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 .
Election/Restrictions
The present application remains examined under applicant’s election without traverse of Group I in the reply filed on 06/12/2025.
Claims 54-60 remain withdrawn as being directed to a nonelected invention.
Claims 41-53 are directed to the elected invention and have been examined on the merits.
Information Disclosure Statements
The information disclosure statement (IDS) submitted on 09/18/2025 and 05/06/2026 are in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Amendments
Claim 41 no longer recites the approximation “about” and has had minor typographic changes.
Claims 43-45 no longer recite the approximation “about”.
Claim 49 has had minor typographic changes and no longer recites “any combinations comprising one or more of these”.
Claims 52-53 have had minor typographic changes.
Claims 61-63 are newly added.
Drawings
Previous objection to the drawings
The drawings were objected to for minor informalities. Applicant has made the appropriate corrections. Accordingly, the objection is withdrawn and the newly filed drawings are accepted.
Claim Objections
Previous objections to the claims
Claim 41 was objected to for various minor informalities. Applicant has made the appropriate corrections except for removal of the bullet points. It appears that the first four bullet points were removed (as shown with strikethrough) but the 5th-9th bullet points do not have strikethrough. Accordingly, it appears that these bullet points are still present.
Claims 49 and 51-53 were objected to for minor informalities. Applicant has made the appropriate correction and the objections are therefore withdrawn.
Maintained objection to the claims
Claim 41 is objected to because the use of bullet points in this claim is improper. Claims are required to be complete sentences and where claims set forth a plurality of elements or steps, each element or step should be separated by a line indentation (37 CFR 1.75(i)). Accordingly, applicant should remove the bullet points because the use of separate lines and indentations is sufficient to delineate each step.
Appropriate correction is required.
New objection to the claims
Claims 61 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims for the reasons discussed in the “Allowable Subject Matter” section of this action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112:
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Previous rejections under 35 U.S.C. § 112(b)
RE: Rejection of claims 41-53 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claims 41 and 43-45 were rejected for reciting the indefinite approximation “about”. In response, applicant has removed all uses of this term.
Claims 42 and 46-53 were rejected because although they did not recite the approximation, they inherited the indefinite language by virtue of their dependency on the above claims.
Because applicant has removed the approximation, the rejection is withdrawn.
RE: Rejection of claim 49 under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 49 was rejected for failing to properly depend from claim 41. Applicant has made the appropriate correction and the rejection is therefore withdrawn.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Previous rejection under 35 U.S.C. § 102
RE: Rejection of claims 41-42, 45, and 47-50 under 35 U.S.C. 102(a)(1) as being anticipated by Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023).
Applicant traverses the rejection of record by arguing that Cornaggia teaches comparing the assay result with a reference curve based on a volume of a known amount of Amylase HR and Amylase SD but it is “not described or taught how the standard curve is generated or whether it is selectively created to be associated with a certain extraction procedure” (Remarks, p. 11, par. 6).
Applicant supports this argument by stating that the inventors of the present invention have “realized that a large time saving may be obtained by merely extracting some of the target enzyme from the grain material tested” (Remarks, p. 12, par. 1; referring to [0020] of the specification).
Applicant’s argument have been fully considered but is not sufficient to overcome the rejection of record. Although the Examiner appreciates that the methods described in the instant specification may differ in part from Cornaggia, the claim is generic to any “standard curve associated to the preselected extraction procedure and representing absorbance parameter as a function of target enzyme activity”. As discussed in the rejection of record, Cornaggia teaches Cornaggia teaches that all biochemical assays were performed in duplicate and the average value was taken, then fluorescence values were obtained by subtracting the blank from the averaged values and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (p. 405, left col., par. 1 through right col., par. 1). Thus, the results represented by Cornaggia’s absorbance parameters are represented as a function of target enzyme activity. And although Cornaggia may not have used the identical extraction procedure, the standard curve used by Cornaggia is nonetheless “associated to the preselected extraction procedure” because the standard curve is used in conjunction with the extraction procedure in order to determine 4-MU concentration (i.e., an absorbance parameter as a function of target enzyme activity).
For at least this reason, the rejection of record is proper and has been maintained. The text of the rejection has been modified only to remove reference the “about” limitations.
Maintained but modified rejection under 35 U.S.C. § 102
Claims 41-42, 45, and 47-50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023).
