DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 06/01/2026 has been entered.
Claims 1, 5-9, 11-14 and 17 are pending in this application.
Applicant’s amendment to the claims filed 06/01/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 06/01/2026 in response to the final rejection mailed on 03/11/2026 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
Claims 1 and 17 are objected to for the phrase “wherein pooled phenotypic antibiotic resistant testing either or both: (A) …, and or (B)” beginning in line 3 of part (b)(ii). In the interest of improving claim form, Applicant should consider an amendment to recite “wherein pooled phenotypic antibiotic resistant testing: (A) …, and/or (B)”.
Claims 1 and 17 are objected to for the phrase in part (c) of “comparing results from (i) and (ii)”. In the interest of improving claim form, Applicant should consider an amendment to recite “comparing results from (i) and (ii) of part (b)”.
Claim Rejections - 35 USC § 112(b)
Claims 1, 5-9, 11-14 and 17 are newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is newly stated and necessitated by claim amendment.
Claims 1 (claims 5-9, 11-14 dependent therefrom) and 17 are indefinite for the phrase in part (d) of “excluding a therapeutic agent if … (B) one or more resistance genes of a therapeutic agent are present and the urine sample is resistant to said therapeutic agent”. As there are two recitations of “a therapeutic agent”, it is unclear if the therapeutic agent to be excluded is the same therapeutic agent corresponding to the one or more resistance genes, and additionally which therapeutic agent is being referenced by “said therapeutic agent”.
Claims 1 (claims 5-9, 11-14 dependent therefrom) and 17 are indefinite for the phrase in part (b)(ii) of “wherein the urine sample is resistant to one or more therapeutic agents when the urine sample is above a predetermined threshold, and the urine sample is resistant to one or more therapeutic agents susceptible to one or more therapeutic agents when the urine sample is below a predetermined threshold”. There is no limitation in the claims or definition in the specification for the predetermined threshold required to determine whether the sample is resistant or susceptible to the treatment. As said determination of susceptibility or resistance is required to determine concordance or discordance and therefore carry out the claimed method, the broadly recited “predetermined threshold” for determining whether a sample is resistant or susceptible encompasses any threshold, and renders the scope of the claimed method indefinite.
Claim Rejections - 35 USC § 112(a)
Claims 1, 5-9, 11-14 and 17 are newly rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) 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, at the time the application was filed, had possession of the claimed invention. This is a new matter rejection and is necessitated by amendment.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims.” See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description.” According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.”
Claims 1 (claims 5-9, 11-14 dependent therefrom) and 17 have been amended to recite “(d) excluding a therapeutic agent if (A) discordance is present or (B) one or more resistance genes of a therapeutic agent are present and the urine sample is resistant to said therapeutic agent”. According to applicant’s instant remarks in paragraph 1 of page 9, “Support for the amended claims is found throughout the specification and drawings”. However, there is no apparent descriptive support for the limitation “(d) excluding a therapeutic agent if (A) discordance is present or (B) one or more resistance genes of a therapeutic agent are present and the urine sample is resistant to said therapeutic agent” in the original application as filed. Absent descriptive support, the noted limitation is considered to introduce new matter into the claims. Applicant is invited to show support for the limitation at issue.
