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 of Group I, claims 75-93 in the reply filed on August 22, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Objections
Claim(s) 89 and 90 is/are objected to because of the following informalities:
Claim 89, line 1: “electrochemical measurement” should be “electrochemically measuring”
Claim 90, line 3: “the oxidizing electrode and the reducing electrode” should be “the oxidizing electrode or the reducing electrode”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim(s) 78 and 90 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The term “substantial” in claim 78 is a relative term which renders the claim indefinite. The term “substantial” for a substantial amount of the cerumen or the compound of the cerumen is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 90 recites the limitation "the working electrod" in line 2. It is unclear whether this working electrode is the first or the second electrode. It is suggested to be “the first working electrode.”
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim(s) 75, 77, 80, 82, 85-89, and 91-93 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster (T.A. Webster, Electrochemical detection of Pseudomonas aeruginosa in human fluid samples via pyocyanin, Biosensors and Bioelectronics 2014(60), pp. 265-270) in view of Naz (I. Naz, Assessment of Antimicrobial Activity of Cerumen (Earwax) and Antibiotics against Pathogenic Bacteria Isolated from Ear Pus Samples, Microbiol. Res. 2020(110, 8565, pp. 5-10) and Herane-vives (WO 2019/123392), evidenced by Sismaet, (H.J. Sismaet, Electrochemical sensors for identifying pyocyanin production in clinical Pseudomonas aeruginosa isolates, Biosensors and Bioelectronics 2017(17), pp. 65-69) and Goluch (E.D. Goluch, Microbial Identification Using Electrochemical Detection of Metabolites, Trends in Biotechnology, 2017 (35), pp. 1125-1128).
Regarding claim 75, Webster teaches a method for detecting an infection in a subject's ear (Title; [Abstract]: pathogen Pseudomonas aeruginosa; p. 265, col. 2, ¶2: ear infection caused by P. aeruginosa), comprising,
(a)-(b): obtaining a sample ([Abstract]: biological fluids from healthy individuals spiked with P. aeruginosa);
(c) measuring a presence, absence, or amount of a compound ([Abstract]: SWV scans of biological fluids from healthy individuals spiked with P. aeruginosa showed a clear pyocyanin response), optionally wherein the compound is redox-active and associated with the infection (as evidenced by Sismaet, [Abstract]: pyocyanin is a redox-active biomarker), wherein measuring comprises contacting the compound with an electrochemical sensor (p. 266, col. 2, para. 1: CH Instruments) comprising a working electrode (p. 266, col. 1, last para.: carbon working electrode) and a reference electrode (p. 266, bridging para. of col. 1-2: Ag/AgCl reference electrode), and electrochemically measuring a current flow (Fig. 1; p. 267, para. 2: the resulting current), which is correlated with the presence, absence or amount of the compound (p. 268, Fig. 3: maximum current vs. pyocyanin concentration).
Webster further discloses ear infections is caused by P. aeruginosa in ear secretions, and pyocyanin is used as a diagnostic marker for identification of P. aeruginosa infections (p. 265, col. 2, para. 2). Webster fails to disclose the sample is a sample of cerumen, obtained by being adsorbed onto an applicator or the extracting the cerumen from the applicator comprising contacting the applicator with a solvent.
However, Herane-vives teaches obtaining a sample of cerumen, e.g., earwax sample, by any suitable means (p. 10, l. 30), for example, using an applicator (Fig. 1; p. 14, l. 27: an elongated sponge 8; p. 9, ll. 12-13: a cellulose sponge may be an effective, economical and safe material for its extraction). The earwax is obtained by inserting the tip with the sponge 8 in the ear and rotating the sponge 8 inside the ear canal (p. 15, ll. 17-18). For preparation of samples (p. 11, l. 14), the cerumen was extracted by contacting the applicator with a solvent (p. 11, l;. 24-25: Phosphate Buffered Saline (PBS) solution).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster by incorporating the steps of obtaining the cerumen sample from the ear canal followed by extracting the cerumen using PBS buffer as taught by Herane-vives because the disclosed device would provide an effective, safe and hygienic self-extraction of earwax (p. 9, ll. 25-26) to obtain suitable specimen for the subsequent detection and analysis (p. 9, ll. 19-20). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Regarding claim 77, Webster teaches wherein the cerumen is exuded from the subject's ear, and/or wherein the cerumen is obtained from the subject's ear canal (p. 265, col. 2, para. 2: ear secretions obtained from patients with ear infections caused by P. aeruginosa).
Regarding claim 80, Webster teaches wherein the infection is a Pseudomonas aeruginosa infection (p. 265, col. 2, para. 2: ear secretions obtained from patients with ear infections caused by P. aeruginosa).
