DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed October 27, 2025, has been received and entered.
Claims 1-17 and 23 are cancelled.
Claims 18-22 and 24-37 are pending. Claims 32-34 are withdrawn.
Claims 18-22, 24-31, and 35-37 are examined on the merits.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was ma
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 18-22, 24-31, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Nath (Desalination and Water Treatment. 2015. 54: 481-501) in view of Pearce (US 5,455,331. Listed on IDS filed 6/3/22), Dumetz (Biochimica et Biophysica Acta. 2008. 1784: 600-610), McPherson (Acta Crystallogr. F. Struct. Biol. Commun. 2014. 70(Pt 1): 2-20), and Wu (WO 01/05243. Listed on IDS filed 6/3/22).
Nath discloses separation of individual valuable biomolecules, including beta-lactoglobulin and alpha-lactalbumin, from whey using a series of different MWCO cross-flow ultrafiltration (UF) membranes (page 482, right column, last paragraph; Table 1 on page 483). The process of ultrafiltration was conducted in four-stage diafiltration (DD) mode (abstract; page 489, left column, second paragraph; page 496, left column). Their method exploited the exclusive property of beta-lactoglobulin of dimerization at pH 5.4 in order to obtain a reasonable separation between alpha-lactalbumin and beta-lactoglobulin (page 483, first paragraph). See Figure 2 on page 488, which shows separation using the second-to-last UF membrane of the series, a 5 kg-mol-1 UF membrane, in order to separate lactose as the permeate and obtain a retentate comprising beta-lactoglobulin and alpha-lactalbumin (page 487, left column, last paragraph). A portion of that retentate was treated with NaOH to make its pH of 5.3-5.55 (page 487, left column, last paragraph), such as pH 5.4 as shown in Figure 2. The product adjusted to a pH of 5.4 (Figure 2) meets limitations of step a) of instant claim 18 since it is directed to a ‘whey protein solution’ comprising beta-lactoglobulin (BLG) and alpha-lactalbumin (ALA), said whey protein solution having a pH of 5.4 which falls within the claimed pH range of 5-6. Thus Nath meets limitations of step a) of instant claim 18.
Nath teaches that the retentate of pH 5.4 is subjected to 30 kg mol-1 UF membrane separation, which is the final ultrafiltration step (page 487, right column, first paragraph; Figure 2). The retentate obtained from that final separation step comprises beta-lactoglobulin of a high purity, while alpha-lactalbumin is passed as the permeate from that separation (page 496, left and right columns; page 497, left column; Figure 10 on page 497). This meets limitations of step c) of instant claim 18 since the final ultrafiltration step it is directed to separating BLG (as separated into the retentate) from the mother liquor, and recovering at least some of the mother liquor (the permeate obtained from the 30 kg mol-1 UF membrane separation, which comprises ALA). The permeate obtained in the final step of Nath meets the limitation of step d) of instant claim 18 of providing a first composition derived from the recovered mother liquor.
Nath differs from the claimed invention in that Nath does not expressly disclose:
the product comprising BLG and ALA having a pH of 5.4 that is fed to the final UF membrane (directed to the claimed ‘whey protein solution’ of step a) of instant claim 18) comprises the BLG in non-aggregated form, is supersaturated with respect to BLG, and comprises at least 5% (w/w) ALA relative to a total amount of protein;
step b) of instant claim 18 of crystallizing non-aggregated BLG in the supersaturated whey protein solution (the product comprising BLG and ALA having a pH of 5.4 of Nath) in salting-in mode, thereby obtaining BLG crystals and mother liquor, so that the BLG separated from the mother liquor (the final ultrafiltration step of Nath) is in the form of BLG crystals; and
step f) of instant claim 18 of drying the first composition derived from the recovered mother liquor (the permeate obtained in the final ultrafiltration step of Nath) or a pH-adjusted first composition (obtained by adjusting the final permeate to pH 2.5-4.9 or pH 6.1-8.5), and that their method is for preparing an edible, alpha-lactalbumin-enriched whey protein composition.
Regarding differences (a) and (b) (Nath does not teach that in their ‘whey protein solution,’ the BLG is in non-aggregated form, BLG is supersaturated, and comprises at least 5% (w/w) ALA relative to a total amount of protein; Nath does not teach step b) of instant claim 18):
Pearce discloses a process for the manufacture of enriched alpha-lactalbumin and enriched beta-lactoglobulin fractions comprising a step (a) of treating the whey to achieve a reduction in the specific gravity and ionic strength of the whey to levels which should not be less than 25% of their original value (column 1, lines 52-56; column 2, lines 1-5). The preferred method of reducing specific gravity and ionic strength of the whey or concentrated whey is by diafiltration using a batchwise or continuous procedure (column 2, lines 40-42). Then the process comprises a step (b) of adjusting the pH of the whey to a value in the range of 3.80 to 5.50 (column 2, lines 6-9). Thereafter, the process comprises heating the pH-adjusted whey and maintaining that elevated temperature to permit aggregation of a portion of the protein content of the whey (step (c)), cooling the whey and maintaining at the cooler temperature to permit flocculation of the aggregated protein (step (d)), separating the aggregated protein containing alpha-lactalbumin from the mother liquor (step (e)), and if desired, recovering beta-lactoglobulin from the mother liquor (step (f)) (column 2, lines 10-25). The beta-lactoglobulin is present in a recovered, clarified phase, i.e. beta-fraction, (column 2, line 67 through column 3, line 2).
