Prosecution Insights
Last updated: August 16, 2026
Application No. 18/306,195

DETECTION OF AN ANALYTE OF INTEREST BY NANOESI MASS SPECTROMETRY

Non-Final OA §103
Filed
Apr 24, 2023
Priority
Oct 22, 2020 — EU 20203220.7 +1 more
Examiner
FRITCHMAN, REBECCA M
Art Unit
1758
Tech Center
1700 — Chemical & Materials Engineering
Assignee
Roche Diagnostics Operations Inc.
OA Round
3 (Non-Final)
46%
Grant Probability
Moderate
3-4
OA Rounds
8m
Est. Remaining
82%
With Interview

Examiner Intelligence

Grants 46% of resolved cases
46%
Career Allowance Rate
302 granted / 661 resolved
-19.3% vs TC avg
Strong +36% interview lift
Without
With
+35.8%
Interview Lift
resolved cases with interview
Typical timeline
4y 0m
Avg Prosecution
69 currently pending
Career history
748
Total Applications
across all art units

Statute-Specific Performance

§101
5.0%
-35.0% vs TC avg
§103
59.5%
+19.5% vs TC avg
§102
9.1%
-30.9% vs TC avg
§112
20.4%
-19.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 661 resolved cases

Office Action

§103
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 . Detailed Action This is the Non-Final Action for application 18/306195 response filed 06/10/2026. Claims 1-10, 12, 14 & 16-21 are pending and have been fully considered. Claims 11, 13 & 15 have been cancelled. Claim 21 has been newly added. Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/10/2026 has been entered. Claim Rejections - 35 USC §103 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. Claims 1-4, 6, 10, 12, 14 & 21 are rejected under 35 U.S.C. 103 as being obvious over MANGER in US 20060099116 in view of OUYANG in US 20180294148 and further in view of HUANG in US 20160282371. With respect to Claim 1, MANGER teaches of method of detection of levels of proteins and other analytes in serum or urine (paragraph 0096-0098). MANGER teaches of providing the sample. MAGNER teaches that enzyme binding can occur before injecting the analyte sample into the analytical device. This can be considered pretreating the sample through broadest reasonable interpretation (BRI) (paragraph 0078, 0096). MANGER further teaches of analyzing the sample through nanospray or nanoelectrospray mass spectrometry and specifically of using it in a static environment (paragraph 0008, 0030-0032, 0076, 0093-0094). If it is unclear that the static environment nano-ESI used, OUYANG is used to remedy this. OUYANG teaches of a method for analysis of a sample (abstract), and further teaches of using static nanoESI to do this (paragraph 0226). It would have been obvious to one of ordinary skill in the art to used the static nano-ESI as is done in OUYANG in the method of MANGER due to the advantages static nano-ESI offers as being an ESI source without having to maintain or deal with additional solvent pumping OUYANG, (paragraph 0226). OUYANG and MANGER does not call out specifically the dilution and derivatization of the sample. HUANG is used to remedy this and teaches of methods and kits for solid phase extraction, derivatization with crown ether containing derivatizing agents, and mass spectrometry of the derivatized analytes (abstract). Specifically, HUANG teaches of providing a pretreated sample (paragraph 0035), derivatizing the analyte of interest in the sample which can be pretreated (paragraph 0051-0053), diluting the sample which can be pre-treated and which can be a body fluid which is a plasma sample involving adding a buffer dilution/amount to the sample (paragraph 0066-0075, 0208, 0236), and determining the level of the analyte of interest in the sample which can be pretreated using ESI-mass spectrometry (paragraph 0016, 0037, 0093, 0095-0096, 0106). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to derivatize the sample as is done in HUANG in the method of MANGER due to the advantages derivatization offers for improved HPLC behavior, significantly improved tandem MS/MS sensitivity, and makes lipophilic analytes more hydrophilic (HUANG, paragraph 0051). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to dilute/buffer the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages buffer dilutions offers for improved elution of desired components (HUANG, paragraph 0016-0018, 0040-0041). With respect to Claim 2, MANGER and OUYANG teaches of the claims as shown above, but does not specifically call out no extra/intervening steps as claimed. HUANG is used to remedy this and teaches of performing the method without any manual steps (paragraph 0088) and that the steps can be chromatography (paragraph 0089) or extraction (paragraph 0083). HUANG teaches that extra steps are optional and not required—therefore making the claimed invention of no extra steps between a and b, b and c, and c and d obvious. Specifically, HUANG teaches that the sample “may,” be purified with centrifugation of chromatography or centrifugation, filtration (extraction) or precipitation,” but the “may,” indicates that these steps are not required (abstract, paragraph 0037). HUANG does not teach that the sample is freeze dried or lyophilized—so this does not happen, again as instantly claimed. HUANG teaches that the instant methods, “may,” include chromatography, again meaning that it is not required so also may not include this as instantly claimed (paragraph 0016) and specifically that the liquid chromatography can be “and/or,” with the mass spectrometry—again reading on the instant claims of performing without chromatography (paragraph 0115). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the methods as id done in HUANG in the method of MANGER and not others as is claimed, due to the advantage this offers for “streamlining,”/quickening analysis (HUANG, paragraph 0002). With respect to Claim 3, MANGER and OUYANG teaches of the above but does not teach of the method being automated. HUANG teaches of the method being automated (paragraph 0010, 0089-0090, 0221, 0230, 0250). It would have been obvious to one of ordinary skill before the effective filing date of the instant invention to automate the claimed device as is done in MANGER and OUYANG in the method of HUANG due to the advantage this offers for lowering the requirement for operator involvement during the purification of the analyte so it can be minimized and therefore potentially resulting in savings of time and costs, and eliminate or reduce the opportunity for an operator error (HUANG, paragraph 0089). With respect to Claim 4, MANGER and OUYANG teaches of the method being performed outside the body in a device so it is in vitro (abstract). HUANG teaches of the method being performed outside the body so it is in vivo (outside of body), since a plasma sample is taken from the body and then used outside the body (paragraph 0008-0009, 0041). With respect to Claim 6, MANGER and OUYANG does not call out specifically the dilution and derivatization of the sample. HUANG is used to remedy HUANG teaches of using a derivatization compound which may covalently bond to certain selected analytes (paragraph 0052, 0053, 0056). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to derivatize the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages derivatization offers for improved HPLC behavior, significantly improved tandem MS/MS sensitivity, and makes lipophilic analytes more hydrophilic (HUANG, paragraph 0051). With respect to Claim 10, MANGER teaches of providing the sample. MAGNER teaches that enzyme binding can occur before injecting the analyte sample into the analytical device. This can be considered pretreating the sample through broadest reasonable interpretation (BRI) (paragraph 0078, 0096). MANGER further teaches of analyzing the sample through nanospray or nanoelectrospray mass spectrometry and specifically of using it in a static environment (paragraph 0008, 0030-0032, 0076, 0093-0094) and further of using a flowrate of from about 1nL/min to about 150 nL/min, which includes flow rates within the claimed range (paragraph 0032). With respect to Claim 12, MANGER teaches of a device and method of detection of levels of proteins and other analytes in serum or urine (paragraph 0096-0098). The device is used for diagnostics (paragraph 0093). MANGER teaches of providing the sample. MAGNER teaches that enzyme binding can occur before injecting the analyte sample into the analytical device. This can be considered pretreating the sample through broadest reasonable interpretation (BRI) (paragraph 0078, 0096). MANGER further teaches of analyzing the sample through nanospray or nanoelectrospray mass spectrometry and specifically of using it in a static environment (paragraph 0008, 0030-0032, 0076, 0093-0094). MANGER and OUYANG does not call out specifically the dilution and derivatization of the sample. HUANG is used to remedy this and teaches of methods and kits for solid phase extraction, derivatization with crown ether containing derivatizing agents, and mass spectrometry of the derivatized analytes (abstract). Specifically, HUANG teaches of providing a pretreated sample (paragraph 0035), derivatizing the analyte of interest in the sample which can be pretreated (paragraph 0051-0053), diluting the sample which can be pre-treated and which can be a body fluid which is a plasma sample involving adding a buffer dilution/amount to the sample (paragraph 0066-0075, 0208, 0236), and determining the level of the analyte of interest in the sample which can be pretreated using ESI-mass spectrometry (paragraph 0016, 0037, 0093, 0095-0096, 0106). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to derivatize the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages derivatization offers for improved HPLC behavior, significantly improved tandem MS/MS sensitivity, and makes lipophilic analytes more hydrophilic (HUANG, paragraph 0051). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to dilute/buffer the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages buffer dilutions offers for improved elution of desired components (HUANG, paragraph 0016-0018, 0040-0041). With respect to Claim 14, MANGER and OUYANG teaches of the device as shown above for Claims 1 & 12. They do not teach of it being included with a kit. HUANG teaches of a system and kit and method kits for solid phase extraction, derivatization with crown ether containing derivatizing agents, and mass spectrometry of the derivatized analytes (abstract). HUANG teaches the kit can include a derivatization compound which may covalently bond to certain selected analytes (paragraph 0052, 0053, 0056). HUANG further teaches that the kit can comprise solvents to be mixed with/dilute the analytes (paragraph 0017, 0041). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to derivatize the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages derivatization offers for improved HPLC behavior, significantly improved tandem MS/MS sensitivity, and makes lipophilic analytes more hydrophilic (HUANG, paragraph 0051). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to dilute/buffer the sample as is done in HUANG in the method of MANGER and OUYANG due to the advantages buffer dilutions offers for improved elution of desired components (HUANG, paragraph 0016-0018, 0040-0041). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use as kit as is done by HUANG with the method of Claim 1 as is done in HUANG in the method of MANGER and OUYANG since kits offer the advantage of convenience of providing the necessary components to perform the disclosed methods (HUANG, paragraph 0206). With respect to Claim 21, MANGER teaches of ionization occurring at a nozzle/a capillary nozzle outside the mass spectrometer (paragraph 0091, 0032, 0093-0094). Claims 5, 7-9 & 16-20 are rejected under 35 U.S.C. 103 as being obvious over MANGER in US 20060099116 in view of OUYANG in US 20180294148 in view of HUANG in US 20160282371 and further in view of CARELL in WO 2018141821 (as cited on IDS dated 04/24/2023). With respect to Claim 5, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for Claim 1. They do not teach of the sample being hemolyzed. CARELL is used to remedy this and more specifically teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts. Further, the present invention relates to methods for the mass spectrometric determination of analyte molecules (abstract). Further, CARELL teaches of hemolyzing the pretreated sample and hemolyzed whole blood (Page 7, last paragraph & Page 8, first paragraph). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success to hemolyze as is done in CARELL in the methods of MANGER and OUYANG and HUANG due to the advantage hemolyzing would have for breaking down the whole blood sample and therefore quantification of the analyte (CARELL, Page 7, last paragraph & Page 8, first paragraph). With respect to Claim 7, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 6. They do not teach of specific covalent bonding and forming of complex with the derivatization compound having the claimed formula of X-L1(-Y- Z) which has the claimed mass and net charges and is capable of forming the claimed ions during mass spectrometric analysis. CARELL is used to remedy this and teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts (abstract). CARELL further teaches of using the compound X-L1-Y (L2 -z)r & X-L1-Y-L2-Z, which reads on the claimed formula A. It is noted that CARELL says a salt thereof can also be used and that Z is a charged unit, X is a reactive unit capable of covalent bonds as claimed and L1 is a linker/spacer (Page 2, last paragraph and formula & Page 3 all & bottom formula & also see pages 4-6 and the formulas throughout those pages). CARELL further teaches of covalently bonding the molecule with the analyte of interest (Page 3, line 24-25), and even further that the Z can have a charge of 0 or 1 and has a mass which can be considered m1 as any mass can be considered m1. This also applied to the claimed, “compound is capable of forming at least one daughter ion having a mass m2<m1 and net charge of z2<z1 after fragmentation,” as the taught compound is “capable of,” this. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent to covalently bond to the analyte of interest as is done in CARELL in the methods of HUANG and MANGER and OUYANG since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 8, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for Claim 1. They do not teach of the derivatization compound being one of the claimed compounds. CARELL is used to remedy this and more specifically teaches of using 1,2,4-trizolin-3,5-diones (Page 16, paragraph 2, lines 6-8). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of using this compound as a derivatization agent as is done in CARELL in the methods of MANGER and OUYANG and HUANG since this compound is capable of acting as a dienophile and therefore are useful in detection (CARELL, Page 16, paragraph 2, lines 6-8). With respect to Claim 9, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 6. They do not teach of the derivatization compound having the claimed formula of X-L1(-Y- Z). CARELL is used to remedy this and teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts (abstract). CARELL further teaches of using the compound X-L1-Y (L2 -z) r & X-L1-Y-L2-Z, which reads on the claimed formula A and that these are the general formulas that can be adjusted with the claimed component parts, X, L1, Y and Z. It is noted that CARELL says a salt thereof can also be used and that Z is a charged unit, X is a reactive unit capable of covalent bonds as claimed and L1 is a linker/spacer (Page 2, last paragraph and formula & Page 3 all & bottom formula & also see pages 4-6 and the formulas throughout those pages). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent as is done in CARELL in the methods of MANGER in view of OUYANG in view of HUANG since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 16, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 6. They do not teach of specific covalent bonding and forming of complex with the derivatization compound having the claimed formula of X-L1(-Y- Z). CARELL is used to remedy this and teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts (abstract). CARELL further teaches of using the compound X-L1-Y (L2 -z)r & X-L1-Y-L2-Z, which reads on the claimed formula A. It is noted that CARELL says a salt thereof can also be used and that Z is a charged unit, X is a reactive unit capable of covalent bonds as claimed and L1 is a linker/spacer (Page 2, last paragraph and formula & Page 3 all & bottom formula & also see pages 4-6 and the formulas throughout those pages). CARELL further teaches of covalently bonding the molecule with the analyte of interest (Page 3, line 24-25). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent to covalently bond to the analyte of interest as is done in CARELL in the methods of HUANG and OUYANG and MANGER since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 17, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 6. They do not teach of the permanent charge comprising a permanent net charge. CARELL further teaches of covalently bonding a derivatization molecule with the analyte of interest (Page 3, line 24-25). CARELL further teaches that the molecule has a permanent net charge (Page 2, lines 9-10). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent to covalently bond to the analyte of interest as is done in CARELL in the methods of HUANG and MANGER and OUYANG since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 18, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 6. They do not teach of specific covalent bonding and forming of complex with the derivatization compound having the claimed formula of X-L1(-Y- Z), wherein L1 is specifically linear or branched. CARELL is used to remedy this and teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts (abstract). CARELL further teaches of using the compound X-L1-Y (L2 -z) r & X-L1-Y-L2-Z, which reads on the claimed formula A. It is noted that CARELL says a salt thereof can also be used and that Z is a charged unit, X is a reactive unit capable of covalent bonds as claimed and L1 is a linker/spacer (Page 2, last paragraph and formula & Page 3 all & bottom formula & also see pages 4-6 and the formulas throughout those pages). CARELL further teaches that L1 is a linear or branched spacer (Page 21, last paragraph). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent to covalently bond to the analyte of interest as is done in CARELL in the methods of MANGER in view of OUYANG in view of HUANG since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 19, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for claim 9. They do not teach of the permanent charge comprising a permanent net charge. CARELL further teaches of covalently bonding a derivatization molecule with the analyte of interest (Page 3, line 24-25). CARELL further teaches that the molecule has a permanent net charge (Page 2, lines 9-10). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of using the derivatization agent to covalently bond to the analyte of interest as is done in CARELL in the methods of HUANG and MANGER and OUYANG since it has been shown to allow extremely sensitive determination of molecules and allows for obtaining of accurate and quantitative MS data (CARELL, Page 2, 2nd to last paragraph). With respect to Claim 20, MANGER in view of OUYANG in view of HUANG teaches of the claimed invention as shown above for Claim 1. They do not teach of the sample being hemolyzed. CARELL is used to remedy this and more specifically teaches of methods and reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts. Further, the present invention relates to methods for the mass spectrometric determination of analyte molecules (abstract). Further, CARELL teaches of hemolyzing the pretreated sample and hemolyzed whole blood (Page 7, last paragraph & Page 8, first paragraph). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of hemolyzing as is done in CARELL in the methods of HUANG and MANGER and OUYANG due to the advantage hemolyzing would have for breaking down the whole blood sample and therefore quantification of the analyte (CARELL, Page 7, last paragraph & Page 8, first paragraph). Response to Arguments Applicant's arguments filed 06/10/2026 with respect to the prior art have been fully considered but they are not persuasive. Applicant argues that the instant amendment fundamentally changes the scope of the rejection. The examiner agrees. Therefore, a new primary reference was used as shown above. Applicant argues about the TRIMPIN reference. The examiner notes that this reference is no longer used. With respect to the rejection of dependent Claim 10, and Claims 5, 7-9, & 16-20 and the OUYANG and CARELL references, applicant argues that OUYANG and CARELL “confirms that TRIMPIN does not teach convention nanoESI,” and that, “OUYANGS static nanoESI is fundamentally different from TRIMPIN’s inlet ionization method.” Again, with respect to this, the examiner notes that the TRIMPIN reference is no longer used. Further applicant argues that OUYANG teaches of use of the static nanoESI for lipid species, which is different from quantification of analytes in biological matrices. The examiner disagrees with this and notes that lipids can be the claimed analytes, and that lipid are also found in biological matrices. Further, the newly used reference MANGER does in fact teach of using static nanoESI as instantly claimed on samples like blood, as claimed, as shown in the above rejection. Applicant further argues that OUYANG, CARELL, TRIMPIN (which is no longer used), and HUANG are disparate teachings with no reasonable expectation of success, and that all of these methods are directed towards different analytical problems and therefore one would not combine to arrive at the claimed invention, but does not elaborate on this in any meaningful way. Therefore—the examiner disagrees with applicant’s argument. Specifically, the examiner notes that if there is in fact a specific analytical problem being claimed, it is unclear what it is, since only very very broad claim language of derivatizing, diluting, pretreating and measuring some kind of analyte is claimed. Therefore, as broadly claimed, this broad methos relates to the same analytical problems as the prior art pieces as all are measuring some kind of analyte, which is the instant claims are as well. Applicant further argues that the claimed invention has unexpected/surprising synergistic results and that these results are that the combination of derivatization and static nanoESI leads to signal amplification that is significantly higher than the expected combination of the individual components.” The examiner notes that this does not seems unexpected. Pretty much all mass spectrometry analysis uses some form of derivatization. Further--- the prior art above shows specific advantages to nano ESI mass spec and static nanoESI mass spec. Further--- it is not clear if there are actually “unexpected,” results, if applicant has even claimed what these results are due to. As claimed--- it seems if they are even in fact present it seems that it is any derivatization analyte and any static nanoESI. As shown above, the prior art makes this obvious. Applicant further argues that “static,” nanoESI is used to achieve these results. The examiner again, notes that the first two pieces of prior art teach of the claimed static nanoESI as claimed, so the claimed results or accuracy and sensitivity would not be unexpected with respect to the new grounds of rejection as shown above. The examiner notes, that the increased sensitivity does not seem to be for any and every analyte, as instantly claimed, but instead are for very particular analytes as shown on the chart on page 17 of remarks dated 06/10/2026. The examiner notes, that none of these specific analytes are claimed, nor is their LOD or improvement factor, nor is anything with respect to sensitivity. Therefore, applicant’s arguments are not sufficient to overcome the prior art. All claims remain rejected. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. TRIMPIN in US 20140166875. TRIMPIN is used to remedy this and more specifically teaches of a method for achieving high throughput analysis of samples using solvent assisted ionization inlet includes an ionizing system with a heated inlet channel and a pressure differential across the inlet channel, pipette tips serially aligned with the inlet to a mass spectrometer, and a system of mapping data generated by mass spectrometry (abstract). TRIMPIN further teaches of using nanoESI for assisting ionization for mass spectrometry (paragraph 0165). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success of using nanoESI mass spectrometry as is done in TRIMPIN in the method of HUANG, due to the analytical advantages nanoESI provides such as higher ion abundances and lower background (TRIMPIN, paragraph 0165). Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel, can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
Read full office action

Prosecution Timeline

Apr 24, 2023
Application Filed
Nov 24, 2025
Non-Final Rejection mailed — §103
Feb 24, 2026
Response Filed
Mar 18, 2026
Final Rejection mailed — §103
Jun 10, 2026
Request for Continued Examination
Jun 14, 2026
Response after Non-Final Action
Jun 22, 2026
Non-Final Rejection mailed — §103 (current)

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Prosecution Projections

3-4
Expected OA Rounds
46%
Grant Probability
82%
With Interview (+35.8%)
4y 0m (~8m remaining)
Median Time to Grant
High
PTA Risk
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