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 included in the prosecution are claims 1, 4, 14 and 21-23.
Applicants' arguments, filed 06/29/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 22 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection.
Claim 22 recites discrete solid particles. The claim fails to comply with the written description requirement since such limitation is not disclosed in the specification. At best, the specification discloses on page 18, line 16 wherein micronized fenofibrate are particles, but nowhere does it disclose wherein the particles are discrete solid particles.
Claim 23 recites wherein the composition is bioequivalent to a co-administration of a rosuvastatin immediate-release tablet and a fenofibrate immediate-release tablet, as determined by 90% confidence intervals for Cmax and AUC failing within 80-125% for both rosuvastatin and fenofibrate. The claim fails to comply with the written description requirement since the specification does not disclose wherein the claimed invention is bioequivalent to any co-administration of a rosuvastatin immediate-release tablet and fenofibrate immediate-release tablet. According to page 46, lines 5-9 of the specification, the composition is specifically bioequivalent to the concomitant administration of a 160 mg fenofibrate immediate-release tablet and a 20 mg rosuvastatin immediate-release tablet.
Response to Arguments
Applicant argues that a person of ordinary skill in the art would understand that, in the context of a solid dosage form such as a tablet, micronized particles inherently refer to physically separate, solid particulate entities, rather than dissolved or molecularly dispersed forms.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not provided objective evidence supporting their assertion. Therefore, Applicant’s argument is merely speculative and not persuasive.
Applicant argues that the specification does not describe fenofibrate as being dissolved, or molecularly dispersed, and therefore implicitly supports the presence of individual solid particles.
The Examiner does not find Applicant’s argument to be persuasive. Particles that are not dissolved or molecularly dispersed may be agglomerated with another type of particle, thus making it not a discrete solid particle. As such, Applicant’s argument is unpersuasive.
Applicant argues that a person of ordinary skill in the art would understand that bioequivalence expressed using standard regulatory criteria (i.e., 90% confidence interval for Cmax and AUC within 80-125%), is a well-established framework in the pharmaceutical field, and Applicant’s specification provides sufficient guidance linking the claimed formulation to this outcome.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not provided objective evidence supporting their assertion. Therefore, Applicant’s argument is merely speculative and not persuasive.
Claim Rejections - 35 USC § 112(b) - New
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 4, 21 and 22 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites the limitation "the fenofibrate" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the fenofibrate” is referring to the micronized fenofibrate of claim 1 or to an additional fenofibrate that is present in the fenofibrate layer. It should be noted that if the former, the claim would not be further limiting since claim 1 recites wherein the micronized fenofibrate is present as discrete solid particles. Neither claim 1 nor claim 4 recite wherein an additional fenofibrate is incorporated; therefore, clarity is needed.
Claim 21 recites the limitation "wherein the rosuvastatin layer further comprises rosuvastatin calcium, and wherein the rosuvastatin is the pharmaceutically acceptable salt of rosuvastatin." There is insufficient antecedent basis for this limitation in the claim. It is unclear whether “the rosuvastatin is the pharmaceutically acceptable salt of rosuvastatin” refers to rosuvastatin calcium or to the rosuvastatin in claim 1. If the former, the claim is still indefinite since claim 21 recites “further comprises” and it is unclear if the rosuvastatin calcium is in addition to the rosuvastatin or the pharmaceutically acceptable salt thereof in claim 1 or if rosuvastatin calcium is the rosuvastatin or the pharmaceutically acceptable salt thereof of claim 1.
Response to Arguments
Applicant argues that the rosuvastatin calcium is the pharmaceutically acceptable salt of rosuvastatin present in the rosuvastatin layer, not an additional component.
The Examiner does not find Applicant’s argument to be persuasive since it is not clear from the claim language that rosuvastatin is not an additional component since the claim recites the term “further comprises.”
Claim 22 recites the limitation "having the defined PSD and span" in the last line. There is insufficient antecedent basis for this limitation in the claim. It is unclear if the defined PSD and span is what is recited in claim 1 or is from elsewhere. If the former, it should be noted that this would make the claim not further limiting since all of the limitations in claim 22 is recited in claim 1.
Claim Rejections - 35 USC § 112(d) - New
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 22 is 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 22 fails to further limit claim 1 since all the limitations are recited in 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 - New
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.
