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 27 March 2026 is acknowledged.
Applicant has overcome the following by virtue of amendment of the specification and the claims: (1) the objection to the abstract has been withdrawn; (2) the objections to the claims have been withdrawn; (3) the rejection under 35.U.S.C. § 112(b) has been withdrawn; (4) the provisional nonstatutory double patenting rejections have been withdrawn.
The status of the claims upon entry of the present amendment stands as follows:
Pending claims: 1-2, 4, 6, 9-10, 12-16, 21, 25, 28, 32, and 43-45
Withdrawn claims: None
Previously canceled claims: 3, 5, 7-8, 11, 17-20, 22-24, 26-27, 29-31, 33, 36-37, 40, and 42
Newly canceled claims: 34-35, 38-39, and 41
Amended claims: 1-2, 9, 12-15, 21, 25, 28, and 32
New claims: 43-45
Claims currently under consideration: 1-2, 4, 6, 9-10, 12-16, 21, 25, 28, 32, and 43-45
Currently rejected claims: 1-2, 4, 6, 9-10, 12-16, 21, 25, 28, 32, and 43-45
Allowed claims: None
Claim Objections - Warning
Applicant is advised that should claim 1 be found allowable, claim 43 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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, 10, 12-15, 21, 25, 28, 32, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Habeych Narvaez et al. (hereinafter “Habeych”) (US 2022/0240538 A1) as evidenced by Ru et al. (Ru, W., Pang,Y., Gan, Y., Liu, Q., & Bao, J. (2019). Phenolic Compounds and Antioxidant Activities of Potato Cultivars with White, Yellow, Red and Purple Flesh. Antioxidants, 8(10), 419. https://doi.org/10.3390/antiox8100419).
Regarding claims 1 and 43, Habeych teaches a method for separation of proteins from first salts and phenolic compounds in a liquid comprising said proteins dissolved in said liquid, said method comprising the steps of:
i) providing a liquid comprising proteins dissolved in said liquid, said liquid further comprising one or more first salts, phenolic compounds, and insoluble fibers – Habeych teaches a method for isolating a native tuber protein isolate ([0013] – [0020]). At least one tuber is processed to obtain an aqueous liquid (tuber processing water) comprising tuber protein ([0066]). The protein is native (i.e., soluble/dissolved), and the aqueous liquid may comprise starch ([0067]), and residual cell wall fragments ([0070]), which are forms of insoluble fiber. Starch removal is preferred, but not required ([0067]). Water obtained from tuber cutting processes is a preferred type of tuber processing water ([0069]). Salts present in the tuber processing water (i.e., first salts) are replaced by diafiltration ([0035]). As evidenced by Ru, potatoes contain free and bound phenolic compounds in the peel and flesh (p. 1, Introduction, ¶ 2 – p. 3, ¶ 2). Therefore, the tuber/potato processing water of Habeych necessarily comprises phenolic compounds.
ii) subjecting said liquid to a first cross-flow membrane diafiltration process wherein at least a portion of the first salts and at least a portion of the phenolic compounds migrate across the membrane into a first permeate and the proteins and said insoluble fibers 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]). It is noted that solids removal is not required (see claim 1, where solids removal is optional). 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]). One of ordinary skill in the art would expect that cell debris/insoluble fiber would be retained by a MWCO of 20-300 kDa. At least a portion of at least the free phenolic 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.
Habeych teaches, “The retentate from the ultrafiltration was subjected to further treatment comprising diafiltration against a salt solution having 0.33 or 50.66 [sic, 0.66] wt. % NaCl [i.e., second salt]…” ([0144]). In preferred embodiments, an ultrafiltration pretreatment is performed using the same setup as the diafiltration step (i.e., the same filter) ([0078]). Therefore, continued filtration as diafiltration would result in the claimed first cross-flow membrane diafiltration process wherein at least a portion of the first salts and at least a portion of the phenolic compounds migrate across the membrane into a first (diafiltration) permeate and the proteins and said insoluble fibers are retained in a first (diafiltration) retentate.
iii) adding water, or one or more second salts and water, to the first retentate, while continuing the membrane diafiltration process, to create a diafiltrate containing at least a portion of said phenolic compounds and the added second salts – Habeych teaches that the diafiltration retentate may be subjected to a second, third, or even further diafiltration stage ([0051]). Therefore, continued diafiltration would result in additional phenolic compounds crossing the membrane. The resulting diafiltrate would also comprise the second salts since these ions would pass through pores of the filter.