Dumetz investigated the phase behavior of beta-lactoglobulin A and B by preparing samples at constant salt concentration with increasing concentration, or at constant protein concentration with increasing salt concentration (abstract and paragraph bridging pages 603 and 604). At low salt concentration, beta-lactoglobulin B crystallized around its isoelectric point, which is pH 5.2 (page 605, last paragraph). This is disclosed as “salting-in behavior” (page 605, last paragraph).
McPherson provides a review of protein crystallization (page 2, first paragraph). McPherson states, “Crystallization of a macromolecule absolutely requires the creation of a supersaturated state” (page 6, right column, last paragraph). In order to promote supersaturation, matters are altered so that the solubility of the protein in a sample is significantly reduced, thereby rendering the solution supersaturated (page 7, paragraph bridging left and right columns). This may be performed through several approaches, including altering the protein itself or altering the degree of attraction of one protein molecule for another, which both can be accomplished by a change of pH (page 7, right column, first paragraph). Also, methods for creating supersaturation are listed in Table 1 on page 7, which include the approach of removing salt (decreasing ionic strength), salting in.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art that as the product adjusted to pH 5.4 fed to the last UF membrane in Nath (directed to the claimed ‘whey protein solution’) undergoes ultrafiltration, its resulting retentate is supersaturated with respect to BLG, which is non-aggregated, such that BLG crystals subsequently form in the retentate. One of ordinary skill in the art would have expected supersaturation of BLG, which is non-aggregated, and subsequent BLG crystal formation because the ultrafiltration of Nath, which involves diafiltration, would have been expected to decrease the ionic strength of the whey and provide the BLG in non-aggregated form (based on the teachings in Pearce, in particular, column 2, lines 40-42 and column 2, line 66 through column 3, line 2), thereby resulting in a low salt concentration at the BLG’s isoelectric point (pH 5.4) that is recognized as yielding BLG crystals (based on the teachings in Dumetz). As the product comprising BLG is at pH 5.4 in Nath, then there would have been a reasonable expectation of obtaining supersaturation of BLG followed by BLG crystal formation because a pH change is known in the art as an approach for obtaining supersaturation of a protein (based on the teachings in McPherson) and BLG was found to form crystals at a similar pH near the isoelectric point (as taught in Dumetz). Also, the skilled artisan would have expected supersaturation of BLG followed by BLG crystal formation because it is known in the art that supersaturation must occur for crystallization of a macromolecule, e.g. protein, and because decrease in ionic strength, also known as “salting in,” is a recognized technique for creating supersaturation of a protein (based on the teachings of McPherson).
Additionally, since the method of Nath includes multiple prior steps of separating other proteins from the whey before the final ultrafiltration step such that the proteins of interest are limited to BLG and ALA (does not necessarily mean that other proteins are not present), then it would have been obvious that the retentate of the final ultrafiltration step, up to the point of supersaturation of BLG and before BLG crystallization (directed to the claimed ‘whey protein solution’), comprises a weight percent of ALA relative to the total amount of protein (primarily ALA + BLG) that falls within the broad claimed weight percent range of ‘at least 5% (w/w) ALA relative to a total amount of protein.’ The lower limit of 5% (w/w) ALA of instant claim 18 is so low that it would have been obvious that the retentate comprising supersaturated BLG, up to the point of BLG supersaturation and before BLG crystallization, comprises ALA that is at or above that lower limit. Therefore, Nath in view of Pearce, Dumetz, and McPherson renders obvious steps a) and b) of instant claim 18.
Since Nath in view of Pearce, Dumetz, and McPherson renders obvious BLG crystals developed in the retentate obtained of the final ultrafiltration step, then the final ultrafiltration step is directed to separating the BLG crystals from the mother liquor, and recovering at least some of the mother liquor (the permeate of the final ultrafiltration step, comprising ALA). The permeate comprising ALA obtained from the final ultrafiltration step is directed to ‘a first composition derived from the recovered mother liquor.’ Therefore, the process rendered obvious by the references also meets step d) of instant claim 18.
