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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/03/2025 has been entered.
Priority
This application claims benefit of priority to Republic of Korea Patent Application No. KR10-2019-0129324 filed on 10/17/2019. This application is also a 371 of PCT/KR2020/012364 filed on 10/17/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, a translation of the certified copy of the Korean patent document was not provided. As such, the priority date of the instant application is the PCT date, 10/17/2019.
Amendments and Claim Status
In the reply filed 11/03/2025, Applicant amended claims 1-2, 4, 8 and 17-18 and canceled claims 5-7.
Claims 1-4 and 8-18 are currently pending and under examination.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites “concentrating a culture broth to a first concentration of the 5’-inosine acid in the culture broth is from 150 g/L to 360 g/L” in lines 5-6. This portion of the claim is grammatically awkward. For example, replacing ‘of’ with ‘until’ so the above recited portion would recite “concentrating a culture broth to a first concentration until the 5’-inosine acid in the culture broth is from 150 g/L to 360 g/L.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4 and 8-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “concentrating a culture broth to a first concentration …” in line 5 of the claim. It is unclear what culture broth is being referred to. Lines 3-4 recite “culturing a microorganism that produces 5’inosinic acid to obtain a microorganism culture,” however, the next line, line 5, recites ‘a culture broth,’ not a ‘microorganism culture broth.’ Thus, it is unclear whether the culture broth that is being concentrated is the microorganism culture broth or another culture broth. Therefore claim 1, and all claims dependent upon claim 1, are rendered indefinite.
Claim 1 recites the limitation "concentrating a culture broth to a first concentration of the 5’-inosine acid" in line 5. There is insufficient antecedent basis for this limitation in the claim. The claim does not previously recite ‘5’-inosine acid,’ but recites ‘5’-inosinic acid’ in line 3 of the claim. Thus, there is insufficient antecedent basis for ‘the 5’-inosine acid’ in the claim.
Claim 9 recites the limitation "comprising cooling formed crystals after the concentrating" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Reciting ‘the concentrating’ is attempting to establish antecedence to a particular step, the concentrating step. However, claim 1, the claim from which 9 depends, now recites two concentrating steps. Thus, there is insufficient antecedent basis for this limitation in the claim. It is suggested to amend claim 9 to recite the particular concentration step the cooling occurs after. For example, Applicant could amend the claim to recite “comprising cooling formed crystals after the concentrating of the pH-adjusted culture broth.”
Claim Rejections - 35 USC § 103
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.
Claims 1-4, 8-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (CN 101918576 A, 12/15/2010) (IDS Reference of 06/22/2023) (New translation provided).
Regarding claims 1 and 17, Hong et al. disclose a method of preparing disodium 5’-inosinate from 5’-inosinic acid via a method that uses only a small amount of organic solvent (See entire document, Abstract). Using a large amount of hydrophilic organic solvent causes impurities to be extracted which results in reduced inosinic acid content, negatively affecting the crystallization process (Page 2, Sentence 8). Therefore, Hong et al. experimented on how to increase the yield and purity of crystals while also minimizing the amount of organic solvent used.
Regarding their specific method, Hong et al. disclose:
A method for preparing 5'-disodium inosinate, wherein the method comprises: The first step is to separate and remove fungal cells from the fermentation broth of the inosinic acid-producing strain; In the second step, concentrating the fermented liquid; In the third step, the pH value of the concentrated fermented liquid is adjusted to 6-10; The fourth step is to heat the fermented liquid after adjusting the pH so that the pre-crystallized 5'-disodium inosinate is completely dissolved; Step 5, cooling the fermentation broth containing dissolved disodium 5'-inosinate crystals; and In the sixth step, a hydrophilic organic solvent is added to the cooled fermented liquid to crystallize disodium 5'-inosinate (Claim 1 of Hong et al.).
Hong et al. further disclose the second step of condensing stops when the concentration of inosinic acid is 200-300 g/L (Claim 2 of Hong et al.). This condensing step occurs before the pH is adjusted and reads on the second part of instant claim 1 which states “concentrating a culture broth to a first concentration of the 5’-inosine acid in the culture broth is from 150 g/L to 360 g/L, and the adjusting the pH of the concentrated culture broth to be from 7.4 to 8.0.”
Regarding the limitation of concentrating the pH-adjusted culture broth to a concentration of 5’-inosinic acid from 400 g/L to 550 g/L to provide a slurry containing disodium 5’-inosinate crystals, it is noted the instant Specification states:
The concentrating of the pH-adjusted culture broth may be to reduce the amount
of moisture in the culture broth. The concentrating may be to evaporate moisture by applying heat to the culture broth. The concentrating may be performed on the culture broth at a temperature of 50 °C or more, 60 °C or more, 70 °C or more, 80 °C or more, 90 °C or more, 50 °C to 90 °C, 50 °C to 80 °C, 50 °C to 70 °C, 50°C to 60 °C, 60 °C to 90 °C, 60 °C to 80 °C, 60 °C to 70 °C, or 60 °C to 65 °C. The concentrating may be to perform concentration under reduced pressure. The concentrating may be performed until disodium 5'-inosinate crystals are formed by increasing the concentration of 5'-inosinic acid in the culture broth (Specification, Paragraph [17]).
