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
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 30, 2026 has been entered.
Status of Claims
No claim amendments are made.
Claims 1-16 are pending and currently under examination.
Priority
This application 18/201,920 filed on 05/25/2023 is a continuation in part of International Application Serial No. PCT/PT2021/050044, filed December 17, 2021, which claims the benefit of United Kingdom Patent Application Serial No. 2019954.3, filed December 17, 2020, United Kingdom Patent
Application Serial No. 2106133.8, filed April 29, 2021 and United Kingdom Patent Application Serial No. 2109826.4, filed July 7, 2021. The certified copy of GB application No. 2019954.3, 2106133.8, 2109826.4 are filed on 09/13/2023.
It’s noted priority applications are clinical trial design for treating early Parkinson with L-dopa/DDCi and opicapone, and no clinical data/efficacy data treating early Parkinson’s patients without clinically diagnosed motor complications are disclosed. Instant Tables 2-16 in Efficacy analysis, Sensitivity analysis etc. are not disclosed in GB application No. 2019954.3, No. 2106133.8, No. 2109826.4 and PCT/PT2021/050044.
Information Disclosure Statement
The information disclosure statement filed 12/03/2025 is being considered by the Examiner. Reference written in foreign language is considered to the degree of English abstract or patent family of foreign patent by Examiner.
Action Summary/ Response to Arguments
Applicant's remarks filed 04/30/2026 have been fully considered, but NOT persuasive to overcome rejections under 35 U.S.C.§ 103 and double patenting rejections on the record.
Maintained rejection:
I. Rejections of claims 1-16 under 35 U.S.C.§103 over: 1) Reichmann (Translational Neurodegeneration, 2020, 9(1):9) in view of Soares da Silva’ 468; 2) Soares da Silva’ 468 in view of Ettcheto (Expert Opinion On Drug Discovery, 2020, Vol. 15, No. 9, 993–1003).
II. Rejections of claims 1, 5, 7-12, 14-16 over US patent No. 10,357,468 B2 and US patent application No.18/032,034 on the ground of double-patenting.
All claims are rejected based on the same prior art in last office action mailed on 12/04/2025. No claim amendments are made in instant request for continued examination. Thus, this office action based on the same prior art on the record is made Final.
It’s noted US application No. 18/370,005 (now abandoned), a continuation of instant application, claims the same subject matter as instant application and was also rejected based on the same prior art.
Rejections under 35 U.S.C.§103
Applicant argues about interpretation of the claims: 1). motor complications are distinct from motor symptoms in early Parkinson's disease; 2). the instant claims are directed to patients at early stage of Parkinson's disease exhibiting clinically diagnosed motor signs and symptoms although not detectable motor complication. Applicant further argues Levodopa/ Carbidopa/ entacapone (LCE) failed as a treatment for early-stage Parkinson's disease (See Abstract of Exhibit C) and none of the cited documents suggest that opicapone (or any other COMT inhibitor) should be used in the treatment of early-stage Parkinson's disease (Remarks, page 4-9).
RESPONSE: The Examiner does not dispute early- and later-stage Parkinson's disease are distinct stages of disease with different treatments. It’s also acknowledged that COMT inhibitors (opicapone, entacapone) were licensed to treat later stages of Parkinson's disease. However, instant claims do not specifically define the patients without clinically diagnosed motor complications at early-stage Parkinson's disease. Nonetheless, motor signs and symptom exist at almost all stages of Parkinson’s disease which has substantial effect on patients’ quality of life and control of motor signs and symptom is a key clinical need for almost all PD patient. As explained in previous office action mailed on 12/04/2025, the failure of entacapone treating early-stage Parkinson's is irrelevant and is NOT teaching away because opicapone and entacapone have different structures, different chemical and physical properties, different biological activity, different pharmacokinetic and pharmacodynamic parameter. The failure of levodopa/ carbidopa/ entacapone (LCE) for treating early-stage Parkinson's disease does not necessarily discourage a skilled artisan from exploring other COMT inhibitor (e.g. opicapone) in adjunct therapy with levodopa/DDCi. To the contrary, in search for alternative treatment in different Parkinson's patient population, a skilled artisan would be motivated to explore alternative COMT inhibitor, e.g. opicapone in adjunct therapy with levodopa/ DDCi based on the beneficial teaching of opicapone over entacapone by prior art.
