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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on October 27, 2025 has been entered.
Status of Application
Receipt of Applicant’s remarks and amended claims filed on October 1, 2025 is acknowledged.
Claims 1-4, 6-8, 11, 13-20, 22, 24-25, and 29 are pending in this application.
Claims 5, 9-10, 12, 21, 23, and 26-28 have been cancelled.
Claims 1 and 11 have been amended.
All pending claims are under examination in this application.
Maintained Rejections
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 1-4, 6-8, 11, 13-15, 18-20, 22, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Gulati et al. (US 2009/0220593), as evidenced by Zaid (A comprehensive review on pharmaceutical film coating: Past, Present, and Future, Drug design, Development, and Therapy, 2020:14 4613-4623).
Gulati discloses a multiple unit extended dosage form of quetiapine or oral administration, wherein each unit comprises a core containing quetiapine and one or more of pharmaceutically acceptable excipients coated with a rate-controlling coating (abstract).
Multiple unit extended release dosage forms include a multiplicity of individual coated units that achieves a slow release of drug over an extended period of time, and includes prolonged, controlled, extended, and delayed release profiles. Multiple units can be granules, pellets, compacts, beads, spheroids, and the like (paragraph 0028).
The rate controlling coatings may comprise one or more of water soluble polymers or water insoluble polymers (paragraph 0019, 0030).
Examples of the rate controlling polymers include ammonio methacrylate copolymers and methacrylic acid copolymers (paragraph 0020), which are pH sensitive polymers and cellulose acetate and ethyl cellulose (paragraph 0021-0022), which are pH neutral polymers.
In addition to the rate controlling polymer coating, a seal coat may optionally be applied. Examples include cellulose acetate, ethyl cellulose, hydroxypropylmethylcellulose, polyethylene glycol, and polyvinylpyrrolidone (paragraph 0032), which are all pH neutral polymers.
Example 2 discloses a composition of Extended release coating pellets comprising
461 mg of quetiapine
80.42 mg Eudragit RS30D (a pH neutral polymer)
20.10 mg Eudragit RL30D (a pH sensitive polymer),
Which is 4.3% pH sensitive polymer and 17.4% pH neutral polymer.
The instant claims differ from the references only in the specific percentage pH neutral polymeric component in relation to the weight of the active in the core. However, It would have been deemed prima Facie obvious to one having ordinary skill in the art at the time of the invention to optimize the percentage the coating materials in order to achieve the desired dissolution profile of the active agent because the determination of a specific percentage having the optimum therapeutic effect is well within the level of one having ordinary skill in the art, and the artisan would be motivated to determine optimum amounts to get the maximum effect of the active compounds. Therefore, the invention as Whole has been prima face obvious to one of ordinary skill in the art at the time the invention was made. It is additionally noted that subsequent examples utilize different percentages of each polymer, see for examples 6-7.
The examples additionally recite quetiapine and pharmaceutically acceptable excipients. Not additional active agents are recited for inclusion in the core. Therefore, it is the position of the Examiner that the core consists of quetiapine and pharmaceutically acceptable excipients.
Regarding claims 2-4, as noted above, multiple unit extended release dosage forms include a multiplicity of individual coated units that achieves a slow release of drug over an extended period of time, and includes prolonged, controlled, extended, and delayed release profiles.
Regarding claim 6, as noted above, Example 2 discloses Eudragit RS30D (a pH neutral polymer) and Eudragit RL30D (a pH sensitive polymer).
Regarding claim 7, as noted above, the drug core consists of quetiapine and one or more pharmaceutically acceptable excipients (abstract).
Regarding claim 8, a coating of Opadry can be applied to the final tablets. The instant specification discloses the terms “non-functional coating” or “non-functional film coat” in the context of the present disclosure refers to a coating that does not materially affect the release of quetiapine or a pharmaceutically acceptable salt thereof from the formulation or dosage form. A non-functional coating or non-functional film coat may still include some functions not related to the dissolution of quetiapine, such as taste, color, or physical integrity.
Regarding claim 11, suitable excipients include disintegrants, glidants, lubricants, and solvents (paragraph 0034).
Regarding claims 13-14, as noted above, the multiple units can be granules, pellets, compacts, beads, spheroids, and the like (paragraph 0028) and filled into capsules or sachets (paragraph 032).
