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
This office action is in reply to the application filed on 16 November 2023. Claims 1-7 and 9-10 are amended. Claims 8 and 11-19 are cancelled. Currently, claims 1-7 and 9-10 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 February 2024 was filed after the mailing date of the application on 16 November 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The use of the terms Vaseline (pg. 15, line 327; pg. 26, line 579), Lubri Wax (pg. 15, line 329), Tween 80 (pg. 16, line 371), Witepsol (pg. 17, line 373), Subanal (pg. 17, line 374), Tween (pg. 17, line 376), Monolan (pg. 17, line 376), Tego-G (pg. 17, line 377), Hydrokote SP (pg. 17, line 378), Hydrokote 25 (pg. 17, line 378), Hydrokote 711 (pg. 17, line 379), Mitotracker Green (pg. 34, line 749), Easy Blue (pg. 35, line 766), PolyFect (pg. 37, line 812), Lipofectamine 2000 (pg. 38, line 832), Sonde (pg. 39, line 855), which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A review of the language of the rejected claims indicates that these claims are drawn toward “a method of preventing or treating sarcopenia, comprising the step of administering JC1-40 or a pharmaceutically acceptable salt thereof to a subject in need thereof. A description of the term “a method of treating or preventing a disease or disorder…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984). Accordingly, claiming “a method of treating or preventing a disease or disorder…” in the absence of knowledge as to what the Applicant regards as “a method of treating or preventing a disease or disorder…” is not a description of “a method of treating or preventing a disease or disorder…”. In Applicant’s originally filed specification, background art, expounds upon sarcopenia and sarcopenic obesity, mitochondrial function and a relationship to the “complex pathogenesis of sarcopenia, such as oxidative stress, cell death, inflammation and so on”, and RORα transcription factor and promotion of muscle differentiation. However, the applicant only demonstrates applications to in vitro activation behavior including C2C12 myoblasts treated with JC1-40, where mitochondria staining showed increased fluorescent staining compared to the control, where the implied conclusion is that “the mitochondrial membrane potential was increased”, and RNA extracted from C2C12 myoblasts treated with JC1-40 and associated with mitochondrial components showing increased expression levels. Expression levels of NRF1, TFAM, PGC-1α, NRF-1, and NRF-2 were also measured. Further in vitro demonstration included TFAM dependency on RORα and an in vivo experiment utilizing diet induced animal model where higher expression levels of COX4 and TFAM in experimental animals compared to control implied significant improvement of sarcopenia. Applicant does not demonstrate that the product is capable of the claimed method of “preventing or treating sarcopenia, to the breadth and scope of which broadest reasonable interpretation requires. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. “In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.” One of skill in the art would not recognize from the disclosure that the applicant was in possession of “ a method of treating or preventing a disease or disorder…” as claimed.
It is also known that there are significant challenges translating in vitro and in vivo studies to a clinical setting and that not all in vitro and in vivo studies can be directly translated to the clinical setting. Indeed, J. M. McKim (Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo resistance, Combo. Chem. & High Throughput Scr. 2010, 13, 188-206) emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior cell or animal models (Introduction). As the specification discloses working examples only performed in vitro and in vivo, one of skill in the art would not recognize that the Applicant was in possession of “a method of preventing or treating sarcopenia” in a clinical setting.
