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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 17-19, in the reply filed on 9/24/2025 is acknowledged.
Claims 20-29 are herein withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/24/2025.
Priority
This application is a National-Stage entry of PCT/JP2021/006153, filed 2/18/2021. Applicant’s claim for the benefit of a prior-filed application JP2020-106467, filed 6/19/2020, and JP2020-028722, filed 2/21/2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that English language translations of the foreign priority applications JP2020-106467 and JP2020-028722 have not been made of record in the instant application in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/19/2022, 9/21/2022, 2/27/2023, 3/27/2024, and 12/4/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements and the cited references therein are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
At multiple locations in the specifications, formal binomial names of species appear without being italicized. See for example: “Saccharomyces cerevisiae” ([0157]); “Candida inconspicua” and “Ogataea parapolymorpha” (both in [0175]). When using the binomial name, the genus and species should always be capitalized. Appropriate correction is required.
TRADE NAMES, TRADEMARKS, AND OTHER MARKS USED IN COMMERCE:
The use of the terms SEPHADEX, SUPERDEX, ULTROGEL ([0155]), and HISCREEN CAPTO Q ([0169]), which are each a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks (see MPEP 608.01(v) and 608.01(u)). Appropriate correction is requested.
Drawings
The drawings are objected to because Figures 2, 3, 6, 10, 11-1, 11-2, 12, and 13 are presented in a horizonal manner. However the Figure legends are not oriented in the same manner. Amendments such that the labels are turned to be in the same direction as the Figure illustrations is requested.
See 37 CFR 1.84 which states: “(i) Arrangement of views . One view must not be placed upon another or within the outline of another. All views on the same sheet should stand in the same direction and, if possible, stand so that they can be read with the sheet held in an upright position. If views wider than the width of the sheet are necessary for the clearest illustration of the invention, the sheet may be turned on its side so that the top of the sheet, with the appropriate top margin to be used as the heading space, is on the right-hand side. Words must appear in a horizontal, left-to-right fashion when the page is either upright or turned so that the top becomes the right side, except for graphs utilizing standard scientific convention to denote the axis of abscissas (of X) and the axis of ordinates (of Y).”
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(b)
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.
Claim 19 is 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.
Claim 19 recites “A method for monitoring a state of a sample which uses the device according to Claim 17”.
MPEP 2173.05(q) establishes that “[a]ttempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph”.
In the instant case, the claim recites “a method for monitoring a state of a sample”, in the preamble of the claim, but this does not give any practical boundaries or structure to the method claim. The phrase “a state of a sample” is broad and is not limited to any particular substrate and/or any particular sample types. Therefore, the claim is so broad as to include any possible uses of the device. The claim recites “uses the device according to claim 17”. This does not provide any steps for performing the method. No steps of contacting the device with a sample, allowing the sample and device to incubate, gathering data, and/or analyzing the resulting data output are recited. Further, although the device includes a “lactate dehydrogenase” no indication of what substrates or samples the method will be used for is provided. However, it is understood that the method is for detecting levels of lactate in the sample.
As no steps or practical limitations for the method of using the device have been delineated, the resulting claim is indefinite because the practical limits of the claim protection which is sought cannot be determined.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 17 recites a device comprising an action part for allowing a flavin-dependent lactate dehydrogenase which maintains about 20% or more of an initial activity when kept at 37°C for a minimum of 15 hours according to option (C).
The dependent claims 18 and 19 do not practically limit the encompassed structure by further limiting the identity of the provided flavin-dependent lactate dehydrogenase.
No specific structure, sequence, or origin of the flavin-dependent lactate dehydrogenase is recited in claims 1-3. The claims thus encompass any possible enzyme having the activity described as “flavin-dependent lactate dehydrogenase” (with the classification E.C. 1.1.2.3, see the reference document titled “BRENDA: EC1.1.2.3”, included on the accompanying PTO-892) and having the functional features instantly claimed regarding the long term stability.
