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 Claims
Receipt of Remarks/Amendments filed on 08/11/2025 is acknowledged. Claims 1-14 are amended. Claims 1-15 are currently pending and are examined on the merits herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority based on an application filed in Republic of India on 02/04/2022. It is noted, however, that applicant has not filed a certified copy of the IN202241006098 application as required by 37 CFR 1.55.
Information Disclosure Statement
No information disclosure statement has been received as of the date of this action.
Withdrawn Objections and Rejections
Claims 2-3, 5, 7, and 10-13 were objected to for informalities. Applicant’s amendments to the claims have overcome some of the objections but not all. The remaining objections are presented below.
Claims 2-3, 5-6, 10, and 12 were rejected under 35 U.S.C. 112b. Applicant’s amendments to claims 2, 3, 5, 10, and 12 have overcome the rejections and the rejections are withdrawn.
The following objections and rejections are maintained or necessitated by amendment:
Claim Objections
Claims 2-3 and 10 are objected to because of the following informalities:
Claims 2 and 3 contain awkward phrasing, for the ease of the reader please amend to the following: “the amount of pseudoephedrine or a salt thereof the core is…” and “the amount of pseudoephedrine or a salt thereof the immediate release coating is…”;
Claim 9 has added the phase “consisting of”, however, it is not underlined to indicate new subject matter as is required in a proper response;
Claim 10 recites “in an amount of 40% to 60% of by total weight” which appears to be a typographical error. Please correct to “in an amount of 40% to 60% of
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Azpitarte, I. O., et al. (WO 2022/023463 A1, 02/03/2022, on record), hereinafter Azpitarte in view of Wang, J., et al. (US 8,703,193 B2, 04/22/2014, on record), hereinafter Wang as evidenced by JRS Pharma. (2022). Vivacoat - Nutra. (on record), hereinafter JRS Pharma and Almoshari, Y., et al. (2022). Osmotic Pump Drug Delivery Systems-A Comprehensive Review. Pharmaceuticals (Basel). 15(11):1430 (on record), hereinafter Almoshari.
Azpitarte discloses a multi-layer oral pharmaceutical composition comprising a matrix core, comprising a decongestant and a combination of at least two cellulose derivatives, a first layer comprising a cellulose derivative and an optional second layer comprising bilastine. The oral dosage form of the composition has a reproducible profile characterized by a controlled release of the decongestant over a period in excess of twelve hours and preferably at least 16 hours and an immediate release of bilastine after oral administration (abstract).
In a most preferred embodiment, the matrix core comprises 180 mg of pseudoephedrine as the decongestant (p. 6, lines 17-19). In a particular embodiment, preferably wherein the decongestant is present and is pseudoephedrine, the first layer comprises from 50 to 70 mg of pseudoephedrine, more preferably 60 mg (p. 11, lines 20-22). These milligram amounts read on the milligram amounts of pseudoephedrine of claims 3 and 9.
The matrix core may comprise: from 60 wt% to 100 wt% of the total amount of the decongestant (i.e., pseudoephedrine); from 20 to 40 wt% of hydroxypropyl methylcellulose (i.e., a water soluble extended release polymer, hereinafter HPMC); from 30 to 50 wt% of microcrystalline cellulose; from 0.1 to 2 wt% of magnesium stearate; and optionally, from 0.1 to 1 wt% of polyvinylpyrrolidone (i.e., pharmaceutical excipients) (p. 22, lines 7-15; p. 23, lines 15-23). This embodiment reads on I of claims 1 and 9. Regarding the amount of hydroxypropyl cellulose, both the Azpitarte range and the instantly claimed range encompass 40%. 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.
The first layer comprises: an inner layer, comprising a cellulose derivative; and/or an outer layer, of a further excipient selected from a coating system comprising a cellulose derivative, and a decongestant. In such embodiment, the inner layer is preferably a sealing layer, which reads on II of claims 1 and 9, and the outer layer is preferably an immediate release layer of the decongestant, which reads on V of claim 1 (p. 11, line 28 – p. 12, line 5). More specifically, the outer layer comprises VIVACOAT ® PA-1P-000 and from 20 to 40 wt%, or more specifically 25 to 35%, of a decongestant, with respect to the total weight of decongestant (p. 25, lines 1-15), which further reads on V of claim 1. VIVACOAT® is HPMC based, as evidenced by JRS Pharma, which further reads on V of claim 9.
In a particular embodiment of the process of preparation, the cores are obtained by a direct compression method (p. 29, lines 27-28), which reads on claim 12.
