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 .
Priority
This Application is a continuation-in-part to U.S. Application No. 18/105,030 filed on 02/02/2323 which is a division of U.S. Application No. 17/210,646, filed March 24, 2021, which is a continuation-in-part of U.S. Application No. 17/157,000, filed January 25, 2021, now U.S. Patent No. 11,793,778, which is a continuation of U.S. Application No. 16/381,202, filed April 11, 2019, now U.S. Pat. No. 10,925,843, which claims the benefit of U.S. Provisional Application No. 62/659,564, filed April 18, 2018.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 18/105,030, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claim 2 of the instant application which claims the solid beta-hydroxybutyrate composition of claim 1, wherein the composition contains greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component. There is no support found in U.S. Application No. 18/105,030 for the ranges as claimed in claim 2 of greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt. Thus, the effective filing date of claim 2 is the actual filing date of August 18, 2025.
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 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/105,030 (U.S. Publication No. 2023/0201145 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of copending ‘030 are drawn to a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component. Thus the cited claims of the instant application would be anticipated over the cited claims of copending ‘030.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/217,111 (U.S. Publication No. 2023/0346721 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of copending ‘030 encompass to a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component. Although the beta-hydroxybutyric acid composition of copending ‘111 is combined with water, the composition of copending ‘111 is first provided in solid or powder form prior to mixing with an aqueous carrier (see claims 20 and 21). Thus the cited claims of the instant application would be anticipated over the cited claims of copending ‘030.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/442,809 (U.S. Publication No. 2026/0130875). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application are drawn to a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component and wherein the beta-hydroxybutyric acid is enriched with the S isomer or pure S-beta-hydroxybutyric acid, whereas the cited claims are drawn to an aqueous composition comprising pure S-beta-hydroxybutyric acid or beta-hydroxybutyric acid is enriched with the S isomer. Accordingly, it would have been obvious to a person of ordinary skill in the art to use the composition of the instant claims to prepare the aqueous composition of copending ‘809 with a reasonable expectation of success. Thus the cited claims of the instant application and the cited claims of copending ‘809 are mutually obvious and thus not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,533,331. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application are drawn to a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component and wherein the beta-hydroxybutyric acid is enriched with the S isomer or pure S-beta-hydroxybutyric acid, whereas the cited claims of ‘331 are drawn to an aqueous composition comprising pure S-beta-hydroxybutyric acid or beta-hydroxybutyric acid enriched with the S isomer. Accordingly, it would have been obvious to a person of ordinary skill in the art to use the composition of the instant claims to prepare the aqueous composition of ‘331 with a reasonable expectation of success. Thus the cited claims of the instant application and the cited claims of ‘331 are mutually obvious and thus not patentably distinct.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11,806,324 B2 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of ‘324 are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Claims 1-27 of ‘324 claim an aqueous beta-hydroxybutyric acid composition formulated as a nutritional supplement, or for addition to water, beverage, or food product, for ingestion by oral delivery to provide exogenous ketone bodies that exogenously increase blood ketone level in a mammal, the composition comprising: water; and 0.4% w/v to 55% w/v of exogenous beta-hydroxybutyric acid in monomeric form at least partially dissolved in the water, wherein the composition is free or substantially free of beta-hydroxybutyrate salts so as to contain less than 0.8% of total beta-hydroxybutyrate salts and greater than 99.2% of the exogenous beta-hydroxybutyric acid by combined weight of the exogenous beta-hydroxybutyric acid and any beta-hydroxybutyrate salts, wherein the composition is free of 1,3-butanediol and ketone esters, wherein the composition is a nutritional supplement that provides a unit dose of about 0.5 gram to about 25 grams of the exogenous beta-hydroxybutyric acid to exogenously increase blood ketone level in a mammal.
The difference between the cited claims of the instant application and the cited claims of ‘324 is the instant claims claim a solid composition, whereas, ‘324 claims an aqueous composition.
However, the claims of ‘324 encompass the same solid beta-hydroxybutyrate composition as claimed comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a greater amount of the beta-hydroxybutyric acid than the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, since in order to form the aqueous composition of ‘324, the solid composition as claimed would have been combined with water to form the composition of the ‘324 claims.
Thus the cited claims of the instant application would be anticipated over the cited claims of ‘324.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,925,843 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘843 are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Claims 1-20 of ‘843 claim a composition for increasing ketone body level in a subject, the composition comprising: a dietetically or pharmaceutically acceptable carrier; one or more beta-hydroxybutyrate salts; one or more acetoacetate salts; beta-hydroxybutyrate free acid; and optionally acetoacetate free acid, wherein the form may be a powder, tablet or capsule (claims 9 and 16).
The claims of ‘843 do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of ‘843 which claim a composition for increasing ketone body level in a subject, the composition comprising: a dietetically or pharmaceutically acceptable carrier; one or more beta-hydroxybutyrate salts; one or more acetoacetate salts; beta-hydroxybutyrate free acid; and optionally acetoacetate free acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of ‘843 containing up to 99% of the beta-hydroxybutyrate free acid and 1% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings.
Thus the cited claims of the instant application are rendered obvious over the claims of ‘843.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,793,778 B2 (Provided on IDS) in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of ‘778 are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Claims 1-20 of ‘778 claim a composition for administering ketone bodies to a subject, comprising: one or more beta-hydroxybutyrate salts; one or more acetoacetate salts; beta-hydroxybutyrate free acid; and optionally acetoacetate free acid, wherein the form may be a powder, tablet or capsule (claim 10).
