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 .
Status of the Application
Receipt of the Response and Amendment after Non-Final Office Action filed 13 April 2026 is acknowledged.
Applicant has overcome the following by virtue of amendment of the claims: (1) the objection to claim 1 has been withdrawn.
The status of the claims upon entry of the present amendment stands as follows:
Pending claims: 1, 4, 8, 11-14, 16, 18, 27-30, 34-38, 40-41, and 45-46
Withdrawn claims: 36-38, 40-41, and 45
Previously canceled claims: 2-3, 5-7, 9-10, 15, 17, 19-26, 31-33, 39, and 42-44
Newly canceled claims: None
Amended claims: 1
New claims: None
Claims currently under consideration: 1, 4, 8, 11-14, 16, 18, 27-30, 34-35, and 46
Currently rejected claims: 1, 4, 8, 11-14, 16, 18, 27-30, 34-35, and 46
Allowed claims: None
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, 4, 8, 11-14, 18, 27-30, 34-35, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Habeych Narvaez et al. (hereinafter “Habeych”) (US 2022/0240538 A1) in view of Yap et al. (Yap, P.Y., Jain, A., and Trau, D. (2019). Quantification of Soluble Starch from Fresh Potatoes Using Photopette. Retrieved from Tip Biosystems website: https://www.tipbiosystems.com/wp-content/uploads/2023/12/ANE01-Starch-application-note_2019_v6.pdf), and Garidel et al. (Garidel, P., Kuhn, A.B., Schäfer, L.V., Karow-Zwick, A.R., and Blech, M. (2017). High-concentration protein formulations: How high is high?. Eur J Pharm Biopharm, 119, pp. 353-60. https://doi.org/10.1016/j.ejpb.2017.06.029).
Regarding claim 1, Habeych teaches a method for separation of (a) potato proteins and insoluble fibers from (b) first salts and phenolic and/or glycoalkaloid compounds in potato fruit juice or a derivative thereof, said method comprising the steps of:
(i) providing a potato fruit juice or a derivative thereof, comprising:
potato proteins – At least one tuber is processed to obtain an aqueous liquid (tuber processing water) comprising tuber protein ([0066]), for example potato fruit juice as obtained after starch isolation ([0067]), or water from cutting potatoes ([0068] – [0069]).
insoluble fibers – the aqueous liquid may comprise starch ([0067]), and residual cell wall fragments ([0070]), which are forms of insoluble fiber.
one or more first salts – salts present in the tuber processing water (i.e., first salts) are replaced by diafiltration ([0035]).
phenolic and/or glycoalkaloid compounds – the method also comprises a step of glycoalkaloid removal ([0091]), indicating the presence of glycoalkaloids in the potato fruit juice.
(ii) subjecting said potato fruit juice or the derivative thereof provided in step (i) to a first cross-flow membrane filtration process wherein water and at least a portion of the first salts and at least a portion of the phenolic and/or glycoalkaloid compounds migrate across the membrane into a first permeate and wherein the potato proteins are retained in a first retentate – Habeych discloses pretreatment steps such as concentration, dilution, pH adjustment, flocculation, solids removal and/or heat treatment, that can be carried out in any order ([0070]). In a much-preferred embodiment, concentration pretreatment is achieved through cross-flow ultrafiltration ([0074]). In a case of a tuber processing water with a relatively high quantity of suspended solids, (e.g, juice with high quantities of cell debris (i.e., insoluble fiber) which has not undergone a solids removal step), preferred membranes have a molecular weight cut-off (MWCO) of 20-300 kDa ([0077]). In a case of tuber processing water with a relatively low quantity of cell debris/insoluble fiber, preferred membranes have a MWCO of 3-100 kDa. Given these teachings, one of ordinary skill in the art would have selected a MWCO within the disclosed range that retained proteins of interest and insoluble fibers in the retentate. At least a portion of the glycoalkaloid compounds, being small molecules, would migrate across the membrane into the permeate. Likewise, at least a portion of the salt ions would also migrate across the membrane into the permeate. In Example 3, to which steps the disclosed invention is not limited, Habeych teaches, “The potato processing water was ultrafiltrated using a spiral-wound membrane with a molecular weight cut-off (MWCO) of 5 kDa…” ([0143]).
(iii) adding aqueous diafiltration liquid containing one or more salts to the first retentate obtained in step (ii) to form a diluted first retentate having a conductivity of between 1 mS/cm and 50 mS/cm and subjecting said diluted first retentate to a second cross-flow membrane filtration as diafiltration, to create a second permeate being a diafiltrate containing at least a portion of said phenolic and/or glycoalkaloid compounds and salts and a second retentate comprising potato proteins, salts, and insoluble fibers – “The retentate from the ultrafiltration [i.e., first retentate] was subjected to further treatment comprising diafiltration against a salt solution having 0.33 or 50.66 [sic, 0.66] wt. % NaCl [i.e., one or more salts]…This resulted in a potato protein isolate solution [i.e., second retentate].” ([0144]). “Each diafiltration step entails dilution of protein solution volume VPJ with diafiltration volume VDF in a ratio as indicated and concentrating the diluted protein solution back to the original volume by ultrafiltration.” ([0152]). “[I]t is essential that during the whole isolation process, the conductivity is relatively high. The salt solution against which the diafiltration is performed must have a conductivity of at least 5 mS/cm, and the feed solution must have a conductivity of 2-20 mS/cm.” ([0040]). “Preferably, the conductivity of the solution to be diafiltered (the diafiltration feed solution or feed) remains within the ranges herein specified.” ([0054]). Habeych further discloses that when the salt concentration was increased from 0.33% to 0.66%, the TGA (i.e., glycoalkaloid) content of the dried protein isolate was lower ([0148] and [0146], Table 2, Experiment 6, “Total TGA content”), indicating that at least a portion of glycoalkaloids pass through the filter during the diafiltration process. The resulting diafiltrate would also comprise salts since these ions would pass through the disclosed 5 kDa molecular-weight cut-off filter.
Habeych does not discuss that the potato fruit juice or derivative thereof has an absorbance at 600 nm in the range of 0.1 to 50, as determined by spectrophotometry on samples diluted in 0.05 M potassium phosphate at pH 7.0, wherein the amount of light of wavelength 600 nm passing through a liquid sample in a spectrophotometer using 10 mm light path cuvettes is measured. Habeych also does not discuss that the first retentate has a true protein concentration in the range of 5 g/L to 200 g/L. Habeych further does not discuss that the diluted first retentate has an absorbance at 600 nm in the range of 0.01 to 50.
Regarding the absorbance at 600 nm, Yap teaches measuring potato starch/insoluble fiber using the absorbance at 600 nm of a solubilized starch-iodine complex (p. 1, col. 1, ¶¶ 3-4). Increasing absorbance at 600 nm values indicate higher starch/insoluble fiber concentrations (Table 1). The method provides a linear range at a starch concentration from 0.05-0.35 mg/mL, which corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3). One of ordinary skill in the art would have recognized that this method could also be applied to a potato fruit juice or derivative thereof to indicate the amount of starch/insoluble fiber therein.
