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 .
Response to Arguments
Applicant's arguments filed August 31, 2026 have been fully considered but they are not persuasive. Amendments to the current set of claims have minorly changed the scope of the claimed invention, resulting in a modification of the previous prior art rejections using the same prior art references.
On page 6 of the Remarks section as indicated by the page number at the bottom of each page, Applicant discusses the status of the current claims, and the amendments made to the claims.
On pages 6-12, Applicant summarizes the previous 103 prior art rejections of independent Claims 1, 10 & 20. Applicant also summarizes the 103 prior art rejections of the dependent claims. Then, Applicant argues against the previous references used disclosing the currently claimed invention of independent Claims 1, 10 & 20. Applicant asserts that the claims require a particular relationship between stationary-phase binding and subsequent strong-acid elution, noting that the Examiner has indicated that primary reference Hu does not disclose certain limitations as does secondary reference Prince in Claims 1, 10 or 20 for example. The Examiner notes here that while each cited reference does not disclose each and every limitation as indicated, the combination of different disclosures from these references together disclose the claims. The Examiner considers this remark by Applicant to be piecemeal analysis, and thus unpersuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant then argues that it is not a matter of what the cited references individually contain, but whether the cited evidence and articulated reasoning establish that the proposed combinations would operate in the manner now expressly required in these claims. Applicant argues that Hu does not provide a teaching such as retention of the claimed plurality as arsenic species bound to anionic and cationic functional groups of the stationary phase. Here, the Examiner notes that secondary reference Prince discloses a method with a stationary phase containing anionic and cationic functional groups, (See paragraph [0126], Prince), wherein the plurality of arsenic species are retained, (See paragraph [0018], [0181], Prince), on the mixed mode column by binding to the anionic and cationic functional groups of the stationary phase, (See paragraph [0181], [0137], Prince). The Examiner notes that Prince discloses this feature instead of Hu so this is also piecemeal analysis. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that reference Fekete does not establish the claimed stationary phase binding relationship. The Examiner notes that Fekete is an evidentiary reference showing that Hu operates in a mixed mode operation instead. Fekete is not relied upon to disclose or establish the claimed stationary phase binding relationship, secondary reference Prince as described above is. The Examiner indicates this remark is piecemeal analysis and is thus unpersuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
On pages 8-9, Applicant argues that Prince discloses various features but not that it establishes the operation resulting from such a modification. Applicant argues that the arsenic species bound to the stationary phase should be subsequently eluted with the strong acid according to different retention times. The Examiner notes that secondary reference Miyashita discloses the elution feature instead, not Prince. Prince discloses the binding of metal ions to a stationary phase of both cationic/anionic functional groups. The Examiner notes that this argument by Applicant regarding the elution feature and Prince is piecemeal analysis, which is unpersuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Next, Applicant argues that Miyashita discloses a materially different chromatographic system and interaction mechanism, in which Miyashita uses fluorocarbon stationary phases and that the separation of the arsenic species was not enough. Applicant also argues that the anionic arsenic species interacts weakly and the cationic arsenic species interacts strongly with anionic groups. The Examiner notes here that it is not specified how much elution must occur and just how strong the binding is between anionic and cationic groups, just that elution with a strong acid occurs and that there is binding for both types of groups. The Examiner finds this argument unpersuasive as a result. Applicant also argues that a different mobile phase in Miyashita provides the best separation instead. Applicant concludes that the results in Miyashita demonstrate why the mere existence of acid-induced elution in Miyashita does not establish the behavior of the material different stationary-phase system as in the rejection. The Examiner notes here that there is not a question of a degree of elution and the level of performance required in the claim. The Examiner also notes that it is not required what kind of stationary phase is in the chromatography column. Rather, both Hu and Miyashita employ the use of HPLC in which RPLC is a subset of HPLC. The Examiner notes that Prince already discloses using both anionic and cationic functional groups. Prince also notes the use of C18 stationary phase, (See paragraph [0137], Prince), as in Hu, and Miyashita discusses the use of C18 stationary phase in conjunction with the fluorocarbon stationary phase as well, (See “Introduction”, Miyashita). As a result, the Examiner finds Applicant’s arguments here piecemeal analysis, and unpersuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
On page 10, Applicant argues that the obviousness combinations and statements have to yield predictable results., but argues that the rejection does not establish why acid-elution behavior observed by Miyashita using its fluorocarbon stationary phase would carry over to arsenic species using the proposed modification involving Prince. The Examiner notes that Miyashita explicitly elutes arsenic species with HNO3 using the fluorocarbon stationary phase, (“the overall elution of the As species in the case of HNO3 was more than two times faster”, “See “Results and Discussion”, Miyashita), and that Miyashita discusses the use of both C18 and fluorocarbon stationary phase as in its Introduction, and that no specific type of stationary phase has actually been claimed. For these reasons, the Examiner finds that the references establish overlapping subject matter in the same field of endeavor, and may be combined with a reasonable expectation of predictable results. The Examiner finds Applicant’s remarks here unpersuasive as a result.
