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
Summary
This is the Final Office Action based on application 18/020690 election response filed 03/03/2026.
Claims 1-9 & 16 are pending and have been fully considered.
Claims 10-12 and 21-22 are cancelled
Claims 13-15 & 17-20 are withdrawn.
Response to Arguments
Applicant's arguments filed 03/03/2026 have been fully considered but they are not persuasive.
The examiner notes that applicant has amended independent Claim 1, but has amended it in a confusing way which makes the claim unclear. See the 112 (b) rejection below as the claim now claims that the derivatization agent is both a broader class of derivatization agent, and a narrower class of derivatization agent, and it is unclear which applicant intends.
Since this is the case, a 112 (b) rejection is added as shown below. Also, the 101 rejections and 102 and 103 rejections are maintained also due to this affect.
Further--- it seems applicant has not presented any arguments whatsoever with respect to the prior art which was used. This is confusing, especially given the way in which the claims were amended. If the claimed compound which applicant amended in Claim 1 is novel or has surprising or unexpected results with respect to what is claimed in Claim 1— applicant might make an argument to this affect. However, again—as claimed, in the way in which amended, the claim is left open to a broader interpretation than the compound which was amended 03/03/2026.
The examiner notes also that Claims 13-15 & 17-20 in the instant application remain listed as withdrawn. Leaving the claims as so, mean that the examiner will not be able to move forward with this case is an expedited manner upon applicant’s response if they remain as so.
This means the case would be accruing days on the examiners docket upon response from applicant if the examiner were made to call applicant’s representative, who would then need to contact applicant’s client, which at least seems to be partially an applicant in a significantly different time zone, therefore delaying matters.
Pending withdrawn claims 13-15 & 17-20 would not be rejoined with the pending examined claims upon response since they differ in subject matter from the claims which have been examined. Pending withdrawn Claims 13-15 & 17 require a different derivatization agent from that which was elected and which is also significantly different from the one which was amended into independent Claim 1. Claims 18-20 are drawn towards a different statutory category of invention than those which were examined. They are drawn towards a composition while the instant claims are drawn towards a method. Therefore, Claims 18-20 also differ in subject matter greatly from the claims which have been examined and would not be rejoined.
Even further--- applicant has made no effort to amend the pending withdrawn claims in any way at all, much less in a way in which would align them with the amendments made to instantly pending examined Claim 1. Therefore— applicant doing so after-final, and the examiner needed to examine these claims after-final, would be burdensome on the examiner if the examiner were to search and check any amended withdrawn claims after-final, as the examiner is not given any time for this after-final. Therefore, for all of the reasons above, the pending withdrawn claims 13-15 & 17-20 would not be rejoined, if the 112 (b) issues were cleared in an after-final response.
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 1-9 & 16 and those dependent therefrom 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.
With respect to Claim 1, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 1 recites the broad recitation that the derivatization agent can be “a substituted or non-substituted phenacyl bromide (PAB) and derivatives thereof,” and that the derivatization agent is the compound amended into the instant claim dated 03/03/2026 of, the formula for “2-Bromo-4'-(1-pyrrolidinyl) acetophenone,” (again represented by the compound shown amended into Claim 1 on 03/03/2026) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 2-9 & 16 are rejected by virtue of their dependency on Claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-9 & 16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and law of nature (natural correlation) without significantly more.
Step 1: Independent Claim 1 is directed towards a method.
Step 2A, Prong One: Independent Claim 1 recites, “analyzing a sample,” and “analyzing the derivatized one or more analytes.” These read through BRI and observation, which is a mental process and therefore and abstract idea, which is a judicial exception. See MPEP 2106.04 (a).
Step 2A, Prong Two: For independent Claim 1, the analyzing is not integrated into a practical application. After the analyzing is done, nothing further if performed, so there is no practical application.
Step 2B: In addition to the judicial exception, independent Claim 1 recites the additional limitation of “reacting a sample containing or suspected of containing one or more analytes having at least one of a carbonyl and a phenolic functional group with a derivatization agent…. Wherein the derivatizing agent comprises a substituted or non-substituted phenacyl bromide and derivatives thereof.” Using phenacyl bromide as a derivatization agent is well understood, routine and conventional (WURC) in the art. Therefore, this does not add anything significantly more to the instant claims.
The dependent claims undergo a similar analysis.
Claims 2-9 specify either what the sample is such a body fluids, blood, etc., of what the analyte is such as fatty acids, amino acids, hormones, estrogens, or eicosanoids such as prostaglandin. This does not to practically apply. Further, these types of samples and analytes are WURC in the art, so do not add significantly more.
Claim 16 specifies that the analysis is performed by mass spectrometry. As claimed at the level of generality claimed, mass spectrometry is WURC in the art so does not add significantly more. Also, this does nothing to practically apply.
