DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 28, 30-38 and 40-49 are pending.
The examiner recommends deleting the comma after “tablet” in claim 28, ln. 1.
Withdrawn Rejections
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 38 and 49 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 38 recites the limitation “the siliconized microcrystalline cellulose” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 38 depends from claim 32, which does not recite siliconized microcrystalline cellulose.
Claim 38 also recites the limitation “the crospovidone” in line 10. There is insufficient antecedent basis for this limitation in the claim. Claim 38 depends from claim 32, which does not recite crospovidone.
Claim 49 recites the limitation “the siliconized microcrystalline cellulose” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 49 depends from claim 48, which does not recite siliconized microcrystalline cellulose.
Claim 49 also recites the limitation “the crospovidone” in line 9. There is insufficient antecedent basis for this limitation in the claim. Claim 49 depends from claim 48, which does not recite crospovidone.
The examiner recommends that Applicant amend claims 38 and 49 to delete the term “the” from the recitations discussed above.
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.
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 28, 30-38, 40-43 and 45-49 are rejected under 35 U.S.C. 103 as being unpatentable over Fanara et al. (WO 01/51033 A1) in view of Eeckman et al. (US 8,435,564).
Regarding claim 28, Fanara et al. teach solid pharmaceutical compositions with controlled release in combination with one or more solid pharmaceutical composition allowing the immediate release of active substances. This makes it possible to obtain, in a single administration, both the immediate release of a first active substance and the prolonged release of the same or of a second active substance. Fanara et al. teach a solid pharmaceutical composition comprising: A. at least one layer comprising an active substance and excipients which allow the immediate release of said active substance after administration, and B. at least a second layer which allows the controlled release of the same or a second active substance, comprising said same or second active substance, at least one matrix-type excipient, at least one enteric-soluble polymer and at least one basifying agent (pg. 5-6). Fanara et al. teach that these combined solid pharmaceutical compositions may be in the form of a tablet in which at least one layer A is attached to at least one layer B (pg. 6). Examples of hydrophilic matrices preferably used according to the present invention are hydroxypropyl methylcelluloses (pg. 4). The active substances include levetiracetam and piracetam (pg. 5; Claim 2). Fanara et al. further teach an example comprising Methocel® K15M (Hypromellose K15M) as the hydrophilic matrix (Example 3).
Fanara et al. do not explicitly disclose that the active substance is brivaracetam and that the HPMC is Hypromellose K100M or K200M, as instantly claimed.
Eeckman et al. teach a sustained release pharmaceutical composition in the form of a tablet comprising, as active ingredient, brivaracetam and, as excipient within the core of the tablet, 5% to 80% per weight of at least one hydrophilic matrix agent, with respect to the total weight of the core of the tablet (col. 1, ln. 65 to col. 2, ln. 2; col. 4, ln. 42 to col. 6, ln. 25; Claims). Suitable hydrophilic matrix agent includes hydroxypropyl methylcellulose, including Methocel® K15M and Methocel® K100M (col. 2, ln. 13-39 and 49-52; col. 5, ln. 1 to col. 6, ln. 25; Examples 1 and 3-6; Claim 1).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare tablet according to Fanara et al. comprising an immediate release layer and an extended release layer, wherein the active substance in both layers is brivaracetam and the hydrophilic matrix agent is hypromellose K100M. Such would have been obvious because Fanara et al. teach levetiracetam and piracetam as acceptable active substances, and Eeckman et al. teach sustained release compositions comprising brivaracetam as the active substance. It is noted that brivaracetam is a structurally similar derivative of levetiracetam and piracetam, and all three active substances are used for the treatment of epilepsy, as taught by both Fanara et al. and Eeckman et al. Also, Fanara et al. teach controlled release matrix that make it possible to slow down the release of the active substance, wherein the hydrophilic matrix preferably comprise hydroxypropyl methylcellulose such as Methocel® K15M, and Eeckman et al. teach a sustained release pharmaceutical composition comprising a hydrophilic matrix agent that is a water dispersible rate controlling polymer, wherein the hydrophilic matrix agent includes Methocel® K15M and K100M. Thus, it would have been obvious to include hypromellose K100M as a rate controlling hydrophilic matrix agent in the extended release layer of the tablet according to Fanara et al.