Claim Rejections - 35 USC § 103
Claims 1, 5-9, 11-12, 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (US 2020/0010874; cited in the form PTO-892 mailed 11/02/2023; herein referred to as Wang) in view of Brown et al. (U.S. Patent No. 10,106,847; cited in the form PTO-892 mailed 11/02/2023; herein referred to as Brown) and Schmolke et al. (US 2019/0032115; cited in the form PTO-892 mailed 11/02/2023; herein referred to as Schmolke).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 1 is drawn to a method of providing a therapeutic solution to treat polymicrobial urinary tract infection (UTI) or suspected polymicrobial UTI in a patient by determining discordance, the method comprises:
(a) determining if the patient has a polymicrobial UTI by subjecting a portion of a urine sample obtained from the patient to genetic identification testing for detecting and identifying one or more organisms in the urine sample; wherein if genetic identification testing detects and identifies one or more organisms in the urine sample, then the patient has a polymicrobial urinary tract infection,
(b) subsequently,
(i) subjecting a portion of the urine sample to genetic resistance marker testing for detecting and identifying one or more resistance genes in the one or more organisms in the urine sample; wherein one or more resistance genes are present in the urine sample when the one or more resistance genes are detected at a level higher than a predetermined threshold; and
(ii) subjecting a portion of the urine sample to pooled phenotypic antibiotic resistance testing, wherein the pooled phenotypic antibiotic testing either or both:
identifies one or more therapeutic agents to which the polymicrobial infection is resistant, and/or
identifies one or more therapeutic agents to which the polymicrobial infection is susceptible,
wherein the one or more organisms of the polymicrobial infection in the sample are not first isolated before phenotypic antibiotic resistance testing,
wherein the urine sample is resistant to one or more therapeutic agents when the urine sample is above a predetermined threshold, and the urine sample is resistant to one or more therapeutic agents susceptible to one or more therapeutic agents when the urine sample is below a predetermined threshold;
(c) determining discordance or concordance for the one or more therapeutic agents by comparing results from (i) and (ii), wherein
wherein discordance is present when
(A) one or more resistance genes of a therapeutic agent are absent, and the urine sample is resistant to said therapeutic agent, or
(B) one or more resistance genes of a therapeutic agent is present, and the urine sample is susceptible to said therapeutic agent;
wherein concordance is present when
(A) one or more resistance genes of a therapeutic agent are absent, and the urine sample is susceptible to said therapeutic agent, or
(B) one or more resistance genes of a therapeutic agent is present, and the urine sample is resistant to said therapeutic agent;
(d) excluding a therapeutic agent if (A) discordance is present or (B) one or more resistance genes are present and the urine sample is resistant to said therapeutic agent; and
(e) selecting one or more therapeutic agents for the therapeutic solution in which concordance is present and the urine sample is susceptible to said therapeutic agent; and
(f) providing the therapeutic solution to a medical professional for use in determining treatment for the polymicrobial infection in the patient, wherein the therapeutic solution comprises one or more therapeutic agents selected from (e) that are effective for treating the polymicrobial infection.
The limitation in part (f) of claim 1 of “providing the therapeutic solution to a medical professional for use in determining treatment for the polymicrobial infection in the patient” is considered an intended use of the recited therapeutic solution by a medical professional according to MPEP 2111.02.II, as the claimed method does not require the recited determination of a treatment for the polymicrobial infection, but only requires the providing of the therapeutic solution to the medical professional.
Wang describes methods for identifying antibiotic resistant bacteria, quantifying bacteria growth, and applying antibiotic susceptibility tests [abstract].
Regarding the limitation in claim 1 step (a) of subjecting a portion of a urine sample obtained the patient to genetic identification testing for detecting and identifying two or more species in the sample, wherein the genetic identification testing is capable of detecting either or both bacterial species or fungal species, Wang teaches a method of detecting bacteria in a biological sample that includes "amplifying DNA of the unidentified bacteria ... using PCR … and identifying the species of the unidentified bacteria by determining a first melting curve of the unidentified bacteria and comparing it to one or more melting curves of known bacteria stored in a computer” [para 5], wherein a biological sample includes “whole blood, plasma, serum RBC fraction, urine, saliva cerebrospinal fluid, semen, sweat… [etc.]” [para 0005]. Wang also describes a single-cell analysis assay wherein the method is applied to single cells in a small volume for “identifying and qualifying the growth of individual cells” [para 0053], which would be capable of identifying one or more species from a sample.