Habeych does not explicitly discuss said insoluble fibers being present in said liquid at a concentration in the range of 0.1 to 30 mg/ml based on the dry weight of the fiber.
However, Habeych does teach at least one pretreatment of the tuber processing water including concentration or dilution, and that the pretreatment is important in order to prevent clogging of filters and membranes ([0070]). Therefore, the amount of insoluble fiber is a result effective variable; too much insoluble fiber would result in clogging of filters and membranes, and Habeych teaches dilution of the starting material as necessary as a means to avoid this problem. Additionally, too dilute of a tuber processing water would require extra processing time, so it would be advantageous to concentrate the tuber processing water to a concentration of solids, including insoluble fibers, that allows faster processing, yet avoids clogging filters and membranes.
As such, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention to determine the optimal concentration for the insoluble fibers present in the process of Habeych, through routine experimentation, to avoid clogging the filters and membranes used in the process, including a concentration of 0.1 to 30 mg/ml as claimed. Absent any evidence of criticality of the claimed range, this limitation is rendered obvious.
Claim 1 is therefore rendered obvious.
Regarding claim 10, Habeych teaches the method according to claim 1.
Habeych also teaches that the method further comprises the step of adjusting the pH of said liquid to a pH in the range of pH 4.8 to pH 10 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 of pH 4.8-10 overlaps the disclosed range of pH 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).
and wherein when a calcium and/or magnesium salt is added to the retentate prior or during the diafiltration step iii, the pH of the retentate remains within the range of pH 2 to pH 4.5 – Habeych teaches that the salt solution (i.e., diafiltration solution) may be CaCl2 ([0046]), and that the pH of the diafiltration feed solution is preferably lower than 4.0 ([0044]). Habeych teaches that the pH remains the same throughout all diafiltration stages ([0054]). The claimed range of pH 2-4.5 overlaps the disclosed range of lower than 4.0. 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).
It is noted that the claim language, “wherein when a calcium and/or magnesium salt is added to the retentate prior or during the diafiltration step iii, the pH of the retentate remains within the range of pH 2 to pH 4.5” does not positively recite an active method step, and is not necessarily limiting. The clause, “the pH of the retentate remains within a range of pH 2 to pH 4.5” is an observation of the effect of adding a calcium and/or magnesium salt to the retentate prior to or during the diafiltration step iii, which is not a required step of the method as claimed. This clause is therefore regarded as optional.
Therefore, claim 10 is rendered obvious.
Regarding claim 12, Habeych teaches the method according to claim 1.
Habeych also teaches that the method further comprises the step of adjusting the conductivity of said liquid to a conductivity in the range of 2-500 mS/cm – “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 teaches the method according to claim 1.
Habeych also teaches that the proteins are proteins from plants – “native tuber protein” ([0013]).
or wherein the proteins are selected from the group consisting of protease inhibitors, lipoxygenase, polyphenol oxidase, acid and alkaline phosphatase, or mixtures thereof – “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 teaches the method according to claim 1.
Habeych also teaches that the liquid 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 15, Habeych teaches the method according to claim 1.
