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 .
Election/RestrictionsThe requirement to elect between Group I, claims 1-2, 5-8, 10, 12, 14-16 and 25-30, drawn to a pharmaceutical pellet composition; Group II, claims 17-18, drawn to a method of making a pharmaceutical pellet composition; and Group III, claim 31, drawn to a method of using a pharmaceutical pellet composition to treat attention deficit hyperactivity disorder; are withdrawn upon further consideration. Claims from all groups were found to be taught in one source.
Status of the Claims
In the Reply filed 3 April 2026, Applicant amended the claims; however, the restriction requirement has been completely withdrawn. Accordingly claims 1-2, 5-8, 10, 12, 14-18, and 25-31 are pending.
Specification
The use of the terms EUDRAGIT®, KOLLICOAT®, SYLOID®, and CAB-O-SIL®, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claim 6, 7, and 16 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. Claims 6 and 7 recite the limitation "the water-insoluble polymer” in line 2 of each claim. However, claim 1 does not contain a “water-insoluble polymer.” There is insufficient antecedent basis for this limitation in the claim. For prior art purposes, claim 6 will be interpreted as “wherein the cellulose acetate-based polymer and the pore former are present in a weight ratio of from about 50:50 to about 99:1.” For prior art purposes, claim 7 will be interpreted as “wherein the cellulose acetate-based polymer and the plasticizer are present in a weight ratio of from about 70:30 to about 99:1.”
Claim 16 recites the limitation "bead/seed, or a granule" in line 2 of the claim. However, claim 1 does not contain a “bead/seed, or a granule.” There is insufficient antecedent basis for this limitation in the claim. For prior art purposes, claim 16 will be interpreted as “wherein the core is a nonpareil pellet, bead/seed, or granule.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 16 recites “bead/seed, or a granule”. However, claim 1 does not contemplate any of those objects and so claim 16 fails to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-2, 5-8, 10, 12, 14-18, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Boehm (WO 2005065673, of record, see IDS filed 09/11/2023).
Regarding instant claims 1 and 2, claim 1 of Boehm teaches a solid dosage formulation comprising a matrix, wherein the matrix comprises: a pharmaceutically effective amount of atomoxetine or a pharmaceutically acceptable salt thereof; and a wax material. Boehm further specifies the sustained-release (dosage) preparations may be made in conjunction with a multiparticulate system, such as pellets [0071], so the solid dosage formulation reads on the claimed pharmaceutical pellet composition. The matrix reads on the instant claimed core containing a drug. Boehm teaches the matrix is coated with a coating composition (claim 4) and that the coating composition is a functional coating composition (claim 5). Boehm teaches a press-coat dosage form comprising a coating composition comprising a hydrophilic polymer (claim 20), and that the hydrophilic polymer comprises a hydrophilic cellulose polymer (claim 27). Boehm also discloses the formulations described herein may be coated with a functional or nonfunctional coating, which may include a polymer, for example cellulose acetate, cellulose acetate butyrate, cellulose triacetate, cellulose acetate phthalate, and combinations comprising one or more of the foregoing polymers [0341, 0343-0344]. Regarding the method of obtaining the release profile, Boehm teaches a similar method that can be optimized: the release profile, of the atomoxetine dosage form is obtained by immersing the dosage from in 750 ml of 0.1 N HCl for 2 hours at 37 °C at a speed of 100 rpm and then adding 250 ml of 0.2 M sodium phosphate buffer to the dissolution media to afford at pH of 6.2. Alternatively the atomoxetine release rate data is obtained for a dosage form in USP Apparatus 2 at 50 rpm using 900 ml of water [0272]. Regarding the release profile, Boehm teaches a similar release profile that can be optimized: a dissolution profile in 0.1 N HCl such that at 1 hour after combining the dosage form with a dissolution media 5 to 15% of the atomoxetine or atomoxetine salt is released, at 2 hours after combining the dosage form with the dissolution media 10 to 25% of the atomoxetine or atomoxetine salt is released [0277]. Boehm discloses release-modifying agents, which affect the release properties of the release-retarding material, may optionally be used. The release-modifying agent may, for example, function as a pore-former [0069]. Boehm discloses the sustained-release profile of atomoxetine release in the formulations can be altered by altering the manner in