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
The Applicant’s reply filed on 6/17/26 is acknowledged. Claims 1, 2, 4-7, 10-20 are pending. Claims 16-20 have been withdrawn. Claims 1 and 14 have been amended. Claims 1, 2, 4-7 and 10-15 are under consideration.
Rejections Withdrawn
The rejection of Claims 1-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amended claims.
Rejections Maintained and New Grounds of Rejections
Information Disclosure Statement
Acknowledgement is made of Applicant’s information disclosure statements (IDS) submitted on 7/1/26. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 of this title, 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 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 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, 2, 4-7, 10-12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Vepuri et al. (US 2016/0128943; cited previously).
Vepuri et al. teach formulations comprising a combination of extended release components, rapid release components, immediate release components, and delayed release components which are combined to provide caffeine dosage forms having the desired release profile and/or pharmacokinetic parameters (e.g. paragraph 0024).
Vepuri et al. teach an oral tablet formulation, comprising:
a first component comprising caffeine (i.e. a xanthine derivative); and
a second component comprising caffeine and EUDRAGIT L100 (i.e. a xanthine derivative and an enteric excipient)(e.g. Examples, paragraph 0078; Claim 1).
Vepuri et al. teach that the coating may comprise zein (e.g. paragraph 0086, 0097; Claim 17). Vepuri et al. do not teach an amount of zein, but they exemplify a second component comprising caffeine and Eudragit L-100 at 8 wt% (i.e. a xanthine derivative and an enteric excipient)(e.g. Example 6, Batches 176 and 177). It would have been obvious to one of ordinary skill in the art at the time of filing to replace the Eudragit L-100 of Batches 176 and 177 with zein, as Vepuri et al. teach them to be suitable polymers (e.g. paragraphs 0086 and 0097). In addition, as Vepuri et al. do not teach a general concentration range for polymers, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to vary the zein concentration through routine experimentation to arrive at the concentration of 5.5-10% in order to optimize the resulting product.
Regarding the release profiles, Vepuri et al. teach that a dissolution of the composition releases 25-70% of the caffeine within about 30 minutes to about 3 hours post-administration, at least about 75% of the caffeine is released within about 4 hours post-administration, at least about 90% of the caffeine is released within about 5 hours post-administration, at least about 95% of the caffeine is released within about 6 hours post-administration, and about 100% of the caffeine is released within about 7 hours post-administration (e.g. Claim 7), and further that the first component provides for an immediate release of up to about 50% of the total caffeine within about one hour after administration under physiological conditions, and wherein the second component provides release of the remaining caffeine that is delayed until at least 3 hours after administration, and release occurs up to about 8 hours after administration under physiological conditions (e.g. claim 9). These values refer to the total caffeine concentration of the formulation as a whole, and Vepuri otherwise does not distinguish between release from the first or second compositions versus release from the composition as a whole. However, in Table 2 in paragraph 0125, Lot #52-180/D releases 51% of the caffeine by 1 hr. Lot #52-180/D is provided in paragraph 0123 and comprises a tablet core of 200 mg caffeine and an immediate release layer of 200 mg of caffeine. If 51% of the total caffeine is released in the first hour and 50% of the caffeine is contained in the outer immediate release later (i.e. first composition), then 100% of the caffeine in the first layer is released in the first hour. Additionally, Lot #52-180/D releases 71% of the caffeine by 3 hr. If 71% of the total caffeine is released in the first hour and 50% of the caffeine is contained in the outer immediate release later (i.e. first composition), then 100% of the caffeine in the first composition is released and the remaining 21% is that of the core (i.e. second composition), which would be 42% of the second composition (math: 71% of 400 mg is 284 mg, which leaves 84 mg of the second composition, and 84/200 is 42%), which is slightly below the claimed range of 50 by weight or more. Additionally, Lot #52-180/D releases 98% of the caffeine by 8 hr. If 98% of the total caffeine is released in the first hour and 50% of the caffeine is contained in the outer immediate release later (i.e. first composition), then 100% of the caffeine in the first composition is released and the remaining 48% is that of the core (i.e. second composition), which would be 96% of the second composition (math: 98% of 400 mg is 392 mg, which leaves 192 mg of the second composition, and 192/200 is 96%).
