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 . Applicant’s amendment filed 4/9/2026 is acknowledged. Claims 1, 3, 6, 13, 15, 16, 28, 32, 37, 41, 43, 44, 48 have been amended. Claims 7-9, 11-12, 14, 18-20, 22-27Claims 1-6, 10, 13, 15-17, 21, 28-29, 32-33, 37, 41, 43-44, 48 and 49 are pending. All of the amendment and arguments have been thoroughly reviewed and considered.
Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims.
This action is made Final.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/9/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Previous Rejections
Rejection Status
(a) The objection to the specification is withdrawn in view of Applicant’s amendment to the specification.
(b) The claim objection directed to the claims 15, 32, and 43 is withdrawn in view of Applicant’s amendment.
(c) The claim rejection under 35 USC 112 is withdrawn in view of Applicant’s amendment of the claims.
(d) The claim rejection under 35 USC 02(a)(1) is withdrawn in view of Applicant’s amendment of the claims.
New Ground(s) of Rejections
THE NEW GROUND(S) OF REJECTIONS WERE NECESSITATED BY APPLICANT’S AMENDMENT OF THE CLAIMS:
Claim Rejections - 35 USC § 112
4. 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.
5. Claim 15, 32, and 43 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
(a) Claims 15, 32, and 43 as amended still contains the trademark/trade name “Triton X-114, NP-40, Arlasolve 200, Brij O10, Brij 96/97, Brij 35” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. It is suggested deleting the trade names and symbols and replace with only the generic names. MPEP states that the use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name." (See MPEP 2173.05(u).
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
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.
8. Claim(s) 1-6, 10, 13, 15-17, 21, 28, 29, 32, 33, 37, 41, 43, 44, 48 and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Talepour et al {Talepour, used interchangeably herein} (WO 2019/222862, citation made of record in prior Office action) in view of Jarvius et al (US 20180223327, August 2018).
Regarding 1, 10, 28, 41 and 48, Talepour et al teach a method and compositions are provided for the selective lysis of eukaryotic cells and the separation of microbial cells. Blood cells and/or other eukaryotic cells in a sample, may be selectively lysed by adding, to the sample, a blood lysis reagent including saponin and an alkaline buffer, and optionally sodium polyanethole sulfonate and a non-ionic surfactant, thereby forming a mixture, and agitating the mixture. Microbial cells in the mixture may then be separated, for example, using a separation method such as centrifugation or filtration, and optionally detected or cultured in growth media. Blood lysis reagent compositions are provided that are suitable for preserving the intactness of microbial cells upon mixing with the sample. In example embodiments in which the sample is a blood sample, the blood lysis reagent composition may be selected to avoid or reduce the presence of visible blood debris upon centrifugation or filtration (abstract and page 2-3).
Talepour et al teach in a first aspect, there is provided a method of separating microbial cells from a sample, the method comprising: mixing a blood sample and a blood lysis reagent, the blood lysis reagent comprising saponin, sodium polyanethole sulfonate and an alkaline buffer, to obtain a mixture having a concentration of saponin between 0.75 and 60 mg/ml, a concentration of sodium polyanethole sulfonate between 0.35 and 50 mg/ml and a pH between 7.8 and 10 and prior to mixing wherein the pH of the mixture of about 10 (see e.g., page 39); and separating microbial cells from the mixture (page 3, pages 3-19). Talepour et al teaches in the Figures the following:
FIG. 2 shows a schematic of an example system for performing automated centrifugation and washing with an integrated fluidic processing cartridge.
FIGS. 3A to 3C illustrate an example integrated fluidic processing cartridge configured for extraction of a sample directly from a collection tube, and subsequent centrifugation and washing, to obtain a concentrated and purified suspension of microbial cells.
FIG. 4 provides a flow chart illustrating an example method for performing automated centrifugation and washing.
FIG. 5A shows images of centrifuge tubes after performing hemolysis of whole blood samples with different volumes using an equal volume of type 1 blood lysis reagent containing saponin and sodium polyanethole sulfonate (SPS), followed by two centrifugal washes.
FIG. 5B shows images of centrifuge tubes after performing hemolysis of whole blood samples with different volumes using an equal volume of type 2 blood lysis reagent containing Triton X-100, SPS, and a carbonate-bicarbonate buffer, followed by two centrifugal washes.
