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 .
Applicant’s arguments, filed 10/17/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Election/Restrictions
Newly submitted claims 21-24, directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Original claims 1-20, drawn to a method of manufacturing a creatine supplement, classified in A61K 9/16.
Newly added claims 21-24, drawn to a coated creatine supplement, classified in A61K 9/0095.
The inventions are independent or distinct, each from the other because:
The two inventions are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make another and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP 806.05(f)). In the instant case the process as claimed for making a co-granulated supplement can be used to make another materially different product, such as a co-granulated and coated non-creatine pharmaceutical.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search burden and/or examination burden if restriction were not required because one or more of the following reasons apply:
The inventions have acquired a separate status in the art in view of their different classification.
The inventions have acquired a separate status in the art due to their recognized divergent subject matter.
The inventions require a different field of search (e.g., searching different classes /subclasses or electronic resources, or employing different search strategies or search queries).
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 21-24 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Status
Claims 1-10 and 21-36 are pending.
Claims 21-24 are withdrawn.
Claim Rejections - 35 USC § 112(a) or pre-AIA 1st ¶ - New Matter
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 1-10 and 25-36, 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.
Claim 1 recites “at least 2% by weight gamma cyclodextrin.” The full range of this limitation does not appear to be supported by the instant specification where cyclodextrins are recited to range from 0-10 wt% (see ¶ 19). Here, at least 2 wt% includes amounts above 10 wt%, which does not appear to be supported in the original disclosure.
Claim 6 recites “at least 75% by weight disodium phosphocreatine.” The full range of this limitation does not appear to be supported by the instant specification where disodium phosphocreatine is recited to range from 75-95 wt% (see ¶ 57). Here, at least 75 wt% includes amounts above 95 wt%, which does not appear to be supported in the original disclosure.
Claim 6 also recites “at least 2% by weight polyethylene glycol.” The full range of this limitation does not appear to be supported by the instant specification where polyethylene glycol is recited to range from 0-10 wt% (see ¶¶ 17, 57). Here, at least 2 wt% includes amounts above 10 wt%, which does not appear to be supported in the original disclosure.
Claim 6 also recites “at least 5% gamma cyclodextrin.” The full range of this limitation does not appear to be supported by the instant specification where cyclodextrins are recited to range from 0-10 wt% (see ¶ 19). Here, at least 5% includes amounts above 10 wt%, which does not appear to be supported in the original disclosure.
Claim 25 recites “at least 75% by weight distribution disodium phosphocreatine.” The full range of this limitation does not appear to be supported by the instant specification where disodium phosphocreatine is recited to range from 75-95 wt% (see ¶ 57). Here, at least 75 wt% includes amounts above 95 wt%, which does not appear to be supported in the original disclosure.
Claim 25 also recites “at least 2% by weight of gamma cyclodextrin.” The full range of this limitation does not appear to be supported by the instant specification where cyclodextrins are recited to range from 0-10 wt% (see ¶ 19). Here, at least 2 wt% includes amounts above 10 wt%, which does not appear to be supported in the original disclosure.
Claim 32 recites a method comprising “coating disodium phosphocreatine” and then “co-granulating the coated creatine compound.” This method does not appear to have support in the instant specification where it appears that every recitation of the method involves the active steps of co-granulating disodium phosphocreatine with gamma cyclodextrin to form a granular composition, and then coating the granular composition with a methacrylate copolymer (see original claims 1, 12, 17, 18, ¶¶ 21, 58, 59). Here, while co-granulating and then coating appears to have support, coating and then co-granulating do not.
Claim 32 also recites “at least 2% by weight gamma cyclodextrin.” The full range of this limitation does not appear to be supported by the instant specification where cyclodextrins are recited to range from 0-10 wt% (see ¶ 19). Here, at least 2 wt% includes amounts above 10 wt%, which does not appear to be supported in the original disclosure.
Claims 2-5, 7-10, 26-31, and 33-36, are also rejected for the same reasons for depending upon independent claims 1, 25, and 32.
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
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 is 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 6 recites “at least 5% gamma cyclodextrin,” and it is unclear if the 5% is intended to be by weight, volume, mass, etc. For purposes of examination, the claim is interpreted as 5% by weight, consistent with the percentages for components (i) and (ii).
