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 .
Status of claims
Claims 1-11, 21 and 22 as amended and new claims 23-31 as filed on 12/08/2025 are under examination in the instant office action.
Claims 12-20 were cancelled by applicants.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
New claim 31 is rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Murray et al (“A rapid broth dilution technique utilizing hemoglobin for determining antibiotic susceptibility of microorganisms”. Journal of Microbiological Methods, 1994, 19, pages 155-165).
The cited reference by Murray discloses a system for determining antibiotic susceptibility of microorganisms or for detecting antimicrobial resistance of bacteria in a biological sample (see entire document including page 158, section 2.9), wherein the system comprises:
a plurality of containers or tubes, each containing a portion of a biological sample with bacteria to be tested (page 158, section 2.9);
a detecting agent or hemoglobin disposed into the plurality of containers or tubes (page 158, section 2.9); wherein detecting agent hemoglobin produces optically detectable changes in color responsive to bacterial respiration or growth (see page 156, lines 20-21); and
an antimicrobial agent or antibiotics disposed in some of the plurality of containers or tubes (page 158, sections 2.8 and 2.9).
The cited system is used for measuring oxygen consumption as indication of bacterial growth; and it is practiced in a “closed system” as explicitly stated by the cited reference (page 157, paragraph 2.5, last line). Thus, the containers (tubes containing diluted biological samples) are sealed with “sealing” material (whether “film” or cover or else) that provide for identical effect as “to limit oxygen exchange with environment” within the broadest reasonable meaning of the claim 31.
Thus, the cited reference by Murray anticipates new claim 31.
Claims 1-4, 6, 7, 11, 21, 22 as amended and new claims 23-25, 27-30 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Matsui et al (“A Rapid ATP Bioluminescence based Test for Detecting Levofloxacin Resistance Starting from Positive Blood Culture Bottles”. Scientific Reports. Nature Research. 2019, 9, article number 13565, pages 1-9).
The cited reference by Matsui discloses a system as intended for detecting antimicrobial resistance of bacteria in a biological sample comprising “a diluted blood culture” (see entire document including abstract and figure 1), wherein the system comprises:
a plurality of containers or tubes containing a portion of a biological sample comprising “a diluted blood culture” from positive blood cultures bottles (see figure 1); wherein the blood culture was not subjected to bacterial isolation (isolation of pure bacterial isolates) from positive blood cultures but bacterial cultures are directly taken from positive blood cultures bottles (page 2, par. 2-3);
a detecting agent (luciferin-luciferase reagent) disposed into containers (page 7, section measurement of ATP levels) which produces fluorescence or optically detectable changes (see figure 2) responsive to bacterial viability, thus, growth and/or respiration; and
an antimicrobial agent (LVFX or levofloxacin antibiotic) disposed in some of the plurality of containers (figure 1).
Thus, the cited reference by Matsui anticipates claim 1.
As applied to claim 2: containers or tubes contain different or various concentrations of antibiotic LVFX (page 2, par. 3, line 8), thus, “a first amount” and “a second amount” within the broadest reasonable meaning of the claims as intended for determination of MIC.
As applied to claim 3: detecting agent provides for optical or visual detection of bioluminescence depending on bacterial viability, thus, including growth and/or respiration under effect of different (increasing) concentrations of antibiotic.
As applied to claims 4, 21 and 22: the system comprises an imaging device for detecting optical changes or changes in bioluminescence under effect of different concentrations of antibiotic (page 7, section “measurements of ATP levels).
As applied to claim 6: luciferin/luciferase reagent is sensitive to oxygen.
As applied to claim 7: luciferin is considered a chromophore.
As applied to claim 11: culture tubes are commonly/routinely sealed for the very least reason to avoid undesirable contamination.
Further, as applied to claim 21: the system comprises “control” tube without antibiotic (figure 1) as intended to detect optical changes relative to changes in tube with antibiotic within the meaning of the claims.
Further, with respect to claim 22 it is noted that claim-recited limitations drawn to detecting and comparing changes within 12 hours are not structural elements of the product itself (claimed “system”) but they are intended uses limitation of the claimed “system”. Moreover, the cited reference teaches that the system allows for measurements of changes after incubation for 2-6 hours (figure 1).
As applied to claim 23 (new claim 23): the cited system of Matsui comprises:
a plurality of containers or tubes containing a portion of a biological sample comprising “a diluted blood culture” from positive blood cultures bottles (see figure 1); wherein the blood culture was not subjected to bacterial isolation (isolation of pure bacterial isolates) from positive blood cultures but bacterial cultures are directly taken from positive blood cultures bottles (page 2, par. 2-3);
a detecting agent (luciferin-luciferase reagent) disposed into containers (page 7, section measurement of ATP levels) which produces fluorescence or optically detectable changes (see figure 2) responsive to bacterial viability, thus, growth and/or respiration;
an antimicrobial agent (LVFX or levofloxacin antibiotic) disposed in some of the plurality of containers (figure 1);
a “control” tube without antibiotic (figure 1) as intended to detect optical changes relative to changes in tube with antibiotic within the meaning of the claims; and
an imaging device for detecting optical changes or changes in bioluminescence under effect of different concentrations of antibiotic (page 7, section “measurements of ATP levels).
The claim 23-recited limitation drawn to determination of MIC within 12 hours is not a structural element of the product itself (claimed “system”) but it is an intended use limitation of the claimed “system”. Moreover, the cited reference teaches that the system allows for measurements of changes after incubation for 2-6 hours (figure 1).
As applied to claim 24: in the cited system the diluted positive blood culture comprises “blood components” (at least serum and contaminating bacteria) within the broadest reasonable meaning of the claim.
