Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Detailed Action
Summary
This is the Non-Final Office Action based on application 19/462819 response filed 07/01/2026.
Claims 17, 20-21 & 23-24 are pending and have been fully considered.
Claims 1-16, 18-19 & 22 are cancelled.
The examiner notes that applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 17, 20-21 & 23-24 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over CHEN in Measurement of 25-hydroxyvitamin D3 (25 OHD3) and 25-hydroxyvitamin D2 (25OHD2) in human serum using liquid chromatography-tandem mass spectrometry and its comparison to a radioimmunoassay method in view of VICCHIO in Quantification and Kinetics of 25-Hydroxyvitamin D3 by isotope dilution liquid chromatography/thermospray mass spectrometry (as cited on IDS dated 05/07/2026) in view of PETERS in US 20060263886.
With respect to Claim 17, CHEN teaches of a method of measuring vitamin D molecules by liquid chromatography mass spectrometry and specifically of using the internal standard which is hexadeuterated-25OHD3 (abstract), which is the same as applicant’s instantly claimed 25OHD3- [24,24,24,25,25,25]-2H6 internal standard, or in the very least the genus of the claimed species. CHEN further teaches that the internal standards are obtained from Sythetica (which means they are obtained in a package from somewhere else), so in a kit--- though the words kit or package are not used.
CHEN also teaches of using a specific amount of the internal standard, which reads on the claim “amount sufficient for performing,” and of performing LC/MS (Page 8, column 1, 2.2, paragraph 1, Page 7, column 2).
If it is unclear however the CHEN teaches of the deuterations being at the claimed carbon positions of 24 and 25 or 6 and 19, VICCHIO is use to remedy this.
VICCHIO teaches of a method for liquid chromatography mass spectrometry which measured 25-hydroxyvitamin D3(abstract). VICCHIO further teaches of using (6, 19, 19-2H3)25-hydroxyvitamin D3 (abstract) which is the same as applicant’s instant 25OHD3- [6,19,19]-2H3. VICCHIO teaches that this compound is synthesized (abstract and Page 54, column 1, paragraph 2). VICCHIO teaches that this compound as a label (abstract) as a stable isotope tracer (Page 53, column 2, paragraph 2) and that the samples including the stable isotope tracer are analyzed by liquid chromatography mass spectrometry (abstract & Page 54, column 1, paragraph 1). VICCHIO also teaches of using a specific amount of 6, 19, 19-2H3)25-hydroxyvitamin D3, which reads on the claim “amount sufficient for performing,” and of performing LC/MS (Page 54, column 2, paragraph 2, Page 53, column 2, 2nd to last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use to stable isotope label as is done in VICCHIO in the method using an internal standard, as the isotopic internal standard of CHEN due to the advantage the stable isotopic label using in VICCHIO offers for the quantification of vitamin D3 metabolites (Page 54, column 1, paragraph 1).
If it is unclear that CHEN in view of VICCHIO teach of the claimed kit/packaging, PETERS is used to remedy this.
PETERS teaches of methods of analysis or complex biological samples (abstract), of using isotopic or fluorous labels such as deuterium labels (paragraph 0035, 0041, 0107), and of including the labels/standards in a kit with packaging materials (paragraph 0181). PETERS teaches that molecules such as vitamin D and vitamin D2 can be labeled using the isotopic compounds (paragraph 0220).
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 kit with packaging as is done in PETERS with the materials in CHEN and VICCHIO to aid in detection of vitamin D compounds due to the advantage kits offers in providing the compositions for the methods embodied and instructions for practicing their use conveniently together(PETERS, paragraph 0181).
It is noted the internal standard compounds taught by CHEN and VICCHIO would perform the claimed function of “the isotopically labeled internal standard produces a mass shift in the labeled internal standard relative to the one or more steroid compounds when analyzed by LC-MS,” since this would be a material property of the claimed compound. It is noted however though, that as instantly claimed no method is claimed but instead only a kit, so then “when,” is not limiting as no when occurs.
