The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-14 are pending and under consideration.
Priority: This application is a 371 of PCT/JP2023/014802, filed April 12, 2023, which claims benefit to foreign application JP 2022-066081, filed April 13, 2022. A copy of the foreign priority document has been received in the instant application on October 10, 2024 and is not in the English language.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code: see at least paragraph 0024 of the specification submitted October 10, 2024. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over WO ‘150 (WO 2012033150, translated copy provided by Google patents cited herein) in view of ThermoFisher (2020 Introduction to mass transfer in single-use bioreactors, 11 pages). WO ‘150 discloses a method for producing equol, comprising fermenting daidzein with an anaerobic microorganism in a gas phase composed of one or more types of gases containing hydrogen, wherein the anerobic microorganisms are cultured in a culture system comprising a culture tank, where an additional function can be given to the culture tank, utilizing a stirred mixing tank and a bubble column type culture tank (at least p. 1-4). WO ‘150 discloses that by stirring or agitating the culture in the culture tank, it is possible to increase the chance of contacting the medium components and the substrate gas with the anerobic microorganisms and to optimize production efficiency of equol (at least p. 3-4). WO ‘150 discloses that the substrate gas can also be supplied as nanobubbles (at least p. 4). WO ‘150 exemplifies methods for producing equol, comprising dispensing a culture solution 10 mL in a culture, introducing one or more types of gas, including ratios of CO2 and H2 and ratios of N2 and H2, and then cultured with shaking or stirring, and then recovering the produced equol (at least p. 4-5). WO ‘150 discloses commercial production of equol (at least p. 3). WO ‘150 does not explicitly teach a culture solution in an amount 100 L, a stirring power of 0.1 kW/kL or more, and a sparger having a pore size 2 mm or less.
ThermoFisher discloses that bioreactor design, operation, scalability (bench to large-scale production) criteria are dependent on multiple factors, including reactor geometry, agitator selection, power input, mixing, agitator shear, critical control parameter sensing, sparging, and bubble shear (at least p. 1). ThermoFisher discloses gas mass transfer into the liquid phase in stirred bioreactors is usually achieved through either super-surface (i.e. headspace sweep or overlay) or subsurface (i.e. sparging) aeration using a combination of gases (at least p. 1). ThermoFisher discloses that for modern cell culture bioreactors, it is critical to carefully engineer spargers in terms of material, pore size and quantity (at least p. 1). ThermoFisher discloses bubble formation at the sparger surface plays a considerable role in mass transfer performance, smaller bubbles being < 1 mm diameter and intermediate sized bubbles (1-4 mm diameter) (at least p. 5). ThermoFisher discloses a pore size 0.178 mm for a volume 100 L (at least p. 7). ThermoFisher discloses better bubble distribution with higher agitation (power input per volume) rates (at least p. 10).
MPEP 2144.05 notes that “[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).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of the prior art reference and arrive at the claimed method for producing equol, comprising fermenting equol under a gas phase composed of one or more types of gases containing hydrogen, by an anaerobic microorganism, wherein the fermentation conditions include a culture solution of 100 mL in a fermenter (i.e. bioreactor), stirring the culture solution at an agitation rate of 0.1 kW/kL or more and/or introducing one or more types of gases containing hydrogen by a sparger having a pore size 2 mm or less by routine optimization (instant claim 1). The motivation to do so is given by the prior art. WO ‘150 discloses a method for producing equol comprising generally the same steps, features, and conditions recited in at least instant claim 1. WO ‘150 discloses methods for producing equol, comprising dispensing a culture solution 10 mL in a culture, introducing one or more types of gas, including ratios of CO2 and H2 and ratios of N2 and H2, and then cultured with shaking or stirring, and then recovering the produced equol (at least p. 4-5). WO ‘150 discloses that by stirring or agitating the culture in the culture tank, it is possible to increase the chance of contacting the medium components and the substrate gas with the anerobic microorganisms and to optimize production efficiency of equol (at least p. 3-4) and further that the substrate gas can also be supplied as nanobubbles (at least p. 4). ThermoFisher discloses that gas transfer into the liquid phase in stirred bioreactors is achieved by spargers and that for modern cell culture bioreactors, it is critical to carefully engineer spargers in terms of material, pore size and quantity (at least p. 1). ThermoFisher discloses bubble formation at the sparger surface plays a considerable role in mass transfer performance, smaller bubbles being < 1 mm diameter and intermediate sized bubbles (1-4 mm diameter) (at least p. 5) and further discloses better bubble distribution with higher agitation (power input per volume) rates (at least p. 10). ThermoFisher discloses a pore size 0.178 mm for a volume 100 L (at least p. 7). Therefore, one of ordinary skill would have reasonable motivation to arrive at the recited fermentation conditions including a culture solution in an amount 100 L, a stirring power of 0.1 kW/kL or more, and a sparger having a pore size 2 mm or less by routine optimization because the prior art discloses a method for producing equol comprising generally the same steps, features, and conditions recited and further disclose fermentation conditions including sparger pore size and agitation rate can be designed and optimized. One of ordinary skill would have a reasonable expectation of success because fermentation conditions including sparger pore size and agitation rate were known parameters that affect culture conditions and thereby can be monitored and changed for optimizing culture conditions.
