DETAILED ACTION
Status of Application
Receipt of the response to the non-final office action, the amendments to the claims and applicant arguments/remarks, filed 09/10/2025, is acknowledged.
Claims 1-6, 8, 10-20 are pending in this action. Claim 9 has been cancelled. Claim 7 has been cancelled previously. Claim 1 has been amended. Claims 1-6, 8, 10-20 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant's amendments necessitated new ground(s) of 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 is a 371 of PCT/EP2018/055847, filed March 8, 2018, which claims benefit of foreign priority to EP17160206.3, filed March 9, 2017.
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, 10-20 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 independent claim 1 discloses a solid dosage form comprising “a 1st and a 2nd active pharmaceutical ingredient or a pharmaceutically acceptable salt, an isomeric form, a prodrug, or metabolite thereof”. Further, amended claim 1 recites the limitations “wherein the 1st and 2nd active pharmaceutical ingredients or the pharmaceutically acceptable salts, the isomeric forms, the prodrugs, or metabolites thereof are the same” and “the 1st and/or 2nd active pharmaceutical ingredient or the pharmaceutically acceptable salt, the isomeric form, the prodrug, or metabolite thereof is methylphenidate” that is not reasonably clear. In the present case, the active ingredient to be used in the claimed dosage form is not clearly delineated. If the applicant implies the use of methylphenidate as the active ingredient in the claimed composition/product that should be clearly delineated. This limitation was interpreted as best understood as “A solid oral pharmaceutical dosage form comprising methylphenidate”. Clarification is required.
Newly amended claim1 further recites the limitation “wherein 30-50% of methylphenidate is released in a 1st immediate release phase and 70-50% of methylphenidate in a 2nd delayed release phase”. To this point, it is noted that the instant claim discloses a dosage form comprising: (i) an immediate release core comprising a drug; (ii) a 1st delayed release layer comprising an enteric coating; (iii) a 2nd sustained release layer comprising a retard polymer; and (iv) a 3rd immediate release layer comprising the drug. As stated previously, “Claiming a result without reciting what materials produce that result is the epitome of an indefinite claim. Such a claim fails to delineate with any reasonable certainty the requirements of the formulation. Forest Labs., Inc. v. Teva Pharms. USA, Inc. 2017 U.S. App. LEXIS 24877. Further, it is noted that “[i]f a claim is amenable to two or more plausible constructions, applicant is required to amend the claim to more precisely define the metes and bounds of the claimed invention or the claim is indefinite under §112, ¶ 2. Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) (expanded panel).” Clarification is required.
Claims 2-6, 8, 10-20 are rejected as being dependent on rejected independent claim 1 and failing to cure the defect.
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.
Claims 1-6, 8, 10-20 are rejected under 35 U.S.C. 103 as being unpatentable over Goldenheim et al., US 2004/0131680 (hereinafter referred to as Goldenheim), in view of Shojaei et al., US 2007/0264323 (hereinafter referred to as Shojaei), and further in view of Barnscheid et al., US 2014/0356428 (hereinafter referred to as Barnscheid), and Melamed, US 2010/0069402.
Goldenheim teaches solid oral controlled release methylphenidate/drug formulations comprising, e.g., 20 mg of drug (as a single dose), and providing bimodal drug release profile, i.e., (i) a rapid initial release of up to 45% of the dose after 0.25 hr, and (ii) prolonged release of 30-80% of the dose after 4 hr (Claims 1, 8; Title, Abstract). Goldenheim further teaches the use of methylphenidate (containing erythro and threo isomers) or hydrochloride salt thereof for treatment of attention deficit hypoactive disorder and can be administered only once, i.e., in the morning (Para. 0013; 0015, 0028, 0050-0051) as applied to claims 1, 10, 12-14).
