Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The amendment to the claims filed after non-final office action on November 25, 2025 is acknowledged. Claim 1 was amended, claims 3, 16 were canceled and claims 1-2, 4-15, 17-18 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 2, 8-9 remain withdrawn due to being drawn to a non-elected invention species. Claims 1, 4-7, 10-15, 17-18 are examined on the merits of this office action.
*After further review, a second Non-final follows due the new Double patenting rejection presented below..
Withdrawn Rejections/Objections
The rejection of claims 1, 3-7, 10-17 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4, 6-9, 11, 23-30, of copending Application No. 17/596784 (reference application) in view Andreux (WO2017036993 A, cited previously) is withdrawn in view of amendment of the co-pending application to remove ketones from the claims and the amendment of the instant claims filed November 25, 2025.
The rejection of claims 1, 3-7, 10-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/843278 (reference application) in view Andreux (WO2017036993 A, cited previously) is withdrawn in view of amendment of the claims. However, a new nonstatutory double patenting over claims 1-20 of copending Application No. 18/843278 (reference application) in view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61) and Plecko (Pediatr Res 52: 301–306, 2002) is found below.
The rejection of claim(s) 1, 3-7 and 18 under 35 U.S.C. 102(a)(1) as being anticipated by Clarke (US20110237666 A1) is withdrawn in view of amendment of the claims to require a diet rich in protein at least 60 energy% of the composition. A revised rejection is found below to reflect said amendment.
The rejection of claim(s) 1, 3-7, 10-11, 13-14 under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Odum (Toxicol Sci. 2001 May;61(1):115-27) is withdrawn in view of amendment of the claims to require a diet rich in protein at least 60 energy% of the composition. A revised rejection is found below to reflect said amendment.
The rejection of claim(s) 1, 3-7, 10-18 under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Andreux (WO2017036993 A, cited in Applicant’s IDS) and Foegedin (Whey Protein Products, “Encyclopedia of Dairy Sciences, second edition, 2011, cited in Applicant’s IDS) as evidenced by Sigma-Aldrich (β-lactoglobulin from Bovine Milk, Information Sheet, Sigma-Aldrich, accessed on 8/11/2022, cited in Applicant’s IDS) is withdrawn in view of amendment of the claims to require a diet rich in protein at least 60 energy% of the composition. A revised rejection is found below to reflect said amendment.
Maintained/Revised Rejections
Claim Rejections – 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-7, 10-15, 17-18 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating specific populations in need of inducing autophagy with specific autophagy inducing agents (ketone monoesters as taught in Clarke in elderly patients), does not reasonably provide enablement for use of Ketones broadly to treat any patient in need of inducing autophagy. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
Claim 1 claims “A method of inducing autophagy in an individual in need thereof, the method comprising administering to the individual a composition comprising an effective amount of an autophagy inducer comprising a ketone, wherein the autophagy inducer is administered in combination with aa diet rich in protein, wherein the diet rich in protein is at least 60 energy % of the composition.” Claims 6-7 claim wherein the individual is ageing and or has sarcopenia or frailty and at risk of developing sarcopenia or frailty. The claim extends to any ketone (i.e. B-hydroxybutyrate, acetoacetate, ketone salts, ketone esters) in combination with a high protein diet. The claims cover any patient in need of autophagy, including diverse populations such as elderly humans, burn patients and critically ill patients with multi organ dysfunction and any Ketone.
Autophagy induction is highly complex and context-dependent biological process. In some conditions (aging and sarcopenia), induction may be beneficial, while in others (sepsis, neurodegeneration, critical illness) excessive autophagy could be harmful. Because the biological outcome depends on the tissue type, disease state, and metabolic environment, a person of ordinary skill would not consider autophagy induction to be a predictable art.
The State of the Prior Art and the predictability or unpredictability of the art
The art teaches that some ketones can induce autophagy (i.e. acetoacetate in dystrophic mice, see Zou). However, these teachings are limited to specific models and cell types and do not provide general guidance for sarcopenia, frailty, critical illness broadly and ICU myopathy. Thus, the prior art only partially supports the invention and does not establish enablement across the breadth of the claims.
