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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/28/2025 has been entered.
Amendments Received
Amendments to the claims were received and entered on 11/28/2025.
Applicants attention is directed to the proper method of amending the claims as per MPEP 714, 37 CFR 1.121 Manner of making amendments in application. Applicants attention is directed to the currently amended claim 1 which appears to be amended from that of previous claim 1, as it existed in the paper of 03/28/2025. Applicants amendment should properly show appropriate markings (i.e. strike-through, underlining, etc…) of the amended text.
The current recitation in claim 1 “(a) adding the a working cell bank” does not show the proper markings relative to the same recitation in previous claim 1 “(a) adding
Please use proper markings in all future amendments. This is required to clarify the record and prosecution and avoid issues that result from a lack of clarity of the record and prosecution.
Status of Claims
Claims 15 and 17 are cancelled.
Claims 1-14, 16, 18 and 25 are currently pending and under consideration.
Priority
The present application claims status as a 371 (National Stage) of PCT/IB2020/062252 filed on December 19, 2020. Acknowledgment is made of applicant’s claim for benefit under 35 U.S.C. 119(e) of Provisional application No. 62/951,549, filed on December 20, 2019. The present application and all claims are being examined with an effective filing date of December 20, 2019. In future actions, the effective filing date may change due to amendments or further review of priority documents.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/28/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objections
In view of Applicant’s amendments, the objection to claim 1 is hereby withdrawn.
Withdrawn Rejections
In view of Applicant’s cancellation of claims 15 and 17, all rejections of claims 15 and 17 are now moot and hereby withdrawn.
In view of Applicant’s amendments, rejections of claims 3-4, 7, 9 and 12-14 under 35 USC § 112(b) are hereby withdrawn.
In view of Applicant’s amendments, rejection of claims 1-2, 4, 6-8, 11, 16, and 25 under 35 USC § 103 over Yun and Donovan ;rejection of claims 3 and 5 under 35 USC § 103 over Yun and Donovan, further in view of Ho et al.; claim 10 under 35 USC § 103 over Yun and Donovan, further in view of Bradshaw et al.; claims 13-14 under 35 USC § 103 over Yun and Donovan, further in view of Plantz et al., and claim 18 under 35 USC § 103 over Yun and Donovan, further in view of Yang, Smith, and Segecova et al. are hereby withdrawn.
Claim Objections
Claim 1 (and claims 2-14, 16, 18, and 25 dependent therefrom) are objected to because of the following informalities:
Line 3 of claim 1 recites “(a) adding the a working cell bank…”, which should be amended to remove the “the”, according to a previous amendment filed on 03/28/2025 (see above note).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-14, 16, 18, and 25 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 the limitation "the first VTPM and second VTPM consisting of a wheat peptone…" in line 12. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of a VTPM consisting of the recited components. In the interest of advancing prosecution, the examiner is interpretating the above as “the first VTPM and second VTPM consists of…”
Appropriate response and clarification is requested.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-14, 16, 18, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Kyoung-Yun et al. (US Patent No. 9926549B2, herein “Yun”, cited in a previous office action), Ho et al. (KR101434558B1, English translation, cited in a previous office action), Smith MV, Pierson (Effect of reducing agents on oxidation-reduction potential and the outgrowth of Clostridium botulinum type E spores. 1979, Appl Environ Microbiol 37: 978-984, herein “Smith”, cited in a previous office action), Segecova et al. (Advancement of the cultivation and upscaling of photoautotrophic suspension cultures using Chenopodium rubrum as a case study, Plant Cell, Tissue and Organ Culture (PCTOC) (2018) 135:37–51, cited in a previous office action), Donovan, Stephen (US8008044B2, cited in a previous office action), Bradshaw et al. (Regulation of neurotoxin complex expression in Clostridium botulinum strains 62A, Hall A-hyper, and NCTC 2916, Anaerobe 10 (2004) 321–333, cited in a previous office action), and Plantz et al. (Detection of non-host viable contaminants in Pichia pastoris cultures and fermentation broths. J Ind Microbiol Biotechnol (2003) 30: 643–650, cited in a previous office action).
The instant claims and instant specification do not define the term “ph-adjusting agents”. Accordingly, under the broadest reasonable interpretation, the term encompasses agents used to control, maintain, or stabilize pH conditions in a culture medium. In microbial fermentation systems, such pH control is not limited to acids and bases, but also includes salts incorporated to maintain buffering capacity and ionic strength.
