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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/1/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
Applicant’s remarks and amendments filed on 4/20/2026, in response to the Non-Final Office Action mailed 12/18/2025, are acknowledged and have been fully considered.
Applicant’s amendment to the claims filed 4/20/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Any previous rejection or objection not mentioned herein have been withdrawn based upon Applicant’s amendments to the claims.
Drawings
Replacement drawings were received on 20 April 2026. These drawings are accepted. The previous objection to the drawings is herein withdrawn.
Election/Restrictions
Amended claim 19 and newly submitted claims 33-39 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
REQUIREMENT FOR UNITY OF INVENTION
This restriction requirement amends the requirement mailed 6/26/2025, in response to the amendment to claim 19.
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 17-18 and 30-32, drawn to a device for monitoring a state of a sample, wherein the device comprises an action part for allowing flavin-dependent lactate dehydrogenase to act on a sample, and a system comprising the device.
Group II, claims 26-27 (20-25 are now cancelled), drawn to methods for producing a lactate dehydrogenase having the particular recited sequences.
Group III, claims 28-29, drawn to methods for evaluating a state of a sample comprising using a lactate dehydrogenase.
Group IV, claims 19 and 33-39, drawn to a method for monitoring the levels of lactic acid in a sample which comprises i) bringing a lactate dehydrogenase into contact with the sample, and ii) measuring lactic acid.
Groups I and II, and Groups I and III, lack unity of invention because the groups do not share the same or corresponding technical feature (as previously set forth in the requirement mailed 6/26/2025). Group I recites a device for monitoring a state of a sample, wherein the device comprises an action part for allowing flavin-dependent lactate dehydrogenase. It is noted that allowing the enzyme does not necessarily require that the enzyme is present in the device, and the device does not comprise the enzyme.
Groups II, III, and IV lack unity of invention because even though the inventions of these groups require the technical feature of a lactate dehydrogenase which has an amino acid sequence represented by SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:12 or an amino acid sequence having 70% or more of identity thereof, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Fosmer et al. (US PGPub No. 20190264182). Fosmer recites heterologous lactate dehydrogenase genes that comprise an overexpressed cytochrome b2 (cytochrome CYB2, having EC 1.1.2.3) gene (claims 1 and 7), wherein the heterologous CYB2 gene encodes for a polypeptide having an amino acid sequence which includes SEQ ID NO: 17 ([0008]). SEQ ID NO: 17 of Fosmer is 99.8% identical to the instantly claimed amino acid sequence of SEQ ID NO:4, and has 100% sequence identity to the region of amino acid residues at positions 113 to 505 of SEQ ID NO:4 (as in claim 20).
Regarding Group I and newly enumerated Group IV, Group I recites a device for monitoring a state of a sample, wherein the device comprises an action part for allowing flavin-dependent lactate dehydrogenase. It is noted that allowing the enzyme does not necessarily require that the enzyme is present in the device, and the device does not comprise the enzyme. Group IV recites a method that comprises bringing a lactate dehydrogenase into contact with the sample, and ii) measuring lactic acid. There is no requirement for a device or a system in the amended claim 19. Thus, the two groups do not explicitly require a shared technical feature.
Even if the putative shared technical feature of a lactate dehydrogenase having at least one of the recited functional features (as in claims 17 and 19) of:
(A) a flavin-dependent lactate dehydrogenase which maintains about 20% or more of an initial activity when it is elapsed at 37°C for 10 days in a solution,
(B) a flavin-dependent lactate dehydrogenase which maintains about 20% or more of an initial activity when it is elapsed at 37°C for 3 days or longer in a solution, or
(C) a flavin-dependent lactate dehydrogenase which maintains about 20% or more of an initial activity when it is elapsed at 37°C for 15 hours or longer in a solution to act on a sample”,
or having one or more of the structural features (as recited in claims 30 and 33) of:
(a) an amino acid sequence consisting of amino acids at positions 110 to 502 of SEQ ID NO:4 or an amino acid sequence having 70% or more of identity thereof;
(b) an amino acid sequence consisting of amino acids at positions 113 to 505 of SEQ ID NO:7 or an amino acid sequence having 70% or more of identity thereof;
(c) an amino acid sequence consisting of amino acids at positions 112 to 503 of SEQ ID NO: 10 or an amino acid sequence having 70% or more of identity thereof; and
(d) an amino acid sequence consisting of amino acids at positions 102 to 499 of SEQ ID NO: 12 or an amino acid sequence having 70% or more of identity thereof,
could be considered a shared technical feature, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of 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). As previously discussed, 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; pg. 1286, left col; pg. 1286, section 2.2). 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, and properties of proteins are innately tied to and arise from their amino acid sequences. 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 NO: 10 herein, would have identical properties regarding stability if so tested. For these reasons, it is clear that the art teaches flavin-dependent lactate dehydrogenases derived from the thermophilic organism Ogataea parapolymorpha (Hansenula polymorpha), which would intrinsically have the required functional properties.
