Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of claims
No new or amended claim set has been submitted––only new arguments/remarks have been submitted on 03/10/2026 regarding the previous claim set filed 07/07/2025 and its corresponding non-final rejection filed 09/10/2025. Per the claim set submitted on 07/07/2025: Claim 1 is currently amended. Claims 4 and 8 are canceled. Claim 2-3, 5-7, and 9-24 are previously presented. Claims 1-3, 5-7, and 9-24 are pending and under examination.
Priority
This application is a 371 of PCT/EP2009/006707, filed on 09/16/2009. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application GERMANY 102008048729.5, filed on 09/24/2008. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Rejections maintained in view of arguments/remarks: Prior arts unchanged, mapping of prior arts modified to address arguments, obviousness rationale unchanged.
Claim 1-3, 5-7 and 9-24 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US Patent No. 71152281 to Singh et al in view of US 8153159 to Parikh, Johansson et al (European Journal of Pharmaceutics and Biopharmaceutics, 2001, 52:3; 347-357) and WO 2005023198 to Hickey et al (Hickey).
Instant claims are directed to a tablet comprising an inner phase comprising a plurality of first particles each containing an active agent and a coating and/or releasing the active in a modified manner, and spherical particles distinct from the first particles, which contain a second active ingredient having a density of less than 0.8 g/ml and an absolute porosity in a range of from 0.5 to 30%; an outer phase distinct from the inner phase, comprising one or more excipients in non-granulated form wherein the plurality of first particles and the spherical particles together make up at least 75% of the total weight of the tablet and the weight of the outer phase makes up not more than 25 percent of the total weight of the tablet.
US Patent No. 71152281 to Singh teaches a process for preparing, and a pharmaceutical composition of modafinil dosage forms for oral administration, wherein the dosage form includes a mixture of coarse particles (7-25% by weight of modafinil particles having a diameter greater than 220 micron) and fine particles (93-75% by weight of modafinil particles having a diameter less than 220 micron) of modafinil (abstract). Singh teaches micronizing the drug increases solubility but also causes poor flow properties and an increased chance of agglomeration ((col. 1, l 37-49).
Singh teaches modafinil having different particle sizes and therefore meet the instant claimed, “distinct particles”. The composition further includes mixing of the particles with excipients to form a blend, granulating the blend and mixing with extragranular pharmaceutically excipients, and compressing into a tablet (col. 1, l 55-col. 2, l 16). Table 1 shows intragranular component and an extragranular component. The extragranular component, which meets the instant outer phase, makes up 22.5mg and 477mg, which amounts to about 4.7% of outer or extragranular phase. The intragranular phase includes two different types of modafinil particles, and other excipients such as lactose, starch, croscarmellose sodium and povidone, whereas the extragranular phase include croscarmellose sodium (read on a disintegrant- see col. 5, l 43-46), and talc, colloidal silicon dioxide and magnesium stearate (which read on lubricants- col. 6, l 6-14). As seen from Table 1, the intragranular and extragranular phase are different from each other and therefore meet the instant “distinct” limitations.
With respect to the instant outer phase “not more than 25% of the total weight of the tablet”, it is to be noted that the total outer phase makes up (22.5%), which meets the instant limitations of claims 1, 3 and 6. Thus, the tablet composition of Singh meets the instant two sets of particles in an inner portion of the tablet and an outer phase that makes up no more than 25% of the tablet weight.
Singh teaches that the dissolution of modafinil particles can be modified by varying the ingredients to select a desired dissolution profile (col. 7, l 13-27) and hence meets the instant limitation “releasing the active ingredient in a modified manner” of claims 1 and 4 because instant claims recite “releasing the active ingredient in a modified manner” and “a coating” in an alternative manner. Singh teaches that the active agent is modafinil and is employed in different particle sizes,
For claim 19 and 20, Singh does not teach the exact distribution of the two types of particles. However, Singh teaches two different modafinil particle types having different particle sizes, and thus meet instant claimed, “same active agent in both first and spherical particles”.
