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 18/706,958 filed on 02 May 2024, 371 of PCT/CN2022/129456 filed on 03 November 2022, claiming foreign priority from CN20211131163.1 filed on 08 November 2021. Claims 1 and 3-10 are amended. Claim 2 is canceled. Currently, claims 1 and 3-10 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 02 May 2024 and 11 November 2025 were filed on and after the mailing date of the application on 02 May 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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, 3-4, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (Safety and efficacy of Edaravone Dexborneol versus Edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomized, double-blind, multiple-dose, active-controlled clinical trial, Stroke and Vascular Neurology 2019, 4, e000221).
Xu discloses the combination therapy of Edaravone Dexborneol as a neuroprotective agent, Dexborneol being a food additive with an anti-inflammatory effect in animal ischaemic stroke models, inhibiting the production or expression of inflammation-related proteins and prevents brain injury or impairment whereas Edaravone acts as a free radical scavenger. Xu also discloses that Edaravone Dexborneol is recognized as a neuroprotective agent, used in a 4:1 ratio, demonstrating synergistic effect and longer treatment time, indicating that the protective effective of the combination on cerebral ischaemic injury was better than Edaravone alone (pg. 109 – introduction). Xu’s study affirmed the safety and efficacy of Edaravone Dexborneol, involving 385 patients, and confirming the safety and tolerability of the combination (abstract)
As such, Xu anticipates claim 1 through the combination therapy of Edaravone Dexborneol as neuroprotective agents in the context of ischemic injury.
Concerning the limitations of claim 3, wherein the weight ratio of the 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) or the pharmaceutically acceptable salt thereof to Dexborneol is 10:1 to 1:8, are met as Xu discloses the use of Edaravone Dexborneol used in a 4:1 ratio (pg. 109 – introduction).
Regarding the limitations of claim 4, wherein the weight ratio of Edaravone or the pharmaceutically acceptable salt thereof to Dexborneol is 7.5:1 to 2.5:1, are met as Xu discloses the use of Edaravone Dexborneol used in a 4:1 ratio (pg. 109 – introduction).
With respect to the limitations of claim 6, wherein the weight ratio of Edaravone or the pharmaceutically acceptable salt thereof to Dexborneol is 4:1, are met as Xu discloses the use of Edaravone Dexborneol used in a 4:1 ratio (pg. 109 – introduction).
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Safety and efficacy of Edaravone Dexborneol versus Edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomized, double-blind, multiple-dose, active-controlled clinical trial, Stroke and Vascular Neurology 2019, 4, e000221) in view of Wu et al. (The synergetic effect of Edaravone and Borneol in the rat model of ischemic stroke, Eur. J. Pharma. 2014, 740, 522-531).
Xu discloses Edaravone Dexborneol as a combination therapy agent used for their neuroprotective effects within the context of post ischemic injury.
Xu does not, however, disclose the use of Edaravone Dexborneol in a 5:1 ratio.
Wu rectifies this as they optimized the proportion of Edaravone to Borneol in vivo with explored ratios of 2:1, 4:1 or 8:1, finding that results from treatment of 4:1 were better than the other two groups (pg. 525 – optimal proportion of Edaravone to Borneol). A prima facie case of obviousness exists where claimed ranges “overlap or lie inside ranges disclosed by the prior art”. See MPEP § 2144.05.
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider the use of 5:1 ratio of Edaravone Dexborneol as it is within the optimized range as taught by Wu. Optimization of the dosing ratio would necessarily be refined as part of the research process as a person of ordinary skill in the art would be motivated to do so as to obtain the desired clinical outcome or improved clinical outcome. Moreover, it is well-known that dosages may vary between patients due to parameters such as patient mass, gender, co-morbidities, age, etc. Therefore, the limitations of claim 5 can be construed as a conclusion from the optimization process.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of Allen et al. (Ansel’s pharmaceutical dosage forms and drug delivery systems 10th edition, Wolters Kluwer Health 2005).
Xu discloses Edaravone Dexborneol as a combination therapy agent used for their neuroprotective effects within the context of post ischemic injury.
They do not, however, teach additional details about the composition further comprising a pharmaceutically acceptable excipient.
This shortcoming is fixed by Allen who extensively covers many topics within the field of drug formulation, including, but not limited to, typical properties of select excipients, incompatibilities, safety, related substances, along with numerous other examples in categories such as disintegrants, adhesives, and surfactants (select reading; pg. 1 – section I: introduction to drugs, drug dosage forms, and drug delivery systems; pg. 101 – section II: drug dosage form and drug delivery system design)
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to explore well known and documented excipients in consideration for the desired pharmaceutical compositions.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of Wang et al. (Shared risk and protective factors between Alzheimer’s disease and ischemic stroke: a population-based longitudinal study, Alzheimer’s Dement. 2021, 17, 191-204).
Xu discloses Edaravone Dexborneol as a combination therapy agent used for their neuroprotective effects within the context of post ischemic injury.
They do not, however, disclose where the cognitive impairment refers to Alzheimer’s disease, vascular dementia, mild cognitive impairment, and other types of dementia.
Wang fixes this by teaching a cohort study involving 2459 older individuals, mean age 71.9 years, exploring shared risk and protective factors, finding that both models shared significant factors such as low education, sedentary lifestyle, and heart disease (abstract). Both models, despite different pathogeneses, arise from multiple factors, suggesting correlated vascular pathologies, e.g. atherosclerosis, and interacted with neurodegenerative pathologies that precede cognitive impairment, Alzheimer’s, and dementia. Additionally, the two models share similar protective factors such as psychosocial factors including social networks, leisure activities, and psychosocial well-being (pg. 192 – introduction). Wang further teaches that vascular dysfunction, atherosclerosis, and deposition of amyloid in cerebral vessels may partially explain the common underlying mechanism between Alzheimer’s and ischemic stroke, including hypoperfusion and hypoxia caused by atherosclerosis, mitochondrial dysfunction due to impairment with oxidative respiration, insulin resistance, amongst others. It is reasonable to assume then, that a therapy such as Edaravone Dexborneol that operates post-trauma, would be efficacious to both in the context of ischemic stroke, as demonstrated by Xu, and Alzheimer’s with the numerous correlated factors as described by Wang (pg. 201).
As such, it would be prima facie obvious, to a person of ordinary skill in the art, before the effective filing date, to consider the use of Edaravone Dexborneol in the treatment of Alzheimer-related dementia as Wang teaches the similarities between ischemic stroke and Alzheimer’s while Xu teaches the use of the combination therapy to treat post-ischemic stroke patients.
Regarding the limitations of claim 9, wherein the cognitive impairment refers to Alzheimer’s disease, vascular dementia, and mild cognitive impairment, are met as Wang teaches the social psycho and pathological similarities between Alzheimer’s and ischemic stroke, which can be treated with Edaravone Dexborneol combination therapy.
Regarding the limitations of claim 10, wherein the cognitive impairment refers to Alzheimer’s disease, vascular dementia, and mild cognitive impairment, are met as Wang teaches the social psycho and pathological similarities between Alzheimer’s and ischemic stroke, which can be treated with Edaravone Dexborneol combination therapy.
Summary
Claims 1, 3-4 and 6 are rejected under 35 U.S.C. 102(a)(1). Claims 5 and 7-10 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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