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 June 18, 2026 is acknowledged. Claims1-2 were amended, claims 3, 12, 16, 18 were canceled and claims 1-2, 4-11, 13-15 and 17 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 2, 8-9 remain withdrawn as being drawn to a non-elected species/invention. Claims 1, 4-7, 10-11, 13-15 and 17 are examined on the merits of this office action.
*After further review, a third non final follows due to the new Double patenting rejection presented below which was filed after the mailing of the last office action.
Withdrawn Rejections/Objections
The rejection of claim(s) 1, 4-7 and 17 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over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71) and Kouw (J Nutr 2017;147:2252–61) is withdrawn in view of amendment of the claims filed June 18, 2026.
The rejection of claim(s) 1, 4-7, 10-11, 13-14, 17 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applied to claims 1, 4-7, 17 above, in further view of Odum (Toxicol Sci. 2001 May;61(1):115-27, cited previously) is withdrawn in view of amendment of the claims filed June 18, 2026.
The rejection of claim(s) 1, 4-7, 10-15 and 17 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from Bovine Milk, Information Sheet, Sigma-Aldrich, accessed on 8/11/2022, cited in Applicant’s IDS) is withdrawn in view of amendment of the claims filed June 18, 2026.
The rejection of claims 1, 4-7, 10-15, 17-18 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view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61) and Plecko (Pediatr Res 52: 301–306, 2002) is withdrawn in view of amendment of the claims filed June 18, 2026.
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, 10-11, 13-15 and 17 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while describing autophagy induction using various inducers and citing publications concerning beta hydroxybutyrate (BHB), does not reasonably enable administration of BHB in combination with the claimed high protein dietary composition to induce autophagy in an individual in need thereof across the full scope of the claims. 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 BHB in combination with a diet rich in protein, wherein the diet rich in protein is at least 60 energy % of the composition and at least 50 wt% of the protein is selected from casein, whey protein, pea protein or soy protein. Claims 4-7 claim wherein the individual is ageing and or has sarcopenia or frailty and at risk of developing sarcopenia or frailty. The claims are not limited to a particular tissue, disease state, metabolic condition, or physiological circumstance. Rather, the claims broadly encompass administration of BHB to induce autophagy in any individual meeting the recited limitations.
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 specification cites publications describing BHB and autophagy, including Camberos Luna and Gomora Garcia (references cited in Applicant’s IDS).
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). However, such knowledge would not supply the missing guidance necessary to determine whether administration of beta hydroxybutyrate in combination with the claimed dietary composition induces autophagy throughout the full scope of the claims without extensive experimentation.
Amount of Guidance/ The Presence or Absence of Working Examples
The specification generally identifies BHB as an autophagy inducer and describes standard assays for detecting autophagy. However, the specification provides no working examples in which BHB is administered to any animal o human subject to indue autophagy. Instead, Applicants have provided NPL references (provided in the IDS filed June18, 2026) describing in vitro neuronal cell culture experiments performed under glucose deprivation. The specification provides no experimental guidance regarding effective dosages of BHB, routes of administration, treatment duration, biomarkers confirming induction of autophagy in vivo, or administration of BHB in combination with the claimed high protein diet.
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 full scope of the presently claimed methods.
The Quantity of Experimentation Necessary
A person of ordinary skill in the art would be required to determine whether administration of BHB in combination with the claimed dietary composition induces autophagy across the broad range of individuals encompassed by the claims, including different tissues disease states and physiological conditions. Such experimentation would require extensive in vivo studies to determine effective dosages, routes of administration, treatment durations, appropriate biomarkers for confirming autophagy induction and efficacy across the various patient populations encompassed by the claims. The specification provides insufficient guidance for conducting these studies without undue experimentation. Taking into account the breadth of the claims, the absence any in vivo BHB working examples, the limited in vitro neuronal data relied upon by the specification, the unpredictability of autophagy biology, and the quantity of experimentation required, the specification does not reasonably enable one of ordinary skill in the art to practice the full scope of the claimed invention without undue experimentation.
Response to Applicant’s Arguments
Applicants argue that amendment of the independent claim 1 to recite BHB overcomes the enablement rejection because the specification cites Camberos Lucas, Gomora Garcia and Coronado Monroy which allegedly demonstrates that DBHB stimulates autophagy. Applicant further argues that one of ordinary skill in the art would have understood that the spermidine data in the specification could be replaced with BHB to achieve the same synergistic effect with high protein.
