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
Claims 1-8 and 11-14 are pending
Claims 7-8 and 11-14 is withdrawn from examination as being drawn to a nonelected specie.
Claims 1-6 are under consideration in the instant office action.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6) and Specie 1 b (composition of claim 1 further comprising the compound of formula ( I) in their response dated 01/05/2026 is acknowledged.
Examination of the claims are conducted to the extent they read on the elected species. Claim 5 drawn to composition further comprising compound of formula (II) is rejoined and examined,. Claims 7-8 and 11-14 is withdrawn from examination as being drawn to a nonelected specie.
Claims 1-6 are under examination and the requirement for restriction is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/15/2023 and 01/06/2026 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application is a U.S. national stage entry of PCT international
application no. PCT/CN2021/112813, filed on August 16, 2021, which claims the right of priority for]_to the prior application with the patent application number of CN 202010827343.0, entitled "Stable Pharmaceutical Composition" and was submitted to the China National Intellectual Property Administration on August 17, 2020.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-6 are rejected under 35 U.S.C. 103(a) as being unpatentable over Yong et al. (CN 111346090, referenced in instant IDS. English translation is provided) as evidenced by Dexborneol data sheet (downloaded from the internet on 11/06/2025) and Rong et al. (CN106727287 (referenced in the instant IDS, English translation provided,) further in view of Humeniuk (WO 2021/229466)
Instant claims are drawn to a pharmaceutical composition, wherein the pharmaceutical composition comprises comprising: 1.0-3.0 mg/ml of edaravone, 0.2-1.0 mg/ml of dextrocamphol, 0.95-1.05 mg/ml of sodium metabisulfite, propylene glycol, and water for injection, wherein edaravone and dextrocamphol are active ingredients, and dextrocamnphol has a structural formula of
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Yong et al. discloses pharmaceutical compositions comprising 3-methyl-
1-phenyl-2-pyrazolin-5-one, 3-n-butylphthalide (edaravone) and alcohol, where in the alcohol is preferably dexborneol (another name for dexcamphanol, which has the same structure as instantly claimed, see the attached dexborneol sheet as evidence), and they disclose sodium metabisulfite as an antioxidant (Claims 1-4, page 2, lines 13-15,Pages 2-3-Examples 1-6). They disclose that the ratio of edaravone to dexborneol is 1:0.1-4 preferably 1:0.3-1.2. They disclose concentrations of their components in the formulations are 0.16 mg/ ml edavarone and 0.05 mg/ml dexborne0l (example 7), 0.833 mg/ml edaravone and 0.05 mg/ml dexborneol (example 8), 0.083 mg/ml edaravone and 0.0.1 mg/ml dexborneol (example 9), 0.25 mg edaravone and 0.083 mg/ml dexborneol (example 10). They also disclose the use of sodium metabisulfite as being useful to ensure the stability of the compound (see par [0067] the sodium metabisulfite in their examples ranged from 0.083 mg/ml to 0.16667 mg/ml.
Rong et al. discloses a high-concentration injection of edaravone and natural borneol, comprising: 0.9 wt % -5 wt % of edaravone; 0.225 wt % -1.25 wt % of natural borneol; 5-25 wt % of polyethylene glycol 4005 wt %; 4-15 wt % of ethanol; 0.004-0.02 wt % of sodium metabisulfite; the balance of water for injection (Abstract). They disclose that sodium metabisulfite is added as an antioxidant (page 1) . They disclose the concentration of edaravone ranges between 10 mg/ml to 30 mg/ml, Borneol ranges from 2.5-7.5 mg/ml, sodium metabisulfite is between 0.05 mg /ml to 0.1 mg/ml (examples 1-4).
With regards to instant claim 4-6, Neither references disclose the composition further containing a compound of formula I or formula II . However , the amount of these compounds claimed is 0.3% or less, which is inclusive of 0 amount of the compound. The two references do not teach the presence of these compounds which translates to 0 or none and therefore the renders the claims 4-5 obvious.
The references also do not teach the instantly claimed concentration of sodium bisulfite which is 0.95-1.05 mg/ml.
However, Humeniuk discloses edaravone compositions comprising sodium metabisulfite as and antioxidant at concentrations ranging from 0.1-1.0 mg/ml (see page 3, 6th para). They disclose that this antioxidant protects the active substance from oxidants and under thermal stress and they also recite that the formation of impurities in the drug product with sodium metabisulfite was minimal (page 15, 1st para).
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Yong et al. and Wong et al. both of whom teaches a stable composition of edaravone in combination with dexcamphanol and sodium metabisulfite and polyethylene glycol as claimed. The composition of edaravone with the other components as claimed in the instant composition was well known in the art at the time of this application. It would have been obvious to a person of ordinary skill in the art to optimize the sodium metabisulfite concentration recited by Yong et al. and Rong et al. with the amounts suggested by Humeniuk et al. Further it would be within the skill of an ordinary artisan to be able to modify the weight ratio and amounts of the different ingredients in the composition to obtain maximum stability. The concentrations as claimed can be arrived at by a person of ordinary skill in the art with routine experimentations, without exercising inventive skills, with guidelines provided by the references above. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). . As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in arriving at the instant claims, absence of evidence to the contrary.
Conclusion
Claims 1-6 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dierdre (Renee) Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691