DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on January 7, 2026. Claims 1 and 4-16 are pending in the application.
Status of Objections and Rejections
All rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 4-9, and 12-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Onuma (US 2016/0209359) in view of Oishi (US 2010/0006436), and further in view of Breadmore (US 2019/0353614).
Regarding claims 1, 5, and 12-14, Onuma teaches a sample analysis method ([Abstract]), comprising:
separating a protein from a sample comprising the protein ([Abstract]: separating hemoglobin in a sample), in an alkaline solution by capillary electrophoresis ([Abstract]),
wherein separation of the protein is performed (¶24: fractions of hemoglobin in a sample can be separated), and
the alkaline solution comprises a cationic polymer ([Abstract]).
Onuma fails to teach the separation is performed in a presence of a cationic low- molecular compound having two or three primary amino groups, and the alkaline solution comprises the cationic low-molecular compound, and a content ratio of the cationic low-molecular compound with respect to a total mass of the alkaline solution is from 0.01 mass% to 10 mass% (claim 1) or wherein the cationic low-molecular compound comprises ethylenediamine (claim 5) or wherein a content ratio of the cationic low-molecular compound with respect to a total mass of the alkaline solution is from 0.05 mass% to 5 mass% (claim 12) or wherein a content ratio of the cationic low-molecular compound with respect to a total mass of the alkaline solution is from 0.1 mass% to 3 mass% (claim 13) or wherein a content ratio of the cationic low-molecular compound with respect to a total mass of the alkaline solution is from 0.3 mass% to 1 mass% (claim 14).
However, Oishi teaches a method for measuring hemoglobin (¶13), using a migration path having an inner surface coated with a cationic substance to be immobilized on the inner surface (¶14). A low-molecular-weight hydrophilic compound having a cationic group is linked to the inner surface of the migration path by a covalent bond (¶26). The hydrophilic compound having a cationic group may have a repetitive structure such as dimer and trimer as long as its molecular weight is 800 or less (¶51), and an example is ethylenediamine (¶54). The desirable lower limit of the concentration of the solution containing the hydrophilic compound having a cationic group is 0.1% by weight, and the desirable upper limit thereof is 30% by weight (¶63), which overlaps the claimed ranges of the claims 1 and 12-14. Further, Onuma teaches the capillary channel is preferably coated with a cationic substance (¶47), which may be the cationic polymer or a silane coupler having a cationic functional group (¶48), suggesting the electrophoresis solution may include the cationic polymer only or both cationic polymer and the cationic coating substance. Breadmore teaches the separation channel or capillary may be pre-coated or coated in situ (¶101). Thus, the combined Onuma, Oishi, and Breadmore render it obvious that a cationic substance (Onuma, ¶47), e.g., ethylenediamine (Oishi, ¶54), can be used to coat the capillary channel in situ (Breadmore, ¶101), i.e., in the alkaline solution.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma by incorporating the hydrophilic low-molecular-weight compound comprising a cationic group of Oishi (Oishi, ¶26; e.g., ¶54: ethylenediamine) into the alkaline solution of Onuma (Onuma, ¶55) for in situ coating (Breadmore, ¶101) because the hydrophilic low-molecular-weight compound comprising a cationic group would coat the inner surface of the migration path and thus the migration path having the cationic inner surface would avoid non-specific adsorption of measurement components and enable high accuracy measurement (Oishi, ¶17). Here, Choosing from a finite number of identified, predictable solutions (i.e., pre-coated or coated in situ), with a reasonable expectation of success is prima facie obvious. MPEP 2141(III)(E). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Examiner notes that the hydrophilic low-molecular-weight compound having a cationic group of Oishi does not have to substitute the cationic low-molecular weight of Onuma because the former is for coating the migration path while the latter is a pH adjuster.
Regarding claim 4, Onuma, Oishi, and Breadmore disclose all limitations of claim 1, but fail to teach wherein a ratio of a content ratio of the cationic low-molecular compound to a content ratio of the cationic polymer in the alkaline solution is from 0.001 to 1000.
