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 .
Claims 1-9, 12-13, 20, 23-28 and 30-31 are pending and under examination.
Priority
Acknowledge is made that this application is continuation of U.S. Patent Application No. 17/667,746, filed February 9, 2022, which is a continuation of U.S. Application No. 15/291,061, filed October 11, 2016, which claims the benefit of U.S. Provisional Patent Application Nos. 62/239,775 and 62/239,780, both filed October 9, 2015.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/09/2025 is being considered by the examiner.
Claim Objection
Claims 25, 29 and 30 are objected to reciting PEG as ingredient (j), which is recited as ingredient (i) in claim 24. Applicants need to be consistent through all the claims. Proper correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 26 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 26 is rejected for reciting “similar”. This is indefinite because it was unclear from the specification what applicant intended to cover by the recitation of "similar” dissolution profile. MPEP 2173.05 (b) III C.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-2, 4-7 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Davis et al. (US20030049318).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Davis et al. teaches novel pharmaceutical sustained release formulation of guaifenesin and at least one additional drug ingredient. The formulation may comprise a hydrophilic polymer, preferably a hydroxypropyl methylcellulose, and a water-insoluble polymer, preferably an acrylic resin, in a ratio range of about one-to-one (1:1) to about nine-to-one (9:1), more preferably a range of about three-to-two (3:2) to about six-to-one (6:1), and most preferably in a range of about two-to-one (2:1) to about four-to-one (4:1) by weight. This formulation capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject. The invention also relates to a modified release product which has two portions: a first portion having an immediate release formulation of guaifenesin and a second portion having a sustained release formulation of guaifenesin, wherein one or both portions has at least one additional drug ingredient. The modified release product has a maximum guaifenesin serum concentration equivalent to that of an immediate release guaifenesin tablet, and is capable of providing therapeutically effective bioavailability of guaifenesin for at least twelve hours after dosing in a human subject (abstract). The present invention is directed to a sustained release formulation for oral administration comprising guaifenesin and at least one drug ingredient and methods of manufacture thereof. In particular, the invention is directed to a sustained release formulation which maintains a therapeutically effective blood concentration of guaifenesin and at least one drug ingredient for a duration of at least twelve hours. The present invention further relates to a modified release bi-layer tablet containing guaifenesin and at least one drug ingredient which demonstrates a maximum serum concentration equivalent to an immediate release tablet yet maintains a therapeutically effective blood concentration of guaifenesin for a duration of about twelve hours ([0003]). This invention relates to a novel sustained release pharmaceutical formulation comprising guaifenesin and at least one drug ingredient. The tablet is capable of releasing therapeutically effective amounts of guaifenesin over an extended period, i.e. twelve or more hours and at least one additional drug ingredient immediately, over an extended period, or both ([0012]). This invention also encompasses a modified release composition which comprises two discrete portions (e.g. a bi-layer tablet, or capsule), an immediate release formulation and a sustained release formulation. Each formulation comprises a specific quantity of guaifenesin and may optionally contain at least one additional drug ([0018]). As the bi-layer tablet of the present invention also contains at least one additional drug ingredient, the additional drug ingredient can be formulated within the sustained release formulation, immediate release formulation, or both. In one embodiment, the bi-layer tablet of the present invention maintains serum concentration levels of at least one additional drug at a therapeutically effective level for at least a twelve hour period without an increase in the drug strength of the dosage form ([0020]). FIG. 14 is a graph demonstrating the plasma concentrations of dextromethorphan HBr following the administration of 1200 mg guaifenesin and 60 mg dextromethorphan HBr to volunteers in three different formulations ([0037]). In a preferred embodiment, the at least one additional drug ingredient can be present within the sustained release formulation, the immediate release formulation, or both depending upon the desired effect ([0043]).