Yun teaches a medium composition for culturing Clostridium botulinum comprising at least one plant-derived peptone selected from the group consisting of… wheat gluten hydrolysate (column 3, lines 62-67), correlating to the limitation of a wheat peptone, including APF medium candidate 9, which consists of 20 g/L wheat peptone (Hy Pep 4601N), 10 g/L glucose, sodium chloride (pH adjusting agent), K₂HPO₄ (pH adjusting agent), and Na₂HPO₄ (pH adjusting agent) (Columns 21-22, Table 10). Yun also teaches a method for producing botulinum toxin comprising culturing C. botulinum in the medium comprising a plant-derived peptone (wheat peptone) to produce botulinum toxin and recovering the produced botulinum toxin (column 4, lines 1-5), correlating to the recited step (c). Specifically, in Example 1, Yun teaches that a culture tube containing 4 plant derived peptones (including wheat peptone, i.e., “Hy Pep 4601N”), glucose and sodium chloride (correlating to a pH adjusting agent), also referred to as an animal protein-free medium (APF), is inoculated with C. botulinum, to obtain a primary seed culture, i.e., a working cell bank (WCB) (column 7, lines 5-39, including Table 1). Yun further teaches that the primary seed culture was also subject to a secondary seed culture, wherein the primary seed culture was inoculated into a culture bottle containing sterile medium having the same composition used to produce the primary seed culture, correlating to the recited in step (a), for 8-15 hours. Specifically, 8 ml of primary seed culture was inoculated into a culture bottle containing 800 ml of sterile APF medium, which equates to 1% volume ratio of WCB to the VTPM (column 7, lines 39-46). It is noted here that the secondary seed culture correlates to a “pre-culture” and the culture bottle correlates to the “first container” containing a first VTPM, as claimed, which is then used for further culturing described below. Yun then teaches that the secondary seed culture is used to perform the “main culture”, to produce botulinum toxin, correlating to the recited step (b). With respect to temperature, both the seed culture and the main culture (steps “a” and “b”) were performed at a temperature of 35° C (column 7, lines 39 and 45; column 8, line 2). Specifically, 9.3 L of the medium described above “was prepared and placed in a 10-liter incubator (i.e., second container containing a second VTPM), followed by sterilization of the medium. Nitrogen was supplied to make anaerobic conditions. The secondary seed culture in the 1-liter culture bottle (i.e., first container with first VTPM)…was inoculated into a 10-liter incubator through an inoculation line…” (column 7 lines 50-53 and column 8, lines 1-6). Yun teaches the use of the same VTPM (same composition) in all of the containers throughout the fermentation process from primary seed culture to toxin production and recovery, as described above. With respect to the media composition, Yun teaches experimental preparations of APF media during screening for plant-derived peptones having a positive effective on C. botulinum growth, including APF medium candidate 9, which consists of 20 g/L wheat peptone (Hy Pep 4601N), 10 g/L glucose, sodium chloride (pH adjusting agent), K₂HPO₄ (pH adjusting agent), and Na₂HPO₄ (pH adjusting agent) (Columns 21-22, Table 10). With respect to the type of botulinum toxin, Yun teaches that the botulinum toxin may be botulinum toxin type A (column 6, lines 39-41). Yun does not teach wherein the medium described above also consists of about 5-50 g/L yeast extract, 0.05-0.50 g/L cysteine hydrochloride monohydrate, 0.05-0.50 g/L medical antifoam C emulsion, water, and does not expressly disclose the pH of the medium described above, as required in claim 1; wherein the container used in steps (a) and (b) is a fermentation bag, as recited in claim 3; or expressly teach that the anerobic environment described above is one in which the dissolved oxygen concentration is less than 1%, as recited in claim 5; wherein the step (a) is conducted until OD600 reaches the range of about 0.1 to about 1.0, as recited in claim 10; and wherein contamination by other microorganisms is tested after step (a), but before step (b), and after step (b), but before step (c), as recited in claims 13-14, respectively.