Regarding claim 41, Cornaggia teaches a colorimetric and fluorometric method for measuring α-amylase (EC 3.2.1.1) activity in sprout-damaged wheat (i.e., a method of determining activity of a target enzyme of a grain material).
With respect to providing a fluid extract sample of the grain material using a preselected extraction procedure, Cornaggia teaches the following.
Cornaggia teaches milling wheat (i.e., a grain material) to pass a 0.5 mm mesh (i.e., to a predetermined particle size distribution)(p. 406, left col., par. 3).
Cornaggia teaches extracting α-amylase (i.e., preparing an extract from the milled substance) by adding 15 grams of the ground wheat sample (i.e., a preselected amount of the milled grain material) to 120 mL of buffer A (i.e., a preselected amount of liquid extraction buffer) and mixing (i.e., thoroughly mixing) and incubating the sample for 20 minutes (i.e., up to 20 minutes) with regular manual stirring (i.e., thoroughly mixing)(Id.).
Cornaggia teaches centrifuging and discarding the pellet (i.e., taking the fluid extract sample of the liquid extraction buffer)(Id.).
Thus, Cornaggia teaches the claimed step of providing a fluid extract sample of the grain material using a preselected extraction procedure.
With respect to providing a dyed and/or chromogenic substrate for the target enzyme, Cornaggia teaches the addition (i.e., provision) of pre-equilibrated Amylase SD, Amylase HR, BzCNPG7, and BzMUG7 reagents (p. 406, right col., par. 7; p. 407, left col., par. 2 through right col., par. 2). BzCNPG7 and BzMUG7 are chromogenic substrates which contain 2-chloro-4-nitrophenyl or 4-methylumbelliferyl- groups (p. 407, Figure 2; p. 409, left col., par. 1; p. 410, left col., par. 1). The amylase SD and HR “are essentially the same” however, the 4-nitrophenyl- group is instead α-linked (p. 409, left col., par. 1).
With respect to subjecting the fluid extract sample to the substrate for a preselected incubating time, Cornaggia teaches mixing the fluid extract and the chromogenic substrate and incubating (i.e., subjecting the fluid extract sample to the substrate) for 20 minutes (i.e., a preselected incubating time)(p. 407, left col., par. 2 through right col., par. 2).
With respect to determining the target enzyme activity of the grain material, Cornaggia teaches the following.
Cornaggia teaches that after subjecting the sample to the substrate for a preselected incubating time, the absorbance is read at 400 nm (p. 407, left col., par. 2 through right col., par. 2)(i.e., determining an absorbance parameter of dye released from the substrate into the fluid extract sample or colored reaction product formed). See Figure 2 (p. 407) which shows the release of phenolate ions in solution (i.e., released from the substrate into the fluid extract sample or colored reaction product formed) after cleavage of the substrate and addition of the dilute basic solution (p. 409, left col., par. 1). Because the released 4-nitrophenyl- and 2-chloro-4-nitrophenyl- groups are chromogenic groups, their release is considered to be a dye within the context of the claim.
With respect to correlating the determined absorbance parameter to a standard curve associated to the preselected extraction procedure and representing absorbance parameter as a function of target enzyme activity, Cornaggia teaches that all biochemical assays were performed in duplicate and the average value was taken, then fluorescence values were obtained by subtracting the blank from the averaged values and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (p. 405, left col., par. 1 through right col., par. 1). Thus, the results represented by Cornaggia’s absorbance parameters are represented as a function of target enzyme activity.
Thus, Cornaggia teaches the method of claim 41.
Regarding claim 42, as discussed above, Cornaggia teaches the method of claim 41. Cornaggia teaches that the wheat (i.e., the grain material) was milled to pass a 0.5 mm mesh. Thus, because Cornaggia’s wheat was milled to pass through the mesh of this size, there is a reasonable expectation that at least 90% by weight of the grain material passes a sieve of 0.5 mm or less.
Regarding claim 45, Cornaggia teaches that the extraction occurs at 40°C (a value falling within the range of a temperature from 10°C to 40°C)(p. 406, left col., par. 3).
Regarding claim 47, Cornaggia teaches that the absorbance parameter of the fluid extract sample with released dye is measured at 400 nm (p. 406, right col., par. 1 and 7; p. 407, left col., par. 2-3 and right col., par. 3; p. 411, Table 1). This is an absorbance parameter which comprises at least one wavelength absorbable by the dye (see p. 409, right col., par. 1 which discusses the detection of the phenolate ions at 400 nm).