Reichmann (2019) and incorporated reference teach opicapone has advantage over entacapone: “ In one pharmacokinetic study, opicapone (50 mg once daily) significantly increased levodopa bioavailability compared with both placebo and entacapone (200 mg TID) by increasing substantially the trough plasma levels and each dose systemic exposure time (half-life) by at least 1 h (See page 2/9, left column, 2nd para). Please note the Reichmann data is consistent with the data as Applicant argues at page 11 of Remarks.
Soares da Silva’ 468 also teaches similar advantage of opicapone over entacapone, wherein levodopa extent of exposure (AUC) was significantly increased up to 78.9% and 73.7% with 75 mg-OPC in comparison to placebo and ENT, respectively (See Example 2).
Ettcheto (2020) reviews the preclinical discovery/development, pharmacology, pharmacokinetics, safety profile of OPC, evaluates clinical and post-marketing data of OPC and concludes “OPC is a third generation COMT inhibitor with a novel structure. It has an efficacy and tolerability superior to its predecessors, tolcapone (TOL) and entacapone (ENT)” (See Expert Opinion). Fabbri (2018) reviews pharmacological properties, clinical efficacy, and safety profile of opicapone (aka OPC, BIA 9-1067) as a novel and effective L-dopa adjunct treatment for Parkinson’s disease. Fabbri (2018) teaches “opicapone (OPC) has been developed to provide higher COMT inhibitory potency and avoid liver toxicity compared with previous COMT inhibitors (e. g. tolcapone, entacapone)”(See page 1529).
Jenner (2021, Applicant’s Exhibit B) teaches experimental biochemistry and pharmacology of opicapone: “The persistent enzyme inhibition produced by opicapone translates into functional activity that can be seen both invitro and in-vivo experimental models. In liver and kidney homogenates from rats treated orally with opicapone, tolcapone or entacapone, opicapone produced a more marked and more sustained inhibition of COMT than the other drugs. The effects on levodopa (in conjunction with a DDC inhibitor) metabolism also reflects the long-lasting inhibition of COMT produced by opicapone” (See page 1023, left column). Jenner further teaches the effect of opicapone on levodopa pharmacokinetic profile: “In patients with PD, administration of opicapone dose dependently increases levodopa bioavailability by up to 95% dependent on dose and duration of levodopa administration. As assessed by AUC, opicapone was more effective in increasing levodopa exposure than occurred after entacapone administration, reflecting its sustained COMT inhibition that endures over 24 hours. Administration of opicapone also increased the minimum plasma concentration (Cmin) for individual levodopa doses by up to 3.1-fold. This is an important facet of opicapone’s action as the avoidance of low plasma levodopa trough levels is associated with a reduction in motor fluctuations. There may also be another advantage of the dissociation between opicapone’s pharmacokinetic profile and its functional activity. In some PD patients, entacapone absorption interferes with levodopa absorption, resulting in a delayed levodopa tmax and reduced Cyax on simultaneous administration This might explain an apparent lack of response to entacapone in some individuals. While there is also a potential interaction between levodopa and opicapone when given at the same time, its once daily bedtime administration (at least 1 hour before or after levodopa combinations) and rapid plasma clearance minimizes any interaction with levodopa based on drug absorption”(See page 1024 right column).
Unlike levodopa/ carbidopa/ entacapone (LCE), instant claimed DDCi genus is not limited to specific DDCi and drawn to broad scope of adjunct therapy. In search for alternative treatment for Parkinsons’ disease, a skilled artisan would be motivated to explore opicapone adjunct therapy with levodopa/DDCi for different Parkinson's patient population and reasonably expect opicapone/ levodopa/DDCi would provide alternative treatment for control of motor signs based on the beneficial teachings of prior art and general knowledge of treatment for Parkinson's disease.
