DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Pending claims 38-47 have been examined on the merits. The previous filed claims have been cancelled, and claims 38-47 are newly added.
New Grounds of Rejection Necessitated by Newly Added Claims
Claim Rejections - 35 USC § 112 (Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 38-47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 38 recites “motor symptoms associated with Dementia with Lewy Bodies;” however, the specification does not provide an adequate written description of that specific therapeutic use. Although, the specification identifies dementia with Lewy Bodies (DLB) as a form of Lewy body dementia and reports that the PRESENCE study evaluated mevidalen in patients with mild-to-moderate Lewy body dementia, including DLB, and which also assessed motor and non-motor symptoms; however, the specification does not distinctly describe the claimed method as treatment of motor symptoms associated with DLB. Instead, the specification primarily describes motor symptoms in the context of Parkinson’s disease and parkinsonism, including bradykinesia, rigidity, tremor, gait, and postural abnormalities. The specification further describes parkinsonism as the defined motor syndrome underlying Parkinson’s disease and discusses treatment of those motor symptoms in connection with Parkinson’s disease. Therefore, the specification only provides an overlap between DLB and Parkinson’s disease dementia, which to suggest that DLB patients meeting Parkinson’s disease criteria, may be considered to have Parkinson’s disease. For these reasons, a POSITA would view such disclosure as distinct to the claimed method, meaning the specification does not necessarily demonstrate possession of the presently claimed method which explicitly directed to motor symptoms associated with DLB.
The specification’s failures to disclose proper description of “motor symptoms associated with Dementia with Lewy Bodies”, thereof supports the conclusion that the specification lacks adequate written description of the claimed subject matter indicating that Applicant was not in possession of the entirety of the claimed genus at the time of filling of the instant application in view of the disclosure of the application as filed.
New Grounds of Rejection Necessitated by Newly Added Claims
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 (i.e., changing from AIA to pre-AIA ) 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 in order 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 38-43 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Beadle et al., WO 2014/193781, in view of McKeith et al., Neur. 2017 Jul 4;89(1):88-100, Wilbraham et al. Clin Pharmacol Drug Dev. 2021 Apr;10(4):393-403.
Regarding claims 38 and 47, Beadle (page 1-4 and 6) teaches compounds of formula I are positive allosteric modulators (PAMs) of the dopamine 1 receptor (DI) is useful in improving motor symptoms display in Parkinson’s disease (PD). Beadle (page 4) discloses a compound of formula I is “2-(2,6-dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydroisoquinolin-2(lH)yl]ethenone,” comparable to the structure of mevidalen in the specification (page 3). Beadle (page 1) further discloses that mevidalen is known to improve motor symptoms in PD. Beadle, however, does not explicitly teach motor symptoms associated with DLB.
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However, McKeith (page 89-90, and 94-95) discloses that parkinsonism is a motor manifestation shared by PD and Dementia with Lewy Bodies (DLB). This is because parkinsonian features are common in DLB and that parkinsonism in PD presents similar motor symptoms including rest tremor and bradykinesia, those symptoms are the only core clinical feature that is present in in a patient with DLB. Therefore, a POSITA would reasonably understand that motor symptoms of DLB significantly overlap with parkinsonian motor symptom presented/observed in PD. Base on this, knowing PD and DLB share dopaminergic dysfunction resulting to motor symptoms including bradykinesia and tremor, and that mevidalen is a known dopamine positive allosteric modulator to improve motor symptom in PD. Therefore, a POSITA would have reasonably expected that modulating dopaminergic signaling with mevidalen would likewise improve corresponding motor symptoms in DLB and parkinsonism including bradykinesia, and tremor, to arrive at the claimed invention.
Regarding claim 39-43, and as applied to claim 38 above, Wilbraham (page 1-5) discloses oral administration of mevidalen (LY3154207), once daily at doses 15-150 mg, and demonstrated central nervous system penetration at clinically administered doses. While Wilbraham does not disclose 10 mg dose, however, a POSITA would have reasonably investigated lower doses, at least lower than 15 mg, as a routine of finding the lowest effective dose, for the purpose of minimizing dose-related adverse effect. Therefore, given that mevidalen is a centrally acting D1 receptor positive allosteric modulator, and can regulate motor functor in PD, DLB and parkinsonism, thus, a POSITA would be motivated to combine the teachings Beadle and McKeith in view of Wilbraham to select a clinically evaluated dose for therapeutic use for PD, DLB, and parkinsonism, and arrive at the claim invention.