Applicants arguments have been fully considered but not found persuasive. Applicants amendment narrows the claimed autophagy inducer from ketones generally to BHB and therefore addresses the portion of the enablement rejection directed to the breadth of the ketones. However, the amendment does not overcome the remaining enablement deficiency because the specification still fails to enable the full scope of the amended claims. The claims are directed to a method of inducing autophagy in an individual in need thereof by administering BHB in combination with a high protein dietary composition, including aging individuals and individuals having or at risk of sarcopenia or frailty. The specification does not provide any working example in which BHB is administered to an animal or human subject in combination with the claimed dietary composition to induce autophagy. Camberos-luna reports in vitro experiments performed in cultured cortical neurons under glucose deprivation and concludes that D-BHB stimulates autophagic flux under those energy deficient conditions while improving neuronal survival. Likewise, Gomora Garcia investigates D-BHB in neuronal cells and evaluates mitochondrial quality control and the autophagy lysosomal pathway. Coronado Monroy similarly reports cellular studies in astrocytes. None of these references demonstrates administration of BHB to an individual or establishes induction of autophagy throughout the broad range of individuals encompassed by the claims.
Applicant further contends that one of ordinary skill in the art would understand that the spermidine data in the specification could be replaced with BHB to achieve the same synergistic effect. However, this assertion is unsupported by any working example or experimental data contained in the specification. The specification contains only a working example using spermidine and does not demonstrate that BHB, when administered in combination with the claimed high protein dietary composition, produces the claimed induction of autophagy in an individual. Enablement must be supported by the disclosure itself and cannot rest upon unsupported assertions that one embodiment could simply be substituted for another across the full scope of the claims. Accordingly, while Applicant has narrowed the identity of the ketone to BHB, the specification still lacks sufficient guidance, working examples, and in vivo data demonstrating administration of BHB in combination with the claimed dietary composition to induce autophagy in an individual across the full scope of the amended claims. Therefore, the rejection under 35 USC 112(a) is maintained.
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, 10-11, 13-15, 17 remain 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 (BHB in particular). 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.
Response to Applicant’s Arguments
Applicant notes that terminal disclaimers would be premature at this stage in examination because the present claims are not yet otherwise allowable, and thus the final version of these claims is not yet known. Furthermore, the claims of the co-pending applications may also be amended during examination. As a result, at a later state of examination, the claims of the co-pending applications may no longer be alleged to be the same as the present application. At such time when the claims of the present application are otherwise allowable, Applicant will reconsider any remaining double patenting rejections. Accordingly, Applicant respectfully requests that the provisional double patenting rejections be withdrawn or held in abeyance until claims are otherwise allowable in the present application.
Applicant’s arguments have been fully considered but not found persuasive. The rejection is properly maintained while the cited applications remain pending. Applicant’s assertion that the claims of the co-pending applications may be amended during prosecution is speculative and does not overcome the present rejection. Thus, the provisional nonstatutory double patenting rejection is maintained.
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, 10-11 and 13-14 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), Kouw (J Nutr 2017;147:2252–61),Andreux (WO2017036993 A, cited in Applicant’s IDS) and Plecko (Pediatr Res 52: 301–306, 2002).
Regarding claims 1 and 4,Clarke teaches administration of 3 hydroxy butyl 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 claim 6, Clarke expressly discloses administering to elderly/geriatric patients (see paragraph 0036, claim 9).
Regarding claim 7, Clarke expressly discloses administering 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; BHB as the autophagy inducer and wherein the protein formulation wherein at least 50 wt% of the protein is casein (or soy or pea protein).
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 whey 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.
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, a whey protein) which is from an animal source and in particular a milk protein and an unhydrolyzed protein and also whey protein isolates and concentrates (see claim 9).
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).
Plecko teaches of orally supplementing B-hydroxybutyrate (see abstract) to increase levels thereof.
Regarding the 60 energy% of the composition and greater than 8 g protein/100 kcal, 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 higher 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).
Regarding use of BHB as the ketone, 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 predictable 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.
Regarding the specific protein amount (WT% and type), It would have been obvious before the effective filing date of the claimed invention to combine Clarke’s in view of Chanet, Kouw and Plecko BHB 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 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 (see MPEP 2112).