Applicant agues about the Examiner’s interpretation of instant data in Table 4 and Table 13 , but concedes: “the data does not show that opicapone slows disease progression in early Parkinson's disease patients, which it was not powered to do. Instead, it shows that for early Parkinson's disease patients without motor complications, opicapone improves the symptomatic treatment as measured by MDS-UPDRS Part III (Figures 1 and 2), MDSUPDRS Pait II+III (Figure 3) and reported an improvement in their clinical condition (PGI-I; Figure 4a)” (Remarks page 10). Applicant further argues “surprising nature of the effect” compared to Reichmann, Soares da Silva '468 and combination thereof ( Remarks, page 9-15).
RESPONSE: As Applicant admits, opicapone-treated patients still developed motor complications (5.5%) compared to placebo-treated patients (9.8%) indicating opicapone does not slow disease progression in early Parkinson's disease patients. As disclosed by instant Spec( See page 31) : No significant effects were observed for the MDS-UPDRS Part 1, MDS-UPDRS Part IV or PDQ-39 total scores. The alleged symptomatic treatment of motor signs in earlier Parkinson’s is not considered statistically significant to be unexpected based on the combined teachings of prior art and general knowledge of Parkinson’s treatment.
Applicant’s arguments about Soares da Silva '468 (Remarks, page 12-15) are directed to different embodiment and NOT persuasive. Soares da Silva’ 468 is Applicant’s own work teaching the use of opicapone for treatment of Parkinson’s disease. Although Soares da Silva’ 468 does not explicitly recite the negative limitation “without clinically diagnosed motor complications”, Soares da Silva’ 648 teaches embodiments of slowing or delaying progression of PD wherein a patient is diagnosed with PD but previously untreated for, or a patient who has not previously been treated with levodopa (Col. 5, lines 44-64; Col. 10, lines 13-50, claims 3 and 12). These untreated patients are construed as encompassing patients without clinically diagnosed motor complications since they have not been treated with levodopa and motor complications are related to levodopa therapy. Although Soares da Silva’ 648 does not provide experimental data specifically for patients at early stage of Parkinson’ disease, Applicant cannot negate the broad teachings of its own work based on the absence of experimental data or direct teaching for the claimed embodiment.
Applicant argues prior art COMT inhibitors are ineffective in treating early Parkinson's disease and efficacy observed at one stage of Parkinson’s disease cannot be extrapolated to patients at another stage (Remarks, page 15-16).
RESPONSE: The relevant matter is not whether opicapone treats early Parkinson's disease by itself, but whether the prior art provide teaching to investigate / explore opicapone/levodopa/DDCi adjunct therapy for treating different Parkinson’s patient. Opicapone adjunct therapy in combination of levodopa/ DDCI has been approved in Europe since 2016 for treating motor fluctuations of Parkinson's disease which also involves controlling motor signs/symptoms, wherein the dosage regimen, adverse events, TEAE, safety profile have been thoroughly studied as elaborated in prior art (Reichmann, Soares da Silva’ 468, Ettcheto, Fabbri, Ferreira, Jenner, etc.). A skilled artisan would be motivated to explore/ investigate opicapone levodopa/ DDCI adjunct therapy for treating other PD patients (including different stages) and reasonably expect opicapone/levodopa/ DDCI adjunct therapy provide alternative treatment for control of motor signs/symptoms in PD patients whether the patients is with or without clinically diagnosed motor complication.
Regarding reasonable expectation of success, the examiner agrees that physiology of Parkinson's disease changes in different stages. However, lack of direct extrapolation does not establish instant observed result as unexpected. The function/biological activity of opicapone is the property of opicapone whether the patient is with or without clinically diagnosed motor complication/ motor fluctuation. The reasonable expectation of success is not that prior art have to predict the absolute therapeutic effectiveness/efficacy of the drug. "Obviousness does not require absolute predictability of success." Id. at 903, 7 USPQ2d at 1681. As stated in MPEP 2143.02. I : “Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute"))”.
As elaborated in documented 103 rejection, Reichmann teaches opicapone as an effective adjunct option for management of motor fluctuations in levodopa-treated PD patient wherein opicapone was generally well tolerated and significantly improved both motor and non-motor symptoms. Soares da Silva’ 468 collectively teaches a method of slowing or delaying the progression of PD and/or slow the progression of motor symptoms by administering opicapone to untreated PD (de nova) patients or a patient who has not previously been treated with levodopa. A skilled artisan would reasonably expect opicapone/levodopa/DCCI exhibit certain efficacy in controlling the motor symptoms/signs since opicapone (50 mg once daily) significantly increased levodopa bioavailability as taught by Reichmann. Thus, the discovery of opicapone improving therapeutic effect of levodopa therapy at early- stage Parkinson's disease patients are not unexpected to POSA based on the combined teachings of prior art.
