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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/23/2026 has been entered.
The office acknowledges Applicants filing of the claim amendments and arguments on 1/28/2026. Claims 11, 30 and 33 have been amended. Claims 1-5, 10, 12-22, 31-32 have been cancelled. Claims 6-9, 11, 23-30, 33 are pending. Claims 23-29 are withdrawn from further consideration pursuant to 37 C.F.R. 1.142(b), as being drawn to non-elected subject matter. Applicants’ arguments have been fully considered. Rejections not reiterated from previous office actions are hereby withdrawn. Arguments, which are directed to withdrawn rejections are thus rendered moot. The arguments in regards to the reiterated rejections/references from the previous office action are addressed below. In light of the claim amendments and further consideration the following modified and/or new rejections have been applied. The action is made non-final. Claims 6-9, 11, 30, 33 read on the elected invention and are examined based on the merits herein.
Response to Applicant’s Arguments
(i) Wolfe in view of Sah:
Applicants argue that the alleged obviousness by the Patent Office here is influenced by hindsight, based on an understanding of the benefits disclosed in the present specification of a co-formulation. It is clear that each cited reference discloses only a single component and hence cannot render a co-formulation obvious unless there are reasons to combine such teachings. It is argued there is no motivation to combine the cited references for multiple reasons. Further argued is that the principal purpose of combining one or more anabolic amino acids with thymol is for the autophagy agent to potentiate the musculoskeletal effect of the anabolic amino acids. Given that autophagy is not mentioned by Wolfe, a skilled artisan would not be motivated to combine the teachings of Wolfe with Sah. There exists a prima facie incompatibility of the teachings of the cited references which would deter the skilled person from combining them, as anabolic amino acids are established to be autophagy-inhibiting, and thymol autophagy-inducing. The skilled artisan would not expect the combination to enhance the effect of the other, but to compete and counteract.
In response, no hindsight reasoning was employed in rejecting the claims over the prior art because it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As stated below in the rejection, Wolfe is relied upon for teaching the compositions comprising amino acids to stimulate muscle protein synthesis, which may optionally comprise thymol. Sah is explicit in teaching thymol in subjects with sarcopenia and enhance skeletal muscle endurance and performance in sedentary patients and in the elderly. Hence a skilled artisan would have found it obvious to add thymol to the composition comprising leucine and administer the composition with sarcopenia or subjects in need of increase in muscle mass with a reasonable amount of success. One would have been motivated to arrive at the composition comprising both the agents and use it in muscle loss therapy is to achieve additive or synergistic therapeutic benefits. Thus the claimed method would have been obvious over Wolfe and Sah. Both amino acid, e.g. leucine and thymol is known in the to increase muscle mass and strength. Hence a skilled artisan would have found it obvious to combine them in a formulation and administer to e.g. subjects with muscle loss. See In re Susi, 169 USPQ 423, 426; In re Kerkhoven, 205 USPQ 1069. Thus, combining them flows logically from their having been individually taught in the prior art.
As to applicants arguments in regards to Wolfe not teaching autophagy and that incompatibility of the teachings of the cited references which would deter the skilled person from combining them, as anabolic amino acids are established to be autophagy-inhibiting, and thymol autophagy-inducing, it is not required that the references teach the mechanisms or those of ordinary skill in the art recognize the inherent characteristics or the function of the prior art, specifically, discovery of the mechanism underlying a known process does not make it patentable. Further, it is also noted that Applicants motivation need not be the same as that of the applicants. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. The law, however, “does not require that the references be combined for the reasons contemplated by the inventor.” In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992). As stated in the rejection one of ordinary skill in the art would have been motivated to combine leucine and/or isoleucine with thymol to increase muscle mass.
The instant method is to ‘administering a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials to an individual in need thereof’. An individual in need thereof can be subjects with sarcopenia or elderly subjects (See instant claims 6 and 7). The reason to combine prior art need not be the same as that of Applicants. Because a motivation-to-combine analysis is a flexible one, and “any need” known in the field and addressed by the patent can provide a reason to combine prior art, in analyzing whether there existed a reason to combine the prior art as asserted, one can consider “the so-called ‘known technique’ rationale.” That the prior art has a different reason to combine the compounds of x and y is no moment as long as there is a sufficient reason to make the combination. See In re Kemps, 97 F.3d 1427, 1430 (Fed. Cir. 1996) (“[T]he motivation in the prior art to combine the references does not have to be identical to that of the applicant to establish obviousness.”). Further the prior art need not teach explicitly teach regarding the principle purpose of combining one or more anabolic acids as applicants have argued. Administration of the same composition formulated from the combined prior art teachings would results in the same pharmacological effects including enhancement of the effects as argued.
