DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-9 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group (II) in the reply filed on 04/07/2026 is acknowledged.
Claims 1-3 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/07/2026.
Secondly, Applicant’s election without traverse of lorecivivint/SM-04690 as the species of therapeutic agent and frailty as the species of age-related disorder in the reply filed on 04/07/2026 is acknowledged.
Priority
Acknowledgement is made of the national stage entry of PCT/RU2022/050044 filed 02/09/2022, which claims foreign priority to Application 2021103259 filed 10/02/2021.
Claim Rejections - 35 USC § 112-Paragraph A
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 4-9 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 the treatment of the age-related disorders comprising administering a compound of Tables 1ab, Table 1c or Table 1d does not reasonably provide enablement for the prevention of any age-related disorder. 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples, (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) The breadth of the claims: The breadth of the claims is directed to the treatment of any age-related disorder as well as the prevention of developing any age-related disorder in a subject in need comprising administering a therapeutically effective amount of a compound within Tables 1ab, Table 1c and Table 1d. As shown in claim 6, the genus of age-related disorders embraces the following diseases including
(2) The nature of the invention: The nature of the invention is treating distinct age-related and lifespan disorders comprising administering distinct compounds within Tables 1ab, Table 1c and Table 1d of the present specification.
(3): The State of the Prior Art: Yazici (Arthritis and Rheumatology Vol. 72 pages 1694-1706. Published 2020) and Deshmukh (Osteoarthritis and Cartilage Vol. 27 pages 1347-1360 published 2019) represents the state of the prior art. Yazici and Deshmukh each teach treating the age-related disorder osteoarthritis in a subject in need comprising administering a therapeutically effective amount of the elected anti-aging species SM-04690. As evidenced by Deshmukh, the age-related disease of osteoarthritis is associated with elevated levels of Wnt signaling via upregulation of CLK2. (Deshmukh Osteoarthritis and Cartilage Vol. 27 pages 1347-1360 published 2019 (Figure 8a-8e). As further evidenced by Deshmukh and Yazici, SM-04960 effectively inhibited Wnt pathway activation by inhibiting CLK2 (Yazici Arthritis and Rheumatology Vol. 72 pages 1694-1706 (2020)) (page 1695; Deshmukh Figure 8). Said anti-aging species SM-04960 therapy resulted in amelioration of at least one symptom of said age-related disease or condition, which is pain (Yazici page 1703 right col.) Nowhere within the boundaries of the reference does either Yazici or Deshmukh disclose that the administration of the elected species SM-04690 would be effective at treating the age-related disease or disorder, such as Alzheimer’s disease, cancer, or Parkinson’s disease in a subject in need, nor prevent the development of said age-related disease or disorders in a subject.
Greicius (Journal of Neurol Neurosurg Psychiatry Vol. 72 pages 691-700 Published 2002) also represents the state of the prior art. Greicius teaches diagnosis and taxonomy of the age-related disorder Alzheimer’s disease. Greicius teaches that Alzheimer’s disease symptoms include deficits in at least two areas of cognition, progressive worsening of memory and other cognitive functions without any other neurological disorder that could explain the cognitive decline, the development of amyloid plaques, neurofibrillary tangles and neuronal loss, wherein the plaques and tangles lead to neuronal loss (page 692 left-right col.). Post-mortem analysis of brain tissue for the characteristics of amyloid plaques is considered necessary for a definitive diagnosis. This is because the art has yet to recognize its presence in essentially all cases. However, to achieve diagnostic status took years of evaluating procedures, both pre and post-mortem, confirming that every case had a degree of this pathology. Even so, diagnostic application is often problematic given variable peptide expression patterns among clinically similar and dissimilar disease states (page 696-697). Greicius further teaches that while there is promise of many agents to prevent Alzheimer’s disease, none have yet proven to be effective (page 693 left col., page 697 right col.).
Given that there a only a few factors that are recognized to have moderate, if any, predictive value in determining the likelihood that patients develop such a disease or to even determine whether patients actually have such a disease, since many of the early signs of Alzheimer’s disease are common complaints of aging or result from other neurological conditions, such as depression, where memory impairment is not present, one of ordinary skill in the art would not accept on its face Applicant's statement that the onset of the age-related mediated disorder Alzheimer’s disease could be effectively prevented using the presently claimed compounds embodied within Tables 1ab, 1c and 1d of the instant specification.
In fact, such complexity of diagnosis precludes a common, art-accepted protocol for preventing or delaying the onset of Alzheimer’s disease in any patient, given that the circumstances or risk factors are unique to that individual and must be considered on a case-by-case basis when determining the most effective approach to in delaying or preventing Alzheimer’s disease, let alone the fact that while there is promise of many agents to prevent Alzheimer’s disease, none have yet proven to be effective.