With respect to Claim 20, CHEN teaches of a method of measuring vitamin D molecules by liquid chromatography mass spectrometry and specifically of using the internal standard which is hexadeuterated-25OHD3 (abstract), which is the same as applicant’s instantly claimed 25OHD3-[24,24,24,25,25,25]-2H6 internal standard, or in the very least the genus of the claimed species. CHEN further teaches that the internal standards are obtained from Sythetica (which means they are obtained in a package from somewhere else), so in a kit--- though the words kit or package are not used.
CHEN also teaches of using a specific amount of the internal standard, which reads on the claim “amount sufficient for performing,” and of performing LC/MS (Page 8, column 1, 2.2, paragraph 1, Page 7, column 2).
If it is unclear however the CHEN teaches of the deuterations being at the claimed carbon positions of 24 and 25 or 6 and 19, VICCHIO is use to remedy this.
VICCHIO teaches of a method for liquid chromatography mass spectrometry which measured 25-hydroxyvitamin D3(abstract). VICCHIO further teaches of using (6, 19, 19-2H3)25-hydroxyvitamin D3 (abstract) which is the same as applicant’s instant 25OHD3- [6,19,19]-2H3. VICCHIO teaches that this compound is synthesized (abstract and Page 54, column 1, paragraph 2). VICCHIO teaches that this compound as a label (abstract) as a stable isotope tracer (Page 53, column 2, paragraph 2) and that the samples including the stable isotope tracer are analyzed by liquid chromatography mass spectrometry (abstract & Page 54, column 1, paragraph 1).
VICCHIO also teaches of using a specific amount of 6, 19, 19-2H3)25-hydroxyvitamin D3, which reads on the claim “amount sufficient for performing,” and of performing LC/MS (Page 54, column 2, paragraph 2, Page 53, column 2, 2nd to last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use to stable isotope label as is done in VICCHIO in the method using an internal standard, as the isotopic internal standard of CHEN due to the advantage the stable isotopic label using in VICCHIO offers for the quantification of vitamin D3 metabolites (Page 54, column 1, paragraph 1).
It is noted the internal standard compounds taught by CHEN and VICCHIO would perform the claimed function of “the isotopically labeled internal standard produces a mass shift in the labeled internal standard relative to the one or more steroid compounds when analyzed by LC-MS,” since this would be a material property of the claimed compound. It is noted however though, that as instantly claimed no method is claimed but instead only a kit, so then “when,” is not limiting as no when occurs.
If it is unclear that CHEN in view of VICCHIO teach of the claimed kit/packaging, PETERS is used to remedy this.
PETERS teaches of methods of analysis or complex biological samples (abstract), of using isotopic or fluorous labels such as deuterium labels (paragraph 0035, 0041, 0107), and of including the labels/standards in a kir with packaging materials (paragraph 0181). PETERS teaches that molecules such as vitamin D and vitamin D2 can be labeled using the isotopic compounds (paragraph 0220).
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 kit with packaging as is done in PETERS with the materials in CHEN and VICCHIO to aid in detection of vitamin D compounds due to the advantage kits offers in providing the compositions for the methods embodied and instructions for practicing their use conveniently together(PETERS, paragraph 0181).
With respect to Claim 21, CHEN teaches of the vitamin D metabolite being 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 (title and abstract).
With respect to Claim 23, CHEN teaches of a method of measuring vitamin D molecules by liquid chromatography mass spectrometry and specifically of using the internal standard which is hexadeuterated-25OHD3 (abstract), which is the same as applicant’s instantly claimed 25OHD3-[24,24,24,25,25,25]-2H6 internal standard, or in the very least the genus of the claimed species. CHEN further teaches that the internal standards are obtained from Sythetica (which means they are obtained in a package from somewhere else), so in a kit--- though the words kit or package are not used.
If it is unclear however the CHEN teaches of the deuterations being at the claimed carbon positions of 24 and 25 or 6 and 19, VICCHIO is use to remedy this.
