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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 August 2025 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 22 August 2025.
CLAIMS UNDER EXAMINATION
Claims 1, 31-39 and 45-54 are pending and have been examined on their merits.
PRIORITY
Foreign Priority document GB1610932.4, filed on 22 June 2016, is acknowledged.
Claim 1 has been amended to recite “allowing a lipid phase …to separate from other constituents of the broth in the gravity separator only by gravity and without heating”. GB1610932.4 does not positively or negatively recite heating in the gravity settler.
There is not support for the claim limitation. PCT/GB2017/051205 does not provide support for the claim limitation. The specification filed on 21 December 2018 does not provide support for this limitation. This limitation has support in the claims filed on 22 August 2025. Regarding claims 31 and 45: The Foreign Priority document does not provide support for all of the species recited in the claims (e.g. terpenoids).
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
REJECTIONS
New rejections have been necessitated by claim amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended to recite “allowing a lipid phase …to separate from other constituents of the broth in the gravity separator only by gravity and without heating”.
A search of the instant specification does not recite a step of heating in a gravity settler.
MPEP 2173.05(i): Negative Limitations
Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims
Therefore the claim amendment presents new matter. An amendment to the claims or the addition of a new claim must be supported by the description of the invention in the application as filed. In re Wright, 866 F.2d 422, 9 USPQ2d 1649 (Fed. Cir. 1989). Applicant is required to cancel the new matter in the reply to this Office Action. Claim 52 is included in this rejection because it depends from claim 1.
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 51 and 54 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 51 has been amended to recite a range of “at least” 57% to 86%. It is unclear if the claim means “57% to 86%”. The metes and bounds of the claim are unclear. Appropriate correction is required. Dependent claim 54 is included in this rejection.
Claim Rejections - 35 USC § 102
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 1 and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dolman et al. (previously cited; Integrated sophorolipid production and gravity separation. Process Biochemistry 54 (2017) 162-171).
Dolman et al. teach a method for the integrated gravity separation of sophorolipid from a fermentation broth (Abstract). Figure 3 discloses a fermentation broth comprising a sophorolipid. Dolman teaches transfer to a gravity settling column (see page 163, left column, last sentence; Figure 3). Dolman illustrates two different liquids are formed in the gravity settler. Therefore the art is interpreted to teach the claimed liquid-liquid interface. Figure 3 illustrates fermentation broth is returned to the fermenter and the sophorolipid product (lipid product) is separated in a collection vessel. The gravity settling column is the only separator disclosed by Dolman. Dolman teaches the fermentation uses vegetable oil and rapeseed oil (i.e. vegetable oils) see first paragraph of Methodology on page 163). The art teaches glucose (a sugar) is fed at rates higher than those recited in claim 1 (see Figure 4). Therefore claim 1 is anticipated.
Because the method of claim 1 is anticipated, it would be expected to result in a total lipid production as recited in claim 52.
Therefore Applicant’s invention is anticipated as claimed.
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 1 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (Production of sophorolipids with enhanced volumetric productivity by means of high cell density formation. Biotechnol (2013) 97: 1103-1111) in view of Duran et al. (previously cited; WO215/164324) and Kompala et al. (previously cited; Particle Settling Devices. Patent US11148076 with benefit of PCT / US2015/063195, filed on Dec. 1 , 2015).
Gao teaches volumetric productivity is defined as the mass of product formed per volume and unit time. Gao teaches the ultimate goal of fermentation is to maximize volumetric productivity: to obtain the greatest amount of product in a given volume in the least amount of time (see page 1104, left column, first paragraph).
Gao teaches a method of achieving high time-space efficiency of sophorolipid production with yeast Candida bombicola (Abstract). Gao teaches fermentation (page 1104, right column, first paragraph). At the end of fermentation, sophorolipids are isolated by centrifugation at 8,000 rpm (see page 1104, right column, last paragraph). Because centrifugal force causes sedimentation, separation in a centrifuge is interpreted to read on gravity separator. The centrifuge is not heated.
After centrifugation, the culture mixture was separated into three phases: the upper phase contained primarily culture medium, the intermediate phase contained the sophorolipids and the lower solid phase contained the cells (last paragraph of page 1104 bridging first line of page 1105). Therefore the art teaches a lipid phase is allowed to separate from other constituents of the broth. Because the art teaches gravity and phase separation, a liquid-liquid interface is interpreted to be present between the lipid phase and other constituents. The lipid product is taken from the centrifuge (see page 1105, left column, first paragraph).
Gao teaches “because sophorolipids are an extracellular product, high density cells can technically be reused after an in situ gravitative precipitation of the sophorolipids. The art teaches specific reactors may be developed and optimized for sophorolipid production (page 1108, left column, first paragraph).
