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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/12/2026 has been entered.
Status of Claims
Receipt of Remarks/Amendments filed on 11/18/2025 and 01/12/2026 are acknowledged.. Claims 16-18 are new. Claim 7 is cancelled. Claims 1-6, 8-18 are presented for examination on the merits for patentability.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/19/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
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.
Claims 5 and 12 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 5 requires non-polymeric carrier, but also recites pegylated fatty acids and pegylated vegetable oils. As such, the vegetable oils and fatty acids are attached to polyethylene glycol (PEG), which is a synthetic water-soluble polymer, which makes the metes and bounds of the claim unclear.
Claim 12 is indefinite due to the absence of period at the end of the claim. It is therefore unknown if the claim ends after the recitation of “glyceryl behenate” or if additional features have been left out. As such, the claim is rejected. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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.
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.
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(a) 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 1-6, 8-11, 13 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Nart et al. (Of record), hereinafter Nart, in view of Barlow et al. (US 2011/0269717 A1), hereinafter Barlow.
Nart discloses a study employing carnauba wax for sustained release of two highly soluble compounds, captopril and metformin hydrochloride, in mini-tablet form and teaches two different technological approaches: matrix and reservoir (p. 251, L. Col). These mini-tablets are an excellent platform for sustained release formulations, which is the same as prolonged release formulations. Mini-tablets present other advantages, such as low risk of gastrointestinal tract irritation, reduced variability of drug absorption and low risk of dose dumping, as well as high flexibility of dose adjustment, ease of production etc. (p. 251, L. Col).
Regarding Claims 1, 8, and 15, Nart teaches melt granulation of the drug with carnauba wax, wherein Carnauba wax was melted at 60 °C, and the drug slowly added and stirred until a disperse and homogenous mixture was achieved; the solidified dispersion was manually grounded through a 1000 µm sieve to homogenize the particle size of the granules, which necessarily embeds the caffeine in the continuous phase (Section 2.2.1). Nart teaches the composition of the actives and the carnauba wax as follows, reading on the claimed amounts:
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Minitablets were prepared (Sections 2.2.1.2 and 2.2.1.3). Captopril and metformin hydrochloride were selected as model drugs by Nart because they are water-soluble drugs and are known to be rapidly absorbed following oral administration (p. 251, L. Col).
Nart is silent on the caffeine.
Barlow relates the invention of compositions and methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis via modulation of angiotensin activity by using a modulator alone or in combination with another angiotensin modulator, a neurogenic agent, a neurogenic sensitizing agent, or an with anti-astrogenic agent [0002]. The compositions and methods are useful for the prevention and treatment of central and peripheral nervous systems diseases, disorders, conditions and injuries such as treating neurodegenerative disorders, neurological trauma, depression, anxiety, mood disorders etc. In some embodiments, the angiotensin modulator is an angiotensin-converting enzyme (ACE) inhibitor, and is administered in combination with one or more non-selective phosphodiesterase (PDE) inhibitors [0011]. In preferred embodiments, the ACE inhibitor is selected from a group that includes captopril, and the PDE inhibitor is selected from a group that includes caffeine [0014]. In a more preferred embodiment, The preferred ACE inhibitor/non-selective PDE inhibitor combinations are: captopril and ibudilast, captopril and theophylline, captopril and caffeine [0015]. Barlow expressly teaches a dose-response curve showing the synergistic effect of the combination of captopril and caffeine on neuronal differentiation compared to the effect of either agent alone ([0053]-[0054]; Figs. 20-21; Examples 20-21; Claim 10).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to combine the teachings of Nart and Barlow, and prepare the sustained release mini-tablet formulation comprising captopril of Nart and add caffeine in the formulation. One would have been motivated to do so when treating central and peripheral nervous system diseases and conditions listed supra because Barlow has taught the synergistic effect of using the combination of captopril and caffeine on neuronal differentiation, and that the compositions are useful for treating the said conditions/diseases.