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 (i.e., changing from AIA to pre-AIA ) 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.
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, 2, 3, 9, 10, 25, 27, 28, and 30-34, are rejected under 35 U.S.C. 103 as being unpatentable over Vilallobos (US 20100055178 A1, cited on IDS dated 01/23/2023), in view of Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25, cited on IDS dated 01/23/2023), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004, cited on IDS dated 09/06/2023), Hans et al (US 20150133552 A1), and Byrd (US 20060062849 A1, cited on IDS dated 01/23/2023), as evidenced by Antony (US 20170173100 A1, cited on IDS dated 09/06/2023).
Vilallobos teaches enteric coated creatine compositions for supplementing dietary creatine and facilitating creatine absorption (abs, ¶ 31). The compositions may be prepared according to any method known in art for the manufacture of pharmaceutically acceptable composition, including granulation (¶¶ 18, 21). The resulting dosage forms are coated after the granulation/mixing (ex. 1). The composition may be provided as a tablet, capsule, pellet, microbead, etc., wherein the creatine can be creatine monohydrate, creatine phosphate, etc. (abs). For oral administration, excipients including starch, etc., can be included (¶ 18). The enteric coating method involves spraying the coating agent using a fluidized bed, and is taught by be a dry coating method (¶ 26). The creatine supplements can be used to increase strength and lean body mass (¶¶ 1, 15). The enteric coating may be EUDRAGIT polymers (¶ 28). As evidenced by Antony (US 20170173100 A1), EUDRAGIT polymers are methacrylate copolymers (¶ 78). The coating stabilizes the formulations comprising creatine (¶ 26).
Vilallobos does not teach disodium phosphocreatine, cyclodextrin nor its amounts, an average particle size from 150-850 microns, specifically co-granulating creatine and cyclodextrin, an embodiment as instantly claimed comprising those of claims 2 and 33, an embodiment further comprising alpha or beta cyclodextrin, nor an embodiment as instantly claimed spray dried by fluidized bed technique.
Tricarico et al teaches it was known that disodium phosphocreatine prevents the increase of muscle ion conductance due to muscle reperfusion by preloading the muscle fibers with ATP (abs). The pretreatment of rats with disodium phosphocreatine loaded the extensor digitorum longus muscle with extra ATP, prevented the increase of the total membrane conductance as well as the fiber depolarization and restored the excitability of the fibers (pg. 23 1st col 1st ¶). Treatment with phosphocreatine di-L-arginine did not retore the resting potential nor the threshold current of the ischemic reperfused fibers (pg. 21 2nd col 2nd ¶).
Tricarico et al do not teach cyclodextrin nor its amounts, an average particle size from 150-850 microns, specifically co-granulating creatine and cyclodextrin, nor an embodiment as instantly claimed spray dried by fluidized bed technique.
Fenyvesi teaches inclusion of cyclodextrin in food products and nutraceuticals to improve taste, solubility, stability, and bioavailability (see entire document). The cyclodextrins include alpha, beta, and gamma cyclodextrins (abs).
Fenyvesi does not teach the amount of cyclodextrin nor an average particle size from 150-850 microns.
Hans et al teach powder blends and effervescent tablets comprising creatine monohydrate and gamma cyclodextrin, where gamma cyclodextrin was included at 3.00, 3.50, and 5.00 wt% (ex. F25). Cyclodextrins such as alpha- beta- and/or gamma-cyclodextrin can be included (¶ 177, ex. F25).
Hans et al do not teach the particle size from 150-850 microns.
Byrd teaches it was known to grind creatine formulations to desired particle size for oral formulations that can be more readily formed into tablets (¶¶ 56, 67). The particle sizes ranged from 18 to 60 sieve (i.e., 250-1000 microns) (¶ 46). A typical formulation contains about 70-90 wt% creatine (¶ 50).
Regarding the disodium phosphocreatine of claim 1, it would have been obvious to modify the composition made obvious above by selecting disodium phosphocreatine as the creatine, where phosphocreatine was taught to be suitable by Vilallobos, and where disodium phosphocreatine was known to provide muscles with extra ATP, prevents the increase of total membrane conductance as well as the fiber depolarization and restores the excitability of the fibers, as taught by Tricarico et al.
