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 a 371 of PCT/CN2021/141025 filed 12/24/2024. Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119 (a)-(d) to CN 202110168751.4 filed 02/07/2021, CN 202110337621.9 filed 03/30/2021 and CN 202110678427. 7 filed 06/18/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of the Claims
Claims 12, 14-20 and 22-24 are pending. Claims 12, 16, 18, 20 and 22-24 are amended. Claim 21 is cancelled.
Claims 12, 14-20 and 22-24 (claim set filed 06/09/2026) are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 06/09/2026 are acknowledged. All of the amendment and arguments have been thoroughly reviewed and considered.
For the purposes of clarity of the record, the reasons for the Examiner's withdrawal and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner's response to arguments section.
The previous specification objection has been withdrawn necessitated by amendment of specification.
The previous claims 16 and 18-24 rejections under 35 U.S.C. 112(b) have been withdrawn necessitated by amendment of claims 16, 18 and 22-24.
The previous claims 18-21 and 24 rejection under 35 U.S.C. 112(a) have been withdrawn necessitated amendment of claim 18, i.e. removing limitation for feeding volume and changing limitation for the temperature of fermentation to 20-30°C, that is supported by the specification.
Maintained/Modified Rejections
The following rejections are maintained and/or modified taking into consideration amendment to claims filed on 06/09/2026.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 12, 14-20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Tucaliuc (Tucaliuc et al. Biotechnol. Lett., 2018, 41, 495-502) in view of Poontawee (Poontawee and Limtong Microorganisms 2020, 151, 1-19), Wang (CN 110747188A), Ge (CN 111996136A on record in IDS) and Xiong (CN 109929890A).
Regarding claim 12, Tucaliuc teaches that mupirocin is an antibiotic which can be obtained as a mixture of pseudomonic acids by fermentation of Pseudomonas fluorescens (Abstract). Tucaliuc describes different fermentation medium for production of mupirocin having glucose as the main carbon source for up-to 6% and glycerol at 1% (p. 500, Table 3). Tucaliuc discloses nitrogen source comprising corn steep liquor (0.5%) and soy bean meal (2%) (p. 500, Table 3). The inorganic salts include sulfates, phosphates and chlorides and in particular, KH2PO4 at 0.15%, (NH4)2SO4 at 0.5%, MgSO4 x7H2O at 0.05% and KCI at 0.1% (p. 500, Table 3). Production is performed for 50 hours, at 24-26°C and pH= 5.3-7 (p. 499, left column, last paragraph). Tucaliuc mentions feeding 50% glucose throughout the process (p. 499, left column, last paragraph) and describes feeding the dextrose solution to keep glucose at 0.5% level (p. 499, right column, last paragraph), however does not provide the description of the feeding medium.
Tucaliuc does not teach urea and defoamer in the fermentation medium and does not teach the complete composition of the medium for feed culture.
Poontawee teaches feeding strategies for microbial fermentation (Abstract). Poontawee discloses that during fed-batch fermentation the essential nutrients for cell growth or product formation are intermittently or continuously added to the culture vessel during cultivation. That allows to keep the concentration of limiting nutrients at an optimal level that shortens fermentation time, achieves high cell concentration and increases productivity (p. 2, 3rd paragraph).
Wang teaches method for producing keratinase by bacterial fermentation (Abstract). Wang describes a fermentation medium: "Corn starch 2.5%, corn flour 3.5%, feather flour 1.5%, soy flour 3.5%, corn pulp 3%, sucrose 3.2%, potassium dihydrogen phosphate 1.7%, magnesium sulfate 0.27%, pH 6.5" (p. 2, lines 38-39) and feed medium: "Corn starch 25%, soybean cake flour 5.2%, corn pulp 2.3%, feather flour 1.5%, ammonium sulfate 0.5%, potassium dihydrogen phosphate 0.2%, pH 6.5'' (p. 3, lines 6-7). Fermentation and feed medium have similar components of carbon and nitrogen source and inorganic salts, however, the amount of carbon source, corn starch, is increased from 2.5% to 25% in feed medium. Wang mentions that the method provided higher fermentation activity, higher extraction yield and lower manufacturing cost (p. 3, lines 31-32).