Singh does not explicitly teach the instant claimed coating over the first particles required in claim 1, 2, 3 and 5.
Parikh teaches pharmaceutical compositions comprising modafinil having a desired release profile (abstract), such as sustained effect over a period 6 to 12 hours (col. 4, l 30-38), as modified or pulsatile release (col. 5, l 40-62), and the compositions in the form of tablets, caplets etc (col. 10, l 25-30. Parikh further teaches that the active core of modafinil is coated with one or more coatings (col. 5, l 64-col. 6, l 11). The active core particles are prepared by combining modafinil, binders such as PVP, a dissolution rate controlling polymer such as high viscosity HPMC and other excipients, which are blended to form spherical particles, with the drug being as high as 90% by weight based on the total weight of the extruded or granulated core (col. 6, l 40-50). The drug containing core is coated with several layers including a plasticized enteric polymer, a mixture of insoluble polymeric layer and a plasticized water dispersible/enteric polymer wherein the weight ratio of 10:1 to 1:1, and the total weight of the coatings is about 15 to 80 wt.% and more typically about 20 to 60 weight % based on the total weight of the multi-particulate dosage form (col. 6, l 54-63). Table 1 of Parikh teaches various extended-release formulations.
Thus, it would have been obvious for one of an ordinary skill in the art at the time of the instant invention was made to modify the teachings of Singh to prepare the modafinil particles of Singh as spherical particles and further coat the modafinil particles to arrive at the coated particles of active agents with an expectation provide a desired release profile. One of an ordinary skill in the art would have been motivated to do so because Parikh suggests preparing modafinil particles in the form of spherical particles and further coating the particles with different types of release controlling polymeric materials to provide a desired release of modafinil, such as enteric release, pulsatile release, delayed release etc.
Instant claim 1 recites “releasing the active ingredient in a modified manner” without any specific release pattern. Therefore, one of an ordinary skill in the art would have been able to modify the particles of Singh by choosing an appropriate coating over spherical particles of modafinil based on the desired release profile.
Singh fails to teach the instant claimed percentages the first and spherical particles i.e., make up at least 75% of the total weight of the tablet (claim 1), the weight percentages of claims 12-20, the amount or the proportion of the active agent (claims 22-24) or spherical particles and the percentage proportion of the outer phase, as in claims 7, 12-18.
However, Parikh teaches employing different amounts of active agent (modafinil) i.e., 5-90% (col. 6, l 17-in amounts as high as 50-90%, col. 12, l 55-65; claim 15 of the patent). In this regard, Singh teaches different amounts of active agents with different particle sizes (Table 1).
Further, Hickey teaches modafinil compositions wherein the solubility, dissolution, bioavailability, dose response and stability of modafinil is modulated and shows improved efficacy of the pharmaceutical compositions (Background of the invention – page 4-5). Hickey teaches oral composition (page 6, l 2-3) and teaches modafinil in an amount of up to 95% by weight of the composition (e.g., 95% of a co-crystal) (p. 23, first paragraph; p 26, last paragraph). Hickey teaches that modafinil co-crystals can be administered by controlled or provided as delayed release, or for immediate release of the drug (p 35). The composition is in the form of particles, granules, powder etc. (p 40, last paragraph), and teaches combining extragranular components such as diluents, suitable for tablet compressibility (p 41 and 42). Further, Hickey teaches employing extragranular components in amounts as low as 0.2% by weight of the composition (p 42) and as low as 10% excipients by weight of the composition (p 46).
