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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/09/2026 has been entered.
DETAILED ACTION
Claims 3, 14, 16, 21-27, 29-40, 42-45, 47-48, 51, 53-54 and 57-84 are canceled. Claims 1-2, 4-5, 11-13, 15, 17-20, 28, 41, 46, 49-50, 52, and 55-56 are pending and under consideration in this action.
Priority
The instant claims are entitled to an effective filing date of 08/20/2020.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 56 is 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.
Claim 56 recites the parenthetical phrase “(w/w)” in line 6, which renders the claim indefinite because it is unclear whether the limitation within the parentheses is part of the claimed invention. Therefore, in one interpretation “at least 0.1% (w/w)” is limited to w/w, and under an alternative interpretation the recited (w/w) is exemplary such that the claim encompasses, for example, at least 0.1% w/v.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 46, 49 and 50 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 46, 49 and 50 do not further limit the method of claim 1. Claim 46 recites: [t]he method of claim 1, wherein the method yields an at least 5% higher MALDI score as compared to a comparable method employing a lysis buffer that does not comprise the SDA. Claim 49 recites: [t]he method of claim 1 wherein the ratio of blood cells lysed to cells of the at least one microorganism lysed following the contacting step is at least about 2:1. Claim 50 recites: [t]he method of claim 1, wherein at least about 50%...of the cells of the at least one microorganism remain intact and/or viable following the contacting step. These recitations in claims 46, 49 and 50 are intended results/effects that do not confer structural, or manipulative differences on the scope of the claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2 and 4 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sharma (WO 92/19285).
Claim Interpretation: Instant claim 1 requires contacting a sample comprising blood cells and at least one microorganism with a lysis buffer to generate a treated sample, wherein the lysis buffer comprises a Somatic Cell Digestion Agent (SDA) capable of lysing cells in the sample, wherein the SDA is formula 1 where x is from 8-12 and y is from 6-11, thereby lysing the blood cells in the sample. Based on the claim language, and instant claim 4, nonoxynol-9 is an SDA capable of lysing blood. Therefore, any composition comprising nonoxynol-9 is considered a lysing buffer that lyses blood cells in blood samples comprising at least one microorganism.
Regarding claim 1, Sharma teaches a method comprising a) introducing a disinfectant composition into a blood bag containing blood or a component thereof;
b) mixing the disinfectant composition with said blood or blood component sample to induce contact and thereby kill the viruses and bacteria (i.e. at least one microorganism) present in said sample. See claim 19 of Sharma. Sharma teaches a disinfectant composition comprising nonoxynol-9 (i.e. SDA). See claim 18 of Sharma. Sharma discloses that nonoxynol-9 has red cell lysing properties or a hemolytic effect. See p. 2 line 26 and 29-30. With respect to instant formula 1, nonoxynol-9 is an embodiment where y=9 and x=9.
Regarding claim 2, Sharma teaches a disinfectant composition comprising nonoxynol-9. See claim 18 of Sharma. With respect to instant formula 1, nonoxynol-9 is an embodiment where y=9, which is an integer from 8 to 10 as required.
Regarding claim 4, Sharma teaches a disinfectant composition comprising nonoxynol-9. See claim 18 of Sharma.
Claim 56 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Modak (US 2004/0102429).
Regarding claim 56, Modak teaches mixing a formulation containing 8% nonoxynol-9 with red blood cells. See [0072]. As shown in table 4, the lubricant base plus 8% nonoxynol-9 resulted in lysis. See [0073]. Modak teaches nonoxynol-9 present in lubricants at 9% w/w. See [0068]. With respect to instant formula 1, nonoxynol-9 is an embodiment where x=9, which is an integer from 8 to 12 as instantly required, and where y=9, which is an integer from 6 to 11 as instantly required.
Response to Arguments
Applicant's arguments, filed 02/09/2026, with respect to the previous rejections under 35 U.S.C. §102 have been fully considered but they do not apply to the new grounds for rejection set forth above.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Sharma (WO 92/19285).
The teachings of Sharma with respect to instant claims 1, 2 and 4 are discussed above and incorporated herein.
Claim interpretation: instant claim 5 recites the term “about”, which encompasses variations of ±20%. See paragraph [0033] of the instant specification.
Regarding claim 5, Sharma teaches a composition comprising nonoxynol-9 at a concentration of about 0.5-4%. See claim 4 of Sharma. Sharma discloses that concentration is calculated as gm reagent/100ml aqueous solution. See p. 8 lines 4-5. Therefore, Sharma suggests a nonoxynol-9 concentration of about 5g/L to 40 g/L, which overlaps with the instantly required concentration of about 0.01 g/L to about 10 g/L.
