DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
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 the 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE and the amendments filed on filed on August 13, 2025 have been entered. The claims pending in this application are claims 1-25, 32, and 33 wherein claim 24 has been withdrawn due to the restriction requirements mailed on October 30, 2023. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on August 13, 2025. Claims 1-24, 32, and 33 will be examined.
Claim Objections
Claim 2 is objected to because of the following informalities: “the first type” in (ii) and (iii) should be “the first type of the at least two types of solid disrupting particles”; and (2) “the second type” in (ii) and (iii) should be “the second type of the at least two types of solid disrupting particles”.
Claim 24 is objected to because of the following informalities: (1) “isolating nucleic acids from the lysed and optionally further processed sample” should be “isolating nucleic acids from the lysate and optionally further processing the isolated nucleic acids”; and (2) “the isolated nucleic acid” should be “the isolated nucleic acids”.
Claim 32 is objected to because of the following informality: “comprising isolating DNA from the liquid phase” should be “wherein the nuclei acids are DNA”.
Claim 33 is objected to because of the following informality: “wherein the method comprises isolating DNA from the lysed and optionally further processed sample; and sequencing isolated DNA” should be “wherein the nuclei acids are DNA”.
Appropriate correction is required.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 7, 8, 10, 11, 13, 16, 24, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., (US 2019/0367904 A1, priority date: November 7, 2016) in view of Narva et al., (US 2013/0091601 A1, published on April 11, 2013).
Regarding claims 1, 8, 11, 13, 16, 24, and 33, since the specification teaches that “[R]oot is a plant organ especially rich in microorganisms such as bacteria” (see paragraph [0244] of US 2021/0238580 A1, which is US publication of this instant case), Kemp et al., disclose a lysis method for environment sample such as a root, comprising mechanically disrupting the plant sample in a liquid lysis composition using the second type of the at least two types of solid disrupting particles, wherein the second type of the at least two types of solid disrupting particles has at least two different sizes (eg., 0.1 mm and 0.5 mm beads made by glass or/and metal) and (1) the first particle size of the at least two different sizes lies on average in a range of 0.05 mm to 0.25 mm (eg., 0.1 mm) and (2) the second particle size of the at least two different sizes lies on average in a range of 0.3 mm to 0.9 mm (eg., 0.5 mm) as recited in claim 1, the plurality of particles of the second type of the at least two types of solid disrupting particles are substantially spherical as recited in claim 8, the liquid lysis composition comprises at least one chaotropic agent as recited in claim 11, generating and clearing the lysate as recited in claim 13, the plant sample is selected from leaf, needle, root, stem, seed, fruit and flowers as recited in claim 16, generating a lysate from the plant sample, isolating nucleic acids from the lysate and optionally further processing the isolated nucleic acids; and optionally sequencing the isolated nucleic acids as recited in claim 24, and sequencing the isolated nucleic acids wherein isolated nucleic acids are DNA as recited in claim 33 (see paragraphs [0015], [0018], [0024], [0032], [0067], [0070] to [0072], [0100], [0102], and [142], and claims 1-4, 6, 8, 11, 16-24, and 28).