Regarding gamma cyclodextrin of claim 1, it would have been obvious to further include gamma cyclodextrin to the creatine supplement of Vilallobos, in order to improve the solubility, stability, and bioavailability of the creatine supplement of Vilallobos, where it was known from Fenyvesi to improve such properties in food products and nutraceuticals, and were Vilallobos is directed to formulations for facilitating the absorption of creatine (i.e., bioavailability).
Regarding the wt% of gamma cyclodextrin of claim 1, it would have been obvious to include gamma cyclodextrin at 3.00, 3.50, and 5.00 wt%, which are amounts that were known to be used in formulations comprising creatine, as taught by Hans et al, where all are directed to supplement formulations, thus arriving at the claimed invention. 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 the particle size of claim 1, it would have been obvious to formulate the creatine supplement composition with known particle sizes suitable for granular creatine formulations, such as from 18 to 60 sieve (i.e., 250-1000 microns), as taught by Byrd.
Regarding the active steps of claim 1, it would have been obvious to use known methods of formulating creatine supplements, including granulating the components together (i.e., co-granulating) and then coating the granular composition with a coating, such as EUDRAGIT, in order to stabilize the formulations comprising creatine, as taught by Vilallobos.
Regarding claims 2 and 33, it would have been obvious to further include starch prior to coating, where starch is taught by Vilallobos as part of the tablet, capsule, pellet or microbead, prior to coating.
Regarding claims 3, 27, and 34, it would have been obvious to further include at least one of alpha or beta cyclodextrin, where Hans et al teach blends of cyclodextrins are suitable for compositions comprising creatine compounds.
Regarding claim 9, it would have been obvious to spray dry the granular compound utilizing a fluidized bed technique, as taught by Vilallobos.
Regarding claims 10, 30, and 31, where the claims are directed to a method of manufacturing a creatine supplement, the use of the resulting composition for treating a muscle wasting disorder and enhancing body mass, is intended use. As such, where the method of preparing the creatine supplement as claimed is made obvious above, and where Vilallobos teaches the creatine supplement can be used to increase strength and lean body mass, it would be expected that the creatine supplement would be capable of the claimed intended uses.
Regarding disodium phosphocreatine of claim 25, it would have been obvious to modify the composition made obvious above by selecting disodium phosphocreatine as the creatine, for the same reasons discussed above by Vilallobos and Tricarico et al.
Regarding gamma cyclodextrin of claim 25, it would have been obvious to further include gamma cyclodextrin to the creatine supplement of Vilallobos, for the same reasons discussed above by Fenyvesi et al.
Regarding the wt% disodium phosphocreatine of claim 25, it would have been obvious to modify the combination discussed above, by formulating the creatine supplement comprising 70-90 wt% creatine, as taught by Byrd, where all are directed to supplement formulations, thus arriving at the claimed invention. 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 the wt% of gamma cyclodextrin of claim 25, it would have been obvious to include gamma cyclodextrin at 3.00, 3.50, and 5.00 wt%, for the same reasons discussed above by Hans et al.
Regarding the active steps of claim 25, it would have been obvious to use known methods of formulating creatine supplements, including granulating the components together (i.e., co-granulating), as taught by Vilallobos for the same reasons discussed above.
Regarding claim 28, it would have been obvious to coat the granular composition with a coating, such as EUDRAGIT (methacrylate copolymer), in order to stabilize the formulations comprising creatine, as taught by Vilallobos.
Regarding claim 32, it would have been obvious to formulate a creatine supplement comprising disodium phosphocreatine as taught by Tricarico et al, gamma cyclodextrin as taught by Fenyvesi et al, in amounts of 3.00, 3.50, and 5.00 wt% as taught by Hans et al, with a particle size ranging from 18 to 60 sieve (i.e., 250-1000 microns) as taught by Byrd, for the same reasons discussed above.
