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 .
Priority
Applicant’s claim for the benefit of a prior-filed application (has PRO 63414437, filed on October 07, 2022) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claim Objections
Claim 10 objected to because of the following informalities:
The phrase “wherein mass spectroscopy comprises a tandem quadrupole mass spectrometer or…” should be corrected to read “wherein the mass spectrometry is performed using a tandem quadrupole mass spectrometer or…” for technical and dependency clarity.
Claim 12 objected to because of the following informalities:
The phrase “further comprises” should be corrected to read “further comprising” for proper grammar.
Claim 14 objected to because of the following informalities:
The phrase “the method comprises” should be corrected to read “the method comprising” for proper grammar.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 5 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim recites the limitation “phosphonate group(s),” but the specification describes the fluorinated compound as comprising “phosphate group(s)” (¶[0018]; ¶[0024]; ¶[0031]) and, although the specification generically lists “phosphonates” among possible PFAS functional groups (¶[0050]), the specification does not describe a fluorinated-compound embodiment comprising phosphonate group(s) in the manner recited in Claim 5. Accordingly, the specification fails to reasonably convey possession of a fluorinated compound comprising phosphonate group(s) as of the filing date.
The following is a quotation of 35 U.S.C. 112(b):
(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.
Claims 1-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “the detector” in step (d). There is insufficient antecedent basis for this limitation in the claim. A detector has not been previously introduced in the claim. Claims 2–13, which depend on Claim 1, are similarly defective by virtue of dependency.
Claim 14 recites the limitation “the detector” in step (d). There is insufficient antecedent basis for this limitation in the claim. A detector has not been previously introduced in the claim. Claims 15–16, which depend on Claim 14, are similarly defective by virtue of dependency.
Claim 17 recites the limitation “the detector” in step (d). There is insufficient antecedent basis for this limitation in the claim. A detector has not been previously introduced in the claim.
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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4, 6-10, 12-13, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over EPA Method 8327 (Per-and Polyfluoroalkyl Substances (PFAS) by Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS), 2021, hereinafter EPA) in view of ZELECHONOK (US11307181B1).
Regarding Claim 1, EPA discloses a method for analyzing per- and polyfluoroalkyl substances (PFAS) using a liquid chromatography/tandem mass spectrometry (LC/MS/MS) system (Title, §1.1).
In particular, precautionary measures are employed to minimize problems with measurement precision and bias, including using LC/MS-grade solvents, verifying supplies/reagents and LC-system materials to reduce PFAS contamination, using appropriate containers to avoid analyte loss, placing an isolator column upstream of the sample injection valve to delay contaminants to the analytical column, and following labware cleaning to minimize carryover (§4.3; §4.3.1–§4.3.6).
Consistent with these contamination-control measures, the equipment includes a liquid chromatograph (LC) system described as a UPLC, analytical LC columns including phenyl-hexyl and C18 reversed-phase columns, isolator columns specified as C18 columns, and a tandem mass spectrometry (MS/MS) detector capable of MS/MS analysis, including an example triple quadrupole mass spectrometer with an electrospray ionization source (§6.0–§6.1).
Samples and standards are analyzed under the same LC/MS/MS conditions, including injection volume, consistent with introducing a liquid sample via an injection device (§11.3.2; §11.5.1). Target analytes are qualitatively identified by comparing primary and secondary product ion responses to standards and by comparing retention time in a sample to the isotopically labeled surrogate in the same sample and/or to the target analyte in standards (§11.6). Once a target compound has been identified, the compound is quantified based on the integrated abundance of the primary product ion unless interference problems are observed (§11.7).
However, EPA does not explicitly disclose “the isolator column comprises a stationary phase material comprising a mixed mode with anion exchange surface chemistry.”
ZELECHONOK discloses a high-pressure liquid chromatography system using multiple mixed-mode columns connected to a switching valve (Col. 1, Lns. 30–33).
The high-pressure liquid chromatography system avoids interference from contaminants by initially passing mobile phase containing unwanted material through the first-dimension column as a cleaning column before the second-dimension analytical column. The mixed-mode columns have reverse phase and ion-exchange characteristics to combine sample cleaning and analyte separation in one automated process (Col. 2, Lns. 7–43).