The claims of ‘778 do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of ‘778 which claim a composition for administering ketone bodies to a subject, comprising: one or more beta-hydroxybutyrate salts; one or more acetoacetate salts; beta-hydroxybutyrate free acid; and optionally acetoacetate free acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of ‘778 containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings.
Thus the cited claims of the instant application are rendered obvious over the claims of ‘778.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 11-13, 16-20 and 22-24 of U.S. Patent No. 11,185,518 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4 and 6-19 of U.S. Patent No. 11,129,802 B2 (Provided on IDS) in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS dated 05/01/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.95% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-10 and 19-21 of U.S. Patent No. 11,033,553 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8, 10, 12-13 and 15-18 of U.S. Patent No. 10,980,772 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-12, 14-17 and 19-22 of U.S. Patent No. 11,944,598 B2 (Provided on IDS) in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15-16 and 18-21 of U.S. Patent No. 11,103,470 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,950,616 B2 (Provided on IDS) in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta- hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,329,734 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, and thus the beta-hydroxybutyric acid and beta-hydroxybutyrate salt component would form a crystalline solid as claimed in the instant claims.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,551,455 B2 in view of Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application the cited claims of said patent are substantially overlapping in scope and mutually obvious.
Claims 1-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
The cited claims of the patent either claim a composition for administering ketone bodies to a subject or a method of using a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid.
The cited claims of the patent do not claim the composition contains between 96% and 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol and containing 99-96% of the free acid and 1-4% of the salt or 98-96% of the free acid and 1-3% of the salt and 1% of a ketone ester.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of the patent which claim a composition for increasing ketone bodies in a subject comprising a mixture of beta-hydroxybutyrate salts and beta-hydroxybutyric acid, with the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis comprising a ketone blend containing any two or more of a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol in the preferred embodiments of 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester. Thus a person of ordinary skill in the art would have been motivated to formulate the composition of the patent containing up to 99% of the beta-hydroxybutyrate free acid and at least 1% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Thus a composition comprising 99% beta-hydroxybutyric acid and 1% salt is rendered obvious in view of the cited teachings and thus the cited claims of the instant application are rejected.
Thus the cited claims of the instant application are rendered obvious over the cited claims of the patent.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 6, 11, 12, 14, 16, 18 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arnold U.S. Publication No. 2018/0021274 A1 (Provided on IDS).
Claims 1, 3, 6, 11, 12, 14, 16, 18 and 20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Arnold teaches β-hydroxybutyric acid in combination with β-hydroxybutyrate salts useful to induce ketosis, achieving blood ketone levels of (0.5-6.0 mmol/L), with or without dietary restriction, and without inducing harmfully high mineral loads in the blood (abstract). Arnold teaches that the combination of β-hydroxybutyric acid and salt results in substantial improvements in metabolic biomarkers related to insulin resistance, diabetes, weight loss, and physical performance & endurance in a short period of time (abstract). Arnold teaches that these supplements achieve ketosis and yields a significant elevation of blood ketones and reduction of blood glucose levels, as well as suppress appetite, prevent epileptic seizures, and treat cancer (abstract and [0002]).
Arnold teaches that although it has been believed in the art that mixtures of β-hydroxybutyric acid and βHB salts can cause harmful mineral overload, the present inventors have discovered that when β-hydroxybutyric acid and βHB salts are combined in particular ratios, the resulting composition is not only not harmful, it is actually safer and more effective for inducing ketosis [0008]. Arnold teaches compositions comprising β-hydroxybutyric acid and βHB salts at a ratio between ˜125 parts free acid per ˜7 parts salt to ˜0.4 parts free acid per ˜125.1 parts salt [0008].
Arnold teaches compositions comprising b-hydroxybutyric acid and βHB in a ratio ranging from ˜125 parts free acid per ˜7 parts salt to ˜0.4 parts free acid per ˜125.1 parts salt, and in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜125 parts free acid per ˜7 parts salt to ˜75 parts free acid per ˜57.5 parts salt [0019]. Arnold teaches in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜75 parts free acid per ˜57.5 parts salt to ˜0.4 parts free acid per ˜125.1 parts salt, or the free acid may be combined with the salt or salts in ratios ranging from ˜75 parts free acid per ˜57.5 parts salt to ˜38.5 parts free acid per ˜90 parts salt [0019]. Arnold teaches in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜102 parts free acid per ˜30 parts salt to ˜75 parts free acid per ˜57.5 parts salt, or the free acid may be combined with the salt or salts in ratios ranging from ˜102 parts free acid per ˜30 parts salt to ˜38.5 parts free acid per ˜90 parts salt [0019]. Arnold teaches in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜80.8 parts free acid per ˜50 parts salt to ˜60 parts free acid per ˜70 parts salt, or in certain embodiments, the number of weight parts of βHB free acid per weight parts of βHB salts can be calculated as a function of the weight parts of salt in the mixture, according to the equation y=−1.0577x+133.65, where “y” represents weight parts of free acid and “x” represents weight parts of salt [0019].
Arnold further teaches, in certain embodiments, the composition comprises a mix of free acid, sodium salt, and potassium salt, in a mass:mass:mass ratio of ˜125 parts free acid per ˜3.7 parts potassium salt per ˜3.3 parts sodium salt to ˜0.4 parts free acid per ˜66.3 parts potassium salt per ˜58.8 parts sodium salt such as 125:3.7K:3.3Na, 125:4:66.3K:5.8.Na [0020].
Thus Arnold specifically teaches embodiments wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component, including, in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜125 parts free acid per ˜7 parts salt to ˜75 parts free acid per ˜57.5 parts salt; in certain embodiments, the free acid may be combined with the salt or salts in ratios ranging from ˜102 parts free acid per ˜30 parts salt to ˜75 parts free acid per ˜57.5 parts salt [0019].