Azpitarte combines the above teachings in a single embodiment through example 6. Example 6 teaches a coated formulation, in the form of tablets, comprising pseudoephedrine. The tablets comprise 180 mg of pseudoephedrine hydrochloride, Metolose® 90 SH 4000 SR (i.e., HPMC, p. 43, lines 14-15), Vivapur® 101, Magnesium stearate, PVP K30, and deionized water, which reads on I of claims 1 and 9. The tablets were prepared according to the procedure of example 1 (p. 53, lines 1-2), in which the mix was compressed at a force of 100-130 N to produce the tablets (p. 45, lines 1-2), which reads on the direct compression process of claim 12. The tablets were coated with ethylcellulose as a first layer (p. 53, lines 3-10), which reads on II of claims 1 and 9. The tablets were further coated with a second layer comprising 20 mg of bilastine and 60 mg of pseudoephedrine HCl and 61 mg of Vivacoat® PA-1P-000 (i.e., HPMC) (p. 53, lines 11-20), which reads on V of claims 1 and 9. The core comprises 75% (180 mg) and the outer layer (i.e., the immediate release coating) comprises 25% (60 mg) by total weight of the pseudoephedrine HCl, all of which read on the amounts of pseudoephedrine hydrochloride in claims 1-3 and 9. The tablets of Example 6 differ from the instant invention in that they only contain 27% of Metolose® 90 SH 4000 SR (i.e., HPMC), rather than the 40-60% recited in instant claims 3 and 10. However, Azpitarte teaches that the composition of the invention may comprise up to 40 wt% of hydroxypropyl methylcellulose, as discussed above. Thus, it would have been prima facie obvious to one of ordinary skill in the art to increase the proportion of HPMC in the tablet core to 40 wt% since this is a known and effective amount of HPMC in a tablet core, thereby falling within the instantly claimed range.
The tablet of Azpitarte differs further from the instant invention in that it does not teach an extended-release coating as recited in III of claims 1 and 9, and further defined by claims 4-8 and 11.
Wang teaches controlled porosity for drug release by adding a suitable quantity of pore-forming agents into the semipermeable membrane of tablets (abstract). Wang teaches different formulations of semipermeable membranes which include: 21 g of cellulose acetate, 9 g of polyethylene glycol (6000), and 2 g of dibutyl sebacate (col. 7, example 1); 25 g of cellulose acetate, 11 g of polyethylene glycol (6000), and 2.5 g of dibutyl sebacate (col. 9, example 3); 35 g of cellulose acetate, 12 g of polyethylene glycol (6000), and 3.5 g of dibutyl sebacate (col. 10, example 4). Each of these formulations reads on III of claims 1 and 9, wherein the plasticizer is dibutyl sebacate (claim 11) and the pore-former is polyethylene glycol (claim 1), further reading on instant claims 5-8. The ratio of cellulose acetate to plasticizer (i.e., dibutyl sebacate) to pore former (i.e., PEG) is 1:0.10:0.43, 1:0.10:0.44, and 1:0.10:0.34 for examples 1, 3, and 4 respectively, all of which fall within the weight ratio ranges of claims 4 and 9. Additionally, the weight ratios of Wang are very close to the weight ratio of claim 11. Thus, the instantly claimed weight ratio of claim 11 would have been obvious in view of the teachings of Wang since a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art by are merely close. See MPEP 2144.05. Regarding the weight percent of cellulose acetate, examples 1, 3, and 4 contain 65-69% of cellulose acetate, which falls within the range of III in claim 9. Regarding the weight percent of the mixture of dibutyl sebacate and polyethylene glycol together, examples 1, 3, and 4 contain 31-35% of dibutyl sebacate/polyethylene glycol, which also falls within the range of III in claim 9.
Coating of the core was performed as follows: cellulose acetate was dissolved by acetone with stirring; polyethylene glycol was dissolved with water, the obtained solution was added to the acetone solution of cellulose acetate as above obtained with stirring, to fully dissolve polyethylene glycol, and then dibutyl sebacate was added with shaking, to obtain a coating solution. The core was placed in a coating machine, to which a hot air was charged, and the coating solution was sprayed onto the core while keeping the temperature between 30 and 40oC. (col. 7, lines 54-63; col. 9, lines 33-42; col. 10, lines 30-41).
As compared with existing osmotic pump, the tablets of Wang have prominent advantages, for example: (1) No need of drilling with laser, reduced cost, and can produce controlled release tablets having good releasing effect by using conventional tableting device and coating device; (2) Simplified process, reduced labor intensity, and increased reliability of process; (3) Increased safety of preparation (col. 6, line 41 – col. 7, line 3).