Claim 1, and therefore dependent claims 2-4, and claim 9, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a (1) method of increasing mitochondrial membrane potential in C2C12 cells, (2) increasing mitochondrial quantity in HeLa cells, (3) increasing mRNA expression of mitochondrial constituent genes in C2C12 cells, (4) increasing mRNA and protein expression of mitochondrial biosynthesis regulatory factor and promotor activity enhancement, (5) increasing TFAM expression, and (6) increasing mitochondrial biosynthesis effect on muscle tissue in an animal model, does not reasonably provide enablement for treating sarcopenia in any subject in need thereof. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01 (a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant. A discussion of these factors as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) nature of invention – The applicant’s claims are broad. For example, claim 1, and therefore dependent claims 2-4, are generally recited: are directed to “a method of preventing, improving, or treating sarcopenia, comprising the step of administering a composition comprising JC1-40 or a pharmaceutically acceptable salt thereof as an active ingredient to a subject in need thereof”. Neither the independent claim 1 nor any of the dependent claims define or limit a subject to humans by the claim language. As taught by Cruz-Jentoft et al. (Sarcopenia, Lancet 2019, 393, 2636-2646), sarcopenia is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality (abstract). It can therefore be reasonably construed to encompass any animal or living being that has muscle and lives long enough to suffer from sarcopenia. The subject also neither needs to be “old” or “elderly” and can be considered of any age including juveniles as taught by Jung et al. (Sarcopenia in youth, Metabolism 2023, 144, 155557) where “recent research has revealed causes other than aging that may induce sarcopenia in young people, contrary to adulthood, resulting in exaggerated muscle dysfunction later in life” (abstract). While the Applicant discloses the potential application of the product in the upregulation of pathways presumed associated with mitochondrial function and muscle development, they are not unto themselves demonstrative single agent means of treating sarcopenia. Indeed, the Applicant notes themselves that sarcopenia and related sarcopenic obesity are subsets of the broad category of aging and obesity, that sarcopenia which presents as a decrease in muscle mass and strength, can be one of, but not the only, underlying factor of various diseases and disorders including loss of mobility, chronic liver disease, cardiovascular disease, lung disease, brain disease, and degenerative diseases, of which the product may potentially play a role in the treatment of, but discloses only in vitro and in vivo working examples. It is noted by the Applicant that the current-art treatment involves lifestyle therapies including calorie restriction, and that drugs specifically treating sarcopenia are absent. Consequently, it is reasonable to conclude that the claim of sarcopenia, to what is known to one of ordinary skill in the art, is broad and encompasses numerous underlying factors that are differentiated by types and subtypes, patient populations, etiologies, etc. For example, Beaudart et al. (Health outcomes of sarcopenia: a systematic review and meta-analysis, PLoS ONE 2017, 12, 1, e0169548) teaches that there are several definitions of sarcopenia, but that no worldwide consensus has been reached, though it is an independently recognized condition. Holistically, it is defined as a decline in muscle strength or physical performance, though advancing age is noted not to be the sole or even primary explanation for this loss. Additionally, maintenance or gain in muscle mass doesn’t prevent age-related declines as other factors such as denervation of muscle fibers and other neural changes also contribute. It is also known that there are significant challenges in translating in vitro and in vivo studies to all biological subjects and further to subjects in a clinical setting and that not all can be directly translated. As the specification discloses working examples only performed in vitro and in vivo, one of skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is “a method of preventing or treating sarcopenia” and can be used to prevent and treat the possible breadth of what is already a diverse, ill-defined disease or disorder that appears to arise from multiple factors and pathways and has not been well-defined by the field itself.
(C) The state of the prior art – The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05(a). As taught by Cruz-Jentoft, sarcopenia is defined as a progressive and generalized skeletal muscle disorder, associated with adverse outcomes, and that full agreement on the variables of sarcopenia has yet to be reached. Sarcopenia can even be diagnosed in multiple perspectives, as an acute, sudden disease, possibly arising from disease or sudden immobility, or as an outcome from a chronic condition, to a function-centered model instead of a disease-centered model, in which the capacities of an individual, mental and physical, interacts with the environment. Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for preventing and/or treating sarcopenia as claimed.
