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 .
Response to Arguments
In the Response, dated 5/1/2026, the Applicant has provided amendments to the claims, as well as arguments drawn to the previous rejections.
On pages 8 and 9 of the Applicant’s Arguments, the Applicant contends that amended claim 1 possesses a practical application. While the Applicant has certainly defined that their invention provides for a practical application, the MPEP suggests that there is a need for a specific practical application. See MPEP2106.04(d)(2). Since it has been established that the general steps of the claimed method are known and considered routine, there must be a specific practical application provided in the claim for eligibility under 35 USC 101. When considering the newly added limitation, while it does provide for an application of the claimed method, the limitation lacks specificity wherein the claimed steps would have been obvious to the ordinary artisan. That is to say, if the claim is drawn to testing drinking water, if the water exceeded a contaminant level, this step would have already been performed, regardless of how the contaminant was detected. Whereas in the Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117, 126 USPQ2d 1266 (Fed. Cir. 2018) example, there is an explicit criterion for dosing, based upon data that was acquired using routine and conventional methods. As such, the 35 USC 101 rejection is maintained.
On pages 10-12 of the Applicant’s Arguments, the Applicant asserts that Matsui does not teach the claimed chemical compound. Based upon the Applicant’s Arguments, and the amendment to the independent claim, the claims on now only considered obvious over the prior art, and are no longer considered anticipated. This would be obvious to the ordinary artisan because enzyme kinetics and inhibition testing is routine in the art; this is highlighted by the fact that Matsui teaches the same enzyme with the same general method. The ordinary artisan understands that an enzyme and a substrate create a product; the ordinary artisan understands that an inhibitor inhibits the enzyme-substrate reaction; the ordinary artisan understands that providing a substrate, after potential inhibition, will tell the artisan the degree/effectiveness of inhibition, if there is inhibition present; the ordinary artisan understands that the structure of the inhibitor is immaterial to the steps of the method, and that any compound can be used to determine if it provides for any inhibitor properties. If said compound is a known toxin or environmental contaminant, it would be obvious to the ordinary artisan to use the acquired data to exclude contaminated product.
Prior to amendment, the claimed method [excluding the chemical compound] was wholly and unambiguously anticipated by Matsui, wherein steps for determining if a substance was a cytochrome inhibitor are known; furthermore, these steps would be clear to the ordinary artisan, because these steps can be used to determine the inhibitory affects of a chemical compound on, essentially, any enzyme. Briefly, if an enzyme’s kinetics are known, the ordinary artisan understands that a suspected inhibitor will slow the known kinetics of a pure sample. This is true regardless of enzyme. Therefore, prior to amending, there is nothing non-obvious about the claimed compounds, because any compound can be used in the method to determine if said compound is inhibitory. Since this would be obvious to any ordinary artisan versed in enzymology, this kinetic association between enzyme-substrate-inhibitor would be clear, predictable, and obvious to the ordinary artisan. See MPEP 2141.03. This is further underscored by the fact that many of the claimed compounds are known inhibitors of the claimed cytochrome enzyme, as highlighted by IDS references Koenig, et al (Aquatic Toxicology, 108, 2012 [IDS Reference]) and Narimatsu, et al (Chemico-Biological Interactions, 194, 2011 [IDS Reference]).
On page 12 of the Applicant’s Arguments, the Applicant asserts that there is no motivation to try, nor is there an expectation of success. As stated above, the claims are drawn to a general method of determining inhibition; literally any enzyme can be substituted in for the claimed cytochrome, wherein the claimed method (or that of Matsui) can be used to determine any inhibitors of that particular enzyme. The Applicant is reminded that the claim preamble is drawn to a method of detecting cytochrome inhibitors, wherein the only difference between the claimed method and that of Matsui is that Matsui is more explicit about the purposes for knowing inhibition. While the claimed exclusion of “drug” is noted, it does not change the fact that enzyme inhibition and the information gleaned from Matsui would heavily inform the ordinary artisan that Matsui’s method does not need to be limited to drug inhibition. Finally, Matsui teaches inhibitors of cytochrome that affect drug metabolism; in Matsui, the inhibitor is not necessarily a drug, as defined in the instant claim-set.