The aforementioned response/rationale also apply to rejections of claims 1-16 over Soares da Silva’ 468 in view of Ettcheto under 35 USC §103, and double-patenting rejections over US patent No. 10,357,468 B2 and US patent application No.18/032,034, which are maintained and made Final.
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, 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 non-obviousness.
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 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 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Reichmann et al.( Translational Neurodegeneration, 2020 Mar 4;9(1):9, Applicant’s IDS dated 08/31/2023, # CZ5, “Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study”), in view of Soares da Silva et al. (US 10,357,468 B2, Applicant’s IDS dated 08/31/2023)(maintained).
Reichmann reviews effectiveness, safety and tolerability of opicapone adjunctive therapy in clinical trial OPTIPARK (NCT02847442) which is a prospective open-label, single-arm, multicenter trial evaluating opicapone 50 mg effectiveness in levodopa-treated PD patients experiencing motor fluctuations under clinical practice conditions(See whole paper).
Reichmann disclose that COMT inhibitors have been an established first-line strategy to manage motor fluctuations for over 25 years and are the only adjunct class to directly address the peak-trough variations in plasma levodopa levels that clinically manifest as wearing-off fluctuations. “The third generation COMT inhibitor – opicapone (Ongentys®, BIAL-Portela & Cª, S.A.Portugal) has been approved in Europe since 2016 as adjunct therapy to preparations of levodopa/DDCI for end-of-dose motor fluctuations. Based on rational drug design, opicapone was specifically developed to reduce the
risk of toxicity and improve peripheral tissue selectivity. In one pharmacokinetic study, opicapone (50 mg
once daily) significantly increased levodopa bioavailability compared with both placebo and entacapone (200 mg TID) by increasing substantially the trough plasma levels and each dose systemic exposure time (half-life) by at least 1 h. Phase III studies have established that treatment with opicapone 50mg once daily reduces daily OFF-time ,without significantly increasing ON-time with troublesome dyskinesia versus placebo, and most patients show an improvement in the Clinician’s Global Impression of Change (CGI-C)”(See page 2, left column, Introduction).
Reichmann teaches endpoints were assessed at baseline, 1 month , 3 month and 6 months, primary outcome was CGI-C ,and secondary assessments include the Patient’s Global Impression of Change (PGI-C), WOQ-9 assessments, the Unified Parkinson’s Disease Rating Scale (UPDRS) sections I-IV], the Parkinson’s Disease Questionnaire (PDQ-8)(See page 3, left column; Fig. 3; Table 2). Reichmann discloses inclusion of patients with idiopathic PD identified by Wearing-off Questionnaire (WOQ-9), Hoehn and Yahr stages I-IV (during ON) and treated with 3–7 daily doses of levodopa/DDCI and “key exclusion criteria were atypical parkinsonism, severe unpredictable OFF periods (investigator judgment)… Patients treated with levodopa/DDCI/entacapone before trial entry were to discontinue entacapone at the baseline visit and switch to a levodopa/DDCI formulation. Likewise, separate entacapone was to be discontinued by the baseline visit at the latest”.(See page 2, Study population)(which reads on instant claim 6).
Reichmann discloses the study design of OPTIPARK (NCT02847442): “Patients received opicapone 50 mg capsules once-daily at bedtime, at least 1 hour before or after the last daily dose of levodopa/DDCI. The total duration of treatment was 6 months in UK sites and 3 months in German sites… Investigators were free to adjust total daily levodopa/DDCI doses according to individual need after the baseline visit”( See page 2, Study Design)(which reads on instant claims 7-13).
Reichmann concludes that opicapone was generally well tolerated and significantly improved both motor and non-motor symptoms and quality of patient’s life, and confirms the clinical utility of opicapone 50 mg as an effective adjunct option for the management of motor fluctuations in levodopa-treated PD (See Conclusion, pages 8 and 9).