Regarding difference (c) (Nath does not disclose step f) of instant claim 18 of drying the first composition derived from the recovered mother liquor (the permeate obtained in the final ultrafiltration step of Nath) or a pH-adjusted first composition (obtained by adjusting the final permeate to pH 2.5-4.9 or pH 6.1-8.5), and that their method is for preparing an edible, alpha-lactalbumin-enriched whey protein composition):
Wu discloses that whey proteins have been used in infant formula and as a protein source in nutritional mixtures for humans and animals (page 1, lines 25-26). The whey protein beta-lactoglobulin is not a protein found in human breast-milk, so it acts as an allergen to infants (page 1, lines 26-27). Therefore, it is desirable for whey proteins to have a relatively high concentration of the whey protein alpha-lactalbumin to make it more similar to human milk (page 1, lines 27-30). As such, the art teaches methods of preparing alpha-lactalbumin enriched fractions from whey (page 2, lines 1-2), and this is a primary objective of the invention of Wu (page 2, lines 16-18), particularly achieving a high concentration of alpha-lactalbumin in a protein fraction which is convenient and economical to use (page 2, lines 24-26). Wu teaches drying their alpha-lactalbumin concentrate, wherein drying allows for easier packaging and obtaining a product that remains stable for a longer period of time than the raw concentrate in a liquid or frozen form (page 5, lines 24-25).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to dry the permeate comprising ALA obtained from the final ultrafiltration step (directed to the claimed ‘first composition derived from the recovered mother liquor’) when performing the method rendered obvious by Nath in view of Pearce, Dumetz, and McPherson. One of ordinary skill in the art would have been motivated to do this because it is desirable to dry an alpha-lactalbumin enriched fraction obtained from whey (which the permeate comprising ALA of the invention rendered obvious by Nath, Pearce, Dumetz, and McPherson is directed to) for easier packaging and for maintaining stability for a longer period of time as compared to a raw concentrate in liquid or frozen form, as indicated in Wu, for the desirable result of obtaining an alpha-lactalbumin product useful for infant formulas and nutritional mixtures for humans and animals (directed to ‘an edible, alpha-lactalbumin-enriched whey protein composition’ as recited in instant claim 18). There would have been a reasonable expectation of success because Wu teaches successfully drying an alpha-lactalbumin concentrate obtained from whey to obtain a desirable product. Thus step f) of instant claim 18 is rendered obvious.
As such, Nath in view of Pearce, Dumetz, McPherson, and Wu renders obvious instant claims 18, 26, and 37 (Nath does not disclose using toluene).
Regarding instant claims 19 and 31, Wu teaches that for obtaining an alpha-lactalbumin concentrate, it is preferred that the whey is pasteurized (page 4, lines 13-15). Pasteurization is well known to be directed to heat treatment for the purpose of killing microorganisms. Before the effective filing date of the claimed invention, it would have been obvious to pasteurize the whey when performing the method rendered obvious by Nath, Pearce, Dumetz, McPherson, and Wu because the pasteurization of whey was taught in Wu for obtaining an alpha-lactalbumin product that is a desirable whey protein product. Thus instant claims 19 and 31 (heat-treatment) are rendered obvious.
Regarding instant claim 35 (which depends from instant claim 19), the references do not expressly disclose adjusting the first composition pH of step e) of instant claim 18, and thus further do not expressly disclose performing a physical microbial reduction after that pH adjustment and prior to the drying of the alpha-lactalbumin product. However, Wu discloses that for a method in which whey is processed to obtain a protein fraction having an increased concentration of alpha-lactalbumin, lowering the pH of the alpha-lactalbumin molecule to below 4.0 causes the alpha-lactalbumin molecule to release calcium (page 3, lines 9-10 and 20-23). Once this calcium is removed, the alpha-lactalbumin can be effectively precipitated to form an alpha-lactalbumin concentrate (page 3, lines 24-25). Therefore, in Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), a pH-lowering step is performed in which the pH of the permeate is lowered to 4.0 or below, preferably between about 3.3-3.8 (page 5, lines 8-11). Once the pH of the permeate is lowered to 4.0 or below, the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin may be dried as-is, or neutralized to a pH of 6-7 (page 5, lines 19-21). Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to further include a step of lowering the pH to 4.0 or below (overlapping the claimed range of 2.5-4.9 of step e) of instant claim 18) or about 3.3-3.8 (falling within the claimed range of 2.5-4.9 of step e) of instant claim 18) before the drying step when performing the method rendered obvious by Nath in view of Pearce, Dumetz, McPherson, and Wu. One of ordinary skill in the art would have been motivated to do this because Wu teaches that this results in removing calcium from a permeate comprising alpha-lactalbumin obtained from ultrafiltration and/or diafiltration of whey, which allows the effective precipitation of alpha-lactalbumin to form a concentrate thereof for an alpha-lactalbumin enriched product with desirable applications (e.g. infant formula, protein source in nutritional mixtures). Therefore, the references additionally render obvious step e) of instant claim 18 which is an optional step. For that method rendered obvious by Nath, Pearce, Dumetz, McPherson, and Wu, it additionally would have been prima facie obvious to perform the pasteurization step (see preceding paragraph, directed to physical microbial reduction) at any instance of the process, including between the pH lowering step and the drying step, since it would have the desired effect of obtaining an alpha-lactalbumin enriched product in which whey is pasteurized. Thus instant claim 35 is rendered obvious.