Goldenheim teaches that the final drug product is a solid oral capsule/tablet containing methylphenidate in particulate form such as beads, pellets, granules, etc., wherein each particle contains a series of layers with different release characteristics, i.e., (i) an outer immediate release layer; (ii) a release delaying layer; (iii) a controlled release layer; and (iv) an immediate release core (Para. 0029, 0033, 0055, 0057 as applied to claims 1-3). To this point, Goldenheim specifically teaches that upon oral administration, the formulation provides (i) a rapid dissolution and absorption of the outer layer comprising a portion of the drug in immediate release form, thereby resulting in a rapid rise of the drug to therapeutic plasma levels; followed by (ii) a period of no absorption (due to an enteric coating); followed thereafter by (iii) a controlled release of the drug from the formulation to maintain plasma levels (Para. 0055).
Goldenheim teaches that sustained release coatings may include: (i) pH-dependent coating to release the drug in desired areas of the gastro-intestinal tract (e.g., the stomach or small intestine), wherein said coating may include such polymers as shellac, cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, methacrylic acid ester copolymers, etc. (Para. 0065 as applied to claims 5, 15); and (ii) pH independent coating to achieve optimal release regardless of pH-changes in the environmental fluid by using in said coating alkylcellulosic polymer(s), e.g., ethyl cellulose, hydroxypropyl methylcellulose (i.e., retarded polymer; Para. 0065-0068, 0085 as applied to claims 1, 6, 16-18).
Goldenheim teaches that the release profile of said formulations can be altered by inclusion of additional ingredients/excipients, e.g., binders, plasticizers, lubricants, and/or the beads/pellets may be optionally overcoated with a barrier agent, e.g., to separate the drug from the hydrophobic controlled release coating (Para. 0084, 0085, 0114, 0119 as applied to claims 4 and 8).
Goldenheim provides examples of preparing immediate release beads of methylphenidate HCl and hydroxypropyl methylcellulose (Example 1) that further coated with an enteric coating comprising methacrylic acid copolymer (here as Eudragit® L 30 D-55 plasticized with triethyl citrate and talc; Example 5), and further coated with an immediate release layer comprising the same drug (Example 6A).
Goldenheim does not specifically teach coating a 1st delayed-release layer (an enteric layer) with a 2nd sustained release layer (claim 1).
Shojaei teaches multi-layered compositions that can be in form of tablets or capsules, and wherein said compositions may include (i) an immediate release component/layer/core, (ii) a delayed release component having an enteric coating layer that delays the release of the drug for a lag time (Abstract; Para. 0029, 0054; 0063, 0074). To this point, Shojaei teaches that said enteric coating may include such polymers as polyvinyl acetate phthalate, pH dependent methacrylic acid copolymer (Para. 0114, 0137). Further, Shojaei teaches that one can also use “a protective layer” coated over the enteric layer to reduce the water penetration rate through the enteric coating layer, and thus increase the lag time of the drug release, wherein said protective layer may include such polymers as cellulose derivatives (e.g., hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose for providing bimodal drug release), polyvinylpyrrolidone (Para. 0012, 0139).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a protective layer over enteric coating as taught by Shojaei preparing dosage forms taught by Goldenheim. One would do so with expectation of beneficial results, because Shojaei teaches that said approach allows controlling water penetration rate through the enteric coating layer and increasing/controlling the lag time of the drug release.
Goldenheim also does not teach the use of different drugs (i.e., “and/or term” in claim 1), drugs/compounds for abuse protection/prevention (claim 11), and/or the use of said oral dosage forms for treatment of allergic rhinitis (claim 20).
Barnscheid teaches solid, oral dosage forms with bimodal release profile that contain a 1st pharmacologically active ingredient in a prolonged release form and a 2nd pharmacologically active ingredient in an immediate release form (Para. 0060). Barnscheid specifically teaches that said dosage forms include: (i) pharmacologically active ingredients that have a potential of abuse, e.g., methylphenidate or salt thereof (Para. 0142), (ii) coatings that may include such compounds as hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, ethyl cellulose, polyvinylpyrrolidone, polyvinyl acetate, hydroxypropyl methylcellulose, polyvinyl acetate phthalate, etc., and (iii) suitable excipients (Para. 0098-0101). Barnscheid teaches that one can use in said solid dosage forms “gel-formers”, i.e., polymers/compounds forming a gel (e.g., hydroxypropyl methylcellulose, polyethylene oxide, polyvinyl alcohol, etc.) when the dosage form is dissolved in water/alcohol mixtures, allowing thereby to minimize the amount of drug to be drawn into a syringe (Para. 0451-0453).
