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 .
Applicants' arguments, filed July 22, 2026, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Drawings
The drawings were received on July 22, 2026. These drawings are acceptable.
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.
Regarding the obviousness rejections below, Applicants argue that administration of ampreloxetine for 22 weeks is not disclosed by Hegde. The additional references of Pavy-Le Traon et al., Kaufmann et al. Fanciulli et al. also do not disclose such an administration schedule.
These arguments are unpersuasive. When evaluating obviousness, the explicit teaching of the prior art is considered but also taken into account are the implicit and inherent teachings of the prior art and the knowledge of one of ordinary skill in the art. While there is no explicit disclosure of administration of about 10 mg ampreloxetine for at least 22 weeks to a subject as claimed in the applied prior art, when those factors are considered, the method of claim 1 is rendered obvious by Hegde and the determination of the optimal dosing regimen such as the length of administration for a particular patient that would be carried out by one of ordinary skill in the art. Applicants have not provided any arguments as to why such optimization would not be routine and/or the non-obvious nature of the selection of the patient population based on certain classification criteria and levels for scales that are known in the art for use in evaluating patients with multiple system atrophy.
Applicants also argue there was no reasonable expectation of success of ampreloxetine being safe and effective for treating nOH (neurogenic orthostatic hypotension). Further confirmatory studies were to be conducted due to the accelerated approval of the drug for this indication. Two other drugs, droxidopa and midodrine hydrochloride, were not known to provide efficacy beyond a short period of time with no effectiveness past 2 weeks being demonstrated for droxidopa in the treatment of this condition. The known information for these two other drugs means a person skilled in the art would not have had a reasonable expectation of success that ampreloxetine administration as claimed would be a safe and effective treatment for prolonged periods of time, let alone for at least 22 weeks.
These arguments are unpersuasive. The need for further confirmatory studies by regulating authorities that approved drugs for use is not the same standard as for a prima facie case of obviousness. While the information provided via the other drugs, without citation to the source of the information is noted, arguments without factual support are mere allegations and are not found persuasive. Applicants do not establish any nexus between the structure and/or mechanism of action of these other treatments that would lead one of ordinary skill in the art to conclude that the same issues would reasonably be expected to arise with ampreloxetine. In Hegde, the study compound ampreloxetine was administered once daily for up to 20 weeks in confirmed responder subjects as part of an open label extension study to evaluate efficacy, safety and tolerability (col 29, ln 6 – 27). Based on the evidence of record, one of ordinary skill in the art would have had a reasonably expectation of success that ampreloxetine could be administered in the claimed dosing regimen.
Applicants also argue that unexpected results of the prolonged treatment with the claimed dosing regimen are set forth in the present specification. The 22 week treatment showed effectiveness against various subgroups of nOH patients. Nothing in the cited references suggest the surprising technical effect discussed in the application as filed. One of ordinary skill in the art reading Hegde in view of the approved nOH treatments that lack long term efficacy.
These arguments are unpersuasive. Please see MPEP 716.02 et seq. for a complete discussion regarding allegations of unexpected results. Applicants bear the burden of explaining the evidence offered in support of alleged unexpected results and also establishing what the expected results would be, as without that information, if the observed results are in fact unexpected cannot be determined. The mere fact that other treatments might not be effective for 22 weeks does not establish what the expected results would be for ampreloxetine. Any such evidence must also be reasonably commensurate in scope with the claims and most notably, the claims encompass any time period longer than 22 weeks. It appears that the longest time course studied was 22 weeks and therefore in at least this aspect, the evidence proffered in support of the alleged unexpected results is not reasonably commensurate in scope with the claims.
Claim(s) 14 – 16, 18 and 26 – 28 were rejected under 35 U.S.C. 103 as being unpatentable over Hegde (US 10,238,642). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
Claim(s) 14 – 16, 18, 23 – 28 and 37 were rejected under 35 U.S.C. 103 as being unpatentable over Hegde further in view of Pavy-Le Traon et al. (J Neurol Neurosurg Psychiatry, 2015) and/or Kaufmann et al. (Clin Auton Res, 2012). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
Claim(s) 14 – 16, 18, 19, 23 – 28 and 37 were rejected under 35 U.S.C. 103 as being unpatentable over Hegde and optionally Pavy-Le Traon et al. and Kaufmann et al. further in view of Fanciulli et al. (Mov Disorders, 2019). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
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.
Regarding the nonstatutory double patenting rejections below which all are based on U.S. Patent No. 10,238,642, Applicants argue that the claims of US’642 are silent as to administering ampreloxetine for at least 22 weeks or to subjects having an OSHA composite score of 5 or greater before the administration and/or OSHA item 1 score of 7 or greater before administration. As discussed in greater detail above, the secondary references do not reach or suggest these limitations.
These arguments are unpersuasive. As discussed in greater detail in the Office Action mailed April 23, 2026 and above, determination of the duration of treatment is prima facie obvious and the evidence of record of alleged unexpected results does not outweigh that prima facie case. The selection of the patients to be treated with a particular treatment depending on particular symptoms and the severity of the symptoms is within the skill of those of ordinary skill in the art and there is no evidence of record as to the criticality of the selection criteria or treatment regimen.
Claims 14 – 16, 18, 23 – 27 and 37 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 24 of U.S. Patent No. 10,238,642 optionally in view of Pavy-Le Traon et al. (J Neurol Neurosurg Psychiatry, 2015) and/or Kaufmann et al. (Clin Auton Res, 2012). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
Claims 14 – 16, 18, 23 – 28 and 37 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 24 of U.S. Patent No. 10,238,642 optionally in view of Pavy-Le Traon et al. (J Neurol Neurosurg Psychiatry, 2015) and/or Kaufmann et al. (Clin Auton Res, 2012) further in view of Hegde (US 2018/0055831; Hegde-831). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
Claims 14 – 16, 18, 19, 23 – 27 and 37 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 24 of U.S. Patent No. 10,238,642 optionally in view in of Pavy-Le Traon et al. (J Neurol Neurosurg Psychiatry, 2015) and/or Kaufmann et al. (Clin Auton Res, 2012) further in view of Fanciulli et al. (Mov Disorders, 2019). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 23, 2026 and those set forth herein.
Conclusion
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 Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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