Sharma does not explicitly teach a somatic cell digestion agent (SDA) at a concentration of about 0.01 g/L to about 10 g/L in a lysis buffer.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to optimize the workable range for Sharma’s nonoxynol-9. A person of ordinary skill in the art has good reason to pursue the known options within their technical grasp. There would have been a reasonable expectation of success because Sharma provides a concentration range that overlaps with the instantly claimed about 0.01 g/L to about 10 g/L. MPEP 2144.05(II)(A) indicates that differences in concentration generally amount to “routine optimization”. “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 1, 2, 4-5, 11-13, 28, 41, 46, 49-50, 52 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber (US 2014/0227723).
Regarding claims 1, 2 and 4, Ingber, in example 17, teaches bacteria present in blood. See [0885]. Ingber teaches preprocessing a test sample, such as whole blood with a preprocessing reagent. See [0211]. The preprocessing reagents include surfactants, cell lysing reagents and degradative enzymes, e.g. nucleases. See [0213]. Exemplary surfactants include nonoxynol-9 (i.e. SDA). See [0223]. With respect to instant formula 1, nonoxynol-9 is an embodiment where y=9 and x=9.
Ingber teaches nonoxynol-9 amongst lists of other surfactants.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to select nonoxynol-9 from the list taught by Ingber. One of ordinary skill in the art would have been motivated to do so because Ingber suggests that nonoxynol-9 can be used in a preprocessing step for hemolyzing blood cells. See [0212]. There would have been a reasonable expectation of success because Ingber teaches a finite list of surfactants to choose from.
Regarding claim 5, Ingber teaches a processing buffer that comprises about 5% (i.e. 5g/100ml) to about 15% (i.e. 15g/100ml) surfactant. See [0222]. Therefore, Ingber suggests a concentration of about 50 g/L to about 150 g/L.
Ingber does not teach a somatic cell digestion agent (SDA) at a concentration of about 0.01 g/L to about 10 g/L in a lysis buffer.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to optimize the concentration Ingber’s nonoxynol-9 surfactant. A person of ordinary skill in the art has good reason to pursue the known options within their technical grasp. There would have been a reasonable expectation of success because Ingber suggests a starting surfactant concentration range of about 50 g/L to about 150 g/L from which one of ordinary skill in the art could have optimized. MPEP 2144.05(II)(A) indicates that differences in concentration or temperature generally amount to “routine optimization” and will not support patentability unless there is evidence indicating the claimed feature is critical. “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 11, Ingber teaches preprocessing reagents that include degradative enzymes, e.g. nucleases. See [0213].
Regarding claim 12, Ingber teaches a process for detecting a microbe in a test sample. As shown in Fig. 17, the process comprises preprocessing the test sample, processing the test sample, capturing the microbe, separating the microbe (i.e. isolating) and detecting the microbe. See [0207].
Claim Interpretation: instant claim 13 recites “pure” culture and/or inoculum, which is interpreted as encompassing any culture and/or inoculum from the at least one isolated microorganism from the treated sample.
Regarding claim 13, Ingber teaches capturing, separating (i.e. isolating) and detecting a microbe. See [0207]. Ingber teaches microbeads for microbe capture. See [0028]. Ingber teaches culturing a microbe bound on microbead on a microbe-compatible culture medium, e.g. plated on agar. See [0336]. Isolated microbes can be used for analyses. See [0339]. In example 5, Ingber teaches plating microbeads with bound Candida on agar plates, incubating, and then counting Candida (i.e. an analysis). See [0758].
Regarding claim 28, Ingber teaches preprocessing reagents including surfactants, anticoagulants, and salts. See [0213]. Anticoagulants include sodium citrate. See [0227].
Regarding claim 41, Ingber teaches identifying a microbe bound to a microbe-binding molecule or substrate based on a microbe signature determined by mass spectrometric analysis. See claim 238 of Ingber.
Regarding claim 46, Ingber teaches bacteria present in blood. See [0885]. Ingber teaches detecting microbes including Staphylococcus epidermidis. See [0449]. Ingber teaches preprocessing a test sample, such as whole blood with a preprocessing reagent. See [0211]. The preprocessing reagents include surfactants. See [0213]. Exemplary surfactants include nonoxynol-9 (i.e. SDA). See [0223]. Ingber teaches that a surfactant can be dissolved in a buffer solution in any amount, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268]. Ingber discloses that for identification of microbe species, a microbe/microbial fragment signature library can be established. See [0192]. Ingber teaches MALDI-TOF analysis. See [0190].