Habeych also teaches that said proteins, first salts and said phenolic compounds are in solution in said liquid, and wherein the liquid is water – As mentioned above, Habeych discloses tuber processing water, for example potato fruit juice as obtained after starch isolation ([0067]), was used as raw material for production of a total native protein isolate ([0137]). Salts present in the tuber processing water are replaced by diafiltration ([0035]). Habeych is silent regarding phenolic compounds. However, Ru evidences potatoes contain free and bound phenolic compounds in the peel and flesh (p. 1, Introduction, ¶ 2 – p. 3, ¶ 2). Therefore, the tuber/potato processing water of Habeych necessarily comprises phenolic compounds. The claimed components are in solution as claimed, particularly since the proteins are isolated in native form ([0032]).
Therefore, claim 15 is rendered obvious.
Regarding claim 21, Habeych teaches the method according to claim 1.
Habeych also teaches that the one or more second salts and water added to the first retentate is an aqueous solution of said second salt(s) in said water – “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., second salt]” ([0144]). The salt solution, with no indication of any substantial proportion of non-water liquid components, would be an aqueous solution.
wherein the one or more second salts are selected from sodium, potassium, ammonium, calcium or magnesium salts of a mineral acid or an organic acid – (NH4)2HCO3 ([0049]).
or wherein the one or more second salts are selected from salts of monovalent inorganic anions and cations – NaCl, KCl ([0046]).
Therefore, claim 21 is rendered obvious.
Regarding claim 25, Habeych teaches the method according to claim 1.
Habeych also teaches that the conductivity of the first retentate remains within the range of 1 to 50 mS/cm during step ii and step iii – “It has been found that for any solution comprising a native protein isolate as herein defined, 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]).
wherein the pH of the first retentate remains within the range of pH 2 to pH 10 during step ii and step iii – the pH of the diafiltration feed solution is preferably 5.5-7.0 ([0044]). “Preferably, the conductivity of the solution to be diafiltered (the diafiltration feed solution or feed) remains within the ranges herein specified. Preferably in this embodiment, the pH remains the same throughout all diafiltration stages.” (0054]). “In further preferred embodiments, the salt solution may have a pH of… 5.5-8.0…In preferred embodiments, this pH is maintained throughout the diafiltration.” ([0050]). Since the pH of both the diafiltration feed solution and the salt solution are within the claimed range throughout the diafiltration process, the pH of the first retentate would also be within the claimed range.
and wherein the first retentate remains with a temperature in the range of 1 to 60 °C during step ii and step iii – “…the method is performed so as to keep the temperature of the tuber processing water below 40° C during the pretreatment, the diafiltration and any other step prior to drying.” ([0103]). The disclosed range of below 40 °C overlaps with the claimed range of 1-60 °C. 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 25 is rendered obvious.
Regarding claim 28, Habeych teaches the method according to claim 1
Habeych also teaches that step iii comprises adding one or more second salts and water to the first retentate, while continuing the membrane filtration process, to create a diafiltrate containing at least a portion of said phenolic compounds and the added second salts – “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., second salt]…” ([0144]). In preferred embodiments, an ultrafiltration pretreatment is performed using the same setup as the diafiltration step (i.e., the same filter) ([0078]). Therefore, continued filtration would result in additional phenolic compounds crossing the membrane. The resulting diafiltrate would also comprise the second salts since these ions would pass through pores of the filter.
wherein the addition of the one or more second salts and water in step iii is performed substantially continuously and at substantially the same flow rate as the first permeate migrates through the membrane continuously – “In preferred embodiments, the diafiltration is performed as a continuous (cross-flow) process. Operation flux can for example be between 3 and 300 l/(h m2).” ([0038]).
Habeych is silent as to the one or more second salts and water being added at substantially the same flow rate as the diafiltrate migrates through the membrane.
However, logic dictates that since the process is disclosed as being continuous, one of ordinary skill in the art would have found it obvious to add the diafiltration solution at substantially the same flow rate as the diafiltrate migrates across the membrane to maintain the continuity of the process and flux rate.
and wherein the addition of the one or more second salts and water in step iii is performed in portions – Habeych teaches that the diafiltration retentate (i.e., first retentate) may be subjected to a second, third, or even further diafiltration stage ([0051]), indicating stages of adding “portions” of the one or more second salts and water.
and wherein the total volume of water added during the diafiltration step iii is in the range of 4 to 20 times the volume of the first retentate – “Diafiltration is preferably performed at dilution rate of 5:1 to 1:10, preferably, 1:1 to 1:10 (feed:salt solution)...” ([0051]). The claimed range of 1:4 to 1:20 overlaps the disclosed range of 1:1 to 1:10. 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).