In a further embodiment, the sustained release formulation may comprise a combination of guaifenesin and at least one additional drug ingredient, wherein the additional drug ingredient includes, but not limited to, an antitussive such as dextromethorphan hydrobromide, codeine, hydrocodone, a decongestant such as phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride or ephedrine, an antihistamine such as chlorpheniramine maleate, brompheniramine maleate, phenindamine tartrate, pyrilamine maleate, doxylamine succinate, phenyltoloxamine citrate, diphenhydramine hydrochloride, promethazine, and clemastine fumerate, an analgesic such as aspirin, ibuprofen, naprosin, and acetaminophen, or combinations thereof. Preferably, the drug ingredient is dextromethorphan hydrobromide, pseudoephedrine hydrochloride, or a combination thereof ([0045]). Hydrophilic polymers suitable for use in the sustained release formulation include: one or more natural or partially or totally synthetic hydrophilic gums such as acacia, gum tragacanth, locust bean gum, guar gum, or karaya gum, modified cellulosic substances such as methylcellulose, hydroxomethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethylcellulose, carboxymethylcellulose; proteinaceous substances such as agar, pectin, carrageen, and alginates; and other hydrophilic polymers such as carboxypolymethylene, gelatin, casein, zein, bentonite, magnesium aluminum silicate, polysaccharides, modified starch derivatives, and other hydrophilic polymers known to those of skill in the art or a combination of such polymers ([0046]). A sustained release formulation of the present invention may further comprise pharmaceutical additives including, but not limited to: lubricants such as magnesium stearate, calcium stearate, zinc stearate, powdered stearic acid, hydrogenated vegetable oils, talc, polyethylene glycol, and mineral oil; colorants such as Emerald Green Lake and various FD&C colors; binders such as sucrose, lactose, gelatin, starch paste, acacia, tragacanth, povidone polyethylene glycol, Pullulan and corn syrup; glidants such as colloidal silicon dioxide and talc; surface active agents such as sodium lauryl sulfate, dioctyl sodium sulfosuccinate, triethanolamine, polyoxyethylene sorbitan, poloxalkol, and quarternary ammonium salts; preservatives and stabilizers; excipients such as lactose, mannitol, glucose, fructose, xylose, galactose, sucrose, maltose, xylitol, sorbitol, chloride, sulfate and phosphate salts of potassium, sodium, and magnesium; and/or any other pharmaceutical additives known to those of skill in the art. Colorants include, but are not limited to, Emerald Green Lake, FD&C Red #40, FD&C Yellow #6, FD&C Yellow #10, or FD&C Blue #1. In one preferred embodiment, a sustained release formulation further comprises magnesium stearate and Emerald Green Lake. In another preferred embodiment, a sustained release formulation further comprises magnesium stearate and FD&C Blue #1 Aluminum Lake Dye ([0050]). A sustained release formulation of the present invention can comprise at least two drug ingredients, at least one hydrophilic polymer, at least one water-insoluble polymer, and at least one pharmaceutical additive in any appropriate percent quantity which permits dissolution of drug ingredients that results in a therapeutically effective serum concentration profile for a full twelve hours. In a preferred embodiment, a sustained release formulation comprises from about 75% to about 95% guaifenesin by weight, from about 1% to about 15% by weight of a additional drug ingredient, from about 1% to about 10% hydroxypropyl methylcellulose, from about 0.5% to about 2.5% acrylic resin, from about 0.4% to about 1.5% magnesium stearate, and from about 0.01% to about 1% colorant by weight. In a more preferred embodiment, a sustained release formulation comprises from about 80% to about 90% guaifenesin by weight, from about 3% to about 10% by weight of a additional drug ingredient, from about 2% to about 5% hydroxypropyl methylcellulose, from about 1% to about 1.5% acrylic resin, from about 0.7% to about 1% magnesium stearate, and from about 0.03% to about 0.13% colorant by weight ([0051]). The immediate release formulation may comprise guaifenesin and various pharmaceutical additives such as lubricants, colorants, binders, glidants, surface active agents, preservatives, stabilizers, as described above and/or any other pharmaceutical additives known to those of skill in the art. In yet another preferred embodiment, an immediate release formulation may comprise about 47% to about 58% guaifenesin, about 3% to about 5% of at least one additional drug ingredient, about 32% to about 42% microcrystalline cellulose, about 2% to about 5% hydroxypropyl methylcellulose, about 3% to about 8% sodium starch glycolate, and about 0.3% to about 0.5% magnesium stearate by weight ([0068]). The bi-layer tablet may be manufactured according to any method known to those of skill in the art. The resulting tablet may comprise the two portions compressed against one another so that the face of each portion is exposed as either the top or bottom of the tablet, or the resulting tablet may comprise the sustained release portion in the center coated by the immediate release portion so that only the immediate release portion is exposed. In a preferred embodiment, a bi-layer tablet of the present invention comprises the two portions compressed against one another so that the face of each portion is exposed ([0069]).
