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 .
Priority
The instant application was received 23 July 2024; it is a continuation of PCT/CN2022/140875, filed 22 December 2022, and claims foreign priority to CN202210086893.0, filed 25 January 2022. Acknowledgment is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
Status of the Claims
The listing of claims filed 14 August 2024 has been examined.
Claims 1-12 are pending.
Claim 10 is amended.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 23 July 2024 is acknowledged and has been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it uses phrases which can be implied, specifically the phrase, “The present disclosure provides…” A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites, “…doxepin hydrochloride in preparation of an anti-Coxsackievirus B drug.” The word “the” appears to be missing. Examiner suggests amending to, “…doxepin hydrochloride in the preparation of an anti-Coxsackievirus B drug.” [Emphasis added.]
Appropriate correction is requested.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 and 11-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because claims 1-3 and 11-12 recite a “use” of a product per se, and therefore do not fall within at least one of the four categories of patent-eligible subject matter. “Use”-type claims are not considered to be statutory subject matter under US patent practice. “Use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961) ("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101"). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967). See MPEP 2173.05(q). Examiner recommends the claims be amended to recite a method of use.
Claim Rejections - 35 USC § 112(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 1-3 and 10-12 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 10 recites the limitation "the medically acceptable auxiliary material”. There is insufficient antecedent basis for this limitation in the claim. Examiner recommends changing “the” to “a”.
Claims 1-3 and 11-12 recite “use” of a product. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05(q). Accordingly, the instant “use” claims are indefinite because the claims recite use of a product without setting forth any active steps defining how the use is practiced, leaving the metes and bounds of the claim unclear.
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.
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 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (CN 113827586 A) in view of Richelson (Richelson, E. “Tricyclic Antidepressants and Histamine H1 Receptors” Mayo Clin Proc 54:669-674, 1979) and Matsumori (Matsumori et al. “Ceterizine a histamine H1 receptor antagonist improves viral myocarditis” Journal of Inflammation 7(39), 2010).
Regarding claims 1-6 and 10-12, Yang teaches the use of nortriptyline hydrochloride, a tricyclic antidepressant, in the preparation of anti-enterovirus drugs (¶ [n0001]; ¶ [n0018]) and some enteroviruses include enterovirus 71, which causes hand-foot-mouth disease in infants and young children (¶ [n0002]), coxsackievirus B3, and coxsackievirus B4 (¶ [n0008]). Yang states, “…nortriptyline hydrochloride has a strong inhibitory effect on enteroviruses, providing a direction for the treatment and prevention of enterovirus infectious diseases.” (¶ [n0005]). Specifically, Yang indicates the antiviral mechanism involves inhibiting the replication of enterovirus nucleic acid, inhibiting expression of viral proteins, and inhibiting infection within cells (¶ [n0016]). In addition to nortriptyline hydrochloride, the anti-enterovirus drugs described by Yang may also comprise pharmaceutically acceptable excipients, such as fillers, disintegrants, binders, diluents, lubricants, sweeteners, and colorants (¶ [0013]-[n0014]). Possible dosage forms disclosed by Yang include granules, tablets, pills, capsules, injections, or dispersants (¶ [n0015]).
Yang does not explicitly teach doxepin hydrochloride.
Richelson teaches tricyclic antidepressants, including doxepin hydrochloride and nortriptyline (p. 670, Fig. 1), have various pharmaceutical activities including as serotonin and norepinephrine reuptake inhibitors and blockade of α-adrenergic, histamine H1, and histamine H2 receptors (p. 669, Bottom Paragraph). Among the tricyclic antidepressants studied, doxepin hydrochloride displayed the highest histamine H1 receptor binding affinity (p. 669, Abstract; p. 670, Fig. 1).
Richelson does not explicitly teach using doxepin hydrochloride in preparing an anti-Coxsackievirus B drug.
