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
Election/Restriction
Acknowledgement is made of Applicant’s election with traverse in the reply filed on 05/29/2026: i) Group I invention; ii) compound species having following structure,
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The traversal is based on the ground that instant compounds are intended to treat acute lung injury by oral administration which must first possess high lipophilicity to be successfully absorbed through the gastrointestinal mucosa...The multiple alternatives disclosed in the original claim 1 are designed based on the same inventive concept... the components are interchangeable and are expected to achieve the same intended effect.
Applicant’s argument is fully considered, but NOT persuasive. Please note intended function/result do not necessarily contribute to the structural limitation of the compounds. The common
structure of instant compounds,
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, is already taught by Lin et al. (CN11068484027/CN201910865566). Groups I-III invention and species lack unity because there is no special technical feature in view of prior art. Thus, the restriction requirement is deemed proper and made final.
Claims 4-14 are withdrawn, as being drawn to nonelected inventions.
The elected species, compound 4, (+) B3e (Spec, [0048]) is a compound of formula I, wherein R is bromo. The elected species (CAS# 2982661-47-0 ) entered STN database on September 27, 2023.
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The elected species, compound (+) B3e is rejected as obvious over Lin et al (CN11068484027/CN201910865566) under following 103 rejection. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Status of Claims
Claims 1-14 are pending in the instant application.
Claims 4-14 are withdrawn, being drawn to nonelected inventions.
Claims 1-3 are currently under examination.
Priority
This instant application 18/603,126, filed 03/12/2024, a continuation of international PCT application No. PCT/CN2023/086315, filed on April 4, 2023, which claims the priority benefit of China application No. 202310227402.4, filed on March 9, 2023.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of foreign application CN202310227402.4 was filed on 04/23/2024 in Chinese, no English translation is included in the certified copy of CN202310227402.4. Applicant’s right of foreign priority is not perfected due to lack of English translation thereof.
Information Disclosure Statement
The information disclosure statements filed 03/12/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the relevant reference listed in IDS are being considered by the examiner. Reference written in foreign language is considered to the degree of English abstract or patent family of foreign patent by Examiner.
Specification
Instant specification disclosed natural compound derivatives with complex structures, but without IUPAC nomenclature. It’s noted instant specification disclosed 18 compounds wherein R is hydrogen, halogen, alkyl or alkoxyl, etc. The nomenclature of compounds and description thereof is ambiguous and not clear. For example,
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The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
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 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. ( CN 110684027, hereafter Lin’027, Applicants’ IDS dated 03/12/2024 ), in view of Patani et al. ( Chem. Rev. 1996, 96, p 3147-3176) , and Li et al. (Natural Product Research, Vol. 30, August 2015, pp.1-8, hereafter “Li 2015”, Applicants’ IDS dated 03/12/2024, “Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives").
Lin’027 discloses synthesis of natural product (+)-balasubramide derivatives, dextrofluorobalasubramide and biological activities thereof, e.g. neuroprotective, antioxidative, and anti-neuroinflammatory effects (See abstract, Background, Example 1, comparative Examples 1-9; Table 1; claims 1-2).
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Lin’027 explicitly teaches compound 3C-20, wherein
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(See Example 1) (which reads on instant claimed compound R =R1=R2=H). Lin’027 also teaches halogen substitute (e.g. F, Br, etc.) on the phenyl group of R, e.g. Formula V, VI, VII, (See comparative Example 4-6).
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Lin’027 teaches dextrofluorobalasubramide derivative with halogen substitute (e.g. F, Cl, Br, etc.) exhibit improved lipid solubility for penetration through blood brain barriers with unchanged cytotoxicity(See abstract).
The difference of Lin’ 027 compound (+)3C-20 and instant elected species is R on the benzene ring of indole moiety: hydrogen verse Br/halogen.
Patani teaches bioisosterism approach for the rational modification of lead compounds. Patani teaches classical monovalent bioisosteres, for example, fluorine vs hydrogen replacement, interchangeable fluorine, chloro, bromo, hydroxy, thiol, methyl, etc. based on Grimm’s Hydride Displacement Law and/or Erlenmeyer’s Broadened Classification of Grimm’s Displacement Law (See page 3149, 3152-3154).
Li 2015 teaches asymmetric synthesis of natural product (+)-balasubramide (3j) and its derivatives (3a–3i), and in-vitro biological activities, e.g. anti-neuroinflammatory and neuroprotective effects (See whole article).
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Li 2015 teaches substitutes, e.g. fluoro, chloro, bromo, NO2, etc. on the 6-phenyl group of (+)-balasubramide, wherein compounds at 10uM markedly inhibited LPS-induced pro-inflammatory cytokine TNFα release in BV-2 microglial cells. (See Figure 3 and 4; Table 1 and Table S4; ).
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According to MPEP 2144.09 (I), A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
It would have been prima facie obvious for one of ordinary skilled in the art to explore more balasubramide derivatives based on combined teachings of Lin’ 027 and Li 2015, together with experimentation/optimization based on general knowledge of structure similarity/ bioisosteric modification of SAR study as taught by Patani, and arrive at instantly claimed invention with reasonable expected success. A skilled artisan would be motivated to explore halogen substitute on the indole moiety because halogen (e.g. fluoro, chloro, bromo) are commonly known bioisosteric replacement for hydrogen in SAR study of biologically active compounds as taught by Patani and illustrated in Lin’ 027 and Li 2015, and both Lin’ 027 and Li 2015 teach embodiments with halogen substitute on the benzene ring exhibit favorable activity and/or property.
For example, compound 3C-20 taught by Lin ‘027 could have been modified by introducing bromo/ halogen substitute on the benzene ring of indole moiety and arrived at instant elected species.
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One of ordinary skilled in the art would have had reasonable expectation of success in producing instant claimed invention based on the combined teaching of prior art, together with general knowledge of structure similarity/ bioisosteric modification for SAR study. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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/LIYUAN MOU/ Examiner, Art Unit 1628
/JARED BARSKY/ Primary Examiner, Art Unit 1628
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