DETAILED ACTION
Status of Application
Receipt of the response to the non-final office action, the amendments to claims and applicant arguments/remarks, filed 06/23/2026, is acknowledged.
Claims 1, 6, 8-12 are pending in this application. Claims 2-5, 7, 13 have been cancelled previously. Claims 1, 6, 12 have been amended. Claims 1, 6, 8-12 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant's amendments necessitated new ground(s) of objection and rejection presented in this office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
This application, filed January 30, 2021, claims benefit of foreign priority to IN202041004130, filed January 30, 2020 (in English).
Terminal Disclaimer
The terminal disclaimers, filed 10/08/2024, disclaiming the terminal portion of any patent granted on this application, which would extend beyond the expiration date of the prior Patent No. 11,975,011, and any patent granted on reference application No. 17/508,238, have been reviewed and are accepted. The terminal disclaimers have been recorded.
Claim Objections
Claim 12 is objected to because of the following informality: Claim 12 comprises the typographic error “1.0-3.0% of w/w colloidal silicon dioxide-as” that needs to be corrected to “1.0-3.0% w/w of colloidal silicon dioxide as” or clarified. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6, 8-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Newly amended claim 1 recites the limitation “as measured by USP apparatus II (paddle)” that is unclear. To this point, it is noted that parenthetical expressions are not permissible, which do not contribute to clearness or exactness in stating applicant’s invention (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). This limitation was interpreted as best understood as “as measured by USP apparatus 2 paddle” (see Specification, Example 3 and/or www.agilent.com). Clarification is required.
Newly amended claim 6 (dependent on claim 1) recites the limitation “wherein the core minitablet does not exceed 100% w/w in total” that is not reasonably clear. In the present case, it is unclear what said limitation does imply – the core minitablet does not exceed 100% based on the weight of a coated tablet? Clarification is required.
As stated previously, claim 10 and/or 11 (both dependent on claim 1) recite the limitations “seal coating polymer” (claim 10), and/or “seal coated surface” (claim 11). To this point, it is noted that neither the claims nor the instant specification provides a clear definition for said terms. Therefore, one of ordinary skill in the art would not be reasonably appraised of the scope of the invention. Further, it is noted that claim 1 discloses coated minitablet providing a specific in vitro release profile (see claim 1). In the present case, it is unclear what seal coat polymers should be used for providing/controlling said claimed property. Clarification is required.
Claim 12 (depending on claim 1) recites the limitation “the retarding agent“ as a component of compositions claimed in claim 1. Said independent claim, however, does not include or identify the role/use of “a retarding agent". Therefore, there is insufficient antecedent basis for this limitation in the claim. Therefore, the metes and bounds of the claim 12 cannot be determined. Clarification is required.
Claim 12 (depending on claim 1) discloses the use of 6.5-10 wr% of glyceryl dibehenate in “step a”; and further teaches the additional use of 1-3.5 wt% of glyceryl dibehenate in “step c”. To this point, it is noted that independent claim 1 discloses coated minitablets comprising 6.5-10 wt% of glyceryl dibehenate. Therefore, it is unclear how claim 12 narrows the scope of the claim upon which it depends. Clarification is required.
Claims 8 and 9 are rejected as being dependent on rejected independent claim 1 and failing to cure the defect.
Claim Rejections - 35 USC § 103 - MAINTAINED
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.
Claims 1, 6, 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Bowe et al., US 2015/0056275 (hereinafter referred to as Bowe), Otterbeck, US 2013/0189356; Shukla et al., US 2009/0169622 (hereinafter referred to as Shukla), in view of Valducci et al., WO 2017/125856A1 (hereinafter referred to as Valducci).
