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
The amendments made to the claims on 09/26/2025 have been entered.
Information Disclosure Statement
The information disclosure statements (IDS) submitted 08/20/2025 and 04/28/2025 have been considered.
Status of Claims
Claims currently pending are claims 1, 8, 11, and 16-20.
Claims currently withdrawn are claims 11 and 16-20.
Claims under examination are claims 1 and 8.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1, 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Levin II (CA3068254A1, published 12/27/2018) in view of Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75), Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42), Prabhakar (US4140755, published 1979) .
In regards to claim 1, Levin II is broadly to compounds derived from trimetazidine (structure shown below).
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Levin II on p. 6 and p. 23 teaches the compound CV8972 shown below:
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Levin II on p. 81 denotes the hydrochloric acid salt of the compound above as CV8972.
Levin II on p. 28 further contemplates embodiments of its invention, which include the CV8972 molecule above, as pharmaceutical compositions.
Levin II on p. 28, l. 2-3 contemplates oral administration.
Levin II on p. 93, table 66 teaches dose amounts of the CV8972 compound ranging from 142.08 mg to 779.06 mg.
Levin II teaches compositions comprising compound (X) above do not explicitly have the erodible polymer composed of two polymeric forms with specific properties or extended-release formulations. This is bridged by the combination of Aswathy, which teaches biphasic polymers of HPMC, and Maggi, which teaches extended-release tablets.
In regards to claims 1 and 8, Aswathy at p. 47, table 1 teaches biphasic HPMC layers (F7-F11). The same table also teaches mixtures wherein trimetazidine hydrochloride constitutes 10% by weight of a 200 mg mixture (F1-F11). Aswathy explicitly teaches trimetazidine but does not teach compound (X) of claim 1 or explicitly state CV8972. However, applicant in the specifications, p. 1, l. 25 states CV-8972 is a modified form of trimetazidine. Therefore, one of ordinary skill in the art would recognize that CV8972 and the compound of formula (X) are alternatively useable or equivalent.
Further, Aswathy teaches controlled-released administration as discussed on p. 44, sec. Introduction and on p. 68-69, Sec. Conclusion.
In regards to claim 1, Abrahamsson et al (herein after Abrahamsson) at p. 70, sec. 2.1 teaches hydrophilic gel matrix tablets comprised of approximately 50% HPMC.
Abrahamsson does not explicitly teach viscosity grade, cP, or methoxyl substitution.
In regards to claim 1, Maškova et al (herein after Maškova) on p. 697, Table 1 teaches “Commercial products of HPMC, viscosity grade and typical viscosity values for 2% (w/v) aqueous solution (measured at 20oC)” shown below:
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The table gives the inherent properties of HPMC forms including viscosity measurements, methoxyl substitution percentage, and hydroxypropoxyl substitution.
In regards to claim 1, which states “wherein the pharmaceutical composition is formulated as a 200 mg 8-hour modified release oral tablet,” Maggi in its abstract teaches double-layer tablets comprising HPMC which can slow drug delivery rate to a range of “a few hours up to 24h.”
Levin II teaches the compound (X) shown above as a pharmaceutical compound. Aswathy teaches HPMC and biphasic HPMC combinations as drug delivery compounds. Abrahamsson and Maškova teach the specific characteristics of the HPMC polymers, showing that the claimed characteristics are properties that can be selected via the various HPMC polymers. Maggi teaches the extended-release properties of the tablets.
The only element not explicitly taught by that art is the limitation “such that the geometric mean t1/2 of trimetazidine in a subject following administration of the pharmaceutical composition is between 6.5 hours and 9.5 hours.” Regarding this limitation, the instant specification states that the compound CV8972 above is “subsequently converted in the body to trimetazidine.” Therefore, trimetazidine is a metabolite of the CV8972 and the concentration present within the body would be caused by administering a certain dose of the CV8972. This limitation would be obvious because it is within the skillset of one of ordinary skill to formulate a composition from a known compound with known polymers to achieve a specific concentration by varying the concentrations of each component of the sustained-release agent, evidence to the contrary.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 105 USPQ 233, 235 (CCPA 1955). The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the solvents taught by the cited references), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Additionally, Prabhakar discuss tablets formulated for sustained release and provide motivation to one of ordinary skill in the art. Prabhakar in col. 1, l. 10-28 discusses the advantages of sustained release of a single dose of a pharmaceutical compound. Prabhakar states “The convenience of administering a single dose of medication which release active ingredient over an extended period of time as opposed to the administration of a number of single doses at regular intervals has long been recognized in the pharmaceutical art. The advantage to the patient and clinician in having consistent and uniform blood levels of medication over an extended period of time are likewise recognized.”