VICCHIO teaches of a method for liquid chromatography mass spectrometry which measured 25-hydroxyvitamin D3(abstract). VICCHIO further teaches of using (6, 19, 19-2H3)25-hydroxyvitamin D3 (abstract) which is the same as applicant’s instant 25OHD3- [6,19,19]-2H3. VICCHIO teaches that this compound is synthesize (abstract and Page 54, column 1, paragraph 2). See Claim 17 reason for combination.
With respect to Claim 24, CHEN teaches of a method of measuring vitamin D molecules by liquid chromatography mass spectrometry and specifically of using the internal standard which is hexadeuterated-25OHD3 (abstract), which is the same as applicant’s instantly claimed 25OHD3-[24,24,24,25,25,25]-2H6 internal standard, or in the very least the genus of the claimed species. CHEN further teaches that the internal standards are obtained from Sythetica (which means they are obtained in a package from somewhere else), so in a kit--- though the words kit or package are not used.
If it is unclear however the CHEN teaches of the deuterations being at the claimed carbon positions of 24 and 25 or 6 and 19, VICCHIO is use to remedy this.
VICCHIO teaches of a method for liquid chromatography mass spectrometry which measured 25-hydroxyvitamin D3(abstract). VICCHIO further teaches of using (6, 19, 19-2H3)25-hydroxyvitamin D3 (abstract) which is the same as applicant’s instant 25OHD3- [6,19,19]-2H3. VICCHIO teaches that this compound is synthesize (abstract and Page 54, column 1, paragraph 2). See Claim 20 reason for combination.
Response to Arguments
Applicant’s arguments, see response dated 07/01/2026, with respect to the rejection(s) of claim(s) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of CHEN in view of VICCHIO in view of PETERS.
The examiner notes that a new rejection was made in the priorly used reference did not teach of the compounds amended into the instant independent claims , which were priorly in the dependent claims, amendments dated 07/01/2026. The prior art now teaches of the claimed compounds, and all that is required in the claimed kits are one of the claimed compounds and some form of packaging. Everything else as claimed is intended use and is not limiting in the claims.
The examiner has reviewed the Declaration by Dr. Nigel Clarke dated 07/01/2026. Though it was informative, it was not the reason the prior grounds of rejection was overcome and instead it was due to the prior art not teaching the compounds as now claimed in the independent claims.
Applicant’s arguments with respect to claim(s) have been considered but are moot because the new ground of rejection does not rely on the specific combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
All claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
NETZEL in US 20110301063 teaches of methods and materials involved in simultaneously determining (i.e., multiplexing) the levels of an analyte in biological samples from multiple subjects using high pressure liquid chromatography-tandem mass spectrometry (LC-MS/MS). For example, methods and materials for derivatizing vitamin D metabolites in samples obtained from multiple subjects (e.g., humans), and combining samples for simultaneous analysis in a single assay (abstract). NETZEL further teaches of using internal standards for the vitamin D, which are deuterated including hexadeuteratated-25-hydroxyvitamin D.sub.3 as an internal standard (paragraph 0019, 0027).
GRANT in US 20080128606 teaches of methods and systems using liquid chromatography/tandem mass spectrometry (LC-MS/MS and 2D-LC-MS/MS) for the analysis of endogenous biomarkers, including steroid hormones, such as estrone and estradiol, thyroid hormones, such as free thyroxine, and metabolites, such as 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, in biological samples (abstract). GRANT also teaches of forming deuterated versions of the compounds (paragraph 0125).
COLDWELL in “Stable isotope-labeled vitamin D, metabolites and chemical analogs: synthesis and use in mass spectrometric studies.”
COLDWELL teaches assays for the detection of vitamin D (which is a steroid compound), and of using an isotopically labeled standard of the vitamin D, wherein the isotope is a deuterated variant of a vitamin D compound and of it’s use as an internal standard—“deuterated 25-hydroxyvitamin D3,” ( abstract & Page 419, column 2, “synthesis of labeled standards of vitamin D and metabolites,”-Page 420, column 2, paragraph 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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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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