Claim 28 is therefore rendered obvious.
Regarding claim 32, Habeych teaches the method according to claim 1.
Habeych also teaches that step iii comprises a second phase of diafiltration following the addition of one or more salts and water wherein the diafiltration is continued with the addition of water without adding any further salts and wherein, step iii is continued with water and without the addition of further salts until the conductivity of the retentate is less than 10 mS/cm – “The DF retentate may be subjected to a second, third or even further DF stage.” ([0051]). “In preferred embodiments, diafiltration is performed against a salt solution throughout all diafiltration stages. In a further preferred embodiment, in particular in cases where the salt solution was applied at relatively high conductivity within the ranges herein specified, the diafiltration against a salt solution can be followed by 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]). The disclosed “essentially free of salt” is considered to lie inside the claimed conductivity range of the retentate of less than 10 mS/cm.
Therefore, claim 32 is rendered obvious.
Regarding claim 44, Habeych teaches the method according to claim 1.
Habeych also teaches microfiltration as a pretreatment ([0087]). Habeych teaches that microfiltration is preferably performed over membranes having a pore size of 0.1 to 10 µm (Id.).
Given that both the instant application and Habeych are toward recovering protein from protein-containing solutions, it would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to remove the vast majority of the insoluble fiber to obtain a relatively pure protein product. One of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention because following a microfiltration step as disclosed by Habeych using a membrane with a pore size of e.g., 10 µm would result in all of the insoluble fibers retained in the diafiltration retentate being small enough to pass through a 50 µm filter.
Claim 44 is therefore rendered obvious.
Claims 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Habeych Navarez et al. as applied to claim 1 above, and further in view of Mortensen (WO 2019/057257 A1, cited on the IDS filed on 4 December 2023).
Regarding claims 2 and 4, Habeych teaches the method according to claim 1.
Habeych does not teach that the method further comprises a germicidal step applied directly to the liquid comprising proteins, or applied during and/or in between the membrane processing steps, or wherein the germicidal step is applied to the liquid of step i and/or the first retentate of step ii (re: claim 2) and wherein the germicidal step comprises the exposure of the liquid and/or first retentate to high intensity UV light, and wherein the germicidal step comprises passing of the liquid comprising proteins through a photo bioreactor illuminating high intensity UV light to said liquid (re: claim 4).
However, Mortensen teaches a photo bioreactor, which enables a germicidal treatment of liquids utilizing UV-C (i.e., high intensity UV) light and is capable of germicidal treatment of highly opaque liquids (p. 1, lines 1-5). Mortensen teaches that the photo bioreactor utilizes light filters to prevent higher light wavelengths from contacting the liquid, avoiding photo oxidation of components, which would enhance bitter and bad flavor in the food product, and heating of the liquid (p. 2, lines 16- 22). The photo bioreactor is used for cold pasteurization of liquid food products (p. 3, lines 13-15). The photo bioreactor comprises one or more spiral-shaped tubes extending from an inlet end to an outlet end (p. 5, lines 29-32), and as such is suitable for in-line integration to a process stream.