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have combined the teachings of Levin II, Aswathy, Maškova and Abrahamsson.
One of ordinary skill in the art would have been motivated to combine the teachings in efforts to create controlled-release composition.
Maintained Double Patenting Rejections
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.
Patented Cases
Claim 1 and 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 of U.S. Patent No. 10,556,013 (previously co-pending application No. 16/011,196) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The claims in the ‘013 patent are drawn to the compound of formula (X) and e.g. oral, compositions thereof. As discussed in the 103 rejections above, Levin II and Aswathy together teach the claimed compound (X) together in a composition with biphasic HPMC polymer as an excipient. Maškova, and Abrahamsson make obvious the specific characteristics claimed including cP, viscosity, and concentrations. Levin II, Maggi and Prabhakar make obvious the specific dosage and extended-release form.
Therefore, the combination of the U.S. Patent No. 10,556,013 with the cited prior art above make instant claim 1 obvious.
Claims 1 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,793,807 (previously application 17/540,653) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75), Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
Claims 1 and 8 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,730,733 (previously application 17/540,657) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
Claims 1 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,969,422 (formerly application 17/540,638) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
Claims 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-10 of U.S. Patent No. 11,844,840 (formerly application 17/828,640) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
Claims 1 and 8 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-32 of U.S. Patent No. 10,953,102 (formerly application 16/722,691) in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
Co-pending Applications
Claims 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, and 14-17 of copending Application No. 17/439,763 in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the instant claims. While the co-pending application ‘763 claims a compound which is pegylated (functionalized with polyethylene glycol moieties which are -CH2CH2O-), claim 17 states that the compound is CV8972.
The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 39 of copending Application No. 17/282,584 in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the reference claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 8 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of copending Application No. 17/614,826 in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the reference claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17/922,890 in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the reference claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10 and 22-25 of copending Application No. 17/614,815 in view of Levin II (CA3068254A1, published 12/27/2018), Aswathy et al (IJPPR.Human, 2018; Vol. 13 (1):43-71), Abrahamsson et al (European Journal of Pharmaceuticals and Biopharmaceutics, 46, 1998, 69-75) and Maškova et al (Journal of Controlled Release, 324, 2020, 695-727), Maggi (European Journal of Pharmaceutics and Biopharmaceutics, 1999, 48, 37-42) and Prabhakar (US4140755, published 1979).
The compound known as CV8972 is claimed within the reference claims. The same rationale given in the 103 rejection applies here. In view of references cited above, of which Levin II teaches CV8972 as a pharmaceutical composition, the instant claims are obvious.
This is a provisional nonstatutory double patenting rejection.
Response to arguments
Applicant in their remarks filed 09/26/2025 states “A prima facie case of obviousness based on a combination of references requires a finding that all elements of a claimed invention are found in that combination of prior art.” Applicant continues and states “that none of Levin II, Aswathy, Abrahamsson, Maškova, and Prabhakar…teach the specific formulation claimed that’s for 200 mg oral of tablet of a compound of formula (X) to release over 8 hours such that the maximum level of the compound of formula (X) is less than or equal to 6 μ/mL and that results in a geometric mean t1/2 of trimetazidine between 6.5 hours and 9.5 hours.”
Applicant continues that “The claimed pharmaceutical compositions claimed allow for effective and safe levels of trimetazidine in a subject delivered over an extended that would not be possible from trimetazidine delivery directly.”
The arguments are found unpersuasive because, while the specific geometric mean t1/2 is not discussed in the references, it is a result of administering the compound above.
The instant specification states that the compound CV8972 above is “subsequently converted in the body to trimetazidine.” Therefore, trimetazidine is a metabolite of the CV8972 and the concentration present within the body would be caused by administering the CV8972. The critical elements that are known within the art are the CV8972 compound and polymeric forms of HPMC. Even further, delayed-release formulations are well known within the art. Motivation to make optimized formulations for delayed release is discussed in Prabhakar.
The remaining limitation, which is “that the geometric mean t1/2 in a subject following administration” is between 6.5 hours and 9.5 hours, does not overcome the rejection because it is within the skillset of one of ordinary skill to formulate a composition from a known compound with known polymers to achieve a specific concentration.
It has not been shown how the specific geometric mean would be unachievable with what was known within the art at the time of the effective filing date and/or it has not been shown how the specific limitation is a significant and unexpected result from the combination of polymers and compound. Therefore, the rejection is maintained.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624