Reichmann does not explicitly indicate use of opicapone (OPC) adjunctive therapy in patients without clinically diagnosed motor complications or other negative limitations recited in instant claims. However, It would have been obvious to one of the ordinary skilled in the art to further explore therapeutic efficacy/effectiveness of opicapone adjunctive therapy to combination of levodopa and DDCI in other PD patients who have shown motor signs and symptoms whether they are clinically diagnosed with motor complications or not. A skilled artisan would be motivated to explore more therapeutic application of opicapone adjunctive therapy to combination of levodopa and DDCI based on the teachings of prior art and experiment/optimization(e.g. dosing regimen, patient population, etc.) based on general knowledge of PD treatment because opicapone adjunctive therapy might provide better control of motor signs and symptom which is a key clinical need for almost all PD patient (including the patients without clinically diagnosed motor complications) and has substantial effect on patients’ quality of life.
Consistent with Reichmann, Soares da Silva et al. disclose a method of slowing or delaying the progression of Parkinson’s disease by use of COMT inhibitor opicapone together with levodopa and decarboxylase inhibitor (e. g. carbidopa or benserazide) in patients who may have been experiencing motor symptoms (See e.g. Col 5. lines 20-60; Col. 9, lines 1-45; Col. 10, line 13-47; Table 1, Examples 1 and 2; claims 1-21) (please note carbidopa or benserazide are also dopa decarboxylase inhibitor DCCi as disclosed in instant specification page 1, line 28). Soares da Silva et al. discloses levodopa is administered from 2 to 10 times a day, opicapone is administered once a day, more suitably not at or near mealtime, at least an hour before or after a meal and at least an hour before or after the last administration of levodopa, for example before going to bed (at bedtime)(See Col. 10, lines 3-9; Col. 14, lines 40-49; Examples, claims 1, 4-11, 16-19) (which reads on instant claims 5-13).
Soares da Silva disclose “PD is a heterogeneous disorder with a clinical presentation that varies substantially from patient to patient. Current clinical guidelines (EMA 2012 guideline EMA / CHMP /330418/2012 rev. 2) provide that the clinical diagnosis of PD requires bradykinesia and at least one of the following: resting tremor, muscular rigidity and postural reflex impairment (core symptoms)(See Col. 1, lines 43-50). “For early untreated PD ( de nova) patients, a clinical goal be achieved is to slow the progression of motor symptoms by assessing change in UPDRS. For stable treated PD patients, a clinical goal to be achieved is to slow further decline of motor impairment, prevent progression of disability, and prevent motor and non-motor complications”(See Col. 3. lines 62-67) (please note “stable” PD is considered as the period of time when patients are enjoying the benefits of their levodopa therapy without diagnosed motor complications as disclosed in instant specification page 18). Soares da Silva et al. also teaches endpoints assessment include UPDRS, PD questionnaire (PDQ-39), Non-Motor Symptom Scale (NMSS), PD Sleep Scale (PDSS) and safety assessments (including Columbia Suicide Severity Rating Scale(C-SSRS), Modified Minnesota Impulsive Disorders Interview (mMIDI)( See Col. 15, lines 45-52; Figs. 1 and 2).
Although Soares da Silva does not explicitly recite the negative limitation “without clinically diagnosed motor complications”, Soares da Silva teaches embodiments of slowing or delaying progression of PD wherein a patient is diagnosed with PD but previously untreated for, or a patient who has not previously been treated with levodopa, indicating patients might have no motor complications which is mostly associated with dopaminergic medication (e.g. levodopa) (Col. 10, lines 13-45, claims 3 and 12). Soares da Silva’ 468 collectively teaches a method of slowing or delaying progression of PD and/or slow the progression of motor symptoms by administering opicapone to untreated PD (de nova) patients or a patient who has not previously been treated with levodopa without clinically diagnosed motor complications.