Regarding instant claim 20, since the method of Nath includes multiple prior steps of separating other proteins from the whey before the final ultrafiltration step such that the proteins of interest are limited to only BLG and ALA (does not necessarily mean other proteins are not present), then it would have been obvious that the retentate obtained during the final ultrafiltration step, up to the point of supersaturation of BLG and before BLG crystallization (directed to the claimed ‘whey protein solution of step a)’), comprises a weight percent of BLG relative to the total amount of protein (mainly ALA + BLG) that falls within the broad claimed weight percent range of ‘at most 90% w/w BLG relative to a total amount of protein.’ The upper limit of 90% w/w BLG of instant claim 20 is so high that it would have been obvious that the retentate comprising supersaturated BLG comprises BLG that is at or below that upper limit. Thus instant claim 20 is rendered obvious.
Regarding instant claim 21, since there were multiple ultrafiltration steps of whey before the final ultrafiltration step in Nath, then the retentate obtained during the final ultrafiltration step up to the point of BLG supersaturation and before BLG crystallization (directed to the claimed ‘whey protein solution’) is directed to a ‘whey protein concentrate’ as claimed. That is, since the whey proteins BLG and ALA are concentrated in the retentate in question, then said retentate is a whey protein concentrate. Thus instant claim 21 is rendered obvious.
Regarding instant claim 22, the decrease in ionic strength in the final ultrafiltration step as rendered obvious by the references is directed to ‘reducing the conductivity’ given the correlation between ionic strength and conductivity of a solution. Though Nath in view of Pearce, Dumetz, McPherson, and Wu does not expressly disclose the ratio between conductivity and the total amount of protein of their retentate of the final ultrafiltration step up to the point of BLG supersaturation and before BLG crystallization (directed to the claimed ‘whey protein solution’), it would have been an obvious result that through that final ultrafiltration, the ionic strength (correlating to conductivity) is decreased over time such that at least at one instance the ratio between the conductivity (correlating to ionic strength) and the total amount of protein of the retentate falls within the claimed range of at most 0.3 mS/cm per weight percentage of total protein relative to the total weight of the retentate (directed to ‘whey protein solution’). Thus instant claim 22 is rendered obvious.
Regarding instant claim 24, the decrease in ionic strength in the final ultrafiltration step as rendered obvious by the references is directed to ‘reducing the conductivity’ given the correlation between ionic strength and conductivity of a solution. Also, the teaching in Nath of adding NaOH to obtain a pH of 5.4 meets the claimed limitation of ‘adjusting the pH.’ Thus instant claim 24 is rendered obvious.
Regarding instant claims 25 and 36, it would have been obvious to the person of ordinary skill in the art to separate the BLG crystals from any liquid of the final retentate when performing the method rendered obvious by Nath, Pearce, Dumetz, McPherson, and Wu because the BLG is a valuable biomolecule from whey having pharmaceutical importance (page 482, right column, last paragraph and Table 1 on page 483 of Nath). In doing such a separation in which liquid is removed, then it is obvious that the solids content of the BLG crystals falls within the broad ranges of ‘at least 30% w/w’ of instant claim 25 and ‘at least 40% w/w’ of instant claim 36. In removing as much liquid as possible from the BLG crystals, then the solids content is maximized to a high level. Thus instant claims 25 and 36 are rendered obvious.
Regarding instant claims 27 and 28, as discussed above, Wu discloses that whey proteins have been used in infant formula and as a protein source in nutritional mixtures for humans and animals (page 1, lines 25-26). The whey protein beta-lactoglobulin is not a protein found in human breast-milk, so it acts as an allergen to infants (page 1, lines 26-27). Therefore, it is desirable for whey proteins to have a relatively high concentration of the whey protein alpha-lactalbumin to make it more similar to human milk (page 1, lines 27-30). In Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin concentrate obtained may then be dried as-is (page 5, lines 19-21). Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to further concentrate the ALA in the ALA-containing permeate, such as by ultrafiltration as taught in Wu, when performing the method rendered obvious by Nath, Pearce, Dumetz, McPherson, and Wu because an alpha-lactalbumin concentrate from whey is a desired product as indicated in Wu, useful for infant formulas and nutritional mixtures for humans and animals. Therefore, instant claim 27 (protein concentrate is an ALA concentrate) is rendered obvious. Additionally, it would have been obvious to the skilled artisan to concentrate the ALA in the permeate of the method rendered obvious by the references to a high extent that results in obtaining a product (directed to the claimed ‘first composition’) that has a weight percentage of ALA relative to total protein that falls in the claimed range of ‘at least 5% higher than that of the recovered mother liquor’ because whey proteins having a high concentration of ALA is desirable, as pointed out by Wu. Thus instant claim 28 is rendered obvious.