Regarding claim 82, Webster in view of Herane-vives discloses all limitations of claim 75. Webster fails to teach wherein the solvent comprises: an aqueous solution, wherein the aqueous solution comprises buffering agents.
However, Herane-vives teaches sample preparation (p. 11) by homogenizing the sample with Phosphate Buffered Saline (PBS) solution (p. 11, ll. 24-25).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster by utilizing PBS buffer for extracting step as taught by Herane-vives. The suggestion for doing so would have been that PBS buffer is a suitable material for extracting biomarker from earwax and the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Regarding claim 85, Webster teaches wherein the compound is a quorum sensing molecule ([Abstract]: pathogen Pseudomonas aeruginosa by detecting the presence of pyocyanin). As evidenced by Goluch, use of metabolites to identify bacterial infections, i.e., the concept is exemplified by bacterial cell-cell communication, is known as quorum sensing (p. 1126, col. 2, para. 1); for example, pyocyanin is a valid biomarker for the identification of infections caused by P. aeruginosa (p. 1127, col. 3, para. 1).
Regarding claims 86-87, Webster teaches wherein the quorum sensing compound is a phenazine compound (for claim 86) and wherein the phenazine compound is pyocyanin and wherein the presence, absence, or amount of pyocyanin is indicative of the presence, absence, or extent of a Pseudomonas aeruginosa infection (for claim 87; [Abstract]: pathogen Pseudomonas aeruginosa by detecting the presence of pyocyanin; here pyocyanin is a phenazine compound).
Regarding claim 88, the designation “wherein if the current flow through the working electrode is less than about 10 nA, then the microorganism associated with the infection is nonviable or absent” does not further limit the method as claimed because it does not require an active step of the method. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Regarding claim 89, Webster teaches wherein the electrochemical measurement is square wave voltammetry (p. 266, col. 1, para. 3: using square wave voltammetry SWV).
Regarding claim 91, Webster teaches wherein the presence, absence or amount of the compound is measured as current flow through the working electrode (p. 267, Fig. 1: pyocyanin reacts at the working electrode releasing electrons).
Regarding claim 92, Webster teaches wherein the working electrode is comprised carbon (p. 266, col. 1, last para.: carbon working electrode); and wherein the reference electrode is comprised of silver (Ag), silver chloride (AgCl) (p. 266, bridging para. between col. 1-2: Ag/AgCl reference electrode).
Regarding claim 93, the designation “wherein the method informs: the administration of one or more antibiotics upon a positive test for infection; the withholding of one or more antibiotics upon a negative test for infection; and/or the selection of an appropriate antibiotic for the infectious agent upon a positive test for infection” does not further limit the method as claimed because it does not require an active step of the method. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Claim(s) 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster in view of Herane-vives, and further in view of Newman (WO 2012/149058).
Regarding claim 76, Webster in view of Herane-vives discloses all limitations of claim 75, but fails to teach the method further comprising estimating a number of viable cells of a microorganism associated with the infection based on the presence, absence or amount of the compound determined in step (c).
However, Newman teaches a method for interfering with viability of bacteria by inactivating a phenazine and/or one or more phenazine related pathways in the bacteria (¶279), for example, the bacterium Pseudomonas aeruginosa (¶281). The inhibiting can be performed by interfering with quorum sensing of the bacteria, by reducing the amount of phenazine in the bacteria (¶280). Inactivating a phenazine and/or a phenazine-related pathway in the bacteria would reduce survivability and/or antibiotic resistance of the bacteria (¶59). The “viability” refers to whether or not a bacterial cell is able to maintain itself or recover its potentiality (¶60). Methods for evaluating the viability of bacteria after the disclosed method include measurement of colony forming units and cell counts.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by incorporating the step of estimating a number of viable cells of the bacterium associated with the infection as taught by Newman because it would provide an evaluation of the viability of bacteria and their resistance to the antibiotic (¶¶59-60). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Claim(s) 78-79 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster in view of Herane-vives, and further in view of Sismaet.
Regarding claims 78-79, Webster in view of Herane-vives discloses all limitations of claim 75. Webster and Herane-vives fail to teach wherein the extracting comprises: removing a substantial amount of the cerumen from the applicator; wherein the extracting occurs in a collection tube, on the surface of the electrochemical sensor (claim 78) or wherein the applicator is a sterile swab and wherein the sterile swab comprises an adsorbent portion that is substantially cotton (claim 79).
However, Sismaet teaches sterile, media-free swabs used to collect P. aeruginosa clinical isolates for electrochemical testing, and each swab was placed into a labeled, round-bottom tube for transport (p. 66, col. 1, para. 3). For each sample, the swab was directly placed onto the sensor to cover the sensing region with fluid (p. 66, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by incorporating the steps by removing the obtained cerumen from the applicator, e.g., a cotton swab, into tubes for electrochemical sensing by directly placing the swab onto the sensor as taught by Sismaet because it is a suitable method to obtain P. aeruginosa clinical isolates for electrochemical testing and diagnosis of infection. Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Claim(s) 81 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster in view of Herane-vives, and further in view of Bork (US 2018/0245124).