Ge teaches fermentation of Pseudomonas fluorescence producing mupirocin (paragraphs 0002, 0004). Ge discloses that addition of sodium molybdate and urea significantly improved cell activity of bacteria and the yield of mupirocin (paragraph 0011). Ge describes that urea was added at 0.1-1% (paragraph 0014). Ge used glucose and glycerol as carbon source and corn steep liquor as nitrogen source (paragraph 0015).
Xiong teaches microbial fermentation and production of mycophenolic acid (Abstract). Xiong describes the composition of the fermentation medium which contains GPE defoamer at 0.4-0.6 g/L (paragraph 0020) which corresponds to 0.04-0.06%. Xiong mentions that the fermentation medium contains the sunflower seed cake powder which not only provides nutrients, but also plays antifoaming role and allows to reduce the amount of GPE (paragraph 0032). Xiong mentions that foam produced during microbial fermentation poses a risk of bacterial contamination (paragraph 0007).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Tucaliuc and Poontawee and apply fed-batch fermentation strategy described by Poontawee to fermentation of Pseudomonas fluorescence for production of mupirocin as taught by Tucaliuc. One would have been motivated to make this combination since Poontawee teaches that feeding essential nutrients shortens fermentation time, achieves high cell concentration and increases productivity. A skilled artisan would have reasonably expected success in this combination because Tucaliuc and Poontawee teach microbial fermentation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Wang teaching and prepare feeding medium based on fermentation medium with increase in the main carbon source, glucose, and use it for fermentation based on Tucaliuc and Poontawee teachings. One would have been motivated to do so since Tucaliuc teaches feeding 50% glucose, the main carbon source, throughout the fermentation process and the dextrose solution to keep glucose at 0.5% level, Poontawee teaches feeding essential nutrients and Wang describes feed medium containing similar to fermentation medium components and 10-fold increase in the amount of main carbon source in feed medium. A skilled artisan would have reasonably expected success in that because Tucaliuc, Poontawee and Wang teach microbial fermentation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Ge teaching and include urea in the fermentation medium for production of mupirocin based on Tucaliuc, Poontawee and Wang teachings. One would have been motivated to do so with reasonably expected success since Tucaliuc and Ge teach production of mupirocin and disclose the same components of the fermentation medium for the carbon source and nitrogen source and Ge showed that addition of urea improved cell activity of bacteria and the yield of mupirocin.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Xiong teaching and include GPE defoamer in the feeding medium based on Tucaliuc, Poontawee, Wang and Ge teachings. One would have been motivated to do so with reasonably expected success since Xiong teaches that foam produced during microbial fermentation poses a risk of bacterial contamination and describes using GPE in the fermentation medium.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentration of GPE defoamer in the feeding medium and increase the concentration over that of 0.04-0.06% in Xiong teaching. One would have been motivated to do so with reasonably expected success since Xiong describes that presence of sunflower cake powder in the medium allows to reduce the amount of GPE and hence the amount of GPE can be optimized based on the composition of the medium and it is within the skills of the artisan in the field to optimize the concentration of the ingredient in the fermentation medium.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentration of other ingredients in the feeding medium. One would have been motivated to do so to achieve the high productivity level of mupirocin and efficiency of the fermentation process. A skilled artisan would have reasonably expected success with that since it is within the skills of the artisan in the field to optimize the concentration of the ingredients in the fermentation medium.
Although Tucaliuc does not explicitly teach bean cake powder as nitrogen source it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that soy bean meal and soybean flour used as nitrogen source in Tucaliuc teaching can be replaced with bean cake powder. One would have been motivated to do so with reasonably expected success since bean cake powder originates from the same plant, the same part of the plant, i.e. beans, has the same powder form and hence will provide the same nutrition to bacterial culture.
Thus, Tucaliuc, Poontawee, Wang and Xiong teachings render claim 12 obvious.
