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 a 2nd, Non-Final Office Action based on application 18/125708 response filed 12/18/2025.
Claims 1-12, 14 & 16 are pending and have been fully considered.
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.
Claims 1-12, 14 & 16 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, c) requires “determining the level of Vitamin D or metabolites thereof,” however it is unclear if by this if applicant is referring to the Vitamin D and metabolites which are released or not.
Further, with respect to Claim 1 it is unclear what the releasing reagent itself really is. There is a “-,” bulleted list of 4 items that the releasing reagent can comprise and then there is also an “or,” clause which indicates that the releasing reagent can be 3-hydroxybenzoic acid or 2,4-dihydroxybenzoic acid. There is no “and,” required in the bulleted list, and therefore it is unclear in the claimed bulleted list if all parts of this list are required or not, and if instead each bullet is and “or.” Therefore, the claims are unclear need cleared up.
Claim 2, says that the releasing agent can be one of 3 options, however claim 1 requires that the releasing agent salt requires both a benzoate anion and a sodium or ammonium cation. The compounds listed in Claim 2 do not all require benzoate. For example, at least ammonium- salicylate does not and also 3-methylsalicylate does not. Therefore, applicant seems to be improperly broadening Claim 1, by including additional options. Therefore, the claims are unclear. The same applies to the releasing reagent claims in Claims 3, 5.
With respect to Claims 3 & 5, they state that, the releasing agent is “sodium 3-methylsalicylate.” Claim 1 from which Claim 3 depends on requires that the releasing agent is not sodium salicylate. Sodium 3-methylsalicylate is a type of sodium salicylate. Therefore, Claims 3 & 5 seem to be broadening the claim from what was claimed in Claim 1 and therefore the claims are unclear and confusing.
With respect to Claim 6, “the level of salicylic acid,” fails to have proper antecedent basis,” as a level of salicylic acid was not mentioned priorly in the claims.
With respect to Claim 14, it claims a, “kit,” which is “configured for use,” and then specifies in words the method of Claim 1. It is unclear what exactly makes a kit, “configured for use,” in a method and if this requires that the claim has any more structural elements other than the concrete parts claims of “a container containing the releasing reagent,” and the “instructions for use.”
Further with respect to Claim 14, it is claimed that the releasing reagent within the container is provided “in an effective level to release Vitamin D and metabolites thereof.” For Claim 14--- as the reagent is provided in a container and no actual action is taken of releasing the vitamin D, it is unclear what this “effective level,” is since what the effective level is since what the effective level is depends on how much sample is used.
Claims 4, 7-12 & 16 are also rejected by virtue of being dependent on Claim 1.
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, 7-12, 14 & 16 are rejected under 35 U.S.C. 103 as being obvious by GARRITY in WO 02057797 (As cited on IDS dated 08/18/2023) in view of KOBOLD in US 20100285603.
With respect to Claims 1 & 14, GARRITY teaches of methods and kits for determining a concentration of a vitamin D component by using/treating with a releasing component for releasing vitamin D from its binding protein prior to measurement (abstract, claims 1, 19, 66; p. 10).
GARRITY further teaches of the releasing component further comprises a salicylate or the like, such as 8-anilino-1- naphthalenesulfonic acid (ANS). GARRITY even further teaches that the salicylate (or the like molecule, again which is ANS) is a metal salicylate, for example sodium salicylate--- or this can read on sodium ANS as instantly claimed. The release composition preferably comprises about 0.5 to about 5% of a metal salicylate (or metal ANS). GARRITY specifically teaches that the reagent can be substantially free of a salicylate and the like (Page 5, lines 10-14), again reading on the instant claims. All releasing agent possibilities in the claim are claimed as alternatives to one another.
GARRITY teaches that the releasing agent is used at an effective level to release Vitamin D from it’s binding protein (Page 10, lines 11-19).
GARRITY does not teach of determining the level of vitamin D using mass spectrometry, nor of the releasing reagent comprising benzoate compounds.
KOBOLD is used to remedy this. Specifically, KOBOLD teaches of method of measuring a vitamin D metabolite (determining level) in a sample, the method comprising the steps of (a) treating said sample with a vitamin D metabolite releasing reagent under conditions appropriate to release a vitamin D metabolite from vitamin D-binding protein and not to cause protein precipitation, (b) subjecting the treated sample obtained in step (a) to a chromatographic separation, and (c) measuring a vitamin D metabolite during or after said chromatographic separation (abstract).