Therefore, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Habeych with the teachings of Yap to provide a potato fruit juice with an absorbance at 600 nm in the range of 0.1 to 50 as claimed. One of ordinary skill in the art would have been motivated to consult Yap to determine a method to measure the amount of starch/insoluble fiber at various stages throughout the filtration/purification process, including pre-filtration, and in the retentate and permeate after filtering in order to monitor inputs and outputs of the filtration steps and to determine efficiency of the method. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Yap demonstrates that starch/insoluble fiber can be detected by using the absorbance at 600 nm as a readout, and that starch in a concentration range of 0.05-0.35 mg/mL corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3).
Although the absorbance at 600 nm in the cited prior art differs from that of the claimed invention, one of ordinary skill in the art would have adjusted the starting PFJ during routine optimization of the method such that the amount of starch/insoluble fiber in the PFJ did not substantially interfere with the filtration process. MPEP § 2144.05(II) states where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Absent any evidence of criticality of the claimed range of 0.1 to 50 and given the breadth of such a range, it would have been obvious for one of ordinary skill in the art to have adjusted the absorbance at 600 nm during routine optimization to result in an amount of starch/insoluble fiber in the PFJ that allows successful filtration, thereby arriving at an absorbance at 600 nm within the claimed range.
Furthermore, in the same way, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to form a diluted first retentate for diafiltration having an absorbance at 600 nm of between 0.01 and 50, as claimed. Habeych teaches that diafiltration is preferably performed at a dilution rate of 1:1 to 1:10 of feed:salt solution ([0051]). This process effectively dilutes the retentate back to the starting volume and up to 10-fold less than the starting volume, which would result in an absorbance at 600 nm reflecting such dilution. For instance, a starting PFJ/derivative with an absorbance at 600 nm of 0.1 would be ultrafiltered, and then diluted for diafiltration such that the absorbance is 0.1 to 0.01, as in claim 1.
It is noted that while the method of Yap is not the same as the claimed method of “spectrophotometry on samples diluted in 0.05 M potassium phosphate at pH 7.0, wherein the amount of light of wavelength 600 nm passing through a liquid sample in a spectrophotometer using 10 mm light path cuvettes is measured”, both methods provide the absorbance at 600 nm of the potato fruit juice sample. In the present case, the absorbance at 600 nm of the potato fruit juice sample is a property of a specific product used in the positively recited steps of the claimed method. The means of measuring the absorbance at 600 nm is not a positively recited step of the claimed method. As such, the matter of how the absorbance at 600 nm is determined is similar to a product-by-process limitation. MPEP § 2113 states, “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process”, In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Further, “although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product”, In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir.1983). Therefore, absent evidence of criticality regarding the presently claimed means of measuring the absorbance at 600 nm, and given that Yap meets the requirements of the claimed absorbance at 600 nm, Yap clearly meets the requirements of claim 1.
Regarding the true protein concentration of the first retentate, Garidel discloses monoclonal antibody (i.e., native protein) drug formulations at high concentrations ranging between 50 and 150 mg/mL (i.e., g/L), and that formulations at these concentrations have specific solution, stability, and colloidal properties that differ from formulations at a low protein concentration (e.g., at 10 mg/mL) (p. 353, Abstract). Garidel teaches challenges associated with high-concentration protein formulations, stating that protein solubility and solution properties are key factors at high concentrations, and “at high protein concentration >100 mg/ml, the solution becomes crowed and protein-protein interactions become more relevant. As a consequence of increased protein concentration, opalescence and especially viscosity may strongly increase.” (p. 354, col. 1, ¶ 4). Garidel further discloses that ultrafiltration/diafiltration (UF/DF) is the most used and appropriate method for concentrating proteins, however “the strong, non-linear dependence of viscosity on protein concentration sets limits to the application range of UF/DF procedures. The high viscosity induces strong backpressures in the UF/DF systems and the filtration flow is strongly reduced, thus making the process challenging to develop.” (p. 354, col. 2, ¶ 4).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Habeych with the teachings of Garidel to ensure that the true protein concentration of the first and second retentates is in the range of 5 g/L to 200 g/L as claimed. First, Habeych teaches that the proteins are isolated in the native form and are isolated via ultrafiltration/diafiltration. Garidel teaches that at protein concentrations >100 mg/mL, viscosity may strongly increase (p. 354, col. 1, ¶ 4) and the increased viscosity makes UF/DF challenging (p. 354, col. 2, ¶ 4). Therefore, one of ordinary skill in the art would have been motivated to keep the protein concentration of the retentates below 100 mg/mL, and closer to the disclosed lower protein concentration of 10 mg/mL (p. 353, Abstract) in the ultrafiltration and diafiltration processes of Habeych to maintain a viscosity that permits successful filtration processes, and for the same reasons would have had a reasonable expectation of success given the teachings of Garidel.
For these reasons, claim 1 is rendered obvious.
Regarding claim 4, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the method further comprises the step of subjecting the second retentate to the claimed “fifth” membrane filtration process resulting in a “fifth” retentate, wherein at least a portion of the salts migrate across the membrane into a “fifth” permeate – Analogous to the workflow of instant Figure 4, Habeych teaches that after a diafiltration with a salt solution, the retentate (i.e., second retentate) is subjected to salts removal via “a diafiltration stage against water at lower conductivity, or against regular water, in order to remove salts and isolate native tuber protein essentially free of salt” ([0053]). As such, salts migrate across the membrane into a “fifth” permeate. Therefore, claim 4 is rendered obvious.
Regarding claim 8, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the aqueous diafiltration liquid containing one or more salts contains one or more second salts that are added to the aqueous diafiltration liquid and that are different from the one or more first salts – Habeych discloses sulfite added to tuber processing water during starch processing, which is removed by the method ([0112]). The disclosed sulfite is seen as the first salt. Habeych also teaches that the diafiltration is performed against a salt solution ([0045]) preferably comprising a chloride salt, such as sodium chloride, potassium chloride, or calcium chloride ([0046]). The disclosed chloride salts are seen as second salts that are different than the first salt. Therefore, claim 8 is rendered obvious.
Regarding claim 11, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the method further comprises the step of adjusting the pH of said potato fruit juice or the derivative thereof to a pH in the range of 4.5 to 8.5 prior to said first cross-flow membrane filtration process – “The pretreatment may include one or more pH adjustments.” ([0080]). “For example, a pH adjustment to 4.0-5.5 can be used to precipitate at least part of the patatin fraction…” ([0082]). The claimed range overlaps the disclosed range. In a case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists, MPEP § 2144.05(I). Therefore, claim 11 is rendered obvious.
Regarding claim 12, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the method further comprises the step of adjusting the conductivity of said potato fruit juice or the derivative thereof to a conductivity in the range of 2-500 mS/cm prior to said first cross-flow membrane filtration process – “pretreatment results in a pretreated tuber processing water having a conductivity of 2-20 mS/cm…” ([0020]). The disclosed range lies within the claimed range. Therefore, claim 12 is rendered obvious.