Regarding instant claims 29 and 30, Wu discloses that for a method in which whey is processed to obtain a protein fraction having an increased concentration of alpha-lactalbumin, lowering the pH of the alpha-lactalbumin molecule to below 4.0 causes the alpha-lactalbumin molecule to release calcium (page 3, lines 9-10 and 20-23). Once this calcium is removed, the alpha-lactalbumin can be effectively precipitated to form an alpha-lactalbumin concentrate (page 3, lines 24-25). Therefore, in Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), a pH-lowering step is performed in which the pH of the permeate is lowered to 4.0 or below, preferably between about 3.3-3.8 (page 5, lines 8-11). Once the pH of the permeate is lowered to 4.0 or below, the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin may be dried as-is, or neutralized to a pH of 6-7 (page 5, lines 19-21). Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to further include a step of lowering the pH to 4.0 or below (overlapping the claimed range of 2.5-4.9 of instant claim 29) or about 3.3-3.8 (falling within the claimed range of 2.5-4.9 of instant claim 29) before the drying step when performing the method rendered obvious by Nath in view of Pearce, Dumetz, McPherson, and Wu. One of ordinary skill in the art would have been motivated to do this because Wu teaches that this results in removing calcium from a permeate comprising alpha-lactalbumin obtained from ultrafiltration and/or diafiltration of whey, which allows the effective precipitation of alpha-lactalbumin to form a concentrate thereof for an alpha-lactalbumin enriched product with desirable applications (e.g. infant formula, protein source in nutritional mixtures). Therefore, the references render obvious instant claim 29 (directed to an embodiment of step e) of instant claim 18). Additionally, after the pH lowering, it would have been obvious to the person of ordinary skill in the art to further perform the steps of concentrating the permeate through ultrafiltration after the pH lowering, and then adjusting the pH to 6-7 (overlapping the claimed range of 6.1-8.5 of instant claim 30) before drying when performing the method rendered obvious by Nath in view of Pearce, Dumetz, McPherson, and Wu. One of ordinary skill in the art would have been motivated to do this because Wu teaches these steps for obtaining an alpha-lactalbumin enriched product with desirable applications (e.g. infant formula, protein source in nutritional mixtures). Thus instant claim 30 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.
Claims 18-22, 24-31, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-9, 12-18, 20, 21, 43, 44, 48, 49, 54, and 55 of copending Application No. 16/472,277 in view of Wu.
The claims of `277 are drawn to a method of preparing an edible composition comprising β-lactoglobulin (BLG) in isolated form, the method comprising the steps of
a) providing a whey protein solution comprising BLG and at least one additional whey
protein, said whey protein solution:
- is supersaturated with BLG and has a pH in the range of 5-6,
- comprises BLG in an amount of at most 85% w /w relative to the total amount of protein, and
- has:
I) a ratio between the-conductivity of the whey protein solution normalized to 25
degrees C and in mS/ cm and the total amount of protein in % w/w relative to the total weight of the whey protein solution, in which the ratio is at most 0.3,
II) a UF permeate conductivity normalized to 25 degrees C of at most 7 mS/cm of the whey protein solution, or
III) a combination of I) and II);
b) crystallizing BLG in the supersaturated whey protein solution in salting-in mode; and
c) separating BLG crystals from the remaining whey protein solution, wherein none of steps a), b), or c) use toluene.
In particular, see independent claim 1 of `277 which includes limitations of instant claim 18, and wherein step c) of claim 1 of `277 includes the limitation of instant claim 37. Also, the ‘remaining whey protein solution’ of claim 1 of `277 corresponds to the mother liquor/first composition of steps c) and d) of instant claim 18. The steps of claims 1 of `277 meet limitations of steps a)-d) of instant claim 18.
Independent claim 1 of `277 differs from instant claim 18 in that claim 1 of `277 does not recite a method of preparing an edible, alpha-lactalbumin-enriched whey protein composition, wherein the whey protein solution of its step a) (meeting limitations of step a) of instant claim 18) comprises at least 5% (w/w) alpha-lactalbumin (ALA) relative to a total amount of protein, and step f) of drying the ‘remaining whey protein solution’ (directed to the claimed ‘first composition’).
However, claim 5 of `277 recites that the whey protein solution of step a) comprises at least 5% w/w alpha-lactalbumin (ALA) relative to the total amount of protein.