Claims 1, 4, 14 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Holm et al. (US 2008/0131503, Jun. 5, 2008) (IDS reference) (hereinafter Holm) in view of Grenier et al. (US 2005/0095297, May 5, 2005) (hereinafter Grenier), Kocevar et al. (WO 2014/009436, Jan. 16, 2014) (hereinafter Kocevar), Kayser et al. (US 2008/0096900, Apr. 24, 2008) (hereinafter Kayser), and Lerner et al. (WO 2007/075171 A1, Jul. 5, 2007) (hereinafter Lerner).
Holm discloses a pharmaceutical composition for oral administration comprising a fixed dose combination of a first solid pharmaceutical composition containing fenofibrate as the active substance and a second solid pharmaceutical composition containing an HMG-CoA reductase inhibitor such as a stain as the active substance, wherein the first and the second pharmaceutical compositions are present in separate entities in a single solid dosage form. For example, a multilayer tablet or two-layer tablet (abstract). The HMG-CoA reductase inhibitor may be rosuvastatin or a pharmaceutically acceptable salt thereof (¶ [0029]). The first and second pharmaceutical compositions are present in at least two separate layers (¶ [0026]). The first composition may comprise micronized crystalline fenofibrate (claim 28). The active substance(s) may be released relatively fast in order to obtain an enhanced on-set of action (¶ [0078]). The solid dosage form comprises from about 100 to about 170 mg of fenofibrate, such as 160 mg, and from about 5 to about 80 mg of statin, such as 20 mg (¶ [0073]). In one embodiment, about 70% w/w/ or more of the fibrate and/or the statin is released from the composition within about 20 min or 15 min when tested in an in vitro dissolution test (¶ [0085]). The composition may contain one or more pharmaceutically acceptable excipients (¶ [0033]). Suitable excipients include lactose as a filler, diluent and/or binder (¶ [0042]), microcrystalline cellulose as a filler, diluent and/or binder (¶ [0042]), croscarmellose sodium as a disintegrant (¶ [0044]), and crospovidone as a disintegrant (¶ [0044]). The lactose may be lactose monohydrate (¶ [0087]). The composition may also comprise one or more surfactants for improving solubility characteristics of the active substance (¶ [0049]). It is within the skills of the average practitioner to select a suitable vehicle being pharmaceutical acceptable, capable of dispersing or fully or at least partly dissolving the active substance using general knowledge and routine experimentation (¶ [0054]).
Holm differs from the instant claims insofar as not teaching wherein the micronized fenofibrate has D(v,50) of more than 0.04 µm and less than or equal to 20 µm.
However, Grenier discloses a pharmaceutical formulation comprising nanoparticles of a fibrate (abstract). The D50 particle size of fenofibrate is in the range 350-750 nm (0.35-0.75 µm) (¶ [0028]). The particle size is a volume average particle size (¶ [0027]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the fenofibrate of Holm to have a D50 particle size in the range of 350-750 nm (0.35-0.75 µm), wherein the particle size is a volume average particle size, since Holm does not disclose a particle size for the fenofibrate and this is a known and effective particle size for fenofibrate used in pharmaceutical compositions as taught by Grenier.
The combined teachings of Holm and Grenier do not teach wherein a width of the particle size distribution expressed as span is from 1.2 to 3
However, Kocevar discloses a nanosuspension comprising abiraterone acetate in the form of particles having a particle size in the range of less than 5000 to 10 nm. It is preferred that the span, i.e. the width of the particle size distribution, is narrow. A narrow span results in better reproducibility of results from batch to batch. The span is from 30 to 0.01 (page 6/40).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the span of fenofibrate to be 30 to 0.01 since this range results in better reproducibility of results from batch to batch as taught by Kocevar.
The combined teachings of Holm, Grenier, and Kocevar do not teach wherein the composition comprises sodium lauryl sulfate, lactose anhydrous, and rosuvastatin calcium.
However, Kayser discloses a pharmaceutical composition (abstract). To aid dissolution of the compound of the composition into an aqueous environment a surfactant might be added as a wetting agent. Suitable surfactants include sodium lauryl sulfate (¶ [0198]). One may dilute the compound of the composition with diluents such as anhydrous lactose (¶ [0193]). Medicaments such as rosuvastatin calcium may be added to the composition (¶ [0260]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Holm discloses wherein the composition comprises one or more surfactants for improving solubility characteristics of the active substance. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated sodium lauryl sulfate into the composition of Holm since it is a known and effective surfactant for aiding in dissolution as taught by Kayser.