Bowe teaches controlled-release solid dosage forms of mesalamine (also known as 5-aminosalicylic acid and/or 5-ASA) for treatment of inflammatory bowel disease, wherein said dosage forms comprise a plurality of coated mini-tablets having a diameter of 2-5 mm (Claim 7; Abstract; Para. 0005-0007 as applied to claims 1, 12), and wherein said mini-tablets may include:
(a) a core comprising mesalamine (5-ASA; e.g., in an amount of 80 wt%) in combination with pharmaceutically acceptable carrier that may include a diluent, a binder, a lubricant, a plasticizer, a filler, etc., and specifically teaches the use of (Para. 0008-0009, 0011, 0014-0017; 0030, 0055, 0071-0072, 0081, 0092-0099 as applied to claim 1, 6, 8): (i) glyceryl behenate, magnesium stearate, polyethylene glycol, e.g., having molecular weight of 100-10,000 Da, or 750 Da (i.e., a lubricant); etc. and a mixture thereof; (ii) ethyl cellulose, calcium stearate, stearic acid (i.e., a retarding agent); (iii) colloidal silicone dioxide, talc (i.e., a glidant); (iv) polyvinylpyrrolidone, hydroxypropyl cellulose, acacia, hydroxypropyl methylcellulose/hypromellose (i.e., a binder); (v) lactose, lactose monohydrate, starches, microcrystalline cellulose, mannitol (i.e., a diluent); (vi) crospovidone (i.e., a disintegrant);
(b) an outer coating comprising ethyl cellulose (i.e., hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., a hydrophilic polymer), wherein the coating comprises 1-6 wt% of said mini-tablet (Para. 0008, 0012, 0032, 0074, 0101, 0106-0107 as applied to claims 1, 9);
(c) an optional coating (Para. 0008, 0009, 0074, 0104 as applied to claim 10, 11).
Bowe teaches that said coated mini-tablets may include 80-90 wt% of mesalamine/5-ASA by weight of the mini-tablet core (Para. 0112-0113), and further teaches that coated mini-tablets can be aggregated together to provide dosage forms/compositions of 1-2000 mg of active agent (Claim 14; Para. 0068 as applied to claim 1).
Bowe teaches that the core of said mini-tablets may include (based on the weight of the core): 10-40 wt% of a diluent (Para. 0203-0206); 1-10 wt % of a binder (Para. 0207-0209); 0.5-5 wt % of a lubricant (Para. 0210-0213 as applied to claim 6).
Bowe provides examples of using in the outer coating ethyl cellulose (i.e., a hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., a hydrophilic polymer) at a weight ratio of 0.66 (Para. 0413, 0414), and/or of using ethyl cellulose in an amount of about 1% (Para. 0404 as applied to claims 1, 9).
Bowe teaches a process of manufacturing said coated mini-tablets comprising (i) mixing or granulating a mixture of active pharmaceutical agent and optional excipients; (ii) drying the mixture to a residual amount of water of 0-5% and passing dry granules through mesh screen of size #20-#75; (iii) directly compressing said mixture into mini-tablets; (iv) coating the mini-tablets with an optional undercoat composition comprising a water-soluble polymer; and further (v) coating the mini-tablets with a top-coat with a top-coat composition comprising a polymer that modifies release of the active pharmaceutical agent (Para. 0007; 0069-0073 as applied to claim 12).
Otterbeck teaches oral controlled release compositions suitable for the treatment of the intestinal tract (e.g., inflammatory intestinal disorders), wherein said compositions comprise pellets that include (i) a core comprising 5-aminosalicylic acid (5-ASA), a salt or a derivative thereof as an active agent and 1-21 wt% of a matrix forming polymer(s) by the weight of the core; (ii) an enteric coating that may include ethyl cellulose (i.e., hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., hydrophilic polymer) (Claim 1; Abstract; Para. 0021-0024, 0027-0028; 0049); and (iii) also may include additional coatings (Para. 0031). Otterbeck further teaches that the core may include polyvinylpyrrolidone, microcrystalline cellulose, silica, corn starch, magnesium stearate, lactose, polyethylene glycol, talc, etc. (Para. 0033), and wherein said pellets have a size of 0.1-3 mm (Claims 7, 13; Para. 0037). Otterbeck teaches that said approach allows lowering active compound concentrations in the blood with a simultaneously higher concentration of the active compounds in the intestine, as a result of which the side effect potentially caused by the systemically available active compound or its metabolites, is markedly reduced (Para. 0038, 0039).