FIG. 1 is a schematic representation of a stationary phase with a ligand structure that performs as mixed-mode chromatography material with anion exchange properties (Col. 2, Lns. 65–67). The stationary phase comprises a rigid supporting material such as silica gel with an ion-bearing functional group and a hydrophobic functional group chemically attached to the surface, and ligands extending from the surface carry negative ions (Col. 4, Lns. 26–34).
Advantageously, the first-dimension cleaning column disclosed by ZELECHONOK avoids interference from contaminants, which mitigates the problems that interferences and sample-to-sample variability shorten column life due to irreversibly retained contamination and drive the use of long cleaning procedures and guard columns (Col. 1, Ln. 47–Col. 2, Ln. 3). In view of EPA’s fluorinated compound analysis method, a person skilled in the art would incorporate the mixed-mode anion-exchange stationary phase for the isolator column to delay the elution of contaminant fluorinated compounds to the analytical column for the stated benefit with predictable results.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the mixed-mode anion-exchange stationary phase, as disclosed by ZELECHONOK, into the contaminant-delay step performed by the isolator column in the fluorinated compound analysis method by EPA.
Regarding Claim 2, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. EPA discloses that at least one type of fluorinated compound is a polyfluoroalkyl or perfluoroalkyl substance (§1.0).
Regarding Claim 3, modified EPA makes obvious the fluorinated compound analysis method of Claim 2. EPA discloses polyfluoroalkyl substances having 3 to 5 carbon atoms, such as PFBA (C4) and PFPeA (C5) (§6.1, Table 1).
Regarding Claim 4, modified EPA makes obvious the fluorinated compound analysis method of Claim 2. EPA discloses polyfluoroalkyl substances having more than 5 carbon atoms, such as PFHxA (C6) through PFDA (C10) and longer (§6.1, Table 1).
Regarding Claim 6, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. ZELECHONOK discloses that the stationary phase material comprises a mixed mode with anion exchange surface chemistry (Col. 4, Lns. 26–34). It would have been obvious to use the mixed-mode anion-exchange stationary phase material for the analytical column.
Regarding Claims 7 and 8, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. EPA discloses that the analytical column comprises a stationary phase material comprising a reversed phase surface chemistry, such as C18 alkyl-bonded surface chemistry (§6.1.2).
Regarding Claims 9 and 10, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. EPA discloses that the mass spectrometer is capable of tandem mass spectrometry (MS/MS) analysis and is specifically a triple quadrupole mass spectrometer (§6.1.4).
Regarding Claim 12, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. EPA discloses identifying target analytes based on mass spectrometry ion responses and retention time, and quantifying an identified target compound based on the integrated abundance of the primary product ion (§11.6; §11.7).
Regarding Claim 13, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. EPA discloses that LLOQs are established to meet project-specific decision levels and regulatory action levels, and that concentrations below the established LLOQ may still be detected and reported (§9.9; §9.9.4).
Regarding the limitation “the concentration of at least one type of fluorinated compound in the liquid sample is less than 0.1 ng/L,” this describes a property of the liquid sample (as received) rather than a step of the method, and therefore adds no patentable weight to the claimed method. See MPEP § 2111.04.
Regarding Claim 17, EPA discloses a method for analyzing per- and polyfluoroalkyl substances (PFAS) using a liquid chromatography/tandem mass spectrometry (LC/MS/MS) system (Title, §1.1).
In particular, precautionary measures are employed to minimize problems with measurement precision and bias, including verifying supplies and LC-system materials to reduce PFAS contamination (§4.3) and placing an isolator column upstream of the sample injection valve to delay contaminants to the analytical column (§4.3.5).
Consistent with these contamination-control measures, the equipment includes a liquid chromatograph (LC) system described as a UPLC, analytical LC columns including phenyl-hexyl and C18 reversed-phase columns, isolator columns specified as C18 columns, and a tandem mass spectrometry (MS/MS) detector (§6.0–§6.1). Samples are analyzed using the same LC/MS/MS conditions as used to generate the initial calibration (§11.5.1).
However, EPA does not explicitly disclose that “at least one column comprises a stationary phase material possessing a mixed mode with anion exchange surface chemistry.”