Applicants argue that new and unexpected results are provided by the present claims as detailed in the experimental data set forth in the Example of the specification.
As evidenced by Figure 3 of the present application, the combination of thymol and anabolic acids provides an unexpected synergistic effect on muscle function, superior to the sum of the individual components. Administration of the co-formulation as claimed resulted in an improved force-frequency response in aged mice, even exceeding that of untreated adult mice. The technical effect of the claimed invention extends beyond that of the independent disclosures of the prior art.
The cited references alone or in combination do not suggest and cannot have foreseen any such synergistic effect. None of these references disclose a composition comprising an effective amount of thymol or carvacrol in combination with anabolic amino acids. Therefore, although they disclose individual components of the claimed composition, they cannot teach towards a synergistic composition comprising the claimed ingredients which concomitantly promote protein synthesis and removal of damaged materials with enhanced effectiveness. As set forth in In re Soni, "when an applicant demonstrates substantially improved results [...] and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary." (Emphasis added) 54 F.3d at 751. Thus, the unexpected results rebut any alleged prima facie case of obviousness based on the combinations of the cited references.
The Patent Office asserted that the claims were not commensurate in scope with the data provided by the application. Without conceding this point, Applicant submits that the present claims (reciting a combination of thymol and/or carvacrol and Leucine and/or Isoleucine) are supported and enabled by the examples of the description across the entirety of their breadth.
In response, Applicants demonstrate the effects of a mixture of amino acids (AA) (leucine, isoleucine, valine, proline, glycine, lysine and cysteine) and in combination with thymol. The specification states that maximal strength and the force-frequency relationship were significantly improved with AAs supplementation but was further improved with the mix of AAs and thymol suggesting a better improvement in muscle function (Fig 3). The instant claims are to the use of the combination of leucine and/or isoleucine with thymol and/or carvacrol. From the data provided the effect is from the combination of the mixture of AAs with thymol. There are seven amino acids in the mixture with specific amounts. Applicants have not provided any data in regards to the individual administration of isoleucine and/or leucine with thymol and/or carvacrol alone. Since there is no data for thymol or carvacrol by itself or with leucine and/or isoleucine (anabolic amino acids) it cannot be determined whether it is additive or synergistic effects with the specific anabolic amino acids, isoleucine and/or leucine. Further applicants have not provided any data in regards what dosage amount of amino acid or amino acids and carvacrol and/or thymol was administered to arrive at the data. It is noted that the claims do not require an effective amount of the composition for administration in the method. The demonstrated data do not teach what effective amount was used to arrive at Fig. 3. In fact the instant specification teach that ‘The therapeutically effective dose can be determined by the person skilled in the art and will depend on a number of factors known to those of skill in the art, such as the severity of the condition and the weight and general state of the individual’ (See [00107]).
It is noted "[s]ynergism, in and of itself, is not conclusive of unobviousness in that synergism might be expected." In re Kollman, 595 F.2d 48, 55 n.6 (CCPA 1979). From the prior art teachings a skilled artisan would have found it obvious to arrive at the composition comprising thymol and an anabolic amino acid (e.g. leucine or isoleucine) and administer to a subject in need thereof (e.g. subjects with sarcopenia). One would have been motivated to arrive at the composition comprising both the agents and use it in muscle loss therapy is to achieve additive or synergistic therapeutic benefits.
ODP rejections:
that this stage in prosecution is premature for terminal disclaimers because the instant claims are not identified as otherwise allowable, and thus the final version of these claims is not yet known. At such time when the present claims are otherwise allowable, Applicant will reconsider any remaining double patenting rejections.
In response, the rejections have been maintained (but modified necessitated by the amendments) for the reasons provided below.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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) 6-9, 30 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Wolfe (WO 2019/090061 A1, publication date 20190509) in view of Sah (IDS: US 20170326075).