Shukla teaches delayed release compositions for the treatment of colonic disorders and diseases, wherein said compositions can be in a form of tablet and include (i) a core comprising 50-80 wt% of 5-ASA/mesalamine in combination with pharmaceutically acceptable adjuvants, disintegrants, binders, glidants, lubricants and/or diluents; and (ii) a coating comprising a mixture of ethyl cellulose/hydrophobic polymer and hydroxypropyl methylcellulose/hydrophilic polymer present at a ratio of from 1:0.67 to 1:5.7 (Abstract; Para. 0003, 0004, 0030-0032). To this point, Shukla teaches that the core may include: (i) starch, lactose, calcium phosphate, stearic acid (i.e., diluent; Para. 0023); (ii) polyvinyl pyrrolidine, starch (i.e., binder; Para. 0023, 0024); (iii) crospovidone, sodium starch glycolate, croscarmellose sodium (i.e., disintegrant; Para. 0023); (iv) magnesium stearate, stearic acid, polyethylene glycol, glyceryl behenate (i.e., lubricant; Para. 0023, 0024); (v) silicon dioxide, talc (i.e., glidant; Para. 0024); (vi) ethyl cellulose, calcium stearate, stearic acid, (i.e., retarding agent; Para. 0023, 0024), and (v) may include additional coating layers (Para. 0027-0029).
Though the cited prior art teaches the use of glyceryl behenate as a constituent of the core, said prior art does not teach the use of glyceryl dibehenate (claim 1).
Valducci teaches modified-release high-dosage tablets for treating inflammation in the colon, wherein said tablets consist of a core containing 5-ASA/mesalamine and at least one gastro-resistant coating (Abstract; Page 1). Valducci teaches that the core may include lubricants, e.g., glycerol dibehenate, magnesium stearate, stearic acid, sodium stearyl fumarate; glidants, e.g., colloidal anhydrous silica; binders, e.g., polyvinylpyrrolidone, hydroxypropyl cellulose, and other additives (Claim 2; Pages 3-4). Valducci further teaches the use of the coating that present in an amount of 5-15 wt% of the total weight of the tablet and consists of polymers having pH-dependent features leading to a release of the active ingredient only when the tablet reaches high pH values, i.e. in the colon, e.g., polymers having carboxylic groups, which in acidic environment are hydrogenated and devoid of charge (thus insoluble), but which become soluble when they lose the hydrogen in basic environment, due to the appearance of a negative charge, and also teaches that said polymers are present in a weight ratios in the range of from 1:0.5 to 1:19 (Page 4). Further, Valducci teaches that said tablets may include 500-2000 mg of 5-ASA/mesalamine, i.e., in an amount of 75-96 wt% by weight of the core (Page 3), and/or 70-95% by the total weight of the tablet (Claim 3; Page 3), and wherein said tablets begin to melt once they reach the colon (Page 6).
Therefore, it is the examiner’s position that the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because every element of the invention has been collectively taught by the combined teachings of the references. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to try such excipient as glyceryl dibehenate as taught by Valducci preparing tablets as taught by Bowe, Otterbeck and Shukla, because it is prima facie obvious to combine compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a new composition to be used for the very same purpose, i.e., delivering of the claimed active agent to the colon. MPEP 2144.06.
With regard to the concentrations/ratios as instantly claimed, it is noted that differences in experimental parameters such as concentration of compounds in a composition will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such parameter is critical. The prior art teaches formulations comprising the same components/compounds. The determination of suitable or effective concentration/composition can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art. 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.
