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
This action is in response to Applicant’s amendment filed November 5, 2025 in reply to the First Office Action on the Merits mailed May 8, 2025. Claim 1 has been amended; claim 5 has been canceled; and claims 16-18 have been newly added. Claims 2-4 and 6-15 have previously been canceled. Newly added claims 16-18 are hereby also canceled as being directed to non-elected subject matter. Claim 1 is currently under examination in the application.
Withdrawal of Prior Objection - Abstract
The abstract of the disclosure has been satisfactorily amended. Therefore, the objection to the abstract presented in the First Office Action on the Merits mailed May 8, 2025 is hereby withdrawn.
Claim Objections
Claim1 is objected to because the recited elements of the Markush group should be separated by commas instead of semicolons. Specifically, there should be a comma instead of a semicolon between “2-mercapto-5-benzimidazole sulfonate” and “and thiosalicylate”.
Appropriate correction is required.
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 1 is rejected under 35 U.S.C. 103 as being unpatentable over Sherine et al. (Scientific Reports. 2019; 9:621), in view of Tzeng et al. (Crystal Growth and Design. 2004; 4(3): 573-577), and Leung et al. (Inorg Chem. 2013; 52(8): 4593-4602).
Applicant Claims
Applicant’s elected subject matter is directed to a silver coordination complex with antimicrobial activity having the formula [Ag+(L2-)2]3-, wherein L is 2-mercapto-4-methyl-5-thiazole acetic acid.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Sherine et al. disclose that each of silver (Ag) and gold (Au) can form coordination complexes with thioamides, such as 2-mercaptobenzothiazole (MBT); that the silver-MBT (AgMBT) coordination complexes typically exhibit antimicrobial activity; and that for the AgMBT coordination complex, silver is bound to the mercapto (-SH) group of MBT.
Tzeng et al. disclose that 2-mercapto-4-methyl-5-thiazole acetic acid is another 2-mercapto-thioazole compound that can form coordination complexes with metals, such as gold.
Leung et al. disclose that anionic, bi-coordinated complexes between silver and compounds with a thiol group, such as e.g. glutathione, can be produced in alkaline (e.g. pH 11) aqueous solution, which deprotonates the thiol group, and the higher free thiolate concentration under these conditions promotes formation of higher complexes, e.g. in the case of glutathione, the [Ag(Glu)2]5- species is formed, due in part to the strong tendency of the thiolate sulfur atom to form bridges between silver ions.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Sherine et al. do not explicitly disclose that the thioamide ligand is 2-mercapto-4-methyl-5-thiazole acetic acid, and that the silver complex is anionic and bi-coordinated. These deficiencies are cured by the teachings of Tzeng et al. and Leung et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Sherine et al., Tzeng et al. and Leung et al., outlined supra, to devise Applicant’s presently claimed silver complex.
Sherine et al. disclose that each of silver (Ag) and gold (Au) can form coordination complexes with thioamides, such as 2-mercaptobenzothiazole (MBT); that the silver-MBT (AgMBT) coordination complexes typically exhibit antimicrobial activity; and that for the AgMBT coordination complex, silver is bound to the mercapto (-SH) group of MBT. Since Tzeng et al. disclose that 2-mercapto-4-methyl-5-thiazole acetic acid is another 2-mercapto-thioazole compound that can form coordination complexes with metals, such as gold; and since Leung et al. disclose that anionic, bi-coordinated complexes between silver and compounds with a thiol (-SH) group, such as e.g. glutathione, can be produced in alkaline (e.g. pH 11) aqueous solution, which deprotonates the thiol (-SH) group, and the higher free thiolate concentration under these conditions promotes formation of higher complexes, e.g. in the case of glutathione, the [Ag(Glu)2]5- anionic, bi-coordinated species is formed, due in part to the strong tendency of the thiolate sulfur atom to form bridges between silver ions; one of ordinary skill in the art would thus be motivated to complex silver with 2-mercapto-4-methyl-5-thiazole acetic acid under alkaline conditions (e.g. pH 11), with the reasonable expectation of success of forming an anionic, bi-coordinated silver complex with 2-mercapto-4-methyl-5-thiazole acetic acid, which complex will exhibit antimicrobial activity.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed November 5, 2025 have been fully considered but they are not found persuasive.
i) Applicant contends that “the rejection uses the claims as a guide to selectively pick from the art to recreate what is claimed”, that “Shering…discloses silver coordination complexes with 2-mercaptobenzothiazole (MBT)…but fails to teach or suggest” the ligand “2-mercapto-4-methyl-5-thiazoleacetic acid” and “the MBT ligand disclosed by Sherine is structurally distinct from the specifically claimed ligands and would not result in the same anionic bi-coordinated complex structure”; that “Tzeng…teaches gold coordination complexes…but fails to disclose or suggest silver coordination complexes or any antimicrobial activity”; that “the glutathione ligand in Leung results in a pentavalent anionic complex (5-) which is structurally and electronically different from the claimed trivalent anionic complex (3-)” and “Leung evaluates Ag(I) complexes of amino-acid thiols…not the mercapto-thiazole ligands of claim 1”; and thus “there would be no reasonable expectation of success that would lead the skilled person to the claimed complex” but “instead…the Examiner’s rationale relies on impermissible hindsight”.
