DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 1 and 5-8 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al., (US 2006/0228808) in view of Weiskopf et al., (J. Mass. Spectrom. 2001; 36: 71-78).
Regarding claim 1, Clarke et al., teach a method for detecting vitamin D metabolites comprising adding one or more internal standards to a sample (paragraph 0045), purifying vitamin D metabolites and the internal standards by solid phase extraction and affinity chromatography (paragraphs 0016, 0018, 0045), and determining the concentration of vitamin D metabolites and the internal standards by tandem mass spectrometry comprising electrospray ionization or atmospheric pressure chemical ionization (paragraphs 0039, 0045, 0048). Reference to Clarke et al., does not explicitly teach the steps performed in the order of claim 1; however, the Examiner notes that the selection of any order of performing process steps is prima facie obvious absent any new or unexpected results (see MPEP 2144.04 IV C). Clarke et al., do not teach derivatizing the vitamin D metabolites and the internal standards with PTAD.
Weiskopf et al., teach a method of examining vitamin D3 analogues by mass spectrometry wherein vitamin D is derivatized by PTAD (Abstract, Introduction pages 71-72, Materials and derivatization of vitamin D compounds pages 72-73). Weiskopf et al., also teach utilizing mass spectrometry with electrospray ionization (Mass Spectrometry page 73). Weiskopf et al., teach that PTAD derivatization is advantageous because it provides structurally selective ions for monitoring side chain metabolism in triple quadrupole and quadrupole ion mass spectrometers (conclusions page 78).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Clarke et al., wherein PTAD is utilized as a derivatization agent in order to provide structurally selective ions for monitoring side chain metabolism with triple quadrupole and quadrupole ion mass spectrometers as taught by Weiskopf et al.
Regarding claims 5 and 6, Clarke et al., do not teach a m/z ratio of 314.12±0.5.
Weiskopf et al., teach detection of PTAB derivatized vitamin D3 analogues wherein PTAD derivatives yield a major ion product at a m/z ratio of 314 (Introduction page 72 right column). Weiskopf et al., teach that PTAD derivatization is advantageous because it provides structurally selective ions for monitoring side chain metabolism in triple quadrupole and quadrupole ion mass spectrometers (conclusions page 78).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Clarke et al., wherein PTAD is utilized as a derivatization agent in order to provide structurally selective ions for monitoring side chain metabolism with triple quadrupole and quadrupole ion mass spectrometers as taught by Weiskopf et al.
Regarding claim 7, Clarke et al., teach utilizing high turbulence liquid chromatography (paragraphs 0017, 0037).
Regarding claim 8, Clarke et al., teach determining vitamin D in a serum sample (paragraph 0036).
Claim 2 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al., (US 2006/0228808) in view of Weiskopf et al., (J. Mass. Spectrom. 2001; 36: 71-78), and further in view of Clarke et al., (US 2006/0228809).
Regarding claim 2, Clarke et al., ‘808 in view of Weiskopf et al., do not teach d3-1α,25(OH)2D3 as the internal standard.
Clarke et al., ‘809 teach a method for detecting vitamin D wherein the internal standard is an isotope of a vitamin D metabolite (paragraph 0046). Clarke et al., also teach the internal standard being a deuterated vitamin D metabolite (paragraph 0046). Clarke et al., teach that it is advantageous to utilize a vitamin D metabolite as an internal standard as a means of generating a standard curve in order to calculate the quantity of the vitamin D metabolite (paragraph 0046).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Clarke et al., ‘808 in view of Weiskopf et al., wherein an isotope of a vitamin D metabolite is utilized as an internal standard in order to calculate the quantity of the vitamin D metabolite as taught by Clarke et al., ‘809.
Allowable Subject Matter
Claims 3 and 4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the prior art of record does not teach or suggest a method for determining an amount of 1α,25(OH)2D3 wherein the internal standard comprises 1α,25(OH)2D3-[6,19,19-2H, and wherein ionizing produces fragment ions having an m/z ratio of 574.37±0.5 and 314.12±0.5. Reference to Clarke et al., is the prior art reference closest to the instant claims. Clarke et al., teach a method for detecting vitamin D metabolites comprising adding one or more internal standards to a sample (paragraph 0045), purifying vitamin D metabolites and the internal standards by solid phase extraction and affinity chromatography (paragraphs 0016, 0018, 0045), and determining the concentration of vitamin D metabolites and the internal standards by tandem mass spectrometry comprising electrospray ionization or atmospheric pressure chemical ionization (paragraphs 0039, 0045, 0048). Clarke et al., do not teach the internal standard being 1α,25(OH)2D3-[6,19,19-2H as recited in the claims. Clarke et al., also do not teach fragment ions having m/z ratios of 574.37+0.5 and 314.12+0.5. As such, reference to Clarke et al., do not meet the limitations of claims 3 and 4.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DWAN A GERIDO whose telephone number is (571)270-3714. The examiner can normally be reached Mon-Fri 10-6.
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/DWAN A GERIDO/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
