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 Final Action for application 18/306195 response filed 02/24/2026.
Claims 1-10, 12, 14 & 16-20 are pending and have been fully considered.
Claims 11, 13 & 15 have been cancelled.
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, 12, & 14 are rejected under 35 U.S.C. 103 as being obvious over HUANG in US 20160282371 in view of TRIMPIN in US 20140166875.
With respect to Claim 1, HUANG 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 (paragraph 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).
HUANG does not teach of using, “nano” ESI mass spectrometry.
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).
With respect to Claim 2, HUANG 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).
With respect to Claim 3, HUANG teaches of the method being automated (paragraph 0010, 0089-0090, 0221, 0230, 0250).
With respect to Claim 4, 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, HUANG teaches of using a derivatization compound which may covalently bond to certain selected analytes (paragraph 0052, 0053, 0056).
With respect to Claim 12, 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). Specifically, HUANG teaches that the system includes chromatography and a detector which is a mass spectrometer (paragraphs 0088, 0087, 0095-0098), and that it is capable of carrying out the method of Claim 1. See Claim 1 rejection.
With respect to Claim 14, 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).
Claims 5, 7-9 & 16-20 are rejected under 35 U.S.C. 103 as being obvious over HUANG in US 20160282371 in view of TRIMPIN in US 20140166875 and further in view of CARELL in WO 2018141821 (as cited on IDS dated 04/24/2023).
With respect to Claim 5, HUANG in view of TRIMPIN 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 HUANG and TRIMPIN 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, HUANG in view of TRIMPIN 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 TRIMPIN 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, HUANG in view of TRIMPIN 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 HUANG and TRIMPIN 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, HUANG in view of TRIMPIN 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 HUANG and TRIMPIN 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, HUANG in view of TRIMPIN 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 TRIMPIN 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, HUANG in view of TRIMPIN 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 TRIMPIN 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, HUANG in view of TRIMPIN 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 HUANG and TRIMPIN 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, HUANG in view of TRIMPIN 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 TRIMPIN 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, HUANG in view of TRIMPIN 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 TRIMPIN 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).
Claim 10 is rejected under 35 U.S.C. 103 as being obvious over HUANG in US 20160282371 in view of TRIMPIN in US 20140166875 and further in view of OUYANG in US 20180294148.
With respect to Claim 10, HUANG 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 (paragraph 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).
HUANG does not teach of using, “nano” ESI mass spectrometry.
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, pipet 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 (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).
HUANG in view of TRIMPIN do not teach of the use of “static,” nanoESI.
OUYANG is used to remedy this and 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 and one would have had reasonable expectation of success in using static ESI as is done in OUYANG in the method of HUANG and TRIMPIN since it offers the advantage of being an ESI source without having to maintain or deal with additional solvent pumping OUYANG, paragraph 0226).
Response to Arguments
The prior claims objections and 112 rejection are overcome due to the amendments made 02/24/2026.
Applicant's arguments filed 02/24/206 with respect to the prior art have been fully considered but they are not persuasive.
With respect to the prior art, applicant argues that there is no motivation to combine the instantly used references, nor is the reasonable expectation of success, since applicant argues that TRIMPIN, the secondary reference is fundamentally flawed and “does not teach conventional nanoESI mass spectrometry.”
The examiner disagrees with applicant’s argument that TRIMPIN is “fundamentally flawed,” especially with respect to how broad instant Claim 1 is worded.
Applicant argues that fundamental flaw in TRIMPIN is that it teaches of ionization occurring inside a heated inlet channel (TRIMPIN, paragraph 0165), and not conventional nanoESI where ionization occurs at an emitter tip outside the mass spectrometer inlet.
With respect to this, even if this is the case--- the examiner notes that Claim 1, and the “nanoESI mass spectrometry,” in Claim 1 is very broadly claimed. Therefore--- even if the nanoESI mass spectrometry in TRIMPIN is slightly different from what is considered to be “conventional,” mass spectrometry, the examiner notes that that claims do not claim the ionization occurring at an emitter tip outside the mass spectrometry inlet (which applicant argues is the conventional nanoESI mass spec). Therefore, as TRIMPIN teaches of in the very least, a version of nanoESI mass spectrometry, it reads on the claims and the rejection is maintained. If applicant means something more specific, then they should claim it.
Applicant argues that the “conventional nanoESI,” used in the instant applicant requires, “ionization occurring at an emitter top outside the mass spectrometer intel,” that the sample is “loaded by single-use pipette tips into an emitter,” of using “flow rates below 1uL/min,” with a “flow rate of 50 to 500 nl/min,” and of using “Advion Triversa Nanomate.” Applicant argues that these are “critical,” differences between the instant invention and TRIMPIN, but yet---- does not claim any of this things that are supposedly critical. Therefore, as patentability determinations are made with respect to what is actually claimed, these arguments are not commensurate in scope with the claims and therefore are unconvincing to the examiner.