Ingber does not teach yielding an at least 5% higher MALDI score as compared to a comparable method employing a lysis buffer that does not comprise the SDA. However, Ingber teaches identifying microbe species and MALDI-TOF analysis.
The instant specification discloses identifying microorganisms by MALDI-TOF/MS. See [0003]. In example 1, the specification teaches identifying Staphylococcus epidermidis isolated from positive blood cultures using different lysing agents namely saponin and nonoxynol-9. The concentration of each lysing agent is 0.52% (w/w). The score for acceptance of identification is 2.0 for standard database. See [0071]. Therefore, the instant specification indicates that at least 5% higher MALDI scores for S. epidermidis identification are achieved when nonoxynol-9 is present in a concentration of 0.52% (w/w).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to recognize that Ingber’s process yields at least 5% higher MALDI score as compared to a comparable method employing a lysis buffer that does not comprise the SDA based on the disclosure in the instant specification, because Ingber suggests: lysis buffers comprising nonoxynol-9 (i.e. SDA) at concentrations including 0.52% (v/v) (i.e. equivalent to 0.52% w/w) [0268]; identifying bacteria [0192]; S. epidermidis [0449]; and MALDI-TOF ([0190]). As such, Ingber renders the instantly claimed method obvious, so the properties would therefore necessarily follow.
Claim Interpretation: instant claim 49 requires the ratio of blood cells lysed to cells of at least one microorganism lysed following the contacting step to be at least about 2:1.
Regarding claim 49, Ingber teaches adding preprocessing reagent to a sample for hemolyzing blood cells. See [0212]. The preprocessing reagents include surfactants. See [0213]. Exemplary surfactants include nonoxynol-9 (i.e. SDA). See [0223]. Ingber teaches that a surfactant can be dissolved in a buffer solution in any amount, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268].
Ingber does not teach a ratio of blood cells lysed to cells of the at least one microorganism lysed following the contacting step that is at least about 2:1.
The instant specification discloses that the final concentration of the SDA when combined with the sample is not limited so long as SDA is used at a concentration that will hemolyze at least a portion of the blood cells, while leaving at least a portion of the microorganism in the sample intact and/or viable. The final concentration of SDA when contacted with the sample can be about, at least or at most 0.001%, 5%, or a number between the values by volume. See [0043].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention that the nonoxynol-9 (i.e. SDA) in Ingber’s lysing reagent necessarily results in a ratio of blood cells lysed to cells of the at least one microorganism lysed that is at least about 2:1, based on the disclosure in the instant specification, because Ingber suggests that the surfactants including nonoxynol-9 can be dissolved in a buffer solution in any amount. Ingber also suggests that hemolysis is a result of adding a preprocessing reagent comprising a nonoxynol-9 surfactant to a sample. Ingber further suggests surfactant amounts of about 0.001% (v/v) to about 5% (v/v).
Claim Interpretation: instant claim 50 requires at least about 50% of the cells of the at least one microorganism to remain intact and/or viable following the contact step.
Regarding claim 50, Ingber teaches adding preprocessing reagent to a sample for hemolyzing blood cells. See [0212]. The preprocessing reagents include surfactants. See [0213]. Exemplary surfactants include nonoxynol-9 (i.e. SDA). See [0223]. Ingber teaches that a surfactant can be dissolved in a buffer solution in any amount, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268].
Ingber does not teach at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99% of the cells of the at least one microorganism to remain intact and/or viable following the contact step
The instant specification discloses that the final concentration of SDA when contacted with the sample can be about, at least or at most 0.001%, 5%, or a number between the values by volume. See [0043].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention that the nonoxynol-9 (i.e. SDA) in Ingber’s lysing reagent necessarily results in at least about 50% of the at least one microorganism remaining intact and/or viable, based on the disclosure in the instant specification, because Ingber suggests that the surfactants including nonoxynol-9 can be dissolved in a buffer solution in any amount. Ingber also suggests that hemolysis is a result of adding a preprocessing reagent comprising a nonoxynol-9 surfactant to a sample. Ingber further suggests surfactant amounts of about 0.001% (v/v) to about 5% (v/v).