As the technical features were known in the art at the time of the invention, they cannot be considered special technical features. Therefore, Groups I-IV lack unity of invention under PCT Rule 13 because they do not share the same or corresponding special technical feature.
Since applicant has received an action on the merits for the originally presented invention, Group I has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 19 and 33-39 are herein withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 26-29 remain withdrawn as previously set forth.
Claims 17-18 and 30-32 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 112(b) - New
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 31 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 31 recites the limitation: “the flavin-dependent lactate dehydrogenase is at least one member selected from the group consisting of an amino acid sequence of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12 and an amino acid sequence having 70% or more of identity thereof.” The elements “SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12 and an amino acid sequence having 70% or more of identity thereof” renders the claim indefinite because it is unclear if “thereof” is referencing only SEQ ID NO:12 or any of SEQ ID NO:s 4, 7, 10, or 12.
The claim is also indefinite because the Markush-style list includes elements not actually disclosed, thereby rendering the scope of the claims unascertainable. A Markush-type list of alternatives is limited to only closed groups. See MPEP § 2173.05(h). However, the recited claim limitation is essentially open, as “an amino acid sequence having 70% or more of identity thereof” opens the claim elements to a massive number of possible sequences that may be selected. Because one skilled in the art cannot determine its metes and bounds due to an inability to envision all of the compounds defined by the Markush group, the claim is rendered indefinite.
Claim Interpretation
Claims 31 and 32 recite that the flavin-dependent lactate dehydrogenase is at least one member selected from the group consisting of an amino acid sequence of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12 (or, for claim 31, as best interpreted under the B.R.I., one having 70% sequence identity to any one of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12). It is noted that the “consisting of” is used to refer to the Markush grouping, and is not considered to limit the sequence of the lactate dehydrogenase. Thus, these claims are interpreted under the B.R.I., in light of the specification, as requiring a sequence that comprises all of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:12, but does not exclude additional amino acids (if the sequence “consists of” had been used). Claim 31 may also have a sequence having at least 70% sequence identity to one of these; and the lactase dehydrogenase activity of claim 17 is also present.
Claim Rejections - 35 USC § 112(a) - Maintained
Modified as necessary due to Applicant’s Amendments
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 17-18 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 claim 18 does 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 17 and 18. These claims 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 is also rejected under 35 U.S.C. § 112(a), because the claim requires the device comprising an FMN-LDH enzyme according to claim 17 and fails to practically further limit the selection of the enzyme to just those sufficiently described.
Response to Arguments
Applicant's arguments on page 10 of the remarks filed 4/20/2026 regarding the rejections under 35 U.S.C. § 112(a) have been fully considered but they are not persuasive.
Applicant argues that the claims do not cover “any and all” flavin-dependent LDH enzymes. Applicant’s argument is not persuasive. The claims at issue are drawn to an apparatus, a device that comprises these enzymes. In claims 18 and 19, the flavin-dependent LDH enzymes are only defined by functional attributes. The functional attributes are those pertaining to the activity and the stability of the enzyme under specific conditions (See MPEP § 2114 regarding inherency and functional limitations in apparatus claims and see § 2111.04 regarding that “The broadest reasonable interpretation of a system (or apparatus or product) claim having structure that performs a function, which only needs to occur if a condition precedent is met, requires structure for performing the function should the condition occur.”). Because the claims recite the enzyme by activity and functional properties only, they can encompass any sequence of enzymes, but they must be tested or otherwise known to have the property. Only the sequences recited in the disclosure and thoroughly tested herein have been shown to fulfill these limitations, and thus the disclosure does not adequately describe that any additional enzymes were in possession of the inventors at the time of filing. MPEP § 2163.II.A.3.a.ii) describes that “Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014)”. In the instant case, only 3 flavin-dependent LDH enzymes (PkLDH, OgLDH, and CaLDH) were shown to possess the recited 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). Thus, there is clearly unpredictability in this art, and the full breadth of the claim is not described in sufficient detail and the rejections of claims 17 and 18 are maintained.