With respect to the recited yeast extract and water in the claimed medium, Ho et al. discloses a method of producing C. botulinum toxin type A using a medium comprising plant-derived peptone(s). In one embodiment, the medium consists of at least two components selected from the group consisting of phytone peptone, plant tryptone, and soytone and water, in a medium containing glucose, yeast extract and sodium thioglycolate. Ho et al. further teaches wherein the yeast extract is in amount of 0.5% to 2% based on weight. It is noted that 0.5% weight per volume equates to 5 g/L and 2% weight per volume equates to 20 g/L, which falls within the claimed range. Therefore, Ho et al. establishes concentrations of yeast extract between 5-20 g/L in fermentation media, which falls within the claimed range, and water, which is routinely used as a solvent in fermentation media, for the production of C. botulinum toxin type A. Additionally, Yun discloses a “medium that is in current use” that comprises 10 g/L yeast extract (columns 6-7, Example 1 and Table 1), which falls within the claimed range and further establishes that an amount between 5 g/L and 50 g/L would have been obvious to a person of ordinary skill in the art, as yeast extract at these concentrations were routinely used in bacterial fermentation. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) – see MPEP 2144.05.
With respect to the l-cysteine hydrochloride monohydrate, Smith discloses the effect of the reducing agent cysteine hydrochloride on the oxidation-reduction potential and the outgrowth of Clostridium botulinum type E spores. Smith teaches that low amounts of cysteine hydrochloride added to broth or media, promote and enhance C. botulinum growth. Notably, the greatest growth was observed at a concentration of 0.05%, which correlates to 0.50 g/L.
With respect to the medical antifoam c emulsion, Segecova et al. teaches the use of Medical Antifoam C emulsion in cultures of Chenopodium rubrum due to “biofouling”, specifically 600 ppm of Medical antifoam C emulsion, which equates to 0.60 g/L. Segecova et al. further teaches that the trapping of biomass (i.e., lost product) from air bubbles is due to agitation as one of the causes (pg. 40 right column last para-pg. 41, left column, 1st para), which would lead a person of ordinary skill in the art to include antifoam emulsion in fermentation media, especially where agitation is employed. It is noted that the specification defines “about” to mean “up to plus or minus 15%...” (pg. 10, para 0042). In the context of the instant claims, the recitation of “about 0.5 g/L” encompasses up to 0.575 g/L (slightly below the amount disclosed by Segecova et al.), with respect to the amount of antifoam recited in claim 18. Pursuant to MPEP 2144.05 I., a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close, such that one skilled in the art would have expected them to have the same properties. Therefore, selection of a slightly lower antifoam concentration within the claimed range represents a routine optimization of a known process parameter to achieve effective foam control.
Donovan teaches media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions, wherein the growth media is substantially free of animal derived products (Abstract). More specifically, Donovan teaches a soy-based fermentation media comprising glucose and L-cysteine, among other ingredients. With respect to pH level of said media, Donovan teaches “for optimal levels of toxin production, the initial pH (before autoclaving) of the soy-based fermentation media ranges preferably between approximately 5.5 to 7.1. Preferably the initial pH of the fermentation medium is between approximately 6.0 to 6.2” (column 14, lines 46-50). Additionally, Donovan discloses an exemplary preparation method of the fermentation medium wherein the pH is 6.8 (columns 15-16, Example 3, “Preparation of an Animal Product Free Fermentation Media for Clostridium Botulinum”).
With respect to the limitation reciting a fermentation bag in claim 3 and the dissolved oxygen level recited in claim 5, Ho et al. teaches a method for producing Clostridium botulinum toxin using a plant-derived component-containing medium and a flexible closed container (pg. 1, para 0001). More specifically, Ho et al. discloses a method of producing C. botulinum toxin type A, wherein a non-animal derived component medium comprising soytone, plant tryptone, phytone peptone, sodium thioglycolate, yeast extract and glucose is injected into a fermentation bag, then inoculated with a seed culture of C. botulinum and then incubated at 37°C (pg. 4-5, para 0044-0051). Ho et al. also teaches “the closed vessel may be air impermeable so that the culture medium and the cells can be maintained under oxygen-free conditions until the cultivation is completed at the time of inoculation. Therefore, the culture is maintained anaerobically…” (pg. 2, para 0009). It is noted that “oxygen-free” conditions correlates to an environment having no oxygen, or zero percent oxygen, which is less than 1% oxygen, as recited by instant claim 5.