Regarding claim 52, Ingber teaches a processing or capture buffer with a pH ranging from about 6 to about 10, which overlaps with the instantly claimed requirement for the lysis buffer to be acidic (i.e. pH <7). See [0268].
Regarding claim 55, Ingber does not teach saponin or polidocanol. Therefore Ingber meets the instantly claimed limitation.
Claims 15 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ingber (US 2014/0227723), as applied to claims 1, 2, 4-5, 11-13, 28, 41, 46, 49-50, 52 and 55 above, and further in view of Kircher (US 2015/0125895, as previously relied upon).
Regarding claim 15, Ingber teaches identifying a microbe bound to a microbe-binding molecule or substrate based on a microbe signature determined by mass spectrometric analysis. See claim 238 of Ingber. Ingber discloses that substrates with captured microbial material can be directly subjected to MALDI-TOF analysis without separation of the captured microbial materials. See [0187].
Ingber does not teach depositing the at least one microorganism on a surface adapted to be placed in an apparatus configured to determine the identity of the at least one microorganism by mass spectrometry; treating the deposited sample with a volatile acid solution, wherein the volume percent of the volatile acid is at least 70% of the volatile acid solution combined with the deposited sample; and placing a matrix over the treated deposited sample.
Kircher teaches MALDI-TOF/MS (i.e. mass spectrometry) identification. Specifically, Kircher teaches suspending a bacterial pellet in deionized water. A portion of the suspension is spotted (e.g. deposited) onto a MALDI-TOF/MS target plate (e.g. a surface adapted to be placed in mass spec.) for bacterial identification and allowed to air dry. Formic acid (e.g. volatile acid) of a 70% aqueous solution is overlaid onto the dried spotted sample and allowed to air dry. The dried sample is overlaid with MALDI-TOF/MS matrix solution. See [0061].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to apply Kircher’s mass spectrometry identification process to Ingber’s captured microbial materials (i.e. at least one microorganism). One of ordinary skill in the art would have been motivated to do so because Kircher suggests using MALDI-TOF/MS for the rapid identification of microbial cells from positive blood culture samples (see [0013]). There would have been a reasonable expectation of success because Ingber discloses that the captured microbial material can be directly subjected to MALDI-TOF (see [0187]).
Regarding claim 17, Kircher teaches overlaying a dried spotted sample [containing bacteria] with formic acid (e.g. volatile acid) in a 70% aqueous solution. See [0061].
Regarding claim 18, Kircher, in example 2, teaches spotting a portion of a bacterial pellet suspension onto a MALDI-TOF/MS target plate for bacterial identification and allowed to air dry. Formic acid is overlaid onto the dried spotted sample and allowed to air dry. The sample is overlaid with a MALDI-TOF/MS matrix solution, which is prepared with 47.5% acetonitrile (e.g. organic solvent), and allowed to air dry before identification by MALDI-TOF. See [0061].
MPEP 2144.04(IV)(C) states that “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results”.
Regarding claim 19, Kircher teaches pre-treating a portion of each PBC (positive blood culture) sample with a choline chloride solution. After incubation with the choline chloride solution, 8 ml of each “lyse and wash” buffer is added to the sample. See [0060].
Regarding claim 20, Kircher teaches pre-treating a portion of each PBC sample with 0.5 ml of a 20% choline chloride solution. See [0060]. With respect to instant formula 2, choline chloride aligns with an embodiment in which R1, R2 and R3 are each separately methyl groups and X is a negative Cl.
Response to Arguments
Applicant's arguments, filed 02/09/2026, with respect to the previous rejections under 35 U.S.C. §103 have been fully considered but they do not apply to the new grounds for rejection set forth above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-5, 11-13, 15, 17-20, 28, 41, 46, 49-50, 52, and 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No.11225681 in view of Ingber (US 2014/0227723), Kircher (US 2015/0125895, as previously relied upon) and Modak (US 2004/0102429).