Regarding claim 13, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the potato proteins are selected from the group consisting of patatin and protease inhibitors – “the tuber protein isolate is isolate comprising native protease inhibitor and native patatin. In further much preferred embodiments, the tuber protein isolate is a total native tuber protein isolate.” ([0030]). Therefore claim 13 is rendered obvious.
Regarding claim 14, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the potato fruit juice or the derivative thereof is pretreated by centrifugation and/or filtration to remove insoluble material of a particle size larger than 10 microns prior to said first cross-flow membrane filtration process – Habeych discloses solids removal as a pretreatment step ([0085]), which can be filtration, centrifugation, cycloning, decanting, nanofiltration or microfiltration ([0086]). Microfiltration is preferably performed over membranes having a pore size of 0.1-10 μm ([0087]). As such, insoluble material of a particle size larger than 10 microns is removed. Therefore, claim 14 is rendered obvious.
Regarding claim 18, Habeych, Yap, and Garidel teach the method according to claim 4.
Habeych also teaches that the claimed “fifth” retentate is further treated with a “sixth” cross-flow membrane filtration process whereby the potato protein and insoluble fibers are concentrated in a “sixth” retentate and the salts migrate through the membrane to create a “sixth” permeate – Analogous to the workflow of instant Figure 4, Habeych teaches that after a diafiltration with a salt solution, the retentate (i.e., second retentate) is subjected to salts removal via “a diafiltration stage against water at lower conductivity, or against regular water, in order to remove salts and isolate native tuber protein essentially free of salt” ([0053]). Habeych further discloses that the ultrafiltered potato fruit juice can be subjected to multiple diafiltration steps ([0156]). As such, Habeych teaches an embodiment where salts are removed from the claimed “fifth” retentate in by using water as the diafiltration solution such that the salts migrate through the membrane, creating a “sixth” permeate and concentrating the proteins and insoluble fibers in a “sixth” retentate. Therefore, claim 18 is rendered obvious.
Regarding claim 27, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych does not discuss that the absorbance at 600 nm is in the range of 0.2 to 45 during step (ii) and (iii).
However, as described regarding claim 1 above, Habeych as modified by Yap teaches the method wherein the potato fruit juice or derivative thereof contains insoluble fibers, and a method for determining and optimizing an absorbance at 600 nm of the potato fruit juice or derivative thereof.
Although the absorbance at 600 nm in the cited prior art differs from that of the claimed invention, one of ordinary skill in the art would have adjusted the starting PFJ during routine optimization of the method such that the amount of starch/insoluble fiber in the PFJ did not substantially interfere with the filtration process. MPEP § 2144.05(II) states where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Absent any evidence of criticality of the claimed range of 0.2 to 45, and given the breadth of such a range, it would have been obvious for one of ordinary skill in the art to have adjusted the absorbance at 600 nm during routine optimization to result in an amount of starch/insoluble fiber in the PFJ that allows successful filtration, thereby arriving at an absorbance at 600 nm within the claimed range.
Therefore, claim 27 is rendered obvious.
Regarding claim 28, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych does not teach that the absorbance at 600 nm, as determined using the method described in claim 1, of the first retentate and the second retentate remains within the range of 0.01 to 100 during step (ii) and (iii).
However, as described regarding claim 1 above, Habeych as modified by Yap teaches the method wherein the potato fruit juice or derivative thereof contains insoluble fibers, and a method for determining and optimizing an absorbance at 600 nm of the potato fruit juice or derivative thereof. Habeych further teaches that pretreatment prior to diafiltration involving microfiltration and ultrafiltration, as measured by solids (°Bx) at start and end of the process, results in concentration by up to about 85% (5.9 °Bx at start to 10.8 °Bx at end) (([0146], Table 2, Operation 1). In the same example, for diafiltration, the retentate is diluted 3:1 with diafiltration solution (VDF:VPJ). Habeych therefore discloses concentration by up to about 85% and dilution by 300% for diafiltration in one example. The claimed method requires a starting absorbance at 600 nm of 0.1 to 50, and that the absorbance remains within the range of 0.01 to 100 through step (ii) (first filtration) and (iii) (diafiltration). These required ranges provide for a concentration of 85% and dilution by 300% as disclosed.
It is seen that the degree of concentration and dilution would likewise be reflected as measured by the absorbance at 600 nm as performed in Habeych as modified by Yap proposed regarding claim 1. Claim 28 is therefore obvious for the same reasons and with the same expectation of success as described regarding claim 1 above.
Regarding claim 29, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych does not teach that the true protein concentration of the first retentate is in the range of 8 g/L to 180 g/L.
However, Garidel discloses monoclonal antibody (i.e., native protein) drug formulations at high concentrations ranging between 50 and 150 mg/mL (i.e., g/L), and that formulations at these concentrations have specific solution, stability, and colloidal properties that differ from formulations at a low protein concentration (e.g., at 10 mg/mL) (p. 353, Abstract). Garidel teaches challenges associated with high-concentration protein formulations, stating that protein solubility and solution properties are key factors at high concentrations, and “at high protein concentration >100 mg/ml, the solution becomes crowed and protein-protein interactions become more relevant. As a consequence of increased protein concentration, opalescence and especially viscosity may strongly increase.” (p. 354, col. 1, ¶ 4). Garidel further discloses that ultrafiltration/diafiltration (UF/DF) is the most used and appropriate method for concentrating proteins, however “the strong, non-linear dependence of viscosity on protein concentration sets limits to the application range of UF/DF procedures. The high viscosity induces strong backpressures in the UF/DF systems and the filtration flow is strongly reduced, thus making the process challenging to develop.” (p. 354, col. 2, ¶ 4).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Habeych with the teachings of Garidel to ensure that the true protein concentration of the first and second retentates is in the range of 8 g/L to 180 g/L as claimed. First, Habeych teaches that the proteins are isolated in the native form and are isolated via ultrafiltration/diafiltration. Garidel teaches that at protein concentrations >100 mg/mL, viscosity may strongly increase (p. 354, col. 1, ¶ 4) and the increased viscosity makes UF/DF challenging (p. 354, col. 2, ¶ 4). Therefore, one of ordinary skill in the art would have been motivated to keep the protein concentration of the retentates below 100 mg/mL, and closer to the disclosed lower protein concentration of 10 mg/mL (p. 353, Abstract) in the ultrafiltration and diafiltration processes of Habeych to maintain a viscosity that permits successful filtration processes, and for the same reasons would have had a reasonable expectation of success given the teachings of Garidel. Therefore, claim 29 is rendered obvious.