Wolfe discloses the use of amino acid supplements to improve muscle protein, in particular discloses a nutritional composition comprising an effective amount of amino acids which stimulates muscle protein synthesis in a subject the composition; for e.g. the composition comprising histidine, isoleucine, leucine, lysine, methionine etc. (Abstract, claim 1). In one aspect, the present disclosure provides a composition comprising amino acids at a concentration of about 3 5 to 3 8 % leucine (claim 1). Wolfe disclose that as humans age the body's ability to digest protein becomes less efficient. Muscle mass loss starts from the age of 30 years at a rate of 3-8% per decade and accelerates from 60 years of age. This loss reaches up to 35-40% in elderly over 70, and hence, sarcopenia is especially prominent in elderly. Consequently, age associated progressive loss of muscle mass increases the risks of injury and disability [0004]. The reference teaches that it has been discovered that nutritional compositions comprising a mixture of essential amino acids and arginine, including substantial amounts of leucine, effectively stimulate muscle protein synthesis. Advantageously, the formulation was found to be effective in adults where stimulation of muscle protein synthesis is less efficient [0013]. It is taught that thymol can be added as a preservative [0038]. Wolfe teach that the amino acid composition of the invention may also be in the form of intact protein or peptide, provided that the protein or peptide comprises the amino acids of the invention in the correct concentrations relative to each other [0017]. It is taught that large dosages of dietary protein are required to stimulate muscle protein synthesis. The anabolic effects of nutrition are principally driven by the transfer and incorporation of amino acids captured from dietary protein sources, into skeletal muscle proteins [0004]. Administration includes oral, parenteral (e.g. intravenous) [0033].
Wolfe is not explicit in teaching administering a composition comprising thymol.
Sah disclose therapeutic methods comprising the administration of thymol or carvacrol for modulating muscle atrophy, performance, recovery, generation, or maintenance in animals (abstract). Sah disclose that thymol and carvacrol increase calcium cycling in skeletal muscle by activating either TRPV3 ion channels and/or via activation of the sarcoplasmic reticulum calcium release channel [0008]. In vivo, it has been determined that sedentary mice supplemented with thymol for 5 weeks have significantly improved locomotor capacity, increased muscle mass, and enhanced thermogenesis compared to vehicle-treated mice (Fig. 1-9, [0063]-[0067], claims 1-11, 31-33). A method for treating a disease or condition in an animal wherein activation of the sarcoplasmic reticulum calcium release channel is indicated comprising administering thymol wherein the disease or condition is sarcopenia (claims 31-32). Sah teach administration of 20 mg/lg/day of thymol, orally to mice [0067]; compositions and preparations should contain at least 0.1% of active compound. The percentage of the compositions and preparations may, be varied and may conveniently be between about 2 to about 60% of the weight of a given unit dosage form. The amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained [0048]. Sah teach muscle loss/atrophy is a condition associated with several causes, such as aging (sarcopenia), cancer and other diseases (cachexia), chronic illness/immobilization and poor nutrition [0005]. Further taught is that these compounds can be used to: 1) enhance skeletal muscle endurance and performance in sedentary patients and in the elderly; 2) prevent skeletal muscle atrophy in the chronically ill or immobilized; 3) improve overall metabolic health by increasing basal metabolic rate via increased lean body weight and reduced adiposity in the obese; or 4) prevent the negative effects of prolonged space flight on skeletal muscle (atrophy) [0009].
From the teachings of Sah a person skilled in the art before the effective filing date of would have found it obvious to add thymol to the composition comprising leucine because Sah teach that thymol increases muscle mass, and treating condition like sarcopenia. A person skilled in the art would have been motivated to administer a composition comprising leucine and thymol to subjects with sarcopenia or subjects in need of increase in muscle mass with a reasonable amount of success. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed.
As to claim 6-7, the prior art references teach the use of leucine or thymol in ageing population and subjects with sarcopenia. As to claim 8, Sah teach muscle loss is associated with cancer patients and some of the subjects may be critically ill at the last stage. Hence it would have been obvious to a skilled artisan to administer a composition comprising leucine and thymol to such subjects to improve muscle mass. As to claim 9, Sah is explicit in teaching that thymol compound can be used to enhance skeletal muscle endurance and performance in sedentary patients and in the elderly. Myopathy refers to a group of diseases that primarily affect the skeletal muscles, causing weakness and impaired muscle function. Hence a skilled artisan would have found it obvious to administer a composition comprising thymol and leucine to myopathy subjects to improve muscle function and muscle weakness. As to claim 33, Wolfe and Sah teach oral administration of the active agent(s). Hence a skilled artisan would have found it obvious to orally administer the composition comprising the anabolic amino acid(s) and thymol.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Wolfe (IDS: WO 2019/090061 A1, publication date 20190509) in view of Sah (IDS: US 20170326075) and further in view of Cuesta-Triana et al. (Advances in Nutrition, Volume 10, May 2019, p S105-S119).