Autophagy is known to be unpredictable: it may be beneficial, neutral or harmful depending on context. The outcome of ketone administration cannot be reliably predicted across all patient populations. This lack of predictability increases the burden on a person of ordinary skill in the art and weights against enablement.
The Relative Skill of Those in the Art
The relative skill of those in the art is high. A person of ordinary skill would have higher level of training in molecular biology, physiology or pharmacology with knowledge of autophagy markers (i.e. LC3, p62 and Atg proteins). While such a person could measure autophagy, they would lack the guidance to identify effective dosing regimens and confirm efficacy in the diverse patient populations covered by the claims without extensive trial and error experimentation.
Amount of Guidance/ The Presence or Absence of Working Examples
The specification generically lists ketones as one possible class of inducers and provides a description of standard assays for autophagy detection. However, it gives no guidance/direction as to how ketones should be administered, what doses are effective, or how their activity varies across the many claimed disease settings. The only concrete example (spermidine plus high protein diet in mice) does not provide meaningful guidance for ketones.
The specification includes one example: spermidine administered in drinking water to healthy mice on defined diets. No ketone examples are provided. No human or disease model data is provided. Therefore the working examples do not reasonably support the ketone embodiments or the wide patients scope of the claims.
The Quantity of Experimentation Necessary
A person of ordinary skill in the art would need to test each ketone type (BHB, AcAc, esters, salts) in multiple disease contexts (aging, sarcopenia, frailty, critical illness, trauma, ICU myopathy etc..) to determine whether autophagy is actually induced.
This represents undue experimentation, requiring extensive in vivo and clinical testing across conditions not demonstrated in the specification.
Taking into account the breadth of the claims, the narrow scope of the working examples, the unpredictability of autophagy biology, and the quantity of experimentation required, the specification does not provide sufficient guidance to enable a person of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation. Accordingly, claims directed to ketone autophagy inducers in individuals in need of autophagy are not enabled.
Response to Applicant’s Arguments
Applicant argues “Applicant respectfully disagrees and submits that the experimentation needed to practice the invention is NOT undue or unreasonable. Indeed, the specification includes both in vitro and in vivo animal model examples, which constitute working examples that correlate with the claimed invention. The data in the specification shows that a combination of high protein and an autophagy inducer has a synergistic effect on the induction of autophagy. This is shown in Figures 1 and 2. These figures shows the results from young mice fed with (i) a standard diet, (ii) a high protein diet or (iii) a low protein diet; together with an autophagy inducer (spermidine) in the drinking water. LC3-I and LC3-II protein amounts were then measured in skeletal muscle. LC3-I and LC3-II are both autophagy markers - but the particular relevant marker to look at is LC3-II. An increase in LC3-II is indicative of an increase in autophagosome formation - i.e. an increase in autophagic flux. An increase in LC3-II levels is indicative of increased levels of autophagy in the cell. Figure 2 is the densitometry analysis of the western blots of Figure 1. The data shows that the combination of high protein (60% of the energy of the composition) and spermidine significantly increased the levels of LC3-II over a high protein diet alone and significantly increased the levels of LC3-II over a normal diet with added spermidine. That is, the data proves that an autophagy inducer and a high protein diet act synergistically to increase autophagy levels in muscle cells.
As disclosed in the specification, the autophagy inducer may be selected from any one of a list of known autophagy inducers. In the Examples, spermidine is used as a representative example, but the skilled person would appreciate that the same effect would be seen with a different autophagy inducer, such as ketone, in combination with a high protein diet. Further, the Patent Office notes that "[t]he claim extends to any ketone (i.e. B- hydroxybutyrate, acetoacetate, ketone salts, ketone esters) in combination with a high protein diet. The claims cover any patient in need of autophagy." The Patent Office also asserts that the specification "gives no guidance/direction as to how ketones should be administered, what doses are effective, or how their activity varies across the many claimed disease settings. The only concrete example (spermidine plus high protein diet in mice) does not provide meaningful guidance for ketones. The specification includes one example: spermidine administered in drinking water to healthy mice on defined diets. No ketone examples are provided. No human or disease model data is provided." For at least the reasons set forth above, the present claims fully comply with the requirements of 35 U.S.C. §112(a). Accordingly, the enablement rejection should be reconsidered and withdrawn.