Kemp et al., does not disclose mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles wherein a first type of the at least two types of solid disrupting particles are one or more non-spherical disrupting particles having a size of 1.5 mm to 15 mm as recited in claim 1, wherein the first type and the second type of solid disrupting particles differ from each other in shape and/or material and wherein the first type has at least discontinuity that is an edge, and the second type is provided by a plurality of particles that are substantially spherical as recited in claim 2, the surface of the first type of the at least two types of solid disrupting particles contains a first part and a second part, whereby the first part and the second part meet by forming an edge as recited in claim 3, the first type of the at least two types of solid disrupting particles has a shape selected from a cone, a cylinder, a cube, a triangle, a rectangle, a ballcone and a satellite as recited in claim 4, the first type of the at least two types of solid disrupting particles is a single solid disrupting particle as recited in claim 7, and said mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles is performed sequentially or simultaneously as recited in claim 10. However, Kemp et al., teach that “[T]he plurality of beads may be made of plastic, glass, ceramic, mineral, metal and/or any other suitable materials. In certain embodiments, the beads may be made of non-magnetic materials. In certain embodiments, the beads are rotationally symmetric about at least one axis (e.g., spherical, rounded, oval, elliptic, egg-shaped, and droplet-shaped particles). In other embodiments, the beads have polyhedron shapes. In some embodiments, the beads are irregularly shaped particles. For example, the beads can be glass, ceramic, silicon (e.g., fumed silica or pyrogenic silica, colloidal silica, silica gel), metal, steel, tungsten carbide, garnet, sand, or sapphire beads” and “[T]he beads of different sizes allows for the efficient lysis of the samples. In particular embodiments, the beads comprise a mixture of beads of 0.1 mm and 0.5 mm diameter beads, such as at a ratio of 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 or 2:1, 3:1, 4:1, 5:1, 6:1 by volume. Other mixtures and ratios are contemplated and may be preferred depending on the types of beads used. For instance, a single large steel ball mixed with a plurality of 0.1 mm and 0.5 mm beads to help break down large materials such as tissues. In addition, 2.0-5.0 mm beads maybe used to help break down tissues (e.g. insect, plant, animal). Further 2.0 mm and 0.1 mm represents a preferred embodiment as it is ideal for the disruption of infectious disease carrying vectors (e.g. insects) and the organism they harbor maybe a tough to lyse gram positive bacteria or yeast” (see paragraphs [0070] and [0072]).
Narva et al., teach to disrupt tissue samples using three tungsten beads and isolate RNA from the tissue samples (see paragraphs [0317] to [0319]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 1-4, 7, and 10 by mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles wherein a first type of the at least two types of solid disrupting particles are one or more non-spherical disrupting particles (ie., polyhedron shapes) having a size of 1.5 mm to 15 mm wherein the first type and the second type of solid disrupting particles differ from each other in shape and/or material and wherein the first type has at least discontinuity that is an edge, and the second type (ie., spherical shaped beads) is provided by a plurality of particles that are substantially spherical, the surface of the first type of the at least two types of solid disrupting particles contains a first part and a second part, whereby the first part and the second part meet by forming an edge, the first type of the at least two types of solid disrupting particles has a shape selected from a cone, a cylinder, a cube, a triangle, a rectangle, a ballcone and a satellite, the first type of the at least two types of solid disrupting particles is a single solid disrupting particle, and said mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles is performed sequentially or simultaneously in view of the prior arts of Kemp et al., and Narva et al.. One having ordinary skill in the art would have been motivated to do so because Kemp et al., teach that “[T]he plurality of beads may be made of plastic, glass, ceramic, mineral, metal and/or any other suitable materials. In certain embodiments, the beads may be made of non-magnetic materials. In certain embodiments, the beads are rotationally symmetric about at least one axis (e.g., spherical, rounded, oval, elliptic, egg-shaped, and droplet-shaped particles). In other embodiments, the beads have polyhedron shapes. In some embodiments, the beads are irregularly shaped particles. For example, the beads can be glass, ceramic, silicon (e.g., fumed silica or pyrogenic silica, colloidal silica, silica gel), metal, steel, tungsten carbide, garnet, sand, or sapphire beads” and “[T]he beads of different sizes allows for the efficient lysis of the samples. In particular embodiments, the beads comprise a mixture of beads of 0.1 mm and 0.5 mm diameter beads, such as at a ratio of 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 or 2:1, 3:1, 4:1, 5:1, 6:1 by volume. Other mixtures and ratios are contemplated and may be preferred depending on the types of beads used. For instance, a single large steel ball mixed with a plurality of 0.1 mm and 0.5 mm beads to help break down large materials such as tissues. In addition, 2.0-5.0 mm beads maybe used to help break down tissues (e.g. insect, plant, animal). Further 2.0 mm and 0.1 mm represents a preferred embodiment as it is ideal for the disruption of infectious disease carrying vectors (e.g. insects) and the organism they harbor maybe a tough to lyse gram positive bacteria or yeast” (see paragraphs [0070] and [0072]) while Narva et al., have successfully disrupted tissue samples using three tungsten beads and isolated RNA from the tissue samples (see paragraphs [0317] to [0319]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 1-4, 7, and 10 by mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles formed by mixing the first type of the at least two types of solid disrupting particles (eg., 2-5 mm polyhedron shape beads) and the second type of the at least two types of solid disrupting particles (eg., 0.1 and 0.5 mm spherical beads) taught by Kemp et al., in view of the prior arts of Kemp et al., and Narva et al., in order to help break a plant sample from a root.