(D) The level of one of ordinary skill in the art - MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
These hurdles render application of “a method of preventing or treating sarcopenia, comprising the step of administering JC1-40 or a pharmaceutically acceptable salt thereof to a subject in need thereof” to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E) Existence of working examples & (F) amount of direction or guidance by the inventor – The prior art, such as that taught by Cruz-Jentoft, outlines three main conditions of differential diagnosis of sarcopenia including malnutrition, cachexia, and frailty. The epidemiology of sarcopenia, while skewed to an older cohort, affects a broad arrangement, in both sexes, and varying populations differently, with a multitude of frequent underlying causes including, but not limited to, nutritional issues such as low protein intake, inactivity such as bed rest, latrogenic such as drug-related, and diseases including bone and joint diseases, cardiorespiratory diseases, metabolic disorders, endocrine disorders, neurological disorders, cancer, and liver and kidney disorders. Treatment is broadly categorized into non-pharmacological and pharmacological approaches, where an example of a non-pharmacological approach could involve resistance exercise. Cruz-Jentoft notes that there is no specific drug to cite in a pharmacological approach and that ten pharmacological interventions are advised including vitamin D, combined oestrogen-progesterone, dehydroepiandrosterone, growth hormone, growth hormone-releasing hormone, combined testosterone-growth hormone, insulin-like growth factor-1, pioglitazone, testosterone, and angiotensin-converting enzyme inhibitors. Conversely, the specification does not demonstrate, as previously established, a means to prevent or treat sarcopenia generally in all possible forms. For instance, the results in Example 6 of the instant specification describe sarcopenia induced by a high-fat diet and treatment with JC1-40. As previously discussed, obesity can be a corollary to sarcopenia but is not a necessarily a direct cause of, and as a consequence, it is not sufficiently evident that sarcopenia has been established in the mice of the study. Additionally, the histology images provided in Fig. 6B do not make evident the differences between low fat diet, high fat diet, vehicle and JC1-40 treated gastrocnemius tissues. While there may be specific details evident to the originator of the data, there are issues to a person of ordinary skill in the art, such as the specific characteristics of sarcopenia to look for and identity of the different features in the slides. It is also not readily apparent that there is a significant difference in the fluorescence from COX4 and TFAM antibodies between the two vehicles and experimental slides from the drawings provided. Furthermore, neither the prior art nor the instant specification describes a reasonable expectation that an administration of a cosmetic composition comprising JC1-40 would improve muscular function. The instant specification describes the formulation for a cosmetic composition largely as lotions, creams, and other topical applications. Without evidence, as the example provided is oral and ingested, there is no reason to expect that a topical application would be enabled. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims.
(G) Quantity of experimentation needed to make or use the invention – Taken, together, the prior art demonstrates that the disease/disorder of sarcopenia, arises from multiple factors, can be diagnosed in multiple ways, can be defined in several ways, and can be broadly treated by several means with necessarily ambiguous outcomes due to the broad nature of the population being treated. This covers a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates selective activation activity on specific biological mechanisms, it does not demonstrate how the species JC1-40 would be able to matriculate into a preclinical candidate, much less a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claim invention and the unpredictability in successful application as described by claims 1-4 and 9, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in preventing or treating sarcopenia. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claim and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kyu et al. (Pharmaceutical composition for prevention or treatment of cancer comprising ROR activating regulator, KR20160132534A, 2016).
Kyu discloses the following structure as a pharmaceutical composition, named JC1-40, including as pharmaceutically acceptable salt, as compared to claim 1:
PNG
media_image1.png
210
478
media_image1.png
Greyscale
Regarding claims 2 and 4-6 “wherein” clauses, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In this case, the wherein clause expresses the desired result: in claim 2, JC1-40 is an activator of RORα protein; in claim 4, where JC1-40 satisfies at least one of the following: a) increasing mitochondrial membrane potential, b) increasing mitochondrial quantity, and c) increasing mitochondrial biosynthesis; in claim 5, JC1-40 increases the expression or activity of a gene or protein selected from the group consisting of SDHA, COX5A, MCAD, PGC-1α, NRF1, NRF2α, and TFAM; and claim 6, expression of TFAM gene or protein is dependent on RORα. The wherein clause does not recite any active steps in which protein levels and mitochondrial biosynthesis are measured and determined. Additionally, the wherein clause recites a property of RORα, as evidenced by the instant specification that JC1-40 is an activator of RORα, and that increased RORα expression promotes muscle differentiation, expression of FGF21, activation of mitochondrial complex II, and formation of super-complexes. Thus, it would be reasonable to expect that the application of JC1-40 would produce the expected downstream effects. As such, this clause does not further narrow the scope of the claimed method. See MPEP 2112.02.
Kyu teaches that the JC1-40 composition contains a RORα activity modulator that can suppress cancer proliferation by activating RORα activity in cancer cells (0002), as compared to claim 2.
Kyu also teaches that the disclosed compound can be effectively administered, depending on a patient’s age, sex, and weight, between 1 to 5,000 mg/kg, or converted to µM, between 3.5 to 17,500 µM, as compared to claim 3. See MPEP §2144.05.
Additionally, Kyu discloses in the section Experimental Results, Changes in hepatoma cell lines due to RORα overexpression, that PDK and PDH expression levels decreased and increased, respectively, in a RORα concentration dependent manner, implying the promotion of oxidative phosphorylation of pyruvate rather than glycolysis, resulting improving mitochondria biosynthesis, as compared to claim 4.
As such, claims 1-4 are anticipated by Kyu and rejected.
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 non-obviousness.