Patent claim 1 recites a method for isolating and concentrating viable microorganisms from a positive blood culture sample comprising: mixing a portion of a positive blood culture sample with a buffer for isolating and concentrating viable microorganisms from a positive blood culture sample, the buffer consisting of: a nutrient base solution consisting of casein peptone at a concentration in the buffer of about 8 g/L to about 35 g/L, sodium chloride at a concentration in the buffer of about 2 g/L to about 10 g/L, soy peptone at a concentration in the buffer of about 1.5 g/L to about 15 g/L, and potassium phosphate at a concentration in the buffer of about 0.5 g/L to about 5 g/L and optionally at least one other nutrient; at least one non-ionic detergent consisting of saponin at a concentration in the buffer of about 0.01 g/L to about 10 g/L and polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether [i.e. Triton™ X-100] at a concentration in the buffer of 0.335 g/L; optionally, ammonium chloride; and at least one thiol consisting of L-cysteine at a concentration in the buffer of about 0.01 g/L to about 2.5 g/L and sodium thioglycolate at a concentration in the buffer of about 0.01 g/L to about 2.5 g/L, wherein the relative amounts of the nutrient base solution, the at least one non-ionic detergent, and the at least one thiol in the buffer are selected to preserve the viability of S. pneumoniae, to produce a mixture, wherein the amount of the buffer relative to the positive blood culture sample is such that blood cells in the positive blood culture sample are lysed and the viability of the microorganisms in the positive blood culture sample is preserved [relevant to instant claims 49 and 50]; optionally, incubating the mixture; centrifuging the mixture to produce a pellet [e.g. isolating at least one microorganism] and a supernatant; discarding the supernatant while retaining the pellet; resuspending the pellet with the buffer to create a resuspended pellet; centrifuging the resuspended pellet to produce a second supernatant and a second pellet; and discarding the second supernatant while retaining the second pellet containing the viable microorganisms.
Patent claim 2 recites the method of claim 1, wherein the portion of the positive blood culture sample is mixed with an equal volume of buffer to produce the mixture.
Patent claim 3 recites the method of claim 1, further comprising resuspending the second pellet in a solution and performing at least one downstream testing of the resuspended second pellet selected from the group consisting of identification of the microorganisms by mass spectrometry, phenotypic identification, antimicrobial susceptibility testing, and molecular testing.
The patent claims lack: contacting a sample comprising blood cells and at least one microorganism with a lysis buffer comprising instant formula 1 where x is 8-12 and y is 6-11 (relevant to instant claim 1), wherein y is 8-10 (relevant to instant claim 2), wherein SDA is nonoxynol-9 (relevant to instant claim 3); wherein the lysis buffer comprising one or more proteinases and/or one or more nucleases (relevant to instant claim 11); isolating the at least one microorganism from the treated sample (relevant to instant claim 12); further comprising preparing a plated culture and/or an inoculum from the at least one isolated microorganism and analyzing the at least one isolated microorganism from the plated pure culture and/or inoculum (relevant to instant claim 13); further comprising depositing at least one isolated microorganism on a surface to be placed in a mass spectrometry apparatus; treating the deposited sample with formic acid, wherein the volume percent is about 70% to about 90%; and placing a matrix over the treated deposited sample (relevant to instant claims 15 and 17); wherein prior to treating the deposited sample with a volatile acid solution, treating the deposited sample with an organic solvent and drying the deposited sample (relevant to instant claim 18); further comprising contacting the sample with a choline containing solution (relevant to instant claims 19-20); further comprising identifying the at least one microorganism (relevant to instant claim 41); wherein the method yields an at least 5% higher MALDI score (relevant to instant claim 46); wherein the ratio of blood cells lysed to cells of at least one microorganism lysed following the contact step is at least about 2:1 (relevant to instant claim 49); wherein at least 50% cells of at least one microorganism remain intact and/or viable (relevant to instant claim 50); wherein the lysis buffer is acidic (relevant to instant claim 52); and it excludes, e.g. saponin and/or polidocanol (relevant to instant claim 55).
However, Ingber teaches preprocessing reagents including surfactants and degradative enzymes, e.g. nucleases. See [0213]. Surfactants include nonoxynol-9 (i.e. SDA) and Triton™ x100. See [0223] (relevant to instant claims 1,2, 4 and 11). Ingber teaches separating the microbe (i.e. isolating) and detecting the microbe. See [0207] (relevant to instant claim 12). Ingber teaches plating microbeads with bound Candida on agar plates, incubating, and then counting Candida (i.e. an analysis). See [0758] (relevant to instant claim 13). Kircher mass spectrometry identification where a portion of a suspension is spotted onto a MALDI-TOF/MS target plate for bacterial identification and allowed to air dry and formic acid (e.g. volatile acid) in a 70% aqueous solution is overlaid onto the dried spotted sample and allowed to air dry. The dried sample is overlaid with MALDI-TOF/MS matrix solution which is prepared with 47.5% acetonitrile (e.g. organic solvent). See [0061] (relevant to instant claims 15, and 17-18). Kircher teaches pre-treating blood cultures with choline chloride. See [0060] (relevant to instant claim 19-20). Ingber teaches MALDI-TOF analysis. See [0190]. Ingber teaches Staphylococcus epidermidis. See [0449]. Ingber teaches preprocessing whole blood with a preprocessing reagent. See [0211]. The preprocessing reagents include surfactants. See [0213]. Ingber teaches that a surfactant can be dissolved, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268] (relevant to instant claims 46, and 49-50). Ingber teaches a processing buffer with a pH ranging from about 6 to about 10. See [0268] (relevant to instant claim 52). Ingber does not teach saponin, or polidocanol (relevant to instant claim 55).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute the nonoxynol-9 of Ingber for the polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether [i.e. Triton™ X-100] recited in patent claim 1, and to further apply the mass spectrometry identification of Kircher in order to process a sample.