Claims 44-46 are rejected under 35 U.S.C. 103 as being unpatentable over McKeith, Beadle, Wilbraham as applied to claims 38-43, in further view of Biglan et al., WO2020/131671.
Regarding claims 44-46, and as applied to claim s 38-43, the combined teachings of McKeith, Beadle and Wilbraham indicate that administration of mevidalen is beneficial for improving motor symptoms associated with PD, DLB and parkinsonism. However, the prior art does not explicitly teach criteria for evaluating improvement using MDS-UPDRS Part II or III.
Biglan (page 49-52) discloses a randomized, placebo controlled 12-week study administering orally mevidalen (LY3154207), once-daily, as treatment regimens against PD, Parkinson’s disease dementia (PDD), and DLB, as an example. Biglan (page 51-52) identifies MDS-UPDRS Part I-III as a measure for assessing motor function after the treatment. Thus, a POSITA would have reasonably recognized that MDS-UPDRS Part I-III is used as an assessment matric to evaluate treatment effectiveness at 12 weeks, relative to placebo. Therefore, it would have been obvious to a POSITA to combine the teachings of McKeith, Beadle, and Wilbraham in view of Biglan, to assess motor symptoms improvement using MDS-UPDRS Part I-III at the 12-week endpoint as a routine clinical measure of motor function, because treatment endpoint assessment is critical for dose adjustment and evaluating treatment effectiveness.
New Grounds of Rejection Necessitated by Newly Added Claims
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 38-43 and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, and 16-25 of U.S. Patent No. USPN 12,642,794 “US patent’794” in view of Wilbraham et al. Clin. Pharmacol. Drug Dev. 2021 Apr; 10(4):393-403.
Although the claims at issue are not identical, they are not patentably distinct from each
other because the claimed method in US patent '794 obviates the claimed method of the instantly rejected claims. For example, US patent’794 claims methods of treating dopanergic CNS disorders, including Lewy body dementia using LY3154207 (mevidalen). Furthermore, US patent’794 also discloses that LY3154207 may improve a variety of domains important to people with Lewy Body Dementias including signs of Parkinsonism.
Claim 1 of the US patent ‘794 recites method of treating a dopaminergic CNS disorder by orally administering LY3154207 at 10 mg to 75 mg per day. While the US patent’794 does not explicitly disclose the exact phrase “motor symptoms with dementia with Lewy Bodies,” however, US patent’794 (abstract; col.1 to 6) categorizes Lewy Body dementia as a CNS disorder and treatable with the claim compound. This is also supported by claims 10, 20 and 23 of US patent ‘794 which recite the method of claim 1, wherein the dopaminergic central nervous system disorder is dementia with Lewy bodies or Lewy body dementia. Regarding daily, claims 1-8, and 16-25 recite LY3154207 doses of 10 mg to 75 mg, which is comparable to that of the instant claims 39-43 recite “effective dose of mevidalen is from 10 to 50 mg.” While the instant claims do not explicitly use the phrase LY3154207, however, William discloses LY3154207 is identical to mevidalen. This is supported by US patent’794, which discloses the phrase “LY3154207 (mevidalen).” Therefore, a POSITA would have recognized “motor symptoms with dementia with Lewy Bodies” is a form of dopaminergic CNS disorder, and it would have been obvious to administer LY3154207 to treat “motor symptoms with dementia with Lewy Bodies” with a daily dose of LY3154207 (mevidalen). Therefore, claims 1-8, 10, and 16-25 of the US patent ‘794 render instant claims 38-43 and 47 not patentably distinct.
Given the instant claims and US patent’794 recite comparable therapeutic use, LY3154207 (mevidalen), patient population, and dosing regimens, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. 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.
/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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