The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 4, 2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 19-24, 26-30 are canceled. Claims 1-18, 25, 31-35, 36-52, 53 are under consideration.
Priority: This application is a 371 of PCT/EP2020/050006, filed January 2, 2020, which claims benefit to foreign application EP 19150438, filed January 4, 2019. A copy of the foreign priority document has been received in the instant application on June 21, 2021, and is in the English language.
Objections and Rejections
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.
Claims 18, 25, 36-43, 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Wyrich et al. (WO 2014146780; IDS 11.11.21, previously cited), Mengual et al. (2018 Quantitative RNA Analysis from Urine Using Real Time PCR. In: Schulz, W., Hoffmann, M., Niegisch, G. (eds) Urothelial Carcinoma. Methods in Molecular Biology, vol 1655, ch. 17, pages 227-237) and Mohan (2003 CalBioChem® Buffers Guide: 37 pages; previously cited). Wyrich et al. disclose methods, compositions, devices for stabilizing extracellular nucleic acid population in a cell-containing biological sample (at least abstract). Wyrich et al. disclose a stabilizing composition comprising butanamide, a caspase inhibitor, EDTA, a solvent and/or buffering agent, and one or more poly(oxyethylene) polymers, where the stabilizing composition is suitable for stabilizing cell-containing biological samples, including urine (at least p. 52 lines 39 to p. 53 lines 21; instant claim 18). Wyrich et al. disclose a collection device comprising the stabilizing composition (at least p. 58-60; instant claim 25). Wyrich et al. disclose the stabilizing composition is comprised in a solvent, e.g. water, a buffer, e.g. biological buffer such as MOPS, TRIS, PBS, and the like, and used for stabilization of cell-containing biological samples (at least p. 34 lines 4-7). While Wyrich et al. disclose that the butanamide is used in a concentration that exerts a stabilizing effect on the nucleic acid population (p. 14 lines 6-8), Wyrich et al. also disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34). Wyrich et al. disclose that a compound of formula 1 is effective in achieving a stabilizing effect either alone or when being used in addition to butanamide (p. 19 lines 5-7).
Mengual et al. disclose in the last years, urine is emerging as a biological fluid suitable for analysis (at least p. 227-228). Mengual et al. disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230).
Mohan discloses biological buffers for biological applications have distinctive characteristics including exhibiting pKa values at or near physiological pH (at least p. 10). Mohan discloses commonly used buffers include among others phosphate buffered saline (PBS) having a pH 7.4 (p. 22), tris buffered saline (TBS) having a pH 7.4, (p. 23), tris pKa 8.3 (p. 13), MOPS pKa 7.2 (p. 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed stabilizing composition comprising a caspase inhibitor, EDTA, a solvent and a buffering agent, and one or more poly(oxyethylene) polymers, where the composition does not comprise a butanamide (instant claims 18, 25, 36-43), and a collection device comprising the claimed stabilizing composition (instant claims 18, 25, 36-43), where the stabilizing composition is buffered and has a pH of ~8.0 because Wyrich et al. disclose stabilizing compositions for biological samples, including urine, where the stabilizing composition comprises a caspase inhibitor, EDTA, a solvent and/or buffering agent, one or more poly(oxyethylene) polymers, where the stabilizing composition does not need to comprise butanamide, and Mengual et al. disclose a composition also for collecting urine, comprising EDTA, a buffering agent, at a pH 8.0. One of ordinary skill would have a reasonable expectation of success because the components and/or conditions for collecting and stabilizing a biological fluid, such as urine, were known and disclosed in the prior art.
Regarding instant claim 36, Wyrich et al. disclose the at least one poly(oxyethylene) polymer is polyethylene glycol (at least p. 51 lines 22-24).