ZELECHONOK discloses a high-pressure liquid chromatography system using multiple mixed-mode columns connected to a switching valve (Col. 1, Lns. 30–33).
The high-pressure liquid chromatography system avoids interference from contaminants by initially passing mobile phase containing unwanted material through the first-dimension column as a cleaning column before the second-dimension analytical column. The mixed-mode columns have reverse phase and ion-exchange characteristics to combine sample cleaning and analyte separation in one automated process (Col. 2, Lns. 7–43).
FIG. 1 is a schematic representation of a stationary phase with a ligand structure that performs as mixed-mode chromatography material with anion exchange properties (Col. 2, Lns. 65–67). The stationary phase comprises a rigid supporting material such as silica gel with an ion-bearing functional group and a hydrophobic functional group chemically attached to the surface, and ligands extending from the surface carry negative ions (Col. 4, Lns. 26–34).
Advantageously, the first-dimension cleaning column disclosed by ZELECHONOK avoids interference from contaminants, which mitigates the problems that interferences and sample-to-sample variability shorten column life due to irreversibly retained contamination and drive the use of long cleaning procedures and guard columns (Col. 1, Ln. 47–Col. 2, Ln. 3). In view of EPA’s fluorinated compound analysis method, a person skilled in the art would incorporate the mixed-mode anion-exchange stationary phase for at least one column for the stated benefit with predictable results.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the mixed-mode anion-exchange stationary phase, as disclosed by ZELECHONOK, into at least one column in the fluorinated compound analysis method by EPA.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over EPA in view of ZELCHONOK as applied to claim 1 above, and further in view of LAUBER et al. (US20190086371A1, hereinafter LAUBER).
Regarding Claim 11, modified EPA makes obvious the fluorinated compound analysis method of Claim 1. However, modified EPA does not explicitly disclose "an interior surface of the isolator column is coated with an alkylsilyl coating."
LAUBER discloses the use of vapor deposition coated flow paths for improved chromatography (¶[0002]). The chromatographic device includes a chromatography column downstream of a sample injector, wherein interior surfaces of the chromatography column form part of a fluidic flow path having wetted surfaces, and at least a portion of the wetted surfaces of the fluidic flow path are coated with an alkylsilyl coating (¶[0015]).
Advantageously, the alkylsilyl coating disclosed by LAUBER reduces unfavorable chromatographic secondary interactions between analytes and metallic flow path surfaces while maintaining high-pressure capability for chromatographic separation (¶[0003]; ¶[0008]). In view of modified EPA’s fluorinated compound analysis method, a person skilled in the art would incorporate the alkylsilyl coating for the interior surface of the isolator column for the stated benefit with predictable results.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the alkylsilyl coating, as disclosed by LAUBER, into the interior surface of the isolator column in the fluorinated compound analysis method by modified EPA.
Claims 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over EPA in view of STRAMENGA et al. (Perfluoroalkyl and polyfluoroalkyl substances (PFASs): An optimized LC-MS/MS procedure for feed analysis, 2021, hereinafter STRAMENGA).
Regarding Claim 14, EPA discloses a method for analyzing per- and polyfluoroalkyl substances (PFAS) using a liquid chromatography/tandem mass spectrometry (LC/MS/MS) system (Title, §1.1).
In particular, precautionary measures are employed to minimize problems with measurement precision and bias, including verifying supplies and LC-system materials to reduce PFAS contamination (§4.3) and placing an isolator column upstream of the sample injection valve to delay contaminants to the analytical column (§4.3.5).
Consistent with these contamination-control measures, the equipment includes a liquid chromatograph (LC) system described as a UPLC, analytical LC columns including phenyl-hexyl and C18 reversed-phase columns, isolator columns specified as C18 columns, and a tandem mass spectrometry (MS/MS) detector (§6.0–§6.1). Samples are analyzed using the same LC/MS/MS conditions as used to generate the initial calibration (§11.5.1).
However, EPA does not explicitly disclose that the second fluorinated compound reaches the detector prior to the first fluorinated compound and that the contamination is delayed by at least 1 minute in step (d).