Regarding the claimed properties of the disclosed compositions (i.e., in vitro dissolution profiles recited in claims 1, 12), it is noted that the cited prior art teaches the compositions that are substantially the same as the compositions recited by the instant claims. Thus, it is expected that since the prior art is comprised of the same components, the same beneficial properties and effects would also be provided. Further, it is noted that the fact that applicant has recognized another advantage, which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding claim 12, it is noted that in product-by-process claims, “once a product appearing to be substantially identical is found and a 35 U.S.C. 103 rejection is made, the burden shifts to the applicant to show an unobvious difference.” MPEP 2113. This rejection under 35 U.S.C. 103 is proper because the “patentability of a product does not depend on its method of production.” In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985). As a practical matter, the Patent Office is not equipped to manufacture products by the myriad number of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Therefore, with the showing of the reference, the burden of establishing non-obviousness by objective evidence is shifted to the applicants.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 2019/0105275 - teaches delayed-immediate release compositions/minitablets having a diameter of 1-4 mm and comprising a core comprising at least 85 wt% of 5-ASA (e.g., 0.4-6 g per unit dosage product) and excipients as instantly claimed and a coating comprising ethyl cellulose (i.e., hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., a hydrophilic polymer).
US 2020/0155461 – teaches controlled release (here as delayed-immediate release) compositions/minitablets having a diameter of 1-4 mm and comprising a core comprising at least 85 wt% of 5-ASA (e.g., 0.4-6 g per unit dosage product) in combination with excipients as instantly claimed and a coating comprising ethyl cellulose (i.e., hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., a hydrophilic polymer).
US 2014/0141075 A1 - teaches tablets within a capsule, wherein said tablets comprise a core comprising 5-ASA (50-1,800 mg) in combination with excipients as instantly claimed and a coating comprising ethyl cellulose (i.e., hydrophobic cellulose) and hydroxypropyl methylcellulose (i.e., a hydrophilic polymer), and providing controlled, pH-dependent drug-release profile.
Foppoli et al., (cited previously) – teaches tablets comprising 5-ASA, povidone and crospovidone, glyceryl dibehenate, lactose, hydroxypropyl methylcellulose, polyethylene glycol (PEG 6000), and talc.
US 2022/0047515 - teaches controlled release compositions/minitablets comprising a core comprising mesalazine/5-ASA in combination with excipients as instantly claimed and a coating comprising ethyl cellulose (i.e., hydrophobic cellulose).
Response to Arguments
Applicant's arguments, filed 06/23/2026, have been fully considered, but they were not found to be persuasive for the reasons set forth above. New objections and/or rejections have been added to the record to address newly introduced amendments and/or to clarify the position of the examiner. Additional examiner’s comments are set forth next.
The Declaration under 37 CFR 1.132, filed 06/23/2026, has been considered. To this point, in response to the applicant’s argument that instant invention shows unexpected results that (i) 6.5-10 wt% of glyceryl dibehenate in the core minitablet, and (ii) the coating weight range of 4-10 wt%, wherein said coating comprises a hydrophobic cellulose and hydrophilic polymer present at the weight ratio of 1:9 are required to provide disclosed release profile, it is noted that one skilled in the art would have understood that properties of multicomponent systems depend on compounds included as well as on concentrations of said compounds that define the network of intermolecular interactions, and thereby physical and chemical properties of the system/composition. Therefore, it is expected that different compositions might have different properties. The determination of suitable or effective concentration/composition (for providing/controlling properties of compositions) can be and usually is determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal/desired results, as these are variable parameters attainable within the art. To this point, it is noted that the applicant shows that same compositions work better than others, but does not explain what is unexpected.
In the present case, all cited references are reasonably drawn to the same field of endeavor that is controlled release minitablets/tablets comprising mesalamine/5-ASA as the active agent in combination with other compounds as instantly claimed, wherein said minitablets/tablets are coated with coating(s) comprising compounds as instantly claimed for providing desired/controllable dissolution and/or drug release profile. Therefore, the examiner maintains the position that the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because every element of the invention has been collectively taught by the combined teachings of the references. Further, it is noted that the fact that applicant has recognized another advantage, which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Applicant is advised to clarify the claim language, the structure of the claimed compositions/minitablets and clearly point out the patentable novelty, which the applicant thinks the claims present in view of the state of the art disclosed by the references cited, to place the application in condition for allowance.
Conclusion
No claim is allowed at this time.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA V. TCHERKASSKAYA whose telephone number is (571)270-3672. The examiner can normally be reached 9 am - 6 pm, Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at (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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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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