Regarding Claims 1-5, Nart teaches the concentration of the captopril active at 55.6% and 75%, and the carnauba wax at 44.4% and 25%, with no other additional ingredients (Table 1). Barlow teaches captopril:caffeine ratio of 1:100, 1:31, 1:10, 1:3, 1:1, 3:1, and 10:1 (Example 21). As such, one would start with the concentrations taught by Nart, and modify to include the amount of caffeine according to the ratio taught by Barlow. For example, one would start at the calculated EC50 for captopril and caffeine which resulted in a synergistic combination at 0.156 µM each, i.e.1:1 ratio (Example 20). This means that the active in Nart would be adjusted to 27.8% captopril, and 27.8% caffeine, which is within the claimed range in Claim 1. This can be adjusted up to 55.04% caffeine and 0.56% captopril for the captopril:caffeine ratio of 1:100; at ~55% caffeine, Nart is still within the claimed weight of caffeine in the formulation.
Nart teaches the release profiles for other actives captopril and metformin (Figs. 2 and 3). Regarding the release of captopril and caffeine, Barlow teaches that the pharmaceutical compositions may also be formulated in a sustained release or quick release formulation, making it compatible with Nart [0187]. Barlow further teaches that the pharmaceutical carriers are preferably chosen based upon the intended mode of administration of an angiotensin agent, optionally in combination with one or more other neurogenic agents, neurogenic sensitizing agent or anti-astrogenic agent [0186].
For compositions comprising, for example, 1:100 captopril:caffeine active in carnauba wax, it would be within reason to expect that the release rate would be the same as claimed because the 1% captopril is not expected to negatively impact the release of caffeine and vice versa. As such, the prior art composition must necessarily have the characteristics claimed in Claim 1. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Because there is no other components, the prior art reads on the feature of Claims 2 and 3, wherein the continuous phase comprising 0% of one or more excipients.
Regarding Claim 6, Nart recognizes other excipients in the sustained release formulation, teaching that addition of other excipients in the formulations’ composition allowed the production of mini-tablets with good mechanical strength (Section 2.2.1; Table 2; Conclusion). Nart expressly teaches mixing lubricant to the powder blend prior to compression (Section 2.2.1.2)
Regarding Claim 9, Nart teaches manually grinding the mixture of wax and drug, and sieving through a 1000 µm sieve, which would give granules within the claimed range (Section 2.2.1.1).
Regarding Claim 10, Nart teaches minitablets (Section 2.2.1).
Regarding Claim 11, Nart teaches compositions comprising carnauba wax also comprises stearic acid (Section 2.2.1.2; Table 2).
Regarding Claim 13, Nart also teaches sieving the mixture through 850 µm sieve, which would allow particles less than 850 µm to pass through (Section 2.2.1.2).
Regarding Claims 16-18, these claims depend from Claim 6, which recites the excipients lubricant, diluent, fillers, binders etc. in the alternative. Nart has already met the required excipient by teaching lubricant, and as such, Claims 16-18 are also rendered obvious.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Nart in view of Barlow with Muzikova et al. (Of record), hereinafter Muzikova.
Nart does not teach glyceryl behenate.
Muzikova teaches that lipophilic matrix systems are cheap, easy to prepare and chemically inert; they contain various fat alcohols, waxes and fats, e.g., cetyl alcohol, glyceryl dibehenate, and carnauba wax (p. 91, 1st paragraph). Muzikova discloses the compressibility of tableting materials with different types of binders and various concentrations of glyceryl behenate (C – Compritol 888 ATO) (pp. 91-92). Muzikova teaches that addition of glyceryl dibehenate exerts different impacts on the strength of tablets, with increasing concentration to 20 % increases the strength (Fig. 1; p. 94, last paragraph to p. 95). Muzikova teaches that the release rate of the active substance decreases with increasing content of glyceryl dibehenate (Abstract; p. 97).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to combine the teachings of Muzikova to that of Nart and use glyceryl behenate as carrier, replacing the carnauba wax of Nart. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. See MPEP 2143. In this case, Nart would replace the carnauba wax with glyceryl behenate to increase the strength of the table formulation, and to optimize the prolonged release of the actives.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Nart in view of Barlow, as applied to Claim 1 above, and in further view of Acharya (Of record), hereinafter Acharya.