On pages 10-11, Applicant argues against the combination of Voice and its evidentiary references for Claim 10 because the combination of rejections do not establish that it would perform the binding and subsequent strong-acid elution required by Claim 10. The Examiner notes that no specific argument is provided regarding Voice or the evidentiary references beyond what has already been argued above. The Examiner finds that the combination of Hu, Prince and Miyashita read upon this particular claim feature as explained above. The Examiner finds Applicant’s remarks here unpersuasive.
On page 11, Applicant argues against Claim 20 because Miyashita does not establish that at least two anionic arsenic species are retained as species bound to the anionic and cationic functional groups of the stationary phase and would subsequently be eluted with the strong acid according to different retention times. Here, the Examiner notes that the multiple arsenic species including two anionic arsenic species has already been disclosed by primary reference Hu, arsenite and arsenate. Thus, it is not required for Miyashita to re-establish this principle, so this is piecemeal analysis. Furthermore, the Examiner notes that Miyashita discloses multiple different types of arsenic species being retained and eluted in its examples such as “the separation of the 10 arsenic species” or “the separation of the 11 As species”, (See “Results and Discussion”, Miyashita). The Examiner finds this argument also unpersuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The remainder of the claims do not provide any additional specific arguments or reasons against the current prior art references, and are considered moot.
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.
Claim(s) 1-5, 9, 20-25 & 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., (Hereinafter “Hu”, “Separation methods applied to arsenic speciation”, Comprehensive Analytical Chemistry, Volume 85, Chapter 4, pp. 89-144, 2019, 56 pages total), as evidenced by Fekete et al., (Hereinafter “Fekete”, “Weak to strong ion-pair gradients to expand the selectivity of oligonucleotide separations in reversed phase liquid chromatography – A proof of concept”, Journal of Chromatography Open, 8, 2025, 8 total pages), and as evidenced by Zhang et al., (Hereinafter “Zhang”, “The potential role of malonic acid in the atmospheric sulfuric acid – Ammonia clusters formation”, Chemosphere, 203, 26-33, 2018), in view of Prince et al., (“Prince”, US 2014/0048741), in further view of Miyashita et al., (“Miyashita”, “A Simple and Effective Method for Speciation Analysis of 13 Arsenic Species Using HPLC on a Fluorocarbon Stationary Phase Coupled to ICP-MS”, Analytical Sciences, published Feb. 2021, 6 total pages).
Claims 1-5 & 9 are directed to a method, a method type invention group.
Regarding Claims 1-5 & 9, Hu discloses a method comprising: separating a plurality of arsenic species using a mixed mode chromatography column and a strong acid, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract), the plurality of arsenic species including at least one of each of an anionic arsenic species, (Table 1, “Tree moss”, “AsIII”, known as arsenite, and “AsV”, known as arsenate, according to page 90, Hu), a cationic arsenic species, (Table 1, “Tree moss”, “AsC”; which is arsenocholine according to page 90, Hu), a neutral arsenic species, (Table 1, “Tree moss”, “TMAO”; which is trimethylarsinoxide according to page 90, Hu), and a zwitterionic arsenic species, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu), wherein the mixed mode chromatography column includes a stationary phase, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract).
Hu does not disclose the stationary phase containing anionic and cationic functional groups, wherein the plurality of arsenic species are retained on the mixed mode chromatography column as arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Prince discloses a method with a stationary phase containing anionic and cationic functional groups, (See paragraph [0126], Prince), wherein the plurality of arsenic species are retained, (See paragraph [0018], [0181], Prince), on the mixed mode chromatography column as arsenic species bound to the anionic and cationic functional groups of the stationary phase, (See paragraph [0018], [0181], [0137], Prince).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating the stationary phase containing anionic and cationic functional groups wherein the plurality of arsenic species are retained on the mixed mode column by binding to the anionic and cationic functional groups of the stationary phase as in Prince for “removing heavy metal ions”, (See paragraph [0127], Prince), based on “the requirements of an intended filtration application”, (See paragraph [0121], Prince), providing “performance benefits over the same ion exchange resin used in traditional packed beds or columns”, (See paragraph [0088], Prince).