Regarding the active steps of claim 32, where Vilallobos teaches creatine may be coated with EUDRAGIT, a methacrylate copolymer, and further teaches components can be mixed via granulation, it would have been obvious for the skilled artisan to coat the disodium phosphocreatine made obvious above in order to stabilize the creatine prior to granulating with gamma cyclodextrin. Selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. See MPEP 2144.04(IV)(C).
Claims 2, 6, 7, 26, and 33, are rejected under 35 U.S.C. 103 as being unpatentable over Vilallobos (US 20100055178 A1, cited on IDS dated 01/23/2023), Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25, cited on IDS dated 01/23/2023), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004, cited on IDS dated 09/06/2023), Hans et al (US 20150133552 A1), and Byrd (US 20060062849 A1, cited on IDS dated 01/23/2023), as applied to claims 1, 2, 3, 9, 10, 25, 27, 28, and 30-34 above, and further in view of Daugherty (US 20080306159 A1).
The references are discussed above but does not teach polyethylene glycol nor its amounts.
Daugherty et al teaches an oral creatine supplement comprising creatine and polyethylene glycol, coated with an enteric coating, where the data from the present study indicates that association of polyethylene-glycol (PEG) with the creatine molecule permits creatine it to be more effectively taken up by muscle cells (abs, ¶¶ 12, 52). A creatine to PEG ratio of 99:1 to 50:50, preferably 95:5 to 90:10 by weight, is taught (¶ 13). The most preferable PEGs have an average molecular weight from 3150 to 3685, with the most preferred formulation comprising PEG 3350 (abs, ¶ 23).
Daugherty et al do not teach a single embodiment with the wt% of the components of claim 6.
Regarding claims 2, 6, and 33, it would have been obvious to further include polyethylene glycol, where polyethylene glycol was known to permit creatine to be more effectively taken up by muscle cells, as taught by Daugherty et al.
Regarding the amounts of claim 6, it would have been obvious to modify the combination discussed above, by formulating the creatine supplement comprising 70-90 wt% disodium phosphocreatine, as taught by Byrd, PEG in a creatine to PEG weight ratio from 99:1 to 50:50 (resulting in a range from 0.7-45 wt% PEG), as taught by Daugherty, gamma cyclodextrin at 3.00, 3.50, and 5.00 wt%, which are amounts that were known to be used in formulations comprising creatine, as taught by Hans et al, where all are directed to supplement formulations, thus arriving at the claimed invention. 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).
Further, a skilled artisan would find it obvious to optimize the amount of the individual components in order to achieve desired dosing and effect for the creatine supplement. 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. See MPEP 2144(II)(A).
Regarding claim 7, it would have been obvious to select PEG 3350 as the polyethylene glycol made obvious above, where Daugherty et al teach PEG 3350 is the most preferably polyethylene glycol for the creatine formulations.
Regarding claim 26, it would have been obvious to further include polyethylene glycol, where polyethylene glycol was known to permit creatine to be more effectively taken up by muscle cells, as taught by Daugherty et al.
Claims 4, 29, and 35, are rejected under 35 U.S.C. 103 as being unpatentable over Vilallobos (US 20100055178 A1, cited on IDS dated 01/23/2023), Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25, cited on IDS dated 01/23/2023), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004, cited on IDS dated 09/06/2023), Hans et al (US 20150133552 A1), and Byrd (US 20060062849 A1, cited on IDS dated 01/23/2023), as applied to claims 1, 2, 3, 9, 10, 25, 27, 28, and 30-34 above, and further in view of Krauter (EVONIK, Health Care, 2015, pp. 1-2), as evidenced by Curcio et al (Pharmaceuticals, 2020, 13(6), 131, pp. 1-21).
The references are discussed above but do not teach the specific methacrylate polymers of claims 4, 29, and 35.
Krauter teaches EUDRAGUARD control was a known functional polymer that is used to prevent ingredients from becoming less effective upon contact with stomach acid, allowing controlled release of the active agent in the digestive tract (5th ¶). As evidenced by Curcio et al, EUDRAGUARD control is poly(ethylacrylate-co-methyl methacrylate) (see end of pg. 2).
Regarding claims 4, 29, and 35, it would have been obvious to modify the combination made obvious above by selecting from other known enteric coatings, including EUDRAGUARD control, as taught by Krauter.
