DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 12/17/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-3, 5, 7-8, 10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Kshirsagar et al (US 2011/0064808), in view of Meinicke et al (US 2016/0038501), further in view of Naidu et al (WO 2015/110962 A1) and further in view of Lee et al (US 2009/0082400 A1).
Kshirsagar taught an extended release tablet comprising from about 30 % to about 85 % of levetiracetam and a matrix forming polymer at about 1% to about 50%, of the extended release composition, comprising carbomer as a water dispersible rate controlling polymer. The levetiracetam and carbomer were blended together. At ¶ [0040] and Table 1, Kshirsagar taught that the ingredients of the composition were blended together before compression of the tablet [claim 1; ¶ 0020, step (i); see also ¶s 0031 and 0057]. The tablets were for oral administration [claim 4].
Kshirsagar was silent magnesium hydroxide, and amounts thereof, as recited in claim 1(c).
Meinincke taught pharmaceutical compositions formulated as extended release [0054] metformin [abstract and title], whereby basic buffering agents stabilized the composition. Said stabilization protected against decomposition and degradation (e.g., less than about 0.2 % impurities), even after 6 months at accelerated conditions. The degradation was determined by well-known analytical methods, for example using HPLC methods [0093-96, 0159, 0164, 0169, 0226, 0243, and 0253]. The buffering agent was comprised at 0.07-2.2 % [0121].
Meinincke was not specific that the basic buffering agent was magnesium hydroxide.
However, Naidu taught solid oral pharmaceutical compositions comprising metformin. In particular, the disclosure related to solid oral stable pharmaceutical compositions comprising metformin, whereby with using an alkalizer, it was possible to achieve the stable composition [abstract]. The alkalizer was magnesium hydroxide, and was included at from about 0.25 % to about 5 % of the composition [claims 3 and 4].
Lee taught that magnesium hydroxide, when incorporated with active agents, stabilizes [0566] the active agent, whether the active is metformin [0472] or levetiracetam [0395, 0476]. Lee was drawn to tablets for oral administration [0544].
It would have been prima facie obvious to one of ordinary skill in the art to include,
within Kshirsagar, magnesium hydroxide, as taught by Lee and Naidu. The ordinarily skilled artisan would have been motivated to stabilize the active agent, as taught by Meinincke, Naidu and Lee. The ordinarily skilled artisan would have included the magnesium hydroxide at 0.07-2.2 %, as taught by Meinincke, motivated by the desire to stabilize the composition, in order to protect against decomposition and degradation (e.g., less than about 0.2 % impurities) even after 6 months at accelerated conditions, as taught by Meinincke [0093-96, 0159, 0164, 0169, 0226, 0243, 0253].
Specifically, since Lee taught magnesium hydroxide, it would have been prima facie obvious to one of ordinary skill in the art to include, within Kshirsagar, magnesium hydroxide at from about 0.25 % to about 5%, as taught by Naidu. The ordinarily skilled artisan would have been motivated to achieve a stable drug product (e.g., metformin or levetiracetam), as taught by Naidu at the abstract, and at claims 3-4; and, as taught by Lee at [0395, 0472, 0476 and 0566].
The instant claim 1 recites 3-40 % extended release component, 1-20 % buffering component and at least 50 % drug component.
The instant claim 7 recites from about 50 % to about 85 % drug component.
The instant claim 8 recites 3-40 % extended release component, 1-20 % buffering component and 50 % to 85 % drug component.
The instant claim 16 recites 5 to 20 percent extended release component.
Kshirsagar taught a matrix forming polymer at about 1% to about 50%, and from about 30 % to about 85 % of levetiracetam; Meinincke taught the basic buffering agent at 0.07-2.2 %; Naidu taught magnesium hydroxide at from about 0.25 % to about 5 %. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Regarding the instant claim 2, the Examiner notes that the limitation of wherein the drug of said drug component is “subject to hydrolytic degradation” is interpreted as a product-by-process limitation. Product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
Even though product-by-process claims are limited by and defined by the process, the determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as, or obvious from, a product of the prior art, then the claim is unpatentable even though the prior product was made by a different process. In the instant case, Kshirsagar’s pharmaceutical composition of levetiracetam reads on the claimed composition comprising levetiracetam. As such, the patentability of the instant composition does not depend on its method of drug release, and the Applicant’s limitation regarding the hydrolytic degradation of the drug component is not patentable, in view of Kshirsagar et al. MPEP 2113.
Kshirsagar, in view of Meinincke, Naidu and Lee, reads on claims 1-3, 5, 7-8, 10, 12 and 16.
Response to Arguments
Applicant's arguments filed 12/17/2025 have been fully considered but they are not persuasive.
Applicant argued that Kshirsagar is silent regarding improving stability and does not point toward using Carbopol polymer for increasing stability, let alone in combination with magnesium hydroxide or magnesium oxide.
The Examiner responds that the instant application has not shown evidence of improved stability (see the below discussion regarding unexpected results). Further, Kshirsagar was not relied upon to teach magnesium hydroxide, as that was a feature taught by the combination of the references. And one cannot show nonobviousness by attacking references individually, where the rejections are based on combinations of references. See MPEP 2145(IV).