Also, Wu discloses that whey proteins have been used in infant formula and as a protein source in nutritional mixtures for humans and animals (page 1, lines 25-26). The whey protein beta-lactoglobulin is not a protein found in human breast-milk, so it acts as an allergen to infants (page 1, lines 26-27). Therefore, it is desirable for whey proteins to have a relatively high concentration of the whey protein alpha-lactalbumin to make it more similar to human milk (page 1, lines 27-30). As such, the art teaches methods of preparing alpha-lactalbumin enriched fractions from whey (page 2, lines 1-2), and this is a primary objective of the invention of Wu (page 2, lines 16-18), particularly achieving a high concentration of alpha-lactalbumin in a protein fraction which is convenient and economical to use (page 2, lines 24-26). Wu teaches drying their alpha-lactalbumin concentrate, wherein drying allows for easier packaging and obtaining a product that remains stable for a longer period of time than the raw concentrate in a liquid or frozen form (page 5, lines 24-25).
It would have been prima facie obvious to apply the limitation of claim 5 of `277 to claim 1 of `277 and its dependent claims. In doing so, then the remaining whey protein solution of step c) (directed to the claimed ‘mother liquor’ and ‘first composition’) necessarily comprises ALA since ALA is not removed from the whey protein solution in the steps of claim 1 of `277 in view of claim 5 of `277. Consequently, it would have been obvious to the person of ordinary skill in the art to dry the remaining whey protein solution of (directed to the claimed ‘first composition derived from the recovered mother liquor’) when performing the method of claim 1 of `277 in view of claim 5 of `277. One of ordinary skill in the art would have been motivated to do this because it is desirable to dry an alpha-lactalbumin product obtained from whey (which the remaining whey protein solution of claim 1 of `277 in view of claim 5 of `277 is directed to) for easier packaging and for maintaining stability for a longer period of time as compared to a raw concentrate in liquid or frozen form, as indicated in Wu, for the desirable result of obtaining an alpha-lactalbumin product useful for infant formulas and nutritional mixtures for humans and animals (directed to ‘an edible, alpha-lactalbumin-enriched whey protein composition’ as recited in instant claim 18). There would have been a reasonable expectation of success because Wu teaches successfully drying an alpha-lactalbumin concentrate obtained from whey to obtain a desirable product. Thus claim 1 of `277 in view of claim 5 of `277 and Wu renders obvious instant claims 18, 26, and 37. Likewise, claim 5 of `277 in view of Wu renders obvious instant claims 18, 26, and 37.
Regarding instant claims 19 and 31, Wu teaches that for obtaining an alpha-lactalbumin concentrate, it is preferred that the whey is pasteurized (page 4, lines 13-15). Pasteurization is well known to be directed to heat treatment for the purpose of killing microorganisms. It would have been obvious to pasteurize the whey protein solution when performing the method rendered obvious by claim 1 of `277 in view of claim 5 of `277 and Wu because the pasteurization of whey was taught in Wu for obtaining an alpha-lactalbumin product that is a desirable whey protein product. Thus claim 1 of `277 in view of claim 5 of `277 and Wu renders obvious instant claims 19 and 31 (heat-treatment).
Regarding instant claims 29 and 35 (which depends from instant claim 19), Wu discloses that for a method in which whey is processed to obtain a protein fraction having an increased concentration of alpha-lactalbumin, lowering the pH of the alpha-lactalbumin molecule to below 4.0 causes the alpha-lactalbumin molecule to release calcium (page 3, lines 9-10 and 20-23). Once this calcium is removed, the alpha-lactalbumin can be effectively precipitated to form an alpha-lactalbumin concentrate (page 3, lines 24-25). Therefore, in Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), a pH-lowering step is performed in which the pH of the permeate is lowered to 4.0 or below, preferably between about 3.3-3.8 (page 5, lines 8-11). Once the pH of the permeate is lowered to 4.0 or below, the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin may be dried as-is, or neutralized to a pH of 6-7 (page 5, lines 19-21). It would have been obvious to the person of ordinary skill in the art to include a step of lowering the pH to 4.0 or below (overlapping the claimed range of 2.5-4.9 of step e) of instant claim 18 and instant claim 29) or about 3.3-3.8 (falling within the claimed range of 2.5-4.9 of step e) of instant claim 18 and instant claim 29) before the drying step when performing the method rendered obvious by claim 1 of `277 in view of claim 5 of `277 and Wu. One of ordinary skill in the art would have been motivated to do this because Wu teaches that this results in removing calcium from a composition comprising alpha-lactalbumin obtained from whey, which allows the effective precipitation of alpha-lactalbumin to form a concentrate thereof for an alpha-lactalbumin enriched product with desirable applications (e.g. infant formula, protein source in nutritional mixtures). Therefore, claim 1 of `277 in view of claim 5 of `277 and Wu additionally render obvious step e) of instant claim 18 which is an optional step, as well as instant claim 29. Further still, it additionally would have been prima facie obvious to perform the pasteurization step (see preceding paragraph, directed to physical microbial reduction) at any instance of the process, including between the pH lowering step and the drying step, since it would have the desired effect of obtaining an alpha-lactalbumin enriched product in which whey is pasteurized. Thus claim 1 of `277 in view of claim 5 of `277 and Wu also renders obvious instant claim 35.