With respect to the volume ratio of pre-culture (i.e., secondary seed culture) to medium, as recited in instant claim 9, Yun teaches that 9.3 L of APF medium was prepared and placed in a 10-liter incubator and the secondary seed culture (described above) was inoculated into said incubator through an inoculation line. Yun does not disclose the amount of secondary seed culture, beyond teaching the inoculation amount of 8 ml of primary seed culture that was used to obtain the secondary seed culture. As such, Yun does not expressly teach a volume ratio of pre-culture to medium between about 1:2 to about 1:50. Pursuant to MPEP 2144.05 II.A., generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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). With respect to the ratio of the C. botulinum pre-culture to the growth medium, it would have been customary for an ordinary skilled artisan to determine the optimal concentration of culture in the medium, which as taught by Yun is directed through an inoculation line and is being continuously monitored, in order to achieve the desired results. Absent evidence or demonstration of unexpected results from the claimed parameters, the optimization of the concentration of C. botulinum pre-culture in the growth medium would have been obvious at the time of Applicant’s invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
With respect to the length of time for conducting step (b), as recited in claim 12, Yun teaches that the secondary seed culture is used to perform the “main culture”, to produce botulinum toxin, correlating to step (b) of instant claim 1. Yun further teaches that the main culture was carried out for and terminated after 100 hours (column 8, lines 10-11). It is noted that the specification defines “about” to mean “up to plus or minus 15%...” (pg. 10, para 0042). In the context of the instant claims, the recitation of “about 80” encompasses up to 92 hours, with respect to the culture time in step (b) of instant claim 1. Pursuant to MPEP 2144.05 I., a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close, such that one skilled in the art would have expected them to have the same properties. Therefore, the claimed culturing time for producing botulinum toxin would have been suggested to one skilled in the art since the prior art teaches a culture time of 100 hours, which is close to the claimed time of up to 92 hours.
Bradshaw et al. teaches the routine practice of adjusting fermentation time based on optical density/cell concentration. Specifically, Bradshaw et al. teaches the pre-culture of three C. botulinum strains inoculated and grown in media “for approx. 8 hours to late log phase (OD600nm ~1.0). It is also noted that cultures were grown in an anaerobic chamber at 37°C (pg. 323 left column, 1st para).
Plantz et al. teaches that “the ability to detect viable contaminants in cultures propagated from the original host-expression system ensures that the integrity and purity of seed banks, fermentation broth, and ultimately the final product are continually controlled and maintained. The method developed to detect such agents must be selective for a broad spectrum of microbes, which may be
present at very low levels, while discriminating from the host organisms.” (Abstract). Plantz et al. discloses a study employing assays and media formulations, specifically designed to inhibit the growth of the desired organism, in this case Pichia pastoris, and the recombinant host strain(s) and recover potentially contaminating organisms(pg. 644-645, Materials and Methods). Plantz et al. teaches from the results of the study that selective media and conditions can be used to recover contaminants at low detection limits (pg. 645-648, Results and Tables). In the Discussion, Plantz et al. teach that a key component in demonstrating process control is to ensure the purity of a microbial culture through all stages of the development and production processes. While the study conducted by Plantz et al. is directed to P. pastoris cultures and fermentation, the teachings of Plantz et al. are applicable to cultures of all microorganisms in all stages of fermentation for the obvious benefit of increased product purity.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Yun which discloses APF medium candidate 9, consisting of 20 g/L wheat peptone, 10 g/L glucose, sodium chloride, K₂HPO₄, and Na₂HPO₄, and the teachings of Ho et al., that yeast extract and water are known and routinely used nutrient and solvent components of fermentation media for culturing C. botulinum, combined with the teachings of Segecova et al. that 0.6 g/L medical antifoam c emulsion is routinely used to control foam formation during fermentation, and the teachings of Smith, that 0.50 g/L cysteine HCl due to its reducing potential promotes and enhances the growth of C. botulinum when added to fermentation medium at low amounts, would have motivated said practitioner to modify the APF medium candidate 9 of Yun, consisting of 20 g/L wheat peptone, 10 g/L glucose, sodium chloride, K₂HPO₄, and Na₂HPO₄, and incorporate the additional ingredients, yeast extract, medical antifoam c emulsion and cysteine HCl and water, for the added benefit of promoting C. botulinum growth and controlling foam during fermentation (claim 1), in the amounts taught by Ho et al., Smith, and Segecova et al. (claim 18). Given that Ho et al. and Smith demonstrate successful methods of producing and enhancing C. botulinum, and Segecova et al. demonstrate the benefit of medical antifoam c emulsion especially in methods that employ agitation, such as Yun’s method, said practitioner would have readily predicted that the combination of teachings would successfully result in a method for the production of botulinum toxin, with a reasonable expectation of success.