which the plasticizer is added [0078], thus mentioning that a plasticizer is added. Boehm acknowledges lag time (release time) and teaches layered pellets or tablets may comprise a surrounding lag time controlling layer [0097-0098] and gives examples of compounds that can be used [104]. Boehm teaches it may be desirable to precisely control the plasma levels of atomoxetine for a number of hours after administration. Pulsed-release formulations, containing some combination of immediate-release, sustained-release, and delayed-release formulations in the same dosage form can be used in place of multiple immediate and sustained-release dosages in such situations. Other types of pulse release formulations are tailored to provide a particular plasma level profile [0033-0034]. Boehm further teaches that to obtain a sustained-release of atomoxetine, the substrate comprising atomoxetine can be coated with an amount of release-retarding material sufficient to obtain a weight gain level from about 2 to about 30%, although the coating can comprise a be greater or lesser weight percent depending upon the desired release rate [0076]. Boehm’s teachings indicate that the release profile is an optimizable parameter. Regarding instant claim 5, Boehm teaches a delayed-release atomoxetine hydrochloride formulation, which contains 45.7 mg atomoxetine hydrochloride in a total weight of 57.84 mg (total weight including the coating and core) (Example 13, from after [0385] to after [0387]). 45.7 mg/57.84 mg = 79% atomoxetine, which falls within the instantly claimed range of from about 20% w/w to about 80% w/w, therefore obviating it.
Regarding claims 6 and 7, Boehm teaches that it may be advantageous to add plasticizer to the ethyl cellulose before using the same as a coating material. Generally, the amount of plasticizer included in a coating solution is based on the concentration of the polymer, e.g., most often from about 1 to about 50 percent by weight of the polymer. Concentrations of the plasticizer, however, can be determined by routine experimentation [0344]. The limitation about 1 percent by weight of the polymer means the plasticizer would be 1 percent and the polymer (cellulose acetate) would be 100 percent, which converts to a ratio of 1:100, or 100:1 if listing the polymer first. Using the same logic, 50 percent would convert to a ratio of 100:50. A polymer:plasticizer range of about 100:50 to about 100:1 would overlap on the range of a weight ratio of from about 70:30 to about 99:1 in instant claim 7, thereby obviating it. Boehm’s plasticizer would also read on the pore-former in instant claim 6 because Boehm teaches suitable plasticizers, include, but are not limited to polyethylene glycol [0207]. As defined in the instant specification, the pore former can be selected to be polyethylene glycol (page 4, lines 26-28).
Regarding instant claim 8, Boehm teaches an embodiment similar to that of the instantly claimed invention where a pharmaceutical composition comprises atomoxetine salt and polymeric carrier [0313], which partially reads on the instantly claimed core. Boehm states that atomoxetine may be added in free base form, and when atomoxetine is added in free base form, the process comprises adding an acid corresponding to a salt of atomoxetine to the mixture or solution of the free base. The free base is then converted to a salt in situ, for example by addition of an organic acid. A preferred acid is fumaric acid [0317-0318].
Regarding instant claim 10, Boehm teaches the plasticizer is polyethylene glycol or triacetin and also states that other water-insoluble plasticizers can be used (claim 65, [0345]), implying the listed plasticizers are water-soluble, which would read on the instant claim.
Regarding instant claim 12, Boehm teaches "extended-release" is meant to include the release of atomoxetine for at least about 8 hours [0053], which reads on the instantly claimed extended release for at least about 8 hours.
Regarding instant claims 14-16, Boehm teaches atomoxetine cores as granules [0386]. Boehm also discusses a second coating containing the remaining atomoxetine ([0383] and the subsequent table, claims 20-23), which reads on the drug layer comprising atomoxetine in instant claim 14 and the granule containing atomoxetine in instant claim 15. Boehm teaches the core material comprising atomoxetine can be prepared by layering the drug onto a seed, such as for instance a sugar sphere seed [0075, 0099], which reads onto the nonpareil aspect of instant claim 16 because as defined by the instant specification, the term "nonpareil seed" refers to inert material/particles, e.g., pellets, beads, seeds, or granules. In certain embodiments, the nonpareil seed is sugar sphere. (page 13, lines 8-9, 11-12).