Regarding instant claims 1, 2-3, WO ‘150 discloses that to efficiently recover equol, the aeration amount of the mixed gas constituting the gas phase to the culture tank is 0.01 to 2.0 V/V/M gas amount/liquid amount/minute (at least p. 2). ThermoFisher discloses ranges of power/volume input of 10 W/m3-45 W/m3 for large scale culture conditions (p. 10). ThermoFisher discloses better bubble distribution with higher agitation (power input per volume) rates (at least p. 10). Therefore, it would have been obvious to arrive at the recited stirring power of 0.2 kW/kL or more or 0.4 kW/kL or more by routine optimization.
Regarding instant claims 1, 4-5, WO ‘150 discloses that by stirring or agitating the culture in the culture tank, it is possible to increase the chance of contacting the medium components and the substrate gas with the anerobic microorganisms and to optimize production efficiency of equol (at least p. 3-4) and further that the substrate gas can also be supplied as nanobubbles (at least p. 4). ThermoFisher discloses a pore size 0.178 mm for a volume 100 L (at least p. 7). Therefore, it would have been obvious to arrive at the recited sparger pore size of 1 mm or less or 0.5 mm or less by routine optimization.
Claims 1-5, 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over WO ‘150 (WO 2012033150, translated copy provided by Google patents cited herein) in view of ThermoFisher (2020 Introduction to mass transfer in single-use bioreactors, 11 pages) and Zheng et al. (2014 PLoS ONE 9(3): e93163, 11 pages). The teachings of WO ‘150 and ThermoFisher over at least instant claims 1-5 are noted above.
WO ‘150 discloses that in the culture of anaerobic microorganisms, it is necessary to prevent oxygen from being mixed into the continuous culture system (p. 3). WO ‘150 discloses that an anerobic atmosphere can be created by replacing oxygen in the culture tank with an inert gas such as nitrogen (at least p. 3). WO ’150 discloses that the combination of gases comprises one or more gases selected from hydrogen, carbon dioxide, nitrogen, etc. (at least p. 2). WO ‘150 discloses a mass percent concentration of hydrogen is 40-100% in the (p. 2). However, WO ‘150 also discloses equol production at mass concentrations of hydrogen below 40%, including ratios including CO2 80% and H2 20% or N2 80% and H2 20% (at least p. 5).
Zheng et al. disclose that hydrogen gas has been reported to stimulate equol production (at least p. 1). Zheng et al. disclose equol production can alternatively be regulated by a hydrogen-producing prebiotic in vivo/in vitro (at least p. 1). Zheng et al. disclose that the hydrogen-producing prebiotic lactulose corresponded with an increase in hydrogen gas production (p. 9-10).
“[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). MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the recited one or more types of gases containing a hydrogen concentration of 30% or less, including 10% or less and 4% or less because the prior art discloses equol is still produced at H2 concentrations below 30% (WO ’150) and it was further disclosed that equol production can alternatively be regulated by a hydrogen-producing prebiotic (Zheng et al.) (instant claims 6-14). One of ordinary skill would have a reasonable expectation of success because the prior art discloses equol can be produced at hydrogen concentrations below 30%.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marsha Tsay/Primary Examiner, Art Unit 1656
Prosecution Insights