Claims 30-32 recite specific structural features (i.e. sequences) that are demonstrated to have the functional properties, and there is a specific link between the claimed sequence regions and the activity. Thus, the disclosure does support the invention, wherein the flavin-dependent lactate dehydrogenase is at least one member selected from the group recited in claim 30.
Claim Rejections - 35 USC § 103- Maintained
Modified as necessary due to Applicant’s Amendments
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 17-18 and 30-32 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. Further, it would have been obvious to select a lactate dehydrogenase comprising the amino acid sequence of SEQ ID NO:10, as disclosed in UniProt Entry W1QKE8 and for which a similar enzyme is taught in Smutok.
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 (and 10), 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 30, the art (see UniProt entry W1QKE8) teaches an enzyme having an amino acid sequence consisting of amino acids at positions 112 to 503 of SEQ ID NO: 10 or an amino acid sequence having 70% or more of identity thereof. The selection and providing of the enzyme would have been a matter of judicious selection in view of Smutok et al. and W1QKE8.
Claims 31 and 32 recite that the flavin-dependent lactate dehydrogenase is at least one member selected from the group consisting of an amino acid sequence of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12 (or, for claim 31, as best interpreted under the B.R.I., one having 70% sequence identity to any one of SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:12). The disclosed sequence in W1QKE8 comprises a sequence from amino acids 58-558 that is 100% identical to SEQ ID NO:10. Thus, because Smutok teaches using a flavin-dependent lactate dehydrogenase from Ogataea parapolymorpha, selecting one having this specific sequence would have been a matter of judicious selection to one of ordinary skill.
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 (e.g. 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.
Response to Arguments
Applicant's arguments on pages 10-11 of the remarks filed 4/20/2026 regarding the rejections under 35 U.S.C. § 112(a) have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument (see paragraphs 1-3 of page 11) that “Nothing in Smutok or any of the other cited prior art would motivate one skilled in the art to obtain the enzyme of the present claims with any reasonable expectation of success”, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
MPEP § 2141.II.C states that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton."KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 418, 82 USPQ2d at 1396. In the instant case, as discussed above, Smutok teaches an L-lactate-cytochrome c oxidoreductase (EC 1.1.2.3; flavocytochrome b2, FCb2) from Ogataea parapolymorpha and UniProt entry W1QKE8 discloses a sequence for a EC 1.1.2.3 family flavocytochrome b2 enzyme, from this same organism. Therefore, providing a sequence according to UniProt entry W1QKE8 as a lactate sensor would have been obvious in view of the teachings of Smutok. It would have been obvious to select from among known sequences in order to produce the electrode and device of Smutok. In doing so, one would have produced an invention that is essentially the same as that which is instantly claimed, based on the structure of the enzyme. Further, one would recognize that stability is an important part of such a sensor, because, naturally, one hoping to commercialize such an enzyme would see long-term stability. To this end, one of ordinary skill in the art would know that Ogataea parapolymorpha is a thermophilic organisms, as taught in Smutok.
Oja is relied upon for the teaching of general knowledge in the art of detecting analytes and Oja teaches a system comprising an action part or a membrane with a working electrode and an output part connected to a data processing unit. Thus, the combination of these parts with the device and lactate dehydrogenase of Smutok would have been prima facie obvious.
Applicant also argues that the enzyme of Smutok is not the same as that of the present invention and that Smutok does not explicitly teach the claimed 20% or more of an initial activity when it is elapsed at 37°C for 3 days or longer in a solutions (see paragraphs 1-2 of page 11 of the remarks). The instant claims are drawn to a device which, under certain conditions, must allow the enzyme having at least one of these functional limitations to act on a sample.