KOBOLD further teaches of detecting/determine level by mass spectrometry (paragraph 0065). Even further, KOBOLD teaches of using benzoate compounds as the anion for a salt vitamin D releasing agent (paragraph 0038).
KOBLD even further teaches of using a kit for the instant invention as claimed in Claim 14—which has instructions for use (paragraph 0078) and wherein the reagent is in a container/cups(paragraph 0119).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect vitamin D by mass spectrometry as is done in KOBOLD, in the method of GARRITY due to the fact that it offers an advantage in that is it known to achieve separation of individual vitamin D metabolites (KOBOLD, paragraph 0008). It also would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use benzoate compounds and specifically benzoate as the anion in a salt of a vitamin D releasing reagent as is done in KOBOLD, in the method of GARRITY due to the advantage it offers in when combined the with associate cation of being good miscible in water (KOBOLD, paragraph 0038) which offers advantages for extraction of the vitamin D (KOBOLD, paragraph 0008).
With respect to Claims 4 & 16, GARRITY teaches of the releasing component further comprises a salicylate and the like, such as 8-anilino-1- naphthalenesulfonic acid (ANS). GARRITY even further teaches that the salicylate is a metal salicylate, for example sodium salicylate. The release composition preferably comprises about 0.5 to about 5% of a metal salicylate, for example a sodium salicylate. In an alternative embodiment, the releasing composition is substantially free of a salicylate and the like (Page 5, lines 10-14). GARRITY does not call out the releasing agent having an alkyl residue.
KOBOLD is used to remedy this and teaches of the releasing agent being one of 1-Butyl-4-methylpyridinium tetrafluoroborate; 1-Butyl-3-methyl-imidazolium tetrafluoroborate; 1-Butyl-3-methyl-imidazoliumoctylsulfate; 1-Butyl-3-methylpyridiniumchloride; 1-Hexylpyridiniumchloride; 1-Methyl-1-octyl pyrrolidiniumchloride; N-Octylpyridiniumchloride; 3-Carbamoyl-1-octyloxymethyl pyridiniumchloride; KBr; KJ; and KSCN, and of combinations thereof (methyls are alkyl groups) (paragraph 0039).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use an alkyl residue as is done in KOBOLD in the method of GARRITY due to the advantage these reagents offer in being preferable reagents for vitamin D release (KOBOLD, paragraph 0039).
With respect to Claim 7, GARRITY teaches of coupling the vitamin D component to a solid phase (Page 13, line 22-31).
With respect to Claim 8, GARRITY teaches of adding a buffer and alcohol (Page 24, lines 8-20 & Page 25, lines 17-24).
With respect to Claim 9, GARRITY teaches of the vitamin D metabolites abstract, but does not call out what the metabolites are.
KOBOLD is sued to remedy this. KOBOLD teaches of the vitamin D metabolites being vitamin D.sub.2 or D.sub.3 (paragraph 0003-0007). It would have been obvious to one of ordinary skill in the art to detect these vitamin D metabolites as is done in KOBOLD in the method of GARRITY due to the advantage knowledge of the metabolites offers a clinical sample to help a clinician establish a diagnosis (KOBOLD, paragraph 3).
With respect to Claim 10, GARRITY teaches of methods and kits for determining a concentration of a vitamin D component by using/treating with a releasing component for releasing vitamin D from its binding protein prior to measurement (abstract, claims 1, 19, 66; p. 10).
With respect to Claim 11, GARRITY teaches that the method is an automated assay (Example 1).
With respect to Claim 12, GARRITY teaches of what is shown above, but does not teach of the claimed specific LC/MS.
KOBOLD is used to remedy this and more specifically teaches of us HPLC and a mass spectrometer which is a triple quadrupole (paragraph 0104).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect vitamin D by mass spectrometry as is done in KOBOLD, in the method of GARRITY due to the fact that it offers an advantage in that is it known to achieve separation of individual vitamin D metabolites (KOBOLD, paragraph 0008).
Claims 2-3, & 5-6 are rejected under 35 U.S.C. 103 as being obvious by GARRITY in WO 02057797 (As cited on IDS dated 08/18/2023) in view of KOBOLD in US 20100285603 and further in view of ZIELINSKI in US 20140273021 and in further view of Interx in EP 0036145 (as cited on IDS dated 01/18/2023).
