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
This application is the U.S. national stage application, under 35 U.S.C. § 371, of
International Patent Application No. PCT/US2023/012726, filed on February 9, 2023, which claims priority to U.S. Provisional application 63/309524, filed February 12, 2022, filed on June 5, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/12/2024 and 02/09/2026 has been considered by the examiner.
Status of Claims
Claims 1-11 are pending and under examination.
Specification
The abstract of the disclosure is objected to because it fails to provide a concise and definite statement of the technical disclosure. Specifically, the phrase “and the like” in the expression “an oral composition and the like” is vague and indefinite and does not clearly identify the subject matter to which the invention pertains. Further, the abstract appears to contain fewer than the preferred 50 to 500 words set forth in 37 C.F.R. 1.72(b). 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
Claims 3 and 9 are objected to because the expression “in terms of isoquercitrin” renders the claims awkward and difficult to read. Applicant is advised to amend the claims to clarify that component (A) is expressed as L-ergothioneine and component (B) is expressed as isoquercitrin equivalents. No rejection under 35 U.S.C. 112(b) is made because the metes and bounds of the claims are reasonably clear.
Claims 11 is objected to because the phrase “enhancing microorganism growth inhibitory action” lacks hyphenation and is grammatically awkward. Appropriate correction is required. No rejection under 35 U.S.C. 112(b) is made because one of ordinary skill in the art would understand that the phrase refers to enhancement of the microorganism growth-inhibitory action of quercetin or a glycoside thereof.
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 1-6 and 11 rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature exception (i.e., naturally occurring products and combinations thereof) without significantly more. The claim(s) recite(s) naturally occurring products, namely L-ergothioneine or salts thereof and quercetin or glycosides thereof, and combinations thereof. This judicial exception is not integrated into a practical application because the claims merely recite naturally occurring compounds and combination thereof. Although claims 3-6 recite ratio and microorganism-growth-inhibition limitations, the specification demonstrates a synergistic effect only for compositions having weight ratios of 0.025 and 1 (Table 1; paras. [0074]- [0083]). The claims are not limited to those compositions and therefore do not recite a composition having markedly different characteristics from the naturally occurring products. Claim 11 merely recites the intended use of L-ergothioneine or a salt thereof for enhancing the microorganism growth inhibitory action of quercin or a glycoside thereof and does not impose additional structural limitations. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements, considered individually and in combination, merely amount to well-understood, routine, and conventional use of naturally occurring compounds and do not amount significantly more than the judicial exception itself.
Under step 2A, Prong One of the 2019 Revised Patent Subject Matter Eligibility Guidance, claims 1-6 and 11 recite compositions comprising naturally occurring products. Specifically, claims 1-6 recite a composition comprising (A) L-ergothioneine or a salt thereof and (B) quercetin or a salt. Claim 11 recites an agent comprising L-ergothioneine of a salt thereof. L-ergothioneine and quercetin or glycosides thereof are naturally occurring substances. The specification teaches that naturally extracted and purified L-ergothioneine may be used and that L-ergothioneine is abundant in mushrooms (paras. [0027]). The specification further teaches quercetin or a glycoside thereof may be obtained from plants and that naturally derived extracts, concentrates, purified products, and isolated products may be used (paras. [0034]- [0035]). The specification additionally states that L-ergothioneine or a salt thereof and quercetin or a glycoside thereof are compounds found in natural products and foods or beverages that have been consumed (0054]). Therefore, the claims recite naturally occurring products and combinations thereof.
Under Step 2A, Prong Two, the additional elements do not integrate the judicial exception into a practical application. Claims 1 and 2 merely recite combinations of naturally occurring products. Claims 3 further recites a weight ratio of 0.01 to 1.2, and claims 4-6 recite compositions for inhibiting microorganism growth and particular microorganisms. However, the specification demonstrates a synergistic microorganism growth inhibitory effect only for compositions having weight ratio of 0.025 and 1, corresponding to test samples 3 and 4 (paras. [0074]- [0083], Table 1). The claims are not limited to these compositions and encompass numerous compositions for which no markedly different characteristic has been shown. Accordingly, the recited ratio and intended use limitations do not establish that the claimed compositions possess characteristics markedly different from those of the naturally occurring products.