Arnold further teaches that the compositions are optionally administered at doses between about 2 grams and about 50 grams, for example between about 5 grams and about 30 grams, or between about 10 grams and about 20 grams [0023]. For example, the ketone compositions are optionally administered at doses of about 2 grams, about 4 grams, about 5 grams, about 6 grams, about 7 grams, about 8 grams, about 9 grams, about 10 grams, about 11 grams, about 12 grams, about 13 grams, about 14 grams, about 15 grams, about 17 grams, about 19 grams, about 20 grams, about 22. grams, about 24 grams, about 26 grams, about 28 grams, about 30 grams, about 32 grams, about 34 grams, about 36 grams, about 38 grams, about 40 grams, about 42 grams, about 44 grams, about 46 grams, about 48 grams, or about 50 grams [0023].
Thus Arnold specifically teaches dosages within the claimed range as claimed in claim 20 of the instant application.
Arnold teaches in certain embodiments, the β-hydroxybutyric acid or salt is a racemic mixture of D- and L-β-hydroxybutyric acid or salt [0025]. Arnold teaches in certain embodiments the β-hydroxybutyric acid or salt is a single isomer D-β-hydroxybutyric acid or salt [0025]. Arnold teaches that in certain embodiments where the composition is provided as a dry powder, the composition may be assembled by mixing a racemic mixture of the free acid with a salt or set of salts that are enriched or purified for the D isomer, in other dry powder embodiments, the composition may be assembled by mixing a free acid that has been enriched or purified for the D isomer with a racemic mixture of salt or salts [0025]. In certain dry power embodiments, the composition may be assembled using stocks of both free acid and salt or salts that have been enriched or purified for the D isomer [0025]. In certain embodiments, D-β-hydroxybutyric acid powder is mixed with D-β-hydroxybutyrate salt powders [0025]. Arnold teaches that in certain embodiments, racemic β-hydroxybutyric acid liquid is mixed with racemic β-hydroxybutyrate salt powders, and a solution thereof is dried onto a solid substrate carrier (e.g., maltodextrin or dry milk solids) [0025]. In certain embodiments, racemic b-hydroxybutyric acid liquid is mixed with D-β-hydroxybutyrate salts, and a solution thereof is dried onto a solid substrate carrier [0025].
Thus Arnold specifically teaches a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject as claimed.
Arnold teaches that the compositions may further comprise one or more additional ketone precursors or supplements in combination with βHB, including but not limited to acetoacetate, ketone esters, and other compounds that cause a rise in blood ketone levels [0026]. Arnold further teaches that in certain embodiments, the composition may also include one or more nutritional substrates such as free amino acids, amino acid metabolites, vitamins, minerals, electrolytes and metabolic optimizers such as NADH, soluble ubiquinol, tetrahydrobiopterin, α-ketoglutaric acid, carnitine, and/or α lipoic acid, nutritional co-factors, calcium β-methyl-β-hydroxybutyrate, arginine α-ketoglutarate, sodium R-α lipoic acid, thiamine, riboflavin, niacin, pyridoxine, ascorbic acid, citric acid, malic acid, sodium benzoate, potassium sorbate, acesulfame K, aspartame, xanthan gum, or a combination thereof [0029].
Arnold teaches the composition may be consumed as a dry powder, and when the composition is consumed in dry powder form, the composition may optionally be formulated in a tablet, a capsule, a sachet, and/or any other pharmaceutically acceptable dry dosage form known in the art, including a concentrated gel [0036].
Claims 1, 9 and 10 of Arnold claim a dry powder composition comprising b-hydroxybutyric free acid and β-hydroxybutyrate salt, wherein the free acid and salt stand in a mass:mass ratio from ˜125 parts free acid: ˜7 parts salt to ˜0.4 parts free acid: ˜125.1 parts salt, wherein β-hydroxybutyric free acid and β-hydroxybutyrate salt are each present as D isomer. Claims 7 and 8 of Arnold claim the composition comprises both D and L isomers of β-hydroxybutyric free acid and/or β-hydroxybutyrate salt, or wherein the β-hydroxybutyric free acid and/or β-hydroxybutyrate salt is/are present as a racemic mixture. Claim 15 of Arnold claims a pharmaceutical dosage form comprising the dry powder wherein the pharmaceutical dosage form is a tablet or a capsule.
Thus the cited claims of the instant application are anticipated by the teachings of Arnold which specifically teaches a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Claims 1, 3, 11, 12 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS).
Claims 1, 3, 11, 12 and 16 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005].
Llosa et al. teaches that several aspects can include a method for treating the symptoms such as fatigue and cognitive impairment associated with amyotrophic lateral sclerosis, a method for treating concussions and/or traumatic brain injury, as well as a method for enhancing physical performance, and muscle recovery, including the step of administering or consuming a Ketone Blend [0007]- [0008].
Llosa et al. teaches an aspect can include a foodstuff having limited racemic sodium β-hydroxybutyrate, racemic potassium β-hydroxybutyrate, and/or racemic calcium β-hydroxybutyrate in combination with the free acid (D)-β-hydroxybutyrate, and/or (D)-1,3-butanediol, and/or KE such that the preponderance of the composition is non-racemic or enantiomerically enriched [0010].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027].
Thus Llosa et al. specifically teaches a ketone blend comprising beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches that one aspect can include a foodstuff having limited racemic sodium -hydroxybutyrate, racemic potassium -hydroxybutyrate, and/or racemic calcium -hydroxybutyrate in combination with the free acid (D)--hydroxybutyrate, and/or (D)-1,3-butanediol, and/or KE such that the preponderance of the composition is non-racemic or enantiomerically enriched [0010].