Matsumori teaches a histamine H1 receptor antagonist, cetirizine, plays a role in modulating the inflammatory response (p. 5, Col. 1, Middle Paragraph) and suggests cetirizine may be used in treating viral myocarditis (p. 5, Col. 1, Bottom Paragraph), specifically stating their results imply, “…that histamine released from mast cells may play a pivotal role in the pathogenesis of viral myocarditis.” (p. 5, Col. 1, Sentence 1). A skilled artisan would recognize viral myocarditis is the inflammation of heart muscle due to a viral infection, such as a Coxsackievirus B viral infection.
Matsumori does not explicitly teach doxepin hydrochloride.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Yang would have found it prima facie obvious to use doxepin hydrochloride in preparing an anti-Coxsackievirus B drug based on the teachings of Richelson and Matsumori. Yang indicates nortriptyline hydrochloride, a tricyclic antidepressant, may be used in preparing anti-enterovirus drugs, naming Coxsackievirus B3 as one possible enterovirus. Richelson reviews multiple tricyclic antidepressants, including nortriptyline and doxepin, and their relative affinities for the histamine H1 receptor. Matsumori suggests antihistamines, like the H1 receptor antagonist cetirizine, are useful in treating viral myocarditis and a skilled artisan would recognize viral myocarditis is associated with Coxsackievirus B infections. Thus, a PHOSITA would have had a reasonable expectation of success based on the teachings of Yang to try substituting nortriptyline hydrochloride for another tricyclic antidepressant and, based on the teachings of Richelson and Matsumori, would have been motivated to substitute nortriptyline hydrochloride with doxepin hydrochloride, specifically, since Matsumori suggests H1 receptor blockers can attenuate viral myocarditis and Richelson indicates doxepin is a highly potent histamine H1 receptor antagonist relative to other tricyclic antidepressants. Additionally, a skilled artisan would have predicted nortriptyline and doxepin would have similar pharmaceutical activities, owing to the two compounds’ similar structures (Richelson, p. 670, Fig. 1).
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (CN 113827586 A) in view of Richelson (Richelson, E. “Tricyclic Antidepressants and Histamine H1 Receptors” Mayo Clin Proc 54:669-674, 1979) and Matsumori (Matsumori et al. “Ceterizine a histamine H1 receptor antagonist improves viral myocarditis” Journal of Inflammation 7(39), 2010) and further in view of Doxepin Hydrochloride FDA Label, Revised 5/2014 (“FDA”).
With respect to claims 7-9, the combination of Yang, Richelson, and Matsumori fails to teach the concentration of the doxepin hydrochloride in the anti-Coxsackie drug is in a range of 3.125-90 µM.
FDA teaches a doxepin hydrochloride dose may be 25-300 mg/day (p. 2, Col. 1, DOSAGE AND ADMINISTRATION). The molecular weight of doxepin hydrochloride is 315.84 g/mol and dividing 0.025-0.3 g/day doxepin hydrochloride by its molecular weight results in 79.15-949.85 µmol/day. Generally, an average 70 kg human body is assumed to contain approximately 40 L water. Thus, by the Examiner’s calculation, the FDA-recommended daily doxepin hydrochloride concentration can be estimated to be about 1.98-23.75 µM for an average, 70 kg person.
FDA does not explicitly teach using doxepin hydrochloride in preparing an anti-Coxsackievirus B drug.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Yang, Richelson, and Matsumori would have found it prima facie obvious to administer doxepin hydrochloride such that its concentration in the body is 3.125-90 µM based on the teachings of the FDA because the FDA suggests a concentration range (i.e., approximately 1.98-23.75 µM) which overlaps the claimed concentration range. Consequently, a PHOSITA would have had a reasonable expectation of success in administering a dose which would result in a 1.98-23.75 µM concentration since the FDA has suggested this dose is appropriate for other indications, specifically depression (FDA, p.1, Col. 1, INDICATIONS AND USAGE). Thus, a PHOSITA could have used the dosage range disclosed by the FDA as a guide and optimized the amount of doxepin hydrochloride to be administered to a subject based on the desired anti-enteroviral effect.
Conclusion
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/B.L.B./Examiner, Art Unit 1623
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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