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 .
Please note that the Examiner for this application has changed. Any inquiry concerning this communication should be directed to ANDREW TERRY MOEHLMAN.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The translation of the certified copy of Foreign Application CN2022109553014, filed 8/10/2022, is acknowledged. Benefit of priority to 8/10/2022 is acknowledged for claims 1 and 3-9.
Response to Amendment
Applicant’s remarks and amendments filed 10/28/2025, in response to the non-final rejection mailed 8/11/2025, are acknowledged and have been fully considered.
Applicant’s amendment to the claims is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Any previous rejection or objection not mentioned explicitly herein have been withdrawn based upon Applicant’s amendments to the claims.
Claims 1 and 3-9 are pending and have been examined on the merits.
Claim Interpretation
Under the broadest reasonable interpretation (B.R.I.), in light of the specification, the claims are interpreted as being directed to “A method for forming a fungi fermentation product containing N-acetylglucosamine”, the method steps comprising a fungus treatment procedure, a strain activation procedure, and a fermentation procedure to form the fungi fermentation product containing N-acetylglucosamine. Claim 1 also recites “to convert cancer cells into normal cells through a mesenchymal epithelial transition mechanism; wherein: the cancer cells are Huh7 cells;”, which is clearly directed to an intended use of the product produced by the claimed method. Thus, the conversion/transformation of cancer cells into “normal” cells (e.g. cells having an epithelial-like appearance) as stated in the preamble and the following wherein clause requiring Huh7 cells are being treated as an intended use.
In this case, the intended use does not result in any manipulative differences for the claimed production steps (see MPEP § 2111.02.II., “statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art”).
Claim Objections
Claim 7 is objected to because of the following informalities:
Claim 7 was amended to address an issue of indefiniteness. Applicant’s amendment to recite “PDA (Potato Dextrose Agar)” is noted. Although the subject matter of the claim is defined, this abbreviation should be in parenthesis on first use. For improved clarity and proper formalities, it is suggested to amend this to “potato dextrose agar (PDA)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
(Rejection maintained, modified as necessitated by Applicant’s Amendments)
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 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Sun, X et al., (CN113373059) in view of An, Q., et al. ("Sequential solid-state and submerged cultivation of the white rot fungus Pleurotus ostreatus on biomass and the activity of lignocellulolytic enzymes," BioRes. 11(4), 8791-8805. 2016); Chen et al., (“Structural characterization and biological activities of a novel polysaccharide containing N-acetylglucosamine from Ganoderma sinense.” Int J Biol Macromol. 2020 May 6:S0141-8130(20)33174-3); and Tan, et al. (“Bisecting N-Acetylglucosamine Structures Inhibit Hypoxia-Induced Epithelial-Mesenchymal Transition in Breast Cancer Cells.” Front Physiol. 2018 Mar 9;9:210).
Sun et al. teaches a method for increasing the content of adenosine and ergosterol in a fungus mixed fermentation broth. Sun et al. teaches the following steps:
(1) firstly, respectively preparing a plurality of medicinal and edible fungus slant mother strains at the culture temperature of 20-25 DEG C and with the humidity of 45-65% and the culture time of 7-10 days; and (2) after the mother strains are mature, respectively inoculating seed fermentation shake flasks, placing 5-8 glass beads in each flask, and controlling the inoculation amount to be 5-8 square centimeters, wherein the culture temperature is 20-25 DEG C, the rotating speed is 180-240 rpm, and the culture time is 56-72 hours. (Abstract).
Sun et al. further teaches the multiple medicinal and edible fungi in step (1) can comprise two or a combination of two or more of Ganoderma lucidium and Cordyceps sinensis (see Summary of the Invention, [0007]) (broadly disclosing a method comprising a fungus treatment procedure, a strain activation procedure and a fermentation procedure, as required in claim 1 (and claims dependent thereto).
However, Sun et al. does not expressly teach that: the fungus treatment procedure comprises forming a fungi fruiting body (claim 1); the fermentation procedure comprising forming a fungi fermentation product containing N-acetylglucosamine (claim 1); and the duration, weight ratios, heating temperatures, and percent volume of the method steps. Further, the reference does not explicitly teach the intended use for the product wherein the fungi fermentation product containing N-acetylglucosamine is added in a culture medium of cancer cells to induce and transform Huh7 cells cancer cells into “normal” cells (claim 1).