Regarding claim 15, it is Eudragit RD 30D (the pH neutral polymer) is water insoluble.
Regarding claims 18-20 and 24, the instant claims are considered contingent limitations, Applicant’s attention is directed to MPEP 2111.04 II which recites the broadest reasonable interpretation of a system (or apparatus or product) claim having structure that performs a function, which only needs to occur if a condition precedent is met, requires structure for performing the function should the condition occur. The system claim interpretation differs from a method claim interpretation because the claimed structure must be present in the system regardless of whether the condition is met and the function is performed. Since the prior art discloses the same structure as the instant claims, it would necessarily function the same when administered.
Regarding claim 22, since the prior art discloses the same composition as recited in claim 1, it would necessarily have the same dissolution profile, absent a showing of evidence to the contrary.
Regarding claim 25, it is noted that quetiapine is an antipsychotic used to treat schizophrenia (paragraph 0005). Therefore, the formulation of Gulati comprising quetiapine would necessary also treat schizophrenia.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have optimized ratios of polymers within the coating of the granules/ sprinkles/pellets of Gulati in order to achieve the desired dissolution profiles and functionality.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Gulati et al. (US 2009/022-593) as applied to claims 1-4, 6-8, 11, 13-15, 18-20, 22, and 24-25 above, and further in view of Ong et al. (Effects of Hypromellose as a pore former in aqueous ethyl cellulose dispersion: Characterization of Dispersion Properties, Controlled Release Society, Poster Reprint, July 2006).
The teachings of Gulati are discussed above.
Gulati does not disclose the use of a pore former.
Ong discloses hypromellose (HPMC) is commonly used as a pore forming in aqueous ethyl cellulose dispersions.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have used a pore former in the particles of Gulati because flocculation that occurred at HPMC levels in excess of 5% w/w was disrupted with adequate stress, similar to those encountered during coating processes.
Claims 17 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Gulati et al. (US 2009/0220593) as applied to claims 1-4, 6-8, 11, 13-15, 18-20, 22, and 24-25 above, and further in view of Hintz et al. (The effect of particle size distribution on dissolution rate and oral absorption, International Journal of Pharmaceutics, 51 (1989) 9-17).
The teachings of Gulati are discussed above.
Gulati does not disclose the particle size of the sprinkles.
Hintz discloses the rate of dissolution of a solid is dependent upon its solubility, its concentration in solution at a particular time, its diffusivity, and the surface area of the solid (Introduction).
Hintz discloses the particle size and shape can be modified to improve the agreement between simulated and measured particle size distribution and accurately simulating the absorption of a drug based on solubility and particle size weight distribution.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant application in order to adjust and optimize the surface area of the particles and increase solubility, as noted by Hintz.
Response to Arguments
Applicant's arguments have been fully considered but they are not persuasive. Applicant argues:
*Claim 1 has been amended to recite a drug core consisting of quetiapine or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients. The claimed composition does not include an inert core.
The Examiner disagrees with Applicant’s interpretation of the claim language. Pharmaceutically acceptable excipients are by definition an inactive substance that serves as the vehicle or medium for a drug or other active substance. Given its broadest reasonable interpretation, an inert core is thus considered an excipient. As previously suggested by the Examiner, the drug core limitations can be amended to recite “a drug core consisting of a uniform mixture of quetiapine or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients”. A uniform mixture would be structurally different than drug core with an inert core coated with a drug layer.
*Gulati discloses multiple unit extended release dosage form for oral administration. It further mentions “the term multiple unit extended release dosage form” as used herein includes multiplicity of individual coated units in the dosage form that achieves the slow release of drug over an extended period of time, and includes prolonged, controlled, extended and delayed release profiles. The multiple units may be designed as granules, pellets, compacts, beads, spheroids, and the like’’ ({0028]). However, it can be seen from Table 3 & Table 4 of Gulati that quetiapine composition shows release in an acidic media. Further, from the description and the polymers used, a person of ordinary skill in the art would understand that Gulati’s compositions are extended-release dosage form and does not comprise any delayed release component.