Llosa et al. teaches that each of the compounds have chiral centers thus having (D) and (L) isomers [0028]. In a preferred embodiment all of the compounds shall be enantiomerically enriched with respect to the (D) isomer, wherein enantiomerically enriched shall be defined as having greater than 50% concentration, of the D isomers [0028]. Llosa et al. teaches that it should also be noted that only the D enantiomer is active in the body as a source of extracellular fuel that is then transported into the cells [0041].
Llosa et al. teaches that free acid (D)--hydroxybutyrate can be used directly by the body without having to be processed in the liver and can easily cross the blood-brain barrier and free acids can raise ketones in the blood more rapidly than precursors or derivatives [0054]. Free acid (D)--hydroxybutyrate, in levels tolerated by the GI system, can be part of preferred compositions [0054].
Llosa et al. teaches that the free acid of (D)--hydroxybutyrate is a white, odorless crystal with a slightly tart or acidic taste [0050]. It is a mild acid with a pH between, vinegar and lemon juice and can be formulated into most foodstuffs, e.g. drinks, puddings, mashed vegetables, and/or inert fillers [0050]. The acid forms of (D)--hydroxybutyrate are suitable for use orally as they have a pKa of 4.4 which is less acidic than citric acid with pKa of 3.1 and pKa2 of 4.8 and slightly more acidic than acetic acid with a pKa of 4.7 [0050].
Thus Llosa et al. teaches a solid ketone blend for incorporation into foodstuffs to exogenously increase ketone body levels in a subject comprising two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate wherein the Ketone Blend can be in any relative concentration ratios and preferably 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027].
Thus the cited claims are anticipated since Llosa et al. teaches a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta- hydroxybutyric acid and the beta-hydroxybutyrate salt component, and further comprising 1,3-butanediol, wherein in a preferred embodiment all of the compounds shall be enantiomerically enriched with respect to the (D) isomer, wherein enantiomerically enriched shall be defined as having greater than 50% concentration, of the D isomers, or enantiomerically pure (D) isomer.
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.
Claims 2, 4, 5, 7-10, 13, 15, 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold U.S. Publication No. 2018/0021274 A1 (Provided on IDS) as applied to claims 1, 3, 6, 11, 12, 14, 16, 18 and 20 above and further in view of Lincoln et al. (Archives of Biochemistry and Biophysics, Vol. 259, No. 15, pages 149-156, 1987) (Provided on IDS) and Solomon et al. U.S. Publication No. 2006/0165777 A1 (Provided on IDS).
Arnold is as set forth above.
Arnold does not specifically teach a ketone blend wherein the composition contains greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component as claimed in claim 2 of the instant application. Arnold does not teach a premeasured quantity of the beta-hydroxybutyrate composition as claimed in instant claims 4 and 8-10. Arnold et al. does not specifically teach a packet or pouch as claimed in instant claim 5. Arnold et al. does not specifically teach an effervescent tablet as claimed in instant claim 7. Arnold does not teach a non-racemic mixture enriched with S-beta-hydroxybutyric acid or pure S-beta-hydroxybutyric acid as claimed in claims 13 and 15. Arnold does not specifically teach a kit as claimed in instant claims 17 and 19.
Although Arnold does not specifically teach a ketone blend wherein the composition contains greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component as claimed in claim 2 of the instant application, Arnold teaches, in certain embodiments, the composition comprises a mix of free acid, sodium salt, and potassium salt, in a mass:mass:mass ratio of ~125 parts free acid per ~3.7 parts potassium salt per ~3.3 parts sodium salt to ~0.4 parts free acid per ~66.3 parts potassium salt per ~58.8 parts sodium salt such as 125:3.7K:3.3Na [0020]. Thus Arnold teaches an embodiment wherein the combination comprises 125 parts free acid and 7 parts salt which is equivalent to 94.7% free acid and 5.3% salt by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt. This concentration is very close to the claimed greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component as claimed in claim 2 of the instant application.
A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Waite, 168 F.2d 104, 108 (CCPA 1948); In re Scherl, 156 F.2d 72, 74-75 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Swenson, 132 F.2d 1020, 1022 (CCPA 1942); In re Bergen, 120 F.2d 329, 332 (CCPA 1941); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934 (CCPA 1934); In re Lilienfeld, 67 F.2d 920, 924 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); Gentiluomo v. Brunswick Bowling and Billiards Corp., 36 Fed. App'x 433 (Fed. Cir. 2002)(non-precedential)(disagreeing with argument that overlapping ranges were required to find a claim prima facie obvious); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.). Thus claim 2 of the instant application is rendered obvious over the teachings of Arnold, in the absence of secondary considerations such as unexpected results of a demonstration of criticality.
Although Arnold et al. does not specifically teach an effervescent tablet as claimed in instant claim 7, claim 7 is rendered obvious over Arnold which teaches tablets, and thus all kinds of tablets including effervescent tablets as claimed are contemplated in the absence of secondary considerations such as unexpected results.
Although Arnold does not specifically teach a premeasured quantity of the beta-hydroxybutyrate composition as claimed in instant claims 4 and 8-10, Arnold teaches administration of doses between about 2 grams and about 50 grams, and between about 10 grams and about 20 grams, for example, the ketone compositions are optionally administered at doses of about 2 grams, about 4 grams, about 5 grams, about 6 grams, about 7 grams, about 8 grams, about 9 grams, about 10 grams, about 11 grams, about 12 grams, about 13 grams, about 14 grams, about 15 grams, about 17 grams, about 19 grams, about 20 grams [0023]. Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to provide premeasured dosages according to the teachings of Arnold, with a reasonable expectation of easing the administration since premeasured dosages would eliminate the need for measuring and thus lower dosing errors. Thus claims 4 and 8-10 are rendered obvious in view of the cited prior art teachings.