The tablets may be made with any ratio of guaifenesin to at least one additional drug ingredient which results in a blood profile demonstrating appropriate therapeutic effect over extended time periods. As discussed above, the additional drug ingredient may be present in an amount sufficient to mimic the blood serum profile of the commercially available formulation of the drug and not to exceed the maximum dose approved by the FDA for the treatment, prevention, or amelioration of a particular illness or disease. In one embodiment, the ratio in the sustained release formulation of guaifenesin to at least one additional drug ingredient is about one point one-to-one (1.1:1) to about four-to-one (4:1) by weight, preferably, the ratio is about three-to-two (3:2) to about nine-to-one (9:1) by weight, and more preferably, the ratio of guaifenesin to at least one additional drug ingredient is about three-to-one (3:1) to about 20:1 by weight. When present in the immediate release layer, the amount of the at least one additional drug should be sufficient to match the drug release profile of the additional drug within the sustained release profile. Within this embodiment, the ratio in the immediate release formulation of guaifenesin to at least one additional drug ingredient, if present, is about four-to-one (4:1) to about one-to-one (1:1), preferably, the ratio is about nine-to-one (9:1) to about three-to-two (3:2), and more preferably, the ratio of guaifenesin to at least one additional drug ingredient is about nine-to-one (9:1) to about 12:1 by weight ([0071]). The tablets may be made with any ratio of sustained release to immediate release formulation which results in a blood profile demonstrating appropriate therapeutic effect over extended time periods. In one embodiment, the bi-layer tablets comprise guaifenesin distributed within the sustained release formulation and the immediate release formulation wherein the ratio of guaifenesin is about one-to-one (1:1) to about 49:1 by weight ([0072]). The tablets may be made with at least one additional drug only within the sustained release formulation. Optionally, however, the tablets may be made with at least one additional drug distributed within the sustained release formulation and the immediate release formulation ([0073]). In on example ([0131]), the weight ratio of sustained release to immediate release is (157.89+18+4.5+2.25+0.06): (39.476+22.028+5.626+0.188)=182.7 : 67.37, the percentage of sustained release is 73% by weight of total formulation.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Davis et al. is that Davis et al. is not specific enough for anticipation.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce the instant invention.
Regarding claims 1-2 and 20, Davis et al. teaches a pharmaceutical formulation comprising an effect amount of guaifenesin, naproxen (naprosin) and dextromethorphan in the form of tablet with immediate release layer and sustained (modified) release layer (bilayer).
Regarding claim 4, Davis et al. teaches the weight ratio of guaifenesin in sustained release to immediate release layer is 49:1, which indicates 98% of guaifenesin in sustained (modified) release, meets the requirement of substantial amount according to applicant’s specification.
Regarding claim 5, Davis et al. teaches additional active such as dextromethorphan in immediate release, sustained release or in both release portions; since Davis et al. teaches to have for a duration of at least twelve hours drug effect, it is obvious to have all dextromethorphan in sustained release (modified release).