The instant claims recite “an extended release multi-particulate sprinkle dosage form”. It is noted that Gulati discloses the same pH sensitive and pH neutral polymers used on the instant claims. It is the position of the Examiner that the coatings would therefore result in the same functionality as those claimed. It is additionally noted the instant claims do not explicitly recite a delayed release polymer as alleged in the remarks.
Gulati discloses the multiple unit extended release dosage forms are prepared by:
a. loading the inert cores in the coating equipment;
b. optionally, coating the inert cores with a seal coat comprising a solution/dispersion of a suitable polymer;
c. applying a solution/dispersion of quetiapine and one or more of pharmaceutically acceptable excipients in a suitable solvent onto the inert cores;
d. applying a solution/dispersion of rate-controlling polymer and one or more of pharmaceutically acceptable excipients on the drug layered cores; and
e. optionally, applying a solution/dispersion of a suitable polymer in a suitable solvent on the extended release coated cores.
He clearly contemplated the general concept of rate control via delayed/extended coatings. Applicant has not provided any evidence of unexpected results of the combination of coatings. Applicant is reminded that where the general conditions of the claims are met, burden is shifted to applicant to provide a patentable distinction. 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 In re Aller, 220 F.2d 454 105 USPQ 233,235 (CCPA 1955).
It is unclear in Applicant’s arguments if it is being alleged that the particles of Gulati do not disclose the combination of coating layers but rather only one coating layer. Clarification is requested. Paragraph 0032 of Gulati discloses “the seal coat may be applied on the inert core prior to drug layering or between the drug layered cores and rate-controlling coating. Coated cores may be further coated with another coating layer”. As noted above, the seal coating comprises cellulose acetate, ethyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, polyvinylpyrrolidone and the like, which are neutral pH polymers. Therefore, the seal coating would constitute one of the two coating on the drug layer as recited in the instant claims.
*To develop a bioequivalent composition, the present inventors have conduct extensive experimentation and adjust the coating percentage to achieve a release profile similar to that of SEROQUEL XR and was not an routine optimization.
The use of prolonged, controlled, extended, and delayed coating is a routine and common modification to immediate release drug formulations. Applicant has not provided any evidence of non-routine testing or experimentation, as evidenced by the article of Zaid which discloses “pharmaceutical film coating is considered a key part in the production of solid pharmaceutical dosage forms since it gives superior organoleptic properties products. In addition, it can improve the physical and chemical stability of dosage forms, and modify the release characteristics of the drug”. Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
*Gulati does not teach/cover sprinkle administration.
The Examiner disagrees. Gulati discloses the preparation of pellets to be administered in capsules or sachets. Sachets provide a single dose packaging. The recitation of intended use of the particles, pellets, beads, or spheroids is not given patented weight. The recitation of “sprinkle dose” does not provide a structural difference in the disclosed composition of Gulati.
*Hintz discloses dissolution rate of solid is dependent on solubility, its concentration and surface area of the solid. Further, Hintz discloses particle size and shape can be modified to improve agreement between particle size distribution and stimulating absorption of drug based on solubility and particle size distribution (PSD). The Examiner asserts that it would have been obvious for a person of ordinary skill in the art to develop invention of specific PSD and combines teachings of Gulati.
Hintz discloses motivation why one would be motivated to adjust and optimize particle size distribution. He need not disclose motivation for the same use as the instant application.
* Ong alone or in combination with Gulati does not teach combination of two polymers and a pore former and no drug release at an acidic pH. Also, any possible combination of Ong with Gulati does not enable a stable quetiapine sprinkle formulation with specific dissolution profile as claimed. Mere disclosure of pore former HPMC for use with EC does not enable a person skilled in the art to arrive at the presently claimed sprinkle composition of Quetiapine.
The instant claims do not provide for no release at an acidic pH. The claims recite “not more than 10%” in acid stage. Additionally, instant claim 16 recites a ratio of 80:20 to 95:5. Applicant has submitted no evidence of the claimed dissolution over the claimed ratio of polymer: pore former. Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. ir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 11, 13-20, 22, 24-25, and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,690,805. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the pending claims recite a drug core of quetiapine and pharmaceutically acceptable excipients and at least 2 coating over the core comprising a pH neutral polymer and a pH sensitive polymer.
Conclusion
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/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615