According to the B.R.I. of the claim, when viewed in light of the specification, there exists a nearly limitless number of structures comprising different possible sources of the enzyme in combination with any combination of mutations that fall within the claimed scope. Comparatively, the specification only recites a small number of species of the broad genus that meets the recited limitations.
MPEP § 2163.(II)(A)(3)(a) states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The specification fails to reasonably describe the full genus of the claimed invention by providing identifying characteristics or functional properties of the flavin-dependent lactate dehydrogenase such that one could envision which of the claimed species fulfill the claim limitations and which are in possession of the applicant at the effective filing date.
The instant specification does not disclose relevant identifying characteristics, such as key structural or other physical properties, or functional characteristics coupled with a known or disclosed correlation between function and structure, such that the entirety of the claimed genus is encompassed by the description in the disclosure.
The specification demonstrates that flavin-dependent LDH enzymes obtained from some microorganism sources, including Pichia kudriavzevii-derived lactate dehydrogenase (PkLDH), Ogataea parapolymorpha- derived lactate dehydrogenase (OgLDH), and Candida inconspicua-derived lactate dehydrogenase (CaLDH) possess the recited storage stability features ([0175], Fig. 3). The specification also describes that a Saccharomyces cerevisiae-derived lactate dehydrogenase (ScLDH) did not fulfill the functional limitations of the thermostability (Fig. 3).
The working examples describe the testing of mutants derived from PkLDH, however there is no disclosed relationship between the desirable sequences and the improved stability that is deemed sufficient to fulfill the written description requirement. The specific examples of mutants and sequences in the specification include inter alia: PkLDH and PkLDH-96 through PkLDH-104 (see Figure 12), and PkDH, PkLDH/F161L, PkLDH/F187L, PkLDH/ F428L (see Figure 13). These describe different combinations of mutations and truncations.
The data regarding observed properties of these enzymes represent some of the genus, derived from PkLDH, but this amounts to a description of a handful of embodiments of the claimed genus, and does not address the near limitless amount of combinations of mutations and truncations which may be found within the entire claimed genus of enzymes. Nor is there a described correlation between structure and function such that one can predict the effects of different mutations on the thermostability of any of the enzymes within the claimed genus.
Thus, the specification only provides only a relatively small example of the claimed genus, which cannot be considered a sufficient description of a representative number of species by actual reduction to practice of the full breadth of the vast genus. There is no evidence that, at the time of filing, the Applicant possessed additional representative species of the full genus recited in the claims beyond those provided in these working examples.
For these reasons, the disclosure fails to provide adequate written description to support the entirety of the broad genus claim to any and all flavin-dependent LDH enzymes.
Claim 17 is rejected under 35 U.S.C. § 112(a) because the claimed subject matter is not described in the specification in such a way as to reasonably convey to a skilled artisan that the inventor, or a joint inventor, had possession of the claimed invention.
The dependent claims 18-19 are also rejected under 35 U.S.C. § 112(a), because these claims require the device comprising an FMN-LDH enzyme according to claim and fail to practically further limit the selection of the enzyme to just those sufficiently described.
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 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Smutok et al. (“A novel L-lactate-selective biosensor based on flavocytochrome b2 from methylotrophic yeast Hansenula polymorpha” Biosensors and Bioelectronics 20.7 (2005): 1285-1290) in view of UniProt entry W1QKE8 (“L-lactate dehydrogenase (cytochrome) - Ogataea parapolymorpha, integrated into UniProtKB/TrEMBL on 19-MAR-2014, obtained from <uniprot.org/uniprotkb/W1QKE8/entry>) and Oja et al. (US PGPub No. 20190004005).