Regarding instant claim 38, Wyrich et al. disclose the stabilizing composition comprises butanamide, a caspase inhibitor, EDTA, a solvent and/or buffering agent, and one or more poly(oxyethylene) polymers, where the poly(oxyethylene) polymer is polyethylene glycol, where the stabilization achieves stabilization of extracellular nucleic acid (at least p. 66 lines 1-20). As also noted above, Wyrich et al. also disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34), where a formula 1 compound is a primary, secondary, tertiary amide (p. 19 lines 24-26). Wyrich et al. disclose that a compound of formula 1 is effective in achieving a stabilizing effect either alone or when being used in addition to butanamide (p. 19 lines 5-7). Wyrich et al. disclose the chelating agents can include combinations with other chelating agents, such as EDTA and salts of carboxylic acids such as citrate (at least p. 30 lines 15-34). Therefore, it would have been obvious to arrive at the recited stabilizing composition comprising EDTA, sodium citrate, at least one polyethylene glycol, a caspase inhibitor, a buffering agent, an amide, where the composition does not comprise butanamide, where the components disclosed in the stabilizing composition of Wyrich et al. would include a preservative having antimicrobial effects (i.e. EDTA, sodium citrate), and to further arrive at a pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan). The motivation to do so is given by Wyrich et al., which disclose the same components recited are included in a composition for stabilizing cell-containing samples, including urine samples. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components and/or conditions recited form a composition for stabilizing cell-containing samples, including urine samples.
Regarding instant claim 39, Wyrich et al. disclose the stabilizing composition is a liquid (at least p. 51 line 20). Wyrich et al. disclose an EDTA concentration in the range selected from 0.05 mM to 100 mM (at least p. 57 lines 33-35, p. 65 lines 26-27). Wyrich et al. disclose the stabilizing composition is contacted with the urine sample at a volumetric ratio selected from 1:1 to 1:10, including 1:2 to 1:5 (at least p. 67 lines 17-22). Therefore, it would have been obvious to arrive at the recited liquid stabilizing composition comprising EDTA at 100mM up to the solubility limit, sodium citrate, at least one polyethylene glycol, a caspase inhibitor, a buffering agent, an amide, a pH ~8.0, and a ratio of stabilizing composition to sample of 1:1 to 1:10, including 1:2 to 1:5, where the components disclosed in the stabilizing composition of Wyrich et al. would include a preservative having antimicrobial effects (i.e. EDTA, sodium citrate) and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan). The motivation to do so is given by Wyrich et al., which disclose the same components recited are included in a composition for stabilizing cell-containing samples, including urine samples. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components and/or conditions recited form a composition for stabilizing cell-containing samples, including urine samples.
Regarding instant claim 41, it is noted that the claim is still drawn to the recited stabilizing composition regardless of the result to be achieved recited in the wherein clause.
Regarding instant claim 42, Wyrich et al. disclose the container is an evacuated tube (at least p. 59 lines 31-40 ).
Regarding instant claim 43, Wyrich et al. disclose the container comprises the stabilizing composition in liquid form to collect the cell-containing sample where the volumetric ratio of the stabilizing composition to the cell-containing sample is selected from 1:1 to 1:10 and 1:2 to 1:5 (at least p. 60 lines 30-40).
Regarding instant claims 44-45, as noted above, Wyrich et al. disclose a collection device comprising the stabilizing composition (at least p. 58-60) and the collection is for collecting urine (at least p. 60 lines 18-19), where the stabilizing composition is comprised in a solvent, e.g. water, a buffer, e.g. biological buffer such as MOPS, TRIS, PBS, and the like, and used for stabilization of cell-containing biological samples (at least p. 34 lines 4-7). Mengual et al. disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing (at least p. 229-230). Therefore, it would have been obvious to arrive at the recited device comprising a urine sample and the stabilizing composition at a pH ~8.0 for the stabilizing composition and stabilized sample because the prior art (Mengual et al.) disclose the composition for collecting and storing the urine has a pH 8.0 prior to analysis.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that Wyrich et al. and Mohan fail to teach or suggest any specific pH value for the stabilization of extracellular acids in biological samples, let alone urines samples specifically. See Applicant’s remarks p. 10-14.
Applicant’s remarks are not persuasive. Mengual et al. is newly cited as a 103 reference with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230).