Regarding the concentration of brivaracetam in the immediate release layer, Fanara et al. teach that it becomes increasingly advantageous therapeutically to be able to simultaneously orally administer an active substance released immediately after administration, and the same or a second active substance released gradually and regularly after administration. In the case where the same active substance is simultaneously administered in immediate release and in prolonged release, this makes it possible to rapidly release a sufficient dose of active substance to trigger the desired effect and to maintain this effect by a gradual and prolonged release of the same active substance (pg. 3 and 5-6). As for the dose of active substance used, it depends on the effective dose and can therefore vary within very wide limits depending on said active substance (pg. 5).
Eeckman et al. teach that brivaracetam is effective for treating epilepsy, and clinical trials evaluated the efficacy and safety of 5, 20, 50 and 150 mg per day (col. 1, ln. 33-37). Eeckman et al. also teach tablets comprising 20, 50 or 100 mg brivaracetam per tablet (Examples 1-6).
A person of ordinary skill in the art would have been motivated to determine through routine experimentation the effective concentration of brivaracetam in each of the immediate release layer and the extended release layer in order to achieve the desired therapeutic effect, and reduce the administration of active substances to one tablet per day, as reasonably taught by Fanara et al. and Eeckman et al.
Regarding claims 30-31, Fanara et al. teach that the hydrophilic matrices are generally used at a concentration of 20 to 70% (pg. 2). Eeckman et al. teach that the pharmaceutical composition comprises 5 to 80% per weight of hydrophilic matrix agent (col. 2, ln. 53-65; col. 4, ln. 42 to col. 6, ln. 25; Examples 1 and 3-6; Claims 1 and 4).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to determine through routine experimentation the workable range of hydrophilic matrix material, such as hydroxypropyl methylcellulose, for use in the tablets according to Fanara et al.
Regarding claims 32-38 and 48-49, Fanara et al. teach that the solid pharmaceutical compositions may further comprise other excipients such as diluents, binders, disintegrants, lubricants and flow agents, taste masking agents, flavors or colorings as well as film-coating agents (pg. 5-6). The diluents include lactose and dicalcium phosphate; the lubricants include talc, magnesium stearate and colloidal silica; and the disintegrants include modified starches, cellulosic derivatives, alginic derivatives, and pectins (pg. 5-6; Examples 1-3).
Eeckman et al. teach that the sustained release pharmaceutical composition further comprises 0-3 wt.% of a gliding agent, 0-5.5 wt% of a lubricant, 0-75 wt.% of a diluent, and 0-80 wt.% of a binder; wherein the gliding agents include talc, starches, stearic acid and anhydrous colloidal silica; the lubricant includes talc, magnesium stearate, calcium stearate, poloxamer, sodium lauryl sulfate, stearic acid or macrogol; the diluent includes lactose, starch, pregelatinized starch, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose acetate, dextrose, mannitol, sodium phosphate, potassium phosphate, calcium phosphate, fructose, maltose, sorbitol, or sucrose; and the binder includes starch, microcrystalline cellulose, silicified microcrystalline cellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, sucrose, dextrin, maltodextrin, sorbitol, polyvinylpyrrolidone, methylcellulose, or pregelatinized starch (col. 3, ln. 5 to col. 6, ln. 25; Examples 1-6; Claims 9-12).
A person of ordinary skill in the art would have been motivated to prepare tablets according to Fanara et al. comprising diluents, lubricants, and disintegrants within the ranges taught by Fanara et al. and Eeckman et al., wherein the diluents include diluent includes lactose, starch, pregelatinized starch, microcrystalline cellulose, silicified microcrystalline cellulose, cellulose acetate, dextrose, mannitol, sodium phosphate, potassium phosphate, calcium phosphate, fructose, maltose, sorbitol, or sucrose; the disintegrant includes modified starches, cellulosic derivatives; and the lubricant/gliding agent includes stearic acid, talc, magnesium stearate, calcium stearate, or colloidal silicon dioxide, as reasonably taught by Fanara et al. and Eeckman et al.
Regarding claims 40-41, Fanara et al. teach the combination of an immediate release layer and an extended release layer to achieve a therapeutically effective dosage administered once daily. Eeckman et al. teach that considering brivaracetam is classified as BCS I, the resulting in vitro dissolution (USP <711> apparatus no 2) in a buffered aqueous media has to show a drug release of no more than 40% after 1 hour of dissolution, of 35%-80% after 4 hours of dissolution and of no less than 80% after 16 hours of dissolution. Preferably, a profile of no more than 35% after 1 hour of dissolution, of 40%-75% after 4 hours of dissolution and of no less than 80% after 16 hours of dissolution. More preferably a profile of no more than 30% after 1 hour of dissolution, of 45%-70% after 4 hours of dissolution and of no less than 80% after 16 hours of dissolution (col. 1, ln. 54-64).
