DETAILED ACTION
Preliminary Amendment filed on 05/04/2023 is acknowledged. Claims 13-15 are cancelled. Claims 1-12 and 16-21 are pending in the application and are considered on merits, of which, claim 16-21 are newly added.
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 .
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 11 is 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 11 recites: “An analytical system adapted to perform the method of claim 1.” without recite any structural features of the claimed system, instead defining the system solely by its intended use or functional capability (“adapted to perform the method”). Such language does not provide adequate notice of what specific apparatus or system falls within the scope of the claim. It is therefore unclear what distinguishes the claimed analytical system from any conventional analytical instrument, including a general laboratory LC–MS/MS system, that could be configured to carry out the method of claim 1.
A proper system claim must include structural limitations or tangible components (e.g., a mass spectrometer, derivatization module, reagent handling system, processor configured to execute specific operations, etc.) that distinguish the claimed system from the prior art. Since no such structure is recited, the boundaries of the claim cannot be determined with reasonable certainty.
Accordingly, claim 11 is indefinite under §112(b).
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.
Claim(s) 1, 3-6, 9-12, 16, 18 and 21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Joo et al. (Journal of Chromatography B, 2013) (Joo).
Regarding claim 1, Joo teaches A method for determining the presence or level of an analyte of interest having a molar mass of smaller than 200 Da (valproic acid) in a sample (abstract), comprising the steps of
a) providing the sample comprising the analyte of interest, wherein the analyte of interest comprises a carboxylic acid group (page 36, par 6),
b) optionally activating the analyte of interest by the addition of at least one activation reagent (TPP, DTTP) (page 36, par 6),
c) derivatizing the analyte of interest provided by step a) orb) with a nucleophilic derivatization reagent (PA) for forming a derivatized analyte of interest (Fig. 1, page 36, par 6), and
d) determining the presence or level of the derivatized analyte of interest in the sample using mass spectrometry (MS) (page 37, par 1).
Regarding claim 3, Joo teaches that wherein the analyte of interest (VPA) has a molar mass of 150 Da or less (page 36, par 6).
Regarding claim 4, Joo teaches that wherein the analyte of interest is valproic acid (page 36, par 6).
Regarding claim 5, Joo teaches that wherein in step c) an amide of the derivatized analyte of interest is formed (Fig. 1).
Regarding claim 6, Joo teaches that wherein the nucleophilic derivatization reagent comprises an amine group (Fig. 1).
Regarding claim 9, Joo teaches that wherein the analyte of interest is free of a nucleophilic functional group, which could react with the carboxylic acid group of the analyte of interest (abstract).
Regarding claim 10, Joo teaches that wherein the said method comprises an additional step:
e) enriching the sample (centrifuge and dry) (page 36, par 6).
Regarding claim 11, Joo teaches an analytical system adapted to perform the method of claim 1 (page 36, par 6, page 37, par 1).
Regarding claim 12, Joo teaches a sampling tube for collecting a patient sample comprising a nucleophilic derivatization reagent for forming a derivatized analyte of interest in a sample (page 36, par 6),
wherein the one or more analytes of interest is a carboxylic acid having a molar mass of smaller than 200 Da (page 36, par 6).
Regarding claim 16, Joo teaches that wherein the nucleophilic derivatization reagent comprises a primary amine group, a secondary amine group, or a tertiary amine group (Fig. 1).
Regarding claim 18, Joo teaches that wherein the nucleophilic derivatization reagent comprises a primary amine group (Fig. 1).
Regarding claim 21, Joo teaches that wherein the one or more analytes of interest is valproic acid or salicylic acid (page 36, par 6).
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.
Claim(s) 2 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Joo et al. (Journal of Chromatography B, 2013) (Joo).
Regarding claim 2, the Courts have held that to provide a mechanical or automatic means to replace manual activity, which accomplishes the same result, is within the ambit of a person of ordinary skill in the art. (See In re Venner, 120 USPQ 192 CCPA 1958) (see MPEP section 2144.04). Therefore, it would have been obvious to one of ordinary skill in the art to automate the procedure.