Therefore, it would have been obvious to arrive at the recited stabilizing composition having a pH ~8.0 because the prior art (Mengual et al.) disclose the composition for collecting and storing the urine has a pH 8.0 prior to analysis. One of ordinary skill would have a reasonable expectation of success because the components and/or conditions for collecting and stabilizing a biological fluid, such as urine, were known and disclosed in the prior art. In this instance, Wyrich et al. disclose stabilizing compositions for biological samples, including urine, where the stabilizing composition comprises a caspase inhibitor, EDTA, a solvent and/or buffering agent, one or more poly(oxyethylene) polymers, and where the stabilizing composition does not need to comprise butanamide. Mengual et al. disclose a composition also for collecting urine, comprising EDTA, a buffering agent, at a pH 8.0. Therefore, it would have been obvious to incorporate a pH 8.0 as suggested in Mengual et al. in the stabilizing composition of Wyrich et al. comprising a caspase inhibitor, EDTA, a solvent and/or buffering agent, one or more poly(oxyethylene) polymers, and where the stabilizing composition does not need to comprise butanamide because the prior art reasonably disclose the same combination of components and/or conditions in a composition for containing a urine sample.
Applicant asserts that the present application demonstrates unexpected results resulting from the basic pH of the stabilizing composition.
Applicant’s remarks are not persuasive. In this instance, the prior art (Mengual et al.) already recognize a pH ~8.0 for the composition containing the urine sample prior to analysis.
Additionally, as previously noted, it is known that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). MPEP 2123.
Further, MPEP 2144.04 also notes that omission of an element is obvious.
In this instance, Wyrich et al. also disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34), where a formula 1 compound is a primary, secondary, tertiary amide (p. 19 lines 24-26). Wyrich et al. disclose that a compound of formula 1 is effective in achieving a stabilizing effect either alone or when being used in addition to butanamide (p. 19 lines 5-7).
Therefore, Wyrich et al. fairly disclose not including an amount of butanamide in the stabilizing composition when additional stabilizing agents such as caspase inhibitor and/or an amide compound are incorporated into the stabilizing composition.
In this instance, Wyrich et al. and Mengual et al. disclose the same components and/or conditions in a stabilizing composition for the same purpose of stabilizing an extracellular nucleic acid population in a cell-containing biological urine sample and at the same pH recited (pH ~8.0). Wyrich et al. also disclose that an amount of butanamide < 2% (w/v), which includes 0%, is particularly effective (see teachings of Wyrich et al. above).
Therefore, Applicant’s remarks regarding unexpectedly superior and/or surprising properties are not persuasive.
See also the reasons noted on at least p. 7-9 of the December 15, 2025 final office action.
Claims 1-18, 25, 31-52, 53 are rejected under 35 U.S.C. 103 as being unpatentable over Wyrich et al. (WO 2014146780; IDS 11.11.21, previously cited) in view of Mengual et al. (2018 Quantitative RNA Analysis from Urine Using Real Time PCR. In: Schulz, W., Hoffmann, M., Niegisch, G. (eds) Urothelial Carcinoma. Methods in Molecular Biology, vol 1655, ch. 17, pages 227-237), Mohan (2003 CalBioChem® Buffers Guide: 37 pages; previously cited), and evidenced by Qiagen (QIAamp® DNA Micro Handbook for purification of genomic DNA 2014: 40 pages; previously cited). The teachings of Wyrich et al., Mengual et al., and Mohan are noted above.
As noted above, Wyrich et al. disclose methods, compositions, devices for stabilizing extracellular nucleic acid population in a cell-containing biological sample (at least abstract). Wyrich et al. disclose a method for stabilization, comprising contacting the cell-containing sample with the stabilizing composition comprising butanamide, a caspase inhibitor, EDTA, a solvent and/or buffering agent, and one or more poly(oxyethylene) polymers, where the poly(oxyethylene) polymer is polyethylene glycol, where the stabilization achieves stabilization of extracellular nucleic acid (at least p. 66 lines 1-20), where the cell-containing sample is selected from among others urine samples (at least p. 66 lines 30-34, 41), where the stabilization does not involve a cross-linking agent (at least p. 66 lines 26-27). Wyrich et al. disclose the stabilizing composition is comprised in a solvent, e.g. water, a buffer, e.g. biological buffer such as MOPS, TRIS, PBS, and the like, and used for stabilization of cell-containing biological samples (at least p. 34 lines 4-7). As also noted above, Wyrich et al. disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34), where a formula 1 compound is a primary, secondary, tertiary amide (p. 19 lines 24-26), and where that a compound of formula 1 is effective in achieving a stabilizing effect when used alone without butanamide (p. 19 lines 5-7). Therefore, Wyrich et al. disclose not including an amount of butanamide in the stabilizing composition when additional stabilizing agents such as caspase inhibitor and/or an amide compound are incorporated into the stabilizing composition.