The argument is unpersuasive in view of the combination of Smutok, UniProt entry W1QKE8, and Oja because Smutok teaches a lactate sensor having an flavin-dependent lactate dehydrogenase from Ogataea parapolymorpha and UniProt entry W1QKE8 discloses a sequence that is identical to one of the instant invention. Thus, a device as taught in Smutok having the lactate dehydrogenase sequence taught in UniProt entry W1QKE8 would have been obvious to one of ordinary skill in the art, as this is a matter of judicious selection and optimization. Smutok is indeed silent about the exact thermostability recited in the instant claims, however the resulting composition made obvious by Smutok and UniProt entry W1QKE8 would inherently possess the same characteristics of the claimed composition, particularly in view of the similar characteristics which they have been shown to share and by the functions of the amino acid sequence present in each, of which functions are inclusive of those appreciated in the instant disclosure as being present (see MPEP § 2112.02 at Ex parte Novitski, in reference to reference-silent functioning of biological materials providing anticipation of the functions based upon the material itself (noting the reference of “Dart” therein did not appreciate the claimed function but still anticipated the function based on the inherent function of the material, and that the Applicant’s disclosure appreciating the function upon usage thereof as further evidence of the presence of the function).
The applicant’s argument is also unpersuasive because the instant claims are in the alternative and therefore only the minimal amount of stability is actually required (maintains about 20% or more of an initial activity when it is elapsed at 37°C for 15 hours or longer in a solution). Regardless of the activity required, the discovery of an otherwise inherent property, which would have been present regardless in the invention made obvious by Smutok, UniProt entry W1QKE8, and Oja, cannot amount to non-obviousness, when the structure of the combination is otherwise obvious. 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.").
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (see e.g. paragraphs 3-4 of page 11), it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In the instant case, as previously discussed, the combination of Smutok, UniProt entry W1QKE8, and Oja make obvious the structural limitations of the claims. Smutok teaches that the enzyme is from Ogataea parapolymorpha and UniProt entry W1QKE8 discloses a sequence of the same enzyme and activity from Ogataea parapolymorpha. Because one having ordinary skill in the art would know how to find and produce such sequences, this would have been an obvious amino acid to select when producing or optimizing the device of Smutok. Further, Oja is relied upon for the disclosure of a system having an action part comprising a biosensing electrode and a data output part. One having ordinary skill in the art would be adequately motivated to add these features to any such bioanalyte detecting system, including the lactate sensor taught in Smutok. These amount to common features necessary to output the gathered data from the sensor.
Thus, for at least all of these reasons, Applicant’s arguments are not found persuasive, and the rejections of claims 17 and 18 under 35 U.S.C. 103 as being unpatentable over Smutok et al. (Biosensors and Bioelectronics 20.7 (2005): 1285-1290) in view of UniProt entry W1QKE8 (“L-lactate dehydrogenase (cytochrome) - Ogataea parapolymorpha) and Oja et al. (US PGPub No. 20190004005) is maintained. Newly added claims 30-32 are also rejected under 35 U.S.C. 103, for the reasons discussed above.
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 30-32 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. 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.
Therefore, the instant claims 18 and 30-32 would have been prima facie obvious to one having ordinary skill over the subject matter in 6, 8, and 12-13 of App. 18/246,060.
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.
Response to Arguments
Applicant’s argument on pages 11-12 of the remarks has been considered, but is not persuasive. The arguments presented do not specifically point out the supposed errors in the nonstatutory double patenting rejections of record. Applicant’s argument amounts to essentially a request to hold the rejections in abeyance. MPEP § 804.I.B.1 states that “As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance”. The argument is thus not persuasive and the rejection is maintained, as modified above.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
A0A099P7X2_PICKU (UniProt entry dated 07-JAN-2015, retrieved on 02-JUL-2026, provided with included PTO-892) discloses a L-lactate dehydrogenase enzyme from Pichia kudriavzevii that is 99.8% identical to SEQ ID NO: 4.
UniProt Entry AOA4TOX365 (UniProt; retrieved July 31, 2019, on IDS filed 08/19/2022) discloses a L-lactate dehydrogenase enzyme from Candida (Pichia) inconspicua that is 99.8% identical to SEQ ID NO: 7.
UniProt Entry G2Q4S2_THET4 (UniProt entry dated 16-NOV-2011, retrieved on 02-JUL-2026, provided with included PTO-892) discloses a L-lactate dehydrogenase enzyme from Thermothelomyces thermophilus that is 100% identical to SEQ ID NO:12.
Conclusion
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.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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