Regarding claim 30, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches that the solubility of the protein in the first retentate and the second retentate remains within the range of 50 % to 99 % relative to the protein soluble in the potato fruit juice or the derivative thereof – Figure 4 of Habeych demonstrates that solubility is maintained above 60 % when the conductivity of the solution protein solution is greater than 1 mS/cm ([0170]-[0172]). Based on these results, Habeych teaches that the conductivity during diafiltration must be maintained above 5 mS/cm ([0173]), such that > 80% of the protein remains soluble (Figure 4). Habeych also teaches “it is essential that during the whole isolation process, the conductivity is relatively high. The salt solution against which the diafiltration is performed must have a conductivity of at least 5 mS/cm, and the feed solution must have a conductivity of 2-20 mS/cm.” ([0040]). “Preferably, the conductivity of the solution to be diafiltered (the diafiltration feed solution or feed) remains within the ranges herein specified.” ([0054]). Since Habeych teaches that the conductivity must remain over 5 mS/cm throughout the process and that at this conductivity, the proteins remain over 80% soluble, claim 30 is rendered obvious.
Regarding claim 34, Habeych, Yap, and Garidel teach the method according to claim 1.
Habeych also teaches the method further comprising a step of eliminating enzymatic activity by exposing the first retentate obtained in step (ii) prior to step (iii) to pH values between 2.0 and 4.5 in a time and temperature interval sufficient to eliminate at least part of the unwanted enzymatic activity of the potato proteins without adversely affecting functionality of the potato proteins – Habeych teaches that the tuber processing water (i.e., potato fruit juice) is subjected to a pretreatment prior to the diafiltration step (i.e., prior to step (iii)) ([0020]). Pretreatment can comprise at least one of concentration, pH adjustment, solids removal, and/or heat treatment, resulting in a pretreated tuber processing water comprising native protein, and these steps can be performed in any order ([0070]). Concentration is preferably achieved through cross-flow ultrafiltration (i.e., as the claimed step (ii)) ([0074]). Paragraph [0082] reads:
[A] pH adjustment to 4.0-5.5 can be used to precipitate at least part of the patatin fraction…so as to obtain tuber processing water comprising a higher relative quantity of native protease inhibitor. Precipitated protein can subsequently be removed during a step of solids removal as elsewhere defined. This increases the relative quantity of native protease inhibitor in the native tuber protein isolate.
Paragraph [0084] reads:
A heat treatment may also be applied as a pretreatment, provided that the heat treatment does not result in full protein coagulation. For example, a heat treatment to 40-55° C. for 1-120 minutes may remove a significant portion of the patatin, which can subsequently be removed by a solids removal step. Also, it is known that protease inhibitor from tuber has higher heat stability than patatin, and that heating may lead to partial or full denaturation of patatin. Thus, a heating step may be performed in combination with a solids removal step for example to obtain a tuber processing water enriched in native protease inhibitor. For example, a heat treatment at 60-80° C., preferably 70-73° C. can be used to precipitate at least part of the patatin fraction, which can be followed by a step of solids removal, in order to isolate native tuber protein enriched in native protease inhibitor.
The claimed pH range of between 2.0 and 4.5 overlaps with the disclosed pH range of 4.0-5.5. In a case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists, MPEP § 2144.05(I). Furthermore, one of ordinary skill in the art of potato protein purification would have had an understanding of the biochemical properties of the potato proteins and would have used process parameters within the disclosed ranges to obtain desired functional properties of said proteins.
Claim 34 is therefore rendered obvious.
Regarding claim 35, Habeych, Yap, and Garidel teach the method according to claim 34.
Habeych also teaches that the first retentate obtained in step (ii) prior to step (iii) is exposed to:
a pH value between 2.0 and 4.5 – 4.0-5.5 ([0082]);
a temperature in the range of 1-70 °C – 40-55 °C ([0084]); and
in a time span of up to 240 minutes – 1-120 minutes ([0084]).
Therefore, claim 35 is rendered obvious.
Regarding claim 46, Habeych, Yap, and Garidel teach the method according to claim 34. Habeych teaches the claimed steps resulting in eliminating enzymatic activity as described regarding claim 34. MPEP § 2144.04 provides, “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results” In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). Therefore, absent any evidence of new or unexpected results, it would have been obvious to perform the step of eliminating enzymatic activity at any point in the method, including on the second retentate resulting from diafiltration step (iii), as claimed. Claim 46 is therefore obvious.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Habeych Narvaez et al. in view of Yap et al., and Garidel et al. as applied to claim 1 above, and further in view of Edens et al. (WO 97/42834).
Regarding claim 16, Habeych, Yap, and Garidel teach the method according to claim 1.
The cited prior art does not teach that the method further comprises the step of continuing the addition of aqueous diafiltration liquid containing one or more salts to the first retentate while continuing the second membrane filtration process until the second retentate contains less than a target amount of the phenolic and/or total glycoalkaloid compounds, whereby the separation of the potato proteins from phenolic and/or total glycoalkaloid compounds has been achieved, wherein the target amount of remaining phenolic and/or total glycoalkaloid compounds in the second retentate corresponds to less than 5000 mg phenolic and/or total glycoalkaloid compounds per kg potato protein on the basis of dry weight.
However, Edens teaches a method for isolating undenatured potato protein from potato fruit juice comprising a pretreatment, concentration by ultrafiltration using a 5 kDa cut-off membrane, and washing by diafiltration in the presence of bisulfite until salts and metal concentrations reach acceptable levels (p. 5, lines 10-28). Membranes with cut-off ranging from 3-100 kDa are disclosed (p. 3, lines 27-29). HPLC analysis of the freeze-dried powder indicated no detectable levels of glycoalkaloids (p. 5, lines 26-27). Thus, Edens teaches that continual diafiltration of the ultrafiltration retentate comprising molecules over 5 kDa reduces the glycoalkaloid amount to levels undetectable by HPLC.
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to apply the diafiltration wash technique of Edens to the method of Habeych as an improved way to remove glycoalkaloids from the potato protein retentate as claimed. See MPEP § 2143(I)(D). First, Habeych teaches the base method of ultrafiltration and diafiltration of potato proteins from potato fruit juice as described regarding claim 1 above. Habeych teaches that glycoalkaloids can be removed at any step, and that glycoalkaloid extraction is performed by other known techniques, such as adsorption ([0092]) to reach at most 200 mg/kg glycoalkaloids ([0091]). Edens teaches the applicable known technique of continual diafiltration to wash away non-protein components, including glycoalkaloids, such that the final amount of glycoalkaloids in the protein product is undetectable by HPLC (p. 5, lines 21-28). Since Habeych teaches the reduction of glycoalkaloids to at most 200 mg/kg, one of ordinary skill in the art would have recognized that applying the technique of Edens would have yielded predictable results and resulted in an improved system by eliminating the need for an additional adsorption step to remove glycoalkaloids. Therefore, claim 16 is rendered obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending Application No. 18/001,271 (hereinafter ‘271) in view of Habeych Narvaez et al. (US 2022/0240538 A1), Yap et al. (Yap, P.Y., Jain, A., and Trau, D. (2019). Quantification of Soluble Starch from Fresh Potatoes Using Photopette. Retrieved from Tip Biosystems website: https://www.tipbiosystems.com/wp-content/uploads/2023/12/ANE01-Starch-application-note_2019_v6.pdf), and Garidel et al. (Garidel, P., Kuhn, A.B., Schäfer, L.V., Karow-Zwick, A.R., and Blech, M. (2017). High-concentration protein formulations: How high is high?. Eur J Pharm Biopharm, 119, pp. 353-60. https://doi.org/10.1016/j.ejpb.2017.06.029).