Hong et al. disclose the heating in the fourth step, after the pH has been adjusted, is carried out at 55-77°C (Claim 3 of Hong et al.). Thus, though Hong et al. do not explicitly state the fourth step is a ‘concentrating’ step, it appears, absent evidence to the contrary, that the fourth step of warming the pH adjusted fermentation broth step of Hong et al. would necessarily concentrate the fermentation broth because the liquid is being heated which would result in a reduction of moisture in the broth, meaning the broth is more concentrated, as evidenced by the citation from the instant Specification discussed immediately above. Hong et al. further state the cooling of the fifth step is carried out at a rate of 5-10°C an hour and cooled to 20-30°C (Claim 4 of Hong et al.). Then, in step 6, once the fermented liquid is at a temperature of 20°C, the organic solvent is added (Claim 5 of Hong et al.). This indicates organic solvent is not added until after the warming step, wherein the warming step is the second concentrating step as discussed above. Therefore, Hong et al. disclose concentrating the pH adjusted culture broth in the absence of an organic solvent. Additionally, the 6th step of cooling, occurring after the warming step, where the fermentation broth is slowly cooled reads on a providing a slurry containing disodium 5’-inosinate crystals because as the fermentation broth begins to cool, the crystals naturally begin to precipitate, as evidenced by Hong et al. warming the fermentation broth to thoroughly dissolve the pre-crystallized 5'-disodium inosinate in step 4. Then, in step 6, the organic solvent is added, reading on washing the 5'-disodium inosinate by contacting the crystals with a hydrophilic organic solvent.
Hong et al. do not disclose a concentration of 5’-inosinic acid in the pH adjusted culture broth of 400 g/L to 550 g/L.
However, Hong et al. do disclose the precipitation of crystals was based on the supersaturation of inosinic acid in the culture concentrate (Page 3, Embodiment 1, Sentence 3). Thus, supersaturation, being when a solute concentration exceeds its solubility in a given solution, drives the precipitation of crystals. Hong et al. disclose in order to establish the optimal crystallization conditions of disodium 5’-inosinate, the solubility of disodium 5’-inosinate was determined by temperature and organic solvent (Page 3, Embodiment 1, Sentence 1). Figure 1 of Hong et al. is a graph showing the solubility of inosinic acid in concentrated fermented broth based on % of methanol added and Figure 2 of Hong et al. is a graph showing a supersaturation curve of crystals based on the added organic solvent methanol (Page 3, Description of Drawings, Sentences 1-2). Figure 2 of Hong et al. shows supersaturation is reached at a higher concentration (g/L) of inosinic acid when there is 0 methanol present in the concentrated fermented broth. Similarly, Figure 1 of Hong et al. shows the solubility of inosinic acid is higher when 0 methanol is present in the concentrated fermented broth.
“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.” See MPEP 2144.05(II)(A). As such, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine the optimal concentrations of inosinic acid because inosinic acid is an art-recognized result-effective variable wherein the concentration of inosinic acid in a fermentation broth must be high when no organic solvent is present to promote natural crystallization as disclosed by the prior art above. Therefore, the concentration of inosinic acid would have been routinely and predictably optimized to promote the formation of the desired product, disodium 5’-inosinate crystals. Although the prior art does not disclose the specific concentration of 5’-inosinic acid claimed, it would have been conventional and within the skill level of an ordinary artisan to modify the concentration of 5’-inosinic acid in a fermentation broth, via further concentrating, motivated by the desire to reach supersaturation so disodium 5’-inosinate crystals would precipitate.
Regarding claims 2 and 3, Hong et al. disclose the microbial fermented liquid of the invention is cultivated by inoculating inosinic acid producing strains wherein the bacterial strains used for cultivation can be any bacterial strain capable of producing inosinic acid, preferably Corynebacterium sp. (Page 2, Sentence 13). Coryneform bacteria are preferably cultured for production of about 5% - 10% inosinic acid in the fermentation broth (Page 2, Sentence 13). 5% - 10% inosinic acid falls within the claimed range.
Regarding claim 4, Hong et al. disclose the filtered fermented liquid was concentrated by drying under reduced pressure at a vacuum degree of 680 mmHg and a container temperature of 55°C so that the concentration of inosinic acid became 230-260 g/L (Page 3, Step 2: Concentration of the filtered broth).
Hong et al. do not disclose the concentrating of the pH-adjusted culture broth is performed under reduced pressure.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have performed the concentrating of the pH-adjusted culture broth under reduced pressure as Hong et al. do disclose the first concentrating step being performed under reduced pressure. Thus, it would have been obvious to one of ordinary skill in the art to perform the second concentration step, the warming step, under reduced pressure as well motivated by the desire to effectively concentrate the fermentation broth to the desired concentration of inosinic acid.