Claims 1-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kyu et al. (Pharmaceutical composition for prevention or treatment of cancer comprising ROR activating regulator, KR20160132534A, 2016) in view of Cruz-Jentoft et al. (Sarcopenia, Lancet 2019, 393, 2636-2646) and Kim et al. (Liver-specific deletion of RORα aggravates diet-induced nonalcoholic steatohepatitis by inducing mitochondrial dysfunction, Scientific Reports 2017, 7, 16041).
Kyu discloses JC1-40 and subsequent application to RORα activity modulator that can suppress cancer proliferation.
Kyu, however, does not disclose the application of JC1-40 to the prevention, improvement, or treatment of sarcopenia to a subject in need thereof.
Cruz-Jentoft rectifies this deficiency by teaching that sarcopenia is defined as a progressive and generalized skeletal muscle disorder, associated with adverse outcomes, and that a full agreement on the variables of sarcopenia has to be reached in a global consensus. Sarcopenia can even be diagnosed in multiple perspectives, as an acute, sudden disease, possibly arising from disease or sudden immobility, or as an outcome from a chronic condition, to a function-centered model instead of a disease-centered model, in which the capacities of an individual, mental and physical, interacts with the environment. Sarcopenia can also be present in individuals suffering from obesity, identified with both low muscle mass and increased adiposity, but can remain unnoticed when the focus of care is only obesity and can lead to adverse outcomes, as compared to claim 7. Sarcopenia and obesity are noted to share underlying patho-physiological pathways and that the loss of muscle loss of sarcopenia increases the risk of death and disability during observed weight loss when individuals are trying to address obesity.
Cruz-Jentoft also outlines that treatment is broadly categorized into non-pharmacological and pharmacological approaches, where an example of a non-pharmacological approach could involve resistance exercise. Cruz-Jentoft notes that at the time there was no specific drug to cite in a pharmacological approach, but that early evidence from clinical myostatin inhibition trials, recognizing that myostatin acts as a brake on muscle differentiation, have reported that a myostatin antibody was associated with increased muscle mass and improvement in some measures of physical performance in older patients.
Kim teaches that the pathology of sarcopenia has a number of possible underlying mechanisms, including age-related decline in mitochondrial function. In this case, Kim teaches that the process of mitochondrial biogenesis, the expansion of the existing mitochondrial network through both growth and division, is constantly ongoing in myofibers but declines with aging, resulting in the decrease in muscle mass associated with sarcopenia. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is the master regulator of mitochondrial biogenesis and glucose and fatty acid metabolism and also serves as a co-activator for a number of nuclear genes encoding mitochondrial proteins including Transcription factor A of the mitochondria (Tfam) which is a regulator of mitochondrial biogenesis and coordinator of nuclear and mitochondrial genomes, as compared to claims 5 and 6. Kim also teaches that natural and synthetic ligands will bind to RORα to increase the transcriptional activity of target genes by the induction of DNA binding of RORα and recruitment of co-activators including PGC-1α. In the studied models involving patients with nonalcoholic fatty liver disease and animals with nonalcohol steatohepatitis, expression of RORα is severely attenuated, suggesting association, in this case, with the pathogenesis of nonalcoholic fatty liver disease.
While Kim does not explicitly teach activating RORα, it is reasonable to infer that a method of upregulating RORα expression would have the same upstream effects of upregulating PGC-1α, and therefore Tfam. This, in turn, could lead to an improvement in muscle function due to the relationship between mitochondrial function and myofiber growth. Since the combined prior art methods of treating sarcopenia teaches the instantly claimed methods, administration for the same purpose with same effective dose, same target population, it would inherently have the same properties, therefore meeting the limitations of claim 5-6 and 10. Moreover, while the prior art does not explicitly teach these properties, the burden is on the Applicant to show the prior art does not have these properties.
Thus, administering the instantly claimed compounds, could increase mitochondrial biosynthesis and could improve muscle function.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
As such, it is prima facie obvious, to a person of ordinary skill in the art, to consider the use of JC1-40, as an activator of RORα, to improve mitochondrial function through the signaling pathway of RORα to PGC-1α to Tfam upregulation, and consequently improve myofiber growth and division, potentially resulting in increased muscle mass in patient populations suffering from sarcopenia, including sarcopenia obesity.
Summary
Claims 1-4 and 9 are rejected under 112(a). Claims 1-4 are rejected under 35 U.S.C. 102(a)(1). Claims 5-7 and 10 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622