Regarding claim 48, as discussed above, Cornaggia teaches the comparison of the relative fluorescent units to the concentration of 4-methylumbelliferone (p. 405, right col., par. 1). Thus, Cornaggia teaches that the standard further is associated to the dyed or chromogenic substrate.
Regarding claim 49, as discussed above, Cornaggia’s methods are directed to determining activity of α-amylase and the grain material is wheat (i.e., a cereal).
Regarding claim 50, as discussed above, Cornaggia teaches a wheat grain material.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Previous rejection under 35 U.S.C. § 103
RE: Rejection of claims 41-42, 44-45, and 47-50 under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023).
The 103 rejection, as applied to claim 44 has not been argued by applicant.
For at least the reasons discussed above, the rejection of record is proper and has been maintained. The text of the rejection has been modified only to remove reference the “about” limitations and to include rejection of newly added claims 62-63.
RE: Rejection of claims 41-45 and 47-51 under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of Yang et al. (US 2009/0069542 A1).
The 103 rejection, as applied to claim 43 has not been argued by applicant.
For at least the reasons discussed above, the rejection of record is proper and has been maintained. The text of the rejection has been modified only to remove reference the “about” limitations.
RE: Rejection of claims 41-42 and 44-50 under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of Kracun et al. (WO 2016/188533 A1; cited in IDS filed on 04/11/2023).
The 103 rejection, as applied to claims 46 and 51 has not been argued by applicant.
For at least the reasons discussed above, the rejection of record is proper and has been maintained. The text of the rejection has been modified only to remove reference the “about” limitations.
RE: Rejection of claims 41-42, 44-45, 47-50, and 52-53 under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of News Medical (Standard Curve Generation for Colorimetric Assay in the Kinetic or Basic Eppendorf BioSpectrometer®, 2016, https://www.news-medical.net/whitepaper/20160218/Standard-Curve-Generation-for-Colorimetric-Assay-in-the-Kinetic-or-Basic-Eppendorf-BioSpectrometer.aspx, accessed: August 2025).
Applicant asserts that News Medical does not remedy the alleged deficiencies of Cornaggia because it teaches a standard curve based on 10 samples with different and known content in mg/ml. Thus, there are allegedly no features relating to any specific extraction and it is not clear what the mg substance stands for or how it would suggest the correlation using the claimed standard curve.
As discussed in the rejection of record, Cornaggia differs in that it does not teach using reference samples with different and known enzyme activity of the target enzyme. However, it was known in the art that the common principle in colorimetric methods of detection is that the enzyme activity or concentration of an unknown sample is assessed by a calibration curve and the creation of such a curve involves successive measurement of various known standards by a spectrophotometer followed by a regression analysis (News Medical, p. 3, par. 1). As such, it would have been obvious to have modified Cornaggia such that the linear standard curve generated by regression including points of respective pairs of determined absorbance parameters was generated by providing a plurality of grain material reference samples with different and known enzyme activity of the target enzyme (i.e., various standards).
For at least the reasons discussed above, the rejection of record is proper and has been maintained.
Maintained but modified rejections under 35 U.S.C. § 103
Claims 41-42, 44-45, 47-50, and 62-63 are rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023).
The teachings of Cornaggia are set forth above and applied herein. Cornaggia is found to render obvious claims 41-42, 45, and 47-50.
Regarding claims 44 and 63, as discussed above, Cornaggia teaches the method of claim 41 wherein the extraction is performed over 20 minutes.
Although Cornaggia does not teach extraction from 2 minutes to 6 minutes (claim 44) or less than 10 minutes (claim 63), a person having ordinary skill in the art could have arrived at this range of times as a result of routine experimentation. Cornaggia teaches that it was known in the art that extraction could occur simultaneously with assaying and could occur in as little as 2 minutes (p. 409, left col., par. 4). Cornaggia teaches that lower extraction times such as two minutes requires more substrate and may alter the accuracy of the test (p. 409, left col., par. 4 through right col., par. 1). Thus, a person having ordinary skill, when selecting a “preselected extraction procedure” would have been prompted to routinely experiment with various extraction times in order to optimize the process such as by optimizing the target protein activity accuracy. There would have been a reasonable expectation of success because, as discussed above, Cornaggia teaches that it was known that the extraction and assay could occur over this short period of time. Thus, the extraction alone would have similarly been expected to be capable of occurring over time frames as short as two minutes. There is no evidence of record that the claimed range elicits an unexpected or remarkable result.