Regarding the limitation recited in claim 1 step (b)(ii) of subjecting a portion of the urine sample to pooled phenotypic antibiotic resistance testing, wherein phenotypic antibiotic resistance testing either or both: (A) identifies one or more therapeutic agents to which the polymicrobial infection is resistant, and or (B) identifies one or more therapeutic agents to which the polymicrobial infection is susceptible, wherein the one or more organisms of the polymicrobial infection in the sample are not first isolated before phenotypic antibiotic resistance testing; where the urine sample is resistant to one or more therapeutic agents when the urine sample is above a predetermined threshold, and the urine sample is susceptible to one or more therapeutic agents when the urine sample is below a predetermined threshold:
Wang teaches a method of “culturing the unidentified bacteria in a first broth comprising an antibiotic; culturing the unidentified bacteria in a second broth substantially free of the antibiotic … identifying the antibiotic sensitivity or resistance of the unidentified bacteria by comparing the bacteria growth in the first broth with the bacteria grown in the second broth" [para 5] which involves no isolation steps prior to testing.
Wang further teaches “an array of digital reaction chambers for … quantifying the growth of bacteria” wherein “the bacterial sample [and] culture medium ... comprise a fluorescent intercalation dye... After completion of culture … any bacteria-containing compartments will become brightly fluorescent... The growth of ... bacteria species is determined by the average quantification cycle (Cq) derived from the [culture] wells ... the method of determining when a bacteria is antibiotic sensitive or resistant is by comparing difference in average Cq between bacteria species grown in a broth having an antibiotic with the same bacteria species grown in a broth without an antibiotic” [para 7], and wherein “antibiotic resistance may be determined when the differences of average Cq of the bacteria derived from the first broth and the second broth are less than 1.2. Generally, antibiotic sensitivity may be determined when differences of average Cq between the bacteria derived from the first broth and the second broth are greater than 1.2” [para 7], which is considered to correspond to the determination of resistance or susceptibility of a sample compared to a predetermined threshold
Wang does not teach the determination of discordance or the limitations of steps (b)(i) regarding genetic resistance marker testing, step (c) regarding determining discordance or concordance, step (d) regarding exclusion of therapeutic agents, step (e) regarding selecting therapeutic agents for the therapeutic solution in which concordance is present and the sample is susceptible to said agent, and step (f) regarding providing the therapeutic solution to a medical professional.
Brown describes methods for detecting and identification polymicrobial infections using PCR without purification or isolation in a sample [col 3, para 4] to allow improved patient care outcomes [col 3, para 3].
Regarding the limitation in claim 1 step (b)(i) of subjecting a portion of the urine sample to genetic resistance marker testing for detecting and identifying one or more resistance genes in the one or more organisms in the sample; wherein one or more resistance genes are present in the urine sample when the one or more resistance genes are detected at a level higher than a predetermined threshold:
Brown teaches a method comprising an automated test for "identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants of antimicrobial resistance in positive blood culture" [col 26, lines 42-55], where a "determinant of antimicrobial resistance" is defined as "a gene responsible for the development of resistance in the bacteria which actively counteracts the effect of an antibiotic. Particularly, genetic determinants of resistance to methicillin (mecA and mecC) and vancomycin (vanA and vanB) are envisaged. Genes associated with genetic determinants of resistance such as CTX-M, NDM, IMP, OXA, KPC, VIM are envisaged" [col 8 lines 16-23] with further description of the detection of OXA-23, CTX-1, CTX-8 and CTX-25 [Table 2, col 28]. As the methods of Brown include multiplex PCR [col 3, para 4] without purification or isolation, these methods are capable of detecting two or more targets. Brown further teaches limits of detection (LoD Concentrations) of organisms bearing the genetic resistance markers tested in Table 11, and methods for reducing false positive results, and therefore determining positive results compared to a predetermined threshold [col 17, para 6].
Regarding the limitations in claim 1 step (b) of subsequently subjecting a portion of the urine sample to genetic resistance marker testing and pooled AST after genetic identification, Wang teaches the genetic identification of an organism from a sample as well as antibiotic resistance testing as described above, and also teaches that the genetic identification cannot be carried out before AST due to the extraction of nucleic acids required for genetic identification. Brown, however, teaches the use of PCR to identify genetic material in a sample without purification or isolation in a sample [para 0005]. According to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. As Wang discloses a barrier to carrying out a certain order to the disclosed method, and Brown discloses a solution that obviates the barrier disclosed by Wang, one of skill in the art could apply the technique of Brown to the method of Wang to arrive at the claimed order of method steps through routine optimization. Additionally, Wang discloses a method of aliquoting a sample into portions to be subjected to different tests or treatments [para 0028]. One of skill in the art would therefore be expected to conclude the samples disclosed by Wang could be similarly aliquoted to portions for the carrying out of claimed steps (a) and (b) in any order, or concurrently, and such a technique would be considered an optimization of the method of Wang.
