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
Response to Amendments
Applicant's amendment filed on 09/02/2025 is acknowledged.
Status of Claims
Claims 1-16 are pending and currently under examination.
Response to Arguments
Applicant's remarks filed 09/02/2025 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s remarks. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Applicant's arguments including Applicant’s cited other references (Exhibits A-H) have been fully considered, but they are 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 in view of Soares da Silva’ 468; 2) Soares da Silva’ 468 in view of Ettcheto; 3) Fabbri in view of Soares da Silva’ 468 and Ferreira;
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.
Rejections under 35 U.S.C.§103
Applicant's arguments have been focused/ based on that instant invention is directed to a method of treating patients in early stage of Parkinson's disease "without clinically diagnosed motor complications" or “whose motor symptoms are being treated and adequately controlled with levodopa and a DDCI” (Remarks , page 12). The difference between independent claim 1 and 15 is that claim 15 is specifically directed to treating motor signs and symptom of Parkinson’s disease. Independent claim 16 is allegedly directed to Parkinson's disease patients in the early stages of the disease who do not respond to levodopa/DDCI treatment wherein patients have "insufficient control of motor signs and symptoms", which allegedly differs in scope from claim 15 (Remarks, page 5). As such, the instant claims are construed as directed to patients at early stage of Parkinson's disease exhibiting motor signs and symptoms although not clinically diagnosed. It’s noted that motor signs and symptoms are not only initial symptoms of Parkinson's disease and do not only appear in the early stages of the disease, motor signs and symptoms also exist in later stage of Parkinson’s disease such as "wearing off' period wherein patient experiences insufficient control of motor signs and symptoms. As disclosed in instant specification( page 25):” A total score of MDS-UPDRS Part IV A+B+C greater than 0 (zero) is the most preferred definition of clinically diagnosed motor complications. It should be noted that motor complications can be the same as motor symptoms of Parkinson's disease. However, a motor symptom which is initially treatable by levodopa/DDCI therapy, but which re-emerges at a later stage of disease in spite of maintaining levodopa/DDCI therapy, is then considered a motor complication”.
Applicant argues “The invention is based on the surprising discovery that opicapone improves the therapeutic effect of levodopa therapy in early stage Parkinson's disease patients (i.e., patients without motor complications) without causing dyskinesia, despite the fact they could not be expected to benefit from this treatment…Subjects "treated with opicapone presented with a statistically significant lower motor disability compared to placebo, as shown in Figure 1 and Table 4”(Remarks, page 12).
RESPONSE: It’s noted Figure 1 and Table 4 refer to primary endpoint-change in MDS-UPDRS part III (motor symptoms) from baseline to 24 week, which does not support claim 3 wherein two or fewer positive symptoms in WOQ-9 improves after the next dose of levodopa (which is administered multiple time daily). It’s also noted MDS-UPDRS part IV ( motor complication) score at week 24 disclosed by instant specification (Table 13) showed motor complication for OPC group, which contradicts the limitation of patient without motor complications recited in instant claims.
The examiner does not dispute opicapone (50mg) might improve therapeutic effect of levodopa therapy following certain dose regimen in certain early stage Parkinson's disease patients. However, instant independent claims 1, 15 and 16 do not recite any specific DDCI and dose regimen of opicapone, levodopa and DDCI, thus the scope of claims 1, 15 and 16 are extremely broad. Instant alleged therapeutic effect of opicapone in combination with levodopa/DCCI therapy following certain treatment regimen in certain patient population does not commensurate with the extremely broad scope of claims 1, 15 and 16. More importantly, the alleged improvement by opicapone is NOT unexpected because opicapone adjunct therapy to combination of levodopa and DDCI is approved for treating motor fluctuations of Parkinson’s disease which also involve controlling motor signs/symptoms. The function/biological activity of opicapone is the property of opicapone whether the patient is with or without clinically diagnosed motor complication/motor fluctuation. Reichmann teaches opicapone (50 mg once daily) significantly increased levodopa bioavailability compared with placebo. Soares da Silva’ 468 teaches “the use of opicapone to slow the progression of PD by administering to a patient not previously treated with opicapone” wherein “it was observed that, for the patients treated with opicapone from an earlier stage, the PD had progressed less” (See Col. 5, lines 25-64, claims 1-4). A skilled artisan would reasonably expect increased levodopa level by opicapone would exhibit treating/controlling motor signs/symptoms in early stage of PD patient and slow the progression of PD.