Modified Hu does not specifically disclose wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Miyashita discloses arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times, (See page 383, “Results and Discussion”, “HNO3”, “the overall elution of the As species in the case of HNO3 was more than two times faster”, Miyashita).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times as in Miyashita in order because it “showed the highest potential for the separation of a larger number of As species when using simple acid-based mobile phases” in which “the overall elution of the As species in the case of HNO3 was more than two times faster”, (“Results and Discussion”, page 383, Miyashita).
Additional Disclosures Included:
Claim 2: The method of claim 1 wherein the anionic arsenic species is selected from the group consisting of arsenite, methylarsonate, dimethylarsinate, phenylarsonate, and arsenate, (Table 1, “Tree moss”, “AsIII”, known as arsenite, and “AsV”, known as arsenate, according to page 90, Hu).
Claim 3: The method of claim 1 wherein the neutral arsenic species includes trimethylarsinoxide, (Table 1, “Tree moss”, “TMAO”; which is trimethylarsinoxide according to page 90, Hu).
Claim 4: The method of claim 1 wherein the zwitterionic arsenic species includes arsenobetaine, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu).
Claim 5: The method of claim 1 wherein the cationic arsenic species is selected from the group consisting of arsenocholine and tetramethylarsonium, (Table 1, “Tree moss”, “AsC”; which is arsenocholine according to page 90, Hu).
Claim 9: The method of claim 1 wherein separating the plurality of arsenic species further uses an organic solvent, (Table 1, “Tree moss”, “methanol”).
Claims 20-25 & 30 are directed to a method, a method type invention group.
Regarding Claims 20-25 & 30, Hu discloses a method comprising: separating a plurality of arsenic species using a chromatography column and a strong acid, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract), the plurality of arsenic species including at least two anionic arsenic species, (Table 1, “Tree moss”, “AsIII”, known as arsenite, and “AsV”, known as arsenate, according to page 90, Hu), wherein the chromatography column is a mixed mode chromatography column and the mixed mode chromatography column includes a stationary phase, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract), but does not disclose the stationary phase with anionic and cationic functional groups.
Hu does not disclose the stationary phase containing anionic and cationic functional groups, wherein the plurality of arsenic species are retained on the mixed mode chromatography column as arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Prince discloses a method with a stationary phase containing anionic and cationic functional groups, (See paragraph [0126], Prince), wherein the plurality of arsenic species are retained, (See paragraph [0018], [0181], Prince), on the mixed mode chromatography column by binding to the anionic and cationic functional groups of the stationary phase, (See paragraph [0018], [0181], [0137], Prince).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating the stationary phase containing anionic and cationic functional groups wherein the plurality of arsenic species are retained on the mixed mode chromatography column by binding to the anionic and cationic functional groups of the stationary phase as in Prince for “removing heavy metal ions”, (See paragraph [0127], Prince), based on “the requirements of an intended filtration application”, (See paragraph [0121], Prince), providing “performance benefits over the same ion exchange resin used in traditional packed beds or columns”, (See paragraph [0088], Prince).
Modified Hu does not specifically disclose wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Miyashita discloses arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times, (See page 383, “Results and Discussion”, “HNO3”, “the overall elution of the As species in the case of HNO3 was more than two times faster”, Miyashita).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times as in Miyashita in order because it “showed the highest potential for the separation of a larger number of As species when using simple acid-based mobile phases” in which “the overall elution of the As species in the case of HNO3 was more than two times faster”, (“Results and Discussion”, page 383, Miyashita).
Additional Disclosures Included:
Claim 21: The method of claim 20 wherein the anionic arsenic species is selected from the group consisting of arsenite, methylarsonate, dimethylarsinate, phenylarsonate, and arsenate, (Table 1, “Tree moss”, “AsIII”, known as arsenite, and “AsV”, known as arsenate, according to page 90, Hu).
