DETAILED ACTION This office action is in response to the Applicant’s filing dated March 15 th , 2023 . 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. Status of Claims Claims 1-2 5 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed on March 15 th , 202 3 . Acknowledgement is made of Applicant's amendment of claims 5-8, 10, 12-19 and 22-24; and cancelation of claims 26-29 . Priority This application is a 371 of PCT/CA2021/051303 filed on September 17 th , 20 21 ; and has a PRO of 63 / 079 , 508 filed on September 17 th , 2020 . Claim Rejections - 35 USC § 112(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. Claim s 1-20 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 showing R-carvedilol prevents and rescues neuronal hyperactivity and memory loss in 5xFAD mice in vivo in Example 6 (pages 32-33); prevents subiculum neuronal cell loss in 5xFAD mice in vivo in Example 7 (pages 33-34); and rescues memory impairment, LTP deficit and neuron loss in 3xTG mice in vivo in Example 12 (pages 37-38), does not reasonably provide enablement for prevention of memory loss, long-term potentiation impairment, neuronal cell death, neuronal hyperactivity or Alzheimer’s Disease, particularly in humans. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation . In re Wright , 999 F.2d 1557, 1561 ( Fd . Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that: The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt , 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation". The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands , 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman , 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors: 1- the quantity of experimentation necessary, 2- the amount of direction or guidance provided, 3- the presence or absence of working examples, 4- the nature of the invention, 5- the state of the prior art, 6- the relative skill of those in the art, 7- the predictability of the art, and 8- the breadth of the claims These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher , 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons: 1. The nature of the invention, state and predictability of the art, and relative skill of those in the art The invention relates to a method of treating or preventing at least one of the following in a subject: (a) memory loss, (b) long-term potentiation impairment, (c) neuronal cell death and (d) neuronal hyperactivity ; including Alzheimer’s disease, comprising administering a therapeutically effective amount of R-carvedilol to the subject . The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience. The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher , 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al ., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). As illustrative of the state of the art, the examiner cites Sabbagh et al (Neurobiology of Aging, 2013; 34:169–183) ; de Haan et al ( PLoS Computational Biology , (2017), 13(9), e1005707); and Cummings et al ( Alzheimer's Research & Therapy , (2016), 8(39), 1-12 ). Sabbagh, cited for evidentiary purposes , teaches substantial resources and effort have been invested into the development of therapeutic agents for Alzheimer’s disease (AD) with mixed and limited success; research into the etiology of AD with animal models mimicking aspects of the disorder has substantially contributed to the advancement of potential therapies; although these models have shown utility in testing novel therapeutic candidates, large variability still exists in terms of methodology and how the models are utilized; no model has yet predicted a successful disease-modifying therapy for AD (abstract). Sabbagh teaches current pharmacological interventions for AD have symptomatic benefits but do not prevent or delay progressive neurodegeneration (page 169, left, 1 st paragraph). This article demonstrates that the art of developing and testing drugs for preventing Alzheimer’s disease, particularly for use in humans, is extremely unpredictable. De Hann, cited for evidentiary purposes , evaluated strategies for modifying neuronal excitability in a computational Alzheimer’s disease (AD) network model , and reported that therapeutic interventions produce highly unpredictable and sometimes counterintuitive effects. De Haan states , “ the effects of the different types of stimulation and inhibition are quite unpredictable ; in this particular topology, the increased excitability in excitatory neurons apparently leads to a condition where desirable network topology is retained longer ” (page 11, last paragraph; page 12, first paragraph). Although the authors note that this counterintuitive outcome warrants further mechanistic explanation, its occurrence directly illustrates the unpredictable therapeutic behavior of interventions aimed at modifying neuronal hyperactivity in the AD context. This article demonstrates that targeting neuronal hyperactivity in AD involves complex biological responses, and therapeutic outcomes can’t be reliably predicted. Cummings, cited for evidentiary purposes , discusses the recent shift in fo cus toward Disease Modifying T herapy (DMT) approaches in Alzheimer’s disease (AD) , defined as therapies intended to affect the underlying disease process by targeting one or more of the numerous pathological changes characteristic of AD . Cummings reports that, despite extensive effort, numerous candidate agents have failed in clinical development , and that no DMTs have demonstrated a drug-placebo difference in Phase 3 studies or received marketing approval (page 2, left column, paragraph 3). Cummings further explains that these failures stem from an incomplete understanding of AD pathogenesis, the multifactorial etiology and complex pathophysiology of the disease, the slowly progressive nature of AD and the high level of comorbidity occurring in the elderly population (page 2, left column, fourth paragraph ). This reference demonstrates that therapeutic outcomes in Alzheimer’s disease are highly unpredictable, even when treatments are rationally designed to target disease mechanisms. 2. The breadth of the claims Claims 1- 20 are directed to a method of treating or preventing at least one of the following in a subject: (a) memory loss, (b) long-term potentiation impairment, (c) neuronal cell death and (d) neuronal hyperactivity , including Alzheimer’s Disease, comprising administering a therapeutically effective amount of R-carvedilol to the subject. 