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 to add a germicidal step comprising passing the tuber processing water or the first retentate from the first cross-flow membrane filtration step through a photo bioreactor illuminating high intensity UV light, as disclosed by Mortensen, to ensure that the potato protein is food-safe while maintaining the native properties of the proteins. First, Habeych teaches the isolation of native potato proteins ([0006]) for use in human food applications ([0002]), and that it is much preferred that the temperature is kept below 40°C in steps prior to drying to prevent denaturation ([0103]). Since the potato protein isolate is intended for human consumption, and Habeych is silent regarding germicidal treatment for food safety, one of ordinary skill in the art would have been motivated to consult Mortensen to find methods for germicidal treatment of food products that maintain the native properties of said food products. One of ordinary skill in the art would have had a reasonable expectation of success for doing so because Mortensen teaches a photo bioreactor that is used for cold pasteurization of liquid food products (p. 3, lines 13-15), which utilizes light filters to prevent higher light wavelengths from contacting the liquid, avoiding photo oxidation of components, which would enhance bitter and bad flavor in the food product, and heating of the liquid (p. 2, lines 16- 22). The photo bioreactor comprises one or more spiral-shaped tubes extending from an inlet end to an outlet end (p. 5, lines 29-32), and as such is suitable for in-line integration to a process stream, such as before or after a cross-flow membrane filtration step.
Therefore, claims 2 and 4 are rendered obvious.
Claims 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Habeych Navarez et al. as applied to claim 1 above, and further in view of Bell et al. (US 2017/0304774 A1) and Liderfelt et al. (Liderfelt, J. and Royce, J. (2018). Chapter 23 – Filtration Methods for Use in Purification Processes (Concentration and Buffer Exchange). In G. Jagschies, E. Lindskog, K. Lacki, and P. Galliher (Eds.), Biopharmaceutical Processing (pp. 441-453) Elsevier. https://doi.org/10.1016/B978-0-08-100623-8.00023-2).
Regarding claim 6, Habeych teaches the method according to claim 1.
Habeych does not teach that the method further comprises the step of: subjecting the first permeate and/or the diafiltrate from said first cross-flow membrane filtration process to a second cross-flow membrane filtration process, whereby at least a portion of the salts present in the first permeate and/or the diafiltrate migrate across the membrane into a second permeate and the phenolic compounds are retained in a second retentate.
Habeych does not specifically teach that the method further comprises the step of: subjecting the first retentate to a microfiltration membrane filtration process, whereby at least a portion of the proteins soluble in said first retentate migrate across the membrane into a microfiltration permeate with a lower turbidity than the turbidity of said first retentate, wherein the microfiltration permeate is further treated with a third cross-flow membrane filtration process whereby the protein is concentrated in a third retentate and the salts migrate through the membrane to create a third permeate and wherein the third permeate is used as a diafiltration liquid to be added during the microfiltration process to wash out further proteins from the first retentate into the microfiltration permeate.
Regarding the second cross-flow membrane process, Bell teaches a method for separating useable by-products from process water from processing potatoes ([0002]). The process involves a pretreatment to remove unwanted solids, a first cross-flow filtration step to remove starch ([0011]), and a second cross-flow filtration step comprising filtration membranes having increased rejection characteristics or smaller pore sizes, such as ultrafiltration, nanofiltration, or reverse osmosis membranes, than the first filtration unit to provide an essentially clear water permeate stream ([0012]). By-products isolated include polyphenols, glycoalkaloids, and nutritional products ([0012]).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to remove the glycoalkaloids from the permeate and/or diafiltrate from the first cross-flow membrane filtration by a second cross-flow membrane filtration as described by Bell by applying a known technique to a known method. See MPEP § 2143(I)(D). First, Habeych teaches that the ultrafiltration and diafiltration permeate is separately processed by a step of concentration, in particular to obtain tuber free amino acids ([0094]). As established regarding claim 1, the ultrafiltration and diafiltration permeate also comprises phenolic compounds. Bell teaches that by-products, including polyphenols and nutritional products (i.e., amino acids), can be removed from potato process water by filtration, such as nanofiltration, resulting in an essentially clear water permeate ([0012]). Since Habeych teaches that the permeate is treated by filtration ([0094]), and Bell teaches that cross-flow filtration processes such as ultrafiltration, nanofiltration, and reverse osmosis can be applied to process water to extract useful by-products, such as polyphenols and nutritional products ([0012]), the teachings of Bell are applicable to the method of Habeych. Therefore, one of ordinary skill in the art would have recognized that applying the technique of Bell would have yielded the predictable result of reducing the amount of phenolic compounds in the permeate. One of ordinary skill in the art would have recognized that the pore size of the filtration unit could be selected such that at least a portion of the salts migrate across the membrane into a second permeate and the phenolic compounds are retained in a second retentate.