Gao teaches the disclosed method can be used to produce a volumetric productivity of 3.7 to 8.3 (see Table 1).
Gao also teaches the following:
Gao teaches optimizing fermentation parameters to achieve maximum cell density and production (Abstract). Gao teaches the control of substrate feeding rate is important for maximizing both sophorolipid production and volumetric productivity (page 1107, right column, second paragraph). To maintain substrate at their optimal concentration, the feed rate of glucose (hydrophilic substrate) and lipophilic substrate (e.g., rapeseed oil) should be frequently adjusted to yield proper concentrations (same cited section). The feed rate of rapeseed oil and glucose should be frequently adjusted to yield proper concentrations. In this study, glucose and rapeseed oil (v/v) were fed at a ratio between 2.1:1 and 2.2:1 (page 1107, right column, last paragraph).
Gao teaches optimizing fermentation conditions to optimize sophorolipid production. Gao teaches optimizing the feed rate. Gao does not explicitly teach the feed rate recited in claim 1. Gao teaches the cells obtained after gravity precipitation of the sohorolipids can be reused in a reactor optimized for this purpose. The art does not explicitly teach recycling the cells in the disclosed method.
Duran teaches a method of making sophorolipids ([00019). Duran teaches the lipid source can be oils derived from plant-based oils ([00020]). Duran teaches the lipid source is fed into the fermenter between 9 and 40 hours of elapsed fermentation time. A total of 200 g/L of the lipid source is added (based on starting fermentation volume). Examiner notes 200 g/l added over 9 hours is 22 g/l/h. 200 g/l added over 40 hours is 5 g/l/h. This reads on the claimed feed rate.
Kompala et al. disclose a settling device for separating particles from bulk fluid with applications in numerous fields (Abstract). The art teaches the use of a settler comprising a cyclone housing (column 4, lines 40-42). The method includes introducing a liquid suspension of particles into a particle settling device, collecting a clarified liquid from a first outlet port, collecting a concentrated liquid suspension from a second outlet port (column 13, lines 32-40).
The liquid suspension comprises yeast cells (column 14, lines 55-57). The concentrated liquid may include live cells (claim 13, lines 45-46). The clarified liquid collected may comprise hydrocarbons, fatty acids, isoprenoids or polyprenoids (column 15, lines 10-15). Examiner notes these are lipids.
The settler device includes directing a liquid suspension from a bioreactor into the particle settling device (column 15 lines 19-21). The art teaches the device can be used to direct a liquid suspension of cells from a bioreactor or fermentation media into the settler device (column 22, lines 28-31).The art teaches a typical schematic of the attachment of a compact cell/particle settler of this disclosure to any modular bioreactor is shown in Figure 15 (column 36, lines 13-15).
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Examiner notes the embodiment only discloses a cell settler.
Kompala teaches concentrated liquid exits the bottom of the cycle (settler) “due to gravity” (column 26, lines 12-13). Therefore the settler taught by the art is interpreted to be a gravity settler. As illustrated in Figure 15, the art teaches live cells are recycled from the cell settler (208) back to bioreactor (218) using return line (217) (column 36, lines 25-30).
It would have been obvious to use a feed rate of at least 0.5 g/l/h. Gao teaches feeding substrate during fermentation and Duran teaches a feed rate of at least 0.5 g/l/h/ during fermentation. The skilled artisan would optimize the substrate feed rate to achieve high volumetric productivity, as taught by Gao. One would have had a reasonable expectation of success since Gao teaches feed rate can be adjusted and optimized during fermentation to achieve the desired volumetric productivity. See MPEP 2144.05 (Optimization Within Prior Art Conditions or Through Routine Experimentation).
It would have been obvious to return broth and cells to a fermenter following separation. Gao teaches separating of a fermentation broth and teaches cells can be reused. Kompala teaches a fermentation broth produced by gravity settling can be recycled. The skilled artisan would use the system taught by Kompala to reuse the cells in a subsequent fermentation. One would have had a reasonable expectation of success since Gao teaches cells can be reused, and suggests the use of reactors designed for this purpose. One would have expected similar results since Gao and Kompala are both directed to methods of processing fermentation broths to produce a product.
Therefore claim 1 is rendered obvious.
Regarding claim 52: The claim recites the total lipid production. Gao teaches greater than 200 g/L sophorolipid production (see Table 1). Gao teaches optimizing fermentation conditions to achieve high time-space efficiency for volumetric production (Abstract). Gao teaches optimizing the carbon source and nutrient concentration to achieve the maximum cell density (Abstract). Gao teaches adjusting physical parameters of the fermentation (Abstract). The art teaches optimizing the glucose concentration to optimize both cell growth and final cell density in the growth phase (page 1105, right column, first paragraph). The art teaches cell growth is effected by the amount of nitrogen source and other nutrients (page 1106, left column, second paragraph). Gao teaches the control of substrate feeding rate is important for maximizing both sophorolipid.