Claims 4, 5, 29, 35, and 36, are rejected under 35 U.S.C. 103 as being unpatentable over Vilallobos (US 20100055178 A1, cited on IDS dated 01/23/2023), Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25, cited on IDS dated 01/23/2023), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004, cited on IDS dated 09/06/2023), Hans et al (US 20150133552 A1), Byrd (US 20060062849 A1, cited on IDS dated 01/23/2023), and Krauter (EVONIK, Health Care, 2015, pp. 1-2), as applied to claims 4, 29, and 35 above, and further in view of Antony (US 20170173100 A1, cited on IDS dated 09/06/2023) and Patra et al (Future Jour Pharm Sci 3, 2017, pp. 33-45).
The references are discussed above but do not teach the methacrylate copolymer mixture of claims 5 and 36.
Antony is discussed above and further teaches the enteric coatings include EUDRAGIT polymers, EUDRAGUARD polymers, etc. (¶¶ 78, 252). The enteric coatings may include combinations of polymers in any possible ratio (¶ 78).
Antony does not teach the specific methacrylate copolymers of claims 4 or 5.
Patra et al teach EUDRAGIT copolymers were known enteric coatings, including EUDRAGIT E copolymers which are chemically known as poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate (intro, pg. 34 1st ¶).
Regarding claims 4, 29, and 35, it would have been obvious to modify the combination made obvious above by selecting from other known enteric coatings, such as EUDRAGIT E, which is chemically known as poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate, as taught by Patra et al.
Regarding claims 5 and 36, it would have been obvious to modify the combination made obvious above by including a mixture of known enteric coatings, such as EUDRAGIT E, as taught by Patra et al, and EUDRAGUARD control, as taught by Krauter, where Vilallobos et al teach enteric coatings and Antony teaches enteric coatings containing mixtures of polymers were known and can include EUDRAGIT and EUDRAGUARD copolymers.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Vilallobos (US 20100055178 A1, cited on IDS dated 01/23/2023), Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25, cited on IDS dated 01/23/2023), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004, cited on IDS dated 09/06/2023), Hans et al (US 20150133552 A1), Byrd (US 20060062849 A1, cited on IDS dated 01/23/2023), and Daugherty (US 20080306159 A1), as applied to claims 2, 6, 7, 26, and 33 above, and further in view of Antony (US 20170173100 A1, cited on IDS dated 09/06/2023).
The references are discussed above but do not teach an embodiment comprising the amounts of instant claim 8.
Antony is discussed above and teaches it was known to coat tablets with an enteric coating material of 5-20% (¶ 89), with specific embodiments coated until a weight gain of 5-6% (i.e., 5-6 wt%) (¶ 193).
It would have been obvious to modify the combination made obvious above, by formulating the creatine supplement comprising 70-90 wt% disodium phosphocreatine, as taught by Byrd, PEG in a creatine to PEG weight ratio from 99:1 to 50:50 (resulting in a range from 0.7-45 wt% PEG), as taught by Daugherty, cyclodextrin at 3.00, 3.50, and 5.00 wt%, which are amounts that were known to be used in formulations comprising creatine, as taught by Hans et al, and with known coating amounts used for coated supplements, such as from 5-20 wt%, including 5 wt%, as taught by Antony, where all are directed to supplement formulations, thus arriving at the claimed invention. 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).
Further, a skilled artisan would find it obvious to optimize the amount of the individual components in order to achieve desired dosing and effect for the creatine supplement. 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. See MPEP 2144(II)(A).
Response to Arguments
First, Applicants assert none of the cited art teaches or suggests the specific step of co-granulating disodium phosphocreatine with gamma cyclodextrin as recited in amended claim 1. Applicants assert Vilallobos generally teaches that creatine compositions can be granulated by provides no specific teaching regarding co-granulating with cyclodextrin. Applicants assert Fenyvesi teaches that cyclodextrin can improve taste, solubility, stability, and bioavailability in food products and nutraceutical, but does not suggest combining cyclodextrins with disodium phosphocreatine.