In other words, not only is the population in need of such treatment not well defined in the art because of the difficulties associated with making an accurate diagnosis, but the disease is also sufficiently complicated and poorly understood such that the idea that any active agent (including the presently claimed compound within Tables 1ab, 1c and 1d) would be capable of preventing the onset of such a condition via its administration would not have been reasonably expected by the skilled artisan. The artisan would have required sufficient direction as to how the administration of the presently claimed active agent(s) could actually determine the population of patients in need of such delay or prevention and how the presently claimed agent(s) could actually delay or prevent Alzheimer's disease such that the artisan would have been imbued with at least a reasonable expectation of success. Such success would not have been reasonably expected given that the concept of a single agent, or even a combination of agents, that is effective against the development of Alzheimer's disease would have been unique as cited in Greicius above, and, thus, met with a great deal of skepticism.
(4) The level of one of ordinary skill: The level of skill in the art is high and is at least that of a medical doctor with several years of experience in the art of geriatric and neurodegenerative diseases.
(5) The level of predictability in the art:
The level of predictability in the art is low given that the state of the prior art (Greicius) teaches that while there is promise of many agents to prevent Alzheimer’s disease and Parkinson’s disease, none have yet proven to be effective (Greicius: page 693 left col., page 697 right col.).
(6) The amount of direction provided by the inventor and (7) The existence of working examples:
Applicant provides zero in-vitro and in-vivo working examples with a compound of Table 1ab, Table 1c or Table 1d to treat let alone prevent the age-related disorders Alzheimer’s disease and Parkinson’s disease. As cited in page 160 of the present specification, all of the 35 working examples are prophetic.
In light of the fact that the specification fails to provide the skilled artisan with any direction or guidance as to how the prevention of the on-set of the age-related disorder Alzheimer’s disease could actually be achieved, since the disclosure is solely directed to the concept of preventing or treating age-related disorders without a working example, the present specification is viewed as lacking an enabling disclosure of the entire scope of the claimed invention and requiring an undue level of experimentation for this aspect of the invention.
(8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The basis for the present rejection is not simply that experimentation would be required, since it is clear from the state of the prior art and Applicant's disclosure that experimentation in this particular art is not at all uncommon, but that the experimentation required in order to practice this aspect of the invention would be undue. Please reference In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976), which states, "The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue." (emphasis added) Applicant fails to address the unpredictability in the art by providing adequate direction or guidance as to how to practice this aspect of the invention, in terms of disclosing how to use the presently claimed compounds of Table 1ab, Table 1c or Table 1d such that preventing the onset of the age-related disorder Alzheimer’s disease could be reasonably achieved, or even any basis for extrapolating the results shown in the working embodiments. As a result, the specification is viewed as lacking an enabling disclosure of the same.
Claim Rejections - 35 USC § 112-Paragraph B
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 4-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. In claims 4-9, the omitted step is an active step of how to achieve the prevention or treatment of the age related disorder. There is no active step regarding how treatment or prevention of an age-related disease or disorder is to be achieved. For example, one interpretation is that the treatment of prevention of an age-related disease or disorder is to be achieved by the active step of administering a compound selected from the group of all compounds listed in Table 1ab, Table 1c and Table 1d to a subject in need thereof. However, said administration step to a subject is not recited in the claim.
Accordingly, one of ordinary skill in the art prior to the time of the invention would not have been apprised of the metes and bounds of the subject matter for which Applicant was presently seeking protection.
For the purposes of examination, the examiner has interpreted that the treatment or prevention of an age-related disease or disorder requires the administration of selected from the group of all compounds listed in Table 1ab, Table 1c and Table 1d to a subject, and subsequent examination is based on this interpretation.
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.
Claim(s) 4-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yazici (Arthritis and Rheumatology Vol. 72 pages 1694-1706. Published 2020).
Yazici teaches treating osteoarthritis in a subject in need comprising administering a therapeutically effective amount of the elected anti-aging species SM-04690.
Regarding claim 4-6, as evidenced by Deshmukh, osteoarthritis is identified as a species of age-related disease. As evidenced by Deshmukh, the age-related disease of osteoarthritis is associated with elevated levels of Wnt signaling via upregulation of CLK2. (Deshmukh Osteoarthritis and Cartilage Vol. 27 pages 1347-1360 published 2019 (Figure 8a-8e). As further evidenced by Deshmukh and Yazici, SM-04960 effectively inhibited Wnt pathway activation by inhibiting CLK2 (Yazici Arthritis and Rheumatology Vol. 72 pages 1694-1706 (2020)) (page 1695; Deshmukh Figure 8).
