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 .
This is a Final Office Action in response to amendment filed on August 10, 2026.
Claims 1-5 and 17-18 are amended. Claim 19 is cancelled. Claim 20 is newly added. Claims 1-18 and 20 are pending and examined on their merit herein.
Response to Amendment
Claim Objection of claim 5 is withdrawn in view of amendment to the claim.
The rejection of claims 1-3 and 6-14 under 35 U.S.C. 112(b) is withdrawn in view of amendment to the claims.
The rejection of claims 1 and 3 under 35 U.S.C. 102(a)(1) as being anticipated by Sng (American journal of clinical pathology 109.4 (1998): 399-403) is withdrawn in view of amendment to the claims.
The rejection of claims 1-4, 6-8 and 13-15 under 35 U.S.C. 102(a)(1) (a)(2) as being anticipated by Super (Patent US 9632085 B2, 2017) is withdrawn in view of amendment to the claims.
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 (i.e., changing from AIA to pre-AIA ) 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 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 1-15, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Super (Patent US 9632085 B2, 2017) in view of Bertozzi (Patent US10016498B2, 2018) and further in view of Skraba (US PGPUB US20200241010A1, published July 2020).
Claim 1 is drawn to a method to determine if an antibiotic is effective to treat a bacterial infection in a subject comprising: a) contacting a sample from a subject suffering from a bacterial infection with an antibiotic; and b) determining the effect, if any, of the antibiotic on incorporation of a single- or di- D- amino acid into peptidoglycan of the bacterial cell or incorporation of trehalose into the bacterial cell envelope, wherein an antibiotic that reduces, as compared to control without the antibiotic being present, incorporation of the D-amino acid into peptidoglycan of the bacterial cell or inhibited incorporation of trehalose into the bacterial cell envelope is an antibiotic that is effective to treat said bacterial infection in said subject; wherein b) is carried out by a lateral flow assay.
Regarding claim 1, Super discloses a method for determining antibiotic susceptibility of a microbe, the method comprising:
(i) obtaining a sample comprising a microbe….. ; (ii) incubating the …… microbe in the presence of at least one antibiotic agent; and (iii) detecting the growth, viability, or functional response of the microbe to the antibiotic agent,
wherein reduced growth, viability, or function in the presence of the antibiotic agent relative to a reference or control sample indicates that the microbe is susceptible to the antibiotic agent. (Claim 1, also see in more detail, col. 6 and so on, to col. 40)
Thus, Super discloses a method comprising the steps of contacting a bacterial sample with an antibiotic; and determine the effect of the antibiotic on the growth and viability and other functional response of the microbe to the antibiotic agent; therefore determining whether an antibiotic is effective against that bacterium.
Super further discloses that the microorganisms are “extracted and purified from a clinical sample” (e.g., Col 39, line 23-24)—which reads on the instantly recited “sample from a subject suffering from a bacterial infection”.
Super, specifically, in the working example (Example 2), discloses testing the antibiotic Carbenicillin. Super is silent regarding the incorporation of, for example, D-alanine, into peptidoglycan. However, the inhibition of D-ala into peptidoglycan is the inherent property of Carbenicillin and its inherent mode of action. See for evidence in Butler (The Journal of infectious diseases (1970): S1-S8). Thus, by determining the effect of Carbenicillin on the growth or viability of the bacterial pathogen, Super discloses determining, at least indirectly-- by inherently –the effect of Carbenicillin on D-ala incorporation into peptidoglycan.
Regarding claim 2, Super further discloses that (based on the outcome of the previous steps of determining the effects of the antibiotic), “a physician, can prescribe or administer to the subject in need thereof an antibiotic agent or a combination of antibiotic agent to which reduced the cell number …...” (e.g., Col. 38, lines 17-21).
Regarding claim 3, Super also discloses determining resistance of the bacteria to the tested antibiotic (e.g., Col. 27, line 33).
Regarding claims 5-8, Super discloses the pathogen being bacterial pathogen (e.g., Staphylococci, MRSA, etc., Example 2), or bacteria causing diseases such as sepsis ([Col. 58, line 19); or Mycobacterium (line 39-48).
