DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims included in prosecution are claim 13 and 15-32.
Previous Rejections
Applicants' arguments, filed Jan. 26, 2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Response to Election by Original Presentation
Applicant's traverse of the Election by Original Presentation in the reply filed on Jan. 26, 2026 is acknowledged. The traversal is on the ground(s) that Applicant alleges that the common technical feature linking groups I-II constitutes a special technical feature in light of Applicant’s latest amendment to utilize “consisting of” language in claim 13. This is not found persuasive for the reasons recited in the rejection of claim 13 below.
The requirement is still deemed proper and is therefore made FINAL.
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.
1. Claim(s) 13, 15-20, 22-29, and 31-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baek et al. (CA 3,046,296, Jun. 21, 2018) (hereinafter Baek) in view of Maleki et al. (Res in Pharm Sci, 2015, 10(2), pp 95-108) (hereinafter Maleki), Thirulmalai et al. (WO 2017/025981, Feb. 16, 2017) (hereinafter Thirulmalai), and Choudhary (Pharmaguideline, Apr 25, 2019) (hereinafter Choudhary).
Baek teaches an orally disintegrated tablet and a method for producing same, the tablet containing a carbamate compound of chemical formula 1, an isomer thereof, or a pharmaceutically acceptable salt, a solvate or a hydrate thereof, as an active ingredient (Abstract). Formulations of the prior art were disadvantageous in that dissolution rate in the oral cavity was low (Page 3). The orally disintegrating tablet comprises: a carbamate compound of Formula 1 as an active ingredient where formula 1 is as follows:
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wherein, R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, C1-C5 alkyl, halo- C1-C5 alkyl, C1-C5 thioalkoxy and C1-C5 alkoxy; and one of A1 and A2 is CH, and the other is N. In one embodiment of the present invention, the carbamate compound of Formula 1 is carbamic acid (R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl ester of the Formula 2 (satisfies claim 19) (Page 5, Paragraph 5).
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In an embodiment, suitable disintegrants include sodium starch glycolate, hydroxypropyl cellulose, and sodium crosscarmellose (satisfies carrier of claim 13, 17, 18 & 31) (Page 6, Paragraph 2). In one embodiment of the present invention, the content of the carbamate compound is 2.5 to 25 wt% based on the total weight of the orally disintegrating tablet (Page 7, Paragraph 1). Baek’s method of preparing the orally disintegrated tablet involves mixing the carbamate compound of Formula 1 with excipients; and the disintegrant and preparing a granule (i.e., particles of a carbamate compound), prior to a step of mixing said granule with a disintegrant before tableting (satisfies mixing of claim 13) (Page 7-8). The amount of disintegrant mixed with the granule is preferably 4 to 8 wt% based on the total weight of the orally disintegrating tablet (Page 17, Paragraph 4). The orally disintegrating tablet may comprise a lubricant, a glidant and a sweetening agent, etc. (Page 18, Paragraph 2). Preferably, the lubricant is magnesium stearate (satisfies claim 32). The content of the lubricant may be 0.1 to 5 wt% based on the total weight of the orally disintegrating tablet (Page 18, Paragraph 3). From the orally disintegrating tablet, at least 80% of the active ingredient may be eluted within 10 minutes, or at least 90% of the active ingredient may be eluted within 15 minutes (satisfies claim 26-29) (Page 19, Paragraph 2). The dosage of the carbamate compound of Formula 1 or 2 may typically vary but the therapeutically effective amount of the compounds is generally 50 to 500 mg (satisfies claim 16) (Page 19, Paragraph 5).
Baek differs from the instant claims insofar as not disclosing wherein the active ingredient particle size is less than 300 microns nor disclosing wherein the method utilizes direct compression.
However, Maleki discloses that solubility, bioavailability and dissolution rate of drugs are important for achieving in vivo efficacy (Abstract). Furthermore, particle size and shape are important in every stage of solid oral dosage form and fabrication. Particle size affects mixing, granulation, compression and coating of solid dosage forms in the body. Dissolution rate is a function of solubility and particle size and the simplest way to increase the dissolution rate is particle size modification. By reducing particle size of both actives and excipients, via micronization and nanosizing, dissolution rate can be enhanced. This enhancement occurs because when particle size is reduced, the total effective surface area is increased (Pg. 96, Col. 2).
Maleki does not explicitly disclose the particle size as instantly claimed.
