DETAILED ACTION
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 .
Applicant’s response filed 12/29/2025 has been received and entered into the case. Claims 2-4, 11-23 are pending. Claims 11-20 are withdrawn. Claims 2-4, 21-23 have been considered on the merits herein . All arguments and amendments have been considered.
All previous rejections have been withdrawn in light of applicants claim amendments; however, the references have been applied in new rejections herein.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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) 3, 22 is/are rejected under 35 U.S.C. 102(a)(1)and (a)(2) as being anticipated by WO2010014978A1.
WO’978 teaches a method comprising adding an oxidoreductase/oxidase, i.e. 1α-hydroxylase (CYP27B1) to a sample, wherein the oxidoreductase/oxidase is on an electrode to quantify a vitamin D derivative (1α,25(OH)2D3) (p. 1, lines 6-14, p. 4, lines 1-9, p. 5, lines 4-28), and adding a mediator, ABTS, a common redox mediator (p. 8, lines 28-p. 9, lines 1-7). The mechanism of CYP27B1 (oxidoreductase/oxidases) is that it catalyzes the insertion of one oxygen atom from molecular oxygen into its substrate, while reducing the other oxygen atom to water, thereby transferring electrons from a substrate to oxygen. CYP27B1 catalyzes the rate-limiting step in the activation of vitamin D, i.e. hydroxylation of 25-hydroxyvitamin D3 to form 1α,25(OH)2D3. The reference teaches that in vitro electrons can be supplied catalytically and that the catalytic current is directly proportional to the amount of vitamin D derivative (p. 5, lines 13-15, 22-28) which is measured by an electrochemical method (p. 9, Electrochemistry experiments-p. 10, lines 1-3) according to claim 3.
Regarding claim 23, 1α-hydroxylase (CYP27B1) belongs to EC. 1.14, which is a subclass of EC 1.1.
Thus, the reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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(s) 2, 4, 21, 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Adbel-Khalik et al. (Biochem. and Biophys. Res. Comm., 2014, IDS) in view of JPS526594 (IDS).
Abdel-Khalik teaches adding cholesterol oxidase to a serum sample for the quantification of vitamin D metabolites/derivatives (abstract, p. 742, 1st col, 2nd parag., p. 749, 1st and 2nd full parag.). The cholesterol oxidase oxidizes the vitamin D metabolites/derivatives (abstract, p. 749, 1st and 2nd full parag.). The reference also teaches the use of 17βhydroxysteroid dehydrogenase to oxidize vitamin D derivatives .
Regarding claims 21, 17βhydroxysteroid dehydrogenase is a dehydrogenase belonging to EC.1.1.1.51.
Regarding claims 23, cholesterol oxidase is an oxidase belonging to EC.1.1.3.6.
The above reference differs from the claimed invention in that it does not teach the oxidase generates hydrogen peroxide and adding a reagent reacting with the hydrogen peroxide to determine vitamin D derivative concentration by a colorimetric method.
The generation of hydrogen peroxide is taken to be an inherent property/activity of the cholesterol oxidase enzyme.
JP594 teaches adding cholesterol oxidase to a sample and wherein hydrogen peroxide is produced or oxygen is consumed and peroxide or oxygen are quantified to determine an amount of an analyte (cholesterol) in the sample (p. 2, lines 8-12, 41-p. 3, lines 1-4, ex. 1 and 2). JP594 teaches using a reagent which reacts with the hydrogen peroxide produced, i.e. phenol and peroxidase, and color development is measured. The reference teaches measuring both oxygen consumption and the amount of hydrogen peroxide produced to determine the analyte in the sample (p. 2, 2nd to last full sentence, Ex. 2). Regarding claims 23, cholesterol oxidase is an oxidase belonging to EC.1.1.3.6.
Therefore, before the effective filing date of the claimed invention, a posita would have been motivated by the teachings of the prior art which teach the use of an oxidase enzyme in a vitamin D quantification method because the art teaches that an oxidase enzyme is known to oxidize the vitamin D derivative to generate hydrogen peroxide and teaches adding a reagent to the reaction which reacts with the hydrogen peroxide which is used to determine the concentration of the derivative using colorimetric methods. Thus, a posita would have had a reasonable expectation of successfully applying the colorimetric method of JP594 to the Abdel-Khalik to quantify vitamin D derivatives as claimed.
Claim(s) 2-4, 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP2016063750 in view of WO2010014978A1 and JPS526594 (IDS).
JP2016063750 teaches adding an oxidoreductase, i.e. vitamin D hydroxylase and oxidase, with a mediator, i.e. ferroxidin, to a sample and quantifying vitamin D derivative, 25-hydroxyvitamin D to 1α, 25-hydroxyvitamin D2 (abstract, p. 2, p. 6, whole page-p. 7, lines 1-3, p. 10, Production method of1α, 25-hydroxyvitamin D2 section-p. 12). The reference teaches that hydrogen peroxide is generated as a by-product of the reaction (p. 6, 1st parag.). The method also teaches the use of glucose dehydrogenase in the method (p. 6, 1st parag.).
The reference differs from the claimed adding a reagent reacting with the hydrogen peroxide to determine vitamin D derivative concentration by a colorimetric method or using an electrode to determine the concentration of vitamin D by an electrochemical method.