FIG. 6 plots AC.sub.T values for different bacterial species obtained after contacting whole blood samples with a type 2 blood lysis reagent containing Triton X- 100, SPS and a carbonate-bicarbonate buffer, performing centrifugal separation and concentration, heat lysis, and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) as a measure of microbial cell intactness.
FIG. 9B plots AC.sub.T values for different bacterial species obtained after contacting whole blood samples with a type 3 blood lysis reagent containing saponin, SPS, a carbonate-bicarbonate buffer and Triton X-100, performing centrifugal separation and concentration, heat lysis and real-time RT-PCR.
FIG. 12B plots the dependence of the post-mixing pH on the initial buffer concentration (the buffer concentration prior to mixing).
FIGS. 13A and 13B plot ACT values for different bacterial species and three different blood lysis reagent pH values (the pH values were measured prior to mixing with whole blood) after contacting spiked phosphate buffer samples with a type 3 blood lysis reagent with different pH value, containing saponin, SPS, a carbonate- bicarbonate buffer and Triton X-100, performing centrifugal separation and concentration, heat lysis and real-time RT-PCR, where FIG. 13A presents data for a Triton X-100 concentration of 0.75% w/v, and FIG. 13B presents data for a Triton X- 100 concentration of 0.38% w/v.
Talepour et al teach wherein each of the steps can be competed in in less 20 minutes (see e.g., Examples 4-11). Talepour et al further teach wherein the microbial cells is nominally about 10 CFU/ml (example 2, page 87 and page 88, line 3). Talepour also teaches where the pH of the blood lysate after mixing with the buffer is about 7.0 – 8.0 (see page 82, lines 31-33). Talepour also teaches the use of a differential lysis buffer wherein the lysis buffer comprises suitable alkaline buffers which may include borate, carbonate, CAPS (N-cyclohexyl-3-aminopropanesulfonic), CAPSO (3- (Cyclohexylamino)-2-hydroxy-1-propanesulfonic acid), CHES (2-(N- Cyclohexylamino) ethane Sulfonic acid), pyrophosphate, AMP (2-amino-2-methyl-1- propanol), and ethanolamine (page 39, lines 17-24).
At page 82, Telepour states “[I]n one example embodiment, the blood lysis reagent may have a composition such that after the blood lysis reagent is mixed with the blood culture sample, the pH lies within a reagent of 7.8 – 10. In other examples embodiments, the pH of the final mixture may range between 8.2 – 9.5. In other examples embodiments, the pH of the final mixture may lie within arrange bounded by an upper pH value of 10, 9.9, 9.8, 9.7, 9.6, 9.5, and bounded by a lower pH value of 8,0, 8.2, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9.0.”
With regards to the limitation “wherein the differential lysis buffer comprises a buffering substance having a pH buffering rage of about 8.6-11.4 and a nonionic surfactant, the differential lysis buffer having a pH range of about 10-11 prior to mixing the blood sample with the differential lysis buffer”, Telepour teaches that the blood is mixed with a blood lysis buffers comprising saponin, sodium polyanethole sulfonate and with an alkaline buffer, wherein the mixture has a pH of between 8-10 and after mixing the blood the mixture has a pH of about 7.8 to 10. With regards to overlapping ranges,
MPEP 2144.05 states “[I]”.n 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)”. 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)”. "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005)”. Finally, in this regards, MPEP 2144.05 further states that “[A] range can be disclosed in multiple prior art references instead of in a single prior art reference depending on the specific facts of the case. Iron Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1322, 73 USPQ2d 1225, 1228 (Fed. Cir. 2004).”
In a similar method, Jarvius et al teach a method of isolating and identifying a microorganism comprising the steps of introducing a blood or other sample to a culture vessel and then performing a cultured step, wherein the culture system is designed or selected to indicate that microbial growth has occurred, for example by including an indicator substant that yields a signal dependent on microbial growth (e.g., due to pH change, or conversion/consumption of a substrate, or generation of microbial metabolic product, etc.) (0018). Jarvius further teaches in the method, steps for selectively enriching may including lysing any non-microbial cells and selectively recovering microbial cells (0127 – 0134). Jarvis teaches that one or more additional agents, such as reducing agents such as 2-mercaptoethanol or DTT, stabilizing agents such magnesium, pyruvate and humectants and/or chelating agents such as EDTA may be added. The reference teaches that the lysis solution can be buffered at any pH that is suitable to lyse the desired cells and will depend on multiple factors, including without limitations, the type of sample, the cells to be lysed and the detergent used. In some embodiments, the pH can be in a range from 2-13, e.g., 6-13, 8-13 or 10-13. Suitable pH buffers include any buffer capable of maintaining a pH in the desired range, e.g., about 0.05 M to about 1.0 M CAPS ([0134]).