Hence, it would have been obvious for one of an ordinary skill in the art to optimize the amount of active agent in different particles of Modafinil with respect to the total weight of the composition, further choose the desired amount of active agent or the composition of the in the inner phase, and reduce or increase the amount of excipients (in the outer phase) while increasing or reducing the active agents in the inner phase (intragranular) with an expectation to provide the desired dissolution as well as release rate of the active agent from the particles of the tablet (of Singh). One of an ordinary skill in the art would have been motivated to modify because Parikh teaches controlled or modified released of modafinil (col. 4, l 30-67; col. 6, l 13-55) particles for immediate release or time-controlled release (col. 8, l 16-27), and in amounts as high as 90%, and further, Hickey suggests modafinil in amounts as high as 95% by weight and extragranular components in amounts as low as 0.2% by weight of the composition of the tablet. Thus, one of an ordinary skill in the art would have been able to maintain low % outer phase (of Singh-Table I) to the exemplified 22.5% (table 1) or further reduce to even lower amounts, and at the same time increase the amounts of the inner phase to as high as 95% (meets the instant claims 1 and 16-18) to provide optimize the desired rate of release of the active agent such as immediate release or delayed release of modafinil.
Singh does not teach the instant claimed spherical particles having a particle density of less than 0.8 g/ml and an absolute porosity in a range of from 0.5 to 30% of instant claims.
Johansson studied the compression of granules prepared from MCC.
Johansson teaches that compression tableting process of pharmaceutical granules involves fragmentation (fracturing of granules into smaller agglomerates), deformation (a change in shape of individual granules), densification (a reduction in granule porosity) and attrition (primary particles are sheared off from the granules during compression); and that changes in the intragranular porosity would change the propensity of the granules to respond to compression by deformation and fragmentation (introduction). It is taught that the original porosity of the pellets is critical for the evolution of tablet structure and strength during compression. Johansson et al studied the effect of shape and porosity on the compression behavior and tablet forming ability of granular materials formed from microcrystalline cellulose (MCC).
The granules were prepared from microcrystalline cellulose particles. The compression behavior of both types of granular material was evaluated in terms of the degree of compression during tableting, the appearance of the tablets and the size distribution of retrieved aggregates (after deaggregation of the tablets). The compactibility of the granular materials, without and with the addition of a lubricant, was also studied Page 2, 1st paragraph). Sections 2.3.2 & 2.3.3 describe the measurement bulk density, porosity and voidage, and the preparation of tablets. Fig. 5a-c shows the degree of compression of granules and pellets as a function of porosity, shape coefficient and density of the granules, where fig 5a shows that at low porosity required a lower degree of compression, increased irregular shapes increased the degree of compression (5b) and increased density reduced the compression (fig. 5c) and that the bulk density of the granular material before compression controlled the degree of compression (page 11, last para). It is noted that the ranges of porosity and bulk density in fig. 5 includes the claimed ranges of “density of less than 0.8 g/ml and porosity in the range of 0.5 to 30 %.
Therefore, it would have been obvious for one of an ordinary skill in the art at the time of the instant invention was made to further modify the teachings of Singh (modified by Parikh) so as to prepare the two types of active agent containing particles of Singh (with or without a modified coating) with a suitable spherical shape, and also choose the optimum porosity and density in the claimed ranges because, Johansson suggests that the bulk density is a function of the effective density and the packaging density of the porous particles, the latter being affected by particle size, shape and surface roughness, and that the irregular shape of granules causes looser packing and lower density. Thus, Johansson suggests the importance of porosity, density, as well as the sphericity (shape) of the granules or pellets in obtaining the compression strength of the tablets (last para of page 12 & Fig 6 a-c). One of an ordinary skill in the art would have expected to achieve employ a suitable compression force and thus achieve desired tensile strength of the tablet in the teachings of Singh.
With respect claims 9-11, instant claims are directed to a product and not a process. 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, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Response to Arguments
Applicant's arguments filed 03/10/2026 have been fully considered but they are not persuasive.
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).
