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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/15/2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/15/2025 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant’s arguments, see pp. 4-5, filed 07/15/2025, with respect to the objection to claim 1, and rejection of claim 5 under 35 U.S.C. 112(d) have been fully considered and are persuasive. Amendments moot the objection/rejections. The objection/rejections of 07/15/2025 have been withdrawn.
Applicant's arguments filed 07/15/2025 with respect to the obviousness rejection of record have been fully considered but they are not persuasive.
Applicant argues that none of the cited references teach or provide any motivation to combine glyceryl dibehenate and natural waxes/two matrix forming agents in a pharmaceutical composition of caprylic triglyceride. Said teachings/motivation need not be provided by the references or combination thereof, as it is obvious to combine two products known to be useful for the same purpose. That the components are obvious to use individually for the same purpose renders their combination obvious absent unexpected results or a teaching away. See MPEP 2144.06(I). That the references are not drawn specifically to the claimed compositions does not preclude their applicability. Carnauba wax would be expected to impart predictable effects on solubility as taught by Nart regardless of the API. There is no reason a PHOSITA would not expect carnauba wax to impart these effects on a caprylic triglyceride composition. Applicant argues that Nart pertains only to a water soluble drug, but a PHOSITA would not interpret Nart as precluding the application its teachings to drugs of varying solubility. Even if caprylic triglyceride is less soluble than the APIs emphasized by Nart, carnauba wax would be expected to promote its sustained release. Any related argument regarding glyceryl dibehenate also applies. Furthermore, the motivation to apply a reference need not be the same as applicant’s purported motivation, i.e. to increase drug loading. See MPEP 2144(IV). A modified rejection is presented herein in order to address amendments.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 5, 7-20, and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over EP 2319508 A1 to Henderson (hereinafter "HENDERSON") in view of Shekunov et al., "Particle Size Analysis in Pharmaceutics: Principles, Methods and Applications" Pharm Res 24, 203-227 (2007) (hereinafter “SHEKUNOV”), Aburahma et al. “Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals” Expert Opin. Drug Deliv. (2014) 11(12) and Nart et al., "Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs" Materials Science and Engineering C 70 (2017) 250–257.
HENDERSON teaches a formulation comprising 50 g MCT (95% triC8:0) emulsified with 50 g of mono- and di-glycerides combined with 500 mg of L-carnitine (Para. [0039]). The triC8:0 of HENDERSON is equivalent to caprylic triglyceride of instant claim 1 and the amount of caprylic triglyceride of HENDERSON corresponds to about 49.75% by weight of the total composition of caprylic triglyceride (50 g MCT / (50 g MCT + 50 g mono- and di-glycerides + .5 g L-carnitine).
HENDERSON does not teach wherein the composition comprises at least two matrix forming agent present in an amount of between about 20% and about 50% by weight of the total composition, selected from the group consisting of glyceryl dibehenate and natural waxes, wherein the composition is comprised of discrete particles having an average diameter of between about 50 μm and about 350 μm.
SHEKUNOV teaches that “the dissolution performance of matrix-type controlled release tablets is highly influenced by drug’s and/or excipient’s particle size” and further elaborates on specific parameters which are influenced by particle size (p. 206). ABURAHMA teaches the use of Compritol 888 ATO (glyceryl dibehenate) as a matric-forming agent for controlling drug release (p. 1865). NART teaches “the importance of carnauba wax as a lipid excipient in drug delivery systems” and notes its use in melt granulation and drug release modifier in different pharmaceutical dosage forms (p. 250, Introduction).
With respect to claim 1, the difference between HENDERSON and the claimed composition is that the claimed composition requires discrete particles having a specific average diameter of between 50 μm and 350 μm. SHEKUNOV teaches particle size as a result-effective variable in the claimed mode of formulation, namely matrix-type controlled release formulations. To arrive at the claimed particle size in view of HENDERSON is merely the result of routine optimization of a result-effective variable as taught by SHEKUNOV (see MPEP 2144.05(II)).
