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 .
Formal Matters
Receipt of Applicant’s response dated 01/27/2026 is acknowledged.
Claims 31-70 are pending.
Claims 1-30 are canceled.
Election/Restriction
Applicant’s election without traverse of Group I, claims 31-49, in the reply filed on 01/27/2026 is acknowledged.
Applicant has also elected the following in the reply dated 01/27/2026:
Ethylcellulose as the species of modified cellulose;
Polycarbophil as the species of water-insoluble, water-swellable cross-linked polycarboxylic polymer;
Sodium bicarbonate as the species of pH regulator; and
Diltiazem as the species of active substance.
Claims 50-70 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 31-49 are being examined to the extent of the elected species, i.e., the modified cellulose is ethylcellulose, the water-insoluble, water-swellable cross-linked polycarboxylic polymer is polycarbophil, the pH regulator is sodium bicarbonate, and the active substance is diltiazem.
Priority
This application is a 371 of PCT/IB2022/052522 filed 03/21/2022, claiming priority to ITALY 102021000006776 filed 03/22/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Because an English translation of the foreign priority document has not been provided, the effective filing date of the instant application is 03/21/2022.
Information Disclosure Statement
The information disclosure statement (IDS) filed 09/13/2023 has been considered by the Examiner. A signed copy of the IDS is included with the present Office Action.
Claim Objections
Claims 31-32, 40-43, 45-46, and 48 are objected to because of the following:
In line 7 of claim 31, the comma appearing after “earth metal” should be deleted for grammatical correctness;
The extra line appearing between steps b) and c) in claim 31 should be deleted in order to improve claim readability;
In each of claims 31 and 32, for each recitation of temperature, a space should be added between the temperature value and the degree sign (e.g., “80°C” should be amended to “80 °C”);
Each of claims 40-43 and 45-46 should be amended to remove commas appearing after the percent sign in line 1 and/or after “by weight” in line 1 (e.g., Claim 41 should recite “…wherein the Polycarbophil is 30-65% by weight of the total weight of said mixture of powders”); and
In the last line of claim 48, “weight of the mixture” should be amended to “weight of said mixture of powders” in order to improve claim consistency.
Appropriate correction is required.
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 31-49 are rejected under 35 U.S.C. 103 as being unpatentable over Caviglioli et al (Int. J. Pharm., (2013), 458, 74-82, cited in IDS dated 09/13/2023) in view of Nangia et al (US 2008/0260824 A1, published 10/23/2008).
Caviglioli et al teach the preparation of an innovative matrix via thermal treatment on direct compression tablets containing polycarbophil and ethylcellulose for controlled release of diltiazem hydrochloride (See entire document, e.g., Title, Abstract). The preparation involves sieving each component to powders and then mixing together a powder batch of the components, the components being polycarbophil, ethylcellulose, diltiazem hydrochloride, and a diluent, wherein the resulting powder is assayed to ensure uniformity of diltiazem hydrochloride in the powder (e.g., 2.2 in Col. 1 of Page 75). Tablets were then prepared from the resulting powder using a rotation tableting machine at a compression force of 10, 15, or 25 kN (e.g., 2.2 in Col. 1 of Page 75). Thermal treatment of tablets was carried out in an oven heated at 30 °C/min up to the treatment temperature ranging from 120 ± 1 °C to 150 ± 1 °C and was maintained for selected treatment times ranging from 5 to 15 min (e.g., 2.4 in Col. 2 on Page 75). Caviglioli et al exemplify a tablet composition resulting from this preparation comprising 20 wt% of diltiazem hydrochloride, 30 wt% of MicroceLac®100 as the diluent/excipient, 40 wt% of polycarbophil, and 10 wt% of ethylcellulose (e.g., “M26” in Table 1 on Page 77).
Caviglioli et al teach substitution of MicroceLac®100 with other diluents/excipients being dicalcium phosphate anhydrous and lactose anhydrous and found that the substitution did not alter the matrix formation caused by thermal treatment as each of the matrices were able to control drug release without significant differences in their profiles, and the matrix generators are the polycarbophil and ethylcellulose, thus, allowing a choice to be made from different excipients/diluents in the event an excipient/diluent and a drug are incompatible (e.g., 3.4 in Col. 1 of Page 79).
Caviglioli et al do not teach substitution of MicroceLac®100 with sodium bicarbonate.
This deficiency is made up for in the teaching of Nangia et al.