Claims 5, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., in view of Narva et al., as applied to claims 1-4, 7, 8, 10, 11, 13, 16, 24, and 33 above, and further in view of O’Nell et al., (WO 2016/189132 A1, published on December 1, 2016).
The teachings of Kemp et al., and Narva et al., have been summarized previously, supra.
Kemp et al., and Narva et al., do not disclose that the first part is the surface of a frustum of a first cone and the second part is the surface of a frustum of a second cone, the first type of the particles comprises at least one tip which is a frustum of a cone, wherein the larger base of the frustum of the cone that provides the tip is set against the smaller base of the frustum of the cone of the second part and wherein the particle comprises a subportion that is made up of a section or a part of a ball or an ellipse which is set against the smaller base of the frustum of the cone of the first part as recited in claims 5 and 9 and the first type of the at least two types of solid disrupting particles has a weight in the range of 500 mg to 1000 mg, optionally 600 mg to 900 mg and exhibiting a size of 3 mm to 10 mm, optionally 3 mm to 7 mm, or 4 mm to 7 mm as recited in claim 6. However, Kemp et al., teach that the second type of the particles is provided by a plurality of substantially spherical zirconia beads having a size that lies in the range of 0.08 mm to 0.7 mm as recited in claim 9 (eg., see page 9, Table 4).
Since it is known that density equals to weight/volume and 4 mm×6 mm ballcone steel balls has a density of 7.8 g/cm3 and has all characteristics of the first type of the particles recited in item aa) of claims 5 and 9 (see “Ballcone steel Finishing Media”), O’Nell et al., teach that 4 mm×6 mm ballcone steel beads with a height of 4.7 mm has a volume which is 0.1128 cm3 (4 mm×6 mm×4.7 mm=112.8 mm3=0.1128 cm3) (see pages 9-11), 4 mm×6 mm ballcone steel beads taught by O’Nell et al., has a weight which is 879.84 mg (7.8 g/cm3×0.1128 cm3 =0.87984 g=879.84 mg) and has all characteristics of the first type of the particles recited in claims 5, 6, and 9.
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 5, 6, and 9 wherein the first type of disrupting particles are 4 mm×6 mm ballcone steel beads and has a weight which is 879.84 mg in view of the prior arts of Kemp et al., Narva et al., and O’Nell et al.. One having ordinary skill in the art would have been motivated to do so because Kemp et al., teach that “[T]he plurality of beads may be made of plastic, glass, ceramic, mineral, metal and/or any other suitable materials. In certain embodiments, the beads may be made of non-magnetic materials. In certain embodiments, the beads are rotationally symmetric about at least one axis (e.g., spherical, rounded, oval, elliptic, egg-shaped, and droplet-shaped particles). In other embodiments, the beads have polyhedron shapes. In some embodiments, the beads are irregularly shaped particles. For example, the beads can be glass, ceramic, silicon (e.g., fumed silica or pyrogenic silica, colloidal silica, silica gel), metal, steel, tungsten carbide, garnet, sand, or sapphire beads” and “[I]n some embodiments, the beads have a mean diameter of greater than 1 m (e.g. about 2 μm, about 5 μm, about 10 μm, about 20 μm, about 50 μm, about 100 μm, about 200 μm, about 500 μm, about 1 mm, about 2 mm, about 5 mm, about 1 cm, greater than 1 cm)” (see paragraphs [0070] and [0071] while 4 mm×6 mm ballcone steel beads taught by O’Nell et al., has a weight which is 879.84 mg (7.8 g/cm3×0.1128 cm3 =0.87984 g=879.84 mg) and has all characteristics of the first type of the particles recited in claims 5, 6, and 9 and are commercially available, and the simple substitution of one kind of first type of disrupting particles (ie., the 2-5 mm polyhedron particle taught by Kemp et al.,) from another kind of first type of disrupting particles (ie., 4 mm×6 mm ballcone steel taught by O’Nell et al.,) during the process of making the liquid lysis composition recited in claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made because the 2-5 mm polyhedron particle taught by Kemp et al., and 4 mm×6 mm ballcone steel beads taught by O’Nell et al., are used for the same purpose (ie., used as non-spherical particles) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 5, 6, and 9 using 4 mm×6 mm ballcone steel beads taught by O’Nell et al., as the first type of at least two types of solid disrupting particles in view of the prior arts of Kemp et al., and O’Nell et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 12, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., in view of Narva et al., as applied to claims 1-4, 7, 8, 10, 11, 13, 16, 24, and 33 above, and further in view of Joly et al., (US Patent No. 5,639, 635, published on June 17, 1997).