Mengual et al. disclose in the last years, urine is emerging as a biological fluid suitable for analysis (at least p. 227-228). Mengual et al. disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230).
Mohan discloses biological buffers for biological applications have distinctive characteristics including exhibiting pKa values at or near physiological pH (at least p. 10). Mohan discloses commonly used buffers include among others phosphate buffered saline (PBS) having a pH 7.4 (p. 22), tris buffered saline (TBS) having a pH 7.4, (p. 23), tris pKa 8.3 (p. 13), MOPS pKa 7.2 (p. 13).
Qiagen discloses DNA should be maintained at pH > 7.0 and is subject to degradation by acid hydrolysis (at least p. 12).
It would have been obvious one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method for stabilizing a urine sample comprising contacting the urine with a stabilizing composition comprising a caspase inhibitor, EDTA, a solvent and a buffering agent, at least one poly(oxyethylene) polymer where the at least one poly(oxyethylene) polymer is polyethylene glycol, where the components disclosed in the stabilizing composition of Wyrich et al. include a preservative having antimicrobial effects (i.e. EDTA), and further where the stabilizing composition is buffered, has a pH of ~8.0, and does not involve a cross-linking agent and does not comprise a butanamide (instant claims 1-5, 7, 9, 11, 12, 15, 18, 36-37, 40-41, 47, 50). The motivation to do so is given by Wyrich et al. and Mengual et al., which disclose the same components and/or conditions recited are included in a composition for stabilizing cell-containing samples, including urine samples. It would have been obvious to arrive at a pH ~8.0 for the stabilizing composition and stabilized sample because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12). One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components and conditions recited form a composition for stabilizing cell-containing samples, including urine samples.
Regarding instant claim 4, Wyrich et al. disclose the chelating agents can include combinations with other chelating agents, such as EDTA and salts of carboxylic acids such as citrate (at least p. 30 lines 15-34) and Mengual et al. also disclose the composition for containing urine comprises EDTA, pH 8.0 (p. 229-230). Therefore, it would be obvious to combine another chelating agent (i.e. agent for inhibiting bacterial growth) such as sodium citrate with the EDTA in the stabilized composition of Wyrich et al. and Mengual et al.
Regarding instant claims 5, 7, as noted above, Wyrich et al. disclose the stabilizing composition is comprised in a solvent, e.g. water, a buffer, e.g. biological buffer such as MOPS, TRIS, PBS, and the like, and used for stabilization of cell-containing biological samples (at least p. 34 lines 4-7). Mengual et al. disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing (at least p. 229-230). Therefore, it would be obvious to arrive at a pH ~8.0 for the stabilizing composition and stabilized sample because the prior art (Mengual et al.) disclose the composition for collecting and storing the urine has a pH 8.0 prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12).
Regarding instant claim 6, Wyrich et al. disclose the stabilizing composition is contacted with the urine sample at a volumetric ratio selected from 1:1 to 1:10, including 1:2 to 1:5 (at least p. 67 lines 17-22).
Regarding instant claim 8, Wyrich et al. disclose an EDTA concentration in the range selected from 0.05 mM to 100 mM (at least p. 57 lines 33-35, p. 65 lines 26-27). Wyrich et al. disclose an EDTA concentration in the sample is in the range 0.5 to 40 mg/mL, including 20 mg/mL (at least p. 57 lines 37-41). It is known that “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). MPEP 2144.05. It would have been obvious to arrive at the recited EDTA concentration of 100 mM up to the solubility limit in the stabilized composition of Wyrich et al. and where the EDTA concentration in the sample is in the range 20 mg/mL-40 mg/mL in the method of stabilizing a urine sample as disclosed in Wyrich et al. by routine optimization.
Regarding instant claim 10, Wyrich et al. disclose the sample is contacted with at least one poly(oxyethylene) polymer, which is a high molecular weight poly(oxyethylene) polymer having a molecular weight of at least 1500 and a low molecular weight poly(oxyethylene) polymer (at least p. 63 lines 15-24), where it would be obvious to one of ordinary skill that the low molecular weight poly(oxyethylene) polymer is less than the molecular weight of 1500 (which has been identified as the high molecular weight poly(oxyethylene) polymer in Wyrich et al.).