Claim 22: The method of claim 20 wherein the plurality of arsenic species further includes at least one zwitterionic arsenic species, at least one neutral arsenic species, or at least one cationic arsenic species, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu; Table 1, “Tree moss”, “AsC”; which is arsenocholine according to page 90, Hu).
Claim 23: The method of claim 22 wherein the neutral arsenic species includes dimethylarsinate, (Table 1, “Tree moss”, “DMA”, which is “dimethylarsonic acid”, according to page 90, Hu).
Claim 24: The method of claim 22 wherein the zwitterionic arsenic includes arsenobetaine, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu).
Claim 25: The method of claim 22 wherein the cationic arsenic species is selected from the group consisting of arsenocholine and tetramethylarsonium, (Table 1, “Tree moss”, “AsC”; which is arsenocholine according to page 90, Hu).
Claim 30: The method of claim 20 wherein separating the plurality of arsenic species further uses an organic solvent, (Table 1, “Tree moss”, “methanol”, Hu).
Claim(s) 7, 8, 10-15, 17-19 & 27-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., (Hereinafter “Hu”, “Separation methods applied to arsenic speciation”, Comprehensive Analytical Chemistry, Volume 85, Chapter 4, pp. 89-144, 2019, 56 pages total), as evidenced by Fekete et al., (Hereinafter “Fekete”, “Weak to strong ion-pair gradients to expand the selectivity of oligonucleotide separations in reversed phase liquid chromatography – A proof of concept”, Journal of Chromatography Open, 8, 2025, 8 total pages), in view of Prince et al., (“Prince”, US 2014/0048741), in further view of Miyashita et al., (“Miyashita”, “A Simple and Effective Method for Speciation Analysis of 13 Arsenic Species Using HPLC on a Fluorocarbon Stationary Phase Coupled to ICP-MS”, Analytical Sciences, published Feb. 2021, 6 total pages), in further view of Voice et al., (“Voice”, US 2004/0101971), as further evidenced by “Table of Acids”, (“Appendix 5 Chem 1A, B, C, Lab Manual and Zumdahl 6th Ed., George Washington University, obtained from web 10/15/2025, 2 total pages) and as further evidenced by Holl, (“Anion Exchangers: Ion Exchange”, Water Treatment, III, published 2000, 8 total pages).
Regarding Claim 7, modified Hu discloses the method of claim 1 but does not disclose wherein the strong acid has a pKa less than 2.0.
Voice discloses a method wherein the strong acid has a pKa less than 2.0, (See paragraph [0033]; HCl; and as evidenced by “Table of Acids”, pKa of HCl is less than 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating wherein the strong acid has a pKa less than 2.0 as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Regarding Claim 8, modified Hu discloses the method of claim 1, but does not disclose wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof.
Voice discloses a method wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof, (See paragraph [0033]; HCl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Claims 10-15 & 17-19 are directed to a method, a method type invention group.
Regarding Claims 10-15 & 17-19, modified Hu discloses a method comprising: separating a plurality of arsenic species using a chromatography column and a strong acid, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract), wherein the chromatography column is a mixed mode chromatography column, and the mixed mode column includes a stationary phase, (Table 1, “Tree moss”, “CAPCELL PAK” and “Ion-pair RPLC”, and “Ion-pair RPLC”, using “4 mM malonic acid….(pH 3.0)”, and See pages 106-107, Hu; as evidenced by Fekete on pages 1-2 in “1. Introduction” which “the electrostatic and hydrophobic interactions do occur at the same time and therefore the retention mechanism is a mixed mode mechanism”; and as evidenced by Zhang, “Malonic acid…has been identified experimentally and computationally to be a strong acid”, See Abstract), but does not explicitly disclose the strong acid having a counter ion, the counter ion including a weaker anion exchange species than NO3-, or the stationary phase with anionic and cationic functional groups, wherein the plurality of arsenic species are retained as arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Prince discloses a method with a stationary phase containing anionic and cationic functional groups, (See paragraph [0126], Prince), wherein the plurality of arsenic species are retained, (See paragraph [0018], [0181], Prince), on the mixed mode chromatography column by binding to the anionic and cationic functional groups of the stationary phase, (See paragraph [0018], [0181], [0137], Prince).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating the stationary phase containing anionic and cationic functional groups wherein the plurality of arsenic species are retained on the mixed mode column by binding to the anionic and cationic functional groups of the stationary phase as in Prince for “removing heavy metal ions”, (See paragraph [0127], Prince), based on “the requirements of an intended filtration application”, (See paragraph [0121], Prince), providing “performance benefits over the same ion exchange resin used in traditional packed beds or columns”, (See paragraph [0088], Prince).