The teachings of Kemp et al., and Narva et al., have been summarized previously, supra.
Kemp et al., and Narva et al., do not disclose that the chaotropic agent is sodium thiocyanate as recited in claim 12 and the liquid lysis composition comprises sodium thiocyanate in a concentration of 0.7 M to 1.5 M as recited in claim 20. However, Kemp et al., teach that the liquid lysis composition comprises at least one phosphate (ie., NaH2PO4) in a concentration of 0.075 M to 0.3 M (eg., 200 mM) as recited in claim 20 and the at least one phosphate is
sodium phosphate dibasic (ie., NaH2PO4) as recited in claim 21 (see paragraph [0100]). Kemp et al., also teach that examples of chaotropic salts in a lysis buffer include, but are not limited to, guanidine thiocyanate, guanidine hydrochloride, sodium iodide, potassium iodide, sodium isothiocyanate, and urea wherein the concentration of guanidine hydrochloride is 1 to 3 M (see paragraphs [0100], [0112] and [0119]).
Joly et al., teach that “[C]haotropic agent suitable for practicing this method of extraction include e.g., urea and salts of guanidine or thiocyanate, more preferably urea, guanidine hydrochloride, or sodium thiocyanate” and “[G]enerally the concentration of chaotropic agent is about 0.1 to 9 M, preferably about 0.5-9 M, more preferably about 0.5 to 6 M, and most preferably about 0.5-3 M” (see column 12, last paragraph and column 13, first paragraph).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 12 and 20 wherein the chaotropic agent is sodium thiocyanate and the liquid lysis composition comprises sodium thiocyanate in a concentration of 0.8 M to 1.25 M in view of the prior arts of Kemp et al., Narva et al., and Joly et al.. One having ordinary skill in the art would have been motivated to do so because Kemp et al., teach that the liquid lysis composition comprises sodium phosphate dibasic (ie., NaH2PO4) in a concentration of 0.1 M to 0.25 M (eg., 200 mM) and examples of chaotropic salts in a lysis buffer include, but are not limited to, guanidine
thiocyanate, guanidine hydrochloride, sodium iodide, potassium iodide, sodium isothiocyanate, and urea wherein the concentration of guanidine hydrochloride is 1 to 3 M (see paragraphs [0100], [0112] and [0119]) while Joly et al., teach that “[C]haotropic agent suitable for practicing this method of extraction include e.g., urea and salts of guanidine or thiocyanate, more preferably urea, guanidine hydrochloride, or sodium thiocyanate” and “[G]enerally the concentration of chaotropic agent is about 0.1 to 9 M, preferably about 0.5-9 M, more preferably about 0.5 to 6 M, and most preferably about 0.5-3 M” (see column 12, last paragraph and column 13, first paragraph), and the simple substitution of one kind of chaotropic agent (ie., guanidine hydrochloride taught by Kemp et al.,) from another kind of chaotropic agent (ie., sodium thiocyanate taught by Joly et al.,) during the process of making the liquid lysis composition recited in claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made because guanidine hydrochloride taught by Kemp et al., and sodium thiocyanate taught by Joly et al., are used for the same purpose (ie., serving as a chaotropic agent in a lysis buffer) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 12 and 20 using a liquid lysis composition comprising sodium thiocyanate in a concentration of 0.8 M to 1.25 M and sodium phosphate dibasic in a concentration of 0.1 M to 0.25 M in view of the prior arts of Kemp et al., Narva et al., and Joly et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 14, 15, 23, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., in view of Narva et al., as applied to claims 1-4, 7, 8, 10, 11, 13, 16, and 33 above, and further in view of Morrison et al., (US 2019/0083554 A1, priority date: March 28, 2016) and Braid et al., (Journal of Microbiological Methods, 52, 389-293, 2003).