However, Onuma teaches the content of the cationic polymer in the alkaline solution is 0.01% (W/V) from the viewpoint of improving the accuracy of analysis, and more or 5.0% (W/V) from the viewpoint of preventing an increase in solution viscosity, rendering the content ratio of the cationic polymer in the alkaline solution a result-effective variable (¶38). Further, Oishi teaches a hydrophilic compound having a cationic group, e.g., ethylenediamine, having a desirable lower and upper limits of the concentrations from 0.1% to 20% by weight (¶63). The combined Onuma and Oishi would render a ratio of the content ratio of the cationic low-molecular compound to a content ratio of the cationic polymer in the alkaline solution a result-effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma, Oishi, and Breadmore by adjusting the ratio of the content ratio of the cationic low-molecular compound to a content ratio of the cationic polymer within the claimed range because the ratio of the content ratio of the cationic low-molecular compound to a content ratio of the cationic polymer is a result-effective variable and can be optimized through routine experimentation. MPEP 2144.05 (II)(B).
Regarding claim 6, Onuma teaches wherein the protein comprises hemoglobin ([Abstract]).
Regarding claims 7 and 15-16, Onuma, Oishi, and Breadmore disclose all limitations of claim 1, but fail to teach wherein a weight average molecular weight of the cationic polymer is from 15,000 to 150,000 (claim 7) or wherein a weight average molecular weight of the cationic polymer is from 20,000 to 130,000 (claim 15) or wherein a weight average molecular weight of the cationic polymer is from 20,000 to 100,000 (claim 16).
However, Onuma teaches the weight-average molecular weight of the cationic polymer is 10,000 or more and 300,000 or less (¶34), which overlaps the claimed ranges of the claims.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma, Oishi, and Breadmore by adjusting the molecular weight of the cationic polymer within the claimed range because they are suitable molecular weight of the cationic polymer for improving the accuracy while preventing an increase in solution viscosity (¶34). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 8, Onuma, Oishi, and Breadmore disclose all limitations of claim 1, but fail to teach wherein a content ratio of the cationic polymer with respect to a total mass of the alkaline solution is from 0.01 mass% to 10 mass%.
However, Onuma teaches the content of the cationic polymer in the alkaline solution is 0.01% (W/V) from the viewpoint of improving the accuracy of analysis, and more or 5.0% (W/V) from the viewpoint of preventing an increase in solution viscosity, rendering the content ratio of the cationic polymer in the alkaline solution a result-effective variable (¶38).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma, Oishi, and Breadmore by adjusting the content of the cationic polymer in the alkaline solution with respect to a total mass of the alkaline solution within the claimed range because the content of the cationic polymer in the alkaline solution is a result-effective variable and can be optimized through routine experimentation to achieve both improved accuracy of analysis and prevention of an increase in the solution viscosity (¶38). MPEP 2144.05 (II)(B).
Regarding claim 9, Onuma teaches wherein a pH of the alkaline solution is from 8.5 to 12.0 (¶37: the pH of the alkaline solution is preferably 8.5 or higher and preferably 12.0 or lower).
Claim(s) 10-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Onuma in view of Oishi, or alternatively, over Onuma in view of Oishi and Breadmore.
Regarding claim 10, Onuma teaches a capillary electrophoresis solution (¶24: conducting capillary electrophoresis in an alkaline solution), comprising:
a cationic polymer (¶24: the alkaline solution containing a cationic polymer);
wherein the capillary electrophoresis solution is used for separation of a protein by capillary electrophoresis ([Abstract]: separating hemoglobin in a sample by capillary electrophoresis).
Further, the designation “wherein the capillary electrophoresis solution is used for separation of a protein by capillary electrophoresis” is deemed to be functional limitation in apparatus claims regarding to intended use. MPEP 2114 (II). "[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987). Here, Onuma teaches all composition limitations of the presently claimed capillary electrophoresis solution, and thus it is capable of separating a protein by capillary electrophoresis.
Onuma fails to teach a cationic low-molecular compound having two or three primary amino groups, wherein a content ratio of the cationic low-molecular compound with respect to a total mass of the alkaline solution is from 0.01 mass% to 10 mass%.