It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instant invention to further explore therapeutic efficacy/effectiveness of opicapone adjunctive therapy to combination of levodopa and DDCI taught by Reichmann and Soares da Silva for treating other PD patients (including patients without clinically diagnosed motor complications) based on the collective teachings of prior art, together with experiment/optimization(e.g. dosing regimen, patients populations, etc.) based on general knowledge of Parkinson’s disease treatment. Before the effective filing date of instant claimed invention, it was already known that opicapone (OPC, Ongentys®) is a third generation COMT inhibitor approved by EC and FDA as a safe adjunctive therapy to combination of levodopa and DDCI for treating Parkinson’s disease as taught by Reichmann. A skilled artisan would have also known the criteria of MDS-UPDRS scores, wearing-off questionnaire (WOQ-9), PDQ-39, NMSS, etc. and practical recommended therapeutic management of uncomplicated PD and stable treated PD as taught by Soares da Silva.
A skilled artisan would be motivated to further explore therapeutic efficacy of opicapone adjunctive therapy in other PD patients based on the combined teachings of prior arts because both teachings are directed to opicapone adjunctive therapy as safe and effective treatment for motor signs and symptoms in slowing or delaying the progression of PD. The control of motor signs and symptom is a key clinical need for almost all PD patient which has substantial effect on patients’ quality of life. The further exploration of opicapone adjunctive therapy based on combined teachings of prior art , together with experiment/optimization(e.g. dosing regimen, patient populations, etc.) based on general knowledge of PD treatment, would provide an alternative safe and potentially effective treatment for control of motor signs and symptom, slow or delay progression of PD in more patients with Parkinson’s disease including those patients that are not clinically diagnosed motor complications.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of treating Parkinson’s disease. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Soares da Silva et al. (US 10,357,468 B2, Applicant’s IDS dated 08/31/2023), in view of Ettcheto et al. (Expert Opinion On Drug Discovery, 2020, Vol. 15, No. 9, 993–1003, published online May 2020, “The preclinical discovery and development of opicapone for the treatment of Parkinson’s disease, Applicant’s IDS dated 12/18/2023)(maintained).
The collective teachings of Soares da Silva are elaborated in preceding 103 rejection and applied as before. Soares da Silva does not teach other preclinical data and clinical trial of opicapone adjunctive therapy to combination of levodopa and DDCI.
Ettcheto reviews the preclinical discovery/development, pharmacology, pharmacokinetics, safety profile of OPC and evaluates clinical and post-marketing data of OPC (See the whole paper). Ettcheto summarizes preclinical studies with opicapone and clinical finings of two-phase III clinical trials (BIPARK-I, also known as BIA-91067-301, and BIPARK-II, also known BIA-91067-302)( See Tables 1 and 2). Ettcheto states “opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson’s disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Thus, OPC decreases fluctuation in L-DOPA plasma levels and favors more constant central dopaminergic receptor stimulation, thus improving PD symptomatology”( See Introduction in Abstract, page 993).
Ettcheto states “Since there is no cure for PD, the objective of the treatment consists of controlling the motor symptoms primarily through administration of L-DOPA/DDI and improving the quality of life of patients”…“An important challenge in PD treatment is to minimize the ¨off ¨ time and to increase the ¨on¨ time, a property related to the efficacy and the pharmacokinetic properties of the drug. In the absence of disease-modifying treatments, the therapeutic strategy is based on improving treatment with L-DOPA by enhancing the “on ”phenomenon and decreasing the “off” effect. As demonstrated by clinical trials, the latter has been ameliorated with the administration of OPC” (See Expert Opinion, page 1000)
It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instant invention to further explore therapeutic efficacy/effectiveness of opicapone adjunctive therapy to combination of levodopa and DDCI taught by Soares da Silva and Ettcheto for treating other PD patients (including patients without clinically diagnosed motor complications) based on the collective teachings of prior art, together with experiment/optimization(e.g. dosing regimen, administration times, patient populations, etc.) based on general knowledge of Parkinson’s disease treatment. Before the effective filing date of instant claimed invention, it was already known that opicapone (OPC, Ongentys®) is a third generation COMT inhibitor approved by EC and FDA as a safe adjunctive therapy to combination of levodopa and DDCI for treating Parkinson’s disease as taught by Ettcheto. A skilled artisan would have also known the criteria of MDS-UPDRS scores, wearing-off questionnaire (WOQ-9), PDQ-39, NMSS, practical recommended therapeutic management of uncomplicated PD and stable treated PD (e.g. controlling the motor symptoms) as taught by Soares da Silva and Ettcheto.