In response to applicant’s argument (p. 2-3) that the application teaches a multi-particulate tablet having a reduced outer phase without adversely affecting particle properties, including dissolution profile, the argument is not persuasive because:
The recited purpose or alleged advantage does not distinguish the claims from the applied prior art unless the claims recite limitations that are not taught or suggested by the reference. The rejection relies on Singh for the oral tablet framework and intragranular/extra-granular structure, Parikh for spherical/coated modafinil particles and modified release, Johansson for density and porosity properties relevant to compression, and hickey for high active drug loading and reduced excipient/extra-granular amounts. Applicant has further not provided evidence of criticality or unexpected results associated with the claimed outer-phase amount, density, and porosity ranges.
In response to applicant’s argument (p. 2-3) that Hickey is newly cited and that the rejection reflects hindsight, the argument is not persuasive because:
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).
In response to applicant’s argument (p. 3-4) that Singh’s different particle size does not satisfy the claimed distinct first particles and spherical particles because the claims define the particles by additional parameters, the argument is unpersuasive because:
Singh is relied upon for teaching distinct active-containing modafinil particle populations, namely course and fine particles. The rejection does not rely on Singh alone for all particle properties. Parikh teaches preparing modafinil particles as spherical and coated particles for modified-release dosage forms, and Johansson teaches density and porosity relevant to pharmaceutical granules/pellets. Thus, the combined teachings teach or suggest distinct active-containing particle populations having the claimed characteristics.
In response to applicant’s argument (p. 4) that Singh discusses only one kind of granule and therefore does not teach first particles distinct from spherical particles, this argument is not persuasive because:
The rejection does not require one Singh granule to correspond to both claimed particle populations. Singh teaches distinct modafinil particle populations before granulation, and Parikh teaches preparing modafinil particles in spherical and coated/modified release forms. It would have thus been obvious to apply Parikh’s particulate modified release teachings to Singh’s modafinil particle populations to obtain distinct active-containing particle populations as claimed.
In response to applicant’s argument (p. 5-7) that Singh’s coarse and fine modafinil particles together make up only 200 mg of the 499.5 mg tablet (i.e., 40 wt.%), which does not meet the claimed at least 75% limitation, this is not persuasive because:
The rejection does not rely on Singh alone as expressly disclosing the claimed 75 wt.% amount. Singh teaches the oral tablet framework, active-containing modafinil particle populations, and extra-granular excipients. Hickey teaches the high modafinil loading and reduced excipient/extra granular amounts, and Parikh teaches modafinil multi-particulate/coated dosage forms. Thus, an ordinarily skilled artisan would have found it obvious to adjust the relative amounts of active-containing particles and outer/extra-granular excipients to obtain the claimed particle loading and outer phase amount.
In response to applicant’s argument (p. 5-7) that the office action’s characterization of Singh is mutually inconsistent, this argument is not persuasive because:
Singh’s extra granular ingredients correspond to the claimed outer phase because they are added outside the granulated portion before tableting and include excipients such as disintegrants, lubricants, and flow-regulating materials. Singh’s active-containing modafinil particle populations provide the starting particle populations. The rejection relies on Parikh, Johansson, and Hickey to further supply the spherical/coated/modified release features, density/porosity features, and high particle loading/reduced outer phase features.
In response to applicant’s arguments (p. 7) that if Singh’s granules are treated as 95.5 wt.% of the tablet, then Singh has only one type of particle and lacks the claimed distinct first and spherical particles, this argument is not persuasive because:
The rejection does not rely solely on Singh’s granules as the claimed first particles and spherical particles. Singh teaches different active-containing modafinil particle populations, and Parikh teaches forming modafinil particles as spherical and coated/modified release particles. Therefore, the combined references teach or suggest distinct active-containing particle populations even if Singh’s granules themselves are not treated as both claimed populations.
In response to applicant’s argument (p. 8) that Parikh and Johannson do not supply the limitations allegedly missing from Singh, the argument is not persuasive because:
Parikh is relied upon for spherical particles, coated particles, and modified-release modafinil particulate dosage forms. Johansson is relied upon for density and porosity teachings relevant to compression and tableting of pharmaceutical granules/pellets. Hickey is relied upon for high active loading and reduced excipient/extra-granular amounts. The references are not relied upon individually for the claimed limitation––rather the rejection is based on their combined teachings.