Regarding the limitation in claim 1 step (f) of providing the therapeutic solution to a medical professional to determine treatment for the subject, Brown teaches a microbial detection method that includes generating a report on a clinical instrument consisting of organism identification data [col 23, lines 46-55] as well as the system for exchanging report data between hospital and physician [Fig. 2 and cols 50-52].
Schmolke describes methods of determining an infection resistant to antimicrobial drug treatment, methods of selecting a treatment of a patient suffering from an antibiotic resistant infection, and methods of determining an antibiotic resistance profile [abstract], and discusses that the fast and accurate detection of infections and prediction of response to anti-microbial therapy represent a high unmet clinical need which is addressed by the disclosed method [paras 0018-0019].
Regarding the limitations of step (c) in claim 1 of determining discordance or concordance by comparing results from steps (b)(i)-(ii) to identify at least one therapeutic agent that is effective for treating the polymicrobial infection in the patient, the at least one therapeutic agent that is effective for treating the polymicrobial infection is a therapeutic solution:
Schmolke teaches "a method of selecting a treatment of a patient having an infection with a bacterial microorganism of Proteus species, comprising: obtaining or providing a first data set comprising a gene sequence of at least one clinical isolate of the microorganism from the patient; providing a second data set of antimicrobial drug, e.g. antibiotic, resistance of a plurality of clinical isolates of the microorganism; aligning the gene sequences of the first data set to at least one, preferably one, reference genome of the microorganism, and/or assembling the gene sequence of the first data set, at least in part; analyzing the gene sequences of the first data set for genetic variants to obtain a third data set of genetic variants of the first data set; correlating the third data set with the second data set of antimicrobial drug, e.g. antibiotic, resistance of a plurality of clinical isolates of the microorganism and statistically analyzing the correlation; determining the genetic sites in the genome of the clinical isolate of the microorganism of the first data set associated with antimicrobial drug, e.g. antibiotic, resistance; and selecting a treatment of the patient with one or more antimicrobial, e.g. antibiotic, drugs different from the ones identified in the determination of the genetic sites associated with antimicrobial drug, e.g. antibiotic, resistance is disclosed” [para 0142], therefore integrating the evaluation of genetic information (genomes and resistance markers) with phenotypic antibiotic resistance in order to select an effective antibiotic treatment for a patient.
Regarding the limitation in claim 1 of determining discordance, Schmolke teaches the method as described above [reference to para 0142], wherein the determination of an effective therapeutic requires the comparison of data sets in order to analyze correlations between various genetic and phenotypic testing. As such the method of Schmolke wherein the correlation of the presence of genetic resistance markers to antibiotic resistances of clinical isolates is used to select a therapeutic treatment is interpreted to encompass the determination of discordance as recited by the claims as a situation wherein “one or more resistance genes of a therapeutic agent is present, and the sample is susceptible to said therapeutic agent”.