It would have been obvious to combine the compositions of Azpitarte and Wang before the effective filing date of the claimed invention by incorporating the semipermeable membrane of Wang as an additional coating agent to the pseudoephedrine tablet of Azpitarte to yield the instantly claimed invention. Azpitarte teaches a tablet for the controlled release of pseudoephedrine and Wang teaches coatings/membranes with controlled porosity for drug release from a tablet. Thus, one of ordinary skill in the art would have been motivated to coat the tablet of Azpitarte with the membrane of Wang in order to enhance or modify the controlled release of the drug from the tablet core, as reasonably suggested by Wang. Furthermore, one of ordinary skill in the art would have been motivated to use the membrane of Wang since it possesses several advantages such as reduced cost, simplified process, reduced labor intensity, increased reliability, and increased safety. One of ordinary skill in the art would have had a reasonable expectation of success in coating the tablet of Azpitarte with the membrane of Wang since Azpitarte welcomes coating compositions and the membrane of Wang may be applied using conventional spray coating methods.
Regarding the non-osmotic nature of the combined tablet of Azpitarte and Wang, it appears that the semipermeable membrane of Wang is substantially the same as the extended release coating of the instant invention. While Wang independently teaches the preparation of controlled porous osmotic pump tablets, the membranes of Wang do not need to be drilled by laser since they provide controlled porosity for drug release by adding a suitable quantity of pore-forming agents into the membrane (col. 1, lines 14-19). As such, the semipermeable membranes of Wang are not of the conventional osmotic type. The coating membranes of Wang address the same concerns as discussed in the instant specification (p. 3, lines 3-6 of instant specification) by simplifying the preparation process, and greatly reducing the production cost, but also increasing the safety of the preparation (col. 1, lines 19-22), posing the membranes as great alternatives to conventional osmotic pumps. The coating membranes of Wang are also prepared in the same manner as those of the instant invention. The instant specification teaches that the extended release coating is a hydroalcoholic dispersion of Cellulose acetate with suitable coating aids (plasticizer, pore-former, Acetone & purified water) which is sprayed onto the seal coated tablets (Examples 4-8 of instant specification). Wang teaches essentially the same as discussed above. Furthermore, the cellulose acetate, extended release coating of the instant invention also forms a membrane (Example 3-4 and 6 of instant specification). Lastly, Wang teaches that its osmotic pump tablets comprise a permeation enhancer such as sodium chloride or lactose in the tablet core (col. 3, lines 4-8; Examples 1 and 3-4), also known as an osmotic agent. Osmotic agents create the osmotic pressure in the osmotic delivery system as evidenced by Almoshari (section 2.2). As such, the characterization of an “osmotic” tablet is dependent on the presence of a permeation enhancer. Just because the semipermeable membrane of Wang is used in an osmotic tablet, the membrane in and of itself is not osmotic and may still be used to impart controlled release properties in a non-osmotic controlled release tablet. Additionally, Wang sets the semipermeable membrane apart from typical osmotic coatings which require a drilling process.
Given the similarities between the instant extended release coating and the semipermeable membranes of Wang, the Examiner has reason to believe that they are the same. As such, when the tablets of Azpitarte, which do not contain an osmotic agent, are coated with the semipermeable membrane of Wang, it would result in a non-osmotic extended release tablet as gathered from the prior art teachings and Applicants’ own specification.
Regarding the amount of drug released as recited in claim 13, because the composition made obvious by the prior art is identical to the composition of claim 9, the composition must necessarily have the characteristics claimed in claim 13 as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Regarding claim 14, the combined tablet of Azpitarte and Wang comprises a decongestant, which would reasonably be used for the relief of symptoms associated with nasal congestion. However, claim 14 simply recites the intended use of the extended release formulation of claim 1 without reciting any additional structural limitations. Thus, claim 14 is treated as substantially the same as claim 1 and is rejected for the same reasons as claim 1, set forth above.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Azpitarte, I. O., et al. (WO 2022/023463 A1, 02/03/2022, on record), hereinafter Azpitarte in view of Wang, J., et al. (US 8,703,193 B2, 04/22/2014, on record), hereinafter Wang as applied to claims 1-14 above, and further in view of Fan, W., et al. (CN 101708178 A, 05/19/2010, on record), hereinafter Fan.
The combined teachings of Azpitarte and Wang are discussed above.
The combined teachings of Azpitarte and Wang differ from that of the instantly claimed invention in that they do not teach cetirizine or levocetirizine in the immediate release coating as recited in claim 15.