Wolfe and Sah as discussed above. The rejection above is incorporated herein.
The prior art is not explicit in teaching the composition further comprises protein.
Cuesta-Triana teach that the consumption of dairy products by older people may reduce the risk of frailty, especially with high consumption of low-fat milk and yogurt, and may also reduce the risk of sarcopenia by improving skeletal muscle mass through the addition of nutrient-rich dairy proteins to the habitual diet (see Abstract).
From Cuesta-Triana’s teachings a person skilled in the art before the effective filing date of the invention would have found it obvious that dairy products such as milk comprise proteins and they can improve the skeletal muscle mass. Wolfe further teach that the proteins add muscle strength and dietary protein sources can be converted to skeletal muscle proteins. Hence a skilled person from the prior art would have found it obvious to add protein in the instant method with a reasonable amount of success. A person skilled in the art would have been motivated to add the protein (e.g. diary proteins from animal source) to improve the muscle strength in elderly subjects. Thus claim 11 would have been obvious over the combined prior art teachings.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 6-9, 30, 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 16-23 of co-pending Application 18703117 (‘117) in view of Sah (US 20170326075).
The instant method claims are directed to:
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The dependent claims are limited to specific autophagy compounds, specific anabolic amino acids and the individuals (ageing individual, has sarcopenia or frailty, critically ill, with acute kidney injury, has critical illness myopathy) in need thereof.
‘117 reference claims are directed to :
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The dependent claims (16-23) are limited to critically ill subject(s), amino acid composition improves muscle mass and/or strength, enteral administration, subject is administered in an amount including 0.02 g/kg/day, the amino acid composition is administered enterally (claim 5) and to amount of about 0.1% or more of total protein.
The reference claims do not teach thymol in combination with leucine or isoleucine for promoting protein synthesis and removal of damaged cellular materials in a subject in need thereof (e.g. sarcopenia, where muscle loss is experienced).
Sah teachings discussed as above.
From Sah a person skilled in the art would have found it obvious to add thymol in the method of the reference claims to administer a composition comprising leucine and thymol (0.02 g/kg/day would be 1.4 g for a 70 Kg subject) to reduce muscle loss in a subject. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed.
As to claims 6-8, a person skilled in the art from the reference claims and/or from Sah would have found it obvious to administer a composition comprising leucine and thymol to an ageing individual because muscle loss occurs in aging subjects, subjects with sarcopenia, or critically ill patients.
As to claim 9, a person skilled in the art from reference claims and Sah would have found it obvious to administer the composition comprising leucine and thymol to individuals with myopathy because (i) reference claims teach administration of leucine and/or its composition to improve muscle mass and/or strength (ii) Sah is explicit in teaching that thymol compound can be used to enhance skeletal muscle endurance and performance in sedentary patients and in the elderly. Myopathy refers to a group of diseases that primarily affect the skeletal muscles, causing weakness and impaired muscle function. Hence a skilled artisan would have found it obvious to administer a composition comprising thymol and leucine to myopathy subjects to improve muscle function and muscle weakness.
As to claim 33, the reference claims teach administration of the amino acid enterally and Sah teach oral administration. It is noted that enteral includes oral administration. A person skilled in the art from the teaching of the reference claims and Sah would have found it obvious to administer the composition comprising anabolic amino acid(s) and thymol by oral administration.
This is a provisional nonstatutory double patenting rejection.
Claims 6-9, 11, 30, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US 12317914 (‘914) in view of Sah (US 20170326075).
The instant method claims as above.
‘914 reference claims are directed to a method of potentiating a musculoskeletal effect of one or more anabolic amino acids selected from the group consisting of Leucine, Isoleucine, Arginine, Glutamine, Citrulline and mixtures thereof in an individual in need thereof, e.g. ageing individual (claim 4), sarcopenia or frailty (claim 5), the individual has at least one condition selected from the group consisting of (i) critically ill, (ii) acute kidney injury, (iii) chronic kidney injury, (iv) loss of muscle mass from chronic kidney disease, and (v) loss of muscle function from chronic kidney disease (claim 6), wherein the individual has a critical illness myopathy (claim 7), the composition comprises a protein (claim 1), wherein the administering uses at least one route selected from the group consisting of oral, enteral, parenteral and intravenous injection.
The reference claims do not teach thymol in combination with leucine or isoleucine for promoting protein synthesis and removal of damaged cellular materials.
Sah teachings as above.