*It is noted that the compound of 2-Bromo-4'-(1-pyrrolidinyl) acetophenone is found in Claim 1, is not found to be WURC at step 2 B, however the claim is not clear as to whether the claim is limited to only this of the derivatization agent also being “a substituted or non-substituted phenacyl bromide (PAB) and derivatives thereof, which is also in Claim 1, so Claim 1 is rejected under 101.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 6, 9 & 16 is/are rejected under 35 U.S.C. 102 (a) (1) and 102 (a)(2) as being anticipated by WILLACEY in LC-MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide (as recited on IDS dated 02/10/2023).
With respect to Claim 1, WILLACEY teaches of a method of analyzing a sample and profiling the metabolites in those samples by LC-MS/MS, utilizing dimethylaminophenacyl bromide as a derivatization agent. The dimethylaminophenacyl bromide derivatization targets carboxylic acids (which have both a carboxyl group) (title, abstract).
WILLACEY teaches that the method detects analytes including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to it’s alpha carbon) (Page 2, Table 1 & Figure 5). WILLACY further teaches of reacting the sample with the dimethylaminophenacyl bromide derivatization agent (Page 3, column 1, 2.3.1, lines 1-7), and then of analyzing the derivatized analytes by LC-MS/MS (Page 4, column 2, 2.5, Table 2-4 & figure 5—“Tyr,” = tyrosine).
With respect to Claim 2, WILLACEY teaches that the method detects analytes in samples including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to i’s alpha carbon) (Page 2, Table 1 & Figure 5).
With respect to Claim 3, WILLACEY teaches that the method detects analytes in samples including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to i’s alpha carbon) (Page 2, Table 1 & Figure 5). Tyrosine is an amino acid, so reads on, “one or more,” “amino acid.”
With respect to Claim 6, WILLACEY teaches that the method detects analytes in samples including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to i’s alpha carbon) (Page 2, Table 1 & Figure 5). Tyrosine is an amino acid, so reads on, “one or more,” “amino acid.”
With respect to Claim 9, WILLACY teaches of the sample being a biological sample (Page 1, column 1, paragraph 1, Page 8, column 2, paragraph 2, lines 1-2).
With respect to Claim 16, WILLACEY teaches of a method of analyzing a sample and profiling the metabolites in those samples by LC-MS/MS, utilizing dimethylaminophenacyl bromide as a derivatization agent. The dimethylaminophenacyl bromide derivatization targets carboxylic acids (which have both a carboxyl group). WILLACEY further teaches of using positive ionization mode (title, abstract).
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 4 is rejected under 35 U.S.C. 103 as being obvious over WILLACEY in LC-MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide (as recited on IDS dated 02/10/2023) in view of WATKINS in Fluorescent/Ultraviolet Absorbing Ester Derivative Formation and Analysis of Eicosanoids by High-Pressure Liquid Chromatography.
With respect to Claim 4, WILLACEY teaches of a method of analyzing a sample and profiling the metabolites in those samples by LC-MS/MS, utilizing dimethylaminophenacyl bromide as a derivatization agent. The dimethylaminophenacyl bromide derivatization targets carboxylic acids (which have both a carboxyl group) (title, abstract).
WILLACEY teaches that the method detects analytes including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to it’s alpha carbon) (Page 2, Table 1 & Figure 5). WILLACY further teaches of reacting the sample with the dimethylaminophenacyl bromide derivatization agent (Page 3, column 1, 2.3.1, lines 1-7), and then of analyzing the derivatized analytes by LC-MS/MS (Page 4, column 2, 2.5, Table 2-4 & figure 5 — “Tyr,” = tyrosine).
WILLACEY does not teach of the analytes having the carboxyl functional group being eicosanoids.
WATKINS is used to remedy that. WATKINS further teaches of a method for quantitative analysis of eicosanoids. This is done by first forming the ester derivative of the compound with phenacyl bromide (abstract).
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/to detecting eicosanoids as is done in WATKINS with phenacyl bromide due to the fact that the reaction of eicosanoids with phenacyl bromide has for a rapid and simple method for forming esters with exceedingly high UV absorptivity and fluorescent properties which offers advantage for detection (Page 39, column 1, discussion, lines 1-5).
Claim 5 is rejected under 35 U.S.C. 103 as being obvious over WILLACEY in LC-MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide (as recited on IDS dated 02/10/2023) in view of WATKINS in Fluorescent/Ultraviolet Absorbing Ester Derivative Formation and Analysis of Eicosanoids by High-Pressure Liquid Chromatography and further in view of CHHONKER in Quantification of eicosanoids and their metabolites in biological matrices:a review.