Applicant’s arguments have been fully considered but not found persuasive. Applicant argues that the specification provides working examples demonstrating that high protein combined with an autophagy inducer increases autophagy and that a person of ordinary skill would expect similar results with other inducers, including ketones. However, the specification only provides experimental data using spermidine as the autophagy inducer. No experimental data or specific guidance is provided regarding the use of ketones such as b-hydroxybutyrate, acetoacetate, ketone salts, or ketone esters in combination with a high protein diet. However, the claims encompass administration of any ketone autophagy inducer to any patient in need of autophagy. The specification provides no guidance regarding effective dosing, formulation or administration of ketones for inducing autophagy in the claimed contexts. Determining which ketones would function as autophagy inducers, and under what dosing conditions they would achieve the claimed effect, would require undue experimentation. Accordingly, the disclosure does not enable the full scope of the claimed invention.
In summary, the claims encompass the use of any autophagy inducer in combination with a high protein diet. However, the specification provides experimental data for only a single compound, spermidine. The claimed genus includes chemically and mechanistically distinct compounds such as ketones (e.g. B-hydroxybutyrate, acetoacetate, ketone esters). The specification provides no structural characteristics or mechanistic guidance that would allow a person of ordinary skill in the art to identify which compounds within the broad genus of autophagy inducers would function as claimed. Because autophagy may be induced through multiple unrelated biological pathways, determining which compounds within the claimed genus would produce the claimed effect would require substantial experimentation.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4-7 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71) and Kouw (J Nutr 2017;147:2252–61).
Regarding claims 1 and 4,Clarke teaches administration of 3 hydroxybutyl 3 hydroxybutryate (ketone monoester), which is hydrolysed in vivo to yield B-hydroxybutyrate, a ketone body (see paragraph 0045, abstract). Clarke teaches administration to geriatric patients and those with muscle impairment and fatigue (see paragraph 0036, claim 9). Applicant’s own specification identifies elderly/aging patients and muscle impairment as individuals in need of autophagy induction. Clarke further discloses feeding regiments in which protein accounts for 26-27% of dietary energy (Tables 1 and 3) along with the ketone ester. From Table 3, Clarke teaches 26.9% protein of total calories which corresponds to 6.7gram protein/100 kcal.
Regarding claims 1 and 5, Applicants specification (paragraph 0070) admits that ketones, including beta hydroxybutyrate, are autophagy inducers (see PGPUB, paragraph 0070). Therefore the property of inducing autophagy is inherent to Clarke’s composition (see MPEP 2112).
Regarding claim 6, Clarke expressly discloses administering the ketone ester to elderly/geriatric patients (see paragraph 0036, claim 9).
Regarding claim 7, Clarke expressly discloses administering the ketone ester to elderly/geriatric patients (see paragraph 0036, claim 9). Geriatric individuals are inherently recognized in the art as being a risk of developing sarcopenia or frailty due to age associated muscle decline. Clarke further discloses treatment of muscle impairment and fatigue (see paragraph 0036).
Clarke is silent to the protein being at least 60 energy% of the composition and greater than 8 g protein/100 kcal..
Chanet teaches of a study of administering to elderly men a protein enriched shake (see abstract, see table 1). In particular, Chanet teaches a nutritional drink with 56.4 energy % from protein (see abstract, 21 gm way protein, 9 g carbohydrates and 3 gm fat, 150 kcal, see abstract and supplemental data). Chanet teaches that “Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 6 wk of intervention in healthy older adults and may therefore be a way to support muscle preservation in older people” (see conclusion). Regarding claims 4 and 17, Chanet teaches 14 gm protein/100 kcal.
Kouw teaches protein supplementation wherein the protein is administered in a beverage at 100 energy % of the beverage (see “experimental protocol”, “Subjects ingested the beverage that contained….” And “production of intrinsically labeled protein and tracer infusion”) and stimulation of muscle protein synthesis (see conclusion). Regarding claims 4 and 17, Kouw teaches greater than 9 gm protein/100 kcal given 100% energy percent is from protein.