Applicant argued that the skilled artisan would be taught away from combinations that alter the viscosity of Kshirsagar’s formulations, because an essential feature of Kshirsagar is achieving high viscosity for extended release. Applicant argued that the skilled person would not have selected Kshirsagar’s Carbopol polymer for combining with magnesium hydroxide or magnesium oxide, in view of the teachings (achieving a high viscosity for extended release) of Kshirsagar.
The Examiner disagrees. For purposes of argument only, and not as a basis of rejection, the Examiner cites Stabib et al (US 2,912,358 A). The Examiner states that it is known in the art that magnesium hydroxide combines (mixes) with Carbopol polymer. The skilled artisan would not be led away from the combination. As per Stabib, this combination has existed since 1959. At column 9, and lines 10-15, 40-45 and 50-55, Stabib disclosed a mixture of magnesium hydroxide and Carbopol.
Applicant argued that the skilled artisan would have been discouraged to specifically select Carbopol from Kshirsagar and find it compatible with the teachings of the secondary references, and that asserting otherwise can be only based on hindsight analysis based on the unexpected results found by the Applicant.
The Examiner disagrees. In response to the Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See MPEP 2145. In the instant case, the claims were rejected upon a motivation to combine the secondary references with the primary reference, as discussed above. Further, and as discussed below, evidence of unexpected results has not been found.
Applicant argued that the claimed composition achieves an unexpected combination of stability, high active component loading, and desirable dissolution properties. Applicant cited ¶ [0034] in support of said allegation.
The Examiner notes the allegations of unexpected effects. But, these allegations are merely Attorney argument since they are unsupported by fact. The arguments of counsel cannot take the place of evidence of record. MPEP 2145(I). It does not appear that the Applicants have provided evidence in support of these conclusions. As such, the Applicants have the burden of proffering data and establishing results as unexpected and significant. Evidence of unexpected properties may be established by direct or indirect comparative tests. MPEP 716.02(b)(I)(II)(III).
Claim(s) 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kshirsagar et al (US 2011/0064808), in view of Meinicke et al (US 2016/0038501), further in view of Naidu et al (WO 2015/110962 A1), further in view of Lee et al (US 2009/0082400 A1) and further in view of Alsante et al (Advanced Drug Delivery Reviews, 57, 2007, 29-37).
The 35 U.S.C. 103 rejection over Kshirsagar, in view of Meinicke, Naidu and Lee, was previously discussed.
As previously discussed, Kshirsagar, in view of Meinicke, Naidu and Lee taught magnesium hydroxide as a buffering agent (e.g., reads on the claim 11 limitation of a pH of 4-10). Characterization by HPLC was taught by Meinicke [0683-684, 0995, 0997 and at the Examples, throughout].
The combined teachings of Kshirsagar, Meinicke, Naidu and Lee taught accelerated degradation testing conditions, although not the forced degradation testing conditions, as instantly recited in claims 9 and 11. Furthermore, as recited in claims 9 and 11, Kshirsagar was silent impurities.
However, Alsante taught that forced degradation studies facilitate the development of analytical methodology, in order to gain a better understanding of active pharmaceutical ingredient and drug product stability, and to provide information about degradation pathways and degradation products [abstract]. Forced degradation conditions, which are more severe than accelerated stability testing (e.g., >50 °C and 275 % relative humidity), are important from a regulatory perspective, to provide data on degradation products that do not form under accelerated stability conditions [section 1. Regulatory requirements].
It would have been prima facie obvious to one of ordinary skill in the art to include forced degradation testing conditions within the combined teachings of Kshirsagar, Meinicke, Naidu and Lee, as taught by Alsante. An ordinarily skilled artisan would have been so motivated, because forced degradation conditions, which are more severe than accelerated stability testing (e.g., >50 °C and 275 % relative humidity), provide data on degradation products that do not form under accelerated stability conditions [Alsante; section 1. Regulatory requirements].
The instant claims 9 and 11 recite 60-80 °C and 75 % relative humidity for 5 or 12 days. The instant claim 11 additionally recites a pH level of 4-10; no more than 1 % impurities.
Meinincke, Naidu and Lee taught magnesium hydroxide as a buffering agent (e.g., reads on a pH of 4-10); Meinincke taught less than about 0.2 % impurities after 6 months at accelerated conditions; Alsante taught forced degradation conditions, which are more severe than accelerated stability testing (e.g., >50 °C and 275 % relative humidity). A prima facie case of obviousness exists because of overlap, as discussed above.
Regarding the claim 11 limitation of “pH meter’, Kshirsagar was silent measuring pH. Lee taught that the pH was measured [0640], but was silent a “pH meter”.
Nevertheless, the limitation is interpreted as a product-by-process limitation. Specifically, the recitation of “wherein the pH level is measured by making an aqueous dispersion of the tablet using pH meter” is a product-by-process limitation, which is not patentable (see the above discussion regarding product-by-process limitations). In the instant case, the pharmaceutical composition of the combined teachings of the cited prior art (e.g., levetiracetam blended with magnesium hydroxide and carbomer) reads on the claimed composition comprising an admixture of levetiracetam, carbomer and magnesium hydroxide. As such, the patentability of the instant composition does not depend on its method of measuring the pH, and the Applicant’s limitation regarding measuring the pH level by making an aqueous dispersion of the tablet using a pH meter is not patentable, in view of the combined teachings of the cited art. MPEP 2113.
Response to Arguments
Applicant's arguments filed 12/17/2025 have been fully considered but they are not persuasive.
Applicant did not specifically traverse the rejection over Alsante.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612