Regarding claims 13-14, Super discloses that in the method, the identity of the bacteria causing the infection or contamination is not determined (see e.g. in Example 2, there is no step of making an identification of the bacteria). Super discloses that the determining of the effects of the antibiotics via an ELISA assay (Example 2, Col. 2, for example).
Regarding claims 4 and 15, Super discloses that the sample is (isolated) “taken from any environmental source, e.g., but not limited to, food products, water, ponds, food processing plants”, Col. 5, lines 39-41. Note that “food processing plant” reads on the “food production facility” in claim 15.
As discussed above, Super does not directly and explicitly teach, for example, the labeling of D-amino acid as means for directly evaluate the effect of the antibiotics to the growth or viability of the bacteria.
As discussed above, Bertozzi also teaches a method of evaluating/identifying an effective (candidate) antibiotic (antimicrobial), and wherein the method involves directly determining the effect, if any, of the antibiotic on incorporation of a modified D-amino acid (e.g., azide modified D-amino acid which is bioorthogonal functional group) into peptidoglycan present in the bacterial cell. Regarding claim 1, Bertozzi teaches methods of identifying anti-microbial agents, the methods generally involving: a) contacting a bacterial cell with a test agent; and
b) determining the effect, if any, of the test agent on incorporation of a modified D-amino acid (a modified D-amino acid that includes a bioorthogonal functional group such as an azide, an alkyne, or a norbornene group, as described above) into peptidoglycan present in the bacterial cell. ([Col. 36, lines 16-25) Test agents that inhibit incorporation of a modified D-amino acid into the PG of a bacterial cell are considered candidate anti-microbial agents. (Col. 36, lines 45-47). This reads on identifying the effective antibiotics.
Regarding claims 9-12, Bertozzi teaches the azide modified D-amino acid which is bioorthogonal functional group and which is a detectable label (see above); or wherein incorporation of the modified D-amino acid into the peptidoglycan is determined by contacting the cell with a reagent selected from a detectably labeled azide-containing reagent, ….. (Claim 4); wherein the detectable label is a fluorescent label. (Claim 5); wherein the detectable label is a radioactive isotope (Claim 12); and wherein the detectable label is biotin (Claim 13); or the label is detected by antibody binding (Claim 14).
Regarding claim 14, Super teaches that in the step of determining the effects of the antibiotics on the growth or viability of the bacteria, microbe can be detected using ELISA (Col. 28; as well Col. 33-34, regarding the advantages of ELISA). Conversely, Bertozzi teaches biotin to be detected through reaction of biotin and avidin—which is a commonly utilized ELISA method.
Regarding claims 17-18, Super teaches a method to detect low amounts of bacteria in a subject (an ELISA assay having a detection limit of below 160 bacteria for detecting bacteria in a sample from a subject (a method to detect low amounts of bacteria in a subject or site); Col.70, lines 4-7; claims 1-2, 12) comprising: a) labeling bacteria in a sample from a subject or site (labeling bacteria in a sample from a subject or site; column 17, lines 64, 59; column 61, lines 10-12), wherein is labeled with biotin (column 52, lines 1-20); b) capturing said metabolically labeled bacteria with avidin (biotin-avidin (capturing said metabolically labeled bacteria with avidin); column 52, lines 1- 20); or capturing said labeled bacteria with an antibody (column 70, lines 26-35); and c) detecting the signal with an ELISA (detecting the signal with an ELISA; column 33, lines 18-20), or western blot (e.g., by antibody).
Super and Bertozzi does not teach the lateral flow assay.
Skraba teaches lateral flow assay (paragraphs [0008], [0009]) determine if a single sample includes one or more bacterial types indicating a bacterial infection, such as Staphylococcus aureus.
