DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The present Application, filed March 30, 2022, is a National Stage Entry under 35 U.S.C. § 371 of International Patent Application No. PCT/CN2020/119598, filed September 30, 2020, which claims priority to Chinese Patent Application No. CN20190942002, filed September 30, 2019.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 28, 2026 has been entered.
Status of the Claims
In the amendment filed January 28, 2026 claims 1-20 are canceled and new claims 21-27 are added. Claims 21-27 are currently pending and subject to examination herein.
Claim Rejections - 35 USC § 112
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 23 and 26-27 are indefinite:
Claims 23 and 26-27 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.
Claim 23 is indefinite for reciting, “wherein the pharmaceutical composition is administered via a route selected from…,” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. In particular, the recitation of “is administered” seems to suggest that an administration step is required, but this would be improper for a composition claim that isn’t and doesn’t include a method. As such, this recitation will be understood as requiring generally that the composition is formulated or intended for administration via one of the recited routes.
Claim 26 is indefinite for reciting “a method for preparing an agent for improving one or more pathological indicators induced by β-amyloid…wherein the pathological indicators include [(a)-(e)]” because one of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. As a first matter, it would not be clear whether the recited features, including the preambular “for improving one or more pathological indicators” clause and the listing of pathological indicators (a)-(e), merely describes intended uses of the agent that is prepared by the method, or describe properties that the agent must have. In short, it would be unclear whether these recitations limit the agent, and therefore the method of preparing it, in any discernible manner. This uncertainty is exacerbated by the fact that the individual pathological indicators (e.g. “spatial cognitive impairment”) are recited at a generalized level, and it would be unclear how one would determine whether the agent can or does generate the recited improvement. In some cases, it is particularly unclear what would constitute the recited indicator (e.g. an unstated the benchmark for determining “elevated levels of pro-inflammatory cytokines”). For at least these reasons, the recitations of the properties/uses of the agent that is prepared by the method are indefinite, and are treated here as mere intended uses, devoid of patentable weight.
Claim 26 is further indefinite for reciting, “a method of preparing an agent…comprising incorporating the pharmaceutical composition…into the agent,” because it would be unclear what this method step requires. Claim 26 seems to indicate that the pharmaceutical composition of claim 21 or 22 (or the medicament of claim 24 or 25) is not itself an agent for improving the one or more pathological indicators, but must be combined with some other, unnamed component in order to be incorporated into the agent. In short, incorporating the composition into the agent seems to suggest combining the composition with some other component, but it is unclear what that other component is and therefore unclear what constitutes “incorporating the pharmaceutical composition…or the medicament…into the agent.”
Claim 27 is indefinite for reciting, “a method for improving pathological indicators…wherein the pathological indicators include: [(a)-(e)],” because one of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. As above, it would be unclear whether the method must result in improvement of any of the recited pathological indicators and, if so, how one would determine whether this had occurred. As such, these recitations are regarded as mere intended results of the method, devoid of patentable weight, and claim 27 is understand as merely requiring the recited “administering” method step.
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 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.
Claims 21-24 and 27 are obvious over Martinez-Torres and Pourkavoos:
Claims 21-24 and 27 are rejected under 35 U.S.C. § 103 as being unpatentable over the non-patent publication, Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933], BMC Neurol., 8, art. 40, pgs. 1-10 (2008) by Martinez-Torres et al. (hereinafter, “Martinez-Torres”), in view of the non-patent publication, Unique Risks, Benefits, and Challenges of Developing Drug-Drug Combination Products in a Pharmaceutical Industrial Setting, Comb. Prod. Ther., 2, art. 2, pgs. 1-31 (2012) by Pourkavoos (hereinafter, “Pourkavoos”).
Claim 21 recites a pharmaceutical composition comprising acyclovir and dexamethasone, present at a weight ratio within a range of from 500:1 to 100:1.
Martinez-Torres teaches a clinical trial of acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo, for the treatment of herpes-simplex-virus-encephalitis (HSVE - Abstract). Martinez-Torres teaches that subjects in the experimental group received 10 mg/kg intravenous acyclovir three times daily for 14 days and 40 mg intravenous dexamethasone daily for the first four days. Thus, once per day for the first for days, acyclovir and dexamethasone were co-administered. Given a typical body weight of about 70 kg, the daily weight ratio of acyclovir to dexamethasone would be about 50:1, outside but adjacent to the recited range. However, It would have been obvious to one of skill in the art, as a matter of routine optimization, to utilize other concentrations and ratios, at least similar to the concentrations explicitly taught by Martinez-Torres A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.