From Sah a person skilled in the art would have found it obvious to add thymol in the method of the reference claims to administer a composition comprising leucine and thymol (0.02 g/kg/day would be 1.4 g for a 70 Kg subject) to reduce muscle loss in a subject. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed. As to claims 6-9, the patent teach administration of the composition to such subjects. As to claim 11, the reference composition comprises protein. As to claim 33, the reference claims teach administration by enteral, parenteral etc. Thus the claimed method would have been obvious over the reference claims and Sah.
Claims 6-7, 11, 30, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US 11364254 (‘254) or claims 1, 5-14, 16-20, 23, 24 of 18256489 (‘489) and in view of Sah (US 20170326075).
The instant method claims as above.
‘254 reference claims are directed to a method of reducing a loss of muscle functionality, increasing muscle functionality and/or improving recovery of muscle functionality after muscle atrophy in an individual in need thereof, the method comprising administering to the individual a composition comprising (i) 0.01 mg to about 1.0 g of oleuropein per serving as the only polyphenol, (ii) a fatty acid, (iii) branched chain amino acids comprising leucine, isoleucine and valine, (iv) 800 to 1200 IU of Vitamin D per serving, and (v) whey protein, wherein the composition is administered in a daily amount comprising 5 g to 50 g of the whey protein per day; wherein the composition further comprises a protein selected from the group consisting of casein, pea protein, soy protein and combinations thereof; wherein the individual has sarcopenia; wherein the individual is an elderly having mobility issues or muscle weakness.
‘489 reference claims are directed to a method for treating and/or preventing i) a mitochondria-related disease or condition associated with altered mitochondrial function and/or ii) at least one physical state selected from the group consisting of oxidative stress or a condition associated with oxidative stress in an individual in need thereof, the method comprising administering to the individual a composition comprising an effective amount of a combination of at least one glycine or functional derivative, at least one large neutral amino acid selected from the group consisting of Leucine, Isoleucine; the disease or condition include deleterious effects of aging, muscle loss, musculo-skeletal diseases, myopathy, sarcopenia, frailty etc.; wherein the combination or the composition is administered orally, wherein the healthy adult is elderly.
The reference claims do not teach thymol in combination with leucine or isoleucine for promoting protein synthesis and removal of damaged cellular materials.
Sah teachings as above.
From Sah a person skilled in the art would have found it obvious to add thymol in the method of the reference claims to administer a composition comprising leucine and thymol (0.02 g/kg/day would be 1.4 g for a 70 Kg subject) to reduce muscle loss in a subject. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed. As to claims 6-7, the patent teach administration of the composition to such subjects. As to claim 11, the reference composition comprises protein. As to claim 33, it is within the skill of an artisan to administer by enteral, e.g. oral or parenteral, e.g. by injection based on the subject’s medical need. Thus the claimed method would have been obvious over the reference claims and Sah.
Claims 6-7, 30, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of 12576068 (‘068).
The instant method claims as above.
‘068 reference claims are directed to method for preventing and/or treating sarcopenia and/or for improving skeletal muscle mass, skeletal muscle lean mass, skeletal muscle strength and/or skeletal muscle function in an individual in need thereof, the method comprising administering to the individual a unit dosage form of a composition comprising (i) one or more aromatic amino acids (AAAs) in a therapeutically effective amount and (ii) vitamin B6 and the composition comprises amino acids valine, leucine, isoleucine etc.; the composition can be administered orally.
The reference claims do not teach thymol in combination with leucine or isoleucine for promoting protein synthesis and removal of damaged cellular materials.
Sah teachings as above.
From Sah a person skilled in the art would have found it obvious to add thymol in the method of the reference claims to administer a composition comprising leucine and thymol (0.02 g/kg/day would be 1.4 g for a 70 Kg subject) to reduce muscle loss in a subject. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed. As to claims 6-7, the patent teach administration of the composition to sarcopenia subjects and it is noted that sarcopenia occurs with ageing. As to claim 33, the reference teaches oral administration (enteral).Thus the claimed method would have been obvious over the reference claims and Sah.
Claims 6-9, 11, 30, 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 9, 14, 16, 18-20, 29 of co-pending application, 17596779 (‘779) in view of Wolfe (WO 2019/090061 A1, publication date: 20190509).
The instant method claims as discussed above.