Regarding claim 14, Tucaliuc teaches feeding 50% glucose (p. 499, left column, last paragraph). As discussed above for claim 12, the other components in the feeding medium can be similar to fermentation medium. Tucaliuc describes fermentation medium to include glycerol at 1% (Table 3), corn steep liquor (0.5%) and soy bean meal (2%) (p. 500, Table 3). Wang teaches 5.2% soybean cake flour and 2.3% corn pulp for the nitrogen source (p. 3, lines 6-7). Thus, the amount of glucose and glycerol in Tucaliuc teaching reads on claim 14 limitations and amount of corn steep liquor in Tucaliuc teaching and soybean cake flour in Wang teaching is close to claim 14 limitations.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare feeding medium based on Tucaliuc and Wang teachings and optimize the concentration of ingredients in the feeding medium. One would have been motivated to do so to increase efficiency of mupirocin fermentation with reasonably expected success since it is within the skills of the artisan in the field to optimize the concentration of the ingredients in the fermentation medium. Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 14 obvious.
Regarding claim 15, Tucaliuc teaches potassium dihydrogen phosphate and magnesium sulfate in the fermentation medium (p. 500, Table 3). Xiong teaches magnesium sulfate and zinc sulfate in the fermentation medium (paragraph 0020).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Xiong teaching and include zinc sulfate in the feeding medium for production of mupirocin based on Tucaliuc, Poontawee, Wang and Ge teachings. One would have been motivated to do so with reasonably expected success since Tucaliuc discloses that inorganic salts are necessary for mupirocin production and provides examples of using different inorganic salts, including potassium dihydrate phosphate and magnesium sulfate in the mupirocin fermentation and Xiong includes the same salt, magnesium sulfate and additional salt, zinc sulfate, during bacterial fermentation. Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 15 obvious.
Regarding claim 16, Xiong teaches GPE defoamer at 0.4-0.6 g/L (paragraph 0020) which corresponds to 0.04-0.06% in the fermentation medium as described above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Xiong teaching and include GPE defoamer in the feeding medium for production of mupirocin based on Tucaliuc, Poontawee, Wang and Ge teachings and optimize its concentration. One would have been motivated to do so since Xiong teaches that foam produced during microbial fermentation poses a risk of bacterial contamination and describes using GPE in the fermentation medium. One would have been motivated to optimize the GPE concentration to increase efficiency of mupirocin production and since and it is within the skill of the artisan in the field to optimize the concentration of the ingredient in the fermentation medium. A skilled artisan would have reasonably expected success with that because Tucaliuc, Poontawee, Wang, Ge and Xiong teach microbial fermentation. Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 16 obvious.
Regarding claim 17, Tucaliuc teaches pH 5.3-7.0 for fermentation production of mupirocin. Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 17 obvious.
Regarding claims 18, Tucaliuc teaches the inorganic salts during mupirocin production include sulfates, phosphates and chlorides and in particular, KH2PO4 at 0.15%, (NH4)2SO4 at 0.5%, MgSO4 x7H2O at 0.05% and KCI at 0.1% (p. 500, Table 3). Production is performed for 50 hours, at 24-26°C and pH = 5.3-7 (p. 499, left column, last paragraph). Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 18 obvious.
Regarding claim 19, Tucaliuc teaches pH 5.3-7 for mupirocin fermentation (p. 499, left column, last paragraph). Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 19 obvious.
Regarding claim 20, Ge teaches fermentation of Pseudomonas fluorescence producing mupirocin (paragraphs 0002, 0004). Ge describes that fermentation was performed for 120 hours (paragraph 0047) and mentions that the cell activity increased continuously from 24 hours to 120 hours (paragraph 0057).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Ge teaching and perform fermentation for mupirocin based on Tucaliuc, Poontawee, Wang and Xiong teachings for 120 h. One would have been motivated to do so since Ge teaches that the cell activity increased continuously from 24 hours to 120 hours and hence fermentation for 120 hours will provide higher yield of mupirocin. A skilled artisan would have reasonably expected success with that because Tucaliuc and Ge describe microbial fermentation for production of mupirocin. Thus, Tucaliuc, Poontawee, Wang, Xiong and Ge teachings render claim 20 obvious.