Regarding the limitations in claim 1 parts (d) and (e), in view of Schmolke which teaches the comparison of genetic information and resistance testing to select an antibiotic treatment, it would be obvious for one of ordinary skill in the art to exclude therapeutic agents that are discordant as recited in part (d)(A) of the claim, and select therapeutic agents showing susceptibility to said agent and lack genetic resistance markers as recited in part (e) of the claim, particularly as Schmolke teaches evaluating data comprising the antibiotic resistance of isolates, determining the presence of genetic sites associated with drug (e.g., antibiotic) resistance, and selecting a treatment with one or more drugs different from the ones identified in the determination of the genetic sites associated with drug resistance [para 0142].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wang, Brown and Schmolke by using multiplex genetic identification testing via PCR and multiplex antibiotic sensitivity testing via chip assay to evaluate various clinical sample types, as taught by Wang, genetic marker testing targeting specific antibiotic resistance genes and specific bacterial organisms via PCR, the administration of an identified therapeutic agent, and the method of providing a therapeutic solution to a medical professional, as taught by Brown, and the application of antibiotic resistance testing results to identify a treatment for bacterial infection, as taught by Schmolke, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Wang by adding the genetic marker testing of Brown and the application of testing results for treatment identification of Schmolke, because Brown teaches the use of methods for detecting and identifying polymicrobial infections without purification or isolation in a sample provides improved patient care outcomes, and Schmolke teaches that fast and accurate detection of infections and prediction of response to anti-microbial therapy represents a high unmet clinical need. One of ordinary skill in the art would have reasonable expectation of success because Wang and Brown teach the subjecting of clinical samples to genetic identification testing, genetic marker testing, and antibiotic resistance testing using PCR as methods for the identification of specific bacterial organisms and specific antibiotic resistance genes for the treatment of a polymicrobial infection, and Schmolke teaches the application of similar testing results to determine such a treatment.
Regarding claims 5-6, Brown teaches methods utilizing PCR [col 103, lines 42-54] to detect a gram-negative microorganism or antimicrobial resistance gene [col 105, lines 4-6].
Regarding claim 7, Wang teaches an embodiment using “an array of digital reaction chambers for … quantifying the growth of bacteria” wherein “the bacterial sample [and] culture medium ... comprise a fluorescent intercalation dye... After completion of culture … any bacteria-containing compartments will become brightly fluorescent... The growth of ... bacteria species is determined by the average quantification cycle (Cq) derived from the [culture] wells ... the method of determining when a bacteria is antibiotic sensitive or resistant is by comparing difference in average Cq between bacteria species grown in a broth having an antibiotic with the same bacteria species grown in a broth without an antibiotic” [page 2, para 7, col 1, line 1].
Regarding claim 8, Wang further teaches the incubation of sample in the wells of a culture plate as described in the rejection of claim 7.
Regarding claim 9, Wang further teaches measuring organism viability by fluorescence as described in the rejection of claim 7.
Regarding claim 11, Brown teaches detection of the resistance genes CTX-M, NDM, IMP, OXA, KPC, and VIM [col 8 lines 16-23].
Regarding claim 12, Brown teaches that targets of the detection system include Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus [Table 1, cols 27-28], Acinetobacter baumanii, and Citrobacter freundii [Table 2, cols 33-34].
Regarding claim 14, Wang teaches the organisms in a microbial infection are bacteria [para 5].
Regarding claim 17, the claim is drawn to the same process as the method of claim 1 (claims 5-9 and 11-14 dependent therefrom) with the addition of specific limitations on the resistance genes being identified in step (b)(i), and a different step (f) drawn to administering or having administered at least one therapeutic agent identified to the patient, wherein the at least one therapeutic agent is effective for treating the polymicrobial urinary tract infection. Regarding limitation of resistance genes being identified by genetic marker testing, Brown teaches detection of the resistance gene KPC [col 8 lines 16-23] which is understood in the art to be Klebsiella pnueumoniae carbapenamase. Regarding the limitation of step (f), Brown teaches a method of diagnosing a gram-positive or gram-negative infection comprising "obtaining a blood sample; subjecting the sample to a single multiplex polymerase chain reaction (PCR) ... detecting whether a gram-positive bacteria or gram-negative bacterial infection or fungal infection is present by contacting the PCR products with a signal and capture probe and detecting binding between the PCR products and the signal and capture probe; and administering an effective amount of antibiotic or anti-fungal to the diagnosed patient" [page 50, lines 39-59].