3. The amount of direction or guidance provided and the presence or absence of working examples The specification provides data showing R-carvedilol prevents and rescues neuronal hyperactivity and memory loss in 5xFAD mice in vivo in Example 6 (pages 32-33) ; prevents subiculum neuronal cell loss in 5xFAD mice in vivo in Example 7 (pages 33-34); and rescues memory impairment, LTP deficit and neuron loss in 3xTG mice in vivo in Example 12 (page s 37-38 ) ; but this limited in vivo data in 5xFAD and 3xTG mouse models is not sufficient to provide support for the full scope of treatment or prevent ion of memory loss, long-term potentiation impairment, neuronal cell death, neuronal hyperactivity or Alzheimer’s Disease , particularly in humans . Long-term potentiation impairment, neuronal cell death, neuronal hyperactivity and Alzheimer’s disease are broad recitations, and are not necessarily only related to memory loss. The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc ) necessary to achieve treatment across the full scope of the claimed endpoints , noting that the specification provides no support for prevention, of memory loss, long-term potentiation impairment, neuronal cell death, neuronal hyperactivity or Alzheimer’s Disease , particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for memory impairment in 5xFAD and 3xTG mouse models of Alzheimer’s disease . 4. The quantity of experimentation necessary Because of the known unpredictability of the art (as discussed in supra ) and in the absence of experimental evidence commensurate in scope with the claims , the skilled artisan would not accept that any method of claims 1- 20 could be predictably used as a preventative for memory loss, long-term potentiation impairment , neuronal cell deat h, neuronal hyperactivity or Alzheimer’s Disease , particularly in humans . Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action for the methods of claims 1- 20 to use R-carvedilol to treat neuronal cell deat h, neuronal hyperactivity or Alzheimer’s Disease ; or to prevent memory loss, long-term potentiation impairment , neuronal cell deat h, neuronal hyperactivity or Alzheimer’s Disease . Determining if R-carvedilol would treat or prevent the aforementioned conditions or disorders would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra , even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants. Accordingly, the inventions of claims 1- 20 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success. 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)(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 20-25 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Leinert (US 5,071,868 A ). Regarding claims 20-25 , Leinert teaches a pharmaceutical composition comprising R-carvedilol and a pharmaceutical carrier, such as water (column 4, Table and lines 44-51 ; column 8, Example 7 ). Leinert further teaches the pharmaceutical composition can be administered enterally, parenterally, orally or via injection (column 3, second to last paragraph; column 5, first paragraph). Regarding the claim limitations which are directed to the use of the claimed pharmaceutical composition for the treatment of memory loss, long-term potentiation impairment , neuronal cell deat h, neuronal hyperactivity or Alzheimer’s Disease , respectively, such limitation s of the instant claims fail to patentably distinguish the instant claims over the cited prior art because such limitation s are an intended use of the composition (i.e. an intent to use the disclosed pharmaceutical com position as treatment for memory loss, long-term potentiation impairment , neuronal cell deat h, neuronal hyperactivity or Alzheimer’s Disease ), which does not impart any physical or material characteristics to the composition that is not already present in the cited prior art. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See P i tney Bowes Inc. v. Hewlett-Packard Co., 182 F.2d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror , 112 F.3d 473, 378, 42 USPQ2d 1550, 1554 and MPEP 2112.02(II). In the instant case, the claims are directed to a pharmaceutical composition and, thus, would be reasonably expected to be capable of performing the intended use as instantly claimed, absent factual evidence to the contrary and further absent any apparent structural difference between the composition of the prior art and that of the instant claims. Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis ( i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 1, 4, 6-9, 12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al ( Neurobiol Aging , (2011) , 32(12), 2321, 1-12 ) ; in view of Bartsch et al ( European Journal of Clinical Pharmacology , (1990), 38(2), S104-S107 ) . Regarding claim s 1, 4, 6 -9, 12 and 1 5 , Wang teaches the oral administration 1.5mg/kg/day (equivalent to 7.5mg/day in humans) of carvedilol to TgC RND8 mice, which are a model of Alzheimer’s disease (page 2, last paragraph; page 3, first paragraph). Wang discloses that carvedilol improved cognitive function in treated TgCRND8 mice , who performed significantly better when compared to non-treated TgCRND8 mice when evaluated for long term memory consolidation , exhibiting improved spatial memory retention in the Morris Water Maze trial after 24 hours ( page 7, last paragraph; page 8, first paragraph). Wang does not teach the use of isolated R-carvedilol. Bartsch teaches that carvedilol exhibits stereoselective pharmacological activity; wherein R-carvedilol is primarily an α-blocking compound with much less potent ß-blocking properties and hypotensive activity when compared with S-carvedilol, while retaining distinct and predictable adrenergic activity ( page S106, Table 1). Bartsch further discloses that after oral administration, the peak levels and the area under the curve of the plasma concentrations of the R-enantiomer were about 3 times those of the S-enantiomer; indicating a higher systemic exposure of R-carvedilol (page S106, last paragraph ). This established distinction in receptor activity further demonstrates that the individual enantiomers of carvedilol possess predictable and well-characterized biological effects . It would have been prima facie obvious to a person of ordinary skill in the art to isolate, enrich or administer R-carvedilol in place of the racemic mixture , with the reasonable expectation R-carvedilol would retain the beneficial neurologic effects of racemic carvedilol taught by Wang, with a reduced cardiological side effect as taught by Bartsch; effectively permitting increased or sustained dosing, thereby enabling further exploitation of the known neurological effects of carvedilol . The selection of a single enantiomer from a known racemate represents a routine optimization strategy in medicinal chemistry, commonly employed to improve pharmacological, pharmacokinetic or safety profiles, absent evidence of unexpected properties. “[ T ] he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395 . Taken together, a ll of this would result in the method of instant claims 1, 4, 6-9, 12 and 15 with a reasonable expectation of success. Conclusion Claims 1-25 are rejected. No claim is allowed. 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