However, Thirulmalai discloses that carbamate compounds may undergo conventional size reduction techniques in order to provide the desired solubility profile based on different forms of pharmaceutical composition requirements (Pg. 28, Par. 2). In an exemplary embodiment, D(0.5) was measured at 23.5µm and D(0.9) at 46.3µm (Pg. 37, Par. 1).
Accordingly, considering that Baek discloses a need to improved dissolution rate, it would have been obvious for one of ordinary skill in the art ordinary skill in the, prior to the filing of the instant application, to have formulated the active ingredient particles of Baek to have a D(0.5) of 23.5µm and D(0.9) of 46.3µm since Maleki discloses that active ingredient particle size reduction is needed to enhance dissolution rate and Thirulmalai discloses these particle sizes as suitable when attempting to provide an appropriate solubility profile for a carbamate compound.
The combined teachings of Baek, Maleki, and Thirulmalai do not disclose the use of direct compression.
However, Choudhary teaches that manufacturing tablets using direct compression is advantageous as the whole process generally requires fewer steps in implementation without requiring the use of moisture and heat. Further, tablets made as a product of direct compression have faster dissolution properties as compared to those of wet granulation (Page 1, Paragraph 7).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have made the tablet of Baek in view of Maleki and Thirulmalai using direct compression motivated by the desire to utilize a process that requires less steps, does not require the use of moisture and heat, and thereby achieve a tablet with faster dissolution rates as taught by Choudhary.
Regarding claim 1 reciting consisting of language, the instant claim recites “a step of mixing particles of carbamate compound”. As discussed above, Baek’s method involves first formulating these particles or granules before the step of mixing them with a disintegrant (i.e., a pharmaceutically acceptable carrier), prior to tableting. As such, the teachings of Baek satisfy the method which consists of “a step of mixing particles of carbamate compound …. with a pharmaceutically acceptable carrier” as instantly claimed.
Regarding the active ingredient dosage recited in instant claim 16 (i.e., 5 mg to 400 mg), in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(A). As discussed above, the active drug of Baek may be administered in an amount of 50 to 500 mg. Accordingly, because the range recited in the instant claims overlaps with the range disclosed by Baek, the dosage disclosed by Baek meets the instantly recited limitations.
Regarding the dissolution rates recited in instant claims 26-29, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(A). As discussed above, in Baek’s orally disintegrating tablet, at least 80% of the active ingredient may be eluted within 10 minutes, or at least 90% of the active ingredient may be eluted within 15 minutes. Accordingly, because the ranges recited in the instant claims overlap with the ranges disclosed by Baek, the ranges disclosed by Baek meet the instantly recited limitations.
Therefore, the combined teachings of Baek, Maleki, Thirulmalai, and Choudhary render obvious claims
2. Claim(s) 21 and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baek et al. (CA 3,046,296, Jun. 21, 2018) (hereinafter Baek) in view of Maleki et al. (Res in Pharm Sci, 2015, 10(2), pp 95-108) (hereinafter Maleki), Thirulmalai et al. (WO 2017/025981, Feb. 16, 2017) (hereinafter Thirulmalai), and Choudhary (Pharmaguideline, Apr 25, 2019) (hereinafter Choudhary) and further in view of Rui et al. (US 2005/0148643, Jul. 7, 2005) (hereinafter Rui).
The combined teachings of Baek, Maleki, Thirulmalai, and Choudhary are discussed above.
These combined teachings differ insofar as not explicitly disclosing wherein the granule is mixed diluents with lactose hydrate or microcrystalline cellulose.
However, Rui teaches carbamate compounds (Abstract). An "excipient" generally refers to substance, often an inert substance, added to a pharmacological composition or otherwise used as a vehicle to further facilitate administration of a compound (¶ [0216]). The pharmaceutical compositions may comprise excipients such as diluents and disintegrating agents. Suitable disintegrating agents include microcrystalline cellulose and sodium croscarmellose (¶ [0263]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Baek discloses wherein the granule is mixed with a disintegrant. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the method of Baek to comprise mixing the granule of active with microcrystalline cellulose, since it is a known disintegrating agent for use with carbamate compounds as taught by Rui.