Therefore, if would have been prima facie obvious for a person having ordinary skills of art at the time of filing of the instant application, to have combined the bioorthogonal labeling of D-amino acids of Bertozzi as means to directly assay the effects of antimicrobial agents (i.e., antibiotics) or to detect bacterial, with the antibiotic sensitivity test or bacterial detection methods of Super, and arriving at the instantly claimed methods. The PHOSITA would have been motivated because both Super and Bertozzi teach the method of rapidly and sensitively evaluate the growth and viability of bacteria as a means to evaluate the effectiveness of antibiotics, and/or to detect or diagnose an infection or contamination, and that the labeled D-amino acids taught by Bertozzi provide a sensitive and specific assay. The PHOSITA would have reasonable expectation of success given the teachings and success of both Super and Bertozzi.
It would have been obvious to a PHOSITA at the time of the invention to modify the disclosure of Super and Bertozzi, to include a lateral flow assay, as disclosed in Skraba, in order to provide a rapid diagnosis and targeted treatment to patients with a bacterial infection.
Therefore, the claimed inventions as a whole is prima facie obvious over the combined teachings of the prior art.
Claims 16 is rejected under 35 U.S.C. 103 as being unpatentable over Super (Patent US 9632085 B2, 2017) in view of Bertozzi (Patent US10016498B2, 2018) and Skraba (US PGPUB US20200241010A1, published July 2020).as applied to claim 4 as discussed above, further in view of Chia (US PGPUB US 20200157144 A1, published May 2020).
As discussed above, claim 4 is taught by the combined teachings of Super, Bertozzi and Skraba.
Super, Bertozzi and Skraba do not teach decontamination after the contamination is detected.
Chia teaches method of disinfecting a surface against bacterial contamination, comprising applying to said surface a compound of the formula (I) (Claim 17) which is a high microbicide activity and are suited to combat resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA) strains, and which has been assayed by measuring inhibition of bacterial growth (Example 2).
Therefore, it would have been prima facie obvious and within the scope of a PHOSITA, following the detection method taught by the combined teachings of Super and Bertozzi as discussed above, to follow with a decontamination step with any suitable bactericides.
Therefore, the claimed inventions as a whole is prima facie obvious over the combined teachings of the prior art.
Response to Applicant’s Remarks:
Regarding the rejections above, Applicant simple argued that Super and Bertozzi does not teach the lateral flow assay, and that “metabolic labeling of cell macromolecules work well in a research laboratory setting, but they are not well-suited for clinical applications”, as grounds for the assertion that “it would not have been obvious to the PHOSITA at the time of the invention to combine (i) peptidoglycan labeling with (ii) a lateral flow assay to provide a clinically relevant diagnostic tool for use with a sample isolated from a subject with a bacterial infection.”
These arguments have been fully considered but not deemed persuasive.
Firstly, Applicant has not provided any evidence supporting the assertion that “metabolic labeling of cell macromolecules work well in a research laboratory setting, but they are not well-suited for clinical applications”. On the other hand, Ignacio (Org. Biomol. Chem. 2021; 19 (13): 2856–2870. Published March 16, 2021) teaches the use metabolic labeling with trehalose-probes for clinical diagnosis of Mycobacterium tuberculosis and that metabolic labeling with trehalose analogues has shown promise as a novel diagnostic approach for the rapid detection of Mtb infection (p. 2861, left col., para. 1 and 2); and that various trehalose analogues have emerged as novel potential point-of-care diagnostic tools for Mtb (p. 2862, right col., para. 2).
Regarding lateral flow assay, point-of-care lateral flow immunoassays have been used before the filing of the instant application for rapid detection of pathogenic microorganisms. See for example in Wu (Journal of Infection 81.3 (2020): 435-442). Boutal (Diagnostics (Basel). 2022 Jul 19;12(7):1744) also tallied that by October 2020, there have been hundreds of publications regarding clinical application of lateral flow assay (Figure 2), including for rapid detection of antibiotic-resistant microbials.
Lastly, it should be pointed out that the claims are still broad in scope and not limited to specific means or steps that Applicant seem to imply.
Therefore, Applicant’s arguments have not been found to be sufficiently persuasive to overcome the remaining rejections.
Conclusion
No claims are allowed. Claims 1-18 are rejected and claim 20 is objected to for being dependent on rejected base claims.
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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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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