Following is the examiner’s response to Applicant’s argument regarding Rejection over Reichmann (Translational Neurodegeneration, 2020 Mar 4;9(1):9) in view of Soares da Silva (US 10,357,468, Soares da Silva’ 468)
Examiner’s Reasoning
Reichmann teaches 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 and the study design of OPTIPARK (NCT 02847442): “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 examiner agrees that motor fluctuations are characteristic of advanced disease and are not the same as motor signs and symptoms and the difference between Reichmann and instantly claimed invention is the targeted Parkinson’s patient population at different progression stage.
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, indicating patients are without clinically diagnosed motor complications (Col. 5, lines 44-64; Col. 10, lines 13-30, claims 3 and 12)(note: these patients are construed as early stage PD without clinically diagnosed motor complications since they have not been treated with levodopa and motor complications are related to levodopa therapy). Soares da Silva’ 468 teaches therapies aimed to modify disease progression can either prevent or postpone late motor complications or fluctuations and/or delay disease progression: “For early untreated PD ( de nova) patients a clinical goal to 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 34-65). Soares da Silva’ 468 explicitly teaches” a method of slowing or delaying the progression of PD by administering to a patient not previously treated with opicapone” and “the use of opicapone to slow the progression of PD by administering to a patient not previously treated with opicapone” wherein “it was observed that, for the patients treated with opicapone from an earlier stage, the PD had progressed less…a treatment regimen has been shown to slow the progression of PD and so provides a significant development in therapy. As used herein slowing the progression of PD also refers to instances where the progression of PD is delayed by a period of time. For patient treated according to the invention the progression of PD may be delayed by a period of at least one month relative to patients who have not received the treatment of the invention, for example by at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, a least 9 months or at least one year”(See Col. 5, lines 25-64, claims 1-4). As such, 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 early untreated PD (de nova) patients or a patient who has not previously been treated with levodopa without clinically diagnosed motor complications.
As stated in the documented 103 rejection, controlling motor signs and symptom is a key clinical need for almost all PD patients whether they are in early stage or a later stage of Parkinson’s disease. A skilled artisan would be motivated to further explore therapeutic efficacy of opicapone adjunctive therapy in other PD patients including patients without clinically diagnosed motor complications 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.
With respect to Applicant argument about COMT inhibitor, Applicant argues that “purpose for administering COMT inhibitors is for symptom relief, not to alter or slow the course of Parkinson's disease… ” (Remarks, page 11). However, this allegation is in contradiction with the rationale in support of instant invention as stated in instant specification (page 6): “using opicapone to smooth out the delivery of exogenous levodopa in early disease potentially avoids exacerbating the already destabilized basal ganglia processing thereby preventing or delaying the emergence of motor complications”. More importantly, Soares da Silva’ 468 explicitly teaches a method of slowing or delaying the progression of PD and/or slow the progression of PD and/or motor symptoms by administering opicapone to early untreated PD (de nova) patients or a patient who has not previously been treated with levodopa without clinically diagnosed motor complications.
Reichmann teaches “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). As elaborated in others 103 rejections, 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 in treating 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).
Further, 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).
b. Response to Applicant’s “teach away” argument (Remarks, page 14)
Please note “teaching away” can be a high bar and is usually not met by mere disclosure of alternatives or even a description that some teaching is somewhat inferior. MPEP § 2143(E) and §2143.01(I); In re Gurley, 27 F.3d 551 (Fed. Cir. 1994); In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004); Galderma Labs. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir. 2013); Bayer Pharma AG v. Watson Labs., Inc., 874 F.3d 1316, 1327 (Fed. Cir. 2017). Citing In re Gurley and In re Fulton, the Federal Circuit reiterated the proper standard for teaching away as follows: a reference will teach away when it suggests that the developments flowing from its disclosures are unlikely, reasonably, to produce the objective of the applicant’s invention.