An et al. teaches sequential solid-state and submerged cultivation of a white rot fungus, Pleuortus ostreatus. For example, An et al. teaches pre-culture cultivation of P. ostreatus mycelia in a solid substrate medium for initial fungal growth phase followed by a transition to submerged fermentation through adding a liquid culture medium (see Abstract & Methods “Inoculum preparation”) (broadly teaching the fungus treatment procedure comprising forming a fungi fruiting body or mycelium liquid, as required in claim 1 and a strain activation procedure, as required in claim 1). Moreover, An et al. teaches the combination of solid-substrate and submerged fermentation was shown to be superior to only one of the conventional solid-state or submerged fermentation methods (see Conclusions).
Chen et al. teaches Ganoderma is a long-established traditional medicine in China containing several biologically active substances, including polysaccharides, glucosamine, alkaloids, water-soluble proteins, etc., and is known for its varied biological activities including regulation of immunity, antioxidant, anti-tumor and mushroom-poison detoxification properties (broadly teaching anti-cancer properties). Chen et al. further teaches that N-acetylglucosamine can be found in polysaccharide structures of fungi, including Ganoderma sinense (see Introduction, pages 1204-05, broadly teaching a fermentation procedure comprising forming a fungi fermentation product containing N-acetylglucosamine, as required in claim 1).
Tan et al. teaches bisected N-acetylglucosamine inhibits hypoxia-induced epithelial-mesenchymal transition (EMT) in breast cancer cells. Tan et al. teaches bisected N-acetylglucosamine is involved in inhibiting hypoxic EMT-triggering pathways that facilitate tumor growth and metastasis (see Discussion, pages 6-7) (broadly that if N-acetylglucosamine is added in a culture medium of cancer cells, a derivative may promote staying as epithelial cells).
Therefore, before the filing date of the instant invention, it would have been obvious to a person of ordinary skill in the art to have modified the fungus treatment procedure, strain activation procedure and fermentation procedure steps as taught by Sun et al. with the superior sequential solid-state and submersion cultivation step as taught by An et al. because the references teach that such steps were known to one of ordinary skill in the art (i.e. fungal fermentation techniques) at the time of the instant filing.
A person of ordinary skill in the art would have been motivated to have modified the steps in view of the teachings of An et al. that the combination of solid-substrate and submerged fermentation is superior to either fermentation on its own. Further, regarding the presence of N- acetylglucosamine, it is evidenced from the cited teachings of Chen that GlcNAc is inherently present in the polysaccharide structures of fungi (e.g. GlcNAc is an integral part of the cell wall).
Regarding the recited intended use of the produced fungal product, Tan et al. teaches that bisected N-acetylglucosamine inhibits hypoxia induced epithelial-mesenchymal transition (EMT) in breast cancer cells. Although not explicitly teaching mesenchymal to epithelial transition, the reference suggests that an abundance of GlcNAc would favor epithelial cell maintenance.
If not expressly taught by the references, based upon the overall beneficial teaching provided by these references with respect to the ingredients of the composition and methods of making in the manner disclosed therein, the adjustments of particular conventional working conditions, including the duration, weight ratios, heating temperatures, and percent volume of the method steps, are deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan.
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, by performing the methods as claimed to produce a fungal fermentation product.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in the absence of evidence to the contrary. Thus, absent some demonstration of unexpected results or criticality from the claimed parameters, this optimization would have been obvious before the effective filing date of applicant’s claimed invention.
Accordingly, the claimed invention as a whole was at least prima facie obvious, especially in the absence of sufficient, clear and convincing evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants' method/composition(s) with the method/composition(s) of the prior art (including compositions within recited processes), the burden is on applicant to show a novel or unobvious difference between the claimed method/product and the method/ product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Response to Arguments
Applicant's arguments on pages 8-12 with regards to the rejections under 35 U.S.C. § 103 have been fully considered but they are not persuasive.
Applicant’s arguments involving the application of GlcNAc to induce a MET mechanism in Huh7 cells (on pages 9-10) relies on language solely recited in preamble recitations in claim 1. When reading the preamble in the context of the entire claim, the recitation “to convert cancer cells into normal cells through a mesenchymal epithelial transition mechanism; wherein: the cancer cells are Huh7 cells” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. There are no manipulative differences in the method of forming the fungal product that are required of the preamble. The preamble is completely directed to an intended use.
Thus, the preamble of the claim 1 is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Further, in response to applicant's argument that the reference “Tan et al.” is directed to teachings involving a derivative of GlcNAc, “bisected GlcNAc”, this argument is moot because a recitation of the intended use of the claimed invention must result in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If a prior art structure or a product produced by carrying out a method known or suggested in the art is capable of performing the intended use, then it meets the claim. Without considering the intended use recitation of the preamble, a method for forming a fungal product containing GlcNAc, as claimed herein, would have been obvious over the teachings of Sun, An et al., and Chen et al., for all the reasons previously described. In other words, it is evident that from the cited teachings of the Sun, An, and Chen references, the instantly claimed production method would have been obvious, and the product produced by the obvious process would have naturally possessed GlcNAc, and thus would be capable of use in the intended application.