Regarding instant claims 13, 38, 48, as noted above, Wyrich et al. disclose the stabilizing composition comprises butanamide, a caspase inhibitor, EDTA, a solvent and/or buffering agent, and one or more poly(oxyethylene) polymers, where the poly(oxyethylene) polymer is polyethylene glycol, where the stabilization achieves stabilization of extracellular nucleic acid (at least p. 66 lines 1-20). Wyrich et al. disclose the sample is contacted with at least one poly(oxyethylene) polymer, which is a high molecular weight poly(oxyethylene) polymer having a molecular weight of at least 1500, including 3000, or 4500-10000, and a low molecular weight poly(oxyethylene) polymer (at least p. 63 lines 15-24). As also noted above, Wyrich et al. also disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34), where a formula 1 compound is a primary, secondary, tertiary amide (p. 19 lines 24-26). Wyrich et al. disclose that a compound of formula 1 is effective in achieving a stabilizing effect either alone or when being used in addition to butanamide (p. 19 lines 5-7). Wyrich et al. disclose the chelating agents can include combinations with other chelating agents, such as EDTA and salts of carboxylic acids such as citrate (at least p. 30 lines 15-34). Therefore, it would have been obvious to arrive at the recited stabilizing composition comprising EDTA, sodium citrate, a high molecular weight polyethylene glycol having a molecular weight of at least 3000, a low molecular weight polyethylene glycol having a molecular weight of less than 1000, a caspase inhibitor, a buffering agent, an amide, where the composition does not comprise butanamide, where the components disclosed in the stabilizing composition of Wyrich et al. would include a preservative having antimicrobial effects (i.e. EDTA, sodium citrate) and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12). The motivation to do so is given by Wyrich et al., which disclose the same components recited are included in a composition for stabilizing cell-containing samples, including urine samples. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Regarding instant claims 14, 39, 49, as noted above, Wyrich et al. disclose the same components recited in the instant claims and at the same amounts, concentrations, and/or conditions (see above). Wyrich et al. disclose the stabilizing composition is a liquid (at least p. 51 line 20). Therefore, it would have been obvious to arrive at the recited liquid stabilizing composition comprising EDTA at 100mM up to the solubility limit, sodium citrate, a high molecular weight polyethylene glycol having a molecular weight of at least 6000, a low molecular weight polyethylene glycol having a molecular weight of less than 1000, a caspase inhibitor, a buffering agent, an amide, a pH ~8.0, and a ratio of stabilizing composition to sample of 1:1 to 1:10, including 1:2 to 1:5, where the components disclosed in the stabilizing composition of Wyrich et al. would include a preservative having antimicrobial effects (i.e. EDTA, sodium citrate) and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12). The motivation to do so is given by Wyrich et al., which disclose the same components recited are included in a composition for stabilizing cell-containing samples, including urine samples. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Regarding instant claim 15, Wyrich et al. disclose the stabilizing composition stabilizes extracellular DNA in the cell-containing sample, the cell-containing sample being urine (at least p. 36 lines 9-15, 19, 23).
Regarding instant claim 25, Wyrich et al. disclose a collection device comprising the stabilizing composition (at least p. 58-60), where as noted above, the stabilizing composition comprises a caspase inhibitor, EDTA, a solvent and/or buffering agent, at least one poly(oxyethylene) polymer where the at least one poly(oxyethylene) polymer is polyethylene glycol, where the components disclosed in the stabilizing composition of Wyrich et al. include a preservative having antimicrobial effects (i.e. EDTA), does not involve a cross-linking agent and does not comprise a butanamide, and where the stabilizing composition is buffered, has a pH of ~8.0 as suggested in Mengual et al.
Regarding instant claims 31-32, Wyrich et al. disclose a urine collection device for collecting the sample (at least p. 60 lines 17-19) and a container comprising the stabilizing composition, in dried form (at least p. 58-60). Therefore, it would have been obvious to arrive at the recited step of collecting urine in a container (instant claim 31) and then transferring a sample of the collected urine to the container comprising the stabilizing composition that is in dried form to thereby contact the urine sample with the stabilizing composition (instant claim 32), where as noted above, the stabilizing composition comprises a caspase inhibitor, EDTA, a solvent and/or buffering agent, at least one poly(oxyethylene) polymer where the at least one poly(oxyethylene) polymer is polyethylene glycol, where the components disclosed in the stabilizing composition of Wyrich et al. include a preservative having antimicrobial effects (i.e. EDTA), does not involve a cross-linking agent and does not comprise a butanamide, and where the stabilizing composition is buffered, has a pH of ~8.0 as suggested in Mengual et al.