In instant case, Applicant cites a 2010 publication (Exhibit C) that another drug entacapone did not work. First, teaching away is not by other prior art that states something else. A teaching away is a statement in the same document that you should not do something (i.e., a disparagement of a step). The article cited by Applicant is not teaching away but teachings by another person relating to a different drug. The failure of entacopone treating the same patient population is irrelevant to Reichmann and Soares da Silva’ 468 teaching of opicapone because opicapone and entacopone have different structures, different chemical and physical properties, different biological activity, different pharmacokinetic and pharmacodynamic parameter as elaborated above. Further, the cited 2010 publication is prior to Reichmann and Soares da Silva’ 468 and these “teachings away” by 2010 publication may merely mean that something new was learned and taught. Soares da Silva’ 468 is more recent publication by inventor Soares da Silva which explicitly teaches a method of slowing or delaying the progression of PD and/or slow the progression of motor symptoms by administering opicapone to early untreated PD (de nova) patients or a patient who has not previously been treated with levodopa without clinically diagnosed motor complications.
Response to Applicant’s argument “One Cannot Extrapolate Results Obtained At One Stage of Parkinson 's Disease To Other Stages”
Applicant argues the physiology of Parkinson's disease changes in different stages involving different pathological mechanisms, efficacy shown in one stage of Parkinson's disease would not necessarily be effective at other stages… COMT inhibitors as a class are only approved to be administered after the onset of motor fluctuations. Therefore, extrapolation of efficacy at one stage to other stages is neither warranted nor correct (Remarks, page 16).
The examiner agrees the physiology of Parkinson's disease changes in different stages. However, the function/biological activity of opicapone is the property of opicapone whether the patient is with or without clinically diagnosed motor complication/motor fluctuation. A skilled artisan would reasonably expect opicapone in combination with levodopa/DCCI exhibit certain efficacy/activity in controlling the motor symptoms/signs since opicapone (50 mg once daily) significantly increased levodopa bioavailability as taught by Reichmann. Please note 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.
d. Response to Applicant’s argument of reasonable expectation of success(Remarks, page 17).
As MPEP 2143.02. I. stated : “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 above and in documented 103 rejection, 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 early untreated PD (de nova) patients or a patient who has not previously been treated with levodopa(note: these patients are construed as early stage PD without clinically diagnosed motor complications since they have not been treated with levodopa). A person of ordinary skilled in the art would reasonably expect that opicapone adjunct therapy to levodopa and an AADC inhibitor (e.g. DDCI) would slow the progression of PD and/or motor symptoms in patients at early stage of Parkinson’s disease without clinically diagnosed motor complications, in the absence of evidence to the contrary. As such, the discovery of opicapone improving therapeutic effect of levodopa therapy in early stage Parkinson's disease patients are not unexpected to POSITA based on the teachings of Soares da Silva’ 468 by instant inventor.
Applicant cited Teva (Exhibit E) to argue that POSITA lacks motivation to apply opicapone-levodopa adjunct therapy to other patient population and there is no reasonable expectation of success(Remarks, page 17).
RESPONSE: The instant case is different from Teva’s combination therapy involving combination of two drugs which might have drug-drug interaction and safety concern without previously established DDI study. In instant case, opicapone has been approved in Europe since 2016 as adjunct therapy to preparations of levodopa/DDCI for end-of-dose motor fluctuations of PD wherein the dosage regimen, adverse events, TEAE, safety profile have been thoroughly studied as elaborated in prior art (Reichmann, Ettcheto, Fabbri, Soares da Silva’ 468).
In response to Applicant’s argument citing Sanofi infringement case(Exhibit G)(Remarks, page 18), the instant case is not relying on post-hoc analysis of BIPARK-I and II or OPTIPARK for the obviousness analysis. It’s noted that priority applications GB 2019954.3, GB 2106133.8, GB 2109826.4 of instant application are directed to clinical trial design for treating early Parkinson with L-dopa/DDCi and opicapone, and no clinical data of efficacy in early Parkinson’s disease without clinically diagnosed motor complications are disclosed. As elaborated above, 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 early untreated PD (de nova) patients or a patient who has not previously been treated with levodopa(note: these patients are construed as early stage PD without clinically diagnosed motor complications since they have not been treated with levodopa). A person of ordinary skilled in the art would reasonably expect that opicapone adjunct therapy to levodopa and an AADC inhibitor (e.g. DDCI) would slow the progression of PD and/or motor symptoms in patients at early stage of Parkinson’s disease without clinically diagnosed motor complications, especially in the absence of evidence to the contrary.