Fan teaches a compound cetirizine pseudoephedrine sustained-release tablet. The preparation method thereof is as follows: preparing pseudoephedrine or pharmaceutically acceptable salt thereof into sustained-release tablet core, dispersing cetirizine or pharmaceutically acceptable salt thereof in a coating solution evenly, and then coating the surface of the tablet core (abstract). The cetirizine releases rapidly (i.e., immediate release) and pseudoephedrine releases slowly (i.e., extended release). More specifically, the cetirizine in preparation dissolves out more than 85% in 30 min, and more than 90% in 1 h; pseudoephedrine releases slowly in 12 h or 24 h (abstract). Embodiment 2 teaches the preparation of a pseudoephedrine hydrochloride sustained release tablet core comprising pseudoephedrine hydrochloride 100 g; hydroxypropyl cellulose 100 g; magnesium stearate 20 g; calcium 10 g; magnesium stearate 20 g; hydroxypropyl methylcellulose 20 g; 50% ethanol 400 g (¶ [0072]-[0081]). The preparation of the cetirizine coating prescription combines the pseudoephedrine hydrochloride sustained release tablet core 260 g with a coating comprised of cetirizine 5 g; micro mist silica gel 5 g; opadry 30 g; water 600 g (¶ [0084]-[0089]).
It would have been obvious to modify the combined composition of Azpitarte and Wang with the composition of Fan before the effective filing date of the claimed invention by replacing the bilastine in the second layer of Azpitarte and Wang with the cetirizine of Fan to yield the instant invention. Both Fan and the combination of Azpitarte and Wang teach extended release tablets comprising pseudoephedrine in the core and an antihistamine in the immediate release coating. It would have been prima facie obvious to replace the bilastine in the combined tablet of Azpitarte and Wang with the cetirizine of Fan since both are known and effective antihistamines and it is no more than the simple substitution of one known element for another to yield predictable results. One of ordinary skill in the art would have had a reasonable expectation of success in making this modification since both bilastine and cetirizine are taught in immediate release coatings for extended release pseudoephedrine tablets.
Response to Arguments
Applicant's arguments filed 08/11/2025 have been fully considered but they are not persuasive:
In response to Applicant’s arguments against Azpitarte, Wang, and Fan individually (page 3, 4, and 5 of Remarks), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case the rejections are based on a combination of Azpitarte, Wang, and Fan. Additionally, Azpitarte teaches 20 to 40% of HPMC which overlaps with the instantly claimed range. As such, it would have been obvious to use 40% HPMC to achieve the instantly claimed invention since this is a known and effective amount of HPMC to use in the tablets of Azpitarte. Generally, 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.
In response to Applicant’s argument that it is improper to combine Azipatarte and Wang due to the different nature of the formulations (page 4 of Remarks), the Examiner respectfully disagrees. As discussed in the rejection above, Wang teaches controlled porosity for drug release by adding a suitable quantity of pore-forming agents into the semipermeable membrane of tablets. The osmotic nature of the tablet does not arise from the semipermeable membrane itself but rather from a separate permeation enhancer in the tablet core. In fact, the semipermeable membrane of Wang is not osmotic in nature given Wangs discussion of how it differs from existing osmotic pump technology. As such, one of ordinary skill in the art would have concluded that the semipermeable membrane of Wang could function as an extended release coating not only in an osmotic tablet but also in a non-osmotic tablet due to the controlled porosity mechanism of the membrane which is separate from the osmotic mechanism of the permeation enhancer, which is not relied on. This is supported by Applicant’s own disclosure which illustrates that a coating which is substantially identical to Wangs, would provide extended release properties in a non-osmotic tablet such as that of Azipatarte.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (page 4-5 of Remarks), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). While Applicant’s own disclosure is referenced as evidence for the non-osmotic nature of the combined tablet and semipermeable membrane of Wang, it is not relied upon for any obviousness reasoning or motivation. The motivation and reasoning to combine the semipermeable membrane of Wang with the core of Azpitarte is given above in the prior art rejection. In regards to the release profile of the combined tablet as compared to the instantly claimed release profile, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Applicant asserts unexpected results, pointing to the comparison of release profiles for example 2 and examples 7-8 of the present application. Example 2 has a core containing HPMC and extended release coating of ethyl cellulose and hypromellose whereas examples 7-8 have a core containing HPMC and a coating of cellulose acetate, dibutyl sebacate, and PEG as instantly claimed. According to Applicant, examples 7-8 provide a 24 hour release profile comparative to the reference product SUDAFED 24 while example 2 does not (page 5 of Remarks). In order to show unexpected results an affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. See In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). In this case, applicant has not provided a comparison to the closest prior art to sufficiently show unexpected results, as Example 2 of the instant specification does not represent the closest prior art (i.e., the tablet of Azpitarte).
Conclusion
No claims are allowed.
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 SUSANNAH S ARMSTRONG whose telephone number is (571)272-0112. The examiner can normally be reached Mon-Fri 7:30-5 (Flex).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X Liu can be reached at (571)272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616