In view of the teachings of Talepour et al and Jarvius, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have achieved and use the differential lysis buffer in the desired amount for the intended purpose of isolating and identifying a microorganism. Such methodologies are within the ordinary artisans’ capabilities and would only require routine optimization of known reaction components, concentrations, and parameters. Clearly such conventional and trivial modification and optimizations do not contribute towards patentability. Thus, one of ordinary skill in the art would have been motivated to modify the primary references in the manner of the claims to achieve the expected benefits, optimizations and/or expanded applications. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to carry out the claimed methods. MPEP 2131.03 states “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claims 2-3, 10, 37, and 49, Talepour et al teach wherein the steps (b) – (e) can be completed in about 20-75 minutes or less (see e.g., Examples 4-17).
Regarding claim 4, Talepour et al teach wherein the microorganism is a bacterium organism associated with a bloodborne infection (pages 50, 57-60 and Example 1, page 86-87).
Regarding claims 5 and 29, Talepour teaches wherein the identifying includes at least a molecular test or culture-based test (Examples 1-17).
Regarding claims 6, Talepour teaches wherein the identifying includes seps of isolating from the microorganism one or more nucleic acids characteristic of the microorganism, and analyzing the one or more nucleic acids to identify the microorganism present in the blood sample, wherein the identifying comprises amplifying one or more nucleic acid and then detecting the one or more amplified nucleic acids via a real-time PCR assay (see example Figures 6-16 and Example 4-8) or flow cytometry, microscopy, spectroscopy or affinity reactions (page 63, lines 3-11).
Regarding claim 13, 33 and 44, Talepour the teaches the use of a differential lysis buffer wherein the lysis buffer comprises suitable alkaline buffers which may include borate, carbonate, CAPS (N-cyclohexyl-3-aminopropanesulfonic), CAPSO (3- (Cyclohexylamino)-2-hydroxy-1-propanesulfonic acid), CHES (2-(N- Cyclohexylamino) ethane Sulfonic acid), pyrophosphate, AMP (2-amino-2-methyl-1- propanol), and ethanolamine (page 39, lines 17-24).
Regarding claim 15, 16, 32, and 43, Talepour teaches the example embodiments described herein employ Triton X- 100 (known, for example, as polyethylene glycol p-(1,1 ,3,3-tetramethylbutyl)-phenyl ether, Octyl phenol ethoxylate, Polyoxyethylene octyl phenyl ether, 4-Octylphenol polyethoxylated, and t-Octylphenoxypolyethoxyethanol) as a non-ionic surfactant, it will be understood that a type 3 blood lysis reagent suitable for the lysis of blood components and the preservation of intact microbial cells may include a wide range of non-ionic surfactants. Non-limiting examples of suitable non-ionic surfactants include, but are not limited to, alkylglycosides, Brij 35 (C12E23 Polyoxyethyleneglycol dodecyl ether) (15,7), Brij 58 (Cl 6E20 Polyoxyethyleneglycol dodecyl ether) (16), Genapol (13 to 19), alkyl N-methyl glucamide such as MEGA-8, -9, -10, octylglucoside (12,6), Pluronic F127, Triton X-100 (C14H220(C2H40)„) (13,4), Triton X-1 14 (C24H4206) (12, 4), Tween 20 (Polysorbate 20) (16, 7) and Tween 80 (Polysorbate 80) (15) Nonidet P40 sodium deoxycholate, reduced Triton X-100 and or Igepal CA 630 (pages 43, last paragraph bridging top of page 44).
Regarding claim 17, Talepour teaches wherein the concentrating the microorganism from, the lystate includes centration and recovering a pellet fraction comprising the microorganism from a supernatant fraction comprising a lysed blood fraction (see e.g., example 10, page 91).
Regarding claim 21, Talepour teaches multiple embodiments wherein in one embodiment, the method does not include one or more culture steps prior to mixing the blood sample with the differential lysis buffer or DNase step to digest genomic DNA in the lysate (see e.g., Example 10, page 91). Thus, Talepour meets the limitations of the claims recited above.
Conclusion
9. No claims are allowed. 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.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY BENZION can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681
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