Regarding claim 24, Tucaliuc teaches fermentation medium for mupirocin production comprising 6% glucose, 1% glycerol, 2% soybean meal, 0.5% corn steep liquor, 0.5% ammonium sulfate, 0.15% potassium dihydrogen phosphate, 0.05% magnesium sulfate, 0.1% potassium chloride (p. 500, Table 3). Ge teaches that addition of urea at 0.1-1% during mupirocin production (paragraph 0014). Xiong teaches 0.2-0.4% zinc sulfate and 0.04-0.06% GPE defoamer in the fermentation medium (paragraph 0020) as described above. Addition of urea taught by Ge and GPE taught by Xiong to the fermentation medium was discussed above for claim 12.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Xiong teaching and include 0.2-0.4% zinc sulfate in the feeding medium for production of mupirocin based on Tucaliuc, Poontawee, Ge and Wang teachings. One would have been motivated to do so with reasonably expected success since Tucaliuc discloses that inorganic salts are necessary for mupirocin production and provides examples of using different inorganic salts, including potassium dihydrate phosphate and magnesium sulfate in the mupirocin fermentation and Xiong includes the same salt, magnesium sulfate and additional salt, zinc sulfate, during bacterial fermentation. Thus, Tucaliuc, Poontawee, Wang, Ge and Xiong teachings render claim 24 obvious.
Claims 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Tucaliuc (Tucaliuc et al. Biotechnol. Lett., 2018, 41, 495-502) in view of Poontawee (Poontawee and Limtong Microorganisms 2020, 151, 1-19), Wang (CN 110747188A), Ge (CN 111996136A on record in IDS) and Xiong (CN 109929890A) as applied to claim 12 above, and further in view of Zhang (CN 108949845A on record in IDS).
The teachings of Tucaliuc, Poontawee, Wang, Ge and Xiong have been set forth above.
Regarding claims 22 and 23, Tucaliuc teaches fermentation for mupirocin at 24-26°C and pH = 5.3-7 (p. 499, left column, last paragraph). Tucaliuc mentions controlling pH during the fermentation process and feeding and controlling glucose to maintain it at 0.5% level (p. 499, left column, last paragraph, right column, 1st paragraph). Tucaliuc describes collection of the fermentation broth for isolation of the product, mupirocin (p. 499, right column, 2nd paragraph). Tucaliuc, Poontawee, Wang, and Xiong do not teach shake flask culture and seed tank culture with the recited parameters.
Regarding claims 22 and 23, Ge teaches fermentation of Pseudomonas fluorescence producing mupirocin (paragraphs 0002, 0004). Method of Ge includes shake flask seed culture that is transferred to a seed tank after maturity and after the seed culture in the seed tank matures it is transferred to the fermentation tank (paragraph 0025). Ge describes sterilization of the fermentation medium for the recited cultures (paragraph 0026). Ge discloses conditions for the seed tank culture, i.e. 25°C, 18 hours culturing time and inoculation of 100 ml into 10L seed culture medium which corresponds to 1% inoculation amount (paragraph 0044). Ge provides example of inoculation of 300L of seed culture into 4000L of the fermentation medium (paragraphs 00564, 0055) that corresponds to 7.5% inoculation amount and reads on claim 23 limitation. Ge mentions that fermentation produced 6562 μg/ml of mupirocin (paragraph 0047).