Second, Applicants assert that the specific co-granulation of disodium phosphocreatine with gamma cyclodextrin provides unexpected benefits that are not taught or suggested by the prior art. Applicants assert the co-granulation process seeming allows the cyclodextrin to optimally accommodate the creatine while providing optimal protection through the stomach, and the prior art teaches these components as separate additives rather than co-granulated materials with a synergistic effect. Applicants have also provided a declaration discussing the results.
Third, Applicants assert the remaining claims including Tricarico, Daugherty, Antony, and Hans et al, do not remedy the deficiency regarding the lack of teaching or suggestion for the specific co-granulation step recited in the claims.
First, respectfully, this argument is not persuasive. While Vilallobos does not teach gamma cyclodextrin, cyclodextrin was known to improve taste, solubility, stability, and bioavailability in supplemental formulations. Where Vilallobos teaches granulating the components of the tablets, etc., which can then be coated, it would have been obvious for the skilled artisan to co-granulate the disodium phosphocreatine with the gamma cyclodextrin made obvious above, where granulation was a known tablet mixing method, and the components are mixed prior to coating. Simply mixing by granulating disodium phosphocreatine with a component that was known to improve taste, solubility, stability, and bioavailability in supplemental formulations is obvious.
Second, respectfully, this argument is not persuasive. While Examiner agrees that the declaration does indicate unexpected results, the instant claims do not appear to be commensurate in scope with the data as required by MPEP 716.02(d). Applicants have the burden of explaining the results (MPEP 716(b)), but have presented no explanation as to why the present claims should be considered commensurate in scope with the present claims. Examiner is unable to locate data which supports the breadth of the instant claims. The burden of demonstrating unexpected results belongs to Applicants. Applicants must not only demonstrate an unexpected result, but also explain the result and place the claims commensurate in scope with the unexpected results. Here, Applicants rely on a single test to render claims to an oral supplement obvious. Applicants have not explained the nexus between the data and the claims do not appear to be commensurate in scope with the data provided. See MPEP 716.
Here, it appears that the working embodiment tests an unknown wt% of disodium phosphocreatine with what is recited to be a 5% addition of cyclodextrin in the declaration. While the examiner agrees that fig. 1 and table 1 show improved results with the combination of disodium phosphocreatine and cyclodextrin at 5% compared to disodium phosphocreatine and creatine hydrochloride used alone, or creatine hydrochloride with cyclodextrin, it is not clear if these results would be the same across all possible wt% of disodium phosphocreatine and any cyclodextrin amount above 2 wt%. Further, it is unclear what cyclodextrin is used in the results where it is only referred to as cyclodextrin. Where the instant claims recite gamma cyclodextrin, it is unclear if gamma cyclodextrin would have the same improved results than the “cyclodextrin” used in fig. 1 and table 1. This is further supported by the instant specification where the reactivity and dissociation of cyclodextrin and its guest molecules cannot be predicted (see ¶ 14 of the instant specification).
Third, respectfully, this argument is not persuasive. The claims stand rejected for the same reasons discussed above and of record.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10 and 25-36, are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11246846 B2, hereinafter referred to as ‘846, in view of Vilallobos (US 20100055178 A1), Byrd (US 20060062849 A1), Tricarico (Eur. Jour. Pharm., 1995, 287, pp. 17-25), Antony (US 20170173100 A1), Patra et al (Future Jour Pharm Sci 3, 2017, pp. 33-45), and Krauter (EVONIK, Health Care, 2015, pp. 1-2). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims recite an oral supplement comprising creatine (claim 1), trisodium citrate, cyclodextrin selected from alpha, beta, and gamma (claim 29), a methacrylate polymer (claim 30), and PEG (claim 31). The creatine is selected from creatine monohydrate, creatine hydrochloride, creatine phosphate, and the salt forms of these creatines (claims 13, 14). The combined weight percent of cyclodextrin, methacrylate copolymers, and PEG comprises 2-20 wt% (claims 18, 23). The weight ratio of trisodium citrate to active component (i.e., creatine) is from 5:1 to 1:5 (claims 1, 36). The PEG comprises PEG 3350 (claims 20, 21).
The claims of ‘846 do not disclose a method of co-granulating disodium creatine phosphate and cyclodextrin, average granule sizes as instantly claimed, the coatings instantly claimed, nor an embodiment with the amounts of components instantly claimed.