The patent claims lack an SDA of formula 1 wherein x is 8-12 and y is 6-11 and wherein the SDA is present in the composition at a concentration of at least 0.1% (w/v) (relevant to instant claim 56).
However, Modak teaches mixing a formulation containing 8% nonoxynol-9 with red blood cells. See [0072] (relevant to instant claim 56).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine the positive blood culture sample recited in patent claim 1 with the 8% nonoxynol-9 of Modak.
Claims 1-2, 4-5, 11-13, 15, 17-20, 28, 41, 46, 49-50, 52, and 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 8603769 in view of Ingber (US 2014/0227723), Kircher (US 2015/0125895, as previously relied upon) and Modak (US 2004/0102429).
Patent claim 1 recites a method for isolating viable microorganism from a positive blood culture sample determined to contain at least one microorganism therein, comprising: obtaining a positive blood culture sample determined to contain at least one viable microorganism; incubating [e.g. contacting] the sample with a choline-containing solution and a lysis buffer, wherein the lysis buffer lyses blood cells in the sample; isolating the at least one viable microorganism [e.g. lysed blood cells and viable microorganisms are relevant to instant claims 49 and 50] from the remainder of the sample; optionally, preparing a plated pure culture or an inoculum from the isolated viable microorganism; and analyzing the isolated viable microorganism or optional plated pure culture or inoculum.
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Patent claim 4 recites the method of claim 1, wherein the choline-containing solution comprises at least one quarternary ammonium salt containing a N,N,N-trimethylethanolammonium cation selected from the group consisting of the general formula:
wherein R1, R2, and R3 independently represent one selected from the group consisting of a saturated hydrocarbon group, an unsaturated hydrocarbon group, an aromatic group, and combinations thereof; and X represents a negative charged group.
Patent claim 14 recites the method of claim 1, wherein the lysis buffer comprises at least one detergent selected from the group consisting of octyl-B-D-glucopyranoside, n-nonyl β-D-glucoside, octanoyl-N-methylglucamide, nonanoyl-N-methylglucamide, decanoyl-N-methylglucamide, n-dodecyl-β-D-maltoside, n-octyl-rac-2,3-dioxypropylsulfoxide, Triton X-100, saponin, and combinations thereof.
The patent claims lack: contacting a sample comprising blood cells and at least one microorganism with a lysis buffer comprising instant formula 1 where x is 8-12 and y is 6-11 (relevant to instant claim 1), wherein y is 8-10 (relevant to instant claim 2), wherein SDA is nonoxynol-9 (relevant to instant claim 3); wherein the lysis buffer comprising one or more proteinases and/or one or more nucleases (relevant to instant claim 11); isolating the at least one microorganism from the treated sample (relevant to instant claim 12); further comprising preparing a plated culture and/or an inoculum from the at least one isolated microorganism and analyzing the at least one isolated microorganism from the plated pure culture and/or inoculum (relevant to instant claim 13); further comprising depositing at least one isolated microorganism on a surface to be placed in a mass spectrometry apparatus; treating the deposited sample with formic acid, wherein the volume percent is about 70% to about 90%; and placing a matrix over the treated deposited sample (relevant to instant claims 15 and 17); wherein prior to treating the deposited sample with a volatile acid solution, treating the deposited sample with an organic solvent and drying the deposited sample (relevant to instant claim 18); further comprising identifying the at least one microorganism (relevant to instant claim 41); wherein the method yields an at least 5% higher MALDI score (relevant to instant claim 46); wherein the ratio of blood cells lysed to cells of at least one microorganism lysed following the contact step is at least about 2:1 (relevant to instant claim 49); wherein at least 50% cells of at least one microorganism remain intact and/or viable (relevant to instant claim 50); wherein the lysis buffer is acidic (relevant to instant claim 52); and it excludes, e.g. saponin and/or polidocanol (relevant to instant claim 55).