Holm discloses wherein the composition comprises lactose as a diluent. Therefore, it would have been obvious to one of ordinary skill in the art to have incorporated lactose anhydrous into the composition of Holm since it is a known and effective lactose for diluting as taught by Kayser.
Holm discloses wherein the composition comprises a pharmaceutically acceptable salt of rosuvastatin. Therefore, it would have been obvious to one of ordinary skill in the art to have incorporated rosuvastatin calcium into the composition of Holm since it is a known and effective pharmaceutical salt of rosuvastatin as taught by Kayser.
The combined teachings of Holm, Grenier, Kocevar, and Kayser do not teach wherein the micronized fenofibrate is present as discrete solid particles.
However, Lerner discloses a pharmaceutical composition of fenofibrate and a dosage form containing it (abstract). The fenofibrate can be present as discrete molecules or it can be present in aggregates (¶ [00018]).
Holm does not disclose the form of the micronized fenofibrate. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the micronized fenofibrate as discrete particles since this is a known and effective form of fenofibrate for pharmaceutical compositions as taught by Lerner.
Regarding instant claim 1 reciting wherein the fenofibrate layer comprises lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, crospovidone, and sodium lauryl sulfate, and the rosuvastatin layer comprises lactose anhydrous, microcrystalline cellulose, and crospovidone, Holm discloses wherein it is within the skills of the average practitioner to select a suitable vehicle being pharmaceutical acceptable, capable of dispersing or fully or at least partly dissolving the active substance using general knowledge and routine experimentation. Therefore, one of ordinary skill in the art would have arrived at the claimed combination of excipients in each layer through routine experimentation based on the excipients required for dispersing and/or dissolving the active substance in each layer.
Regarding instant claims 1 and 4 reciting that the fenofibrate is not in the form of a solid solution or solid dispersion, Holm discloses in ¶ [0056] wherein it is preferable that the form of the active substance be a solid solution or solid dispersion. Because this is merely a preferred embodiment, it would have been obvious to one of ordinary skill in the art that such form is not required. This is further evident from claim 29 of Holm, which is a dependent claim that recites wherein the first composition comprises a solid solution of fenofibrate. Since this limitation is in a dependent claim, it would have been obvious to one of ordinary skill in the art that Holm does not require the form of fenofibrate to be a solid solution. Therefore, since Holm does not disclose wherein fenofibrate is required to be in the form of a solid solution or solid dispersion, it would have been obvious to one of ordinary skill in the art that the fenofibrate does not need to be in such form.
Regarding instant claim 23, since the composition of Holm is substantially structurally the same as the claimed invention, comprises substantially the same rosuvastatin and fenofibrate as the claimed invention, comprises substantially the same amount of rosuvastatin and fenofibrate as the claimed invention, and immediately releases rosuvastatin and fenofibrate like the claimed invention, the composition of Holm is necessarily bioequivalent to a co-administration of a rosuvastatin immediate-release tablet and a fenofibrate immediate-release tablet like the claimed invention.
Response to Arguments
Applicant argues that Grenier merely describes a median particle size (D50) in the nanometer range and does not disclose or suggest a particle size distribution define by the combined parameters of D(v,10), D(v,50), and D(v,90).
The Examiner does not find Applicant’s argument to be persuasive. Instant claim 1 recites a particle size distribution in which D(v,10) is…, D(v, 50) is …, and/or D(v,90) is…. As such, it is not necessary for the prior art to disclose D(v,10) and D(v,90) along with D(v,50) since the claim recites the term “or.” As such, Applicant’s argument is unpersuasive.
Applicant argues that Kocevar discloses a relatively very broad span range of 0.01 to 30 and does not provide any teachings or preference for the narrowly defined span range of 1.2 to 3. The claimed span range is not an arbitrary selection, but rather a carefully chosen parameter that ensures a controlled and reproducible particle size distribution, which directly impacts the dissolution and bioavailability.
The Examiner does not find Applicant’s argument to be persuasive. In cases involving overlapping ranges, even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). Therefore, the claimed range is still obvious since Kocevar teaches an overlapping range. Additionally, Applicant’s has not shown wherein the claimed range is not an arbitrary selection. As such, Applicant’s argument is unpersuasive.
