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 .
Status of Application
Receipt of Applicant’s remarks and amended claims filed on April 13, 2026 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.
No claims amendments have been submitted.
All pending claims are under examination in this application.
Withdrawn Rejections
Double Patenting
The rejection of claims 1-4, 6-8, 11, 13-20, 22, 24-25, and 29 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,690,805 has been withdrawn in view of the acceptance of the terminal disclaimer.
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:
*The core of Gulati is structurally different from that of the instant claims. The drug core provides a large volume for the incorporation of active substance.
Instant claim 1 recites "drug core consists of quetiapine or a pharmaceutically acceptable salt thereof". Therefore, the pharmaceutical ingredient is limited to only quetiapine, however, the core itself can comprise any additional excipients, which given its broadest reasonable interpretation, includes an inert core. Additionally, the core is disclosed to comprise quetiapine dispersed within it (paragraph 0018).
*The drug core provides a large volume for the incorporation of active substance.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., amount of quetiapine is the drug core) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Paragraph 0018 discloses coating on a core. It is noted the instant claims recite “at least two coating on the drug core wherein one of the at least two coatings comprise a pH sensitive polymer, and a second of the at least two coatings comprise a pH neutral polymer”.
*The Examiner contends that the seal coating in Gulati would constitute one of the two coatings on the drug layer as recited in the instant claims. The Examiner relies on paragraph [0032] of the Gulati. Applicant submits that the Gulati discloses only one Example with seal coating (Refer to Example 1 of Gulati). Gulati discloses that the non-pareil seeds are seal coated and then such seal coated non-pareil seeds are further coated with drug layer (Para [0057]-[0061] of Gulati).
Contrary to Applicant’s assertion, paragraph 0032 discloses the seal coating may be applied on the inert core prior to drug layer OR between the drug layered core and rate controlling coating.
In response to the argument regarding Example 1 in Gulati, Applicant is directed to MPEP 2123 with discloses The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)) and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).
*The Examiner alleges that the Gulati discloses the same pH sensitive and pH neutral polymers used in the instant claims and would therefore result in the same functionality as those claimed. The Examiner also contends that the instant claims do not explicitly recite a delayed release polymer.
The instant claim 1 does not recite specific polymers but rather types of polymers (i.e. pH sensitive and pH neutral polymers). Applicant’s attention is directed to MPEP 2141.03 which discloses the person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). The selection of polymers results in specific dissolution profile would be within the purview of the skilled artisan since dissolution profiles are a common and routinely optimized and adjusted properties with the art.
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).
Furthermore, the tables within Gulati disclose adjustment of polymer concentration can be adjusted to optimize the release profile of the pellets.
*The Examiner contends that Gulati discloses the preparation of pellets to be administered in capsules or sachets and hence teaches sprinkle administration. The present invention relates to sprinkle compositions of quetiapine with a view to provide improved patient compliance, for example, for geriatric patients or patients with dysphagia. The present formulations do not involve complicated dosing, and can be administered through NasoGastric tubes (NGT administration) due to the smaller size of the granules/pellets.
Gulati discloses the preparation of pellets to be administered in capsules or sachets. Sachets provide a single dose packaging. The skilled artisan would immediately envision pellets are disclosed as sprinkle dosing, as recited in the instant claims. Furthermore, no structural difference has been identified in the instant specification recitation of “sprinkle dose” does not provide a structural difference in the disclosed composition of Gulati.
Additionally, instant claim 1 does not recite any particle size range or distribution. Particle size is not recited until dependent claim 29.
Additionally, the concept of opening capsules and sprinkling the contents onto a food product or beverage is a well know dosing strategy, for example, the article by Medicines for Children discloses:
Mixing with Food:
The contents of some capsules can be mixed with a small amount of food. If you are not sure if your child’s capsules can be mixed with food, speak with your child’s doctor or pharmacist.
Open the capsule carefully and mix the contents with a teaspoon of soft food (e.g. yogurt, honey or jam) or a small amount (10 mL, which is about 2 teaspoons) of fruit juice or squash.
Make sure your child swallows it straight away, without chewing. (The capsule contents may have a bitter taste, so you will need to use something strong-tasting to mask it, such as undiluted fruit squash.)
Dissolving in water:
The contents of some capsules can be dissolved in water or juice. Your doctor will tell you how much liquid to use, and how much of it to give your child.
Open the capsule carefully and dissolve the contents in the right amount of water or fruit juice.
Give the mixture to your child straight away, using an oral syringe or medicine spoon. You can get these from your pharmacist.
*Hintz does not disclose quetiapine formulations but merely discloses particle sizes and shapes can be modified to improve agreement between particle size distribution and stimulating absorption.
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).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA S MERCIER whose telephone number is (571)272-9039. The examiner can normally be reached M-F 6:30 am to 4 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615
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