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 Final Office Action based on application 19/462819 response filed 07/23/2026.
Claims 17 & 20-21 are pending and have been fully considered.
Claims 1-16, 18-19 & 22-24 are cancelled.
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 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over IWASAKI in Improved and efficient synthesis of 1 alpha hydroxy-[6-2H} and 1 alpha hydroxy-[ 6, 19, 19, -2H} vitamin D3 derivatives and further in view of TOMIYAMA in Gas chromatography/ mass spectrometric analysis of 24R,25-dihydroxyvitamin D3 using 24,25-dihydroxy{6,19,19-2H} vitamin D3 as internal standard and further in view of PETERS in US 20060263886.
With respect to Claim 17, IWASAKI teaches of compounds which are deuterium-labeled D3 compounds at the 6,19,19 positions of 1-hydroxyvitamin D3 derivatives. IWASAKI teaches that that deuterium labeling at the 6,19, 19 positions of the A ring of vitamin D was also effective for the 1 ,25-dihydroxy compounds (what is instantly claimed) by simple addition of 1,3-dimethyl-2-imidazolidinone as a co-solvent when creating the compound (abstract & Page 399, column 2, 2.7,- title & contents of sections & Page 400, 2.9 title). As all that the instantly claimed kit is required is the claimed compound--- this is considered to teach of the instantly claimed kit.
Though what the compound is used for is intended use and not limiting for the claims, for compact prosecution if it is not clear to one of ordinary skill in the art that this is the case, TOMIYAMA is used to remedy this.
TOMIYAMA teaches of using 24,25-dihydroxy{6,19,19-2H} vitamin D3 as internal standard (which contains/is a derivative the claimed compound) and of eliminating some compounds and giving rise to a base peak—so producing mass shift(abstract).
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 synthetic deuterated at 6,19,19 positions as an internal standard in a method as is done in TOMIYAMA in the method of IWASAKI due to due to the internal standards ability to preferentially eliminate the CH3 (19), which allows for giving rise to other peaks (TOMIYAMA, abstract).
Though again, use in a kit is obvious to one of ordinary skill, in case this is not apparent from and IWASAKI and TOMIYAMA, PETERS is used to remedy this.
PETERS teaches of methods of analysis or complex biological samples (abstract), of using isotopic 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 can be labeled using the isotopic compounds which include deuterium (paragraph 0220), and that the overall label compound is sued in a concentration that is appropriate/sufficient so that is does not compete with other substances (paragraph 0110) and further that the labels amount is proportional to signal intensity (paragraph 0170) and specifically that LC-MS/MS and tandem MS is used and signals are detected(paragraph 0252-0253, 0034, 0159), so this makes the claimed use/providing of standard in an amount sufficient to produce a mass shift during LC/MS, which is not performed in the instant method obvious to one of ordinary skill.
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 of IWASAKI and TOMIYAMA 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 20, IWASAKI teaches of compounds which are deuterium-labeled D3 compounds at the 6,19,19 positions of 1-hydroxyvitamin D3 derivatives. IWASAKI teaches that that deuterium labeling at the 6,19, 19 positions of the A ring of vitamin D was also effective for the 1 ,25-dihydroxy compounds (what is instantly claimed) by simple addition of 1,3-dimethyl-2-imidazolidinone as a co-solvent when creating the compound (abstract & Page 399, column 2, 2.7,- title & contents of sections & Page 400, 2.9 title). As all that the instantly claimed kit is required is the claimed compound--- this is considered to teach of the instantly claimed kit.
Though what the compound is used for is intended use and not limiting for the claims, for compact prosecution if it is not clear to one of ordinary skill in the art that this is the case, TOMIYAMA is used to remedy this.
TOMIYAMA teaches of using 24,25-dihydroxy{6,19,19-2H} vitamin D3 as internal standard (which contains/is a derivative the claimed compound) and of eliminating some compounds and giving rise to a base peak—so producing mass shift(abstract).
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 synthetic deuterated at 6,19,19 positions as an internal standard in a method as is done in TOMIYAMA in the method of IWASAKI due to due to the internal standards ability to preferentially eliminate the CH3 (19), which allows for giving rise to other peaks (TOMIYAMA, abstract).
Though again, use in a kit is obvious to one of ordinary skill, in case this is not apparent from and IWASAKI and TOMIYAMA, PETERS is used to remedy this.
PETERS teaches of methods of analysis or complex biological samples (abstract), of using isotopic 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 can be labeled using the isotopic compounds which include deuterium (paragraph 0220), and that the overall label compound is sued in a concentration that is appropriate/sufficient so that is does not compete with other substances (paragraph 0110) and further that the labels amount is proportional to signal intensity (paragraph 0170) and specifically that LC-MS/MS and tandem MS is used and signals are detected(paragraph 0252-0253, 0034, 0159), so this makes the claimed use/providing of standard in an amount sufficient to produce a mass shift during LC/MS, which is not performed in the instant method obvious to one of ordinary skill.
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 of IWASAKI and TOMIYAMA 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, IWASAKI teaches of using1 ,25-dihydroxy compounds od D3 (what is instantly claimed) by simple addition of 1,3-dimethyl-2-imidazolidinone as a co-solvent when creating the compound (abstract & Page 399, column 2, 2.7,- title & contents of sections & Page 400, 2.9 title).
Response to Arguments
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 combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Since the claims were significantly amended, a new grounds of rejection is made.
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.
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