It would have been obvious before the effective filling date of the claimed invention to administer the ketone composition of Clarke in combination with the high protein nutritional compositions taught by Chanet or Kouw because both references teach protein enriched beverages for elderly individuals to promote muscle metabolism/protein synthesis and preservation. Combining known nutritional interventions used for the same patient population to improve metabolic and muscle function would have represented a predictable use of prior art elements according to their established functions (see MPEP 2143).
Furthermore, it would have been obvious to one of ordinary skill in the art to optimize the protein content (including energy % and protein per 100 kcal) of the administered nutritional composition, including increasing the protein energy percentage to at least 60 energy% because the prior art demonstrates that increasing protein intake in elderly individuals improves muscle metabolism and protein synthesis. Adjusting the protein percentage and amount per 100 kcal within the known range of protein enriched nutritional compositions would have been routine optimization of a result effective variable (see MPEP2144.05).
Claim(s) 1, 4-7, 10-11, 13-14, 17 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71) and Kouw (J Nutr 2017;147:2252–61) as applied to claims 1, 4-7, 17 above, in further view of Odum (Toxicol Sci. 2001 May;61(1):115-27, cited previously).
The combined teachings of Clarke in view of Chanet and Kouw are described in the above rejection. Clarke additionally teaches the standard rodent chow were manufactured by SDS, Essex, UK (see paragraph 0061).
Odum teaches the standard Rodent Diets used from SDS (Essex, UK) are RM1 and RM3 (see table 1, these are also referenced throughout the literature as the standard Rodent Chow from SDS). Odum teaches that both standard rodent chows contain Soybean (protein from plant source) and whey (protein from an animal source).
It would have been obvious to one of ordinary skill in the art at the time of the invention, to understand that the protein in Clarke’s SDS diets would be derived from the conventional protein sources taught in Odum, namely soybean and or whey, since Clarke explicitly relies on SDS diets and Odum establishes their standard rodent chow composition. The motivation to combine arises from the express identification of SDS (essex, UK) diets in Clarke, which are standard diets with known protein sources. One of ordinary skill in the art would have had a reasonable expectation of success in using SDS diets containing soybean and whey protein as disclosed in Odium in the methods of Clarke.
Regarding claim 11, Odum teaches soybean and whey protein in SDS diets. Whey is a milk protein and soybean is a soy protein.
Regarding claim 13, Odum teaches unhydrolyzed soy and whey (see Table 1).
Regarding claim 14, Whey protein is well known in the art to be naturally enriched in BCAAs (leucine, isoleucine, valine). Therefore, Odum’s teaching of whey protein in SDS chow renders obvious the inclusion of BCAAs.
Claim(s) 1, 4-7, 10-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71) and Kouw (J Nutr 2017;147:2252–61) as applied to claims 1, 4-7, 17 above, in further view of Andreux (WO2017036993 A, cited in Applicant’s IDS) and Foegedin (Whey Protein Products, “Encyclopedia of Dairy Sciences, second edition, 2011, cited in Applicant’s IDS) as evidenced by Sigma-Aldrich (β-lactoglobulin from Bovine Milk, Information Sheet, Sigma-Aldrich, accessed on 8/11/2022, cited in Applicant’s IDS).
The combined teachings of Clarke in view of Chanet and Kouw are described in the above rejection. Clarke is silent to the specifics of the diet (protein source, % of the protein source, BCAA, molecular weight of proteins present).
However, Andreux discloses a method of treating a muscle related pathological condition including sarcopenia and age-related sarcopenia (claims 17-18), muscle fatigue (claim 18), age related muscle fatigue (claim 18) comprising administering a composition comprising urolithin (see abstract and claims 1-2, which is a known autophagy inducer as evidenced by Applicant’s specification, paragraph 007, claim 2) and a source of high protein (see claims 1-5, abstract, Figure 1 description).
Regarding instant claims 10-11 and 13, Andreux teaches wherein the protein is casein (see Table 5) which is from an animal source and in particular a milk protein and an unhydrolyzed protein.