Nangia et al teach bioadhesive oral drug delivery formulations, such as in the form of a tablet, for oral delivery of a drug, comprising a compressed core including a drug to be delivered gastrointestinally (See entire document, e.g., [0057]). The cores of tablets and drug eluting devices of the invention may contain one or more excipients, carriers or diluents. These excipients, carriers or diluents can be selected, for example, to control the disintegration rate of a tablet or drug eluting device, and in particular, it is advantageous for the disintegration time to be less than the gastric (or small/large intestinal) retention time (e.g., [0233]). Nangia et al teach that the disintegration time of a tablet may be at least 25% of the gastric retention time, at least 50% of the gastric retention time or at least 75% of the gastric retention time (e.g., [0233]). Nangia et al teach suitable carriers and diluents for use in the formulations comprising one or more drugs as including pharmaceutically accepted hydrogels such as alginate, chitosan, methylmethacrylates, cellulose and derivatives thereof (microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethylcellulose, ethylcellulose), agarose and Povidone, kaolin, magnesium stearate, starch, lactose, sucrose, density-controlling agents such as barium sulfate and oils, dissolution enhancers such as aspartic acid, citric acid, glutamic acid, tartaric acid, sodium bicarbonate, sodium carbonate, sodium phosphate, glycine, tricine and TRIS (e.g., [0235]-[0236]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, based on the teachings of Caviglioli et al and Nangia et al, to provide a preparation of an innovative matrix via thermal treatment on direct compression tablets containing polycarbophil and ethylcellulose for controlled release of diltiazem hydrochloride, wherein the preparation comprises sieving each of and then mixing together a powder batch of the components being polycarbophil, ethylcellulose, diltiazem hydrochloride, and a diluent/excipient, performing an assay on the resulting powder to ensure uniformity of diltiazem hydrochloride in the powder (i.e., a homogeneous mixture), preparing tablets from the resulting powder using a rotation tableting machine at a compression force of 10, 15, or 25 kN, thermally treating the tablets in an oven heated at 30 °C/min up to the treatment temperature ranging from 120 ± 1 °C to 150 ± 1 °C and maintaining for treatment times ranging from 5 to 15 min, wherein the diluent/excipient is selected from pharmaceutically accepted hydrogels such as alginate, chitosan, methylmethacrylates, cellulose and derivatives thereof (microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethylcellulose, ethylcellulose), agarose and Povidone, kaolin, magnesium stearate, starch, lactose, sucrose, density-controlling agents such as barium sulfate and oils, dissolution enhancers such as aspartic acid, citric acid, glutamic acid, tartaric acid, sodium bicarbonate, sodium carbonate, sodium phosphate, glycine, tricine and TRIS, and wherein the preparation results in a tablet composition of 20 wt% of diltiazem hydrochloride, 30 wt% of the diluent/excipient, 40 wt% of polycarbophil, and 10 wt% of ethylcellulose.
One of ordinary skill in the art would have been motivated to substitute MicroceLac®100 as the diluent/excipient in the preparation of Caviglioli et al with those taught by Nangia et al in order to arrive at a tablet with optimized/desired disintegration time, e.g. tablet disintegration time of at least 25% of gastric retention time, at least 50% of gastric retention time or at least 75% of gastric retention time, because Nangia et al teach that excipient/carrier/diluent selection can control the disintegration rate of the tablet and that in particular it is advantageous for the disintegration time to be less than the gastric (or small/large intestinal) retention time, e.g., tablet disintegration time of at least 25% of gastric retention time, at least 50% of gastric retention time or at least 75% of gastric retention time. There would have been a reasonable expectation of success because 1) Caviglioli et al teach that substituting the diluent/excipient does not alter matrix formation due to the matrix generators being the polycarbophil and ethylcellulose components, and therefore, there exists a possibility of choosing from different excipients/diluents and 2) the aforementioned list of suitable carriers and diluents for use in formulations comprising one or more drugs of Nangia et al is compatible with the drug diltiazem (See Par. [0102] of Nangia et al).
Regarding the required ranges of the instant claims, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)). Specifically regarding the required weight ratios, the tablet prepared by the process of Caviglioli et al in view of Nangia et al comprising 30 wt% of diluent/excipient, 40 wt% of polycarbophil, and 10 wt% of ethylcellulose has a weight ratio of diluent/excipient to polycarbophil of 1:1.33, which falls within the range required by instant claim 44, and a weight ratio of ethylcellulose to polycarbophil of 1:4, which falls within the range required by instant claim 47.
Because the innovative matrix produced by the preparation of Caviglioli et al in view of Nangia et al is the same as the matrix produced by the method of the instant claims, the innovative matrix produced by the preparation of Caviglioli et al in view of Nangia et al necessarily is bioadhesive and gastroretentive. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties" (In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). "The fact that appellant 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).
Thus, the preparation of Caviglioli et al in view of Nangia et al renders obvious the method of instant claims 31-49.
Conclusion
No claims are allowable.
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/K.E.O./Examiner, Art Unit 1619
/NICOLE P BABSON/Primary Examiner, Art Unit 1619
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