The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired sophorolipid yield. Therefore claim 52 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 31-38, 45-51 and 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. in view of Kompala.
.
Regarding independent claim 50: The claim recites the limitations recited in claim 1 with the following exception: the method has a volumetric productivity of 2.24 g/l/h. The teachings of Gao as set forth above are reiterated. Gao teaches the disclosed method can produce a volumetric productivity of 3.7 (Table 1). The art teaches fermentation conditions can be optimized to achieve the desired volumetric productivity. Gao teaches the cells obtained after gravity precipitation of the sohorolipids can be reused in a reactor optimized for this purpose. The art does not explicitly teach recycling the cells in the disclosed method. The teachings of Kompala are reiterated.
It would have been obvious to return broth and cells to the fermenter following separation. Gao teaches separating of a fermentation broth and teaches cells can be reused. Kompala teaches a fermentation broth produced by gravity settling can be recycled. The skilled artisan would use the system taught by Kompala to reuse the cells in a subsequent fermentation. One would have had a reasonable expectation of success since Gao teaches cells can be reused, and suggests the use of reactors designed for this purpose. One would have expected similar results since Gao and Kompala are both directed to methods of processing fermentation broths to produce a product.
Gao teaches the volumetric productivity is effected variables including by cell density, carbon source, carbon concentration, feed rate, vessel size and viscosity. The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired volumetric productivity. Therefore claim 50 is rendered obvious.
Gao produces sophorolipids (supra). Sophorolipid is a lipid. Therefore claims 31-32 and 45 are rendered obvious.
Regarding claim 33: Gao teaches the control of substrate feeding rate is important for maximizing sophorolipid production and volumetric productivity (page 1107, right column, second paragraph). To maintain substrate at their optimal concentration, the feed rate of glucose (hydrophilic substrate) and lipophilic substrate (e.g., rapeseed oil) should be frequently adjusted to yield proper concentrations (same cited section). Gao teaches production of sophorolipid is proportional to the dry cell weight (page 1108, left column, last paragraph). The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired volumetric productivity. Therefore claim 33 is rendered obvious.
Regarding claim 34: As set forth above, Kompala teaches the method disclosed in Figure 2 is performed in a circuit system. Moving a broth from a fermenter to a separator, and returning broth from the separator to a fermenter (as taught by Kompala) is interpreted to comprise circulation. Kompala teaches a continuous process (column 34, lines 48-54). The skilled artisan would recycle broth over the course of sophorolipid production to perform a continuous process. One would optimize the amount of broth recycled through the system to reuse cells for subsequent fermentation. Therefore claim 34 is included in this rejection.
Regarding claim 35: Gao taches the production of sophorolipids will increase the viscosity of the system, and thereby decrease mass transfer and aeration, which slow down cell growth (page 1108, last sentence, bridging first two lines of page 1109). The skilled artisan would optimize the concentration of lipid product in the fermenter to prevent increased viscosity, which decreases cell growth. Therefore claim 35 is included in this rejection.
Gao teaches the fermenter has a paddle impeller for agitation (page 1104, right column, first paragraph). Therefore claim 36 is included in this rejection.
Regarding claim 37: Kampala teaches the settler device comprises a cyclone housing (supra). A housing is interpreted to read on a chamber. The setline device comprises inclined surfaces (column 4, lines 25-26). The device may comprise several inclined plates approximating an angled conical surface (column 4, lines 33-36). The art teaches the inclined plates enhance the settling efficiency of the particles from the fluid moving either downward or upward inside the cyclone. The art teaches angles between about 30 degrees and 60 degrees (column 4, line 67 bridging line 1 of column 5). Therefore claim 37 is included in this rejection.
Regarding claim 38: Gao teaches centrifugation (gravity separation) (supra). After centrifugation, the culture mixture was separated into three phases: the upper phase contained primarily culture medium, the intermediate phase contained the sophorolipids and the lower solid phase contained the cells (supra). Therefore the art teaches a lipid phase is allowed to separate from other constituents of the broth. Because the art teaches gravity and phase separation, a liquid-liquid interface is interpreted to be present between the lipid phase and other constituents. Cells are removed (supra). The lipid product is taken from the centrifuge (supra). It is noted Gao teaches glucose in an aqueous solution (water) is fed to the system (page 1107, left column, third paragraph). Therefore the broth contains water and lipid product.