Applicant argues that the combination of cited references does not teach a method having “three steps including a fungus treatment procedure, a strain activation procedure, and a fermentation procedure, as disclosed in the amended claim 1”. This argument has not been found persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Sun et al. teaches a fermentation method that comprises preparing a plurality of medicinal and edible fungal slant mother strains (e.g. a mixed fungal fermentation broth). The strains exemplified on Sun include Ganoderma lucidum and Cordyceps sinensis. The initial step of Sun is a preparation of potato dextrose agar (PDA) slant cultures, which is a solid-state culture, for 7 days. The next step involves a liquid culture medium, with temperatures and rotation speeds encompassing the amounts that are instantly claimed. Thus, Sun does in fact suggest strain activation steps, including steps for performing both solid-state and liquid culturing of a Cordyceps fungus. Although this reference does not expressly teach the claimed durations, such durations of cultures are routine to optimize in the art in order to optimize the yield of a useful fungal product. Further, such co-culturing of these two species, Ganoderma lucidum and Cordyceps sinensis, as exemplified in Sun, would predictably result in a fermentation product having similar properties as that which is produced by the instantly claimed invention.
An teaches, in the previously cited sections of: “Methods, Inoculum preparation” and “Pre-culture for submerged fermentation (Smf)), that “mycelial pellets were harvested and homogenized with a laboratory blender”, and An also teaches that prior to the submerged fermentation, water is added (broadly, water is in the dilution media) and the mixture is autoclaved at 121°C for 30 min (thus broadly, the mixture is sterilized as instantly claimed). Steps of preparing a mycelium such as weighing and cleaning are well-known in the art and do not amount to a critical patentable difference. These preparation steps would have been routine to one of ordinary skill, as evidenced from An. In performing a method made obvious by the combination of An and Sun, the steps of a fungus treatment procedure, a strain activation procedure, and a fermentation, as instantly claimed, would have naturally been performed.
Thus, in response to applicant's argument that the combination of references does not explicitly teach all of the steps of a “fungal treatment procedure”, a “strain activation procedure” and a “fermentation procedure”, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Here, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, An teaches the benefits of subsequent solid-state and liquid state fermentation, and both Sun and An disclose methods for preparing fungus for culturing.
MPEP 2141.II.C states that: "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396.
The claimed preparation steps involving weighing, cleaning, mixing, crushing, and sterilizing a fungal crop media are all known in the art would have been obvious to combine when preparing a mixture culture of cordyceps and a mycelium-forming fungi. Thus, there doesn’t appear to be any inventive difference in the claimed method steps that distinguishes the instant claims from the methods taught by the combination of Sun and An, and steps for routine optimization, which would have all been within the level of ordinary skill in the art.
Regarding the dependent claims, MPEP § 2144.05 describes that the determination of conditions, temperatures, or concentrations can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, when these are recognized variable parameters attainable within the art. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The ratios, temperature, and incubation times recited in the dependent claims would have all been obvious to optimize to one having ordinary skill, in view of the knowledge in the art.
Regarding the Chen and Tan references, although the claimed application of the fungal product is an intended use, Chen does establish that fungi including Ganoderma sp. have polysaccharides comprising N-acetylglucosamine, and Tan teaches that a derivative of N-acetylglucosamine inhibits the epithelial to mesenchymal transition (e.g. promotes cells staying in the epithelial state). The applicant has pointed out that N-acetylglucosamine is transformed to bisecting GlcNAc when applied to target cells due to the effects of a mammalian enzyme, MGAT3. If the substrate of MGAT3 leads to a product that causes inhibition in a transformation to a mesenchymal state, then it stands to reason that application of the substrate GlcNAc would promote activity of this enzyme. Regardless, the intended use recited in the preamble is not practically limiting the claimed production method of the fungal product. These references establish that a fungal product produced by the method made obvious in Sun and An would intrinsically possess GlcNAc and serve essentially the same function as the composition of the instant claims. See MPEP §§ 2111.02 and 2141.02.V.
Thus, the provided arguments have been fully considered and found not persuasive. The claims remain rejected as being obvious over the cited combination of Sun and An, with support from Chen and Tan.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the modified grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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