As applied to claims 25, 29 and 30: claim-recited limitation drawn to detection of changes and determination of MIC within 3-5 or 10 hours is not structural elements of the product itself (claimed “system”) but they are intended uses limitations of the claimed “system”. Moreover, the cited reference teaches that the system allows for measurements of changes after incubation for 2-6 hours (figure 1).
As applied to claim 27: the dilution of blood cultures is done with a culture medium broth (page 2, par. 3, line 6); and the only culture medium broth as disclosed for the cited system is a cation-adjusted Mueller-Hinton broth (page 6, section “methods” par. 2).
As applied to claim 28: the cited system includes bacterial mixtures from diluted positive blood culture bottles but not pure bacterial isolates from blood (figure 1; page 2, par. 3).
Therefore, the cited reference by Matsui anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-11 and 21-31 (as amended and new claims) are rejected under 35 U.S.C. 103 as being unpatentable over Murray et al (“A rapid broth dilution technique utilizing hemoglobin for determining antibiotic susceptibility of microorganisms”. Journal of Microbiological Methods, 1994, 19, pages 155-165) in view of Belanger (“Testing physiologically relevant conditions in minimal inhibitory concentration assays”. Nature Protocols. 2008, 3, 163-175) and Matsui et al (“A Rapid ATP Bioluminescence based Test for Detecting Levofloxacin Resistance Starting from Positive Blood Culture Bottles”. Scientific Reports. Nature Research. 2019, 9, article number 13565, pages 1-9).
The cited reference by Murray teaches a system for a rapid broth dilution technique utilizing hemoglobin for determining MIC and antibiotic susceptibility of microorganisms (as explained above with regard to claim 31). Murray discloses that hemoglobin-based detection system allows for a rapid antibiotic susceptibility testing within 3-4 hours (see abstract).
In particular, the cited reference by Murray discloses a system for determining antibiotic susceptibility of microorganisms or for detecting antimicrobial resistance of bacteria in a biological sample (see entire document including page 158, section 2.9), wherein the system comprises:
a plurality of containers or tubes, each containing a portion of a biological sample with bacteria to be tested (page 158, section 2.9);
a detecting agent or hemoglobin disposed into the plurality of containers or tubes (page 158, section 2.9); wherein detecting agent hemoglobin produces optically detectable changes in color responsive to bacterial respiration or growth (see page 156, lines 20-21); and
an antimicrobial agent or antibiotics disposed in some of the plurality of containers or tubes (page 158, sections 2.8 and 2.9).
The system of Murray also contains “control” tubes/containers without antibiotics or without bacteria (page 158, section 2.9).
The system for determination of MIC of Murray is based on detection of a color change, and it includes a generic imaging device or spectrophotometer (page 157, section 2.4).
But the biological sample in the containers of the cited system of Murray is a pure bacterial cultures or pure clinical bacterial isolate but not a diluted blood cultures.
However, the reference by Belanger teaches that MIC assay systems should be based on physiologically relevant conditions such as blood conditions for clinical applications in selecting antimicrobials against pathogens causing infections (see abstract).
The cited reference by Matsui demonstrates a system for MIC assay comprising a “diluted blood cultures” derived from positive blood cultures bottles without purification of clinical isolates, wherein the system allows for rapid MIC determination within 2-6 hours (entire document including abstract and figure 1).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to substitute “diluted blood cultures” for pure clinical isolates in the system of Murray with a reasonable expectation of success in providing a system for a rapid determination of MIC and antibiotic susceptibility of pathogens causing infections because prior art teaches that MIC assay systems should be based on physiologically relevant conditions, such as blood conditions, for clinical applications in selecting antimicrobials against pathogens causing infections (Belanger) and because systems for MIC assay with diluted blood cultures derived from positive blood cultures bottles have been knonw and used for rapid MIC determinations (Matsui).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Further, with regard to claims 8-9, as drawn to immobilizations of a detection reagent on carrier, the cited reference by Murray teaches that hemoglobin is/can be encapsulated or immobilized within an agar matrix as intended or antibiotic suitability testing of microorganisms (page 156, lines 6-10).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed on 12/08/2025 have been considered but they are moot in view of new grounds of rejections as necessitated by amendment.
The rejection of claims (previously claims 1-7, 10, 11, 21 and 22) under 35 U.S.C. 102 (a) (1) as being anticipated by Elshikh et al (“Resazurin-based 96-well plate microdilution method for the determination of minimum inhibitory concentration of biosurfactants”. Biotechnol Lett., 2016, 38, pages 1015-1019) has been withdrawn because the containers of cited system do not comprise “diluted blood cultures” but pure bacterial cultures diluted in a bacterial culture medium as intended for defemination of MIC.
The rejection of claims (previously presented claims 1-3, 5-7, 10 and 11) under 35 U.S.C. 102 (a) (1) as being anticipated by Murray et al (“A rapid broth dilution technique utilizing hemoglobin for determining antibiotic susceptibility of microorganisms”. Journal of Microbiological Methods, 1994, 19, pages 155-165) has been withdrawn because the containers of cited system do not comprise “diluted blood cultures” but pure bacterial cultures diluted in a bacterial culture medium as intended for defemination of MIC. However, new claim 31 is anticipated by the cited reference as explained above.
With regard to claim rejection under 35 USC § 103 Applicants’ arguments are mostly drawn to specification examples that describe rapid methods for determination of MIC without purification steps of bacterial isolates. The arguments are based on method steps, while claims under examination are directed to a system (product) comprising containers with a biological sample, a detection reagent and antibiotics.
Conclusion
THIS ACTION IS MADE FINAL. 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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Vera Afremova
March 23, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653