Regarding Claims 1, 2, 4 and 5, the profiles disclosed by Vepuri et al. overlap or are adjacent to the claimed release profiles. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (MPEP 2144.05.I). In addition, Vepuri et al. teach that one or more loading dosages can be prepared by creating coated or multilayer coated capsules or tablets, where the rate of dissolution will depend on a number of factors, in some cases including the particular nature of the film-forming polymer and the encapsulated material (e.g. paragraphs 0090). It would have been obvious to one of ordinary skill in the art at the time of filing to vary the tablet composition and therefore vary the rate of dissolution in order to optimize the resulting product to achieve a desired dissolution rate in order to provide caffeine dosage forms having the desired release profile and/or pharmacokinetic parameters. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding Claim 6, Vepuri et al. teach the composition may be a bilayered tablet (e.g. paragraphs 0067-0071, 0108).
Regarding Claim 7, Vepuri et al. exemplify a tablet comprising 320 mg of a first composition 312 mg of a second composition, resulting in a ratio of 1:1.03, which is within the claimed range (e.g. Example 1).
Regarding Claims 10-12, Vepuri et al. teach a coated tablet form having two loading dosage layers and a total loading dosage of 250 mg of caffeine, the outermost/first-most loading dosage layer could contain 200 mg with the second loading dosage layer containing 50 mg (e.g. paragraph 0108).
Regarding Claim 15, Vepuri et al. teach the initial peak blood plasma concentration is reached within about one hour after administration (e.g. paragraph 0112, Claim 29).
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Vepuri et al. (US 2016/0128943; cited previously), as applied to claims 1, 2, 4-7, 10-12 and 15, and further in view of Dulloo et al. (Am J Clin Nutr. 1999 Dec;70(6):1040-5)) and Folger et al. (US 2013/0084332).
Regarding Claims 1, 2, 4-7, 10-12 and 15, the teachings of Vepuri et al. are described supra. Vepuri et al. further teach that the compositions may comprise polyvinylpyrrolidone, microcrystalline cellulose, crospovidone, magnesium stearate and silicon dioxide (e.g. paragraphs 0086, 0088, 0090, 0092, 0094, 0099, 0100, 0101 and 0104; Examples). In addition, a mixture of hydroxypropyl methyl cellulose, triacetin and talc are taught as coating ingredients by Vepuri et al. (e.g. paragraphs 0076, 0084, 0086, 0088, 0092, 0094, 0097; Examples).
Vepuri et al. do not teach the inclusion of green tea extract, wherein the green tea extract includes the xanthine derivative, or the inclusion of medium chain triglyceride. This is made up for by the teachings of Dulloo et al. and Folger et al.
Dulloo et al. investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans (e.g. abstract). Dulloo et al. investigated 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo. Dulloo et al. concluded that green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both (e.g. abstract).
Folger et al. teach taste masked multi-layered particles an inert core, one or more coating layer(s) comprising a pharmaceutically active ingredient (e.g. abstract). Folger et al. teach that the active may be a xanthine derivative (e.g. paragraph 0007, 0138). Folger et al. teach that the composition comprises medium chain triglycerides as an additional ingredient (e.g. paragraph 0207; Claim 23). Folger et al. teach that the composition is a tablet (e.g. Claims 52 and 54).
It would have been obvious to one of ordinary skill in the art at the time of filing to select green tea extract as the source of caffeine for the tablets of Vepuri et al. One of ordinary skill in the art would have predicted success as green tea comprises caffeine and would have been motivated to obtain the additional benefits of thermogenesis and fat oxidation. It further would have been obvious to one of ordinary skill in the art at the time of filing to include the medium chain triglycerides of Folger et al. for use in the composition of Vepuri et al. It would have been obvious to one of ordinary skill in the art to combine the elements as claimed by known methods with no change in their respective functions, and the combination yielding nothing more than predictable results. One of ordinary skill in the art would have predicted success as both Vepuri and Folger teach tablets comprising xanthine derivatives and overlapping excipients. Simple substitution of one known element for another to obtain predictable results is obvious.
Response to Arguments
Applicant's arguments filed 6/17/26 have been fully considered but they are not persuasive.