Smutok teaches an amperometric biosensor which is highly selective to L-lactate, developed using L-lactate-cytochrome c oxidoreductase (flavocytochrome b2, FCb2, of EC 1.1.2.3, also known in the art as flavin-dependent lactate dehydrogenases) isolated from the thermotolerant methylotrophic yeast Hansenula polymorpha (Abstract). Smutok teaches that accurate detection of lactate is important for clinical diagnostics, monitoring athletic performance, monitoring fermentation, and for industrial quality control processes (pg. 1285).
Smutok teaches investigating bioanalytical properties of FCb2-based biosensors, including signal rise time, dynamic range, dependence of the sensor output on the pH value, and the storage stability, and that the proposed biosensor demonstrated a very fast response and a high sensitivity and selectivity for L-lactate determination (Abstract).
Specifically, Smutok teaches an L-lactate-cytochrome c oxidoreductase (EC 1.1.2.3; flavocytochrome b2, FCb2), catalyzes an electron transfer from L-lactate to cytochrome c using FMN instead of NAD+ as the coenzyme (pg. 1286, left col). Smutok states “we describe the use of an FCb2 isolated from a thermotolerant methylotrophic yeast Hansenula polymorpha as biological recognition element in amperometric biosensors. Previously, FCb2 from this source was shown to exhibit higher stability… and hence we anticipated improved sensor characteristics using this enzyme in the development of L-lactate specific biosensors” (pg. 1286, left col).
Smutok describes that amperometric FCb2-based biosensors were evaluated using constant-potential amperometry with a Ag/AgCl/KCl (3 M) reference electrode and a Pt-wire counter electrode. Amperometric measurements were carried out using a bipotentiostat (EP 30, Biometra, Göttingen, Germany) connected to a personal computer via a RS232 port for data acquisition (pg. 1286, section 2.2. Preparation and evaluation of the FCb2-based biosensors).
Smutok also teaches that the FCb2-based amperometric biosensors do not show any cross-sensitivity towards isocitrate and malate (Fig. 5) which are common interferents that have a significant impact when using NAD+-dependent lactate dehydrogenases (see pg. 1289 right col).
Smutok teaches that the biosensor is stable over time when stored at 4°C in 20mM phosphate buffer (see Table 1).
However, Smutok does not explicitly describe that the flavin-dependent lactate dehydrogenase used therein maintains 20% or more of an initial activity when kept at 37°C for at least 15 hours. Neither does Smutok teach a device having an action part, nor an output part.
UniProt entry W1QKE8 describes an enzyme L-lactate dehydrogenase (cytochrome) – from the species Ogataea parapolymorpha, which is said to also be known as Hansenula polymorpha, and references strain DL-1. The UniProt data page indicates that the enzyme is a member of class EC 1.1.2.3, and uses flavin mononucleotide as a cofactor, as instantly claimed. The disclosed sequence in W1QKE8 comprises a sequence from amino acids 58-558 that is 100% identical to SEQ ID NO:10 of the instant invention (see the alignment included at the end of this Action). The instant specification describes SEQ ID NO:9 and the truncated SEQ ID NO:10 as comprising an Ogataea parapolymorpha-derived lactate dehydrogenase (OgLDH) ([0175], FIGs 11-1 and 11-2). The instant disclosure indicates that OgLDH retains most of its initial activity after incubation at 37°C for at least 15 hours and up to over 100 hours (FIG 3A). Properties of proteins are innately tied to and arise from their amino acid sequences. Thus, the property of maintaining activity under incubation at 37° is an inherent characteristic of a sequence having the same sequence and structure, and predictably the enzyme as disclosed in W1QKE8, comprising an identical sequence to SEQ ID NOs 9 and 10 herein, would have identical properties regarding thermostability if so tested.
Oja pertains to method for sensing an analyte utilizing a sensor having a working electrode comprising providing a working electrode with an analyte-specific enzyme and a redox mediator and providing the working electrode to the analyte (Abstract). Oja teaches that the selected analyte may include, inter alia, lactate ([0014]), and that the analyte-specific enzymes can be selected from a nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenase, a flavin adenine dinucleotide (FAD)-dependent oxidase, and/or a flavin mononucleotide (FMN)-dependent oxidase, including lactate oxidases and NAD-lactate dehydrogenases ([0015]-[0016]).