With respect to Claims 2-3, GARRITY teaches of the releasing component further comprises a salicylate and the like, such as 8-anilino-1- naphthalenesulfonic acid (ANS). GARRITY even further teaches that the salicylate is a metal salicylate, for example sodium salicylate. The release composition preferably comprises about 0.5 to about 5% of a metal salicylate, for example a sodium salicylate. In an alternative embodiment, the releasing composition is substantially free of a salicylate and the like (Page 5, lines 10-14). The use of sodium salicylate as the releasing agent reads on the instant claiming of the releasing agent being a salt that comprises a sodium cation. All releasing agent possibilities in the claim are claimed as alternatives to one another.
KOBOLD teaches of using benzoate compounds (paragraph 0038).
Neither GARRITY of KOBOLD teach of the claimed compounds exactly, of sodium 3-methylsalicylate.
ZIELINKSI remedies this and teaches of vitamin D assays where sodium salicylate mixed with 1-ethy-3-methylpyrudium ethyl sulfate (Claim 4, 0017) (these two compounds together would give sodium- 30 methyl salicylate).
It would have been obvious to use the releasing reagents of ZIELINSKI in the methods of GARRITY and KOBOLD due to the known advantages sodium salicylate concentration has on assay signal (ZIELINSKI, paragraph 0017).
Since ZIELINSKI does not teach that the sodium siacylate is sodium 3-methyl siacylate, Interx is used to remedy this.
Interx teaches of sodium 3-methylsalicylate and it’s use as an adjuvant. It would have been obvious to one of ordinary skill to use an adjuvant of sodium siacylate as is done in Interx in the methods of GARRITY, KOBOLD, and ZIELINSKI due to the advantages adjuvants have for enhancing efficacy of other substances (Interx, Example III).
With respect to Claim 5, GARRITY teaches of the releasing component further comprises a salicylate and the like, such as 8-anilino-1- naphthalenesulfonic acid (ANS). GARRITY even further teaches that the salicylate is a metal salicylate, for example sodium salicylate. The release composition preferably comprises about 0.5 to about 5% of a metal salicylate, for example a sodium salicylate. In an alternative embodiment, the releasing composition is substantially free of a salicylate and the like (Page 5, lines 10-14).
GARRITY further teaches of a preferred releasing composition comprises about 0.1 to about 1 M of an aqueous base component, about 0.01 to about 5% of a cyclo-oligomer component and about 0.01 to about 5% of a salicyclate. As discussed above, the releasing composition of this invention is adaptable for use in or with various bio-assay techniques known in the art to determine the concentration of a vitamin D component. For example, in one embodiment, a kit of the present invention comprises a releasing composition and a detecting composition (Page 11, last paragraph).
GARRITY and KOBOLD does not teach of the claimed sodium-3-methyl salicylate concentration, nor of the exact claimed concentration of sodium 3-methylsalicylate.
ZIELINKSI remedies this and teaches of vitamin D assays where sodium salicylate mixed with 1-ethy-3-methylpyrudium ethyl sulfate (Claim 4, 0017) (these two compounds together would give sodium- 30 methyl salicylate).
It would have been obvious to use the releasing reagents of ZIELINSKI in the methods of GARRITY and KOBOLD due to the known advantages sodium salicylate concentration has on assay signal (ZIELINSKI, paragraph 0017).
Further, it would have been obvious to one of ordinary skill in the art to adjust the concentration of the sodium salicylate used as is done in ZELINKSKI, in the methods of GARRITY and KOBOLD since it is known to have an affect on signal intensity (ZIELINSKI, paragraph 0017).
With respect to Claim 6, GARRITY does not teach of determining the level of vitamin D using mass spectrometry.
KOBOLD is used to remedy this. Specifically, KOBOLD teaches of method of measuring a vitamin D metabolite (determining level) in a sample, the method comprising the steps of (a) treating said sample with a vitamin D metabolite releasing reagent under conditions appropriate to release a vitamin D metabolite from vitamin D-binding protein and not to cause protein precipitation, (b) subjecting the treated sample obtained in step (a) to a chromatographic separation, and (c) measuring a vitamin D metabolite during or after said chromatographic separation (abstract).
KOBOLD further teaches of detecting/determine level by mass spectrometry (paragraph 0065).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect vitamin D by mass spectrometry as is done in KOBOLD, in the method of GARRITY due to the fact that it offers an advantage in that is it known to achieve separation of individual vitamin D metabolites (KOBOLD, paragraph 0008).