The aforementioned response/rationale also apply to rejections of claims 1-16 over Soares da Silva’ 468 in view of Ettcheto; over Fabbri in view of Soares da Silva’ 468 and Ferreira 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.
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 directed to 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 08/31/2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. For example, FR 1260080A (Cite No # BL ) is irrelevant with instant application. IDS has been placed in the application file, reference written in foreign language is considered to the degree of English abstract or patent family of foreign patent by Examiner.
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.( 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 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).
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).
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 PK 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 Fabbri et al. (Movement Disorders, Vol. 33, No. 10, 2018. 2018;33(10):1528–1539, Applicant’s IDS dated 08/31/2023, Cite# CA2, “Opicapone for the treatment of Parkinson’s disease: A review of a new licensed medicine”), in view of Soares da Silva et al. (US 10,357,468 B2) and Ferreira et al.(European Journal of Neurology 2013, 20: 5–15, Applicant’s IDS dated 08/31/2023, Cite# CI2, “Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease”).
Fabbri reviews pharmacological properties, clinical efficacy, and safety profile of opicapone (aka OPC, BIA 9-1067) as a novel and effective L-dopa adjunct treatment in treating Parkinson’s disease( See the whole paper). Fabbri teaches “Levodopa (L-dopa) continues to be the most efficacious therapeutic drug for PD treatment. Nevertheless, long-term treatment with L-dopa leads to troublesome motor fluctuations or L-dopa-induced dyskinesia (LID). The control of motor fluctuations is a key clinical need for almost all PD patients. Up to 50% of patients can develop mild motor fluctuations within 2 years of initiating L-dopa therapy and this percentage increases to 70% after 9 years of sustained therapy with substantial effect on patients’ quality of life. End-of-dose motor fluctuations are linked to the short half-life of oral L-dopa (about 60-90 minutes). Catechol-O-methyl transferase (COMT) inhibitors are currently used as add-on therapy to L-dopa for the amelioration of end-of-dose motor fluctuations, as they inhibit peripheral L-dopa metabolism and increase the delivery of L-dopa to the brain. Opicapone (OPC), a new COMT inhibitor has been developed to provide higher COMT inhibitory potency and avoid liver toxicity compared with previous COMT inhibitors that is, tolcapone and entacapone. On June 24, 2016, the European Commission (EC) granted a marketing authorization for the medical product OPC (OngentysR) as adjunctive therapy to preparations of L-dopa/DOPA decarboxylase inhibitors (DDCIs) in adult patients with PD and end-of-dose motor fluctuations who cannot be stabilized on these combinations” (See page 1528, right column; page 1529, left column, 1st and 2nd paragraphs)(which read on instant claims 1 and 15-16 except the negative limitation “ patient is without clinically diagnosed motor complications”).
Fabbri teaches overview on L-Dopa adjunct therapies for motor fluctuations such as partial replacement of L-dopa with a dopamine agonist (DAA), monoamine oxidase type B (MAO-B) inhibitor, or COMT inhibitors( See page 1529, left column; Table 1 Summary of MDS-EBM review on page 1530) and explicitly teaches development of OPC, a long-acting, peripherally selective, once daily, potent third-generation COMT inhibitor including Mechanism of Action, Pharmacokinetics, Effect on L-Dopa Pharmacokinetics, Pharmacodynamics, etc. (See Table 2, Features and properties of opicapone on page 1531). Fabbri further teaches clinical efficacy data of opicapone from preclinical studies and clinical trials including two phase II clinical trial ( EudraCT No. 2008-003869-72, NCT 01568047) and two phase III clinical trials (NCT 01568073(BIPARK-I), NCT 01227655(BIPARK-II)) (See pages 1532-1534; Table 3 on page 1533).
Fabbri teaches study outcome and measurements with Unified Parkinson’s Disease Rating Scale [UPDRS]) including I, II, III and IV (See Table 3 on page 1533) and teaches patients with severe dyskinesias (score > 3 on item 33 of the Unified Parkinson’s Disease Rating Scale [UPDRS]) or severe/unpredictable periods in the OFF state were excluded in the clinical trial of BIPARK I study(See page 1532, right column, Phase 3 Trials).