Oja teaches that an enzymatic biosensor for measuring low nanomolar concentrations of an analyte may be used in an in vivo monitoring system which while positioned in vivo in a user (e.g., human subject) makes contact with the bodily fluid of the user and senses one or more analyte levels contained therein ([0150]). Oja teaches that such in vivo monitoring systems may include one or more reader devices that receive sensed analyte data from a sensor control device, and that said reader devices process and/or display the sensed analyte data, or sensor data, in any number of forms, to the user ([0150]-[0152], FIG. 16).
Oja teaches a method for obtaining a signal from an analyte utilizing a sensor, the sensor including a working electrode and another electrode (e.g., a counter and/or reference electrode) where the working electrode is provided or modified with a catalyst such as an analyte-specific enzyme and an electron transfer agent (e.g., a redox mediator) and that the area of the working electrode that is modified with the analyte-specific enzyme and the redox mediator may be referred to as the sensing element or sensing layer of the working electrode ([0084], FIG 1).
Oja teaches producing devices and systems for monitoring biological analytes ([0028]), including wearable and/or implantable analyte sensor comprising a working electrode having the analyte-specific enzyme and the redox mediator (see Fig. 13 and [0101]-[0110]). Oja teaches in various embodiments, that the biosensor may be configured to be connected to various electrical connections for transmitting the output signals of the sensing region 920 (Fig. 14A, [0108]).
Therefore, before the effective filing date of the claimed invention, to one of ordinary skill in the art it would have been obvious to produce a biosensor for the detection of lactate, as taught in Smutok, comprising a flavin-dependent lactate dehydrogenase derived from Ogataea parapolymorpha (also known as Hansenula polymorpha), wherein the flavin-dependent lactate dehydrogenase comprises a protein sequence as set forth in UniProt Entry W1QKE8, for the expected benefit of a lactate sensing device that has improved thermostability, and to apply the biosensor in a device as taught in Oja for the detection of analytes, comprises an action part or a membrane with working electrode comprising the lactate-detecting enzyme, and an output part connected to a data processing unit.
One would have been motivated to produce a device and system for detecting lactate according to the combined teachings of Smutok and Oja because similar lactate sensing devices are known to the art, and a flavin-dependent lactate dehydrogenase such as the enzyme taught in Smutok provides the expected benefit of improved stability, compared to other known lactate dehydrogenases, as suggested in Smutok. One would have also been motivated by the teachings of Smutok to select a flavin-dependent lactate dehydrogenase from Ogataea parapolymorpha/ Hansenula polymorpha for the express benefit of improved sensitivity and selectivity for L-lactate, because the FCb2-based biosensors taught therein does not interact with common interferents that have a significant impact when using NAD+-dependent lactate dehydrogenases.
Regarding the stability of the enzyme, it is evident from the disclosure that a flavin-dependent lactate dehydrogenase from Ogataea parapolymorpha, having a sequence that is found in SEQ ID NO: 9, would possess the innate property of maintaining enzyme activity for 15 hours or more at 37°C, as so instantly claimed. As such enzymes were known to the art and were utilized as a lactate biosensor prior to the effective filing date, as discerned from Smutok in view of UniProt entry W1QKE8, there would have existed ample motivation to utilize these lactate biosensors in a device for detecting lactate, as discussed above. The improved thermostability is thus an innate characteristic of such enzymes and does not represent a structural or patentable distinction from the prior art.
MPEP § 2112.I. describes that the "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id.
MPEP §2144.09. VII. states that “a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences, in fact, in their respective properties which are determinative of nonobviousness. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, applicant’s recognition of the benefit is not in itself sufficient to distinguish the claimed compound from the prior art. In re Dillon, 919 F.2d 688, 693, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc)”. See also In re Papesch, 315 F.2d 381, 391, 137 USPQ 43, 51 (CCPA 1963) ("From the standpoint of patent law, a compound and all its properties are inseparable.").