Regarding claim 42, Eeckman et al. teach that brivaracetam is effective in the treatment of epilepsy. Clinical trials evaluated the efficacy and safety of brivaracetam (5, 20, 50 and 150 mg per day) in the adjunctive treatment of adult patients (16-65 years) with refractory partial onset seizures, with or without secondary generalization (col. 1, ln. 33-37).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to determine the pharmaceutically effective amount of brivaracetam to include in the tablets according to Fanara et al.
Regarding claims 43 and 45, Fanara et al. teach the compositions may comprise a film-coating agent, and the pharmaceutical compositions can be in the form of tablets, coated or not (pg. 5-6). Eeckman et al. teach that the process may comprise a further coating step in which a solvent, preferably purified water, is added to the coating agent and resulting suspension is sprayed on the core of the tablet (col. 7, ln. 17-20).
A person of ordinary skill in the art would have been motivated to determine through routine experimentation the necessary concentration of coating to be applied to the tablet according to Fanara et al. and Eeckman et al.
Regarding claims 46-47, Fanara et al. teach preparation of separate homogeneous mixtures for the two layers by granulation of the two separate components and compression of the mixture into layers to form a multilayered tablet (pg. 5-6). Eeckman et al. teach preparation of granules by wet granulation, dry granulation or melt granulation, and compressing a mix of granules and other excipients into the form of a tablet (col. 6, ln. 26 to col. 7, ln. 16). The process may comprise a further coating step in which a solvent, preferably purified water, is added to the coating agent and resulting suspension is sprayed on the core of the tablet (col. 7, ln. 17-20).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare the multilayered tablet according to Fanara et al. comprising granulation of the active ingredient and excipient components of the separate layers, and compressing the separate granulated components into a multilayered tablet by known methods, such as compressing the first layer and then compressing the second layer onto the first layer. Also, it would have been obvious to include a coating layer, as reasonably suggested by Fanara et al. and Eeckman et al.
Response to Arguments
Applicant's arguments filed 21 July 2026 have been fully considered but they are not persuasive. Applicant argues that the proportion of active ingredient in the immediate release layer relative to the total mass of the active ingredient (brivaracetam or pharmacologically acceptable salts thereof in the immediate release layer account for 16.0wt% 33.0wt% of the total mass of the active ingredient in the extended release layer and the immediate release layer) is not disclosed or suggested by any of Fanara, Eeckman, or Bosse. Moreover, Fanara, Eeckman, and Bosse do not disclose Hypromellose K100M or K200M.
The examiner respectfully argues that Fanara et al. teach that it becomes increasingly advantageous therapeutically to be able to simultaneously orally administer an active substance released immediately after administration, and the same or a second active substance released gradually and regularly after administration. In the case where the same active substance is simultaneously administered in immediate release and in prolonged release, this makes it possible to rapidly release a sufficient dose of active substance to trigger the desired effect and to maintain this effect by a gradual and prolonged release of the same active substance (pg. 3 and 5-6). As for the dose of active substance used, it depends on the effective dose and can therefore vary within very wide limits depending on said active substance (pg. 5).
Eeckman et al. teach that brivaracetam is effective for treating epilepsy, and clinical trials evaluated the efficacy and safety of 5, 20, 50 and 150 mg per day (col. 1, ln. 33-37). Eeckman et al. also teach tablets comprising 20, 50 or 100 mg brivaracetam per tablet (Examples 1-6).
A person of ordinary skill in the art would have been motivated to determine through routine experimentation the effective concentration of brivaracetam in each of the immediate release layer and the extended release layer in order to achieve the desired therapeutic effect, and reduce the administration of active substances to one tablet per day, as reasonably taught by Fanara et al. and Eeckman et al.
Regarding the claimed hypromellose K100M or K200M, Eeckman et al. teach that the suitable hydrophilic matrix agent includes hydroxypropyl methylcellulose, including Methocel® K15M and Methocel® K100M (col. 2, ln. 13-39 and 49-52; col. 5, ln. 1 to col. 6, ln. 25; Examples 1 and 3-6; Claim 1). It would have been obvious for a person of ordinary skill in the art to substitute Methocel® K100M in the place of Methocel® K15M in the extended release layer of Fanara et al., as Eeckman et al. teach that both Methocel® K15M and K100M are suitable hydrophilic matrix agents for use in extended release tablets.