Said practitioner would further be motivated to adjust the medium of Yun, which has phosphate buffers present in the medium, to a pH level within the range suggested by Donovan, because Donovan teaches that 5.5 to 7.1 is an optimal range of pH level for an APF medium for producing botulinum toxin (claim 1). There is a reasonable expectation of success in making such a modification to the media of Yun, in light of Donovan’s successful fermentation of C. botulinum at a pH of 6.8.
Additionally, the teachings of Bradshaw et al., that a pre-culture of C. botulinum reaches late log phase of the growth cycle at about an OD600 of 1.0, would have also further motivated said practitioner to measure and monitor the OD600 of Yun’s pre-culture to adjust fermentation times based on optical density (i.e., cell concentration), specifically culturing until the late log phase which occurs at approximately OD600 of 1.0, with a reasonable expectation of success because Bradshaw et al.’s teachings are directly related to the growth phase of C. botulinum (claim 10).
Additionally, in view of Ho et al. disclosure that a fermentation bag is a suitable vessel for carrying out the culturing of C. botulinum and production of C. botulinum toxin, in an oxygen-free environment, one of ordinary skill in the art could have substituted one known element (fermentation bag) for another (culture tube or bottle), and the results of the substitution would have been predictable (claim 3). Moreover, it would be obvious to use or substitute the known fermentation bag in the method taught by Yun, since Ho et al. teach the use of a fermentation bag for producing botulinum toxin, and the fermentation bag, culture tube and culture bottle all serve the same function (See MPEP 2144.06 – Substituting equivalents known for the same purpose).
And, given the teachings of Plantz et al., that quality control strategies such as using various media formulations to selectively recover potential contaminants in a culture are advantageous in ensuring purity in fermentation, a person of ordinary skill in the art would have been motivated to modify the method of Yun and implement microbiological purity steps after each fermentative process and culture step, because increased purity is a desired outcome (claims 13-14). Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Accordingly, claims 1-14, 16, 18, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Yun, Ho et al., Smith, Segecova et al., Bradshaw et al., and Plantz et al.
Response to Arguments for Prior Art Rejections
In the response filed on November 28, 2025, Applicant argues that Yun teaches away from the claimed invention due to the inclusion of phosphate salts in the culture medium, that the claimed “consisting of” limitation distinguishes the claimed medium from the prior art, and that the claimed use of wheat peptone results in unexpectedly high toxin yields relative to the prior art. Applicant’s arguments have been considered in full but have not been found to be persuasive.
With respect to Applicant’s argument that Yun teaches away from the claimed invention due to the inclusion of phosphate salts and that the “consisting of” limitation distinguishes the claimed medium from Yun, this argument is not persuasive. As amended, claim 1 recites that the medium consists of specified components including pH-adjusting agents. The specification does not provide a limiting definition of “pH-adjusting agents.” Accordingly, under the broadest reasonable interpretation, pH-adjusting agents encompass compounds capable of adjusting or maintaining the pH of the medium, including buffering salts. Phosphate salts such as K₂HPO₄, and Na₂HPO₄, as disclosed by Yun, are well-known buffering and pH-adjusting agents in microbial fermentation media. Therefore, the inclusion of phosphate salts in Yun does not teach away from the claimed invention but instead falls within the scope of the claimed pH-adjusting agents.
With respect to Applicant’s argument regarding unexpected results, Applicant has not demonstrated results that are unexpected relative to the closest prior art (see MPEP 716.02(e)). Yun demonstrates that plant-derived peptone-based media are capable of producing significant levels of botulinum toxin, at even higher concentrations than those reported by Applicant and differences in toxin yield among known plant-derived peptones represent differences in degree attributable to routine optimization of known variables. Specifically, the finally selected APF medium of Yun, achieves toxin concentration levels of over 31 μg/ml after 48 hours of culture (pg.24,Table 12), compared to Applicant’s almost 4 μg/ml achieved after 69 hours (Fig. 7). Furthermore, Applicant has not shown that the alleged results are commensurate in scope with the pending claims (see MPEP 716.02(d)).
Conclusion
No claim is in condition for allowance.
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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652