With respect to the contention that there would be no expectation of success, it is unclear what criteria the Applicant is considering “success.” As stated above, any enzyme can be substituted into the claimed method in order to find that enzyme’s inhibitors; the claimed method can be generalized to finding inhibitors to any enzyme. Success would be demonstrated based on the fact of whether inhibitors could be accurately defined. Since Matsui’s method is generalized to determining how one compound affects another, any specifically describes enzyme-substrate inhibition, the “success” would be self-evident. That is to say, the ordinary artisan can use Matsui’s method to predictably determine if any substance acts as an inhibitor to cytochrome, because the ordinary artisan understands that a change in the enzyme-substrate kinetics would directly tell said ordinary artisan if there were inhibitory affects.
On pages 13 of the Applicant’s Arguments, the Applicant points to applied examples as evidence of unexpected results. With respect to Example 5, the Applicant contends that this shows the method can demonstrate inhibition in compounds that are not known inhibitors. The ordinary artisan possesses a Masters or PhD in a related field of enzymology, and ample applied experience. It is unclear why the Applicant believes the steps provided by Matsui, and routinely used in laboratory setting, could not be obviously applied to “unknown” compounds to determine their inhibitory status. Additionally, the claims are not exclusively drawn to unknown inhibitors, nor is there any evidence to suggest that the claimed method is used to identify any specific inhibitors; the method merely presents steps to determine if an enzyme inhibitor is present. These steps parallel those taught by Matsui, and could clearly be applied to any other compound.
On page 14 of the Applicant’s Arguments, the Applicant argues that Matsui does not teach “real samples.” It is unclear what a “real sample” is supposed to be, but Matsui provides for aqueous phase detection, which would necessarily fulfill the “water” limitation. Regardless, the ordinary artisan understands that enzymes can be used for any number of situations.
On page 14 of the Applicant’s Arguments, the Applicant states that the instant method provides for “CYP450 as a multigroup analytical biosensor.” It is unclear where to find this limitation in the claims.
The previous rejections have been modified to integrate the new limitations. All of the previous rejections are maintained for the reasons provided above, and in the rejections below.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 4-10, 18, 30, and 31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) a method of detecting inhibitors of cytochrome P450 (CYP450). This judicial exception is not integrated into a practical application because the claims provide for an abstract idea, and do not provide for any steps that tell the artisan how to apply the abstract idea in a meaningful manner.
The independent claim is drawn to a method of detecting inhibitors of the enzyme class CYP450, by exposing the enzyme to a potential inhibitor, providing a substrate for the enzyme, and detecting a signal provided by measurement of the enzymatic substrate or product. There are no claims drawn to methods of instructing the artisan what to do with the acquired data. Based upon the claims, there are several active steps, followed by a mental process of observing. See MPEP 2106.04(a). In order to fully analyze the claims under 35 USC 101, the Applicant is directed to MPEP 2106, especially the flow chart provided in section III.
The first step of the flow chart asks if the claims are drawn to a statutory category. Since the claims are drawn to a method, the claims disclose one of the described statutory categories. Step 2A asks if the claims are directed to an abstract idea. Based upon an analysis of this step, there are 2 active steps of applying inhibitor, and a substrate to the claimed enzyme, and there are 2 “mental steps” of observing the resultant reaction. Since the 2 mental steps are considered abstract ideas (see MPEP 2106.04(a)) the 2 active steps must be analyzed to determine if they comprise steps that the artisan would consider well-understood, routine, and conventional activities. See MPEP 2106.05(d). Given a broad analysis, the active steps are merely applying a test compound to an enzyme, applying a known substrate for the described enzyme, and observing if the substrate is consumed or the product is formed; based upon the rate of substrate consumption, and/or product production, the ordinary artisan can calculate whether the test compound provides inhibitory activity to the enzyme. Given this broad analysis, the claimed method is a routine method for determining if a compound acts as an inhibitor to a compound. See, for example, Matsui, et al (PGPub 2004/0106216) who provides for these broadly described steps in the first claim of the application. Additionally, Matsui shows that the claimed method, using the claimed enzyme should also be considered routine. See paragraph [0002] [0087] and claim 1. Notably, Matsui explicitly shows using the same substrates to the CYP450 enzymes. See paragraph [0089]. When considering other prior art, it was found that Tureinen, et al (European Journal of Pharmaceutical Sciences, 29, 130-138, 2006) provides for 3 independent CYP450 inhibition screening tests, wherein each test generally provides for overlapping steps as those claimed; this further suggests that the claimed active steps should be considered well-understood, routine, and conventional. See page 130, “Abstract” section; page 132 and 133, “Materials and Methods” section.