WO’978 teaches a method comprising adding an oxidoreductase/oxidase, i.e. 1α-hydroxylase (CYP27B1) to a sample, wherein the oxidoreductase/oxidase is on an electrode to quantify a vitamin D derivative (1α,25(OH)2D3) (p. 1, lines 6-14, p. 4, lines 1-9, p. 5, lines 4-28), and adding a mediator, ABTS, a common redox mediator (p. 8, lines 28-p. 9, lines 1-7). The mechanism of CYP27B1 (oxidoreductase/oxidases) is that it catalyzes the insertion of one oxygen atom from molecular oxygen into its substrate, while reducing the other oxygen atom to water, thereby transferring electrons from a substrate to oxygen. CYP27B1 catalyzes the rate-limiting step in the activation of vitamin D, i.e. hydroxylation of 25-hydroxyvitamin D3 to form 1α,25(OH)2D3. The reference teaches that in vitro electrons can be supplied catalytically and that the catalytic current is directly proportional to the amount of vitamin D derivative (p. 5, lines 13-15, 22-28) which is measured by an electrochemical method (p. 9, Electrochemistry experiments-p. 10, lines 1-3) according to claim 3. Regarding claim 23, 1α-hydroxylase (CYP27B1) belongs to EC. 1.14, which is a subclass of EC 1.1.
JP594 teaches adding cholesterol oxidase to a sample and wherein hydrogen peroxide is produced or oxygen is consumed and peroxide or oxygen are quantified to determine an amount of an analyte (cholesterol) in the sample (p. 2, lines 8-12, 41-p. 3, lines 1-4, ex. 1 and 2). JP594 teaches using a reagent which reacts with the hydrogen peroxide produced, i.e. phenol and peroxidase, and color development is measured. The reference teaches measuring both oxygen consumption and the amount of hydrogen peroxide produced to determine the analyte in the sample (p. 2, 2nd to last full sentence, Ex. 2).
Regarding claims 21-23, glucose dehydrogenase is an EC 1.1.1.47 enzyme, and cholesterol oxidase is an oxidase belonging to EC.1.1.3.6.
Therefore, before the effective filing date of the claimed invention, dehydrogenases and oxidases were known to be used in methods of quantifying vitamin D derivatives in redox-mediated methods wherein oxygen is consumed and hydrogen peroxide is generated. The art collectively teaches that mediators and reagents can be added to the reaction and used with an electrode in electrochemical methods or used in colorimetric methods. Therefore, a posita has good reason to pursue known options within his or her technical grasp with a reasonable expectation of successfully quantifying vitamin D derivatives using known enzymes and reagents in electrochemical and/or colorimetric methods.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 3, 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18538143 (reference application) in view of WO2010014978A1.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to methods for quantifying a vitamin D derivative (25-hydroxyvitamin D) comprising adding an oxidase (hydroxylase) and a mediator to a sample. The examined application generically claims a vitamin D derivative and an oxidase and using an electrode in an electrochemical method, while the reference claims are drawn specifically to 25-hydroxyvitamin D (as the derivative), and hydroxylase (an oxidase).
WO’978 teaches a method comprising adding an oxidoreductase/oxidase, i.e. 1α-hydroxylase (CYP27B1) to a sample, wherein the oxidoreductase/oxidase is on an electrode to quantify a vitamin D derivative (1α,25(OH)2D3) (p. 1, lines 6-14, p. 4, lines 1-9, p. 5, lines 4-28), and adding a mediator, ABTS, a common redox mediator (p. 8, lines 28-p. 9, lines 1-7). The mechanism of CYP27B1 (oxidoreductase/oxidases) is that it catalyzes the insertion of one oxygen atom from molecular oxygen into its substrate, while reducing the other oxygen atom to water, thereby transferring electrons from a substrate to oxygen. CYP27B1 catalyzes the rate-limiting step in the activation of vitamin D, i.e. hydroxylation of 25-hydroxyvitamin D3 to form 1α,25(OH)2D3. The reference teaches that in vitro electrons can be supplied catalytically and that the catalytic current is directly proportional to the amount of vitamin D derivative (p. 5, lines 13-15, 22-28) which is measured by an electrochemical method (p. 9, Electrochemistry experiments-p. 10, lines 1-3) according to claim 3. Regarding claim 23, 1α-hydroxylase (CYP27B1) belongs to EC. 1.14, which is a subclass of EC 1.1.
Therefore, it would have been obvious to use a hydroxylase in an electrochemical method for quantifying vitamin D derivatives because the art teaches electrochemical methods comprising the use of electrodes and hydroxylase enzymes for quantifying vitamin D derivatives.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments with respect to the claim(s) have been considered but are moot because the new ground of rejection. While the previous rejections have been withdrawn, the same references are applied in new rejections herein to address applicants claim amendments.
Applicants’ argument is only that the cited references do not teach the limitations of the amended claims, yet do not discuss the references applied against the claims, explaining how the claims avoid the references or distinguish from them.
It is the Examiners position that before the effective filing date of the claimed invention, dehydrogenases and oxidases were known to be used in methods of quantifying vitamin D derivatives in redox-mediated methods wherein oxygen is consumed and hydrogen peroxide is generated. The art collectively teaches that mediators and reagents can be added to the reaction and used with an electrode in electrochemical methods or used in colorimetric methods. Therefore, a posita has good reason to pursue known options within his or her technical grasp with a reasonable expectation of successfully quantifying vitamin D derivatives using known enzymes and reagents in electrochemical and/or colorimetric methods.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO02/073181 (IDS). Using cholesterol oxidase on electrode
WO’181 teaches a method comprising adding an oxidase and dehydrogenase to a sample, wherein the enzymes are on an electrode (p. 3, whole page, p. 5, last parag., p. 7, 2nd full parag.), and adding a mediator capable of mediating electron transfer from the oxidoreductase (p. 4, 6th parag., see examples).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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