GARRITY and KOBOLD does not teach of the of measuring the claimed salicylate, nor of the exact claimed concentration of sodium 3-methylsalicylate.
ZIELINKSI remedies this and teaches of vitamin D assays where sodium salicylate mixed with 1-ethy-3-methylpyrudium ethyl sulfate (Claim 4, 0017) (these two compounds together would give sodium- 30 methyl salicylate).
It would have been obvious to use the releasing reagents of ZIELINSKI in the methods of GARRITY and KOBOLD due to the known advantages sodium salicylate concentration has on assay signal (ZIELINSKI, paragraph 0017).
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to measure/detect with mass spec or other mechanism the concentration of the sodium salicylate used as is done in ZELINKSKI, in the methods of GARRITY and KOBOLD since it is known to have an affect on signal intensity and overall measurement picture (ZIELINSKI, paragraph 0017).
Response to Arguments
Applicant's arguments filed 12/18/2025 have been fully considered but they are not persuasive.
The prior 112 rejections were overcome by amendments made 12/18/2025, however upon further review there were more serious 112 issues with the claims—therefore rejections remain on the record as shown above. Due to this addition of rejections, without substantial amendment to Claim 1, this action is made a Non-Final action.
The examiner notes that the current prior art is the best prior art found, so if applicant rewrites the claims to overcome all 112 issues--- applicant will likely be able to move past this prior art.
With respect to the 103 rejections, applicant argues that the prior art does not teach of the claimed releasing reagents or the required negative limitations, and specifically that the prior art does not teach of (1) specific benzoate-based releasing reagents; and (2) the “free of the addition of sodium salicylate as the releasing reagent.”
The examiner disagrees. Specifically, the secondary reference, KOBOLD teaches of (1). KOBOLD teaches of using benzoate compounds as the anion for a salt vitamin D releasing agent (paragraph 0038).
It also would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use benzoate compounds and specifically benzoate as the anion in a salt of a vitamin D releasing reagent as is done in KOBOLD, in the method of GARRITY due to the advantage it offers in when combined the with associate cation of being good miscible in water (KOBOLD, paragraph 0038) which offers advantages for extraction of the vitamin D (KOBOLD, paragraph 0008).
GARRITY teaches of (2). Specifically, GARRITY teaches of the releasing component comprising a salicylate or the like--- such as 8-anilino-1- naphthalenesulfonic acid (ANS). GARRITY even further teaches that the salicylate (or the like) is a metal salicylate (or the like), and gives the example of sodium salicylate but it can also be other metal salicylates, which in these cases reads on the claimed negative limitation that it is “free of the addition of sodium salicylate,” (Page 5, lines 10-14). Therefore this is not impermissible hindsight as argued by applicant.
The examiner notes that there are many 112 rejections made with respect to the instant claims. The instant prior art is the best found, so if applicant is able to clear up all of the 112 issues through amendments (which might be significant), and also present convincing arguments with respect to the prior art--- it might be easier to move forward at this point.
Applicant argues about the compounds in Claims 2-3 and that none of the pieces of prior art teach of them. The examiner notes that there are 112 issues with respect to Claim 2-3. As unclearly the claims are written, the examiner maintains the rejection on these claims as instantly and unclearly claimed. However, if the claims are cleared up--- the rejections will likely be dropped depending on what amendments are made.
With respect to all other arguments made by applicant--- the examiner tentatively agrees, however the art rejections are maintained at this point in time due to the clarity issues with respect to the claims and due to some of the clarity rejections in the base Claim 1--- it is hard to determine what is actually required by the claim as what is not.
If applicant can clear up all 112 issues with respect to the claims, it should be much easier to move forward with the instant claims.
It is noted that for Claim 14, the purpose or intended use of the reagent does not carry as much weight. Printed instructions are obvious to include with a kit. Claim 14 through BRI cam read as a kit, containing a container and simple reagent (3-hydroxybenzoic acid or 2,4-dihydroxybenzoic acid for example, which are known compounds). The use of these compounds to release vitamin D is not required in these claims. Applicant does not make specific arguments about Claim 14, with respect to the kit--- however the examiner is not convinced by the arguments with respect to Claim 1 for Claim 14.
All claims remain rejected.
Conclusion
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