‘779 reference claims are directed to a method of treating, preventing or managing 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 a combination selected from the group consisting of thymol and carvacrol to an individual in need thereof, wherein the composition has at least one characteristic selected from the group consisting the composition augments a plasma thymol and/or carvacrol level in the individual to a level in a range of 50 to 6000 nmol/L plasma, the composition is administered in a daily serving comprising 50 ug to 10 g of the combination in one or more portions, and the composition comprises the combination in a total concentration ranging from about 0.05 wt. % to about 4 wt.% in the composition.
The dependent claims are limited to composition further comprising a protein; the protein selected from milk protein, soy protein etc.; the composition further comprises an autophagy inducer-is selected from the group consisting of spermidine, urolithin, rapamycin, Torin1, valproic acid, polyphenols, caffeine, metformin, 5' AMP-activated protein kinase (AMPK) activators, L-type calcium channel inhibitors, ketones, and mixtures thereof; wherein the individual is an ageing individual; wherein the individual has sarcopenia or frailty or is at risk of developing sarcopenia or frailty; wherein the individual is critically ill.
The reference claims do not teach amino acid, e.g. leucine in the composition for promoting protein synthesis and removal of damaged cellular materials in a subject in need thereof (e.g. musculoskeletal disorder).
Wolfe teachings as discussed above.
From the teachings of Wolfe a person skilled in the art would have found it obvious to add leucine to the composition of the reference claims to stimulate muscle protein synthesis and treat musculoskeletal disorder. As to the limitation of ‘a composition that concomitantly promotes protein synthesis and removal of damaged cellular materials’, it is noted that administration of the composition comprising thymol and leucine as in the instant claim would exhibit the same properties upon administration to an individual in need thereof (e.g. sarcopenia subjects). Thus claim 30 is addressed. As to claims 6-8, a person skilled in the art from the reference claims and/or from Wolfe would have found it obvious to administer a composition comprising leucine and thymol to an ageing individual because muscle loss occurs in aging subjects, subjects with sarcopenia, or critically ill patients. As to claim 9, a person skilled in the art from reference claims and the prior art would have found it obvious to administer the composition comprising leucine and thymol to individuals with myopathy because (i) reference claims teach administration of leucine and/or its composition for treating musculoskeletal disorder (ii) Wolfe is explicit in teaching that the formulation comprising leucine was found to be effective in adults where stimulation of muscle protein synthesis is less efficient; sarcopenia is especially prominent in elderly; age associated progressive loss of muscle mass increases the risks of injury and disability. Myopathy refers to a group of diseases that primarily affect the skeletal muscles, causing weakness and impaired muscle function. Hence a skilled artisan would have found it obvious to administer a composition comprising thymol and leucine to myopathy subjects to improve muscle function and muscle weakness. As to claim 11, from the reference claims teaches that the thymol composition further comprises protein, e.g. milk, soy proteins. As to claim 33, Wolfe teach oral administration of the composition. It is noted that enteral includes oral administration of the active agent(s). A person skilled in the art from the teaching of the reference claims and Wolfe would have found it obvious to administer the composition comprising anabolic amino acid(s) and thymol by oral administration.
This is a provisional nonstatutory double patenting rejection.
Claims 6, 11, 30, 33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of co-pending application, 18843278 (‘278) or claims 1, 3, 5-7, 10-17, 22-24, 26, 29 of co-pending application, 17686054 (‘054).
The instant method claims as discussed above.
‘278 reference claims are directed to 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. The dependent claims are limited to specific autophagy compounds, thymol, carvacrol etc., amino acids, leucine, isoleucine etc., subject being ageing individual, the composition comprises protein, e.g. plant source, route of administration selected from oral, enteral, parenteral.
‘054 reference claims are directed to method of improving and/or enhancing at least one bone benefit selected from the group consisting 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 at least two anabolic amino acids and one or more autophagy- inducing compounds, wherein the one or more autophagy-inducing compounds comprise thymol. The dependent claims are limited to specific amino acids, e.g. Leucine, Isoleucine, wherein the individual (i) is an aging individual; wherein the composition comprises protein, e.g. plant source and the route of administration includes oral, enteral, parenteral, and intravenous injection.
The instantly claimed method would have been obvious over the reference claims because the reference claims teach administering a composition comprising autophagy compounds, thymol, carvacrol with amino acids, leucine, isoleucine to an ageing individual. Thus enteral administration of the composition comprising the same agents to the same set of subjects as in the instant claims would result in the promotion of the protein synthesis and removal of damaged cellular materials, thus addressing claims 6, 30 and 33. Claim 11 is addressed by the reference claims teaching of the composition comprises protein (e.g. plant source).
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627
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