Regarding claims 6-7, Davis et al. teaches guaifenesin and dextromethorphan Iin both release portion.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 3, 8-9, 12-13, 23-28, 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Davis et al. (US20030049318), as applied for the above 103 rejection for claims 1-2, 4-7 and 20, in view of Vergnault et al. (US20100291209) and Nichols (US20060127473).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Davis et al. teaching has already been discussed in the above 103 rejection and is incorporated herein by reference.
Vergnault et al. teaches Naproxen free base for example is a substance which has an unusually long half life compared with other NSAIDs (about 14 hours). Accordingly, in a dosage form suitable for twice-a-day administration it is preferred if all or substantially all of the naproxen (or a pharmaceutically acceptable salt or derivative thereof) is employed in a phase that is adapted for immediate release. An immediate release naproxen phase will provide effective plasma concentrations of naproxen over a 12 hour period before the next dosage form in the twice-a-day schedule has to be taken ([0021]). Another advantage attendant with employing naproxen (or a pharmaceutically acceptable salt or derivative thereof) in an immediate release phase resides in the fact that large amounts of active agent need to be employed to illicit an anti-inflammatory response and immediate release phases generally require the use of far smaller amounts of excipients than conventional sustained release matrices. It follows that naproxen immediate release phase will occupy a significantly smaller volume than a sustained release phase ([0022]).
Nichols stable pharmaceutical compositions having an unstable active pharmaceutical ingredient (abstract). Various embodiments of the present invention provide compositions with at least two API's ([0021]), including naproxen ([0023]), dextromethorphan hydrobromide ([0024]) and guaifenesin ([0026]). The amount of the additional API's in the formulation may be adjusted to deliver a predetermined dose of the active agent over a predetermined period of time, which may typically vary from 4 to 24 hours ([0029]). Generally, the amount of the API used may be from about 0.01% to about 80% by weight, or from about 0.1% to about 40% by weight, or from about 1% to about 30% by weight, or from about 1% to about 10% by weight ([0030]). An “effective” amount or a “therapeutically effective amount” of an active ingredient refers to a non-toxic but sufficient amount of the agent to provide the desired effect. The amount of active agent that is “effective” will vary from subject to subject, depending on the age and general condition of the individual, the particular active agent or agents, and the like. Thus, it is not always possible to specify an exact “effective amount.” However, an appropriate “effective” amount in any individual case can be determined by one of ordinary skill in the art using routine experimentation ([0031]). Useful inactive ingredients, include but are limited to, binding agents, filling agents, lubricating agents, suspending agents, sweeteners, flavorings and flavor enhancer agents, taste-masking agents, preservatives, buffers, wetting agents, anti-oxidants, colorants or coloring agents, pharmaceutically acceptable carriers, disintegrants, salivary stimulating agents, cooling agents, co-solvents (including oils), pH adjusting agents, effervescent agents, emollients, bulking agents, anti-foaming agents, surfactants, soluble organic salts, permeabilizing agents, glidants and other excipients and combinations thereof. Desirably, the agents are chemically and physically compatible with the API ([0038]). Useful pH adjusting agents include fumaric acid, citric acid, sodium acetate. Useful surfactants include sorbitan esters, docusate sodium, sodium lauryl sulfate, cetriride. Useful soluble organic salts include sodium carbonate, sodium bicarbonate, sodium chloride. Examples of useful binding agents include, but are not limited to, polyethylene glycols, soluble hydroxyalkylcelluloses, polyvinylpyrrolidone, gelatins, natural gums, various celluloses and cross-linked polyvinylpyrrolidone, microcrystalline cellulose, such as Avicel® PH101 and Avicel® PH102 ([0039]). Examples of useful substantially water soluble carriers or filling agents include, but are not limited to, various starches, celluloses, carbohydrates compression sugars or soluble fillers. More particularly, useful fillers include but are not limited to lactose, lactose monohydrate, lactose anhydrous, sucrose, amylose, dextrose, mannitol, inositol, maltose, maltitol, sorbitol, glucose, xylitol, erythritol, fructose, maltodextrins; microcrystalline