Regarding instant claim 12, Andreux teaches wherein at least 50% of the protein is casein (see Table 5, 100% of protein).
Regarding instant claim 14, Andreux teaches wherein the protein can comprise branched chain amino acids in free form (see Table 5).
It would have been obvious before the effective filing date of the claimed invention to combine Clarke’s in view of Chanet and Kouw ketone ester administration with the high-protein dietary compositions of Andreux. One of ordinary skill in the art would have been motivated to combine in order to optimize dietary protein sources and levels to achieve improved muscle health outcomes in elderly or sarcopenic patients with a reasonable expectation of success. There is a reasonable expectation of success since both references are directed at overlapping conditions (sarcopenia, fatigue, muscle loss) in elderly patients.
Furthermore, it would have been obvious to substitute the protein sources of Andreux into the SDS diet framework of Clarke, since both references address age related muscle impairment and one of ordinary skill would have recognized these as conventional dietary proteins in achieving high protein intake.
Regarding claim 15, Foegedin teaches that Whey protein Concentrate comprises greater than 50% of B-lactoglobulin. As evidenced by Sigma Aldrich, B-lactoglobulin has a molecular weight to between 10-20kDA (18 kDA). Thus, WPC comprises at least 50% of a protein that is within the claimed range of size. Nevertheless it would have been obvious to optimize the size of the proteins in the formulation to achieve optimal therapeutic effectiveness and absorption.
Claim(s) 1, 4-7, 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71) and Kouw (J Nutr 2017;147:2252–61) as applied to claims 1, 4-7, 17 above, in further view of Plecko (Pediatr Res 52: 301–306, 2002).
The teachings of Clarke in view of Chanet and Kouw are described in the above rejection. Clarke teaches administration of 3 hydroxybutyl 3 hydroxybutryate (ketone monoester), which is hydrolysed in vivo to yield B-hydroxybutyrate, a ketone body (see paragraph 0045, abstract). Clarke therefore teaches increasing circulating B-hydroxybutyrate levels through administration of a precursor. Clarke doesn’t specifically teach administering beta-hydroxybutyrate. Plecko teaches of orally supplementing B-hydroxybutyrate (see abstract) to increase levels thereof.
It would have been obvious before the effective filing date of the claimed invention to administer B-hydroxybutytrate directly as taught by Plecko in place of or in addition to, the ketone precursor of Clarke because both references teach increasing beta-hydroxybutyrate levels in a subject, and direct administration of the metabolite represents a productable alternative to administration of the precursor (see KSR, MPEP2143 I(B)). Substituting direct administration of a metabolite for administration of a precursor that produces the same metabolite represents a predictable substitution of known element for another to obtain the same result.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 4-7, 10-15, 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/843278 (reference application) in view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61) and Plecko (Pediatr Res 52: 301–306, 2002).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims a method off inducing autophagy in an individual in need thereof comprising administering a ketone. The instant application further claims the protein is at least about 60 energy % and at least 50 wt% of protein is whey (see claim 1); sarcopenia or ageing individual (claims 5-7); protein from an animal source or milk protein (see claims 10-11); 50% weight of protein is whey (claim 12); free form amino acids or non-hydrolyzed protein (see claim 13); molecular weight of protein from 1-20 kDA (claim 15); including carbohydrate and fat (claim 33); beta hydroxybutyrate (claim 18); 9g protein/100kcal (claim 17).
Co-pending application 18/843278 claims A method of improving and/or enhancing at least one of bone mineralization, bone strength, bone mass, and bone mineral density in an individual in need thereof, the method comprising administering to the individual a composition comprising one or more anabolic amino acids, and the composition further comprising one or more autophagy- inducing compounds (claim 1). Co-pending application 18/843278 further claims wherein ketones are the autophagy inducer (claim 2); leucine and isoleucine (claim 3); aging individual (claim 7); composition comprises a protein selected from the group consisting of milk protein, whey protein, caseinate, micellar casein, pea protein, soy protein, and mixtures thereof (claim 11); wherein the composition comprises a component selected from the group consisting of free form amino acids, unhydrolyzed protein, partially hydrolyzed protein, extensively hydrolyzed protein, and mixtures thereof.(claim 12); hydrolyzed protein (Claim 13); wherein the protein has a formulation selected from the group consisting of (i) at least 50% of the protein has a molecular weight of 1-5 kDa of the protein, (ii) at least 50% of the protein has a molecular weight of 5-10 kDa of the protein and (iii) at least 50% of the protein has a molecular weight of 10-20 kDa of the protein (claim 15). Co-pending application 18/843278 is silent to beta hydroxybutyrate as the ketone or at least 60% energy of the composition.