Regarding claim 7, said anti-aging species SM-04960 therapy resulted in amelioration of at least one symptom of said age-related disease or condition, which is pain (Yazici page 1703 right col.)
Regarding claim 8, wherein the anti-aging treatment is a treatment leading to changing to a healthy parameter, such as a mortality risk in the subject, while said limitation is not explicitly taught in the prior art of Yazici, the compound (SM-04690), the active step of administration, and the same patient population (a patient with an age-related disorder of osteoarthritis) are identical to that of instantly claimed. Therefore, the property of the compound to lead to changing to a healthy parameter in the treated patient must necessarily be present in the prior art regimen of Yazici, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, (i.e., the same active agent, SM-04690), and the composition is used in the same manner (i.e., administered in the same manner to the same subject, a patient with the age-related disorder of osteoarthritis), the properties that Applicant discloses and/or claims must necessarily be present. Furthermore, as stated in MPEP 2112.02, “[u]nder the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered anticipated by the prior art device.”
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.
Claim(s) 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Deshmukh (Osteoarthritis and Cartilage Vol. 27 pages 1347-1360 published 2019), Milne (WO2007/102861 published 09/13/2007) and Muscoskeletal Key: Sarcopenia and Frailty (published 2017).
Deshmukh teaches SM-04960 is a potent inhibitor of CLK2 and is efficacious at inhibiting CLK2 expression in a subject in need (abstract, page 1354 right col. Figure 8a-8e).
The difference between the presently claimed methodology and that of Deshmukh is that Deshmukh does not specifically teach administering the elected species SM-04960 to treat frailty in a subject in need
Milne (WO2007/102861 published 09/13/2007) teaches treating age-related sarcopenia in a subject in need comprising administering a therapeutically effective amount of a compound that inhibits CLK2(page 10, page 205 claims 41-44). Milne teaches that administration of CLK2 inhibitors increase muscle ATP, thereby increasing mitochondrial biogenesis and inhibiting oxidative stress that contributes to sarcopenia pathogenesis (pages 118-119). As evidenced by Muscoskeletal Key (published 2017), sarcopenia is a major component of the elected age-related disorder frailty, as skeletal muscle accounts for 1/3 or more of total body mass (page 2). Thus, patients with age-related sarcopenia as taught by Milne comprise the elected age-related disorder of frailty.
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the art-recognized CLK-2 inhibitor SM-04960 to treat age-related sarcopenia and frailty in a subject, wherein sarcopenia is a major component of frailty as skeletal muscle accounts for 1/3 or more of total body mass in view of the combined teachings of Muscoskeletal Key and Milne, arriving at the presently claimed methodology.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, the combination of Milne and Muscoskeletal Key teaches treating age-related sarcopenia in a subject in need comprising administering a therapeutically effective amount of a compound that inhibits CLK2, wherein said CLK2 inhibitor increases muscle ATP, thereby increasing mitochondrial biogenesis and inhibiting oxidative stress that contributes to sarcopenia, wherein sarcopenia is a major component of frailty as skeletal muscle accounts for 1/3 or more of total body mass (Milne: page 10, pages 118-120, page 205 claims 41-44). Considering Deshmukh teaches SM-04960 is a potent inhibitor of CLK2 and is efficacious at inhibiting CLK2 expression in a subject in need, said skilled artisan would have readily predicted that administration of the art-recognized CLK2 inhibitor SM-04960 would have effectively treated age-related sarcopenia in the administered subject, thereby treating the major component of frailty in the afflicted patient.
Regarding the limitation wherein the administered CLK2 inhibitor that leads to changing to a healthier state such as a mortality risk, while said limitation is not explicitly taught in the prior art of Deshmuhk, Milne and Muscoskeletal Key, the compound (CLK2 inhibitor SM-04690), the active step of administration, and the same patient population (a patient with an age-related disorder of sarcopenia) are identical to that of instantly claimed. Therefore, the property of the compound to lead to changing to a healthy parameter in the treated patient must necessarily be present in the prior art regimen of Deshmuhk, Milne and Muscoskeletal Key, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, (i.e., the same active agent, CLK2 inhibitor SM-04690), and the composition is used in the same manner (i.e., administered in the same manner to the same subject, a patient with the age-related disorder of sarcopenia), the properties that Applicant discloses and/or claims must necessarily be present. Furthermore, as stated in MPEP 2112.02, “[u]nder the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered anticipated by the prior art device.”
MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
In the present case the burden is shifted to Applicant to prove that administered CLK2 inhibitor SM-04960 to the patient comprising sarcopenia and frailty as taught by the combination of Deshmuhk, Milne and Muscoskeletal Key does not lead to changing to a healthier state in the administered patient.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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