Therefore, the invention of claims 1, 5-9, 11-12, 14 and 17 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Wang, Brown and Schmolke as applied to claims 1, 5-9, 11-12, 14 and 17 above, and further in view of Rahme et al. (US 2016/0237497; cited in the Form PTO-892 mailed 11/02/2023; herein referred to as Rahme).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 13 is drawn to the method of claim 1, wherein the therapeutic agent is one or a combination of a: penicillin, tetracycline, cephalosporin, quinolone, lincomycin, macrolide, sulfonamide, glycopeptide antibiotic, aminoglycoside, carbapenem, ansamycin, annamycin, lipopeptide, Fosfomycin, monobactam, nitrofuran, oxazolidinone, amphotericin B, isavuconazole, itraconazole, micafungin, Posaconazole, voriconazole, cidofovir, vidarabine, foscarnet, acyclovir, or valacyclovir.
The combined teachings of Wang, Brown and Schmolke as applied to claims 1, 5-9, 11-12, 14 and 17 are described above. These references do not teach specific therapeutic agents corresponding to claim 13.
Rahme describes methods and assays related to the treatment of infection, including diagnosis and prognosis [abstract], and discusses such methods are significantly more accurate than traditional clinical triaging.
Regarding claim 13, Rahme teaches the administration of antibiotics to subjects determined to be at risk of having or developing an infection, wherein antibiotics are defined as "penicillins, cephalosporins, penems, carbapenems, monobactams, aminoglycosides, sulfonamides, macrolides, tetracyclins, lincosides, quinolones, chloramphenicol, vancomycin, metronidazole, rifampin, isoniazid, spectinomycin, trimethoprim, sulfamethoxazole, and the like" [page 11, para 100].
In view of Rahme, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Wang, Brown and Schmolke by using the therapeutic taught by Rahme to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Wang, Brown and Schmolke because Rahme teaches methods that are significantly more accurate than traditional clinical triaging. One of ordinary skill in the art would have had a reasonable expectation of success because Wang, Brown, Schmolke discuss the identification of antibiotic resistances in organisms, and Brown and Rahme teach the administration of different antibiotics to subjects developing an infection for treatment.
Therefore, the invention of claim 13 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: Beginning on page 9 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends Schmolke does not use discordance-driven exclusion and instead relies on correlation; Applicant further contends there is no teaching of determining concordance as a clinically actionable condition or exclusion criteria; Applicant further contends Wang teaches away from the claimed order of steps; Applicant further contends the growth assessment of Wang is not carried out without cell lysis, as DNA measurements are taken upon cell lysis; Applicant further contends there is no guidance in Wang for applying the method to urine samples; Applicant further contends that Brown does not disclose the adaptation of the method to urine samples, and Brown only teaches the detection of antibiotic resistance genes, which does not correspond to functional expression or phenotypic resistance; Applicant further contends the claimed invention produces a surprising discovery of 60% concordance between ABR genes and P-AST results, which is an unexpected discrepancy that could not be predicted by the art. Applicant further contends the claimed invention provides an unexpected result over the CLSI performance thresholds in the art; Applicant further contends Schmolke does not provide a rationale to combine the teachings of Wang and Brown, and adapting Schmolke would require additional steps and undue experimentation.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that Schmolke does not use discordance-driven exclusion and instead relies on correlation, and that there is no teaching of determining concordance as a clinically actionable condition or exclusion criteria:
It is noted that discordance and concordance as recited in the claims are correlations based on the outcomes of genetic identification, genetic antibiotic resistance gene testing, and phenotypic antibiotic resistance testing of samples as disclosed by Schmolke. Schmolke explicitly states to integrate these data to select a drug that the sample is susceptible to and that lacks genetic resistance markers as outlined in the rejection above, which corresponds to both choosing a therapeutic agent that shows concordance as well as not choosing a therapeutic agent that shows discordance.
Regarding the assertion that Wang does not teach the order of steps recited in the claims of genetic testing followed by AST, and instead teaches away from this order:
The description of the Wang method of carrying out AST and genetic identification as inherently incompatible is explained by Wang in [para 0041] as due to the requirement for nucleic acid extraction to perform genetic identification. This statement is not considered a teaching away of carrying out both genetic testing and AST on a sample as asserted because Wang does not criticize, discredit or otherwise discourage carrying out the order of steps recited in the claims. As Wang teaches both of these methods can be used in the disclosed method, and Brown teaches the use of PCR to identify genetic material in a sample without purification or isolation in a sample, one of ordinary skill in the art could apply the technique of Brown to the method of Wang to render obvious the order of steps recited in the claims. Additionally, one of ordinary skill in the art would also have been expected to be knowledgeable of the technique of aliquoting samples, wherein multiple portions of the sample can be subjected to different tests, such as in Wang [para 0028] wherein a sample is disclosed to be divided into 2 portions for different treatments.