Regarding claim 17, Boehm teaches the core material comprising atomoxetine can be prepared by layering the drug onto a seed, such as for instance a sugar sphere seed [0099], which reads onto the nonpareil aspect of instant claim 16 because as defined by the instant specification, the term "nonpareil seed" refers to inert material/particles, e.g., pellets, beads, seeds, or granules. In certain embodiments, the nonpareil seed is sugar sphere (page 13, lines 8-9, 11-12). Boehm teaches a solution of povidone is sprayed onto an active ingredient, which results in granules. Povidone would read onto the instantly claimed water soluble polymer because Boehm teaches dissolving povidone in water [0376], and the resulting granules would read onto the instantly claimed seal coated core. Regarding the method of obtaining the release profile, Boehm teaches a similar method that can be optimized: the release profile, of the atomoxetine dosage form is obtained by immersing the dosage from in 750 ml of 0.1 N HCl for 2 hours at 37 °C at a speed of 100 rpm and then adding 250 ml of 0.2 M sodium phosphate buffer to the dissolution media to afford at pH of 6.2. Alternatively the atomoxetine release rate data is obtained for a dosage form in USP Apparatus 2 at 50 rpm using 900 ml of water [0272]. Regarding the release profile, Boehm teaches a similar release profile that can be optimized: a dissolution profile in 0.1 N HCl such that at 1 hour after combining the dosage form with a dissolution media 5 to 15% of the atomoxetine or atomoxetine salt is released, at 2 hours after combining the dosage form with the dissolution media 10 to 25% of the atomoxetine or atomoxetine salt is released [0277].
Regarding claim 18, Boehm teaches the core material comprising atomoxetine can be prepared by extrusion/spheronization of a mixture comprising the drug and pharmaceutically acceptable excipients [0099], which reads on instantly claimed step (a). Boehm states that the formulations described herein may be coated with a functional coating, which may include a polymer, for example cellulose acetate, cellulose acetate butyrate, cellulose triacetate, cellulose acetate phthalate, and combinations comprising one or more of the foregoing polymers (claim 14, [0341, 0362-0363]). Regarding the method of obtaining the release profile, Boehm teaches a similar method that can be optimized: the release profile, of the atomoxetine dosage form is obtained by immersing the dosage from in 750 ml of 0.1 N HCl for 2 hours at 37 °C at a speed of 100 rpm and then adding 250 ml of 0.2 M sodium phosphate buffer to the dissolution media to afford at pH of 6.2. Alternatively the atomoxetine release rate data is obtained for a dosage form in USP Apparatus 2 at 50 rpm using 900 ml of water [0272]. Regarding the release profile, Boehm teaches a similar release profile that can be optimized: a dissolution profile in 0.1 N HCl such that at 1 hour after combining the dosage form with a dissolution media 5 to 15% of the atomoxetine or atomoxetine salt is released, at 2 hours after combining the dosage form with the dissolution media 10 to 25% of the atomoxetine or atomoxetine salt is released [0277].
Regarding instant claim 29, Boehm teaches the pore-former can comprise one or more hydrophilic polymers, such as hydroxypropylmethylcellulose, hydroxypropylcellulose, and combinations comprising one or more of the foregoing release-modifying agents (hydrophilic polymers) [0142].
Regarding instant claim 30, Boehm teaches a capsule comprising the solid dosage form of the solid dosage formulation of atomoxetine (claims 1, 2, and 19).
Regarding instant claim 31, Boehm teaches a method of treating attention deficit disorder, the method comprising orally administering to a human an oral sustained-release dosage form comprising atomoxetine (claim 102). Attention deficit disorder reads on the instantly claimed attention deficit hyperactivity disorder, and human reads on the instantly claimed subject.
