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 .
Claims 1-5 filed 08 September 2023 are pending.
Priority
This application is a 371 of PCT/JP2022/008078 filed 02/25/2022. This application claims foreign priority to JAPAN JP2021-038597 filed 03/10/2021, under 35 U.S.C. 119(a)-(d). The certified copy of the priority document has been filed in the instant application.
Specification
The abstract of the disclosure is objected to because Structural formula (I) is fuzzy. 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).
The disclosure is objected to because of the following informalities: At page 10 in the specification the synthetic scheme is very fuzzy. In Table 1 at page 16 several entries are fuzzy. The synthetic scheme and Table 1 need to be replaced with clear reaction schemes, titles and all of the other entries in the Table. At page 2, below para 0008, and page 4, below para [0015], the title [Chem. 1] and [Chem. 2] respectively should be replaced by Formula 1 or any other appropriate identifier. This also applies to the formulas at page 7 and the scheme at page 10. At page 10 through page 26 titles for paragraphs and tables appear within the brackets ( ), < >, [ ]. These brackets/parentheses should be deleted. Applicant is also requested to check the specification for such corrections and also consistency of numbering. Appropriate corrections are required.
Claim Objections
Claims 1-5 are objected to because of the following informalities: In claim 1 the title [Chem. 1] should be deleted and the numeral 1 or an appropriate identifier should be inserted after the term ‘formula’ at line 1. The square brackets enclosing the claim numbers should be deleted. Appropriate correction is required.
Drawings
The drawings are objected to because the drawings filed 09/08/2023 are fuzzy. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 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.
Claim(s) 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Kohyama et al (Org. Biomol. Chem. 2016, 14, 10683-10687) in view of Cagnoni et al (J. Org. Chem., 2011, 76, 3064-3077).
Kohyama et al teaches that the mono thiol adducts of the curcumin derivative Y030 exhibit anticancer activity against HCT116 colorectal cancer cells. Y030 is released by thiol adducts through the retro-Michael reaction after treatment with cancer cells (page 10683, right col., Fig. 1, top right; page10696, left col. see under sub-title: Biological evaluation of GO-Y030-thiol adducts and Discussion, lines 1-12; part of the limitation of claim 1 for the formula recited). In Table 1, at page 10685, it is seen that monoadducts also showed anti-cancer activity. According to Kohyama the more hydrophilic the polar functionality of the S-substituent the more efficient the retro thia-Michael reaction (page 10686, left col., Discussion: second full para, lines 1-8). This means that in the mono thiol adduct, if the sulfur bears a hydrophilic polar functionality, it will generate more of the parent compound which is active.
Kohyama et al does not expressly teach attaching an alkoxy-triazole-sugar moiety to the sulfur mono adduct as in instant claim 1.
According to Cagnoni the S-carbohydrate mimetics are usually resistant to metabolic processes and are seen as potential precursors of promising carbohydrate-based therapeutics. They are resistant to enzyme hydrolysis when they are internalized in the cell (page 3064, right col. first full para). In this context, Cagnoni teaches the use of a sugar-triazole-oligoethyleneglycol chain containing moiety as a scaffold. The use of this hydrophilic scaffold represents an interesting approach to improve pharmacokinetics and bioavailability (Abstract; page 3066, Scheme 3, compounds 14a-c). Compounds 14a-c have the sugar-CH2-triazole-oligoethyleneglycol moiety attached to the sulfur atom as in the formula in claim 1. Even though Cagnoni does not teach or suggest the attachment of the curcumin moiety to the sulfur as in claim 1, one of ordinary skill in the art in view of the teachings of Kohyama will recognize that a mono adduct having the sugar-CH2-triazole-oligoethyleneglycol moiety attached to the sulfur atom as in the formula in claim 1 will be a good candidate as a prodrug which will be more soluble and release more of the parent compound that is active against cancer.
Since the parent compound Y030 is active against colorectal cancer one of ordinary skill in the art would use it and its salt as an activator as in claims 2-5 with a reasonable expectation of success.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, the mono thiol adducts of the curcumin derivative Y030 exhibit anticancer activity against HCT116 colorectal cancer cells. Y030 is released by thiol adducts through the retro-Michael reaction after treatment with cancer cells (Kohyama), and Cagnoni teaches the use of a sugar-triazole-oligoethyleneglycol chain containing moiety as a scaffold. The use of this hydrophilic scaffold represents an interesting approach to improve pharmacokinetics and bioavailability. Thus, it is obvious to combine prior art teachings and arrive at the compound as in claim1 and its salts and use them as an antitumor activator for the cancers as in claims 2-5.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Product improvement is the motivation. In view of the combined teachings of the prior art, the artisan would be motivated to look for curcumin derivatives with enhanced anticancer activity.
Conclusion
Pending claims 1-5 are rejected
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693