Claim 13 is rendered obvious since claim 7 of Arnold claims the composition comprises both D and L isomers of β-hydroxybutyric free acid and/or β-hydroxybutyrate salt, and thus the D and L isomers may be in any amount including non-racemic mixtures enriched with either form as claimed.
Claim 15 is rendered obvious in the absence of secondary considerations such as a demonstration of criticality since a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. Structural similarities of chemical compounds have been found to support a prima facie case of obviousness. See, e.g., Dillon, 919 F.2d at 692-93, 16 USPQ2d at 1900-02, In re Merck & Co., 800 F.2d 1091, 1096-97, 231 USPQ 375, 378-79 (Fed. Cir. 1986)In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460,195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious). Thus the use of S-beta-hydroxybutyric acid is rendered obvious over the teachings of Arnold which teaches R-beta-hydroxybutyric acid in the absence of secondary considerations such as unexpected results.
In addition, Lincoln et al. teaches that S-BHB is the unnatural enantiomer of the physiological ketone body R-BHB (page 149). Lincoln et al. teaches that S-BHB is metabolized via mitochondrial activation and is converted into physiological ketone bodies including R-BHB (abstract). Thus Lincoln et al. teaches that S-BHB is converted into the physiological ketone body R-BHB and thus one would expect similar activity for S-BHB as R-BHB. Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to substitute the D-beta-hydroxybutyric acid (which is the R-form) for S-beta-hydroxybutyric acid (which is the L- form) in the method of Arnold et al. since Lincoln et al. teaches that administration of the S-form will produce the R or D form inside the body. Thus administration of the S-form would have been expected to produce similar results as administration of the D or R form as taught in Arnold. Thus the substitution of S-beta-hydroxybutyric acid for D or R- beta-hydroxybutyric acid would have been seen as an obvious alternative to yield predictable results.
With respect to claim 5 of the instant application, which claim the composition is provided in a dosage form such as a packet or pouch, Arnold teaches the composition may optionally be formulated in a tablet, a capsule, a sachet, and/or any other pharmaceutically acceptable dry dosage form known in the art [0036].
Likewise, with respect to claims 17 and 19 drawn to a kit comprising the solid composition, a container in which the composition is placed and one or more dosage forms wherein the one or more dosage forms are selected from a plurality of packets, pouches, tablets, or capsules, Arnold teaches the composition may optionally be formulated in a tablet, a capsule, a sachet, and/or any other pharmaceutically acceptable dry dosage form known in the art [0036].
Solomon et al. teaches that a sachet is a holder or container that holds or contains a dosage form such as tablets or capsules ([0026] and [0034]). Solomon et al. teaches that a sachet represents packaging that may be a sealed foil pack or a holder [0073]. Thus a sachet, which is a small container such as bag or packet, holds a premeasured amount of a composition or a specific number of tablets or capsules.
Thus claim 5 is rendered obvious in view of the teaching in Arnold of a sachet which is a small bag or packet which holds a premeasured amount of a composition. Likewise, a kit comprising the solid composition, a container in which the composition is placed and one or more dosage forms wherein the one or more dosage forms are selected from a plurality of packets, pouches, tablets, or capsules, is rendered obvious since Arnold teach a sachet which is a container such as a packet or pouch which will contain a specific amount of the dry, powder composition, or tablet or capsule form taught in Arnold. Moreover, since Arnold teaches that the composition may be divided and administered over intervals of time, it would have been obvious to a person of ordinary skill in the art to provide more than one sachet with a specific dosage to be administered multiple times [0024].
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 2, 4-10, 13-15, 17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS) as applied to claims 1, 3, 11, 12 and 16 above and further in view of Clarke et al. U.S. Publication No. 2015/0065571 A1 and Lincoln et al. (Archives of Biochemistry and Biophysics, Vol. 259, No. 15, pages 149-156, 1987) (Provided on IDS).
Claims 2, 4-10, 13-15, 17 and 19-20 of the instant application claim a solid beta-hydroxybutyrate composition for oral delivery to increase blood ketone level in a subject, comprising: beta-hydroxybutyric acid; and a beta-hydroxybutyrate salt component; wherein the composition contains a higher concentration of the beta-hydroxybutyric acid than the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component.
Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002]. An aspect can include a foodstuff having free acid (D)--hydroxybutyrate, and/or a (D)--hydroxybutyrate salt, (D)-1,3-butanediol and/or Ketone Ester [0005]. In some embodiments, the free acid (D)--hydroxybutyrate, and the (D)--hydroxybutyrate salt, and (D)-1,3-butanediol, and Ketone Ester can be in a molar ratio of 10±5:5±5:2±2:5±5 [0005]. Llosa et al. teaches that the free acid -hydroxybutyrate can be enterically encapsulated and/or with a buffer to prevent gastric degradation [0005]. Llosa et al. teaches that none of the products currently on the market do anything to prevent significant gastric degradation which can decrease bioavailability by 20%-50% [0005].
Llosa et al. teaches that several aspects can include a method for treating the symptoms such as fatigue and cognitive impairment associated with amyotrophic lateral sclerosis, a method for treating concussions and/or traumatic brain injury, as well as a method for enhancing physical performance, and muscle recovery, including the step of administering or consuming a Ketone Blend [0007]- [0008].
Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. The Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus the teachings of Llosa et al. encompass a ketone blend, without 1,3-butanediol or a ketone ester and containing 99% of the free acid and 1% of the salt.