Accordingly, claims 44 and 63 are obvious over Cornaggia as a result of routine experimentation.
Regarding claim 62, as discussed above, Cornaggia teaches a step of adding a fluid extract sample to the substrate. Cornaggia clearly performed this step at some time interval but does not explicitly teach the amount of time. Although Cornaggia does not specifically teach that this occurs “within 10 minutes from the termination of the extraction and the fluid extract sample has been taken from the liquid extraction buffer”, a person having ordinary skill in the art could have arrived at this limitation through routine experimentation. A person having ordinary skill in the art would have been prompted to perform such experimentation in order to optimize the procedure set forth by Cornaggia.
Claims 41-45, 47-51, and 62-63 are rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of Yang et al. (US 2009/0069542 A1).
The teachings of Cornaggia are set forth above and applied herein. Cornaggia is found to render obvious claims 41-42, 44-45, 47-50, and 62-63.
Regarding claim 43, as discussed above, Cornaggia teaches thoroughly mixing a preselected amount of the milled grain material with a preselected amount of liquid extraction buffer.
Cornaggia teaches using (i.e., withdrawing) 1.5 g (i.e., 1500 mg; at least 10 mg) and mixing with 12 mL (i.e., 8 ml per gram milled grain; a value falling within from 5 ml to 0.5 L per gram milled grain). Cornaggia teaches that the buffer was aqueous (dissolved in dH2O) and at a pH of 5.4 (a value falling within from 4 to 10)(p. 405, right col., par. 2).
However, Cornaggia does not teach that the liquid extraction buffer further comprises a reducing agent.
Nonetheless, Yang et al. (hereinafter Yang) teaches that proteins derived from cereal grains tend to have certain properties such as insolubility in water, mechanical stability, and thermal stability ([0005]). Cereal grain proteins may be extracted from cereal grains and the extraction of protein from grains that haven’t been ground or processed may be difficult ([0006]). Yang teaches a need for a method of extracting high-quality proteins from protein plant-based sources at high yield and low cost ([0011]). To this end, Yang teaches a method for processing a plant-based protein source comprising contacting the plant-based protein source with a protein extraction fluid to dissolve protein from the plant-based protein source into the protein extraction fluid ([0012]). Yang teaches that the protein extraction fluid comprises a protein reducing component for breaking disulfide bonds between proteins and has a pH that is no greater than about 8 (Id.). Finally, Yang teaches that exemplary reducing agents include agents such as dithiothreitol (DTT) or sodium sulfite, which may break disulfide bonds in the proteins and increase their solubility ([0035]).
Accordingly, because Cornaggia teaches a method involving the extraction of a cereal grain protein (α-amylase) with an acidic extraction buffer solution (pH 5.4) and because Yang teaches that cereal grain protein extraction can be improved by the addition of a reducing agent to an acidic extraction solution, it would have been obvious to have modified Cornaggia’s extraction buffer solution such that it further comprises a reducing agent. There would have been a reasonable expectation of success because the addition of the reducing agent would have been expected to improve Cornaggia’s solution. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claim 43 is obvious over Cornaggia in view of Yang.
Claims 41-42, 44-50, and 62-63 are rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of Kracun et al. (WO 2016/188533 A1; cited in IDS filed on 04/11/2023).
The teachings of Cornaggia are set forth above and applied herein. Cornaggia is found to render obvious claims 41-42, 44-50, and 63.
Regarding claim 46, as discussed above, Cornaggia teaches the method of claim 41 including a step of determining the absorbance parameter of dye released from the substrate into the fluid extract sample or colored reaction product formed.
Cornaggia, however, does not teach that the method comprises filtering of solid parts of the substrate prior to this step.