Applicant argues that consistent with In re Peterson, the disclosure of a broad range does not render a specific sub-range obvious in the absence of clear guidance directing a skilled person to that range. Likewise, In re Sebek confirms that selecting a narrow range from a broader one is not obvious unless there is evidence of motivation or recognition of its criticality.
The Examiner does not find Applicant’s argument to be persuasive. It is not clear where in the court cases that it says these assertions. As such, Applicant’s argument is unpersuasive.
Applicant argues that each reference relates to a different context. There is no teaching or suggestion in any of these references that would motivate a person of ordinary skill in the art to combine their teachings to achieve the specific combination of features recited.
The Examiner does not find Applicant’s argument to be persuasive. In order for a reference to be proper for use in an obviousness rejection under 35 U.S.C. 103, the reference must be analogous art to the claimed invention. A reference is analogous to the claimed invention if the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem). See MPEP 2141.01(a). In the instant case, each of the prior art references and the claimed invention are in the same field of pharmaceuticals. As such, each of the prior art references are analogous art and are proper for use in an obviousness rejection. The teachings of each prior art reference and the motivation to use the teachings have been provided in the rejection. Applicant has not explained why the motivation statements are improper. As such, Applicant’s argument is unpersuasive and the rejection is maintained.
Applicant argues that the Examiner’s position that excipient selection is routine does not take into account the complexity of multilayer formulation development, where interactions between excipients and processing conditions are highly unpredictable.
The Examiner does not find Applicant’s argument to be persuasive. It was Holm who teaches that excipient selection is routine. Also, Applicant has not shown with objective evidence wherein interactions between excipients and processing conditions are highly unpredictable. Therefore, Applicant’s argument is merely speculative and unpersuasive.
Applicant argues that Holm expressly identifies solid solutions or solid dispersions of fenofibrate as preferred embodiments.
The Examiner does not find Applicant’s argument to be persuasive. A prior art reference is evaluated for all that it reasonably suggests and is not limited to preferred embodiments. Also, as discussed in the rejection, Holm discloses in ¶ [0056] wherein it is preferable that the form of the active substance be a solid solution or solid dispersion. Because this is merely a preferred embodiment, it would have been obvious to one of ordinary skill in the art that such form is not required. This is further evident from claim 29 of Holm, which is a dependent claim that recites wherein the first composition comprises a solid solution of fenofibrate. Since this limitation is in a dependent claim, it would have been obvious to one of ordinary skill in the art that Holm does not require the form of fenofibrate to be a solid solution. Therefore, since Holm does not disclose wherein fenofibrate is required to be in the form of a solid solution or solid dispersion, it would have been obvious to one of ordinary skill in the art that the fenofibrate does not need to be in such form. As such, Applicant’s argument is unpersuasive.
Applicant argues that bioequivalence is a pharmacokinetic property that depends on multiple formulation variables, including particle size distribution, excipient composition and release behavior. These factors directly influence drug absorption and systemic exposure and cannot be assumed to be identical across different formulations.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not shown with objective evidence that the claimed bioequivalence depends on particle size distribution, excipient composition and release behavior. As such, Applicant’s argument is merely speculative and not persuasive.
Applicant argues that it is only through the combined and coordinated implementation of the claimed features – controlled PSD and span, targeted surfactant use, and layer-specific formulation within a bilayer tablet – that the claimed invention achieves consistent immediate release and the required bioequivalence. This demonstrates a true synergistic effect, which is neither disclosed nor suggested by the cited prior art and would not have been obvious to a person of ordinary skill in the art.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not shown with objective evidence that controlled PSD and span, targeted surfactant use, and layer-specific formulation within a bilayer tablet are critical. As such, Applicant’s argument is merely speculative and not persuasive.
Regarding the status of foreign counterpart applications, the Examiner is not obligated to allow an application just because a foreign patent agency has allowed a similar application. The patent laws of each country vary. The claims in the current application do not appear to be nonobvious and allowable as shown in the rejection above. None of the arguments Applicant presented are persuasive. Therefore, no claims are allowed.
Conclusion
Claims 1, 4, 14 and 21-23 are rejected.
Claim 20 has been withdrawn.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See 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.
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/TRACY LIU/ Primary Examiner, Art Unit 1614
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