Regarding instant claim 20, claim 7 of `277 meets the claimed limitation since the range of ‘at least 1% w/w BLG relative to the total amount of protein’ overlaps the claimed range of ‘at most 90% w/w BLG relative to the total amount of protein.’ Thus claim 7 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 20.
Regarding instant claim 21, claim 9 of `277 meets the claimed limitation. Thus claim 9 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 21.
Regarding instant claim 22, claim 1 of `277 includes the claimed limitation (see I) of step a)). Thus claim 1 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 22.
Regarding instant claim 24, claim 12 of `277 meets the claimed limitation. Thus claim 12 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 24.
Regarding instant claims 25 and 36, claim 18 of `277 meets the limitation of instant claim 25 and its range overlaps with the range of instant claim 36. Thus claim 18 of `277 in view of claim 5 of `277 and Wu renders obvious instant claims 25 and 36.
Regarding instant claims 27 and 28, Wu discloses that whey proteins have been used in infant formula and as a protein source in nutritional mixtures for humans and animals (page 1, lines 25-26). The whey protein beta-lactoglobulin is not a protein found in human breast-milk, so it acts as an allergen to infants (page 1, lines 26-27). Therefore, it is desirable for whey proteins to have a relatively high concentration of the whey protein alpha-lactalbumin to make it more similar to human milk (page 1, lines 27-30). In Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin concentrate obtained may then be dried as-is (page 5, lines 19-21). It would have been obvious to the person of ordinary skill in the art to further concentrate the ALA in the ALA-containing ‘remaining whey protein solution’ (directed to claimed ‘recovered mother liquor’), such as by ultrafiltration as taught in Wu, when performing the method rendered obvious by claim 1 of `277 in view of claim 5 of `277 and Wu because an alpha-lactalbumin concentrate from whey is a desired product as indicated in Wu, useful for infant formulas and nutritional mixtures for humans and animals. Therefore, claim 1 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 27 (protein concentrate is an ALA concentrate). Additionally, it would have been obvious to the skilled artisan to concentrate the ALA in the ALA-containing ‘remaining whey protein solution’ of the method rendered obvious by claim 1 of `277 in view of claim 5 of `277 and Wu to a high extent that results in obtaining a product (directed to the claimed ‘first composition’) that has a weight percentage of ALA relative to total protein that falls in the claimed range of ‘at least 5% higher than that of the recovered mother liquor’ because whey proteins having a high concentration of ALA is desirable, as pointed out by Wu. Thus instant claim 28 is rendered obvious.
Regarding instant claim 30, Wu discloses that for a method in which whey is processed to obtain a protein fraction having an increased concentration of alpha-lactalbumin, lowering the pH of the alpha-lactalbumin molecule to below 4.0 causes the alpha-lactalbumin molecule to release calcium (page 3, lines 9-10 and 20-23). Once this calcium is removed, the alpha-lactalbumin can be effectively precipitated to form an alpha-lactalbumin concentrate (page 3, lines 24-25). Therefore, in Wu’s invention in which alpha-lactalbumin is concentrated in a whey protein concentrate using ultrafiltration and/or diafiltration (e.g. page 4, lines 1-6), a pH-lowering step is performed in which the pH of the permeate is lowered to 4.0 or below, preferably between about 3.3-3.8 (page 5, lines 8-11). Once the pH of the permeate is lowered to 4.0 or below, the permeate is preferably concentrated through ultrafiltration, and then the alpha-lactalbumin may be dried as-is, or neutralized to a pH of 6-7 (page 5, lines 19-21). It would have been obvious to the person of ordinary skill in the art to perform the steps of lowering the pH of the remaining why protein solution (directed to claimed ‘first composition’) to 4.0 or below, concentrating the resulting product through ultrafiltration, and then adjusting the pH to 6-7 (overlapping the claimed range of 6.1-8.5 of instant claim 30) before drying when performing the method rendered obvious by claim 1 of `277 in view of claim 5 of `277 and Wu. One of ordinary skill in the art would have been motivated to do this because Wu teaches that this results in removing calcium from a product comprising alpha-lactalbumin obtained from whey, which allows the effective precipitation of alpha-lactalbumin to form a concentrate thereof for an alpha-lactalbumin enriched product with desirable applications (e.g. infant formula, protein source in nutritional mixtures). Thus claim 1 of `277 in view of claim 5 of `277 and Wu renders obvious instant claim 30.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments, filed October 27, 2025, with respect to the objection to claim 24 and the rejection under 35 U.S.C. 112(b) of claim 22 have been fully considered and are persuasive. Thus the claim objection and this rejection have been withdrawn.