Nonetheless, Kracun et al. (hereinafter Kracun) teaches an enzyme activity assay system and device suitable for determination of biopolymer enzyme degrading activity in liquid samples, which is fast and simple to use (p. 3, lines 23-26). Kracun teaches that the enzyme activity assay can be used to perform quantitative determinations such as by determining the degree of enzyme activity relative to a selected reference (p. 3, line 27 through p. 4, line 2). In Kracun’s enzyme activity assay, Kracun teaches that the well in which the reaction occurs has a filter means and teaches that the filter is suitable for filtering of the possibly degraded biopolymer substrate after a selected incubating time with a sample (p. 18, lines 16-19). Additionally, for optimal filtering it is advantageous to rinse with additional liquid and to withdraw the liquid through the filter means (p. 18, lines 19-21).
Accordingly, because both Cornaggia and Kracun teach an enzyme activity assay involving quantitative determination of enzyme activity through enzyme-mediated degradation of a polymer comprising a dye or chromogenic substance and because Kracun teaches that it is advantageous to filter the sample after incubation in order to filter the possibly degraded biopolymer substrates such as by withdrawing the liquid through a filter means, it would have been obvious to have improved Cornaggia’s method by adding the known technique of filtering of solid parts of the substrate as taught by Kracun. A person having ordinary skill in the art would have recognized that applying Kracun’s technique of filtering solid parts of the substrate would result in an improved system such as by separating the degraded polymers from the reaction. This obviousness is based upon the “Applying a Known Technique to a Known Device (Method, or Product) Ready for Improvement To Yield Predictable Results” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(D).
Thus, claim 46 is obvious over Cornaggia in view of Kracun.
Regarding claim 51, as discussed above, Cornaggia teaches the method of claim 41 wherein the enzyme activity is measured with a dyed or chromogenic substrate such as BzCNPG7, BzMUG7, amylase HR, and amylase SD.
Cornaggia, however, does not teach that the substrate is a gelled biopolymer substrate comprising cross-linked polymeric biomolecules selected from polynucleotides, polypeptides, polysaccharides, or any combinations thereof, wherein the dyed and/or chromogenic substrate is an aerogel or a xerogel.
Nonetheless, as discussed above, Kracun teaches an enzyme activity assay system and device suitable for determination of biopolymer enzyme degrading activity in liquid samples, which is fast and simple to use (p. 3, lines 23-26). Kracun teaches that the enzyme activity assay can be used to perform quantitative determinations such as by determining the degree of enzyme activity relative to a selected reference (p. 3, line 27 through p. 4, line 2). Kracun teaches that the enzyme activity can involve a biopolymer substrate and a solid support structure supporting said biopolymer substrate and the biopolymer substrate can comprise a dyed and water insoluble hydrogel, aerogel or xerogel comprising a network of cross-linked biopolymers (p. 4, lines 12-17; p. 20, lines 14-19). The biopolymer substrate comprises cross-linked polymeric biomolecules selected from polynucleotides, polypeptides, polysaccharides, or any combinations thereof. Specifically, Kracun teaches that xerogels can be used for very accurate and reliable enzyme assays, which are more accurate than prior art substrates and by providing biopolymers in the form of a cross-linked construction in a gelled form, the amount of liquid in the xerogel when re-moisturized is highly reduced compared to the amount of liquid in the original gel, which leads to more accurate assays (p. 5, line 27 through p. 6, line 7). Finally, Kracun teaches that enzymes useful in such an assay include enzymes that are capable of degrading one type of chemical bond of a biopolymer substrate (p. 8, lines 20-26).
Because Cornaggia teaches an assay method involving the use of an α-amylase and a dyed/chromogenic substrate and because Kracun teaches that, in methods for assessing enzyme activity, biopolymer substrates comprising dyed aerogels or xerogels comprising a network of cross-linked biopolymers selected from polynucleotides, polypeptides, polysaccharides, or any combinations thereof can be used for accurate and reliable enzyme assays including in combination with any enzyme capable of degrading one type of chemical bond of a biopolymer substrate, it would have been obvious to have substituted the previously known substrate taught by Cornaggia with one of the previously known substrates taught by Kracun. The result of this substitution would be a functional assay which has an improved accuracy, as taught by Kracun. This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 51 is obvious over Cornaggia in view of Kracun.
Claims 41-42, 44-45, 47-50, 52-53, and 62-63 are rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Journal of the Science of Food and Agriculture, 2016, Vol. 96, pages 404-412; cited in IDS filed on 04/11/2023) in view of News Medical (Standard Curve Generation for Colorimetric Assay in the Kinetic or Basic Eppendorf BioSpectrometer®, 2016, https://www.news-medical.net/whitepaper/20160218/Standard-Curve-Generation-for-Colorimetric-Assay-in-the-Kinetic-or-Basic-Eppendorf-BioSpectrometer.aspx, accessed: August 2025).