cellulose, calcium carboxy methyl cellulose; pregelatinized starch, modified starches, potato starch, maize starch; clays, including kaolin and polyethylene glycols (PEG) including PEG 4000; or combinations thereof. Useful amount of fillers include the range of about 1 to about 99 weight percent, or about 25 to about 95 weight percent or about 40 weight percent to about 95 weight percent of the compositions of this invention ([0040]). A tablet disintegrant may be added to the direct compression process for its wicking (i.e., the ability of particles to draw water into the porous network of a tablet) and swelling ability. Some disintegrants also serve as excellent binders and are able to substantially improve the mechanical strength of the formulation. Suitable disintegrants are carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, crospovidone, sodium starch glycolate, corn starch, insoluble cationic-exchange resins such as polyacrylin, microcrystalline cellulose, croscarmellose. Disintegrants can be added at a concentration ranging from about 0.5% to about 30%. Croscarmellose sodium (cross-linked carboxymethyl cellulose) may be present at a concentration of about 2% to about 10% ([0047]). An effective amount of any generally accepted pharmaceutical tableting lubricant can be added to compress the tablets. An amount within the range from about 0.25% to about 6%, or 0.5% to about 3% by weight can be added. Useful tablet lubricants include magnesium stearate, glyceryl monostearates, palmitic acid, talc, carnauba wax, calcium stearate sodium, sodium or magnesium lauryl sulfate, calcium soaps, zinc stearate, polyoxyethylene monostearates, calcium silicate, silicon dioxide, hydrogenated vegetable oils and fats, stearic acid and combinations thereof ([0048]).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Davis et al. is that Davis et al. do not expressly teach Naproxen in immediate release, sodium bicarbonate and croscarmellose sodium. This deficiency in Davis et al. is cured by the teachings of Vergnault et al. and Nichols.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Davis et al., as suggested by Vergnault et al. and Nichols, and produce the instant invention.
Regarding claims 3, and 12 One of ordinary skill in the art would have been motivated to have naproxen in immediate release because immediate release is suitable for naproxen. Under guidance from Davis et al. teaching naproxen in sustained release, immediate release or both release; Vergnault et al. teaching advantage of immediate release for naproxen such as providing effective plasma concentrations of naproxen over a 12 hour period (meets the requirement of therapeutically effective blood concentration of drug for a duration of about twelve hours in Davis et al.) and requiring less amount of excipient, thus, it is obvious for one of ordinary skill in the art to naproxen only in immediate release and produce instant claimed invention with reasonable expectation of success.
Regarding claims 8-9, since Davis et al. teaches a bi-layer tablet of the present invention comprises the two portions compressed against one another so that the face of each portion is exposed, and also prior art teaches naproxen in immediate release while guaifenesin and dextromethorphan in sustained release, thus, the dissolution profile of guaifenesin and dextromethorphan and dissolution profile are independent from each other, this teaches the dissolution property cited in claims 8-9. Furthermore, since prior art teaches the same formulation, this same formulation must have the same dissolution profile.
One of ordinary skill in the art would have been motivated to include sodium bicarbonate in the composition because sodium bicarbonate is a suitable ingredient in the composition comprising guaifenesin, naproxen and dextromethorphan. MPEP 2144.07. Under guidance from Nichols teaching sodium bicarbonate in the composition comprising guaifenesin, naproxen and dextromethorphan, it is obvious for one of ordinary skill in the art to include sodium bicarbonate in the composition and produce instant claimed invention with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to replace Croscarmellose sodium for sodium starch glycolate in the formulation because this is simple substitution of one known disintegrant for another to obtain predictable results. Under guidance from Nichols teaching Croscarmellose sodium and sodium starch glycolate as disintegrant, it is obvious for one of ordinary skill in the art to replace Croscarmellose sodium for sodium starch glycolate and produce instant claimed invention with reasonable expectation of success.