Applicant argues that Vepuri teaches that its extended release core is encapsulated within one or more coating layers (see examples 1-4 in Vepuri). From the examples in Vepuri, it teaches that in a formulation with a total caffeine content of 400 mg, at least 200 mg of caffeine is encapsulated in the outermost layer. From FIGs. 1 -2 of Vepuri, it can also be understood that the formulation taught in Vepuri releases approximately 50% of the caffeine in the first hour, then experiences a release plateau between one and three hours (the percentage of caffeine released no longer increases), and only resumes release after three hours. Clearly, in terms of the terminology of the present application, the "first composition" in Vepuri releases approximately 50% of the caffeine in the first hour, and the "second composition" in Vepuri does not start to release any caffeine until after three hours later. Therefore, it is believed that Vepuri cannot achieve the technical effect of the present invention whereby the first composition releases 80% by weight or more of the xanthine derivative within 1 hour, and the second composition (having zein enteric coating) releases 50% or more of the xanthine derivative within three hours.
This is not found persuasive. Applicant has claimed the release profile based on a percentage of a “first” and “second” composition, while Vepuri disclose the release profile based on the total composition. When accounting for the percentage of caffeine in the first and second compositions, the profiles of Vepuri are within, overlap, or are substantially similar to the claimed release profile. As described supra, in Table 2 in paragraph 0125, Lot #52-180/D releases 51% of the caffeine by 1 hr. Lot #52-180/D is provided in paragraph 0123 and comprises a tablet core of 200 mg caffeine and an immediate release layer of 200 mg of caffeine. If 51% of the total caffeine is released in the first hour and 50% of the caffeine is contained in the outer immediate release later (i.e. first composition), then 100% of the caffeine in the first layer is released in the first hour. In addition, Vepuri teach that “[i]t is an object of the present invention to provide a caffeine formulation having an initial immediate release of caffeine, followed by a controlled release of product to maintain the levels over time in the body as the caffeine is metabolized and excreted.” Vepuri et al. teach that one or more loading dosages can be prepared by creating coated or multilayer coated capsules or tablets, where the rate of dissolution will depend on a number of factors, in some cases including the particular nature of the film-forming polymer and the encapsulated material (e.g. paragraphs 0090). It would have been obvious to one of ordinary skill in the art at the time of filing to vary the tablet composition and therefore vary the rate of dissolution in order to optimize the resulting product to achieve a desired dissolution rate in order to provide caffeine dosage forms having the desired release profile and/or pharmacokinetic parameters. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Applicant further argues that referring to Preparation Example B3 (Ex3), when a weight proportion of the zein enteric coating as the enteric excipient is 3% by weight of the second composition (as shown in Table 2), it cannot effectively achieve the controlled- release effect. Applicant concludes that Vepuri failed to teach the importance of controlling the amount of zein enteric coating in the second composition, and failed to teach the same dissolution profiles, Applicant believes that Vepuri cannot achieve the same superior properties.
This is not found persuasive. Vepuri does not teach 3% of a zein coating. Vepuri et al. teach that the coating may comprise zein (e.g. paragraph 0086, 0097; Claim 17), and while they do not recite an amount thereof, they exemplify a second component comprising caffeine and Eudragit L-100 at 8 wt% (i.e. a xanthine derivative and an enteric excipient)(e.g. Example 6, Batches 176 and 177). It would have been obvious to one of ordinary skill in the art at the time of filing to replace the 8% Eudragit L-100 of Batches 176 and 177 with 8% zein, as Vepuri et al. teach them to be suitable polymers (e.g. paragraphs 0086 and 0097). In addition, 52-180/D exemplifies approximately 7.7% Eudragit L-100 based on the weight of the second composition. In addition, as Vepuri et al. do not teach a general concentration range for polymers, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to vary the zein concentration through routine experimentation to arrive at the concentration of 5.5-10% in order to optimize the resulting product.
Conclusion
No claim is 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLE PLOURDE BABSON whose telephone number is (571)272-3055. The examiner can normally be reached M-Th 8-4:30; F 8-12:30.
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/NICOLE P BABSON/ Primary Examiner, Art Unit 1619
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