With respect to Claim 5, WILLACEY teaches of a method of analyzing a sample and profiling the metabolites in those samples by LC-MS/MS, utilizing dimethylaminophenacyl bromide as a derivatization agent. The dimethylaminophenacyl bromide derivatization targets carboxylic acids (which have both a carboxyl group) (title, abstract).
WILLACEY teaches that the method detects analytes including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to it’s alpha carbon) (Page 2, Table 1 & Figure 5). WILLACY further teaches of reacting the sample with the dimethylaminophenacyl bromide derivatization agent (Page 3, column 1, 2.3.1, lines 1-7), and then of analyzing the derivatized analytes by LC-MS/MS (Page 4, column 2, 2.5, Table 2-4 & figure 5 — “Tyr,” = tyrosine).
WILLACEY does not teach of the analytes having the carboxyl functional group being eicosanoids.
WATKINS is used to remedy that. WATKINS further teaches of a method for quantitative analysis of eicosanoids. This is done by first forming the ester derivative of the compound with phenacyl bromide (abstract).
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/to detecting eicosanoids as is done in WATKINS with phenacyl bromide due to the fact that the reaction of eicosanoids with phenacyl bromide has for a rapid and simple method for forming esters with exceedingly high UV absorptivity and fluorescent properties which offers advantage for detection (Page 39, column 1, discussion, lines 1-5).
WILLACEY and WATKINS do not teach of the eicosanoid being one of the claimed eicosanoids.
CHHONKER is used to remedy this. CHHONKER more specifically teaches of a method for quantification of eicosanoids and their metabolites by LC/MS/MS (abstract). CHHONKERS further teaches that the eicosanoids which are detected include HODE and HETE (Page 2033, lines 6-27 & Table 1).
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 detecting the claimed eicosanoids as one of the detected compounds in WILLACEU and WATKINS due to the need in the art for better methods of targeted determination of eicosanoids (CHHONKER, Page 2030, Eicosanoids quantification in different biological matrices, full paragraph).
Claims 7-8 are rejected under 35 U.S.C. 103 as being obvious over WILLACEY in LC-MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide (as recited on IDS dated 02/10/2023) and further in view of CHOO in WO 2016111538.
With respect to Claims 7-8, WILLACEY teaches of a method of analyzing a sample and profiling the metabolites in those samples by LC-MS/MS, utilizing dimethylaminophenacyl bromide as a derivatization agent. The dimethylaminophenacyl bromide derivatization targets carboxylic acids (which have both a carboxyl group) (title, abstract).
WILLACEY teaches that the method detects analytes including amino acids in biological samples and specifically including tyrosine, which has both a phenolic functional group (the benzene ring with a hydroxyl group) and also a carboxyl functional group (-COOH attached to it’s alpha carbon) (Page 2, Table 1 & Figure 5). WILLACY further teaches of reacting the sample with the dimethylaminophenacyl bromide derivatization agent (Page 3, column 1, 2.3.1, lines 1-7), and then of analyzing the derivatized analytes by LC-MS/MS (Page 4, column 2, 2.5, Table 2-4 & figure 5 — “Tyr,” = tyrosine).
WILLACEY does not teach of the analytes having the phenolic functional group being an estrogenic hormone.
CHOO is used to remedy this. CHOO teaches of a method for detecting a sex hormone and a method for detecting a sex hormone using the same, the reagent kit comprising: a first reagent comprising a sex hormone and a metal nanoprobe in which a Raman reporter is immobilized; and a second reagent comprising magnetic particles in which an antibody for detecting the sex hormone is immobilized (abstract). CHOO further teaches that the sex hormone is estradiol (Example 3, 3.1), and that the Raman reporter can be 4-azido-2-bromoacetophenone (Page 4, Tech-Solution, paragraph 9) which is another name for a phenacyl bromide.
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 in using a phenacyl bromide Raman reporter as is done CHOO in the method of WILLACEY due to the advantages with Raman Scattering/reporting in that assays which utilize them can quantify target material by measuring the change in intensity of amplified characteristic SERS peaks of Raman reporter molecules. This effect solves the problem of low sensitivity, which is a disadvantage of the and is expected to exceed the accuracy and detection limits of the conventional chemiluminescence assay and radioactivity-based immunoassay (Page 3, 3rd paragraph from bottom).
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.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
ENDO in JP 2005331465 (as cited on IDS dated 02/10/2023) teaches of a measuring method for carboxylic acid excellent in operability and capable of measuring precisely the carboxylic acid, in a novel measuring method for the carboxylic acid using no toxic reagent, and a measuring kit useful for executing the method. ENDO further teaches of detecting the he carboxylic acid by using phenacyl bromide derivative (abstract). ENDO does not teach of the phenacyl bromide derivative in instant Claim 1, however this derivative, amended 03/03/2026 is not the only possible phenacyl bromide entity claimed in Claim 1.
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