Melamed teaches a method of treating attention deficit hyperactivity disorder in patients with allergic rhinitis by administering to said patients compositions comprising methylphenidate in combination with antihistamine (Abstract; Para. 0002, 0012, 0017, 0038-0039, 0057).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use different drugs and/or compounds for abuse prevention as taught by Barnscheid preparing dosage forms taught by Goldenheim and Shojaei. One would do so with expectation of beneficial results, because Barnscheid teaches that said approach provides dosage forms suitable for combination therapy and protected from abuse. It also would be obvious to use/try the dosage forms as taught by Goldenheim, Shojaei and Barnscheid and comprising methylphenidate in combination with a different drug (e.g., antihistamine) to treat allergic rhinitis as taught by Melamed. One would do so with expectation of beneficial results, because Melamed teaches said approach can be used for treating comorbid allergic rhinitis and behavioral disorders either with a single medication or by the synergistic effect created by a plurality of medications.
Regarding the claimed properties of the disclosed compositions (i.e., suitable for administration period of at least 20 hrs; release of active ingredients), it is noted that the cited prior art teaches formulations comprising the same components and active agents (e.g., methylphenidate or salt thereof). 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.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US 2009/0123554 - teaches oral controlled release formulations comprising multi-layer beads comprising: (i) a core comprising methylphenidate or a pharmaceutically acceptable salt thereof; (ii) a controlled release layer coated over the core; (iii) a release delaying layer coated over the controlled release layer; and (iv) an outer layer coated over the release delaying layer and comprising a second portion of methylphenidate or a pharmaceutically acceptable salt thereof.
US 2012/0189695 – teaches extended release pharmaceutical dosage forms comprising a drug (e.g., methylphenidate or an analog, derivative, isomer or enantiomer, polymorph, or prodrug thereof), wherein said dosage forms comprise beads/pellets (comprising a 1st portion of the drug) comprising a sustained-release coating and a controlled release coating, and wherein said coated beads/pellets form a tablet core, and said tablet core further comprising an immediate-release coating comprising a 2nd portion of the drug.
US 6,419,960 and/or US 6,673,367 – teach controlled release formulations/tablets comprising methylphenidate, wherein said formulations/tablets comprise beads containing immediate release core and a series of layers with different characteristics, e.g., an outer immediate release layer, a release delaying layer (enteric coat), a controlled release layer over an immediate release layer, and wherein said tablets can be administered only once, e.g., in the morning.
US 6,322,819 – teaches pulsed dose drug delivery systems/tablets comprising an immediate release component/core comprising an active agent, an enteric delayed release layer, a protective layer, and an immediate release layer.
Response to Arguments
Applicant's arguments, filed 09/10/2025, have been fully considered, and they were found to be partially persuasive. Any rejection not reiterated in this action is withdrawn. New 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.
In response to applicant’s argument that Goldenheim does not disclose/teach compositions that are suitable for an administration period of at least 20 hrs, it is noted that the cited prior art teaches oral solid dosage forms that may include structural elements and/or compounds as instantly claimed and provide bimodal drug release profile. One skilled in the art would have understood that properties of multicomponent systems/product 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/product. Therefore, it is expected that different compositions/products 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 results, as these are variable parameters attainable within the art. Optimization within prior art conditions or through routine experimentation does not support patentability absent comparative evidence of criticality of the claimed range. MPEP 2144.05. Applicant is advised to clarify the claim language, structural constituents/elements and compounds that can be included into the claimed structural constituents for providing claimed/desired properties, 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. 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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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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