Regarding claim 81, Webster in view of Herane-vives discloses all limitations of claim 75. Webster and Herane-vives fail to teach wherein the subject is a non-human animal, a canine, a captive animal, a pet animal, a farm animal, or a zoo animal.
However, Bork teaches a method of bacteria identification for treatment of infectious disease ([Abstract]), in both human and animal healthcare (¶2). Infection of humans or animals may be caused by bacteria, and antimicrobial agents, including antibiotics, are employed to combat the infection (¶4), e.g., ear, throat, udder or uterus etc. (¶10).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by substituting the sample from human’s ear with that from a non-human animal’s ear as taught by Bork because simple substitution of one known element for another to obtain predictable results is prima facie obvious. MPEP 2141(III)(A). Here, the substitution is merely yield predictable results of detecting an infection in an animal’s ear instead of a human’s ear by extracting the cerumen from the animal’s ear.
Claim(s) 83-84 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster in view of Herane-vives, and further in view of Uchida (K. Uchida, A Simple Method for Isolation of Lipopolysaccharides from Pseudomonas aeruginosa and Some Other Bacterial Strains, Agricultural and Biological Chemistry, 2016(51), pp. 3107-3114) and Le Berre (WO 2019/202137).
Regarding claims 83-84, Webster in view of Herane-vives discloses all limitations of claim 82. Webster further discloses the solvent comprises phosphate buffered saline (PBS) (p. 11, ll. 24-25). Webster further discloses some cerumenolytics solutions (for claim 83), such as those containing mineral oils (for claim 84) may have some utility for extracting or removing the secretion (p. 7, ll. 27-29).
Webster and Herane-vives fail to teach wherein the solvent comprises: ethanol.
However, Uchida teaches isolation of bacterial strains, e.g., lipopolysaccharides, from Pseudomonas aeruginosa (Title). The method uses a hot MgCl2-Triton X-100 solution by solubilizing with EDTA-Triton X-100 and precipitating with MgCl2 ([Abstract]). The LPS yield was significantly improved by the addition of 2% ethanol (final 20%) (p. 3112, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by incorporating ethanol in the solvent for extracting bacterial strain from Pseudomonas aeruginosa because an addition of ethanol would significantly improve the extraction yield (p. 3112, col. 2, para. 2).
Webster and Herane-vives fail to teach wherein the solvent comprises: about 1 mM MgCl2.
However, Le Berre teaches producing pyocyanin from P. aeruginosa in Bacto-Peptone (BP) broth, including 20 mg/L BP, MgCl2 1.4g/L, and K2SO4 10g/L (p. 10, ll. 6-7). Here, 1.4g/L MgCl2 in the BP broth is about 15 mM.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by incorporating MgCl2 in the extracting solvent for pyocyanin production from Pseudomonas aeruginosa because it is well known component of the extracting solvent. Further, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I). Further, the desired amount of MgCl2 for the extraction of pyocyanin would be obvious to one of ordinary skill in the art with optimization through routine experimentation. MPEP 2144.05 (II)(B).
Claim(s) 90 is/are rejected under 35 U.S.C. 103 as being unpatentable over Webster in view of Herane-vives, and further in view of Fujiwara (US 2018/0120249).
Regarding claim 90, Webster in view of Herane-vives discloses all limitations of claim 75. Webster further discloses the working electrode is either an oxidizing electrode (p. 267, Fig. 1: pyocyanin reacts at the working electrode, releasing electrons and hydrogens, and is converted to its oxidized form).
Webster and Herane-vives fail to teach wherein the electrochemical sensor comprises a second working electrode.
However, Fujiwara teaches a biosensor for measuring a component by causing a redox reaction of the component and detecting a redox current caused by the redox reaction with an electrode (¶6). In addition, an additional working electrode determines an amount of blood cells or an interfering substance by detecting the redox current on the additional electrode system (¶6). The amount of blood cells or the interfering substance is used to correct the amount of the component (¶6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Webster and Herane-vives by an additional working electrode which is either an oxidizing electrode or a reducing electrode as taught by Fujiwara because the additional electrode would provide a correction means by an amount of blood cells or interfering substance to correct the measured amount of the component (¶6). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Interview with the Examiner
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https://www.uspto.gov/patents/laws/interview-practice#step3. Additionally, a blank email to the Examiner at the time of a telephonic interview can be used for a reply to easily allow for Microsoft Teams communication. Please note, policy guidelines regarding Internet communications are detailed at MPEP §500-502.3, and office policy regarding interviews are detailed at MPEP §713.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795