Regarding instant claims 33-34, Wyrich et al. disclose that the urine collection device can also comprise the stabilizing composition comprising EDTA, in dried form (at least p. 59 lines 17 to p. 60 lines 40).
Regarding instant clams 16-17, 35, Wyrich et al. disclose further processing the stabilized sample to provide a cell sample and a cell-depleted portion and further isolating nucleic acids, including isolating extracellular nucleic acids from the cell-depleted portion of the stabilized sample and isolating nucleic acids from the cells removed from the stabilized sample (at least p. 67 lines 24 to p. 69 lines 4).
Regarding instant claim 42, Wyrich et al. disclose the container is an evacuated tube (at least p. 59 lines 31-40 ).
Regarding instant claim 43, Wyrich et al. disclose the container comprises the stabilizing composition in liquid form to collect the cell-containing sample where the volumetric ratio of the stabilizing composition to the cell-containing sample is selected from 1:1 to 1:10 and 1:2 to 1:5 (at least p. 60 lines 30-40).
Regarding instant claims 44-45, as noted above, Wyrich et al. disclose a collection device comprising the stabilizing composition (at least p. 58-60) and the collection is for collecting urine (at least p. 60 lines 18-19), where the stabilizing composition is comprised in a solvent, e.g. water, a buffer, e.g. biological buffer such as MOPS, TRIS, PBS, and the like, and used for stabilization of cell-containing biological samples (at least p. 34 lines 4-7). Mengual et al. disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing (at least p. 229-230). Therefore, it would have been obvious to arrive at the recited device comprising a urine sample and the stabilizing composition at a pH ~8.0 for the stabilizing composition and stabilized sample because the prior art (Mengual et al.) disclose the composition for collecting and storing the urine has a pH 8.0 prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12).
Regarding instant claim 46, Wyrich et al. disclose an EDTA concentration of 100 mM to 500 mM (at least p. 52 lines 6-8).
Regarding instant claims 51-52, Wyrich et al. disclose after a stabilization period, the method comprises further processing the stabilized sample to provide a cell sample and a cell-depleted portion and further isolating nucleic acids, including isolating extracellular nucleic acids from the cell-depleted portion of the stabilized sample and isolating nucleic acids from the cells removed from the stabilized sample (at least p. 67 lines 24 to p. 69 lines 4).
Regarding instant claim 53, it is known that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). MPEP 2123. Further, MPEP 2144.04 also notes that omission of an element is obvious. In this instance, Mengual et al. disclose a composition comprising EDTA, pH 8.0, which does not comprise a carboxylic acid amide, can contain and store a urine sample before analysis. Therefore, it would have been obvious to one of ordinary skill that to arrive at a stabilizing composition comprising a caspase inhibitor, EDTA, a solvent and/or buffering agent, at least one poly(oxyethylene) polymer where the at least one poly(oxyethylene) polymer is polyethylene glycol, where the components disclosed in the stabilizing composition of Wyrich et al. include a preservative having antimicrobial effects (i.e. EDTA), does not involve a cross-linking agent and does not comprise a butanamide or carboxylic acid amide, and where the stabilizing composition is buffered, has a pH of ~8.0 as suggested in Mengual et al.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive. Mengual et al. is newly cited as a 103 reference with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230).
Regarding Applicant’s remarks on the Qiagen reference, the remarks are not persuasive. As also noted by Applicant, Qiagen discloses that DNA is subject to degradation by acid hydrolysis and that DNA stored in water is subject to degradation by acid hydrolysis (at least p. 12). Therefore, Qiagen reasonably discloses that DNA should be stored or maintained at pH >7.0.
In this instance, Wyrich et al. and Mengual et al. disclose the same components and/or conditions recited are included in a composition for stabilizing cell-containing samples, including urine samples. It would have been obvious to arrive at a pH ~8.0 for the stabilizing composition and stabilized sample because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12). One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components and conditions recited form a composition for stabilizing cell-containing samples, including urine samples.