Fabbri teaches opicapone is administered orally in 25, 50 mg hard capsules once daily at bedtime at least 1 hour before or after L-dopa, for various period of time during the clinical trial (BIPARK-I, BIPARK-II) up to 1 year or 15 months (see Table 2, Table 3; page 1536, left column, Drug Development Program and Regulatory Affairs)(which reads on instant claim 7-9 and 11-13). Fabbri teaches OPC efficacy is confirmed by a second phase 3DB RCT and subsequent OL extension of 1 year ( See right column, page 1536 ) (which reads on 24 weeks of instant claim 12). Fabbri teaches both a high-fat/high-caloric meal and a moderate meal decreased the rate and extent of OPC absorption, with delayed peak plasma levels compared with drug administration under fasting conditions (See page 1530, right column).
As elaborated above, the collective teachings of Fabbri further establishes opicapone (OPC, Ongentys®) as a safe and effective adjunctive therapy to preparations of L-dopa/DOPA decarboxylase inhibitors (DDCIs) in adult patients with PD and end-of-dose motor fluctuations as approved by European Commission (EC) and FDA.
Fabbri does not explicitly teach “opicapone is administered more than 1 hour before or after a meal” recited in instant claim 10.
The collective teachings of Soares da Silva are elaborated in preceding 103 rejection and applied as before. 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).
Fabbri and Soares da Silva do not explicitly indicate use of opicapone (OPC) adjunctive therapy in patients with 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 patients with Parkinson’s disease who have shown motor signs and symptoms whether they are clinically diagnosed or not. Fabbri discloses that 33 trials have been conducted on opicapone(OPC) use, comprising 29 phase 1 trials (with > 1000 subjects exposed to OPC), 2 phase 2 trials, and 2 phase 3 trials. a phase 4 trial (NCT02847442, OPTIPARK) as of 2018 to explore the efficacy and safety of opciapone in treating Parkinson’s disease. 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 , together with experiment/optimization(e.g. dosing regimen, patients populations, 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.
Ferreira summarizes EFNS/MDS-ES (Movement Disorder Society–European Section
,MDS-ES) evidence-based treatment recommendations on therapeutic management of Parkinson’s disease (PD) including treatment recommendations for early and late PD (See whole paper). Ferreira discloses shortening dose intervals and reducing individual doses may postpone the emergence of motor complications in levodopa treatment and further teaches adjunctive therapy (supplementation of levodopa with other antiparkinsonian medications) in stable PD is common clinical practice to improve symptomatic control (See page 8, left column, Levodopa) (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). Ferreira discloses the management of early (uncomplicated) PD for the adjustment of initial therapy in patients without motor complications, such as levodopa with a COMT inhibitor for patients on dopaminergic therapy(See Tables 2 and 3). Ferreira discloses COMT inhibitors reduce the metabolism of levodopa, extending its plasma half-life and prolonging its action and further teaches COMT inhibitors as adjunctive therapy to levodopa/carbidopa (carpidopa is a decarboxylase inhibitor DCCI) in UPDRS part II and III in patients with no or minimal fluctuations, and in patients with de novo PD , and assessment of prevention of motor complications (FIRST-STEP study, STRIDE-PD) (See page 8, left column, Levodopa and COMT inhibitor, right column).
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 Fabbri 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, administration times, 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 Fabbri. It was also known opicapone inhibit peripheral L-dopa metabolism and increase the delivery of L-dopa to the brain as taught by Fabbri. A skilled artisan would have also known the criteria of MDS-UPDRS scores, wearing-off questionnaire (WOQ-9), and practical recommended management of uncomplicated PD and stable PD, e.g. COMT inhibitors adjunctive therapy to levodopa/carbidopa as the adjustment of initial therapy in patients without motor complications, according to EFNS/MDS-ES evidence-based treatment recommendations on therapeutic management of Parkinson’s disease (PD) as taught by Soares da Silva and Ferreira.
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 (e.g. motor fluctuations) 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 PD 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.
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.
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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).
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.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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