A skilled artisan would be motivated to further explore therapeutic efficacy of opicapone adjunctive therapy in other PD patients based on the combined teachings of prior arts because opicapone adjunctive therapy has been approved as safe and effective treatment for motor signs and symptoms in patients experiencing “off’ episode of PD treatment. The control of motor signs and symptom is a key clinical need for almost all PD patient and has substantial effect on patients’ quality of life. The further exploration of opicapone adjunctive therapy based on combined teachings of prior art , together with experiment/optimization(e.g. dosing regimen, administration times, patient populations, etc.) based on general knowledge of PD treatment, would provide an alternative safe and potentially effective treatment for control of motor signs and symptom in more patients with Parkinson’s disease including those patients without clinically diagnosed motor complications.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of treating Parkinson’s disease. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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, 5, 7-12, 14-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 5-8, 11-13, 16-21 of US 10,357,468 B2 (Applicant’s IDS dated 09/19/2023, under “US Patent Document”, Cite# AN1**, applied in preceding 103 rejections). Although the claims at issue are not identical, they are not patentably distinct from each other because they claim methods of treating Parkinson’s disease patient with combination of opicapone, levodopa and a DDCi inhibitor that are prima facie obvious to each other (please note carbidopa or benserazide are also dopa decarboxylase inhibitor DCCi).
Reference claims of US 10,357,468 B2 are directed to method of slowing progression of Parkinson's Disease comprises administering to a patient experiencing motor symptoms , not previously treated with a COMT inhibitor, a combination of opicapone, levodopa and a AADC inhibitor (e. g. carbidopa or benserazide) (please note carbidopa or benserazide are also dopa decarboxylase inhibitor DCCi as disclosed in instant specification page 1, line 28). Although reference claims do not explicitly recite the negative limitation “without clinically diagnosed motor complications”, reference claims 3 and 12 are directed to patient who has not previously been treated with levodopa, indicating patients might have no motor complications which is mostly associated with dopaminergic medication (e.g. levodopa).
It would have been obvious to one of the ordinary skilled in the art to further explore therapeutic efficacy/effectiveness of opicapone adjunctive therapy to combination of levodopa and DDCI taught by reference claims, for treating other PD patients (e.g. without clinically diagnosed motor complications) based on general knowledge of Parkinson’s disease treatment. A skilled artisan would be motivated to further explore therapeutic efficacy of opicapone adjunctive therapy in other PD patients because the control of motor signs and symptom is a key clinical need for almost all PD patient which has substantial effect on patients’ quality of life. The further exploration of opicapone adjunctive therapy would provide an alternative safe and potentially effective treatment for control of motor signs and symptom, slow or delay progression of PD in more patients with Parkinson’s disease including those patients that are not clinically diagnosed motor complications.
The instant application shares at least one common inventor /applicant with the reference patent. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Claims 1, 5, 7-9, 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 17-22 of copending Application No. 18/032,034 (reference application)(maintained).
Reference claims are directed to method of treating symptoms of Parkinson's disease in a patient suffering from unpredictable motor fluctuations, comprises administering to a patient, a combination of opicapone and levodopa. Reference claims 4 and 5 recite combination further comprises a DOPA decarboxylase inhibitor (DDCI) (e. g. carbidopa or benserazide).
Although reference claims are directed to patients suffering from motor fluctuations, it would have been obvious to one of the ordinary skilled in the art to further explore therapeutic efficacy/effectiveness of opicapone adjunctive therapy to combination of levodopa and DDCI taught by reference claims, for treating other PD patients (e.g. without clinically diagnosed motor complications) based on general knowledge of Parkinson’s disease treatment. A skilled artisan would be motivated to further explore therapeutic efficacy of opicapone adjunctive therapy in other PD patients because the control of motor signs and symptom is a key clinical need for almost all PD patient which has substantial effect on patients’ quality of life, whether they are or not clinically diagnosed as motor complication.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The instant application shares at least one common inventor /applicant with the reference patent. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached on (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LIYUAN MOU/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