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 1-18, 25, 31-35, 36-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, 20-21, 34, 38-41, 43, 59 of copending Application No. 15125863 (‘863) (reference application) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘863 application claims are drawn to a method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, and compositions comprising a chelating agent and one or more poly(oxyethylene) polymers. The ‘863 application claims differ from the instant claims by not explicitly reciting that the cell-containing biological sample is a urine sample and that the stabilizing composition is at a pH ~8.0. However, in view of the teachings of Wyrich et al., Mohan, and Qiagen noted above, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘863 applications claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘863 application claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which disclose that urine samples and DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples. Additionally, it would have been further obvious to exclude the butanamide recited in the ‘863 application claims because Wyrich et al. also disclose that a lower butanamide concentration of < 2% (w/v) is particularly effective when additionally using a further stabilizing agent such as a caspase inhibitor and/or a compound according to formula 1 (p. 14 lines 31-34).
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘863 application claims, it would have been obvious to incorporate the noted component and/or element into the ‘863 application claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive. The provisional nonstatutory double patenting rejection is maintained for the reasons noted above.
Claims 1-18, 25, 31-35, 36-52, 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-22, 24-27, 29-32, 34-40 of U.S. Patent No. 11203777 (‘777) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘777 patent claims are drawn to a method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, and compositions comprising a chelating agent and one or more poly(oxyethylene) polymers. The ‘777 patent claims differ from the instant claims by not explicitly reciting that the cell-containing biological sample is a urine sample and that the stabilizing composition is at a pH ~8.0. However, in view of the teachings of Wyrich et al., Mengual et al., Mohan, and Qiagen, noted above, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘777 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘777 patent claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which disclose that urine samples and DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘777 patent claims, it would have been obvious to incorporate the noted component and/or element into the ‘777 patent claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
Regarding instant claim 53, it would be obvious to not include a carboxylic acid amide in the composition for contacting the sample because at least the ‘777 patent claims 17, 25 recite alternatively including an amide.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that the ‘777 patent claims do not recite a pH range or more than 7 but no more than 9.5.
Applicant’s remarks are not persuasive. As similarly noted above, Mengual et al. is newly cited with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230). Therefore, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘777 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims.
Claims 1-18, 25, 31-35, 36-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-7, 9-20 of U.S. Patent No. 11525155 (‘155) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘155 patent claims are drawn to method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with a poly(oxyethylene) polymer, an amide, a caspase inhibitor, and claims reciting compositions comprising one or more poly(oxyethylene) polymers, wherein the cell-containing biological sample is a urine sample (at least claims 1, 9, 17 of the ‘155 patent). The ‘155 patent claims differ from the instant claims by not explicitly reciting a chelating agent and that the stabilizing composition is at a pH ~8.0. However, in view of the teachings of Wyrich et al., Mengual et al., Mohan, and Qiagen, noted above, it would have been obvious to one of ordinary skill to incorporate a chelating agent of Wyrich et al. with the poly(oxyethylene) polymer, amide, caspase inhibitor of the ‘155 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so is given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘155 patent claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which disclose that urine samples and DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘155 patent claims, it would have been obvious to incorporate the noted component and/or element into the ‘155 patent claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that the ‘155 patent claims do not recite a pH range or more than 7 but no more than 9.5.
Applicant’s remarks are not persuasive. As similarly noted above, Mengual et al. is newly cited with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230). Therefore, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘155 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims.
Claims 1-18, 25, 31-35, 36-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-11, 14-16, 18-20 of U.S. Patent No. 10724074 (‘074) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘074 patent claims are drawn to a method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with an amide, caspase inhibitor, and claims reciting compositions comprising an amide and caspase inhibitor. The ‘074 patent claims differ from the instant claims by not explicitly reciting that the cell-containing biological sample is a urine sample, a chelating agent, and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer and that the stabilizing composition is at a pH ~8.0. However, in view of the noted teachings of Wyrich et al., Mohan, and Qiagen, noted above, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘074 patent claims and to further incorporate a chelating agent and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer with the amide and caspase inhibitor of the ‘074 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so is given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘074 patent claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which disclose that urine samples and DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘074 patent claims, it would have been obvious to incorporate the noted component and/or element into the ‘074 patent claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that the ‘074 patent claims do not recite a pH range or more than 7 but no more than 9.5.