Regarding claim 1, claim 17 of ‘271 teaches a method for separation of (a) potato proteins from (b) first salts and phenolic and/or glycoalkaloid compounds in potato fruit juice or a derivative thereof, said method comprising the steps of:
(i) providing a potato fruit juice or a derivative thereof, comprising:
potato proteins; and
one or more first salts; and
phenolic and/or glycoalkaloid compounds;
(ii) subjecting said potato fruit juice or the derivative thereof to a first cross-flow membrane filtration process wherein water and at least a portion of the first salts and at least a portion of the phenolic and/or glycoalkaloid compounds migrate across the membrane into a first permeate and wherein the potato proteins are retained in a first retentate;
(iii) adding aqueous diafiltration liquid containing one or more salts to the first retentate obtained in step (ii) to form a diluted first retentate having a conductivity of between 0.1 mS/cm and 50 mS/cm (i.e., maintaining the conductivity in the range of 1 to 50 mS/cm during step (ii) and (iii), see claim 17), and subjecting the diluted first retentate to a second cross-flow membrane filtration as diafiltration, to create a second permeate being a diafiltrate containing at least a portion of said phenolic and/or glycoalkaloid compounds and salts and a second retentate comprising potato proteins and salts.
Claim 1 differs from ‘271 claim 17 in that claim 17 does not teach that the potato fruit juice or derivative thereof comprises insoluble fibers and has an absorbance at 600 nm in the range of 0.1 to 50. Claim 17 also does not teach that the first retentate has a true protein concentration in the range of 5 g/L to 200 g/L. Claim 17 further does not teach that the diluted first retentate has an absorbance at 600 nm in the range of 0.01 to 50.
Regarding the insoluble fibers, Habeych teaches a method isolating a native tuber protein isolate ([0013] – [0020]) comprising:
(i) providing a potato fruit juice or a derivative thereof, comprising:
potato proteins – At least one tuber is processed to obtain an aqueous liquid (tuber processing water) comprising tuber protein ([0066]), for example potato fruit juice as obtained after starch isolation ([0067]), or water from cutting potatoes ([0068] – [0069]).
insoluble fibers – the aqueous liquid may comprise starch ([0067]), and residual cell wall fragments ([0070]), which are forms of insoluble fiber.
one or more first salts – salts present in the tuber processing water (i.e., first salts) are replaced by diafiltration ([0035]).
phenolic and/or glycoalkaloid compounds – the method also comprises a step of glycoalkaloid removal ([0091]), indicating the presence of glycoalkaloids in the potato fruit juice.
(ii) subjecting said potato fruit juice or the derivative thereof provided in step (i) to a first cross-flow membrane filtration process wherein water and at least a portion of the first salts and at least a portion of the phenolic and/or glycoalkaloid compounds migrate across the membrane into a first permeate and wherein the potato proteins are retained in a first retentate – Habeych discloses pretreatment steps such as concentration, dilution, pH adjustment, flocculation, solids removal and/or heat treatment, that can be carried out in any order ([0070]). In a much-preferred embodiment, concentration pretreatment is achieved through cross-flow ultrafiltration ([0074]). In a case of a tuber processing water with a relatively high quantity of suspended solids, (e.g, juice with high quantities of cell debris (i.e., insoluble fiber) which has not undergone a solids removal step), preferred membranes have a molecular weight cut-off (MWCO) of 20-300 kDa ([0077]). In a case of tuber processing water with a relatively low quantity of cell debris/insoluble fiber, preferred membranes have a MWCO of 3-100 kDa. Given these teachings, one of ordinary skill in the art would have selected a MWCO within the disclosed range that retained proteins of interest and insoluble fibers in the retentate. At least a portion of the glycoalkaloid compounds, being small molecules, would migrate across the membrane into the permeate. Likewise, at least a portion of the salt ions would also migrate across the membrane into the permeate. In Example 3, to which steps the disclosed invention is not limited, Habeych teaches, “The potato processing water was ultrafiltrated using a spiral-wound membrane with a molecular weight cut-off (MWCO) of 5 kDa…” ([0143]).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Claim 17 with the teachings of Habeych to provide a tuber processing water which has not undergone a solids removal step, and to perform ultrafiltration on said tuber processing water using a membrane with a MWCO of 20-300 kDa. One of ordinary skill in the art would have been motivated to use a simple process of ultrafiltering the tuber processing water, thereby avoiding excessive additional pre-processing steps. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Habeych teaches that tuber processing water not having undergone a solids removal step can be ultrafiltered using a membrane with a MWCO of 20-300 kDa ([0077]).
Regarding the absorbance at 600 nm, Yap teaches measuring potato starch/insoluble fiber using the absorbance at 600 nm of a solubilized starch-iodine complex (p. 1, col. 1, ¶¶ 3-4). Increasing absorbance at 600 nm values indicate higher starch/insoluble fiber concentrations (Table 1). The method provides a linear range at a starch concentration from 0.05-0.35 mg/mL, which corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3). One of ordinary skill in the art would have recognized that this method could also be applied to a potato fruit juice or derivative thereof to indicate the amount of starch/insoluble fiber therein.
Therefore, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to further modify the method of claim 17 as modified by Habeych, with the teachings of Yap to provide a potato fruit juice with an absorbance at 600 nm in the range of 0.1 to 50 as claimed. One of ordinary skill in the art would have been motivated to consult Yap to determine a method to measure the amount of starch/insoluble fiber at various stages throughout the filtration/purification process, including pre-filtration, and in the retentate and permeate after filtering. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Yap demonstrates that starch/insoluble fiber can be detected by using the absorbance at 600 nm as a readout, and that starch in a concentration range of 0.05-0.35 mg/mL corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3).
Although the absorbance at 600 nm in the cited prior art differs from that of the claimed invention, one of ordinary skill in the art would have adjusted the starting PFJ during routine optimization of the method such that the amount of starch/insoluble fiber in the PFJ did not substantially interfere with the filtration process. MPEP § 2144.05(II) states where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Absent any evidence of criticality of the claimed range of 0.1 to 50 and given the breadth of such a range, it would have been obvious for one of ordinary skill in the art to have adjusted the absorbance at 600 nm during routine optimization to result in an amount of starch/insoluble fiber in the PFJ that allows successful filtration, thereby arriving at an absorbance at 600 nm within the claimed range.