The references are discussed above.
It would have been obvious to manufacture the oral creatine supplement via known methods, such as by co-granulating creatine, cyclodextrins, trisodium citrate, and PEG, and coating with a methacrylate copolymer, as taught by Vilallobos above and for the same reasons.
It would have been obvious to formulate the oral supplement of ‘846 with known granule particle sizes, such as from 250-1000 microns, as taught by Byrd for the same reasons discussed above.
It would have been obvious to include disodium phosphocreatine as the creatine, for the same reasons discussed above by Tricarico.
It would have been obvious to further include at least one of alpha or beta cyclodextrin, as disclosed by ‘846.
It would have been obvious to include EUDRAGUARD as the methacrylate copolymer coating, for the same reasons discussed above by Antony. Further, it would have been obvious to use other known enteric coatings, such as EUDRAGIT E, as taught by Patra et al, and EUDRAGUARD control, as taught by Krauter.
It would have been obvious to use PEG 3350 as the PEG, as disclosed by ‘846.
Regarding the amounts, a skilled artisan would have found it obvious to adjust the amount of the respective components to provide the desired results based on their art recognized uses.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants assert due to the newly added claim amendments, the nonstatutory double patenting rejection should be withdrawn as the amended claims are now patentably district from the claims.
Respectfully, this argument is not persuasive. The rejection has been modified in view of the newly added claim amendments. The claims stand rejected for the same reasons above and of record.
Claims 1-10 and 25-36, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/716,525 (reference application), hereinafter referred to as ‘525, in view of Vilallobos (US 20100055178 A1), Fenyvesi et al (Critical Review in Food Science and Nutrition, 2016, 15:12, pp. 1981-2004), Byrd (US 20060062849 A1), Antony (US 20170173100 A1), Daugherty (US 20080306159 A1), Hans et al (US 20150133552 A1), Patra et al (Future Jour Pharm Sci 3, 2017, pp. 33-45), and Krauter (EVONIK, Health Care, 2015, pp. 1-2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘525 recite an oral supplement comprising creatine (claims 10, 11, 12, 20), trisodium citrate (claims 12, 30), cyclodextrin, and PEG (claim 30). The oral supplement is enteric coated (claims 9, 19, 27). The creatine may be present as disodium phosphocreatine, creatine monohydrate, creatine HCl, etc. (claim 11, 20). The weight ratio of bioactive component to organic acid sodium salt is from 20:1 to 1:10 (claim 20).
The claims of ‘525 do not disclose a method of co-granulating disodium phosphocreatine and gamma cyclodextrin, average granule sizes as instantly claimed, the coatings instantly claimed, an embodiment with the amounts of components instantly claimed, nor PEG 3350 and its amounts.
The references are discussed above.
It would have been obvious to manufacture the oral creatine supplement via known methods, such as by co-granulating creatine, cyclodextrins, trisodium citrate, and PEG, and coating with a methacrylate copolymer, as taught by Vilallobos above and for the same reasons.
It would have been obvious to formulate the oral supplement of ‘525 with known granule particle sizes, such as from 250-1000 microns, as taught by Byrd for the same reasons discussed above.
It would have been obvious to select from alpha, beta, or gamma cyclodextrins, or mixtures thereof, for the same reasons discussed above by Fenyvesi et al.
It would have been obvious to include EUDRAGUARD as the methacrylate copolymer coating, for the same reasons discussed above by Antony. Further, it would have been obvious to use other known enteric coatings, such as EUDRAGIT E, as taught by Patra et al, and EUDRAGUARD control, as taught by Krauter.
It would have been obvious to use PEG 3350 as the PEG, as taught by Daugherty above and for the same reasons.
Regarding the amounts, it would have been obvious to modify the amounts of each component to those known in the prior art, such as those taught by Byrd, Hans, Antony, and Daugherty, for the same reasons discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants assert due to the newly added claim amendments, the nonstatutory double patenting rejection should be withdrawn as the amended claims are now patentably district from the claims.
Respectfully, this argument is not persuasive. The rejection has been modified in view of the newly added claim amendments. The claims stand rejected for the same reasons above and of record.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612