However, Oishi teaches a method for measuring hemoglobin (¶13), using a migration path having an inner surface coated with a cationic substance to be immobilized on the inner surface (¶14). A low-molecular-weight hydrophilic compound having a cationic group is linked to the inner surface of the migration path by a covalent bond (¶26). The hydrophilic compound having a cationic group may have a repetitive structure such as dimer and trimer as long as its molecular weight is 800 or less (¶51), and the desirable lower limit of the concentration of the solution containing the hydrophilic compound having a cationic group is 0.1% by weight, and the desirable upper limit thereof is 30% by weight (¶63), which overlaps the claimed range. Further, Onuma teaches the capillary channel is preferably coated with a cationic substance (¶47), which may be the cationic polymer or a silane coupler having a cationic functional group (¶48), suggesting the electrophoresis solution may include the cationic polymer only or both cationic polymer and the cationic coating substance.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma by incorporating the hydrophilic low-molecular-weight compound having a cationic group of Oishi (Oishi, ¶26; e.g., ¶54: ethylenediamine) into the alkaline solution of Onuma (Onuma, ¶55) with a surface coating because the hydrophilic low-molecular-weight compound comprising a cationic group would coat the inner surface of the migration path and thus the migration path having the cationic inner surface would avoid non-specific adsorption of measurement components and enable high accuracy measurement (Oishi, ¶17). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Examiner notes that the hydrophilic low-molecular-weight compound having a cationic group of Oishi does not have to substitute the cationic low-molecular weight of Onuma because the former is for coating the migration path while the latter is a pH adjuster.
Alternatively, in response to the alleged that Onuma and Oishi do not explicitly disclose both cationic polymer and cationic low-molecular compound are in the alkaline solution, Breadmore teaches the separation channel or capillary may be pre-coated or coated in situ (¶101). Onuma teaches the capillary channel is preferably coated with a cationic substance (¶47), which may be the cationic polymer or a silane coupler having a cationic functional group (¶48), suggesting the electrophoresis solution may include the cationic polymer only or both cationic polymer and the cationic coating substance.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Onuma and Oishi by incorporating both the low-molecular-weight compound and the cationic polymer into the alkaline solution of Onuma (Onuma, ¶¶47-48) for in situ coating (Breadmore, ¶101). Here, Choosing from a finite number of identified, predictable solutions (i.e., pre-coated or coated in situ), with a reasonable expectation of success is prima facie obvious. MPEP 2141(III)(E).
Regarding claim 11, Onuma teaches a sample analysis kit (¶15), comprising:
a container (¶15) comprising the capillary electrophoresis solution according to claim 10 (as described in claim 10); and
an electrophoresis chip (Fig. 1; ¶69) comprising a sample holding tank (Fig. 1; ¶69: a sample reservoir 11), an electrophoretic liquid holding tank (Fig. 1; ¶69: a running buffer reservoir 12), and a capillary flow path (Fig. 1; ¶69: a capillary channel 10),
wherein the sample holding tank and the electrophoretic liquid holding tank are communicated with each other via the capillary flow path (Fig. 1: indicating the sample reservoir 11 and the running buffer reservoir 12 are communicated with each other via the capillary channel 10).
Response to Arguments
Applicant’s arguments have been considered and they are persuasive.
Applicant argues Oishi discloses coating the capillary prior to separation of capillary electrophoresis, so there is no teaching or suggestion that the low-molecular-weight hydrophilic compound is contained in the alkaline solution (pp. 4-6, for claims 1 and 10). This argument is unpersuasive. Since Onuma teaches the capillary channel is preferably coated with a cationic substance (¶47), which may be the cationic polymer or a silane coupler having a cationic functional group (¶48), it suggests that the coating is by the separation cationic polymer only (self-coating) or the cationic substance (separate coating substance), which are both in the same alkaline solution. Even if the combined Onuma and Oishi do not disclose both cationic polymer and the cationic compound in the alkaline solution, the prior art, Breadmore, is now relied on to teach that the separation channel or capillary may be pre-coated or coated in situ (¶101). Thus, the modification of Onuma and Oishi by Breadmore by choosing from a finite number of identified, predictable solutions (i.e., pre-coated or coated in situ), is obvious to one of ordinary skill in the art.
Applicant argues the electrophoresis solution shows unexpectedly superior results (p. 6, section III). This argument is unpersuasive. Onuma discloses separation of fractions of hemoglobin (at least one of HbS and HbA2) with high accuracy in a short time by conducting capillary electrophoresis in an alkaline solution containing a cationic polymer (¶24), and the capillary channel is preferably coated with a cationic substance (¶47), which may be the cationic polymer itself or a silane coupler having a cationic functional group (¶48). Thus, the capillary electrophoresis solution containing both cationic polymer and cationic substance for coating would be expected to provide better separation performance, for example, high accuracy in a short time (resulting in reduced peak broadening).
Conclusion
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 extension fee 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 CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795