Furthermore, in the same way, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to form a diluted first retentate for diafiltration having an absorbance at 600 nm of between 0.01 and 50, as claimed. Habeych teaches that diafiltration is preferably performed at a dilution rate of 1:1 to 1:10 of feed:salt solution ([0051]). This process effectively dilutes the retentate back to the starting volume and up to 10-fold less than the starting volume, which would result in an absorbance at 600 nm reflecting such dilution. For instance, a starting PFJ/derivative with an absorbance at 600 nm of 0.1 would be ultrafiltered, and then diluted for diafiltration such that the absorbance is 0.1 to 0.01, as in the instant claim 1.
Regarding the true protein concentration of the first retentate, Garidel discloses monoclonal antibody (i.e., native protein) drug formulations at high concentrations ranging between 50 and 150 mg/mL (i.e., g/L), and that formulations at these concentrations have specific solution, stability, and colloidal properties that differ from formulations at a low protein concentration (e.g., at 10 mg/mL) (p. 353, Abstract). Garidel teaches challenges associated with high-concentration protein formulations, stating that protein solubility and solution properties are key factors at high concentrations, and “at high protein concentration >100 mg/ml, the solution becomes crowed and protein-protein interactions become more relevant. As a consequence of increased protein concentration, opalescence and especially viscosity may strongly increase.” (p. 354, col. 1, ¶ 4). Garidel further discloses that ultrafiltration/diafiltration (UF/DF) is the most used and appropriate method for concentrating proteins, however “the strong, non-linear dependence of viscosity on protein concentration sets limits to the application range of UF/DF procedures. The high viscosity induces strong backpressures in the UF/DF systems and the filtration flow is strongly reduced, thus making the process challenging to develop.” (p. 354, col. 2, ¶ 4).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of claim 17 with the teachings of Garidel to ensure that the true protein concentration of the first and second retentates is in the range of 5 g/L to 200 g/L as claimed. First, claim 17 teaches that the proteins are isolated via ultrafiltration/diafiltration. Garidel teaches that at protein concentrations >100 mg/mL, viscosity may strongly increase (p. 354, col. 1, ¶ 4) and the increased viscosity makes UF/DF challenging (p. 354, col. 2, ¶ 4). Therefore, one of ordinary skill in the art would have been motivated to keep the protein concentration of the retentates below 100 mg/mL, and closer to the disclosed lower protein concentration of 10 mg/mL (p. 353, Abstract) in the ultrafiltration and diafiltration processes of claim 17 to maintain a viscosity that permits successful filtration processes, and for the same reasons would have had a reasonable expectation of success given the teachings of Garidel.
For these reasons, claim 1 is rendered obvious. This is a provisional nonstatutory double patenting rejection.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 34 of copending Application No. 18/001,272 (hereinafter ‘272) in view of Yap et al. (Yap, P.Y., Jain, A., and Trau, D. (2019). Quantification of Soluble Starch from Fresh Potatoes Using Photopette. Retrieved from Tip Biosystems website: https://www.tipbiosystems.com/wp-content/uploads/2023/12/ANE01-Starch-application-note_2019_v6.pdf) and Habeych Narvaez et al. (US 2022/0240538 A1).
Regarding claim 1, claim 34 of ‘272 teaches a method for separation of (a) potato proteins and insoluble fibers from (b) first salts and phenolic and/or glycoalkaloid compounds in potato fruit juice or a derivative thereof, said method comprising the steps of:
(i) providing a potato fruit juice or a derivative thereof, comprising:
potato proteins; and
one or more first salts; and
phenolic and/or glycoalkaloid compounds; and
insoluble fibers;
(ii) subjecting said potato fruit juice or the derivative thereof to a first cross-flow membrane filtration process wherein water and at least a portion of the first salts and at least a portion of the phenolic and/or glycoalkaloid compounds migrate across the membrane into a first permeate and wherein the potato proteins are retained in a first retentate, said first retentate having a true protein concentration in the range of 8 g/L to 180 g/L;
(iii) adding aqueous diafiltration liquid containing one or more salts to the first retentate obtained in step (ii) to form a diluted first retentate having a conductivity of between 1 mS/cm and 50 mS/cm and subjecting said diluted first retentate to a second cross-flow membrane filtration as diafiltration, to create a second permeate being a diafiltrate containing at least a portion of said phenolic and/or glycoalkaloid compounds and salts and a second retentate comprising potato proteins, salts and insoluble fibers.
Claim 1 differs from ‘290 claim 34 in that claim 34 does not teach that the potato fruit juice or derivative thereof has an absorbance at 600 nm in the range of 0.1 to 50. Claim 34 further does not teach that the diluted first retentate has an absorbance at 600 nm in the range of 0.01 to 50.
Regarding the absorbance at 600 nm, Yap teaches measuring potato starch/insoluble fiber using the absorbance at 600 nm of a solubilized starch-iodine complex (p. 1, col. 1, ¶¶ 3-4). Increasing absorbance at 600 nm values indicate higher starch/insoluble fiber concentrations (Table 1). The method provides a linear range at a starch concentration from 0.05-0.35 mg/mL, which corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3). One of ordinary skill in the art would have recognized that this method could also be applied to a potato fruit juice or derivative thereof to indicate the amount of starch/insoluble fiber therein.
Therefore, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of claim 34, with the teachings of Yap to provide a potato fruit juice with an absorbance at 600 nm in the range of 0.1 to 50 as claimed. One of ordinary skill in the art would have been motivated to consult Yap to determine a method to measure the amount of starch/insoluble fiber at various stages throughout the filtration/purification process, including pre-filtration, and in the retentate and permeate after filtering. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Yap demonstrates that starch/insoluble fiber can be detected by using the absorbance at 600 nm as a readout, and that starch in a concentration range of 0.05-0.35 mg/mL corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3).
Although the absorbance at 600 nm in the cited prior art differs from that of the claimed invention, one of ordinary skill in the art would have adjusted the starting PFJ during routine optimization of the method such that the amount of starch/insoluble fiber in the PFJ did not substantially interfere with the filtration process. MPEP § 2144.05(II) states where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Claim 34, via independent claim 1 of ‘272, indicates that insoluble fibers may be present in the PFJ/derivative Absent any evidence of criticality of the claimed range of 0.1 to 50 and given the breadth of such a range, it would have been obvious for one of ordinary skill in the art to have adjusted the absorbance at 600 nm during routine optimization to result in an amount of starch/insoluble fiber in the PFJ that allows successful filtration, thereby arriving at an absorbance at 600 nm within the claimed range.
Furthermore, in the same way, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to form a diluted first retentate for diafiltration having an absorbance at 600 nm of between 0.01 and 50, as claimed. Habeych teaches that diafiltration is preferably performed at a dilution rate of 1:1 to 1:10 of feed:salt solution ([0051]). This process effectively dilutes the retentate back to the starting volume and up to 10-fold less than the starting volume, which would result in an absorbance at 600 nm reflecting such dilution. For instance, a starting PFJ/derivative with an absorbance at 600 nm of 0.1 would be ultrafiltered, and then diluted for diafiltration such that the absorbance is 0.1 to 0.01, as in the instant claim 1.
For these reasons, claim 1 is rendered obvious. This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Claim Rejections – 35 U.S.C. § 103: Applicant’s arguments filed on 13 April 2026 have been fully considered, but they are not persuasive.