Regarding claims 22 and 23, Zhang teaches preparation of mupirocin from fermentation medium of Pseudomonas fluorescens (Abstract, paragraph 0007). Zhang describes that fermentation medium contains a carbon source, comprising glucose and glycerol, a nitrogen source, comprising soybean meal powder and corn steep liquor, inorganic salts and other components (paragraphs 0012- 0014). The method of Zhang includes steps of plate culture, slant culture, shake flask culture, seed culture and fermentation culture (paragraphs 0019-0023). The single colony of slant culture is inoculated into shake flask culture medium and incubated at 25-30°C for 10-15 hours to obtain shake flask seed culture solution (paragraph 0021). The shake flask seed culture is inoculated into seed culture medium and cultured until the logarithmic growth phase to obtain seed culture (paragraph 0022). The seed culture is inoculated into the fermentation medium and cultured at 25-30°C for 60-120 hours (paragraph 0023). The pH of the shake flask seed culture medium, the seed culture medium and the fermentation medium is 6.0-7.0 (paragraphs 0040, 0048, 0062). Zhang mentions that using processes in steps such as shake flask culture, seed culture and fermentation cultured resulted in mupirocin content of over 6000 μg/ml in the fermentation broth (paragraph 0065).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add Zhang teaching to method of mupirocin production based on Tucaliuc, Poontawee, Wang and Xiong teachings and include steps of shake flask seed culture and seed tank culture prior to fermentation step performed at pH 6-7 and at 25-30°C for 10-15 hours for shake flask seed culture as described by Zhang. One would have been motivated to do so since Zhang teaches that using steps such as shake flask culture, seed culture and fermentation cultured resulted in mupirocin content of over 6000 μg/ml in the fermentation broth. A skilled artisan would have reasonably expected success in that because Tucaliuc and Zhang teach fermentation method for mupirocin production.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Ge instructions for the shake flask seed culture and seed tank culture including sterilizing culture medium for all steps, 1% inoculation volume, 25°C and 18 hours culturing time for the seed tank culture and inoculation volume of 7.5% for the fermentation culture. One would have been motivated to do so since Ge provides instructions for the fermentation steps and teaches that fermentation culture resulted in mupirocin content of over 6000 μg/ml in the fermentation broth. A skilled artisan would have reasonably expected success in that because Tucaliuc, Zhang and Ge teach fermentation method for mupirocin production with Zhang and Ge following the same protocol steps and similar parameters and production yields.
Thus, Tucaliuc, Poontawee, Wang, Xiong, Ge and Zhang teachings render claims 22 and 23 obvious.
Response to Arguments
Applicant's arguments filed 06/09/2026 have been fully considered but they are not persuasive.
Applicant argues (addressing p. 8-11 of the Remarks) that Tucaliuc does not disclose the necessity of feeding culture and its composition; Poontawee teaches feeding medium containing only carbon sources for lipid and not mupirocin production; the fermentation medium and the feed medium in Wang teaching is different from the present application especially in terms of carbon and nitrogen sources and that the higher fermentation activity and extraction yield in Wang is not explained by the increase in carbon source and Xiong, Zhang and Ge do not teach the feed culture step. Applicant further argues that the products produced by Poontawee, Wang and Xiong are different from mupirocin. These arguments are not persuasive because:
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). It is acknowledged that there is no a single reference that teaches and/or suggests every claim limitation recited in instant claims 1 and 5. However, Applicants are respectfully reminded that the rejections supra are based on obviousness. Pursuant to MPEP 2142, 35 USC 103 authorizes a rejection where, to meet the claim, it is necessary to modify a single reference or to combine it with one or more other references. Since the rejection is based on obviousness, it is unnecessary for every claim limitation to be taught and/or suggested by a single reference. Additionally, 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 instant case, the 103 rejection is based on combination of references, wherein Tucaliuc teaches mupirocin production by fermentation providing conditions for fermentation and composition of fermentation medium, Poontawee teaches that feeding essential nutrients shortens fermentation time, achieves high cell concentration and increases productivity providing motivation to apply fed-batch strategy to fermentation of P. fluorescence during production of mupirocin. Wang describes feed medium containing similar to fermentation medium components and 10-fold increase in the amount of main carbon source in feed medium and motivates to prepare feeding medium based on fermentation medium with increase in the main carbon source. Ge showed that addition of urea improved cell activity of bacteria and the yield of mupirocin providing motivation to include urea in the fermentation medium. Xiong teaches that foam produced during microbial fermentation poses a risk of bacterial contamination and describes using GPE in the fermentation medium suggesting to use GPE in the fermentation medium for mupirocin production. Zhang and Ge teach shake flask culture and seed culture steps of mupirocin synthesis resulting in high productivity yield. Although Poontawee, Wang and Xiong do not teach production of mupirocin, they provide suggestions that can be applied to increase productivity of microbial fermentation.