The teachings of Cornaggia are set forth above and applied herein. Cornaggia is found to render obvious claims 41-42, 44-45, 47-50, 52-53, and 63.
Regarding claim 52, as discussed above, Cornaggia teaches the method of claim 41, including the use of a standard curve. Cornaggia teaches that the α-amylase activity was standardized by adding soluble starch solution to ten tubes containing α-amylase preparation and incubating the mixtures for 0, 3, 6, 9, and 12 minutes then, the absorbance was read at 520 nm against a glucose standard (p. 406, left col., par. 4).
Thus, Cornaggia teaches providing a plurality of grain material reference samples (step 1 of the instant claim), providing a fluid extract reference sample of the grain material reference samples using a preselected reference extraction procedure (step 2 of the instant claim), providing a selected dyed and/or chromogenic reference substrate for the target enzyme for each of the fluid extract reference sample (step 3 of the instant claim), subjecting each of the respect fluid extract reference samples to the respective selected dyed and/or chromogenic reference substrates for a preselected reference incubation time (step 4 of the instant claim), and determining an absorbance parameter of dye released from each of the respective reference substrates into the fluid extract sample and/or colored reaction product formed (step 5 of the instant claim).
However, Cornaggia differs because it teaches the use of the same sample with reactions over different times rather than the same procedure with different enzyme activity and therefore does not teach that the procedure involves using reference samples with different and known enzyme activity of the target enzyme (step 1 of the instant claim).
Nonetheless, News Medical teaches that colorimetric tests permit the measurement of enzyme activity through change in color and such reactions are usually performed within a spectrophotometer (p. 1, par. 2). In enzymatic reactions involving the use of an artificial substrate, a chromophore is released after enzyme cleavage and enzyme activity can be evaluated by the amount of dye released and the time taken for incubation of the enzyme reaction (p. 2, par. 2). The common principle in colorimetric methods of detection is that the enzyme activity or concentration of an unknown sample is assessed by a calibration curve and the creation of such a curve involves successive measurement of various known standards by a spectrophotometer followed by a regression analysis (p. 3, par. 1).
Thus, because Cornaggia teaches the generation of a standard curve using a plurality of reference samples and because “the common principle” in such methods involve the assessment of the enzyme activity or concentration of an unknown sample by successive measurement of various known standards by a spectrophotometer followed by a regression analysis, it would have been obvious to have modified Cornaggia such that the linear standard curve generated by regression including points of respective pairs of determined absorbance parameters was generated by providing a plurality of grain material reference samples with different and known enzyme activity of the target enzyme. This modification would have been expected to improve Cornaggia’s system by allowing the determination of enzyme activity of specific enzymes by providing a plurality of samples having different and known enzyme activity (e.g., enzymes with different kinetics or simply different concentrations of the same enzyme) and therefore a person having ordinary skill in the art could determine the enzyme activity of the target enzyme. There would have been a reasonable expectation of success because the modification merely changes how Cornaggia’s standard curve is generated and therefore the standard curve generated in the modified method could be similarly applied to determine enzyme activity. This obviousness is based upon the “Some Teachings, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Regarding claim 53, as discussed above, Cornaggia in view of News Medical renders obvious the method of claim 52. In said modified method, the selected dyed and/or chromogenic reference substrate is identical to the selected dyed and/or chromogenic substrate.
With respect to the plurality of grain material reference samples with different and known enzyme activity of the target enzyme comprising at least 3 grain material reference samples, Cornaggia’s linear regression analysis includes the use of five (i.e., at least 3) samples (occurring over 0, 3, 6, 9, and 12 minutes; p. 406, left col., par. 4). Thus, in the modified method it would have been obvious to have used at least 3 reference samples, such as 5 reference samples.
Alternatively, it would have been obvious to have experimented with various numbers of reference samples and to have arrived at a number which is “at least 3”. A person having ordinary skill in the art would have recognized that optimizing the number of reference samples would improve the accuracy of the standard curve generated by regression. There is no evidence that modifying the number of reference samples leads to some unexpected or remarkable effect.