Regarding the microfiltration process, Habeych teaches microfiltration as a preferred way to remove solids in pre-treatment of the potato fruit juice ([0087]) and that solids removal may also be performed at another point in the method ([0085]). Habeych further discloses that “…the main protein fractions in…potato protein, are oppositely charged at many pH values. Patatin has a pI of 4.8-5.2, whereas protease inhibitor has a pI of from 5.8 up to 9. Even pH values optimized for solubility cannot prevent aggregation, precipitation and clogging, in particular during diafiltration. It has been found that the conductivity of a solution has great influence on protein solubility, and that low solubility can be offset by increasing conductivity. This is important in particular during diafiltration.” ([0039]). The preferred protein isolate is a tuber protein isolate comprising native protease inhibitor and native patatin with or without any other native tuber proteins ([0030]-[0032]).
It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to add a step of microfiltration of the first retentate after ultrafiltration and diafiltration to retain any aggregated proteins and allow soluble potato proteins to migrate into the microfiltration permeate, thereby reducing the turbidity. First, Habeych teaches that the preferred protein isolate comprises native potato proteins ([0030]-[0032]), and that the pI of proteins of interest (e.g., patatin and protease inhibitors) differs such that aggregation cannot be prevented ([0039]). While maintaining high conductivity through diafiltration helps offset low protein solubility ([0039]), it is reasonably expected that not all of the protein remains completely soluble. Since Habeych also discloses microfiltration as a preferred means of solids removal ([0087]), and that microfiltration steps can be employed throughout the method ([0085]), one of ordinary skill in the art would have been motivated to remove aggregated protein from the first retentate via microfiltration to allow native proteins to selectively pass into the permeate and, for the same reasons, would have been met with a reasonable expectation of success for doing so.
It would have been obvious for one of ordinary skill in the art to implement a subsequent (third) cross-flow ultrafiltration step to concentrate the native protein permeate from the microfiltration step such that the native proteins are retained and the salts pass through. To arrive at the claimed invention, one of ordinary skill in the art would have simply applied known filtration techniques as taught by Habeych regarding a series of filtration steps as disclosed in Example 3 ([0143]-[0144]), and also regarding concentrating permeates as disclosed in paragraph [0094], to the microfiltration permeate. Since these techniques were both known and applicable, one of ordinary skill in the art would have recognized that applying the techniques would have yielded predictable results and resulted in an improved system wherein the purity of native proteins in the protein isolate is increased. See MPEP § 2143(I)(D).
Regarding using the third permeate as a diafiltration liquid to be added during the microfiltration process, Liderfelt teaches methods of ultrafiltration and diafiltration, including continuous-membrane filtration with partial recycling of the retentate (p. 448, Fig. 23.9, annotated below), wherein the permeate is used, at least in part, as the source of a wash solution.
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It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to improve the method of Habeych by applying continuous-membrane filtration as taught by Liderfelt, such that the third permeate is used as a diafiltration liquid to be added during the microfiltration process to wash out further potato proteins from the first retentate into the microfiltration permeate. See MPEP § 2143(I)(D). First, Habeych teaches the base method of a microfiltration process and subjecting the microfiltration permeate to a third cross-flow membrane filtration process. Liderfelt teaches that recirculating the permeate from the second stage aids in washing out all product and minimizing buffer volume (Fig. 23.9, legend), which is an applicable feature and an improvement over the method of Habeych. Therefore, one of ordinary skill in the art would have recognized that applying the technique of Liderfelt would have yielded the predictable result and improvement of washing out all product and minimizing buffer volume.