Additionally, feeding medium in Wang is not used as fermentation medium directly but is suggested to be added to maintain certain level of nutrients similar to Tucaliuc teaching describing feeding 50% glucose throughout the process (p. 499, left column, last paragraph) to keep glucose at 0.5% level (p. 499, right column, last paragraph).
Applicant argues (addressing p. 11 of the Remarks) that the claimed methods achieved: “at least the following unexpected technical effects. The fermentation method for mupirocin according to the claimed invention is suitable for small-scale experiments and kiloliter-scale industrial production. The average fermentation potency of the process may be greater than 8,500 μg/mL, with quality meeting the criteria of USP 41 and EP 9.0. Applicant notes that even for the alleged improved methods in Zhang and Ge, the highest potency taught therein is only about 6,600 μg/mL, much less than that observed in this application.”. These arguments are not persuasive because:
In response to applicant's argument that the average fermentation potency of 8,500 μg/mL was achieved, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In instant case, combination of prior art of Tucaliuc, Poontawee, Wang, Ge and Xiong provides the instant method for mupirocin production as described above and hence is expected to reach potency of 8,500 μg/mL.
Regarding the suitability for kiloliter-scale industrial production, Ge provides example of fermentation for mupirocin production in 5000L fermenter (paragraph 0055) reaching potency of 6621 μg/mL (paragraph 0057).
Assuming arguendo that applicant has shown unexpected data, the presented unexpected results are not commensurate in scope with the claimed invention. “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.” (MPEP 716(d)). In instant case, only Example #5 of Experiment 6 (p. 15) has the same components of the fermentation and feed medium as recited in claim 12 (including corn steep liquor): “The formula of the fermentation medium (W/V): 5.0-6.0% of glucose, 2.0% of bean cake powder, 1.5% of corn steep liquor, 0.15% of urea, 0.5% of ammonium sulfate, 0.10% of potassium dihydrogen phosphate, 0.06% of magnesium sulfate, 0.12% of potassium chloride, 0.2% of zinc sulfate, 1.5% of glycerol and 0.3% of polyether GPE defoamer; The formula of the feed (W/V): 30-50% of glucose, 0.05% of zinc sulfate, 0.06% of magnesium sulfate, 0.05% of potassium dihydrogen phosphate, 0.5% of glycerol, 1.5% of bean cake powder, 1.5% of corn steep liquor and 0.3% of polyether GPE defoamer.” The harvest potency in that experiment was 8870 μg/mL (p. 15). However, these concentrations are not present in claim 12. Claim 12 broadly recites percent content of carbon source, nitrogen source, inorganic salt and defoamer in the fermentation medium and feed medium without specifying percentage for individual components. Besides, the ranges of total amount are broader than in Experiment 6. For instance, the amount of carbon source in the fermentation medium in Experiment 6 is 5.0-6.0% of glucose and 1.5% of glycerol resulting in total of 6.5-7.5%, while claim 12 recites 5-12% of carbon source. The amount of nitrogen source in the fermentation medium in Experiment 6 is 2.0% of bean cake powder, 1.5% of corn steep liquor, 0.15% of urea resulting in 3.65%, while claim 12 recites 2-10% of nitrogen source. Inorganic salts in claim 12 are not specified and can comprise any salt and cover the range of 0.1-1.5% while in Experiment 6 the total amount of inorganic salt in the fermentation medium is 0.98%. The same differences are present for the feed medium. Thus, the high potency of mupirocin production was not shown for the entire claimed range and hence the claims are not commensurate in scope with the unexpected results.
Therefore, the 35 U.S.C. 103 rejection is maintained and modified necessitated by the amendment of claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) 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 LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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