Gao does not teach the concentration of the lipid product recited in claim 38. As set forth above, Gao teaches optimizing fermentation conditions to increase the amount of lipid product produces (supra). The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired volumetric productivity. Therefore claim 38 is rendered obvious. Claims 48-49 are rendered obvious on the same grounds.
Regarding claims 46-47:
Claim 46 recites continuously circulating broth between the fermenter and gravity separator. Kompala teaches broth from the fermenter is circulated to the gravity settler and returned to the fermenter. Therefore all of the broth is returned to the fermenter. Therefore claim 46 is included in this rejection.
Claim 47 recites continuously circulating broth between the fermenter and gravity separator. Kompala teaches broth from the fermenter is circulated to the gravity settler and returned to the fermenter. Therefore all of the broth is returned to the fermenter. Therefore claim 47 is included in this rejection.
Regarding independent claim 51: The claim recites the limitations of claim 50 with the following exception: Claim 51 recites “wherein the method results in a lipid recovery of at east 57% to 86% of the total lipid produced during the product.
The teachings of Gao are reiterated. Gao also teaches multiple extractions using ethyl acetate (page 1105, left column, first paragraph). The extracts are then pooled (same cited section).
It is Examiner’s position the amount of lipid recovery is the result of sophorolipid produced. Gao teaches the volumetric productivity is effected variables including by cell density, carbon source, carbon concentration, feed rate, vessel size and viscosity. The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired sophorolipid yield. One would perform multiple extractions to increase the amount of sophorolipid recovered. Therefore claim 51 is rendered obvious.
Regarding claim 53: The claim recites the total lipid production. Gao teaches greater than 200 g/L sophorolipid production (see Table 1). Gao teaches optimizing fermentation conditions to achieve high time-space efficiency for volumetric production (Abstract). Gao teaches optimizing the carbon source and nutrient concentration to achieve the maximum cell density (Abstract). Gao teaches adjusting physical parameters of the fermentation (Abstract). The art teaches optimizing the glucose concentration to optimize both cell growth and final cell density in the growth phase (page 1105, right column, first paragraph). The art teaches cell growth is effected by the amount of nitrogen source and other nutrients (page 1106, left column, second paragraph). Gao teaches the control of substrate feeding rate is important for maximizing both sophorolipid production and volumetric productivity (page 1107, right column, second paragraph).
The skilled artisan would optimize the conditions taught by Gao to achieve the desired volumetric productivity. One would have had a reasonable expectation of success since Gao teaches these fermentation conditions can be adjusted and optimized to achieve the desired sophorolipid yield. Therefore claim 53 is rendered obvious.
Claim 54 is rejected on the same grounds as claim 53.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Gao in view of Kompala as applied to claim 33 above, and further in view of Duran.
Claim 33 is rejected on the grounds set forth above. The teachings of Gao and Kompala are reiterated.
Regarding claim 39: Gao teaches a lipid phase comprising sophorolipid product (supra). The art teaches controlling fermentation conditions. Gao teaches a pH of 3.5 (page 1104, right column, first paragraph). The feed rate of rapeseed oil and glucose should be frequently adjusted to yield proper concentrations. In this study, glucose and rapeseed oil (v/v) were fed at a ratio between 2.1:1 and 2.2:1 (page 1107, right column, last paragraph). The dissolved oxygen is maintained at 30% by controlling the aeration and agitation rate (page 1104, right column, first paragraph).
Gao does not explicitly teach the feed rate recited in claim 39.
Duran teaches Sophorolipids may be manufactured from a lipid source ([00019]). Duran teaches the lipid source can be oils derived from plant-based oils and/or animal sources, animal fats, or free fatty acids derived from one or more of these sources ([00020]). Duran teaches the lipid source is fed into the fermenter between 9 and 40 hours of elapsed fermentation time. A total of 200 g/L of the lipid source is added (based on starting fermentation volume). Examiner notes 200 g/l added over 9 hours is 22 g/l/h. 200 g/l added over 40 hours is 5 g/l/h. This reads on the claimed feed rate.
It would have been obvious to use a feed rate of at least 0.5 g/l/h. Gao teaches feeding substrate during fermentation and Duran teaches a feed rate of at least 0.5 g/l/h/ during fermentation. The skilled artisan would optimize the substrate feed rate to achieve high volumetric productivity, as taught by Gao. One would have had a reasonable expectation of success since Gao teaches feed rate can be adjusted and optimized during fermentation to achieve the desired volumetric productivity. See MPEP 2144.05 (Optimization Within Prior Art Conditions or Through Routine Experimentation).
Therefore claim 39 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 22 August 2025 are acknowledged. New grounds of rejection have been necessitated by claim amendment.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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