The examiner also notes that the instant claims are read with respect to what the broadest reasonable interpretation (BRI) of the claims are. TRIMPIN reads on the BRI of the instantly claimed nanoESI mass spectrometry. If applicant thinks that the nanoESI shown in the instant disclosure, and that used in TRIMPIN are different, then they should consider amending the instant claim language to reflect the details in the specification which are different from TRIMPIN.
Further—the examiner notes that TRIMPIN 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).
Therefore, there is both reasonable expectation of success and adequate reason for combination of TRIMPIN and HUANG.
Applicant further argues that TRIMPIN, “teaches away from conventional ESI.” Again--- the examiner disagrees, and notes that TRIMPIN does in fact teach of nanoESI, especially in light of the broadest reasonable interpretation of the claims. TRIMPIN even specifically uses the word “nanoESI,” (paragraph 0165) and therefore reads on the instant claims. If applicant means something more specific, or if applicant’s nanoESI is in fact different from that shown in TRIMPIN--- then it is suggested to add clarifying claim language to the claims. Therefore, TRIMPIN does not “teach away,” from “nanoESI mass spectrometry,” which is what is actually claimed and what patentability determinations are based on.
Applicant again argues that a “PHOSITA would have had no motivation to combine and no reasonable expectation of success,” with respect to the primary reference HUANG, and the secondary reference TRIMPIN. The examiner disagrees.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, the examiner notes that HUANG teaches of the broadly claimed, general analysis steps claimed including (providing pretreated sample, derivatization, diluting pretreated sample, and then determination of analyte level by mass spectrometry). HUANG doesn’t teach of nanoESI mass spectrometry, so TRIMPIN is used to remedy this.
TRIMPIN 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). Therefore- especially as generally claimed—there is adequate reason for combination of the two references and also there is reasonable expectation of success.
Applicant again argues that the “claimed invention uses a different approach from both HUANG and TRIMPIN,” and that this different approach involves “conventional nanoESI, at “flow rates of 50 to 500 nl/min,” “ionization occurring at an emitter top outside the MS inlet.”
With respect to this--- the examiner notes that none of this is claimed, and again notes that this argument is not commensurate in scope with the claims and therefore is not convincing.
Applicant further argues that a PHOSITA would have had “no basis,” to expect a combination of HUANG and TRIMPIN would be successful since the prior art “provided no teaching or suggestion that:
Derivatization combined with dilution (rather than concentration) would be effective;
Conventional nanoESI could be used without LC separation; or
The combination would achieve synergistic signal amplification.”
Again- the examiner agrees with applicant as all of these things are not commensurate in scope with the claims, especially with respect to the 2nd and 3rd bullet point. With respect to the 1st bullet point with respect to the derivatization--- the examiner notes that HUANG teaches of providing a pretreated sample (paragraph 0035), derivatizing the analyte of interest in the sample which can be pretreated (paragraph 0051-0053), and diluting the sample which can be pre-treated and which can be a body fluid which is a plasma sample (paragraph 0208, 0236). Therefore- this reads on the claim, and examiner disagrees with applicant’s argument.
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 TRIMPINGs inlet ionization method.”
With respect to this--- the examiner maintains their response, which has already been shown above with respect to applicants arguments about the supposedly “conventional,” nanoESI claimed versus what is taught in OUYANG and CARELL. OUYANG and CARELL do nothing to change the examiners opinion and maintains that TRIMPIN teaches of the instantly claimed nanoESI mass spectrometry through broadest reasonable interpretation.
Applicant further argues that OUYANG, CARELL, TRIMPIN, and HUANG are disparate teachings with no reasonable expectation of success, but does not elaborate on this in any meaningful way. Therefore—the examiner disagrees with applicant’s argument.
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--- TRIMPIN specifically notes that there are analytical advantages of using nanoESI in that it provides higher ion abundances (so a higher amplified signal) and lower background (TRIMPIN, paragraph 0165). 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 nanoESI. As shown above, the prior art makes this obvious.
Applicant further argues that “static,” nanoESI is used to achieve these results. However—the examiner notes that “static,” nanoESI is not claimed in the independent claim and therefore this is not commensurate in scope with the independent claims.
Applicant even further argues that the instant invention provides a counterintuitive approach of diluting the sample after derivatization rather than concentrating it. The examiner notes however--- HUANG teaches of this, so applicant’s arguments are not convincing and specifically teaches that derivatizing the analyte of interest in the sample which can be pretreated is performed (paragraph 0051-0053), and then diluting the sample which can be pre-treated and which can be a body fluid which is a plasma sample (paragraph 0208, 0236). Further--- the examiner notes that as claimed in Claim 1, it is only required that “the pretreated sample,” is diluted, which is referred to in step a), and not the derivatized analyte which is in step b) if instant Claim 1.
Applicant notes that specific limits of detection are achieved with the instant invention for specific analytes, but none of the specific analytes or limits of detection shown in the chart on Page labeled 15 of the instant invention are claimed.
Therefore--- especially as broadly and generally claimed, the examiner disagrees with applicant’s arguments and the rejections are maintained.
All claims remain rejected.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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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.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758