The Examiner, however, would like to point out the following:
1. Neither Sherine, Tzeng, nor Leung has been cited for individually anticipating the elected subject matter under 35 USC 102. Rather, the prior art rejection is under 35 USC 103, based on the combination of the recited references, and what these references teach and reasonably suggest to one of ordinary skill in the art, who is one of ordinary creativity and not an automaton.
2. Sherine, the cited primary reference, discloses that each of silver (Ag) and gold (Au) can form coordination complexes with thioamides, such as 2-mercaptobenzothiazole (MBT); that the silver-MBT (AgMBT) coordination complexes typically exhibit antimicrobial activity; and that for the AgMBT coordination complex, silver is bound to the mercapto (-SH) group of MBT. Since 2-mercapto-4-methyl-5-thiazole acetic acid itself is also a thioamide, and in particular contains the 2-mercaptothiazole core, Sherine alone would no doubt already suggest to one of ordinary skill in the art that 2-mercapto-4-methyl-5-thiazole acetic acid would form a coordination complex with silver. Tzeng strongly reinforces this reasonable expectation, with the express disclosure that 2-mercapto-4-methyl-5-thiazole acetic acid can indeed form coordination complexes with metals, such as gold. Sherine discloses that thioamides, such as 2-mercaptobenzothiazole, can form coordination complexes with either silver or gold. Tzeng discloses that 2-mercapto-4-methyl-5-thiazole acetic acid can form coordination complexes with metals generally, and exemplifies gold. Certainly, one of ordinary skill in the art would reasonably expect that 2-mercapto-4-methyl-5-thiazole acetic acid can also form a coordination complex with silver as well, since silver is a metal and has been shown to form coordination complexes with a thioamide, and in particular one that contains the 2-mercaptothiazole core.
3. A key teaching of Sherine is that silver is bound to the mercapto (-SH, thiol) group. Hence, although 2-mercaptobenzothiazole and 2-mercapto-4-methyl-5-thiazole acetic acid are distinct compounds with some structural differences, both molecules share a 5-membered thiazole ring containing a mercapto group (-SH, thiol) at the 2-position. As disclosed in Sherine, the thiol group is highly effective at coordinating with silver. Therefore, since 2-mercapto-4-methyl-5-thiazole acetic acid, like 2-mercaptobenzothiazole, contains the 2-mercapto-thiazole core, 2-mercapto-4-methyl-5-thiazole acetic acid, like 2-mercaptobenzothiazole, would reasonably be expected to form a coordination complex with silver, which reasonable expectation is significantly strengthened by the disclosure of Tzeng.
4. As far as Applicant’s assertion that Tzeng does not explicitly disclose that the coordination complex between a metal and 2-mercapto-4-methyl-5-thiazole acetic acid exhibits antimicrobial properties, it is noted that the silver coordination complex with 2-mercapto-4-methyl-5-thiazole acetic acid, like the silver coordination complex with 2-mercaptobenzothiazole, would absolutely be expected to exhibit antimicrobial properties, if for no reason other than the silver itself is antimicrobial, as would be very well known in the art generally. Applicant has not provided any evidence to the contrary.
5. Leung discloses that anionic, bi-coordinated complexes between silver and compounds with a thiol group, such as e.g. glutathione, can be produced in alkaline (e.g. pH 11) aqueous solution, which deprotonates the thiol group, and the higher free thiolate concentration under these conditions promotes formation of higher complexes, e.g. in the case of glutathione, the [Ag(Glu)2]5- species is formed, due in part to the strong tendency of the thiolate sulfur atom to form bridges between silver ions. Again, the effect described is based on the thiol group, specifically deprotonating the thiol group, with the higher free thiolate concentration under these conditions promoting formation of higher complexes. Like glutathione, 2-mercapto-4-methyl-5-thiazole acetic acid contains the thiol group, and also coordinates with metals. Therefore, in view of the teachings of Leung, one of ordinary skill in the art would reasonably expect that with pH sufficiently alkaline, 2-mercapto-4-methyl-5-thiazole acetic acid will form a bi-coordinated complex with silver as well. The standard here is a reasonable expectation of success, not an absolute guarantee of success. While there may not be an absolute guarantee of success, there is a reasonable expectation of success. Applicant has not provided any hard evidence to the contrary.
For the foregoing reasons, the 35 USC 103 rejection is hereby maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/DAVID BROWE/Primary Examiner, Art Unit 1617