Because improvements on storage stability and selectivity when using the flavin-dependent lactate dehydrogenase from Ogataea parapolymorpha are taught in Smutok, one would have been adequately motivated to produce a device having such an enzyme, instead of an NAD-dependent lactate dehydrogenase, in view of the combination of the cited art. The stability of the enzyme activity upon its use at 37°C would naturally follow from the suggestions in the prior art, as this appears to be an inherent property of the enzyme having that sequence.
Since the Office does not have the facilities for examining and comparing Applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Regarding claim 18, the device having a working electrode taught in Oja comprises various electrical connections for transmitting the output signals of the sensing region to a data processing unit (i.e. a computer, a separate dedicated device, or a smart phone). A system comprising the active biosensor and an output part would have thus been obvious over the cited combination of Oja and Smutok, in light of UniProt entry W1QKE8.
Regarding claim 19, both Oja and Smutok discuss applying or using a biosensor comprising a working electrode with an enzyme for detecting the presence of a biological material. Smutok teaches that detecting lactate has utility in biomedical, athletic, and industrial settings. Therefore, using the device as made obvious by the combination of the cited art above to detect lactate would have obvious as well to one having ordinary skill in the art.
From the teachings of the references Oja and Smutok- in light of UniProt entry W1QKE8- it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, because Oja teaches devices and systems with working electrodes of biosensing enzymes, and Smutok teaches producing a biosensor for lactate with a FMN-LDH (including the enzyme of UniProt entry W1QKE8).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, as evidenced by the references, especially in the absence of evidence to the contrary.
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 17 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 8, and 12-13 of copending Application No. 18/246,060 (the reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed subject matter of the reference application make obvious the device, system, and methods of the instant pending claims.
The claims of the reference application recite a composition for measuring lactate, comprising a lactate dehydrogenase requiring a flavin compound as a coenzyme, thus a flavin-dependent lactate dehydrogenase (claim 6), wherein the lactate dehydrogenase comprises an amino acid sequence with an identity of at least 70% to one of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 7, or SEQ ID NO: 10 (claim 8). Claim 12 of the reference application recites an electrode comprising the composition of claim 6 (i.e. including the lactate dehydrogenase) and claim 13 recites a lactate sensor comprising the electrode of claim 12.
It is made of record that SEQ ID NOs: 1, 4, 7, and 10 of the reference application 18/246,060 appear to be identical to SEQ ID NOs: 1, 4, 7, and 10 of the instant application. Although not recited in the instantly examined claims, the instant specification exemplifies lactate dehydrogenases comprising SEQ ID NOs: 4, 7, and 10, and indicates that such sequences fulfill the functional limitations of at least 20% remaining activity after 15 hours at 37°C (see the instant FIGs 3A and 3B).
Therefore, it would have been prima facie obvious from the claims of the ‘060 reference application to produce a sensor comprising a working electrode comprising a flavin-dependent lactate dehydrogenases comprising one of SEQ ID NOs: 4, 7, and 10, and such a device would inherently have the improved thermostability occurring from the structure of the enzymes.
One would have been motivated to produce a sensor device having one of the lactate dehydrogenases comprising SEQ ID NOs: 4, 7, or 10, because there are known flavin-dependent lactate dehydrogenase alternatives, each are recited in claim 8 of the reference application, and each are suitable for the desired purpose of detecting lactate in a sample. Additionally, the application of such an enzyme-based sensing device for detecting lactate in a sample, as recited in claim 19, would have been prima facie obvious to one having ordinary skill.
Claim 18 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim over claims 6, 8, and 12-13 of copending Application No. 18/246,060 (the reference application) in view of Oja et al. (US PGPub No. 20190004005).