The teachings of Kemp et al., and Narva et al., have been summarized previously, supra.
Kemp et al., and Narva et al., do not disclose contacting the lysed sample with at least one protein precipitating agent and at least one inhibitor removing agent, providing a mixture and obtaining a liquid phase from the mixture as recited in claim 14 wherein the precipitating agent is ammonium acetate as recited in claim 15. However, Kemp et al., teach isolating nucleic acids such as DNA from the liquid phase as recited in claims 23 and 32 (see paragraph [0107]) and teach that “[I]n some aspects, the lysis buffer comprises a reagent that can facilitate binding including but not limited to chaotropic salts, kosmotropic salts, alcohol, PEG, and cationic detergents” (see paragraph [0018]).
Morrison et al., teach that “[I]n some methods a buffer with a concentration of 10 mM or greater of kosmotropic salts is used. Exemplary kosmotropic salts include ammonium sulfate, ammonium acetate, sodium citrate, sodium acetate, sodium sulfate, potassium phosphate, and cesium chloride, either separately or in any combination. If present, the kosmotropic salts are typically used at a concentration exceeding 10 mM, such as between 0.1 M and 1 M; between 0.2 M and 0.8 M; between 0.3 M and 0.7 M; between 0.4 M and 0.6 M; or 0.5 M” (see paragraph [0008]).
Braid et al., teach removal of PCR inhibitors such as humic substances from soil DNA by chemical flocculation such as using 50 or 100 mM aluminum ammonium sulfate (AlNH4(SO4)2) (see pages 389 and 391-393, and Figures 2 and 3).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 14 and 15 by contacting the lysed sample with at least one protein precipitating agent and at least one inhibitor removing agent, providing a mixture and obtaining a liquid phase from the mixture wherein the precipitating agent is ammonium acetate in view of the prior arts of Kemp et al., Narva et al., Morrison et al., and Braid et al.. One having ordinary skill in the art would have been motivated to do so because Kemp et al., teach that “[I]n some aspects, the lysis buffer comprises a reagent that can facilitate binding including but not limited to chaotropic salts, kosmotropic salts, alcohol, PEG, and cationic detergents” (see paragraph [0018]), Morrison et al., teach that “[I]n some methods a buffer with a concentration of 10 mM or greater of kosmotropic salts is used. Exemplary kosmotropic salts include ammonium sulfate, ammonium acetate, sodium citrate, sodium acetate, sodium sulfate, potassium phosphate, and cesium chloride, either separately or in any combination. If present, the kosmotropic salts are typically used at a concentration exceeding 10 mM, such as between 0.1 M and 1 M; between 0.2 M and 0.8 M; between 0.3 M and 0.7 M; between 0.4 M and 0.6 M; or 0.5 M” (see paragraph [0008]), and Braid et al., teach removal of PCR inhibitors such as humic substances from soil DNA by chemical flocculation such as using 50 or 100 mM aluminum ammonium sulfate (AlNH4(SO4)2) (see pages 389 and 391-393, and Figures 2 and 3). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 14 and 15 by adding ammonium acetate and aluminum ammonium sulfate to the lysis sample in view of the prior arts of Kemp et al., Narva et al., Morrison et al., and Braid et al., in order to precipitating proteins and remove PCR inhibitors from the lysis sample.
Claims 17 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., in view of Narva et al., Morrison et al., and Braid et al., as applied to claims 1-4, 7, 8, 10-16, 23, 24, 32, and 33 above, and further in view of Joly et al..
The teachings of Kemp et al., Narva et al., Morrison et al., and Braid et al., have been summarized previously, supra.
Kemp et al., Narva et al., Morrison et al., and Braid et al., do not disclose that the chaotropic agent is sodium thiocyanate in a concentration of 1.5 M or less as recited in claims 17 and 22. However, Kemp et al., in view of Morrison et al., and Braid et al., teach that the liquid lysis composition comprises at least one chaotropic agent in a concentration of 1.5 M or less wherein a lysed mixture is obtained upon said mechanically disrupting the plant sample in the liquid lysis composition using the at least two types of solid disrupting particles, clearing the lysate, wherein said clearing the lysate comprises separating the lysed mixture that is obtained upon disrupting the plant sample into a solid fraction and a liquid fraction, wherein the liquid fraction is subsequently processed as a lysed sample; contacting the lysed sample with at least one protein precipitating agent and at least one inhibitor removing agent and providing a mixture; and obtaining a liquid phase from the mixture (see above rejections related to Rejection Item Nos: 28 and 29).