Since it is established that the claims comprise well-understood, routine, and conventional steps, followed by an abstract idea, step 2B asks if there are additional elements that provide for significantly more than the judicial exception. The claims do provide for “an application,” wherein the sample is either held or withdrawn in response to “applicable regulations.” However, this limitation does not appear to provide for the specificity as described in the MPEP. See MPEP 2106.04(d)(2). As such, this limitation does not provide for more than the abstract idea.
Since there are no steps that follow the determination step, the claims cannot be considered eligible under 35 USC 101. The listed dependent claims list specific CYP450 enzymes, specific substrates, and specific detection means; none of these dependent claims provide for significantly more than the judicial exception.
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.
Claim(s) 1, 2, 5-10, 18, 30, 31, 36, 38, 41-44 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Matsui, et al (PGPub 2004/0106216). Matsui provides an applied example that reads upon the claimed method. Specifically, Matsui contacts a CYP450 with the potential inhibitor α-naphthoflavone, and the substrate testosterone. Matsui incubates the reaction mixture, then uses optical methods to detect the level of inhibition. See paragraph [0122]. Matsui provides for α-naphthoflavone which not is a “drug;” however, Matsui does not explicitly teach an inhibitor from the claimed listing. However, there is nothing non-obvious about applying other test compounds to CYP450, in order to determine their respective inhibitor power. Matsui teaches a very generalized method that can be used on any enzyme to determine if any compound is an inhibitor of said enzyme. It would be obvious to the ordinary artisan that if the enzyme-substrate kinetics are inhibited by the addition of a compound, said compound must necessarily be an inhibitor.
With respect to claims 1 and 18, as discussed above, Matsui teaches the claimed method. Although α-naphthoflavone is not one of the claimed classes, it would be reasonable to suggest that the ordinary artisan would find it obvious to try any compound that could possibly inhibit CYP450, since there is no limitation on what types of compounds can be tested as possible inhibitors. Finally, Matsui uses optical methods in the applied example, but also teaches other methods of detection. See paragraph [0093] [0122].
With respect to claim 2, α-naphthoflavone does not appear to be a pesticide.
With respect to claim 5, Matsui indicates that products can be determined using known methods of detection and determination. See paragraph [0093].
With respect to claim 6, Matsui teaches many of the claimed substrates, including fluorescein, coumarin, testosterone and progesterone. See paragraph [0104].
With respect to claims 7 and 31, Matsui teaches the same fluorescein and coumarin derivatives. See paragraph [0104].
With respect to claims 8-10 and 30, Matsui teaches all of the same CYP450 enzymes. See paragraph [0087]. Even if Matsui does not list all of the claimed enzymes, there is nothing non-obvious about applying Matsui’s method to any known cytochrome enzyme.
With respect to claim 36, Matsui provides no limitations on the location from where the test sample is acquired.
With respect to claim 38, in the above-cited applied example, Matsui teaches all of the claimed components, including the enzyme, a substrate, a buffer within the claimed pH range, and a signal detector. See paragraph [0122].
With respect to claim 41, as discussed above, Matsui uses testosterone in the applied example, but also teaches all of the other substrates. See paragraph [0104].
With respect to claims 42-44, Matsui teaches all of the same CYP450 enzymes. See paragraph [0087].
With respect to claim 48, Matsui explicitly teaches the inclusion of a NADPH regeneration system. See paragraph [0107].
Conclusion
THIS ACTION IS MADE FINAL. 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 DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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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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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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