Regarding claim 13, Davis et al. teaches surface active agents in the immediate release, and also sodium lauryl sulfate as surface active agents, thus, it is obvious to have sodium lauryl sulfate in immediate release. Prior art teaches sodium bicarbonate, either in the immediate release or sustained release or both, since there are only three choices (finite number), it is obvious to have sodium bicarbonate in immediate release.
Regarding claims 23-26 and 31, prior art teaches a composition comprising guaifenesin, dextromethorphan, naproxen (naprosin), hydroxy propyl methyl cellulose (Hypromellose, sustained release polymer), microcrystalline cellulose (diluent), sodium lauryl sulfate, sodium bicarbonate, croscarmellose sodium (disintegrant), polyethylene glycol (encompassing PEG4000, binder), hydroxyethyl cellulose (sustained release polymer), Magnesium stearate (lubricant). It is within skill of one artisan to optimize the percentage of ingredients under prior art condition through routing experimentation to have the claimed range. MPEP 2144.05. Especially in the absence of evidence of showing criticality of claimed range.
Regarding guaifenesin, dextromethorphan, naproxen; Nichols teaches active agent is about 1-80% by weight.
Regarding Hypromellose and hydroxyethyl cellulose, Davis et al. teaches about 1% to about 10% hydroxypropyl methylcellulose (sustained release polymer) in sustained release portion, and 73% of sustained release portion in the total formulation, thus, the sustained release polymer such as Hypromellose and or hydroxyethyl cellulose from at about 1% -about 7% is obvious.
Regarding microcrystalline cellulose, Nichols teaches microcrystalline cellulose 1-99%.
Regarding sodium lauryl sulfate and magnesium stearate, Nichols teaches lubricants such as sodium lauryl sulfate and magnesium 0.25% to about 6%.
Regarding sodium bicarbonate, optimization through routing experimentation to have 1-10%.
Regarding croscarmellose sodium, Nichols teaches Croscarmellose sodium (cross-linked carboxymethyl cellulose) may be present at a concentration of about 2% to about 10%.
Regarding PEG4000, Nichols teaches polyethylene glycols (PEG) including PEG 4000 at 1-99%.
Regarding claim 27, prior art teaches therapeutical effect of each drug of guaifenesin, dextromethorphan and naproxen for a period of 12h.
Regarding claim 28, it is within skill of one artisan in the art to optimize the dissolution of naproxen (in immediate release) of about 100% within 30 min in pH 6.8 phosphate buffer by routing experimentation. MPEP 2144.05. Especially in the absence of showing criticality of claimed range.
Regrading 31, since prior art teaches the pharmaceutical composition comprising each three drug and excipient, the prior art composition must have the same release profile such as Cmax and AUC in claim 31.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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. Cir. 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 1-9, 12-13, 20, 23-28 and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11278506. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent teaches each limitation of applicant’s claimed invention including guaifenesin, dextromethorphan, naproxen (in immediate release) as well as each excipient and the range, and one artisan immediate recognize the obvious variant of applicant’s claimed invention over patent subject matter.
Claims 1-9, 12-13, 20, 23-28 and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12257218 in view of Nichols (US20060127473). The reference patent teaches guaifenesin, dextromethorphan, naproxen (in immediate release) as well as each Hypromellose, hydroxyethyl cellulose, sodium bicarbonate and sodium lauryl sulfate, but silent about microcrystalline cellulose (diluent), croscarmellose sodium (disintegrant), polyethylene glycol (encompassing PEG4000, binder) and Magnesium stearate (lubricant), which are all known and suitable excipient under guidance from Nichols, therefore, it is obvious to prepare applicant’s claimed inventio with reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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/JIANFENG SONG/Primary Examiner, Art Unit 1613
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