, the initial dose of celiprolol (100 mg/day) and the final/maintenance/maximum therapeutic dose of celiprolol (400 mg/day) are the ones taught by Ong; further, the daily dose is uptitrated in steps of 100 mg increments as in Ong; determining the dosing schedule, i.e. the appropriate intervals of time for dose escalation, in order to reach the maximum dose faster and safely for the patients, is routine for the skilled artisan/clinician.
Further, with respect to claims 47-53, it would have been obvious to administer celiprolol in combination with a beta blocker, or an ARB, or an ACEi, in a method of treating Ehlers-Danlos, because Ong teaches patients suffering from Ehlers-Danlos treated with both celiprolol and blockers of the renin angiotensin system, or with both celiprolol and a beta blocker, where blockers of the renin angiotensin system did not change the effect of celiprolol in said patients.
As such, claims 44-53 are rejected as prima facie obvious.
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 44-53 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-15 of U.S. Patent 11,523,997 (cited in IDS).
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-15 of U.S. Patent 11,523,997 anticipate or render obvious the instant claims.
Claims 1-15 of U.S. Patent 11,523,997 are drawn to a method for treating vascular Ehlers-Danlos syndrome, comprising administering to a patient in need thereof an initial daily dose of about 91.25 mg celiprolol (or 100 mg celiprolol hydrochloride in claim 8) for about 1 month, followed by administering to the patient a second daily dose of about 182.5 mg celiprolol (or 200 mg celiprolol hydrochloride in claim 8) for about 1 month, followed by administering to the patient a third daily dose of about 273.75 mg celiprolol (or 300 mg celiprolol hydrochloride in claim 8) for about 1 month, followed by administering to the patient a fourth daily dose of about 365 mg celiprolol (or 400 mg celiprolol hydrochloride in claim 8).
The method of claims 1-15 of U.S. Patent 11,523,997 recites administration of an initial dosage amount of 100 mg celiprolol hydrochloride, and increasing the daily dose to 400 mg celiprolol in increments of 100 mg celiprolol administered at intervals of about 1 month, thus reaching 400 mg celiprolol in about 3 months (which is about 90 days) of the initial dosage. The about 1-month intervals in claims 1-15 of U.S. Patent 11,523,997 are very close or overlap with the instant intervals of less than 30 days (which include 29 days), rendering the instant method obvious. MPEP 2144.05.I.
Further, with respect to claims 47-53, it would have been obvious to administer celiprolol in combination with a beta blocker, or an ARB, or an ACEi, in a method of treating Ehlers-Danlos because Ong teaches patients suffering from Ehlers-Danlos treated with both celiprolol and blockers of the renin angiotensin system, or with both celiprolol and a beta blocker, where blockers of the renin angiotensin system did not change the effect of celiprolol in said patients.
As such, claims 44-53 are rejected as prima facie obvious.
Conclusion
Claims 44-53 are rejected.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