Regarding instant claims 1, 2, 17 and 18, Boehm does not teach that the composition releases less than or equal to 40% of the atomoxetine or the pharmaceutically acceptable salt thereof, based on the total weight of atomoxetine or the pharmaceutically acceptable salt thereof present in the composition, within 2 hours of coming in contact with 900 mL of a dissolution medium comprising 0.05 M pH 6.8 buffer, measured using USP Apparatus II (paddle) at 50 rpm and 37°C, or that the composition provides a lag time of between about 30 minutes and about 2 hours, during which the composition releases less than or equal to 10% of atomoxetine or a pharmaceutically acceptable salt thereof, measured using USP Apparatus 2 (Paddle), with sinkers, in 900 mL of a dissolution medium comprising 0.05 M of pH 6.8 buffer, at 37°C and 50 rpm. However, Boehm does disclose a similar release profile, a method of obtaining it, and various means to modify the release profile with plasticizers and pore formers to get the desired sustained release of the drug with the sustained release coating that is taught.
At the time of filing, a person of ordinary skill in the art would know that Boehm’s solid dosage formulation is obvious over the instant claims.
A reference is analyzed using its broadest teachings. MPEP 2123 [R-5]. “[W]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Here a skilled artisan would be motivated to rearrange the teaching of Boehm to arrive at the instant claimed invention.
Further, at the time of filing, a person of ordinary skill in the art could use the release rate modifying agents (plasticizers and pore formers), perform tailoring that results in pulse release formulations, and adjust thickness/weight gain of coating, to modify the solid dosage formulation in Boehm for ‘optimization’ of release.
Regarding claim 5, at the time of filing, the person of ordinary skill in the art would know that Boehm's ranges are obvious over the instant claims. Therefore, Boehm obviates that presently claimed. "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 (I) regarding obviousness of ranges).
Claims 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Boehm (WO 2005065673, of record, see IDS filed 09/11/2023) as applied to claims 1-2, 5-8, 10, 12, 14-18, and 29-31 above, in further view of Williams 2000.
As applied above, Boehm teaches the limitations of instant claims 1-2, 5-8, 10, 12, 14-18, and 29-31.
Regarding claim 25, Boehm does not teach that the functional coat consists of the cellulose acetate-based polymer, the pore former and the plasticizer.
Regarding claim 26, Boehm does not teach that the functional coat consists of the cellulose acetate-based polymer and optionally the pore former and plasticizer.
Regarding claim 27, Boehm does not teach that the functional coat consists of the cellulose acetate-based polymer and the plasticizer.
Regarding claim 28, Boehm does not teach that the functional coat consists of the cellulose acetate-based polymer and the pore former.
Williams teaches cellulose acetate phthalate (CAP) is used as an enteric polymer coating for delayed release products, and that Aquacoat® CPD, the most recently introduced product, is an aqueous dispersion of CAP containing 23% polymer, 7% poloxamer and 70% water (page 243, right column, lines 2-5). The polymer would read on the instantly claimed cellulose acetate-based polymer. The poloxamer would read on the instantly claimed pore formers and plasticizers because as taught by the instant specification, in certain embodiments, plasticizers are pore formers (page 12, lines 33-34). The water would not infringe on the “consisting of” limitations because Williams also teaches that the water is evaporated (page 243, right column, line 12).
Therefore, before the effective filing date of the claimed invention, it would be obvious to a person having ordinary skill in the art to combine the solid dosage formulation of atomoxetine of Boehm with the coating of Williams in order to improve permeability. Boehm teaches the lag time controlling layer may be a semipermeable membrane comprising a water resistant polymer that is semipermeable for an aqueous solution, such as gastro-intestinal fluid [0104]. Williams teaches CAP and other cellulosic derivatives were more permeable than acrylic polymers due to their hydrophilicity and less dense molecular arrangements [15] (page 244, left column, lines 9-14). Use of William’s teaching to improve Boehm’s solid dosage formulation for the purpose of improving permeability is an obvious modification and within the purview of the skilled artisan. There would be a reasonable expectation of success because of the reasons described earlier in this paragraph.
Conclusion
Claims 1-2, 5-8, 10, 12, 14-18, and 25-31 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLY S LIU whose telephone number is (571)272-8235. The examiner can normally be reached Monday-Friday 8:00 AM - 5:00 PM.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/ALLY S LIU/Examiner, Art Unit 1611
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