However, Ingber teaches preprocessing reagents including surfactants and degradative enzymes, e.g. nucleases. See [0213]. Surfactants include nonoxynol-9 (i.e. SDA) and Triton™ x100. See [0223] (relevant to instant claims 1,2, 4 and 11). Ingber teaches separating the microbe (i.e. isolating) and detecting the microbe. See [0207] (relevant to instant claim 12). Ingber teaches plating microbeads with bound Candida on agar plates, incubating, and then counting Candida (i.e. an analysis). See [0758] (relevant to instant claim 13). Kircher mass spectrometry identification where a portion of a suspension is spotted onto a MALDI-TOF/MS target plate for bacterial identification and allowed to air dry and formic acid (e.g. volatile acid) in a 70% aqueous solution is overlaid onto the dried spotted sample and allowed to air dry. The dried sample is overlaid with MALDI-TOF/MS matrix solution which is prepared with 47.5% acetonitrile (e.g. organic solvent). See [0061] (relevant to instant claims 15, and 17-18). Ingber teaches MALDI-TOF analysis. See [0190]. Ingber teaches Staphylococcus epidermidis. See [0449]. Ingber teaches preprocessing whole blood with a preprocessing reagent. See [0211]. The preprocessing reagents include surfactants. See [0213]. Ingber teaches that a surfactant can be dissolved, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268] (relevant to instant claims 46, and 49-50). Ingber teaches a processing buffer with a pH ranging from about 6 to about 10. See [0268] (relevant to instant claim 52). Ingber does not teach saponin, or polidocanol (relevant to instant claim 55).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute the nonoxynol-9 of Ingber for Triton X-100 recited in patent claim 14, and to further apply the mass spectrometry identification of Kircher in order to process a sample.
The patent claims lack an SDA of formula 1 wherein x is 8-12 and y is 6-11 and wherein the SDA is present in the composition at a concentration of at least 0.1% (w/v) (relevant to instant claim 56).
However, Modak teaches mixing a formulation containing 8% nonoxynol-9 with red blood cells. See [0072] (relevant to instant claim 56).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine the positive blood culture sample recited in patent claim 1 with the 8% nonoxynol-9 of Modak.
Claims 1-2, 4-5, 11-13, 15, 17-20, 28, 41, 46, 49-50, 52, and 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9631221 in view of Ingber (US 2014/0227723), Kircher (US 2015/0125895, as previously relied upon) and Modak (US 2004/0102429).
Patent claim 1 recites a method for characterizing at least one microorganism in a sample for identification of microorganisms therein, the method comprising:
(a) obtaining a sample containing at least one microorganism, wherein the sample is in a suspension;
(b) depositing at least a portion of the obtained sample on a solid surface adapted to be placed in an apparatus configured to determine the identity of microorganisms by mass spectrometry;
(c) drying the deposited sample;
(d) treating the deposited and dried sample with a volatile acid solution, wherein the volume percent of the volatile acid is at least 70% of the volatile acid solution combined with the sample, and the volatile acid solution is a volatile acid in water or a volatile solution in an organic solvent;
(e) drying the treated sample;
(f) placing a matrix over the treated and dried sample; and
(g) identifying the microorganisms by a mass spectrometry.
Patent claim 4 recites the method of claim 1, wherein the volatile acid solution is formic acid in water at a volume percent of about 80% when combined with the sample.
Patent claim 5 recites the method of claim 1, wherein the volatile acid solution is formic acid in water at a volume percent of about 90% when combined with the sample.
Patent claim 6 recites the method of claim 1, wherein the organic solvent is selected from the group consisting of ethanol, methanol, isopropanol, acetonitrile, acetone, and ethyl acetate.
Patent claim 7 recites the method of claim 1, further comprising using a non-ionic detergent, wherein the detergent can be used during the steps selected from the group consisting of obtaining the sample, treating the sample with the volatile acid solution, and combinations thereof.