Llosa et al. teaches that one aspect can include a foodstuff having limited racemic sodium -hydroxybutyrate, racemic potassium -hydroxybutyrate, and/or racemic calcium -hydroxybutyrate in combination with the free acid (D)--hydroxybutyrate, and/or (D)-1,3-butanediol, and/or KE such that the preponderance of the composition is non-racemic or enantiomerically enriched [0010].
Llosa et al. teaches that each of the compounds have chiral centers thus having (D) and (L) isomers [0028]. In a preferred embodiment all of the compounds shall be enantiomerically enriched with respect to the (D) isomer, wherein enantiomerically enriched shall be defined as having greater than 50% concentration, of the D isomers [0028]. Llosa et al. teaches that it should also be noted that only the D enantiomer is active in the body as a source of extracellular fuel that is then transported into the cells [0041].
Llosa et al. teaches that the free acid of racemic -hydroxybutyrate can be ingested to produce ketones, however, while a fast acting ingredient, -HB free acid has several problems when consumed alone, including it is an acid, similar in acidity to that of lemon juice and consuming too much of the free acid can degrade tooth enamel and/or can cause GI problems [0045]. However, encapsulation of the free acid has been shown to increase pass through from the GI into the blood, thus increasing blood levels of (D)--hydroxybutyrate [0045]. Encapsulations and forms of enteric coating known in the arts may be utilized to help bypass the highly acidic gut and thus prevent gastric degradation of the compound [0045]. In alternate embodiments, the (D)--hydroxybutyrate and/or a Ketone Blend may be administered along with a Ranitidine, Famotidine, or similar stomach acid inhibitors (namely histamine H2 receptor antagonists) to increase the pH of the gut and preserve the efficacy of the compounds [0045].
Llosa et al. further teaches that while the use of pure, free acid form of (D)-.beta.-hydroxybutyrate has been considered dangerous, the quantity that would have to be consumed to cause metabolic problems or GI distress would be quite high [0051]. In moderate quantities, the free acid (D)--hydroxybutyrate can be advantageously combined with, e.g., non-racemic salts of (D)--hydroxybutyrate and/or the non-racemic precursor to (D)--hydroxybutyrate, called (D)-1,3-butanediol, to achieve a more rapid onset of ketone bodies in the blood and higher concentrations than previously explored compositions [0051]. Free acid (D)--hydroxybutyrate is a mild acid slightly weaker in strength than citric acid [0052]. One liter of grapefruit juice contains about 25 grams of citric acid and in some sensitive people that can be enough to cause gastrointestinal distress or aggravate acid reflux, nevertheless, most people can tolerate the acidity of grapefruit juice [0052].
Llosa et al. teaches that free acid (D)--hydroxybutyrate can be used directly by the body without having to be processed in the liver and can easily cross the blood-brain barrier and free acids can raise ketones in the blood more rapidly than precursors or derivatives [0054]. Free acid (D)--hydroxybutyrate, in levels tolerated by the GI system, can be part of preferred compositions [0054]. Another advantage is that embodiments, unlike previous compositions (sometimes administered intravenously or topically), can be orally administered, which is less expensive and easier for the patient [0054].
Llosa et al. teaches that "consuming" may include oral and/or parenteral delivery of the ketones in order to raise blood ketone levels in a user [0059]. Dosing protocols may be simply defined as up to 2 g/kg of body weight per day for the user wherein the dosing of the 2 g/kg may be partitioned throughout the day, or taken all at once [0059].
Llosa et al. teaches that the free acid of (D)--hydroxybutyrate is a white, odorless crystal with a slightly tart or acidic taste [0050]. It is a mild acid with a pH between, vinegar and lemon juice and can be formulated into most foodstuffs, e.g. drinks, puddings, mashed vegetables, and/or inert fillers [0050]. The acid forms of (D)--hydroxybutyrate are suitable for use orally as they have a pKa of 4.4 which is less acidic than citric acid with pKa of 3.1 and pKa2 of 4.8 and slightly more acidic than acetic acid with a pKa of 4.7 [0050].
Llosa et al. teaches treating hair loss, vision impairment, amyotrophic lateral sclerosis (commonly referred to as ALS or Lou Gehrig's disease), concussions, heart disease, diabetes, and traumatic brain injury, in addition to enhancing physical performance [0061]. Llosa et al. teaches that the dosing regimen should be between 5-60 grams 1-3 times per day with the preferred amount to be between 20-40 grams 3 times per day for persons suffering with ALS who display chronic fatigue and chronic cognitive impairment [0064]. Llosa et al. teaches that persons should begin taking (D)-β-hydroxybutyrate and/or Ketone Blend at the first indication of brain trauma or suspected trauma and depending on the severity of the trauma, patients may be required to take the (D)-β-hydroxybutyrate and/or Ketone Blend for 1 week-8 weeks [0065]. In severe cases or when individuals suffer multiple traumas such as in professional football wherein the damage to cells may be permanent and progressive, (D)-β-hydroxybutyrate and/or Ketone Blend should be taken for the rest of their lives, in particular a combination of Ketone Ester and encapsulated free acid using an enteric coating designed to dissolve at different rates through the length of the entire GI system over 8 hours at a dosage of 375 mg/kg, 2 times per day which for an average 70 kg man would be approximately 26 grams, 2 times per day, with ranges between 5-50 grams, 2-3 times per day for the average man, but significantly more for a football player that weighs much more [0065]. If using non-encapsulated or non-coated free acid, it would be preferred to take more smaller doses up to 8 times per day with doses of 2-20 grams per dose [0065]. Athletes may take the ketones up to twice per day with total ketone addition not to exceed 150 grams per day [0066].