Applicant further argues that the list of active substances in Fanara, while extensive, does not include brivaracetam. Thus, "modification" of Fanara would require not simply optimizing ratios and excipients, but would require selecting a specific medication out of a vast design space of possible medications.
The examiner respectfully argues that Fanara et al. teach a finite number of specific active agent examples, including levetiracetam and piracetam. When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. See MPEP 2144.05(II)(B).
It is noted that brivaracetam is a structurally similar derivative of levetiracetam and piracetam, and all three active substances are used for the treatment of epilepsy, as taught by both Fanara et al. and Eeckman et al. Eeckman et al. teach that brivaracetam is a very water soluble active ingredient (ca. 700 mg/ml), and it is not obvious to slow down the release of the drug. Moreover, another problem consists in the reduction of the release rate, while keeping a reasonable size to the pharmaceutical form given to the patients. Surprisingly, it was discovered that it was possible to accurately control the release rate of the drug substance so that it can be administered in a few daily doses, and even in a single daily dose and so to provide a therapeutic effect for at least 16 hours when administered to a patient. Considering brivaracetam is classified as BCS I, the resulting in vitro dissolution (USP <711> apparatus no 2) in a buffered aqueous media has to show a drug release of no more than 40% after 1 hour of dissolution, of 35%-80% after 4 hours of dissolution and of no less than 80% after 16 hours of dissolution (col. 1, ln. 43-64).
Therefore, Eeckman et al. provide motivation to prepare brivaracetam in a dosage form that controls the release rate of the active while maintaining a therapeutically effective dose over an extended period of time.
Regarding the excipients, Fanara et al. and Eeckman et al. teach suitable excipients, including hydroxypropyl methylcellulose, diluents, lubricants and disintegrants, and their effective concentrations, for combining with the active agent to achieve the immediate release layer and the extended release layer. A person of ordinary skill in the art would have been motivated to follow the teachings of Fanara et al. and Eeckman et al. to prepare the multilayered tablet comprising an immediate release layer of brivaracetam and an extended release layer of brivaracetam, wherein the layers comprise the necessary excipients to achieve the desired release profile.
Applicant also argues that while Example 3 of Fanara discloses the use of hypromellose K15M, it does not indicate that the "rapid onset" and "sustained maintenance of effect after a single administration" balance is achieved by adding hypromellose K15M. It does not disclose or suggest the selection of high viscosity grades of hypromellose, such as K100M or K200M, nor does it disclose or suggest the necessity of such selection for achieving the specific release profile of the claimed tablet.
The examiner respectfully argues that Fanara et al. teach solid pharmaceutical compositions with controlled release in combination with one or more solid pharmaceutical composition allowing the immediate release of active substances. This makes it possible to obtain, in a single administration, both the immediate release of a first active substance and the prolonged release of the same or of a second active substance. Fanara et al. teach a solid pharmaceutical composition comprising: A. at least one layer comprising an active substance and excipients which allow the immediate release of said active substance after administration, and B. at least a second layer which allows the controlled release of the same or a second active substance, comprising said same or second active substance, at least one matrix-type excipient, at least one enteric-soluble polymer and at least one basifying agent (pg. 5-6). Fanara et al. teach that these combined solid pharmaceutical compositions may be in the form of a tablet in which at least one layer A is attached to at least one layer B (pg. 6).
Therefore, Fanara et al. teach the desire for a tablet comprising in a single administration an immediate release layer and an extended release layer of the same active substance.
Eeckman et al. teach that suitable hydrophilic gel-forming polymers include, but are not necessarily limited to, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, sodium carboxymethylcellulose, hydroxyethyl cellulose, and polyethylene oxide. For any given polymer type, use of a material with higher average molecular weight provides higher viscosity in aqueous solution of any given concentration; hence use of a higher molecular weight generally enables use of a lesser quantity of polymer to achieve the required retardation of dissolution. The polymers used are usually those that give a viscosity of more than 100 mPa·s in 2 percent aqueous solution (20° C), generally more than 250 mPa·s, and preferably more than 500 mPa·s. Preferred hydrophilic gel-forming polymers are selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose and polyethylene oxide. Especially preferred is hydroxypropyl methylcellulose having 18-29% methoxyl substitution and 7-10% hydroxypropyl substitution, and having a number average molecular weight of at least 20,000 g/mol. Such polymers include those sold by Colorcon under the tradenames Methocel® K4M, Methocel® K15M, Methocel® K100M and Polyox® WSR (col. 2, ln. 18-39).