Nart does not expressly teach the claimed particle size is in the range of particle size of 150 to 250 microns.
Acharya is in the field of caffeine formulation, and teaches a formulation comprising a particulate system comprising caffeine (Claim 1). Acharya teaches pulsed release formulation, and in certain cases, the formulation also has continuous release of caffeine over 2 to 8 hours interval, which encompasses the prolonged release limitation (p. 14).
Acharya recognizes preparing particulate system by different methods, inter alia melt granulation (p. 13). The particle size of the particulate system is in the range of 100 to 1500 micron, preferably in the range of 300 to 750 micron (p. 13). The range overlaps with the range of Nart and that of instant Claims 13-14. 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. Furthermore, particle size is an experimental parameter considered to be a result-effect variable that is within the skill of the ordinary artisan to modify and is commonly carried out in the art as part of routine optimization in formulations; the prior art is evidence to this. It would have been obvious to make a caffeine formulation having granules of particle size within that taught by Acharya and Nart before the effective filing date because the ordinary skilled artisan knew that such claimed size would work for continuous release of caffeine. The references are in the same field of endeavor and they provide a reasonable expectation of success.
Response to Remarks:
Applicant traverses the 103 rejection over Nart in view of Joy, remarking that caffeine has a different mechanism of action and different pharmacodynamics than captopril and metformin, and therefore would not be motivated to use the same release profile of these compounds.
Applicant’s arguments have been considered but are not persuasive. First, the new ground of rejection necessitated by the amendment does not rely on Joy for any teaching or matter specifically challenged in the argument. Second, it appears that one of Applicant’s main contention in the response is the cited rejections are drawn to a basis of obviousness with a different reason or motivation. See In re Kemps, 97 F.3d 1427, 1430 (Fed. Cir. 1996)(“[T]he motivation in the prior art…does not have to be identical to that of the applicant to establish obviousness.” Applicant is further reminded that “[i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls… [A]ny need or problem known in the field of endeavor at the time of the invention and addressed by the patent can provide a reason for combining the elements in the manner claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419-20 (2007). In this case, Bartow showcases a combination of caffeine and captopril as disease treatment, and shows synergistic effect in neuronal differentiation. One would be motivated to incorporate caffeine in the formulation of Nart for a treatment that requires formation of new nerve cells.
Applicant appears to argue that Nart is intended for highly soluble drugs alone and that Nart aimed to employ carnauba wax associated to polymeric ethyl cellulose or Kollicoat SR 30D (polyvinyl acetate dispersion) to sustain the drug release of two highly soluble compounds. According to Applicant, a person of ordinary skill in the art would include the polymer/s in a sustained release formulation based on Nart. Applicant argues improper use of hindsight by the Examiner.
The Examiner traverses this argument. Nart teaches captopril release profile; Bartow teaches the combination of captopril and caffeine has synergistic effect in stimulating neurogenesis; Bartow welcomes immediate release or sustained release formulation of its compositions. Therefore, one would add caffeine to the captopril formulation of Nart to obtain a prolonged release.
Regarding the use of polymers, a preferred embodiment does not constitute a teaching away from other embodiments disclosed within the four corners of the reference, including non-preferred embodiments. Applicant is reminded that the disclosure of a reference must be considered as expansively as is reasonably possible to determine the full scope of the disclosure and, as a result, is most certainly most not limited to that which is preferred. Thus, the fact that polymers are taught in addition to carnauba wax does not negate or direct the artisan away from the broader teaching of the reference, which expressly provides for, and, thus, clearly contemplates the use of non-polymeric carnauba wax alone as instantly claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANICE Y SILVERMAN whose telephone number is (571)272-2038. The examiner can normally be reached M-F, 10-6 EST.
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/J.Y.S./Examiner, Art Unit 1792
/ERIK KASHNIKOW/Supervisory Patent Examiner, Art Unit 1792
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