Patent claim 12 recites a method for preparing a positive blood culture sample for identification of microorganisms therein, the method comprising:
(a) obtaining a positive blood culture sample determined to contain at least one microorganism;
(b) adding a lysis buffer to the obtained sample, wherein the lysis buffer is selected to lyse the blood cells in the sample while the microorganism remains intact;
(c) concentrating the microorganisms in the sample containing lysis buffer, wherein the concentrated sample is a suspension;
(d) separating the concentrated portion of the sample in the suspension from the remainder;
(e) depositing at least a portion of the separated microbial sample in the suspension on a surface adapted to be placed in an apparatus configured to determine the identify of a microorganism by mass spectrometry;
(f) drying the deposited sample;
(g) treating the deposited and dried sample with a volatile acid solution, wherein the volume percent of the volatile acid is at least 70% of the volatile acid solution combined with the sample, and the volatile acid solution is a volatile acid in an organic solvent;
(h) drying the treated sample;
(i) placing a matrix over the treated and dried sample; and
(j) drying the sample.
The patent claims lack: contacting a sample comprising blood cells and at least one microorganism with a lysis buffer comprising instant formula 1 where x is 8-12 and y 7 is 6-11 (relevant to instant claim 1), wherein y is 8-10 (relevant to instant claim 2), wherein SDA is nonoxynol-9 (relevant to instant claim 3); wherein the lysis buffer comprising one or more proteinases and/or one or more nucleases (relevant to instant claim 11); isolating the at least one microorganism from the treated sample (relevant to instant claim 12); further comprising preparing a plated culture and/or an inoculum from the at least one isolated microorganism and analyzing the at least one isolated microorganism from the plated pure culture and/or inoculum (relevant to instant claim 13); further comprising contacting the sample with a choline containing solution (relevant to instant claims 19-20); further comprising identifying the at least one microorganism (relevant to instant claim 41); wherein the method yields an at least 5% higher MALDI score (relevant to instant claim 46); wherein the ratio of blood cells lysed to cells of at least one microorganism lysed following the contact step is at least about 2:1 (relevant to instant claim 49); wherein at least 50% cells of at least one microorganism remain intact and/or viable (relevant to instant claim 50); wherein the lysis buffer is acidic (relevant to instant claim 52); and it excludes, e.g. saponin and/or polidocanol (relevant to instant claim 55).
However, Ingber teaches preprocessing test samples. See [0207]. Ingber teaches preprocessing reagents including surfactants and degradative enzymes, e.g. nucleases. See [0213]. Surfactants include nonoxynol-9 (i.e. SDA) and Triton™ x100. See [0223] (relevant to instant claims 1,2, 4 and 11). Ingber teaches separating the microbe (i.e. isolating) and detecting the microbe. See [0207] (relevant to instant claim 12). Ingber teaches plating microbeads with bound Candida on agar plates, incubating, and then counting Candida (i.e. an analysis). See [0758] (relevant to instant claim 13). Kircher teaches pre-treating blood cultures with choline chloride. See [0060] (relevant to instant claim 19-20). Ingber teaches MALDI-TOF analysis. See [0190]. Ingber teaches Staphylococcus epidermidis. See [0449]. Ingber teaches preprocessing whole blood with a preprocessing reagent. See [0211]. The preprocessing reagents include surfactants. See [0213]. Ingber teaches that a surfactant can be dissolved, e.g. ranging from about 0.001% (v/v) to about 5% (v/v). See [0268] (relevant to instant claims 46, and 49-50). Ingber teaches a processing buffer with a pH ranging from about 6 to about 10. See [0268] (relevant to instant claim 52). Ingber does not teach saponin, or polidocanol (relevant to instant claim 55).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to apply method recited in patent claim 1 to test sample preprocessed with nonoxynol-9 comprising at least one microbe of Ingber, and to further adjust the concentration based on Kircher’s suggestion that doing so may affect the MALDI score in order to process a sample.
The patent claims lack an SDA of formula 1 wherein x is 8-12 and y is 6-11 and wherein the SDA is present in the composition at a concentration of at least 0.1% (w/v) (relevant to instant claim 56).
However, Modak teaches mixing a formulation containing 8% nonoxynol-9 with red blood cells. See [0072] (relevant to instant claim 56).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine the positive blood culture sample recited in patent claim 1 with the 8% nonoxynol-9 of Modak.
Response to Arguments
Applicant's arguments, filed 02/09/2026, with respect to the previous Double Patenting Rejections have been fully considered but they do not apply to the new grounds for rejection set forth above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY C BREEN whose telephone number is (571)272-0980. The examiner can normally be reached M-Th 7:30-4:30, F 8:30-1:30 (EDT/EST).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/K.C.B./Examiner, Art Unit 1657
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