Nevertheless, Joo teaches autosampler (page 36, par 8) to automate the sampling process.
Regarding claim 17, Joo does not specifically teach that wherein the nucleophilic derivatization reagent comprises a secondary amine group. However, secondary amines are closely related, well-known alternatives to primary amines for amide formation (with predictable retention and ionization effects), a POSA would have been motivated to substitute a secondary amine for Joo’s primary amine with predictable results. This is a routine design choice within the same reaction mechanism and the same analytical purpose.
Claim(s) 7 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Joo et al. (Journal of Chromatography B, 2013) (Joo) in view of Maslov et al. (International Journal of Molecular Sciences, 2019, IDS) (Maslov).
Regarding claim 7, Joo does not specifically teach that wherein the nucleophilic derivatization reagent is selected from the group consisting of propylamine, butylamine, or pentylamine. However, Maslov teaches alkylamines, including n-butylamine, to improve mass spectrometry detection of small metabolite analytes (page 3, par 2). Maslov teaches that “The use of n-butylamine showed the greatest superiority in global coverage of sample metabolomic composition in ESI(-) compared with other selected additives.” (page 3, par 2). It would have been obvious to one of ordinary skill in the art to select any of the closely-related primary alkylamines recited in Claim 7 to achieve the same predictable result taught by Maslov, in order to improve MS performance.
Regarding claim 19, Maslov teaches that wherein the nucleophilic derivatization reagent comprises primary linear butylamine (page 3, par 2).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Joo et al. (Journal of Chromatography B, 2013) (Joo) in view of Yan et al. (RSC Advances, 2015) (Yan).
Regarding claim 8, Joo does not specifically teach that wherein the at least one activation reagent is a first activation reagent or a second activation reagent or a combination thereof,
wherein the first activation reagent is selected from the group consisting of NHydroxysuccinimid (OHSu), N-Hydroxysulfosuccinimide (sulfo-OSu), Hydroxybenzotriazole (HOBt) and salts of these compounds, and
wherein the second activation reagent is selected from the group consisting of Dicyclohexylcarbodiimid (DIC), l-Ethyl-3-(3-dimethylaminopropyl)carbodiimid (EDC), N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide, Cyclohexyl-N' -(2-morpholinoethyl )carbodiimide N,N'-Dicyclohexylcarbodiimide, Nmethyl-p-toluenesulfonate, 1,3-Bis( trimethylsilyl)carbodiimide and N,N' -Methanetetraylbis[ 4-methyl ]benzenamine.
However, Yan teaches EDC/NHS activation of carboxylic acids as a widely used approach to form amides. Yan teaches that ““Amide bond formation (or amidation) from carboxylic acid by carbodiimide activation with the assistance of additives such as NHS… is so broadly used… that it would be difficult to overstate its importance.” (page 69939, par 1). Yan further identifies EDC and NHS explicitly “Taking one of the most common activation recipes as an example, namely EDC and an additive of NHS with carboxylic acid…” (page 69939, par 1), and reiterates EDC/NHS activation “efficiently forms an amide with an amine…” (page 69939, par 1). Thus, Yan teaches the exact activation reagent pair recited in Claim 8. It would have been an obvious design choice to select any well-known activation reagent, such as EDC with NHS, to activate the carboxylic acid in Joo prior to amine coupling, because Yan teaches that EDC/NHS is among the most common activation systems for this exact transformation (page 69939, par 1).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Joo et al. (Journal of Chromatography B, 2013) (Joo) in view of Vondenhoff et al. (WO 2019/141779, IDS) (Vondenhoff).
Regarding claim 20, Joo does not teach that wherein in step e) the sample is enriched using magnetic beads. However, Vondenhoof teaches that the sample is enriched using magnetic beads (page 36, line 18-23). It would have been obvious to one of ordinary skill in the art to select magnetic beads for the enrichment of analytes, because the selection is based on its suitability for the intended use.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797