Applicant first argued that Habeych does not disclose or suggest the presently claimed “protein + insoluble fiber: process concept (p. 8, last ¶ - p. 10, ¶ 1). Applicant argued that Habeych is directed to processing a pretreated/relatively clean feed, not to deliberately retaining insoluble fibers as part of the desired retentate/product stream (p. 9, ¶ 1), and that Habeych teaches that the pretreatment may include solids removal that preferably results in a diafiltration feed solution with suspended solids essentially absent, as supported by Habeych’s working examples (p. 9, ¶¶ 2-3). Applicant argued that even if Habeych contains the broad statement that feeds with relatively high suspended solids may be ultrafiltered using memebranes in the 20-300 kDa MWCO range, that disclosure does not amount to teaching that insoluble fibers are to be deliberately retained together with the potato proteins as part of the retentate as in claim 1 (pp. 9-10, bridging ¶). Applicant argued that “at most, Habeych teaches that such feeds can be processed” (Id.).
Applicant’s arguments have been considered, but they are not persuasive. MPEP § 2123 states, “‘The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.’ In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)…Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).”
Referring to paragraph [0085], Habeych states:
Solids removal, in the present context, may be performed in addition to, and preferably subsequent to, another pretreatment step, as described above, but may also be performed as the only pretreatment step. Solids removal as defined here may also be performed at another point in the present method. Preferably however, solids removal is performed during the pretreatment. The pretreatment preferably comprises a step of solids removal.
In considering the entirety of Habeych, it is clear that even though Habeych teaches that solids removal is preferred ([0085]) and the examples of Habeych perform a solids removal step, Habeych also teaches that solids removal may be performed at another point in the method, and that solids removal is not required. Indeed, claim 1 of Habeych lists solids removal as an optional step. Additionally, Habeych provides guidance for ultrafiltration of a tuber processing water, such as juice which has high quantities of cell debris and has not yet undergone a solids removal step ([0077]), and that ultrafiltration is performed using the same setup as the diafiltration setup ([0078]). Therefore, Habeych teaches that ultrafiltration and subsequent diafiltration can be carried out on liquids not having undergone a solids removal step, and does not teach away from diafiltration of liquids containing insoluble fibers.
Applicant next argued that Yap does not disclose the claimed 600 nm absorbance parameter (p. 10, ¶ 2 – p. 11, ¶ 2). Applicant argued that the methods of preparing the sample prior to reading the absorbance at 600 nm of the present application and of Yap are fundamentally different, and Yap does not disclose measurement of the absorbance of PFJ or retentate streams as presently claimed, but measures a chemically generated starch-iodine complex under a different analytical protocol (Id.).
Applicant’s arguments have been considered, but they are not persuasive. Yap teaches measuring potato starch/insoluble fiber using the absorbance at 600 nm of a solubilized starch-iodine complex (p. 1, col. 1, ¶¶ 3-4). Increasing absorbance at 600 nm values indicate higher starch/insoluble fiber concentrations (Table 1). The method provides a linear range at a starch concentration from 0.05-0.35 mg/mL, which corresponds to an absorbance at 600 nm from 0.37-1.80 (Table 1, Figure 3). The method of Yap measures solubilized starch. That is, the starch prior to the solubilization step was insoluble. In this way, Yap quantifies insoluble potato material by measuring the absorbance at 600 nm. Claim 1 requires only that “the potato fruit juice or the derivative thereof has an absorbance at 600 nm in the range of 0.1 to 50.” And “a diluted first retentate having…an absorbance at 600 nm of between 0.01 and 50”. One of ordinary skill in the art would have recognized that this method could also be applied to a potato fruit juice or derivative thereof, as well as retentates and permeates in a filtration process stream, to indicate an amount of starch/insoluble fiber therein.
It is noted that while the method of Yap is not the same as the claimed method of “spectrophotometry on samples diluted in 0.05 M potassium phosphate at pH 7.0, wherein the amount of light of wavelength 600 nm passing through a liquid sample in a spectrophotometer using 10 mm light path cuvettes is measured”, both methods provide the absorbance at 600 nm of a potato fruit juice sample. In the present case, the absorbance at 600 nm of the potato fruit juice sample is a property of a specific product used in the positively recited steps of the claimed method. The means of measuring the absorbance at 600 nm is not a positively recited step of the claimed method. As such, the matter of how the absorbance at 600 nm is determined is similar to a product-by-process limitation. MPEP § 2113 states, “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process”, In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Further, “although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product”, In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir.1983). Therefore, absent evidence of criticality regarding the presently claimed means of measuring the absorbance at 600 nm, and given that Yap meets the requirements of the claimed absorbance at 600 nm, Yap clearly meets the requirements of claim 1.
Applicant next argued that Garidel does not cure the deficiencies of Habeych and Yap (p. 11, ¶ 3). Applicant argued that Garidel is directed to high-concentration monoclonal antibody formulations, and does not concern PFJ, insoluble fibers, phenolic compounds, glycoalkaloids, or the membrane processing of such streams (p. 11, ¶ 4). Applicant argued that Garidel is, at most, a very general statement that viscosity may increase at high protein concentration, and that is insufficient to render obvious the presently claimed concentration range in the very different context of PFJ/insoluble fiber process of claim 1 (Id.).
In response to applicant's argument that Garidel is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Garidel is in the same field of endeavor of protein purification by ultrafiltration/diafiltration, regardless of whether or not the filtered material comprising the protein is PFJ or contains insoluble fibers, phenolic compounds, and/or glycoalkaloids. Habeych teaches that the proteins are isolated in the native form and are isolated via ultrafiltration/diafiltration. Garidel teaches that at protein concentrations >100 mg/mL, viscosity may strongly increase (p. 354, col. 1, ¶ 4) and the increased viscosity makes UF/DF challenging (p. 354, col. 2, ¶ 4). Therefore, one of ordinary skill in the art would have been motivated to keep the protein concentration of the retentates below 100 mg/mL, and closer to the disclosed lower protein concentration of 10 mg/mL (p. 353, Abstract) in the ultrafiltration and diafiltration processes of Habeych to maintain a viscosity that permits successful filtration processes.
Applicant next argued that the present application provides positive support for non-obviousness of the claimed process concept (p. 11, last ¶ - p. 12, ¶ 4). Applicant argued that the present application does not merely define arbitrary ranges; it provides technical support showing that PFJ comprising substantial insoluble fibers can be processed successfully by UF/DF without the kind of pretreatment used in prior art systems (p. 12, ¶ 1). Applicant argued that the disclosures of Example 2 support that the presently claimed process of claim 1 is based on a specific and non-conventional process concept, not on routine optimization of prior art clarified-feed systems (p. 12, ¶¶ 2-3).
Applicant’s arguments have been considered, but they are not persuasive. Applicant is reminded that “[w]hether 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. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. See MPEP § 716.02(d).