Therefore, claim 6 is rendered obvious.
Regarding claim 9, Habeych, Bell, and Liderfelt teach the method according to claim 6.
Habeych and Bell do not teach that the second permeate is used, at least in part, as the source of said water, or one or more second salts and water in claim 1, step iii.
However, Liderfelt teaches methods of ultrafiltration and diafiltration, including continuous-membrane filtration with partial recycling of the retentate (p. 448, Fig. 23.9, annotated below), wherein the permeate is used, at least in part, as the source of a wash solution.
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It would have been obvious for one of ordinary skill in the art, before the effective filing date of the claimed invention, to improve the method of Habeych as modified by Bell and Lederfelt as described regarding claim 6 by applying continuous-membrane filtration as taught by Liderfelt, such that the second permeate is used, at least in part, as the source of said one or more second salts and water in claim 1, step (iii). See MPEP § 2143(I)(D). First, Habeych teaches the base method of a first cross-flow membrane filtration/diafiltration process and subjecting the first permeate to a second cross-flow membrane filtration process as described regarding claim 6. Liderfelt teaches that recirculating the second permeate aids in washing out all product and minimizing buffer volume (Fig. 23.9, legend), which is seen as an applicable feature and an improvement over the method of Habeych. Therefore, one of ordinary skill in the art would have recognized that applying the technique of Liderfelt would have yielded the predictable result and improvement of washing out all product and minimizing buffer volume. Therefore, claim 9 is rendered obvious.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Habeych Navarez et al. and as evidenced by Ru et al. as applied to claim 1 above, and further in view of Xu et al. (Xu, L., & Diosady, L. L. (2002). Removal of phenolic compounds in the production of high-quality canola protein isolates. Food Res Int, 35(1), 23-30. https://doi.org/10.1016/S0963-9969(00)00159-9).
Regarding claim 16, Habeych teaches the method according to claim 1.
Habeych does not specifically teach that the method further comprises the step of continuing the addition of said one or more second salts and water to the first retentate while continuing the membrane filtration process until the first retentate contains less than a target amount of the phenolic compounds, whereby the separation of the proteins from phenolic compounds has been achieved, wherein the target amount of remaining phenolic compounds in the first retentate corresponds to less than 5000 mg phenolic compounds per kg protein on the basis of dry weight and wherein the amount of phenolic compounds having a molecular weight below 10 kD remaining in the first retentate is less than 1500 mg/kg.
However, Habeych teaches that diafiltration is performed as a continuous (cross-flow) process ([0038]), and that the diafiltration retentate may be subjected to a second, third, or even further diafiltration stage ([0051]). The diafiltration conditions provided by Habeych result in a diafiltration retentate comprising clean native tuber protein, with only very small amounts of small molecules, sulfite, and metals ([0052]). For instance, Habeych teaches that the diafiltration retentate comprises at most 200 mg/kg glycoalkaloids. As evidenced by Ru, potatoes contain free and bound phenolic compounds in the peel and flesh (p. 1, Introduction, ¶ 2 – p. 3, ¶ 2). Therefore, the tuber/potato processing water of Habeych necessarily comprises phenolic compounds, and this would have been recognized by one of ordinary skill in the art.
Additionally, Xu teaches that phenolic compounds are known to cause discoloration and off-flavors, such as an unpleasant bitter taste, in vegetable protein products (p. 23, cols. 1-2, transitional ¶). As such, phenolic compounds are considered to be undesirable in plant protein isolates.