Llosa et al. teaches that the ketones can be utilized to address muscle recovery, cancer, autism, fibromyalgia, chronic pain, migraines, stroke, multiple sclerosis, aging, epilepsy, diabetes, weight loss, radiation poisoning, Autism, ADD, Alzheimer's, and Parkinson's as well as provide additional clarity of mind and improved energy levels by safely increasing ketone bodies in the blood [0069] [0070].
Thus Llosa et al. teaches a solid ketone blend for incorporation into foodstuffs to exogenously increase ketone body levels in a subject comprising two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate wherein the Ketone Blend can be in any relative concentration ratios and preferably 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Thus Llosa et al. teaches formulations comprising up to 99% of the free acid which can contain 1% beta-hydroxybutyrate salts and furthermore teaches a ketone blend with a molar ratio of the free acid (D)--hydroxybutyrate:(D)--hydroxybutyrate salt:(D)-1,3-butanediol:Ketone Ester 10±5:5±5:2±2:5±5 [0005].
Llosa et al. does not specifically exemplify a ketone blend wherein the composition contains greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component. Llosa et al. does not teach pure S-forms or S-enriched forms. Llosa et al. does not teach premeasured dosage forms comprising a kit in a container, packet or pouch. Llosa et al. does not teach a tablet or capsule dosage form.
With respect to the limitation that the composition contains greater than 96% and up to 99.5% of the beta-hydroxybutyric acid and from 0.5% to less than 4% of the beta-hydroxybutyrate salt component by combined weight of the beta-hydroxybutyric acid and the beta-hydroxybutyrate salt component., Llosa et al. teaches that a Ketone Blend is defined as a blend of two or more compounds selected from a free acid of -hydroxybutyrate, salt of -hydroxybutyrate, ketone ester of hydroxybutyrate, or 1,3-butanediol which when taken orally shall increase serum levels of (D)--hydroxybutyrate [0025]. Llosa et al. teaches that the Ketone Blend containing any two or more of the above listed compounds can be in any relative concentration ratios and the preferred embodiments shall be as follows: 51-99% free acid, 1-25% Ketone Salt, 1-10% 1,3-butanediol, and 1-49% Ketone Ester [0027]. Therefore Llosa et al. teaches an embodiment wherein the free acid may be in an amount of 99%-96% and the Ketone Salt may be in an amount from 1% to 4%.
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) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").
Furthermore, Llosa further teaches that the free acid can be used directly by the body without having to be processed in the liver and can easily cross the blood-brain barrier [0054]. Free acids can raise ketones in the blood more rapidly than precursors or derivatives [0054]. Llosa further teaches that free acid (D)--hydroxybutyrate, in levels tolerated by the GI system, can be part of preferred compositions [0054]. Llosa further teaches that the free acid (D)--hydroxybutyrate is a mild acid slightly weaker in strength than citric acid [0052]. One liter of grapefruit juice contains about 25 grams of citric acid, and in some sensitive people that can be enough to cause gastrointestinal distress or aggravate acid reflux [0052]. Nevertheless, most people can tolerate the acidity of grapefruit juice [0052]. Thus if most people can tolerate the acidity of grapefruit juice, most people would be able to tolerate the acidity of free acid (D)--hydroxybutyrate which is slightly weaker than citric acid.
Llosa further teaches that free acid (D)--hydroxybutyrate, like grapefruit juice, can cause problems if consumed in quantities greater than, e.g., 150 grams per day or in acute doses above 20-40 grams dissolved in a small amount of water [0053]. Llosa further teaches that the average human will produce a maximum of 150 grams in 24 hours during starvation level ketosis and that same amount can be considered a maximum therapeutic amount of any form of (D)--hydroxybutyrate [0053]. Thus Llosa actually teaches that only very high amounts of the free acid are dangerous and one would not need those very high amounts to achieve the desired effects. Moreover, the teachings of Llosa suggest up to 150 grams per day of the acid is tolerable and furthermore suggest that acute doses of 20-40 grams should be dissolved in large amounts of water to avoid any GI distress.
These teachings suggest the use of pure free acid, with minor amounts of the salts, as claimed in instant claim 2 since the amount of the free acid tolerated would be sufficient to raise ketones in the blood in adequate amounts and the free acid can be used directly by the body without having to be processed in the liver and can easily cross the blood-brain barrier, and free acids can raise ketones in the blood more rapidly than precursors or derivatives. A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006,1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including non-preferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Although Llosa et al. does not teach premeasured dosage forms comprising a kit in a container, packet or pouch or a tablet or capsule dosage form, it would be within the skill of an ordinary artisan to provide the ketone blend of Llosa et al. in forms well-known in the art.
Clarke et al. teaches preparing formulations for increasing ketosis to improve endurance during exercise and to promote muscle recovery following exercise (abstract). Clarke et al. teaches that these formulations contain (D)-beta-hydroxybutyrate esters and 1,3-butanediol (abstract). Clarke et al. teaches that oral administration may be carried out in a single dose or multiple doses [0049]. Clarke et al. teaches that the ketone body or a ketone body ester is provided as a composition in solid form [0054]. Clarke et al. teaches that the composition is a dry powder intended for use with a liquid to produce a liquid composition, a solid bar or product form [0054]. Clarke et al. teaches that the composition may be solid, for example a powder, tablet, bar, confectionary product or a granule and intended for use as a solid oral dose form [0056]. Clarke et al. teaches that the solid composition may be mixed before use with a liquid, preferably water, fruit based liquid or a dairy product, for example milk and yoghurt, to provide a liquid drink for the user [0056]. Milk, fruit juice and water are especially preferred as a carrier for the composition [0056]. The composition may be in the form of a solid or in the form of a liquid composition or a gel [0074]. Suitable solid forms of the composition include a bar or powder suitable for mixing with a liquid, for example water, milk or fruit juice at the point of use [0074]. Clarke et al. teaches a kit comprising the ketone body and a ketone monitor and optionally instructions as to the level of product to consume per unit body weight to achieve a pre-determined level of blood plasma ketone and a dosage regimen to maintain blood plasma ketone at the pre-determined level to reduce muscle breakdown [0080].