In the present case, Applicant’s evidence in Example 2 provides support for providing a potato fruit juice with an OD 600 nm of 2.0 and a true protein concentration of 11.5 g/l, subjecting the provided PFJ to ultrafiltration to concentrate the PFJ 5x. This supports a first retentate having a true protein concentration of 57.5 g/l. The process of Example 2 further supports dilution of the first retentate 1:1 with 3 g/L sodium sulfite, conductivity = 4.1 mS/cm at 18°C, and diafiltration of the diluted first retentate, and repeating the dilution and filtration process 6 times. Example 2 does not describe an absorbance at 600 nm of between 0.01 and 50 for the diluted first retentate. At most, mathematically, the starting OD 600 of 2.0 concentrated 5x to form the first retentate results in a calculated OD 600 of 10 for the first retentate. Upon 1:1 dilution of the first retentate with sodium sulfite, the diluted first retentate would have a calculated OD 600 of 5.0. The evidence provided is not commensurate in scope with the claimed ranges recited in claim 1 of a PFJ with an absorbance at 600 nm in the range of 0.1 to 50, a first retentate with a true protein concentration in the range of 5 g/L to 200 g/L, and a diluted first retentate having a conductivity between 0.1 mS/cm and 50 mS/cm and an absorbance at 600 nm of between 0.01 and 50. The examples are not commensurate in scope with the claimed invention because it cannot be ascertained whether the alleged unexpected result occurs over the entire claimed ranges from the examples provided, and none of the claims are directed toward the specific embodiment provided by the examples.
Regarding claims 34, 35, and 46, Applicant argued that Habeych’s pH/temperature pretreatment teaching does not render obvious the presently claimed step of eliminating enzymatic activity without adversely affecting functionality of the potato proteins because Habeych’s pH/temperature pretreatment is taught in the context of fractionation/precipitation of patatin and generation of a different feed or downstream processing, and not for the purpose as claimd (p. 12, ¶ 5 – p. 13, ¶ 1). Applicant argued that the present application expressly states that the inventors surprisingly found that acidic treatment for a limited time may inactivate unwanted enzymatic activity, particularly esterase and lipolytic activity of patatins, without losing functionality of the proteins, and may improve flavor (p. 13, ¶ 2). Applicant asserted that Example 2 provides experimental support for this teaching in that Example 2 reports that at pH 3.0 and 40 °C, esterase activity was reduced with a factor of 98 after 15 minutes (p. 13, ¶ 3).
Applicant’s arguments have been considered, but they are not persuasive. While Habeych does not discuss that such treatment eliminates or reduces enzymatic activity of the potato proteins without adversely affecting functionality of the potato proteins, Habeych nonetheless discloses the claimed steps as presented in the rejections. When the method steps recited in the prior art reference are substantially identical to those of the claims, claimed properties of the resulting composition are presumed to be present in the composition of the prior art. The burden of proof shifts to the applicant to provide objective evidence (i.e., test data) to the contrary. See In re Best, 562, F.2d 1252, 1254, 195 USPQ 403, 433 (CCPA 1977). MPEP § 2112.01(I).
Indeed, pages 43-45 and Figure 6 of the instant application demonstrate that treatment of the diafiltration retentate with a pH of 3.0 or 4.0 at room temperature or 40 °C for at least 15 minutes reduces esterase activity of the proteins and that functionality is retained after increasing the pH. Where Habeych teaches conducting the steps as claimed, the properties of eliminating or reducing enzyme activity of the potato proteins without adversely affecting functionality of the potato proteins are presumed to be present.
Applicant’s assertion of surprising results is acknowledged, but it is not found to be persuasive. As provided by MPEP § 2145(II), “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979)”, and “‘[t]he fact that appellant 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.’ Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)”.
“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. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. See MPEP § 716.02(d).
In the present case, Applicant has recognized a latent property of performing the claimed method steps, and Applicant’s evidence is not commensurate in scope with the claimed invention. The examples are not commensurate in scope with the claimed invention because it cannot be ascertained whether the alleged unexpected result occurs over the entire claimed ranges from the examples provided, and none of the claims are directed toward the specific embodiment provided. As indicated by Applicant, Example 2 reports that at pH 3.0 and 40 °C, esterase activity was reduced with a factor of 98 after 15 minutes. This embodiment is much narrower than the scope of claims 34, 35, and 46.
Applicant next argued that the application provides a specific rationale for claim 46/ treatment on the second retentate: it is more preferred to expose the second retentate resulting from diafiltration step (iii) to low pH because the polyphenols have then been sufficiently removed, such that the risk of unwanted chemical reactions at acidic pH is eliminated (p. 13, ¶ 3).
Applicant’s argument has been considered, but it is not persuasive. Applicant merely states that performing the low pH step on the second retentate is preferred, but provides no evidence that it is critical.
Regarding claim 16, Applicant argued that claim 16 is non-obvious over the cited prior art because Edens also reflects the conventional clarified-feed approach, and not the presently claimed process in which insoluble fibers are retained together with potato proteins (p. 13, ¶ 6 – p. 14, ¶ 2). Applicant argued that Edens does not disclose the presently claimed endpoint defined as a target amount of phenolic and/or total glycoalkaloid compounds per kg potato protein in the second retentate as recited in claim 16, and as such does not teach or suggest all of the steps of claim 16 (p. 14, ¶ 2).
Applicant’s argument has been considered, but it is not persuasive. As stated in the rejection of claim 16, Edens teaches that continual diafiltration of the ultrafiltration retentate comprising molecules over 5 kDa reduces the glycoalkaloid amount to levels undetectable by HPLC. This process is applicable to the method of Habeych, to yield the predictable result and improved system of removing glycoalkaloid compounds without the need for an additional adsorption step to remove glycoalkaloids. That Edens uses a clarified-feed is immaterial. 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). In the present case, the teachings of Edens are applied to the method of Habeych.
For at least these reasons Applicant’s arguments are not persuasive, and the rejections of claims 1, 4, 8, 11-14, 16, 18, 27-30, 34-35, and 46 under 35 U.S.C. § 103 are maintained.
Double Patenting:
Applicant’s arguments, see pp. 17-18, bridging ¶, filed 27 March 2026, with respect to the provisional nonstatutory double patenting rejections have been fully considered and are persuasive. The provisional nonstatutory double patenting rejections of claims 1, 10, and 12-14 have been withdrawn. Applicant is reminded that any amendments to the copending applications may result in new grounds of double patenting rejection.
Applicant made no substantive arguments concerning the double patenting rejections (p. 14, ¶¶ 4-6). Applicant’s request to hold in abeyance the outstanding provisional nonstatutory double patenting rejections of the pending claims is granted. The February 2, 2026 amendment to claim 1 of 18/001,272 is insufficient to overcome the obviousness-type provisional nonstatutory double patenting rejection at this time. As such, the present double patenting rejections are maintanted.
Conclusion
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.
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/JAMES P. SHELLHAMMER/Examiner, Art Unit 1793
/EMILY M LE/Supervisory Patent Examiner, Art Unit 1793
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