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 Habeych in view of the teachings of Xu to continue the diafiltration of the first retentate until the first retentate contains an amount of phenolic compounds approaching zero, including less than 5000 mg/kg protein, and including an amount of phenolic compounds having a molecular weight below 10 kD remaining in the first retentate less than 1500 mg/kg as claimed. One of ordinary skill in the art would have been motivated to do so in order to provide a diafiltration retentate comprising clean native tuber protein, as is the goal of Habeych ([0052]), such that the isolated protein product does not have an undesirable color or taste. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Habeych teaches that very low amounts of small molecule contaminants can be achieved by the disclosed diafiltration conditions ([0052]). Furthermore, Habeych discloses that ultrafiltration/diafiltration is carried out using a membrane with a molecular weight cut-off size of 5-300 kDa, preferably 30-200 kDa ([0078]). Phenolic compounds with a molecular weight below 10 kDa would easily pass through membranes of the preferred size range.
Therefore, claim 16 is rendered obvious.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Habeych Narvaez et al. as applied to claim 1 above, and further in view of Plank et al. (US 2016/0146770 A).
Regarding claim 45, Habeych teaches the method according to claim 1.
Habeych does not discuss that the insoluble fibers are present in the first retentate in a concentration that results in a pellet when the protein product is dissolved/suspended in 0.05 M sodium phosphate pH 6.5 and centrifuged in a tabletop centrifuge at 4000 G for 30 min.
However, Plank teaches:
The amount of dietary fiber in a sample can be quantified by dissoluting the sample to produce a dietary fiber solution and then centrifuging the dietary fiber solution to produce a pellet and a supernatant liquid. After separating the supernatant liquid from the pellet, the pellet can be analyzed to determine a content of non-dietary fiber components in the pellet. The dietary fiber content in the pellet can be determined from the content of the non-dietary fiber components in the pellet. By using centrifugation to help isolate the dietary fiber in the sample, fiber loss may be minimized, leading to a more accurate determination of the content of dietary fiber in the sample. (see Abstract)
It is noted that the instant claim 45 does not recite an active method step to be performed. Where Habeych teaches the method of claim 1, and where Plank teaches centrifuging a solution comprising dietary fiber and determining the amount of dietary fiber in the pellet, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the insoluble fibers present in the first retentate would result in a pellet when the protein product is dissolved/suspended and centrifuged.
Claim 45 is therefore rendered obvious.
Response to Arguments
Claim Rejections – 35 U.S.C. § 103: Applicant’s arguments filed on 27 March 2026 have been fully considered, but they are not persuasive.
Applicant first argued that Habeych fails to disclose, teach, or suggest presently claimed step ii) of the method of claim 1, particularly subjecting the liquid of step i) to a first cross-flow membrane filtration process wherein the proteins and insoluble fibers are retained in a first retentate (p. 13, ¶ 3). Applicant argued that Habeych teaches away from performing cross-flow membrane diafiltration on a liquid containing insoluble fibers (p. 16, ¶ 4). In support of these arguments, Applicant asserted that Habeych describes that starch is removed from the aqueous liquid (p. 13, ¶ 5-6) and that Habeych teaches that cell wall fragments are by-products to be removed in solids removal prior to the claimed filtration steps to prevent membrane clogging (p. 13, ¶ 7 – p.18, ¶ 2). Applicant asserted that Habeych highlights the requirement that solids removal is essential, and performs a pretreatment step of solids removal in all examples (p. 14, ¶ 3 – p. 16, ¶ 2).
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 diafiltraton 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 further argued that the Examiner selectively picks discrete sections of text from the cited references while ignoring the overall teaching of the document (p. 16, ¶ 5 – p. 17, ¶ 2).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
As discussed above, in considering the entirety of Habeych, the step of solids removal is not required, and Habeych provides guidance for ultrafiltration and subsequent diafiltration of a tuber processing water, such as juice which has high quantities of cell debris and has not yet undergone a solids removal step. Therefore, the teachings of Habeych render the limitations of claim 1 obvious.
For at least these reasons Applicant’s arguments are not persuasive. Claims 1-2, 4, 6, 9-10, 12-16, 21, 25, 28, 32, and 43-45 are rejected under 35 U.S.C. § 103.
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.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JAMES P. SHELLHAMMER/Examiner, Art Unit 1793
/EMILY M LE/Supervisory Patent Examiner, Art Unit 1793
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