Response to Applicant’s Arguments
Applicant argues that amendment of independent claim 1 to incorporate the limitation of former dependent claims 12 and 18 overcomes the pending obviousness rejections because those dependent claims were not included in the prior art rejections.
Applicants arguments have been fully considered but not found persuasive. The claims have been amended and therefore have been reconsidered in light of the amended claim language. The present office action sets forth a new rejection addressing the amended limitations of claim 1. Specifically, the rejection now relies upon Clarke in view of Chanet, kouw, Andreux and Plecko. As explained above, Chanet and Kouw teach the claimed high protein dietary composition. Andreux teaches a protein formulation wherein at least 50 wt% of the protein is casein, as now recited in amended claim 1. Plecko teaches administration of BHB, as now recited in amended claim 1. Thus, the amended limitations have been fully considered and addressed in the present rejection. Therefore, Applicant’s amendment does not overcome the rejection under 35 USC 103.
Claim(s) 15 is rejected under 35 U.S.C. 103 as being unpatentable over Clarke (US20110237666 A1) in view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61),Andreux (WO2017036993 A, cited in Applicant’s IDS) and Plecko (Pediatr Res 52: 301–306, 2002) as applied to claims 1, 4-7, 10-11 and 13-14 and 17 above in further view of 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 references above are silent to the specific molecular weight make up of the proteins in the formulation.
However, 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.
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, 10-11, 13-15, 17 remain 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,cited previously), Kouw (J Nutr 2017;147:2252–61, cited previously) and Luna (cited in Applicants IDS). *All references cited previously.
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 (BHB in particular). 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.
Luna teaches BHB stimulates autophagy (see abstract).
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).
It would have been obvious before the effective filing date of the claimed invention to administer B-hydroxybutyrate as the ketone autophagy inducer taught by Luna (cited in Applicant’s IDS) as the ketone of USAN19/706429 because Luna teaches that BHB is a ketone that indues autophagy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant notes that terminal disclaimers would be premature at this stage in examination because the present claims are not yet otherwise allowable, and thus the final version of these claims is not yet known. Furthermore, the claims of the co-pending applications may also be amended during examination. As a result, at a later state of examination, the claims of the co-pending applications may no longer be alleged to be the same as the present application. At such time when the claims of the present application are otherwise allowable, Applicant will reconsider any remaining double patenting rejections. Accordingly, Applicant respectfully requests that the provisional double patenting rejections be withdrawn or held in abeyance until claims are otherwise allowable in the present application.
Applicant’s arguments have been fully considered but not found persuasive. The rejection is properly maintained while the cited applications remain pending. Applicant’s assertion that the claims of the co-pending applications may be amended during prosecution is speculative and does not overcome the present rejection. Thus, the provisional nonstatutory double patenting rejection is maintained.
Claims 1, 4-7, 10-11, 13-15, 17 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of co-pending Application No. 19/706429(reference application) in view of Chanet (J Nutr 2017;147:2262–71), Kouw (J Nutr 2017;147:2252–61) and Luna (cited in Applicants IDS) 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 (BHB in particular). 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 19/706429 claims “A method for treatment, prevention or management of cellular malfunction, genome damage, or a disease or condition associated with altered mitochondrial function or reduced mitochondrial density, the method comprising administering a composition comprising at least one component selected from the group consisting of thymol and carvacrol to an individual in need thereof.” (claim 1); administering an autophagy inducer such as a ketone (claims 7); ageing individual (claim 8); sarcopenia (claim 9); whey protein or caseinate (claims 4-5); A method comprising administering a composition comprising a combination of an autophagy inducer and high protein, the composition is administered to provide an amount of the combination that concomitantly promotes protein synthesis and removal of damaged cellular materials to an individual in need thereof (claim 11).
Co-pending application 19/706429 is silent to BHB and the specific amounts of protein.
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.
Luna teaches BHB stimulates autophagy (see abstract).
It would have been obvious before the effective filling date of the claimed invention to administer the ketone composition of Co-pending application 19/706429 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 AN19706429 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.
It would have been obvious before the effective filing date of the claimed invention to administer B-hydroxybutytrate as the ketone autophagy inducer taught by Luna (cited in Applicant’s IDS) as the ketone of USAN19/706429 because Luna teaches that BHB is a ketone that indues autophagy.
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/Primary Examiner, Art Unit 1654
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