Regarding the assertion that Wang does not teach the performance of a growth assessment without cell lysis: The claims do not recite limitations of performing a growth assessment without cell lysis.
Regarding the assertion that neither Wang nor Brown disclose guidance for how to process or adapt the method to urine samples; Wang discloses a method of detecting bacteria in a biological sample, wherein a biological sample includes “whole blood, plasma, serum RBC fraction, urine, saliva cerebrospinal fluid, semen, sweat… [etc.]” as stated in the rejection above, and is therefore considered to satisfy the limitations in the claims of subjecting portions of urine samples to various testing protocols.
Regarding the assertion that Brown only teaches the detection of antibiotic resistance genes, which does not correspond to functional expression or phenotypic resistance; Brown teaches a method of identifying pathogenic organisms and determinants of antimicrobial resistance which includes identifying genes explicitly recited in claim 11 as discussed in the rejection above. As such Brown is considered to satisfy these limitations in the claims.
Regarding the assertion that the adaptation of Schmolke would require substantial additional steps and impose undue experimentation; The methods of claims 1 and 17 are stated to “comprise” the steps recited in each claim, respectively. As “comprise” is considered an inclusive and open-ended term that does not exclude additional, unrecited elements or method steps (see MPEP 2111.03), the disclosure of Schmolke is considered to correspond to the relevant limitations of the claims set forth in the rejections above.
Regarding the assertion that the present invention produces a surprising result that meets a long felt but unsolved need by enabling rapid, early, targeted antibiotic therapy, thereby improving patient outcomes, reducing antibiotic resistance, and reducing healthcare costs; The claims do not require enabling a rapid, early therapy that improves patient outcomes, reduces antibiotic resistance, and reduces healthcare costs. The method of claim 1 does not require a target therapy, as step (f) of claim 1 corresponds to providing data to a professional. While the method of claim 17 does require the administration of what would be considered a target therapy in step (f), the limitations of claim 17, including those in step (f), are considered obvious in view of Wang, Brown and Schmolke as discussed in the rejection above.
Regarding the assertion that the claimed invention produces a surprising discovery of 60% concordance between ABR genes and P-AST results, which is an unexpected discrepancy that could not be predicted by the art, and additionally provides an unexpected result over the CLSI performance thresholds in the art; Applicant’s assertion is being interpreted as an allegation of unexpected results.
MPEP 716.02(b).II. states Applicants have the burden of explaining proffered data. As applicant has provided no data, the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(b).II.
MPEP 716.02(b).I. states the burden is on Applicant to establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. As applicant has proffered no data, the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(b).I.
MPEP 716.02(e) states unexpected results must be compared with the closest prior art. Applicant merely states a discordance percentage that is unexpected over the CLSI performance thresholds, citing CLSI Performance Standards for Antimicrobial Susceptibility Testing. 35th ed. CSLI guideline M100. Clinical and Laboratory Standard Institutes; 2025 (reference not provided). As applicant has not provided any experimental details or data, or the data to which this statement of comparison is made, the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(e).
MPEP 716.02(d) states unexpected results must be commensurate in scope with the claimed invention. As applicant has proffered no data and merely recites a discordance value without any supportive information as to the experimental details that produced said discordance value, the unexpected results are not considered commensurate in scope with the claimed invention. Therefore, the allegation of unexpected results does not satisfy the requirements of MPEP 716.02(d).
For these reasons, Applicant’s allegation of unexpected results is considered insufficient to rebut a prima facie case of obviousness.
Conclusion
Status of the claims:
Claims 1, 5-9, 11-14 and 17 are pending.
Claims 1, 5-9, 11-14 and 17 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
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