Thus, claim 53 is obvious over Cornaggia in view of News Medical.
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.
Previous rejections for double patenting
Applicant has not argued the merits of the provisional rejection of record but instead argues that should the claims be in condition for allowance, a terminal disclaimer will be filed. As the claims are not in condition for allowance, the provisional rejection has been maintained but modified to account for amendments to the copending application.
Maintained provisional double patenting rejection.
Claims 41-53 and 61-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-48 of copending Application No. 18/004,114.
Although the claims at issue are not identical, they are not patentably distinct from each other because they encompass overlapping subject matter.
Specifically, the claims of the ‘114 application are directed to methods of determining activity of a target enzyme in a sample including bringing the sample in physical contact with a substrate for the target enzyme (i.e., providing a fluid extract sample of the grain material and providing a dyed and/or chromogenic substrate for the target enzyme including subjecting the fluid extract sample to the substrate for a preselected incubating time), and determining the target enzyme activity.
Although the instant claims differ in that they further specify preparation steps such as milling the grains, preparing an extract, and taking a fluid extract sample, the copending application, nonetheless, is directed to the same experimental steps for the same purpose. There is no evidence of record that the process by which the samples are prepared causes some material difference in the products used in the process. And although the amended claims now require the use of computer systems, the instant claims are generic to the instant claims.
Claim 43 of ‘114 is akin to instant claim 52 and claims 44-45 of ‘114 are akin to instant claim 53.
Claims 44 and 63 refer to specific times in minutes for the “preselected extraction time”, claim 47 of the copending application teach incubation times “at least one minute”. This range overlaps with “less than 10 minutes” and, additionally, it would have been obvious to have experimented with various extraction times in order to optimize the process.
Claim 46 of ‘114 limits the parameter to an absorbance parameter. This limitation is provided in instant claim 41.
Claim 47 of ‘114 limits the incubation to at least one minute. Claim 41 requires a generic incubation time. Therefore, the instant claim is generic to the copending application.
Claim 48 of ‘114 requires a reference incubation of from 5 minutes shorter to 5 minutes longer than the actual incubation time. As discussed above, claim 41 establishes a generic incubation time and claim 52 establishes a reference incubation time (“a preselected reference incubation time”). Thus, the instant claim is generic to the copending claim.
For at least these reasons, the claims in the instant and copending application overlap. Thus, the claims are unpatentable over each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
It is noted that the instant applicant and copending application also may encompass overlapping subject matter with respect to the system for determining enzyme activity in grain material. A rejection has not been made over these claims as the system claims are currently withdrawn. Rejection may be made if the system claims are rejoined in the instant application.
Allowable Subject Matter
Claim 61 is allowable because although Cornaggia teaches correlating an absorbance parameter with a standard curve, it does not teach or suggest that the standard curve is identical to the preselected extraction procedure and represents absorbance parameter as a function of target enzyme activity. As discussed above, Cornaggia obtained the absorbance parameter by subtracting the blank from the averaged values and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (p. 405, left col., par. 1 through right col., par. 1). And, as discussed in the rejection under 35 U.S.C. § 103, News Medical teaches that colorimetric tests permit the measurement of enzyme activity through change in color and such reactions are usually performed within a spectrophotometer (p. 1, par. 2). In enzymatic reactions involving the use of an artificial substrate, a chromophore is released after enzyme cleavage and enzyme activity can be evaluated by the amount of dye released and the time taken for incubation of the enzyme reaction (p. 2, par. 2). The common principle in colorimetric methods of detection is that the enzyme activity or concentration of an unknown sample is assessed by a calibration curve and the creation of such a curve involves successive measurement of various known standards by a spectrophotometer followed by a regression analysis (p. 3, par. 1). As such, it was known in the art to use standards for the purpose of detecting enzyme activity, not for using a standard curve to represent absorbance parameter as a function of target enzyme activity and it would not have been obvious to have modified Cornaggia in such a way because Cornaggia is directed to measuring amylase activity by using an amylase standard.
Conclusion
Claims 41-53 and 62-63 are not allowed.
Claim 61 is allowable if placed in independent form but is objected to for the reason discussed above.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GRANT C CURRENS whose telephone number is (571)272-0053. The examiner can normally be reached Monday - Thursday: 7:00-5:00.
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/GRANT C CURRENS/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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