Alternatively, it is obvious to replace one component for another equivalent component if it is recognized in the art that the two components are equivalent and is not based on the Applicant disclosure. See MPEP 2144.06. As discussed above, Baek discloses wherein suitable disintegrants include sodium croscarmellose. Accordingly, it would have been obvious for one of ordinary skill in the art ordinary skill in the art ordinary skill in the art, prior to the filing of the instant application, to have formulated the method of Baek to comprise mixing the granule of active with microcrystalline cellulose in place of sodium croscarmellose because they are taught as equivalents by Rui.
In regards to the composition comprising both starch glycolate and microcrystalline cellulose, since the use of various disintegrating agents is known individually, the use of the individual species in combination would have been obvious since it is prima facie obvious to combine two compositions, each of which is taught to be useful for the same purpose, in order to form a third composition to be used for the very same purpose; the idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06.
Regarding the amounts of active, disintegrant, and lubricant recited in instant claim 21, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). As discussed above, Baek’s tablet contains 2.5 to 25 wt.% of the carbamate compound, 4 to 8 wt.% of the disintegrant, and 0.1 to 5 wt.% of a lubricant. Accordingly, because the ranges recited in the instant claims overlap with the ranges disclosed by Baek the ranges disclosed by Baek meet the instantly recited limitations.
Regarding the amount of diluent recited in instant claim 21, 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. See MPEP 2144.05(II)(A). As discussed above, diluents are excipients which facilitate administration of a compound, which makes amounts thereof a result effective variable, since amounts directly impact the administration of a compound. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amounts of diluent to yield the desired active compound administration profile.
Therefore, the combined teachings of Baek, Maleki, Thirulmalai, Choudhary, and Rui render obvious claims 21 and 30.
Response to Arguments
Applicant’s arguments with respect to claims 13 and 15-32 have been considered but are unpersuasive.
Regarding Applicant’s argument that Baek does not meet the consisting of language which allegedly indicates “a single step”, as discussed above, the instant claim recites “a step of mixing particles of carbamate compound”. As discussed above, Baek’s method involves first formulating these particles or granules before the step of mixing them with a disintegrant (i.e., a pharmaceutically acceptable carrier), prior to tableting. This satisfies the instant claim because steps (a)-(b) of Baek are direct to making the particles or granules of the carbamate compound. Step (d) corresponds to the claimed tableting step.
Regarding Applicant’s arguments that Baek is directed to a tablet which contains “a first granule and a second granule”, the Examiner has not found anywhere in the Baek disclosure where Baek refers to such a “a first granule and a second granule”. The only inventive granule that Baek refers to that the Examiner has found has been the granule cited in the rejection above and this appears to be a single granule not “a first granule and a second granule”.
Regarding Applicant’s argument that Baek shows that omitting the second granule results in a slower disintegration rate, the Examiner has again reviewed Experimental Examples 1-2 of Baek and Table 3 of Baek and the various disclosures related to them and has not found where Baek discloses “a first granule and a second granule” nor where Baek attributes the improved performance of the inventive tablets to the omission of a “second granule”. In the conclusion paragraph of the dissolution and disintegration test, Baek simply recites “As shown in Table 3, the orally disintegrating tablets of Examples 1 and 2 showed a much faster disintegration rate than the immediate-release tablets of Comparative Examples 1 and 2”. As such, it is unclear where Baek points to the omission of a “second granule” as the factor contributing to poor dissolution/disintegration.
Regarding Applicant’s argument that Maleki does not cure the alleged deficiencies of Baek, the Examiner submits that Maleki cures any alleged deficiencies of Baek where Maleki discloses that active ingredient particle size reduction is needed to enhance dissolution rate.
Regarding Applicant’s argument that Thirulmalai does not cure the alleged deficiencies of Baek, the Examiner submits that Thirulmalai cures any alleged deficiencies of Baek where Thirulmalai discloses particle sizes such as D(0.5) of 23.5µm and D(0.9) of 46.3µm are suitable when attempting to provide an appropriate solubility profile for a carbamate compound.
Regarding Applicant’s argument that Choudhary does not cure the alleged deficiencies of Baek, the Examiner submits that Choudhary cures any alleged deficiencies of Baek where Choudhary discloses provides strong motivation to modify the method of Baek to utilize direct compression.
In light of the foregoing, the Examiner does not find Applicant’s arguments to be persuasive and the rejection is maintained.
Conclusion
Claims 13 and 15-32 are rejected.
Claims 33-41 are withdrawn.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.A./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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