Eeckman et al. further teach that the wet granulation process was found to bring an unexpected positive effect on the drug dissolution, when compared to direct compression process. This unexpected phenomenon could be explained by a synergetic effect of microcrystalline cellulose and hydroxypropyl methylcellulose, as brivaracetam is finely dispersed and/or entrapped in the internal phase. Consequently, smaller pores are created by the dissolution of the active pharmaceutical ingredient, and it has also to diffuse out of the microcrystalline granules. Hence, the dissolution of brivaracetam is further slowed down (col. 6, ln. 60 to col. 7, ln. 3).
Therefore, a person of ordinary skill in the art would have been motivated to select a hydrophilic gel-forming polymer according to Eeckman et al. in order to achieve the required retardation of dissolution, and thus the desired release profile.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that Eeckman discloses only a single-layer extended release tablet containing brivaracetam.
The examiner respectfully argues that Fanara et al. was relied upon for the teaching that a multilayered tablet comprising an immediate release layer and an extended release layer is desirable.
In response to 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 In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues that the core contribution of the present invention is to creatively resolve the seemingly contradictory requirements of "rapid onset" and "sustained maintenance of effect after a single administration" by precisely controlling the proportion of the active ingredient in the immediate release layer relative to the total active ingredient and by limiting the sustained-release matrix to very high viscosity grades of hypromellose, i.e., K100M and K200M.
The examiner respectfully argues that Fanara et al. teach solid pharmaceutical compositions with controlled release in combination with one or more solid pharmaceutical composition allowing the immediate release of active substances. This makes it possible to obtain, in a single administration, both the immediate release of a first active substance and the prolonged release of the same or of a second active substance. Therefore, a person of ordinary skill in the art would have been motivated to prepare a tablet dosage form wherein a therapeutically effective immediate release and extended release profile of active agent, i.e. brivaracetam, is achieved in a single administration. A person of ordinary skill in the art would have been able to determine through routine experimentation the optimum concentration to include in the immediate release layer to achieve a therapeutically effective rapid dose, while also determining an optimum concentration for the extended release layer to maintain the therapeutically effective dose over a prolonged period of time.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Fanara et al. (WO 01/51033 A1) in view of Eeckman et al. (US 8,435,564) as applied to claims 28, 30-38, 40-43 and 45-49 above, further in view of Bosse et al. (US 10,064,856).
Regarding claim 44, Fanara et al. and Eeckman et al. do not explicitly disclose a water-soluble polymer film-forming material and a plasticizer, as instantly claimed.
Bosse et al. teach multilayered tablet comprising anti-convulsants, such as brivaracetam, wherein the tablet comprises at least one immediate release layer and at least one controlled release layer (col. 29, ln. 45; col. 30, ln. 19-27). Bosse et al. teach that the compositions may further comprise coating materials and plasticizers. Examples of coating materials include, for example, hydroxypropyl methylcellulose 2910, aminoalkyl methacrylate copolymer E, polyvinylacetal diethylaminoacetate, macrogol 6000, titanium oxide and the like. Examples of plasticizers include, for example, triethyl citrate, triacetin, macrogol 6000 and the like (col. 64, ln. 7-9 and 35-40).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare tablets according to Fanara et al. and Eeckman et al., wherein the compositions include coating materials and plasticizers, as reasonably taught by Bosse et al.
Response to Arguments
Applicant's arguments filed 21 July 2026 have been fully considered but they are not persuasive. Applicant argues that starting from the pharmaceutical compositions of Bosse, selecting brivaracetam, and modifying with the disclosures of Fanara and/or Eeckman still does not support a conclusion of obviousness.
The examiner respectfully argues that Fanara et al. and Eeckman et al. provide motivation to prepare a tablet comprising an immediate release layer of brivaracetam and an extended release layer of brivaracetam, and a coating. Bosse et al. teach that coating materials include, for example, hydroxypropyl methylcellulose 2910, aminoalkyl methacrylate copolymer E, polyvinylacetal diethylaminoacetate, macrogol 6000, titanium oxide and the like. Examples of plasticizers include, for example, triethyl citrate, triacetin, macrogol 6000 and the like (col. 64, ln. 7-9 and 35-40). Therefore, it would have been obvious to select coating materials and plasticizers taught by Bosse et al. for coating the tablets according to Fanara et al. and Eeckman et al.
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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached 10:00 AM to 6:00 PM, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at (571) 272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.W.S/Examiner, Art Unit 1616
/ERIN E HIRT/Primary Examiner, Art Unit 1616