Martinez-Torres does not expressly teach that, when acyclovir and dexamethasone were co-administered, they were co-formulated (i.e. present together in a single intravenous pharmaceutical composition), however it would have been obvious to co-formulate the acyclovir and dexamethasone for the treatment of HSVE because it was well-known in the art that co-administered active pharmaceutical ingredients can be co-formulated for convenience. See, for example, Pourkavoos.
Pourkavoos teaches fixed-ratio combination drug products can have multiple benefits (Abstract), including improved patient compliance and cost (Abstract, and pg. 14, Simplification of Dosage Regimen). It would have been obvious to combine the acyclovir and dexamethasone of Martinez-Torres into a single fixed-ratio, combination pharmaceutical composition, as taught by Pourkavoos, in order to simplify the dosing regimen.
With respect to claim 22, while the weight ratio of acyclovir to dexamethasone is not within the range recited in claim 22, the difference in weight ratio would have been a matter of routine optimization, particularly where, as here, there is no evidence of criticality of the recited weight ratio. “[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).
With respect to claim 23, the acyclovir and dexamethasone of Martinez-Torres are administered intravenously. With respect to claim 24, the acyclovir and dexamethasone of Martinez-Torres are, by virtue of being administered via intravenous infusion, in solution in a physiologically acceptable medium (e.g. an aqueous solution). Thus, the intravenous solution of Martinez-Torres modified by Pourkavoos constitutes a medicament of claim 24.
With respect to claim 27, as discussed above, this method claim is construed as merely requiring the recited step of administering a composition or medicament of any of claims 21-24 to a patient. Martinez-Torres discloses administering acyclovir and dexamethasone to patients as treatment for HSVE (pg. 2, right column, Treatment with Acyclovir and Study medication (dexamethasone/placebo)). Furthermore, while the recited pathological indicators are not given patentable weight, it is known that HSVE causes, for example, elevated levels of pro-inflammatory cytokines such as IL-6 in the hippocampus (see, for example, the non-patent publication, Experimental herpes simplex virus encephalitis: a long-term study of interleukin-6 expression in mouse brain tissue, Neurosci. Lett., 367, pgs. 289-292 (2004) by Dvorak et al.) and thus the method of Martinez-Torres and Pourkavoos could reasonably be expected to lessen such elevated levels.
Claim 25 is obvious over Martinez-Torres, Pourkavoos, Karpe, and Queckenberg:
Claim 25 is rejected under 35 U.S.C. § 103 as being unpatentable over Martinez-Torres, in view of Pourkavoos, and further in view of the non-patent publication, Formulation Development and Evaluation of Acyclovir Orally Disintegrating Tablets, J. Appl. Pharm. Sci., 02, pgs. 101-105 (2012) by Karpe et al. (hereinafter, “Karpe”) and the non-patent publication, Pharmacokinetics, Pharmacodynamics, and Comparative Bioavailability of Single, Oral 2-mg Doses of Dexamethasone Liquid and Tablet Formulations: A Randomized, Controlled, Crossover Study in Healthy Adult Volunteers, Clin. Therap., 33, pgs. 1831-1841 (2011) by Queckenberg et al. (hereinafter, “Queckenberg”).
Claim 25 recites the medicament of claim 24, in a dosage form selected from various orally administrable dosage forms, such as a tablet. Neither Martinez-Torres nor Pourkavoos expressly teaches this feature, but it would have been obvious to formulate the acyclovir/dexamethasone composition/medicament of Martinez-Torres and Pourkavoos in such an oral form, because oral forms of acyclovir and dexamethasone were well-known in the art and known to carry advantages such as convenience. See, for example, Karpe and Queckenberg.
Karpe teaches orally disintegrating tablets of acyclovir (Abstract) and teaches that oral tablets for drugs such as acyclovir carry many benefits of other administration routes such as avoiding patient non-compliance (pg. 102, left column, third paragraph). Similarly, Queckenberg teaches a comparison of oral liquid and tablet forms of dexamethasone (Abstract), and teaches that both have satisfactory pharmacodynamic parameters. It thus would have been obvious to formulate the formulate the acyclovir/dexamethasone composition/medicament of Martinez-Torres and Pourkavoos as a tablet, as this form of both drugs was well-known and would carry advantages such as convenience and improved patient compliance.
Conclusion
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629