Claim 11 recites an agent for enhancing microorganism growth inhibitory action of quercetin or a glycoside thereof, comprising L-ergothioneine or a salt thereof. The functional language merely expresses the intended use of the agent and does not impose structural limitations on the claimed composition. The claim encompasses naturally occurring L-ergothioneine and salts thereof and therefore does not recite a product possessing markedly different characteristics from naturally occurring products.
Under Step 2B, the claims do not recite additional elements amounting to significantly more than just the judicial exception. The claims merely recite naturally occurring compounds and conventional combinations thereof and therefore do not amount to significantly more than the judicial exception itself.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 11 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Repine et al. (WO2019/089878 A1).
Repine teaches a method for treating a microbial infection in a subject in need of treatment thereof, comprising administering to the subject a therapeutically effective amount of ergothioneine (ERGO), a precursor of ERGO, a salt thereof, or a biologically active analog, or prodrug thereof, wherein the ERGO is the L isomer (L-Ergothioneine). (See claims 1 and 2 and Figs 1A and 1B and the corresponding description on pages 14-15.)
The recitation “for enhancing microorganism growth inhibitory action of quercetin or a glycoside thereof” merely states an intended use or purpose for the claimed agent and does not impose a structural limitation on the claimed composition. The only positively recited component required by claim 11 is L-ergothioneine or a salt thereof.
Repine expressly disclose L-ergothioneine and salts thereof. Accordingly, every limitation of claim 11 is disclosed by Repine et al. and claim 11 is anticipated.
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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Repine et al. (WO2019/089878 A1) in view of Yun et al. (Biochimica & Biophysica Acta-Biomembranes 1800 (2018), 357-363) and Uyanga et al. (Nutrients 2021, 13, 3782).
Repine teaches a composition a method for treating a microbial infection in a subject in need of treatment thereof, comprising administering to the subject a therapeutically effective amount of ergothioneine (ERGO), a precursor of ERGO, a salt thereof, or a biologically active analog, or prodrug thereof, wherein the ERGO is the L isomer (L-Ergothioneine), wherein ERGO is administered with another agent, or agents, effective in preventing or treating a microbial infection, and wherein ERGO is administered with lactoferrin (LF), or a precursor of LF, a salt thereof, or a biologically active analog, or prodrug thereof. (See claims 1-3.) Repine also teaches antimicrobial activity against E. coli. (See Figs. 1A and 1B, and corresponding description). Repine additionally teaches inhibition of E. coli growth using 1 mg/ml LF and ERGO concentrations of 0.2 mM, 1 mM, 5 mM, and 10 mM. (See Figure 2.) So, using ERGO molecular weight = 229.3 g/mol.
Formula: mM x molecular weight ÷ 1000 = mg/ml.
1 nM = 0.001 mol/L, and 1g/L = 1 mg/ml.
0.2 nM ERGO ------- 0.2 mM x 229.3 ÷ 1000 = 0.04586 mg/mL
0.1 mM ERGO ------ 0.1 mM x 229.3 ÷ 1000 = 0.2293 mg/mL
5 mM ERGO ------- 5 mM x 229.3 ÷ 1000 = 1.1465 mg/mL and
10 mM ERGO ------- 10 mM x 229.3 ÷ 1000 = 2.296 mg/mL.
Repine further teaches the other agent may include lactoferrin (LF; lactotransferrin (LTF)). The LF may be a precursor of LF, a salt thereof, or a biologically active analog, and/or prodrug thereof. In these methods, the ERGO may enhance the anti-microbial activities of LF. (See lines 3-5 of page 3.)