With respect to claims 1, 3 and 17-20 it would have been obvious to incorporate glyceryl dibehenate and carnauba wax into the claimed composition in order to modify drug release as taught by ABURAHMA and NART. The Examiner notes that NART is generally directed toward highly soluble drugs, but the portion cited is not limited to such drugs. To include carnauba wax at a specific concentration, such as those recited in claims 1, 7, 8 and 19 would have been routine in the process of optimizing desired particle size in the melt granulation process or desired drug release properties as taught by NART. The combination of two products known to be useful for the same purpose is also obvious.
With respect to claims 5 and 8, the 49.75 % by weight of caprylic triglyceride of the HENDERSON composition (50 g MCT / (50 g MCT + 50 g mono- and di-glycerides + .5 g L-carnitine))would have been prima facie obvious as routine optimization (claim 5) and the instantly claimed range of between about 40% and about 50% by weight of the total composition (claim 8) (MPEP 2144.05).
With respect to claims 9-10, HENDERSON teaches additional formulations comprising various excipients including gelatin capsules and tablets comprising starch (Para. [0047], particularly examples D and E). Starch is a dissolution enhancer (claim 9) and is recited in the list of alternatives of the instant claim (claim 10).
With respect to claim 11, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists (MPEP 2144.05(I)). HENDERSON teaches formulations comprising approximately 0-44% starch (Example D, Para. [0047]) and 0-2% starch (Example E, Para. [0047]) which overlap with the instantly claimed range of about 1% to about 20% by weight of the total composition.
With respect to claim 12, the substitution of one known element for another yields predictable results to one of ordinary skill in the art. In the instant case, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer is an art-recognized dissolution enhancer. To substituted the starch of HENDERSON with the instantly claimed copolymer is merely the substitution of one known element for another.
With respect to claim 13, HENDERSON teaches additional formulations comprising various excipients including a tablet comprising microcrystalline cellulose, magnesium stearate or stearate acid, and fumed and colloidal silicon dioxide (Example E, Para. [0047]). These are art-recognized flow aids.
With respect to claim 14, HENDERSON teaches additional formulation comprising various excipients including a tablet comprising “Silicon dioxide, fumed”. This is equivalent to the instantly claimed “[amorphous] silica gel” recited in the list of alternatives.
With respect to claim 15, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. HENDERSON teaches formulations comprising approximately 0-17% amorphous silica gel (Example E, Para. [0047]) which overlap with the instantly claimed range of about 0.1% to 5% by weight of the total composition.
With respect to claim 16, the substitution of one known element for another yields predictable results to one of ordinary skill in the art. In the instant case, micronized talc of instant claim 16 is an art-recognized dissolution enhancer. To substituted the amorphous silica gel of HENDERSON with the instantly claimed micronized talc is merely the substitution of one known element for another.
With respect to claim 23, the difference between HENDERSON and the claimed composition is that the claimed composition requires discrete particles having a specific average diameter of between 100 μm and 300 μm. SHEKUNOV teaches particle size as a result-effective variable in the claimed mode of formulation, namely matrix-type controlled release formulations. To arrive at the claimed particle size in view of HENDERSON is merely the result of routine optimization of a result-effective variable as taught by SHEKUNOV.
With respect to claim 24, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In the instant case, that the claimed particles exhibit a Carr Index of flowability of less than 10% does not render the composition nonobvious.
With respect to claim 25, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In the instant case, that the claimed composition exhibits the instantly claimed dissolution parameters does not render the composition nonobvious.
With respect to claim 26, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In the instant case, that the claimed composition exhibits the instantly claimed dissolution parameters does not render the composition nonobvious.
With respect to claim 27, the purity of the caprylic triglyceride in HENDERSON is 95%.
Conclusion
Claims 1, 3, 5, 7-20 and 23-27 are rejected. Claims 28-29 remain withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JED A KUCHARCZK/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623