Joly et al., teach that “[C]haotropic agent suitable for practicing this method of extraction include e.g., urea and salts of guanidine or thiocyanate more preferably urea, guanidine hydrochloride, or sodium thiocyanate” and “[G]enerally the concentration of chaotropic agent is about 0.1 to 9M, preferably about 0.5-9M, more preferably about 0.5 to 6M, and most preferably about 0.5-3M” (see column 12, last paragraph and column 13, first paragraph).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 17 and 22 wherein the chaotropic agent is sodium thiocyanate in a concentration of 1.5 M or less in view of the prior arts of Kemp et al., Narva et al., Morrison et al., Braid et al., and Joly et al.. One having ordinary skill in the art would have been motivated to do so because Kemp et al., teach that examples of chaotropic salts in a lysis buffer include, but are not limited to, guanidine
thiocyanate, guanidine hydrochloride, sodium iodide, potassium iodide, sodium isothiocyanate, and urea wherein the concentration of guanidine hydrochloride is 1 to 3 M (see paragraphs [0100], [0112] and [0119]) while Joly et al., teach that “[C]haotropic agent suitable for practicing this method of extraction include e.g., urea and salts of guanidine or thiocyanate more preferably urea, guanidine hydrochloride, or sodium thiocyanate” and “[G]enerally the concentration of chaotropic agent is about 0.1 to 9M, preferably about 0.5-9M, more preferably about 0.5 to 6M, and most preferably about 0.5-3M” (see column 12, last paragraph and column 13, first paragraph), and the simple substitution of one kind of chaotropic agent (ie., guanidine hydrochloride taught by Kemp et al.,) from another kind of chaotropic agent (ie., sodium thiocyanate taught by Joly et al.,) during the process of making the liquid lysis composition recited in claim 1, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made because guanidine hydrochloride taught by Kemp et al., and sodium thiocyanate taught by Joly et al., are used for the same purpose (ie., serving as a chaotropic agent in a lysis buffer) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 17 and 22 using a liquid lysis composition comprising sodium thiocyanate in a concentration of 1.5 M or less in view of the prior arts of Kemp et al., Narva et al., Morrison et al., Braid et al., and Joly et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp et al., in view of Narva et al., Morrison et al., Braid et al., and Joly et al., as applied to claims 1-4, 7, 8, 10-17, 22-24, 32, and 33 above, and further in view of Heaton et al., (US Patent No. 5,538,530, published on July 23, 1996).
The teachings of Kemp et al., Narva et al., Morrison et al., Braid et al., and Joly et al., have been summarized previously, supra.
Kemp et al., Narva et al., Morrison et al., Braid et al., and Joly et al., do not disclose that at least one inhibitor removing agent is aluminum chloride as recited in claims 18 and 19. Since Braid et al., teach removal of PCR inhibitors such as humic substances from soil DNA by chemical flocculation such as using 50 or 100 mM aluminum ammonium sulfate (AlNH4(SO4)2) and “[T]he aluminum cations may preferentially interact with the open and random structure of inhibitory organic polymers such as humic substances, while the helical structure of DNA may protect it from flocculation” (see pages 389 and 391-393, and Figures 2 and 3), Braid et al., indicates that the effect of aluminum ammonium sulfate in removal of PCR inhibitors such as humic substances from soil DNA is based on aluminum cations.