Thus, Repine expressly teaches a composition comprising L-ergothioneine or a salt thereof (claim 1); inhibiting microorganisms’ growth (claim 1); inhibition of E. coli bacterial growth (claims 6 and 10, and examples); and a method of inhibiting microorganism growth comprising administering or adding L-ergothioneine. (See claims 7 and 8.)
Repine does not expressly disclose combining L-ergothioneine with quercetin or glycoside thereof.
Yun discloses isoquercetrin, a glycoside or quercetin, exhibits antibacterial activity against E. coli and also teaches that isoquercetrin inhibits bacterial growth and induces membrane permeabilization, oxidative stress, apoptosis-like death, lipid peroxidation, and membrane dysfunction in E. coli. (See Abstract.)
Uyanga teaches that quercetin interacts favorably with sulfur-containing dietary components and such combinations improve gut health and immunity in animal. (See last paragraph of page 15.)
Primary rationale: It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine the antimicrobial L-ergothioneine taught by Repine with the antimicrobial isoquercetrin taught by Yun because both references teach agents useful for inhibiting microbial growth, including E. coli and one would have reasonably expected that combining two known antimicrobial gents would provide a composition and method having addition or enhanced antimicrobial efficacy against E. coli. Repine expressly teaches that ERGO may be administered with another antimicrobial agent effective for preventing or treating infection caused and that ERGO may enhance the antimicrobial activities of companion antimicrobial agent, such as lactoferrin. (See p. 3, lines 1-5.) Repine further teaches compositions comprising ERGO and another antimicrobial and/or anti-inflammatory agent. (See p. 3, lines 20-29.) Additionally, Uyanga teaches that quercetin interacts with sulfur-containing amino acids to improve gut function and immunity in animals. Because Repine teaches that ERGO is a sulfur-containing compound (see lines 1-19 of page 5) and Yun teaches isoquercetrin is antimicrobial quercetin glycoside effective against E. coli, one of ordinary skill in the art would have reasonably that combining ERGO with isoquercetrin would provide beneficial antimicrobial activity and enhanced efficacy against E. coli with a reasonable expectation of success.
Secondary rationale: It would have been obvious to substitute the antimicrobial isoquerceitrin taught by Yun for the antimicrobial lactoferrin exemplified by Repine because both lactoferrin and isoquercetrin are antimicrobial agents and both serve the same role in the composition of Repine, namely, as the companion antimicrobial agent whose antimicrobial activity in enhanced by ERGO. Repine teaches that lactoferrin is merely one example of another agent effective in preventing or treating infection and further taches compositions comprising ERGO and another antimicrobial and/or anti-inflammatory agent. Therefore, one of ordinary skill in the art would have reasonably expected isoquercetrin to function as another companion antimicrobial agent for ERGO with the expectation of obtaining enhanced antimicrobial activity against microorganisms, including E. coli. Furthermore, Uyanga teaches that quercetin compounds interact favorably with sulfur-containing amino acid to improve gut function and immunity, thereby providing additional support for the compatibility and beneficial interaction between isoquercetrin and the sulfur-containing compound ERGO.
With respect to the ratios claimed, Repine taches different ERGO-to-companion-agent ratios were investigated, ratios of about 0.046 to 2.29 by weight were known to be effective and a ratio of 1.146 overlaps the claimed upper endpoint 1.2. Additionally, Repine teaches ERGO-to-companion-agent weight ratios of about 0.046 to 2.29, including a ratio of approximately 1.146, which overlaps the claimed range of 0.01 to 1.2. optimization of relative amounts of relative amounts of known antimicrobial agents constitutes routine optimization of a result-effective variable as suggested by Repine as Repine teaches to do so, because Repine teaches in lines 20-36 of page 14 bridging lines 1-7 of page 15 that
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and also, because Figure 2 of Repine demonstrates that different ERGO-to-companion-agent ratios affect antimicrobial activity, thereby evidencing that the relative amounts of ERGO and a companion antimicrobial agent influence the desired result and therefore constitutes a result-effective-result.
Conclusion
Claims 1-11 are not allowed.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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