STRAMENGA discloses development, optimization, and validation of an LC-MS/MS analytical protocol enabling quantification of PFAS in animal feeds, including assessing matrix interferences and validating using spiked feed samples (Abstract, Pg. 1).
Similar to the EPA method, the experimentation was performed on a UPLC LC-MS/MS system, and an isolator column was installed between the pump and the injector (§2.4, Pg. 3). The short C18 isolator column was installed between the mixer and the sample loop with the aim of trapping and delaying PFAS originating from the LC system, such that injected analytes are eluted earlier than those originating from tubing contamination (§3.1, Pg. 4–5).
Advantageously, the trapping and delaying of PFAS originating from the LC system disclosed by STRAMENGA enables injected analytes to be eluted earlier than tubing contamination, which mitigates laboratory contamination that limits achieving low detection limits in PFAS analysis (§3.1, Pg. 4–5). In view of modified EPA’s fluorinated compound analysis method, a person skilled in the art would incorporate the method for trapping and delaying PFAS originating from the LC system for the stated benefit with predictable results.
Regarding the limitation “delayed at least 1 minute,” the amount of delay is a result-effective variable. In view of STRAMENGA’s trapping and delaying method, a delay of at least 1 minute would have been a routine optimization to provide sufficient temporal separation between the injected analytes and the delayed contamination.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the method for trapping and delaying PFAS originating from the LC system, as disclosed by STRAMENGA, into the fluorinated compound analysis method by EPA.
Regarding Claim 16, modified EPA makes obvious the method of delaying retention time of a contamination in a liquid chromatography system of Claim 14. STRAMENGA discloses a method for trapping and delaying PFAS originating from the LC system (§3.1, Pg. 4–5).
Regarding the limitation “delayed at least 5 minutes,” the amount of delay is a result-effective variable. In view of STRAMENGA’s trapping and delaying method, a delay of at least 5 minutes would have been a routine optimization to provide sufficient temporal separation between the injected analytes and the contamination.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over EPA in view of STRAMENGA as applied to claim 14 above, and further in view of ZELECHONOK.
Regarding Claim 15, modified EPA makes obvious the method of delaying retention time of a contamination in a liquid chromatography system of Claim 14. However, modified EPA does not explicitly disclose “the isolator column comprises a stationary phase material comprising a mixed mode with anion exchange surface chemistry.”
ZELECHONOK discloses a high-pressure liquid chromatography system using multiple mixed-mode columns connected to a switching valve (Col. 1, Lns. 30–33).
The high-pressure liquid chromatography system avoids interference from contaminants by initially passing mobile phase containing unwanted material through the first-dimension column as a cleaning column before the second-dimension analytical column. The mixed-mode columns have reverse phase and ion-exchange characteristics to combine sample cleaning and analyte separation in one automated process (Col. 2, Lns. 7–43).
FIG. 1 is a schematic representation of a stationary phase with a ligand structure that performs as mixed-mode chromatography material with anion exchange properties (Col. 2, Lns. 65–67). The stationary phase comprises a rigid supporting material such as silica gel with an ion-bearing functional group and a hydrophobic functional group chemically attached to the surface, and ligands extending from the surface carry negative ions (Col. 4, Lns. 26–34).
Advantageously, the first-dimension cleaning column disclosed by ZELECHONOK avoids interference from contaminants, which mitigates the problems that interferences and sample-to-sample variability shorten column life due to irreversibly retained contamination and drive the use of long cleaning procedures and guard columns (Col. 1, Ln. 47–Col. 2, Ln. 3). In view of modified EPA’s method of delaying retention time of a contamination in a liquid chromatography system, a person skilled in the art would incorporate the mixed-mode anion-exchange stationary phase for the isolator column for the stated benefit with predictable results.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the mixed-mode anion-exchange stationary phase, as disclosed by ZELECHONOK, for the isolator column in the method of delaying retention time of a contamination in a liquid chromatography system by modified EPA.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAK L. CHIU whose telephone number is (703)756-1059. The examiner can normally be reached M-F: 9:00am - 6:00pm (CST).
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/TAK L. CHIU/Examiner, Art Unit 1777
/KRISHNAN S MENON/Primary Examiner, Art Unit 1777