However, Applicant’s arguments are unpersuasive with respect to the rejection under 35 U.S.C. 103 of claims 18-22, 24-31, and 35-37 as being unpatentable over Nath in view of Pearce, Dumetz, McPherson, and Wu; and the provisional nonstatutory double patenting rejection over claims 18-22, 24-31, and 35-37 as being unpatentable over claims 1, 2, 5-9, 12-18, 20, 21, 43, 44, 48, 49, 54, and 55 of copending Application No. 16/472,277 in view of Wu.
Regarding the rejection under 35 U.S.C. 103, Applicant argues that crystallization of beta-lactoglobulin (as disclosed by Palmer cited in previously filed response) was not used for production of edible whey protein ingredients as the prior art crystallization methods were complex, time-consuming processes that employed toxic organic solvents, such as toluene, which were not suitable for food products. However, the basis of the rejection is not a crystallization method involving a toxic organic solvent is involved. Moreover, Applicant asserts that it was common knowledge in the industry that proteins had to be highly purified to improve the chances of crystallizing them, citing McPherson (reference of rejection), specifically page 7-8 and highlighting passage on page 8, left column, first paragraph. This teaching in McPherson is also discussed on pages 12-13 of the Remarks. However, though McPherson discloses purity as a factor in protein crystallization (page 8, left column, first paragraph), McPherson does not express the degree of purity that is necessary. The retentate comprising BLG of Nath was obtained through various stages of filtration see Figure 2 of Nath), and thus is considered a product in which BLG had been purified. Applicant also asserts that it was also known that not all proteins could be crystallized – however, Applicant has not provided evidence to support this assertion.
Additionally, Applicant argues that the claimed invention addresses this problem and offers the potential to transform the way whey proteins can be handled and fractionated in the dairy industry, further discussing their discovery of enriching ALA and other whey proteins from crude whey proteins by selectively crystallizing BLG under salting-in conditions and subsequently removing the BLG crystals, thereby providing an efficient and gentle production of ALA-enriched protein compositions, where organic solvents are not used, resulting in the production of food ingredients that are safe for use, particularly in infant formula products. However, the method of Nath does not appear to use an organic solvent to obtain the separation of proteins from the whey (page 487, section 2.4.2), so there would not have been the expectation that the alpha-lactalbumin product of the method rendered obvious by Nath in view of Pearce, Dumetz, McPherson, and Wu is not food-grade for an edible product.
Regarding Nath, Applicant points out that Nath describes a purity of 95% BLG in the 30 kg mol-1 UF retentate ("Retentate Y" as labeled in the arguments) at a given transmembrane pressure (page 497, Fig. 10 and right-hand column, 1st paragraph). Applicant also points out the differences between Nath and the claimed invention. The differences between each of the secondary references Pearce, Dumetz, and Wu with the claimed invention are also discussed by Applicant. Additionally, Applicant discusses several technical aspects related to supersaturation with respect to BLG and the claimed crystallization step b) of claim 18, which Applicant argues that the Examiner may not have considered. First, Applicant asserts that the BLG concentration in Nath is not high enough in Retentate X (as annotated on Figure 2 of the reference in the arguments). Applicant points out that supersaturation of BLG requires a sufficient concentration of non-aggregated BLG. It is then argued that the concentration of BLG in Retentate X in Nath is too low, as demonstrated by Applicant’s description of the ultrafiltration steps of Nath (page 487, right hand side, last paragraph of section 2.4.2) using an exemplary starting volume of 100 L. However, the Examiner disagrees with Applicant’s conclusion that the Step III- retentate (Retentate X) is back to 50% of the original BLG concentration. The steps beforehand involve separating other proteins, namely bovine serum albumin, albumin, lactoperoxidase, and lactoferrin, from BLG, ALA, and ALA (page 487, left column, last paragraph). This is signifies higher purity of BLG as compared to the starting material. The degree of dilution does not speak to purity of BLG. Therefore, the Examiner disagrees with Applicant’s assertion that the skilled artisan would understand that the conditions in Retentate X would be sufficient to lead to supersaturation of BLG.
Applicant also argues that POSITA would not expect Retentate X to contain BLG of sufficient purity to allow for BLG crystallization. These arguments are unpersuasive for the same reasons set forth in the preceding paragraph.
In sum, Applicant’s are unpersuasive with respect to the rejections under 35 U.S.C. 103.
Applicant’s arguments are also unpersuasive with respect to the double patenting rejection. The Examiner is unpersuaded that the claims of `277 would not have led to the POSITA to the realization that an ALA-enriched product can be obtained, in view of Wu.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651