Modified Hu does not specifically disclose wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times.
Miyashita discloses arsenic species bound to the anionic and cationic functional groups of the stationary phase and wherein the bound arsenic species are subsequently eluted from the mixed mode chromatography column with the strong acid according to different retention times,, (See page 383, “Results and Discussion”, “HNO3”, “the overall elution of the As species in the case of HNO3 was more than two times faster”, Miyashita).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Hu by incorporating the plurality of arsenic species are eluted from the mixed mode column with the strong acid according to different retention times as in Miyashita in order because it “showed the highest potential for the separation of a larger number of As species when using simple acid-based mobile phases” in which “the overall elution of the As species in the case of HNO3 was more than two times faster”, (“Results and Discussion”, page 383, Miyashita).
Voice discloses a method, the strong acid having a counter ion, the counter ion including a weaker anion exchange species than NO3-., (See paragraph [0033]; HCl; as evidenced by Holl, NO3- is higher than Cl- on page 1, “Introduction”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating the strong acid having a counter ion, the counter ion including a weaker anion exchange species than NO3- as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Additional Disclosures Included:
Claim 11: The method of claim 10 wherein the plurality of arsenic species includes an anionic arsenic species selected from the group consisting of arsenite, methylarsonate, dimethylarsinate, phenylarsonate, and arsenate, (Table 1, “Tree moss”, “AsIII”, known as arsenite, and “AsV”, known as arsenate, according to page 90, Hu).
Claim 12: The method of claim 10 wherein the neutral arsenic species is selected from the group consisting of trimethylarsinoxide, (Table 1, “Tree moss”, “TMAO”; which is trimethylarsinoxide according to page 90, Hu).
Claim 13: The method of claim 10 wherein the plurality of arsenic species includes a zwitterionic arsenic species, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu).
Claim 14: The method of claim 13 wherein the zwitterionic arsenic species includes arsenobetaine, (Table 1, “Tree moss”, “AsB”; which is arsenobetaine according to page 90, Hu).
Claim 15: The method of claim 10 wherein the plurality of arsenic species includes a cationic arsenic species selected from the group consisting of arsenocholine and tetramethylarsonium, (Table 1, “Tree moss”, “AsC”; which is arsenocholine according to page 90, Hu).
Claim 17: The method of claim 10 wherein the strong acid has a pKa less than 2, (See paragraph [0033], Voice; HCl; and as evidenced by “Table of Acids”, pKa of HCl is less than 1).
Claim 18: The method of claim 10 wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof, (See paragraph [0033], Voice; HCl).
Claim 19: The method of claim 10 wherein separating the plurality of arsenic species further uses an organic solvent, (Table 1, “Tree moss”, “methanol”, HU).
Regarding Claim 27, modified Hu discloses the method of claim 20 but does not disclose wherein the strong acid has a counter ion that is a weaker anion exchange species than NO3-.
Voice discloses a method wherein the strong acid has a counter ion that is a weaker anion exchange species than NO3-, (See paragraph [0033]; HCl; as evidenced by Holl, NO3- is higher than Cl- on page 1, “Introduction”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating wherein the strong acid has a counter ion that is a weaker anion exchange species than NO3- as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Regarding Claim 28, modified Hu discloses the method of claim 20 but does not disclose wherein the strong acid has a pKa less than 2.0.
Voice discloses a method wherein the strong acid has a pKa less than 2.0, (See paragraph [0033]; HCl; and as evidenced by “Table of Acids”, pKa of HCl is less than 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating wherein the strong acid has a pKa less than 2.0 as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Regarding Claim 29, modified Hu discloses the method of claim 20, but does not disclose wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof.
Voice discloses a method wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof, (See paragraph [0033]; HCl).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Hu by incorporating wherein the strong acid includes methanesulfonic acid, ethanesulfonic acid, hydrochloric acid, hydrobromic acid, iodic acid, chloric acid, or any combination thereof as in Voice so that it “protonates the [arsenic species] to a cationic form” and “can be eluted from the medium”, (See paragraph [0033], Voice), to “produce accurate and precise As species concentration”, (See paragraph [0032], Voice).
Conclusion
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/JONATHAN M PEO/Primary Examiner, Art Unit 1779
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