The claims of the reference application recite a composition for measuring lactate, comprising a lactate dehydrogenase requiring a flavin compound as a coenzyme, thus a flavin-dependent lactate dehydrogenase (claim 6), wherein the lactate dehydrogenase comprises an amino acid sequence with an identity of at least 70% to one of SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 7, or SEQ ID NO: 10 (claim 8). Claim 12 of the reference application recites an electrode comprising the composition of claim 6 (i.e. including the lactate dehydrogenase) and claim 13 recites a lactate sensor comprising the electrode of claim 12.
SEQ ID NOs: 1, 4, 7, and 10 of the reference application 18/246,060 appear to be identical to SEQ ID NOs: 1, 4, 7, and 10 of the instant application. Although not recited in the instantly examined claims, the instant specification exemplifies lactate dehydrogenases comprising SEQ ID NOs: 4, 7, and 10, and indicates that such sequences fulfill the functional limitations of at least 20% remaining activity after 15 hours at 37°C, as discussed above.
However, the claims of the ‘060 do not explicitly recite an output part for sending data to a data processing unit, as in the instant claim 18.
The teachings of Oja include all those set forth above. Oja teaches in vivo monitoring systems that include one or more reader devices that receive sensed analyte data from a sensor control device, and that said reader devices process and/or display the sensed analyte data, or sensor data, in any number of forms, to the user ([0150]-[0152], FIG. 16). Oja teaches producing devices and systems for monitoring biological analytes ([0028]), including wearable and/or implantable analyte sensor comprising a working electrode having the analyte-specific enzyme and the redox mediator (see Fig. 13 and [0101]-[0110]).
Oja teaches a method for obtaining a signal from an analyte utilizing a sensor, the sensor including a working electrode and another electrode (e.g., a counter and/or reference electrode) where the working electrode is provided or modified with a catalyst such as an analyte-specific enzyme and an electron transfer agent (e.g., a redox mediator) and that the area of the working electrode that is modified with the analyte-specific enzyme and the redox mediator may be referred to as the sensing element or sensing layer of the working electrode ([0084], FIG 1).
Oja teaches in various embodiments, that the biosensor may be configured to be connected to various electrical connections for transmitting the output signals of the sensing region 920 (Fig. 14A, [0108]).
Therefore, it would have been obvious to produce a system comprising the sensor as described in the claims of the ‘060 reference application, said sensor comprising a working electrode comprising a flavin-dependent lactate dehydrogenases comprising one of SEQ ID NOs: 4, 7, and 10, wherein the system additional contains comprises an output part for sending data to a data processing unit, as taught in Oja, for the predictable benefit of being able to monitor the data and results coming from the lactate sensing device.
One having ordinary skill in the art would be aware of means for outputting, collecting, and displaying data collected when using such a biosensor. The addition of an output part on a working electrode of a biosensor for sending data to a connected device is explicitly described in Oja. Therefore, adapting the flavin-dependent lactate dehydrogenases sensor to include means for outputting the data would result in a lactate-monitoring system, and would there would have existed a reasonable expectation of success, as such data processing units are known to the art.
These are provisional nonstatutory double patenting rejections.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Shimozawa et al. (“Easy preparation of a stable membrane-bound lactate dehydrogenase for application in lactate biosensor.” Int J Anal Bio-Sci Vol, 8(3), published Sept. 2020), is pertinent to the instant invention, and teaches a stable biosensor derived from an E. Coli enzyme. The publication date of this reference is prior to the instant filing date, but after the filing date of the foreign priority document JP2020-028722 (2/21/2020).
Conclusion
Claims 17-19 are rejected.
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/ANDREW T MOEHLMAN/Examiner, Art Unit 1655
/TERRY A MCKELVEY/Supervisory Patent Examiner, Art Unit 1655
Appendix A: sequence alignment of residues 57-558 of UniProt entry W1QKE8 from Ogataea parapolymorpha (Hansenula polymorpha) with SEQ ID NO:10
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