Regarding claim 8, Hong et al. disclose the filtered fermented liquid was concentrated by drying under reduced pressure at a vacuum degree of 680 mmHg and a container temperature of 55°C so that the concentration of inosinic acid became 230-260 g/L (Page 3, Step 2: Concentration of the filtered broth).
Regarding claim 9, See 112b above. Hong et al. disclose the second step, concentrating the fermented liquid; In the third step, the pH value of the concentrated fermented liquid is adjusted to 6-10; The fourth step is to heat the fermented liquid after adjusting the pH so that the pre-crystallized 5'-disodium inosinate is completely dissolved; Step 5, cooling the fermentation broth containing dissolved disodium 5'-inosinate crystals (Claim 1 of Hong et al.). As discussed above, the warming step disclosed by Hong et al. reads on concentrating. Thus, as Hong et al. disclose the 5th step is cooling, which occurs immediately after warming, this reads on cooling the crystals after concentrating.
Regarding claim 10, Hong et al. disclose wherein the 5th step of cooling wherein the fermentation broth is cooled to the temperature of 20-30°C (Claim 4 of Hong et al.). The fermentation broth being cooled to the temperature of 20-30°C spans the entirety of the claimed range of 25°C to 30°C.
Regarding claims 11 and 12, Hong et al. disclose wherein the lower alcohol is methanol (Claim 8 of Hong et al.).
Regarding claim 13, Hong et al. disclose methanol, ethanol, propanol and isopropanol are all organic solvents which can be used in the invention (Page 3, Step 5: Addition of organic solvent).
Regarding claim 14, Hong et al. disclose wherein the concentration of the methanol is 70-95% (v/v) (Claim 9 of Hong et al.).
Regarding claim 15, the sixth step is carried out by adding a hydrophilic organic solvent when the concentrated fermentation broth is at 20ׄ°C wherein the hydrophilic organic solvent is added in an amount of 30-60 (v/v)% of the total amount of the fermentation broth (Page 2, Sentence 10 under ‘Contents of the Invention’).
Claims 1-4 and 8-17 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (CN 101918576 A, 12/15/2010) (IDS Reference of 06/22/2023) (New translation provided) and further in view of Han et al. (CN 101109017 A, 01/23/2008) (IDS Reference of 01/24/2023).
The teachings of Hong et al. are disclosed above.
Regarding claim 16, Hong et al. disclose the product created from the method of preparing disodium 5’-inosinate contains colored substances, sugars, amino acids, organic acids and inorganic that must be removed through purification in order to obtain a product with a quality that can be used as a food additive (Page 2, Sentence 4).
Hong et al. do not disclose contacting the washed crystals with activated carbon in an aqueous solvent to remove a coloring material.
However, Han et al. disclose a method of making 5’-disodium inosinate via microbial fermentation (See entire document, Abstract). Han et al. further disclose utilizing active carbon in a decoloring step (Page 2, Last Paragraph).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized activated carbon in the method of Hong et al. motivated by the desire to remove colored substances and purify the product because activated carbon is a known and effective decoloring agent as taught by Han et al. as this amounts to utilizing a known technique to improve similar products in the same way. Exemplary rationales that may support a conclusion of obviousness include use of a known technique to improve similar products in the same way. See MPEP 2143(I)(C).
Claims 1-4, 8-15 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (CN 101918576 A, 12/15/2010) (IDS Reference of 06/22/2023) (New translation provided) and further in view of Fujinawa et al. (US 4958017 A, 09/18/1990) (IDS Reference of 06/22/2023).
The teachings of Hong et al. are discussed above.
Regarding claim 18, Hong et al. do not disclose adding NaOH to the culture broth after removing the cell bodies and before concentrating the culture broth. It is noted the step being referred to is adjusting the pH.
However, Fujinawa et al. disclose a method for purifying inosine (See entire document, Title). Fujinawa et al. further disclose a mixture containing inosine and guanosine as a starting material, where the mixture is suspended in water at a specific pH range (Column 3, Lines 44-51). For adjusting the pH, an appropriate alkali can be used, preferably sodium hydroxide (Column 3, Lines 55-56).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As such, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used NaOH (sodium hydroxide) as a pH adjusting agent in the method of Hong et al. since the method does not require a specific pH adjusting agent and NaOH is a known and effective pH adjusting agent as taught by Fujinawa et al.
Response to Arguments
Applicant's arguments filed 11/03/2025 have been fully considered but they are not persuasive.
Applicant’s arguments presented with the Request for Continued examination have been fully considered by the Examiner. It is the Examiner’s position that the amended claims are still obvious over the prior art of record as explained in the rejection set forth above. Additionally, Applicant’s arguments were addressed in the rejection set forth above.
Conclusion
Claims 1-4 and 8-18 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653