Thus, prior to the effective filing date of the instant application, solid dosage forms, including tablets, powders, etc. containing ketone bodies were known in the art to be provided in a kit containing a predetermined amount to achieve a pre-determined level of blood plasma ketone and a dosage regimen to maintain blood plasma ketone at the pre-determined level.
Accordingly, prior to the effective filing date of the instant application, it would have been within the skill of an ordinary artisan to determine the form of the formulation based on techniques well-known in the art. Prior to the effective filing date of the instant application as taught by Clarke et al. formulations for inducing a ketogenic state in the form of a powder or tablets for use in a kit containing a predetermined amount was known in the art. Thus, a person of ordinary skill in the art would contemplate preparing the dosage forms of Llosa et al. as taught in Clarke et al. with a reasonable expectation of success. Moreover, placing the formulation in a package such as a container, packet, pouch etc. would have been seen as an obvious component within the skill of an ordinary artisan. Thus in the absence of secondary considerations such as unexpected results, placing the formulation in a container such as a packet or pouch is rendered obvious. Moreover, although Clarke et al. does not specifically teach an effervescent tablet as claimed in claim 7 of the instant application, since Clarke et al. teaches tablet dosage forms all tablets forms are contemplated. Thus in the absence of secondary considerations such as a demonstration of criticality or unexpected results an effervescent tablet is rendered obvious over the cited prior art teachings of a tablet form.
With respect to the claims that claim pure R-forms or R-enriched forms, Llosa et al. teaches that each of the compounds have chiral centers thus having (D) and (L) isomers [0028]. In a preferred embodiment all of the compounds shall be enantiomerically enriched with respect to the (D) isomer, wherein enantiomerically enriched shall be defined as having greater than 50% concentration, of the D isomers [0028]. Thus Llosa et al. specifically teaches embodiments wherein the beta-hydroxybutyric acid is a non-racemic mixture enriched with the (D) isomer which is equivalent to the (R) isomer.
With respect to the claims that claim a non-racemic mixture enriched with S-beta hydroxybutyric acid or pure S-beta hydroxybutyric acid, or a racemic of R and S- beta hydroxybutyric acid, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). Structural similarities of chemical compounds have been found to support a prima facie case of obviousness. See, e.g., Dillon, 919 F.2d at 692-93, 16 USPQ2d at 1900-02, In re Merck & Co., 800 F.2d 1091, 1096-97, 231 USPQ 375, 378-79 (Fed. Cir. 1986) In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers).
Stereoisomers are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.). Thus in the absence of secondary considerations such as unexpected results, the use of pure S-forms or S-enriched forms or a racemic mixture are rendered obvious in view of the cited prior art teachings.
In addition, Lincoln et al. teaches that S-BHB is the unnatural enantiomer of the physiological ketone body R-BHB (page 149). Lincoln et al. teaches that S-BHB is metabolized via mitochondrial activation and is converted into physiological ketone bodies including R-BHB (abstract). Thus Lincoln et al. teaches that S-BHB is converted into the physiological ketone body R-BHB and thus one would expect similar activity for S-BHB as R-BHB. Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to substitute the D-beta-hydroxybutyric acid (which is the R-form) for S-beta-hydroxybutyric acid (which is the L- form) in the method of Llosa et al. since Lincoln et al. teaches that administration of the S-form will produce the R or D form inside the body. Thus administration of the S-form would have been expected to produce similar results as administration of the D or R form as taught in Arnold. Thus the substitution of S-beta-hydroxybutyric acid for D or R- beta-hydroxybutyric acid would have been seen as an obvious alternative to yield predictable results.
Thus, the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Llosa et al. U.S. Publication No. 2018/0057846 A1 (Provided on IDS) as applied to claims 1, 3, 11, 12 and 16 above and further in view of Blazquez et al. (Journal of Neurochemistry, 1999, Vol. 72 No. 4, pages 1759-1768).
Claim 18 of the instant application claims the composition further comprising an additive such as cannabinoids.
Llosa et al. is as set forth above.
Llosa et al. does not teach the addition of an additive such as cannabinoids.
However, Llosa et al. teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance [0002].
Blazquez et al. teaches that cannabinoids stimulate ketogenesis which is the process of producing ketone bodies which are a major source of energy that replace glucose in situations of energy deprivation (see abstract and page 1759).
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Llosa et al. which teaches compositions and methods for producing near instant and/or therapeutic levels of nutritional ketosis, and in particular but not limited to compositions and methods related to the right hand enantiomer in particular in either in its pure enantiomer form or enantiomerically enriched form of a Ketone Blend, including any two or more of the following: (D)--hydroxybutyrate salts, (D)--hydroxybutyrate free acid, (D)-1,3-butanediol, and Ketone Ester, for mitochondrial health, treating other conditions, and physical performance, with the teachings of Blazquez et al. which teaches that cannabinoids stimulate ketogenesis which is the process of producing ketone bodies which are a major source of energy that replace glucose in situations of energy deprivation. Thus, combining cannabinoids to the formulation of Llosa et al. would have been expected to improve the properties of the formulation by causing a larger increase in energy in patients in need thereof. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980). Thus claim 18 of the instant application is rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-20 are rejected. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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