In response to applicant’s argument (p. 8) that Parikh’s teaching of modafinil up to 90 wt.% of the core is irrelevant because it does not disclose the amount of particles relative to the total tablet weight, this argument is not persuasive because:
Parikh is not relied upon alone for the claimed total-tablet particle percentage. Parikh teaches high-drug modafinil cores and spherical/coated modified-release particulate systems. Hickey further teaches high modafinil loading and reduced excipient/extra-granular content. Together with Singh’s tablet formulation, these teachings would have suggested adjusting the amount of active-containing particulate material relative to the tablet weight to overlap with that claimed.
In response to applicant’s argument (p. 8) that Parikh would suggest coating all particles and that coating only one portion of particles is hindsight, the argument is not persuasive because:
Claim 1 does not require all particles to be identical, nor does it prohibit different particle populations from having different characteristics. Multi-particulate dosage forms commonly use different particle populations to obtain desired release behavior. Parikh teaches using coatings to provide controlled delayed, pulsatile, or modified release. Thus, applying coating or modified-release features to one active-containing particle population while maintaining another distinct spherical particle population would have been a predictable formulation choice to obtain a desired release profile, not hindsight.
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).
In response to applicant’s argument (p. 9-10) that Hickey’s disclosure of up to 95 wt.% modafinil is irrelevant because it does not teach placing active ingredients in different particles or maintaining particle characteristics after compression, the argument is not persuasive because:
Hickey is not relied upon alone to teach two distinct particle populations. Singh and Parikh supply the active-containing particulate framework and spherical/coated particle teachings. Hickey is relied upon for its teaching that oral modafinil compositions may include high active loading and reduced excipient/extra-granular content. When combined with Singh and Parikh, Hickey would have suggested increasing the relative amount of active-containing particles and reducing the amount of outer/extra-granular excipients. Applicant’s assertion that particle characteristics would not be maintained is unsupported by evidence.
In response to applicant’s argument (p. 9-10) that Hickeys release control and compressibility teachings are general and do not directly correlate to modafinil amount, the argument is not persuasive because:
The rejection does not require Hickey alone to disclose the entire claimed tablet. Hickey’s teachings are relevant because they show that high-loading modafinil oral compositions, particulate/granular/powder forms, and reduced excipient/extra-granular contents were known. These teachings would have provided one of ordinary skill with a reasonable expectation of success in modifying Singh’s tablet formulation in view of Parikh and Johansson to achieve the claimed loading and release characteristics.
In response to applicant’s argument (p. 10-11) that hickey’s discussion of low excipient amounts is incomplete or misinterpreted because it relates to crystallization-inhibiting excipients and allegedly implies at least 50 wt.% total excipients, this argument is unpersuasive because:
Applicant focuses on one portion of hickey while ignoring hickey’s broader teachings of high modafinil loading and reduced excipient/extra-granular amounts. The rejection relies on hickey for the general teaching that modafinil compositions may be formulated with high active content and reduced excipient content, not for an identical formulation. The claimed percentages would have been reached by routine optimization of known formulation variables in view of the combined teachings of Singh, Parikh, Johansson, and Hickey.
In response to applicant’s argument that neither Hickey nor Singh teaches a tablet comprising both first particles and spherical particles distinct from the first particles, this argument is not persuasive because:
Hickey is not relied upon to teach the distinct particle populations. Singh teaches Distinct modafinil particle populations, and Parikh teaches spherical and coated modafinil particulate dosage forms. Hickey Supplies high active loading and reduced excipient teachings. Therefore, the combined references teach the claimed tablets.
Conclusions
No claim is found allowable.
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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Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/ Primary Examiner, Art Unit 1613
Prosecution Insights