Chanet teaches of a study of administering to elderly men a protein enriched shake (see abstract, see table 1). In particular, Chanet teaches a nutritional drink with 56.4 energy % from protein (see abstract, 21 gm way protein, 9 g carbohydrates and 3 gm fat, 150 kcal, see abstract and supplemental data). Chanet teaches that “Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 6 wk of intervention in healthy older adults and may therefore be a way to support muscle preservation in older people” (see conclusion). Regarding claims 4 and 17, Chanet teaches 14 gm protein/100 kcal.
Kouw teaches protein supplementation wherein the protein is administered in a beverage at 100 energy % of the beverage (see “experimental protocol”, “Subjects ingested the beverage that contained….” And “production of intrinsically labeled protein and tracer infusion”) and stimulation of muscle protein synthesis (see conclusion). Regarding claims 4 and 17, Kouw teaches greater than 9 gm protein/100 kcal given 100% energy percent is from protein.
It would have been obvious before the effective filling date of the claimed invention to administer the ketone composition of US 18/843278 in combination with the high protein nutritional compositions taught by Chanet or Kouw because both references teach protein enriched beverages for elderly individuals to promote muscle metabolism/protein synthesis and preservation. Combining known nutritional interventions used for the same patient population to improve metabolic and muscle function would have represented a predictable use of prior art elements according to their established functions (see MPEP 2143).
Furthermore, it would have been obvious to one of ordinary skill in the art to optimize the protein content (including energy % and protein per 100 kcal) of the administered nutritional composition, including increasing the protein energy percentage to at least 60 energy% because the prior art demonstrates that increasing protein intake in elderly individuals improves muscle metabolism and protein synthesis. Adjusting the protein percentage and amount per 100 kcal within the known range of protein enriched nutritional compositions would have been routine optimization of a result effective variable (see MPEP2144.05).
Plecko teaches of orally supplementing B-hydroxybutyrate (see abstract) to increase levels thereof.
It would have been obvious before the effective filing date of the claimed invention to administer B-hydroxybutytrate directly as taught by Plecko as the ketone of USAN18/843278 because both references teach increasing beta-hydroxybutyrate levels in a subject, and direct administration of the metabolite represents a productable alternative to administration of the precursor (see KSR, MPEP2143 I(B)). Substituting direct administration of a metabolite for administration of a precursor that produces the same metabolite represents a predictable substitution of known element for another to obtain the same result.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4-7, 10-15, 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-13, 21-24, 27-30 of co-pending Application No. 17/254403(reference application) in view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61) and Plecko (Pediatr Res 52: 301–306, 2002) and Andreux (WO2017036993 A, cited in Applicant’s IDS) and Foegedin (Whey Protein Products, “Encyclopedia of Dairy Sciences, second edition, 2011, cited in Applicant’s IDS) as evidenced by Sigma-Aldrich (β-lactoglobulin from Bovine Milk, Information Sheet, Sigma-Aldrich, accessed on 8/11/2022, cited in Applicant’s IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims a method off inducing autophagy in an individual in need thereof comprising administering a ketone. The instant application further claims the protein is at least about 60 energy % and at least 50 wt% of protein is whey (see claim 1); sarcopenia or ageing individual (claims 5-7); protein from an animal source or milk protein (see claims 10-11); 50% weight of protein is whey (claim 12); free form amino acids or non-hydrolyzed protein (see claim 13); molecular weight of protein from 1-20 kDA (claim 15); including carbohydrate and fat (claim 33); beta hydroxybutyrate (claim 18); 9g protein/100kcal (claim 17).