Applicant’s remarks are not persuasive. As similarly noted above, Mengual et al. is newly cited with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230). Therefore, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘074 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims.
Claims 1-18, 25, 31-35, 36-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-20, 22-27 of U.S. Patent No. 10676780 (‘780) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both instant claims and the ‘780 patent claims are drawn to a method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with an amide, caspase inhibitor, and claims reciting compositions comprising an amide and caspase inhibitor. The ‘780 patent claims differ from the instant claims by not explicitly reciting that the cell-containing biological sample is a urine sample, a chelating agent, and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer and that the stabilizing composition is at a pH ~8.0. However, in view of the noted teachings of Wyrich et al., Mohan, and Qiagen, noted above, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘780 patent claims and to further incorporate a chelating agent and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer with the amide and caspase inhibitor of the ‘780 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so is given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘780 patent claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which discloses that DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘780 patent claims, it would have been obvious to incorporate the noted component and/or element into the ‘780 patent claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that the ‘780 patent claims do not recite a pH range or more than 7 but no more than 9.5.
Applicant’s remarks are not persuasive. As similarly noted above, Mengual et al. is newly cited with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230). Therefore, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘780 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims.
Claims 1-18, 25, 31-35, 36-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-27 of U.S. Patent No. 11021733 (‘733) in view of Wyrich et al. (supra), Mengual et al. (supra), Mohan (supra), and Qiagen (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both instant claims and the ‘733 patent claims are drawn to a method for stabilizing a cell-containing biological sample comprising contacting the cell-containing biological sample with an amide, caspase inhibitor, and claims reciting compositions comprising an amide and caspase inhibitor. The ‘733 patent claims differ from the instant claims by not explicitly reciting that the cell-containing biological sample is a urine sample, a chelating agent, and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer and that the stabilizing composition is at a pH ~8.0. However, in view of the noted teachings of Wyrich et al., Mohan, and Qiagen, noted above, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘733 patent claims and to further incorporate a chelating agent and poly(oxyethylene) polymers comprising a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer with the amide and caspase inhibitor of the ‘733 patent claims and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims. The motivation to do so is given by Wyrich et al., which disclose that the components recited in the instant claims and the ‘733 patent claims, including a chelating agent and one or more poly(oxyethylene) polymers, including a high molecular weight poly(oxyethylene) polymer and a low molecular weight poly(oxyethylene) polymer, an amide, a caspase inhibitor, are recognized components in a composition for stabilizing cell-containing biological samples, including urine samples, and Mengual et al. and Qiagen, which discloses that DNA should be maintained at pH > 7.0. One of ordinary skill would have a reasonable expectation of success because Wyrich et al. and Mengual et al. disclose the same components recited form a composition for stabilizing cell-containing samples, including urine samples.
Further regarding the instant dependent claims, if a component and/or element is not explicitly recited in the ‘733 patent claims, it would have been obvious to incorporate the noted component and/or element into the ‘733 patent claims in view of the teachings of Wyrich et al. noted above and at the recited pH ranges in view of the teachings of at least Mengual et al. and Qiagen above.
Reply: Applicant’s amendments/remarks have been considered but they are not persuasive.
Applicant asserts that the ‘733 patent claims do not recite a pH range or more than 7 but no more than 9.5.
Applicant’s remarks are not persuasive. As similarly noted above, Mengual et al. is newly cited with Wyrich et al. and Mohan and disclose that urine is collected in a composition comprising 0.5 M EDTA, pH 8.0, and stored prior to sample processing and analysis (at least p. 229-230). Therefore, it would have been obvious to one of ordinary skill to incorporate the urine sample of Wyrich et al. for the cell-containing biological sample in the ‘733 patent claims, and to further arrive at a stabilizing pH of ~8.0 that is buffered because Mengual et al. disclose a pH ~8.0 for the composition containing the urine sample prior to analysis, where such buffers for arriving at a pH 8.0 are known (Mohan), and it is further known that DNA should be stabilized and/or maintained at a pH > 7.0 (Qiagen p. 12), thereby arriving at the instant claims.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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