Co-pending application 17/254403 A method of treating or reducing risk, incidence and/or severity of at least one physical state selected from the group consisting of oxidative stress, a condition associated with oxidative stress, a reduced level of glutathione, and a condition associated with a reduced level of glutathione, the method comprising administering to an individual in need thereof an effective amount of a combination of Nicotinamide Riboside (NR) and at least one of B-hydroxybutyrate (BHB) or a salt thereof” (claim 1). Co-pending application 17/254403 further claims ageing (Claim 2); administered in a food product (claim 6); treating sarcopenia (claim 13). Co-pending application 17/254403 silent to administering the ketone with high protein from an animal or plant source, at least 60% energy and 9g/100 kcal.
However, Chanet teaches of a study of administering to elderly men a protein enriched shake (see abstract, see table 1). In particular, Chanet teaches a nutritional drink with 56.4 energy % from protein (see abstract, 21 gm way protein, 9 g carbohydrates and 3 gm fat, 150 kcal, see abstract and supplemental data). Chanet teaches that “Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein synthesis and increased muscle mass after 6 wk of intervention in healthy older adults and may therefore be a way to support muscle preservation in older people” (see conclusion). Regarding claims 4 and 17, Chanet teaches 14 gm protein/100 kcal.
Kouw teaches protein supplementation wherein the protein is administered in a beverage at 100 energy % of the beverage (see “experimental protocol”, “Subjects ingested the beverage that contained….” And “production of intrinsically labeled protein and tracer infusion”) and stimulation of muscle protein synthesis (see conclusion). Kouw teaches greater than 9 gm protein/100 kcal given 100% energy percent is from protein.
It would have been obvious before the effective filling date of the claimed invention to administer the ketone composition of Co-pending application 17/254403 in combination with the high protein nutritional compositions taught by Chanet or Kouw because both references teach protein enriched beverages for elderly individuals to promote muscle metabolism/protein synthesis and preservation. Combining known nutritional interventions used for the same patient population to improve metabolic and muscle function would have represented a predictable use of prior art elements according to their established functions (see MPEP 2143).
Furthermore, it would have been obvious to one of ordinary skill in the art to optimize the protein content (including energy % and protein per 100 kcal) of the administered nutritional composition, including increasing the protein energy percentage to at least 60 energy% because the prior art demonstrates that increasing protein intake in elderly individuals improves muscle metabolism and protein synthesis. Adjusting the protein percentage and amount per 100 kcal within the known range of protein enriched nutritional compositions would have been routine optimization of a result effective variable (see MPEP2144.05).
Andreux discloses a method of treating a muscle related pathological condition including sarcopenia and age-related sarcopenia (claims 17-18), muscle fatigue (claim 18), age related muscle fatigue (claim 18) comprising administering a composition comprising urolithin (see abstract and claims 1-2, which is a known autophagy inducer as evidenced by Applicant’s specification, paragraph 007, claim 2) and a source of high protein (see claims 1-5, abstract, Figure 1 description). Andreux teaches wherein the protein is casein (see Table 5) which is from an animal source and in particular a milk protein and an unhydrolyzed protein. Andreux teaches wherein at least 50% of the protein is casein (see Table 5, 100% of protein). Andreux teaches wherein the protein can comprise branched chain amino acids in free form (see Table 5).
Furthermore, it would have been obvious to substitute the protein sources of Andreux into the composition of AN17/25403 in view of Chanet and Kouw, since both address age related impairment and one of ordinary skill would have recognized these as conventional dietary proteins in achieving high protein intake. Foegedin teaches that Whey protein Concentrate comprises greater than 50% of B-lactoglobulin. As evidenced by Sigma Aldrich, B-lactoglobulin has a molecular weight to between 10-20kDA (18 kDA). Thus, WPC comprises at least 50% of a protein that is within the claimed range of size. Nevertheless it would have been obvious to optimize the size of the proteins in the formulation to achieve optimal therapeutic effectiveness and absorption.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/ Examiner, Art Unit 1654