Heaton et al., teach that the humic acid chelates are removed by flocculation with a conventional flocculant (aluminum sulfate, aluminum chloride, polyaluminum sulfate-silicate, ferric chloride, calcium hydroxide, starch and starch derivatives, guar gum, synthetic polymers such as polyacrylamide-acrylic polymers and polyamines, etc.) and settling, centrifugation or filtering” (see column 4, sixth paragraph).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 18 and 19 in view of the prior arts of Kemp et al., Narva et al., Morrison et al., Braid et al., Joly et al., and Heaton et al.. One having ordinary skill in the art would have been motivated to do so because Braid et al., indicate that the effect of aluminum ammonium sulfate in removal of PCR inhibitors such as humic substances from soil DNA is based on aluminum cations (see above) while Heaton et al., teach that the humic acid chelates are removed by flocculation with a conventional flocculant (aluminum sulfate, aluminum chloride, polyaluminum sulfate-silicate, ferric chloride, calcium hydroxide, starch and starch derivatives, guar gum, synthetic polymers such as polyacrylamide-acrylic polymers and polyamines, etc.) and settling, centrifugation or filtering” (see column 4, sixth paragraph), and the simple substitution of one kind of inhibitor removing agent (ie., aluminum ammonium sulfate taught by Braid et al.,) from another kind of inhibitor removing agent (ie., aluminum chloride taught by Heaton et al.,) during the process of performing the methods recited in claims 15 and 17, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made because aluminum ammonium sulfate taught by Braid et al., and aluminum chloride taught by Heaton et al., are used for the same purpose (ie., serving as inhibitor removing agent for removing humic substances from soil) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 18, and 19 using aluminum chloride in a range of 15 mM to 75 mM in view of the prior arts of Kemp et al., Narva et al., Morrison et al., Braid et al., Joly et al., and Heaton et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Response to Arguments
In page 16, third paragraph bridging to page 20, third paragraph of applicant’s remarks, applicant argues that “[A]pplicant respectfully submits that the claims as currently amended in the present application are not obvious in view of the cited references. Specifically, one of ordinary skill in the art would not have been motivated to modify KEMP in view of NARVA as asserted in the Office Action to arrive at the methods currently claimed in the present application with a reasonable expectation of success. In addition, the presently claimed methods have unexpectedly superior properties of efficiently releasing microbial nucleic acids from microorganism comprised in various plant samples, resulting in not only overall high yield but also high amount of microbial nucleic acids. First, one of ordinary skill in the art would not have been motivated to modify KEMP in view of NARVA as asserted in the Office Action to arrive at the methods currently claimed in the present application with a reasonable expectation of success. As discussed in Applicant’s previous submission, the previously cited references in combination fail to teach or suggest the specific combination of the two types of solid disrupting particles as currently recited in the instant claims. The newly cited reference, NARVA, fails to remedy such a deficiency of the previously cited references. Briefly, as previously discussed, KEMP is concerned with providing a technology for reduced biased isolation of nucleic acids from mixed microbial samples (see Abstract). While disclosing the use of a combination of 0.1 mm and 0.5 mm beads in breaking down sample materials and a plurality of beads can be comprised of different materials, sizes and/or shape, KEMP fails to disclose a combination of beads wherein the first type has a size of 0.5 mm and a first shape (and/or material), and the second type has a size of 0.1 mm and a second shape (and/or material) different from the first shape. Consistent with this notion, KEMP in its examples for the 0.1 mm and 0.5 mm diameter mix consistently uses beads of the same material and does not disclose that they differed in shape. In addition, a polyhedron is mentioned only once in KEMP, in paragraph [0070], and is not disclosed in combination with any specific sizes, let alone in relation with the specific bead combination of 0.1 mm and 0.5 mm diameter referred to in KEMP or that a polyhedron shaped particle having a size of specifically 1.5 mm or more should be used. In summary, KEMP fails to teach or suggest the specific combination of the two types of solid disrupting particles as currently recited in the instant claims. NARVA (as well as the other cited references as previously discussed) does not remedy the deficiency of KEMP. Specifically, NARVA concerns nucleic acid molecules and methods of use thereof for control of coleopteran pests through RNA interference-mediated inhibition of target coding and transcribed non-coding sequences in coleopteran pests, and methods for making transgenic plants that express nucleic acid molecules useful for the control of coleopteran pests, and the plant cells and plants obtained thereby (see Abstract, Claims). NARVA is not concerned with devising any particular method for releasing microbial nucleic acids from microorganisms in a plant sample. As such, it is unlikely that one of ordinary skill in the art considering KEMP would have turned to NARVA. Even if the skilled person would have considered NARVA (merely arguendo), NARVA would not have directed the skilled person considering KEMP to modify KEMP towards the claimed methods. In particular, NARVA is silent on the use of non-spherical solid disrupting particles (let alone having a size of 1.5 mm or more for disrupting a plant sample). Thus, similar to KEMP, NARVA also fails to disclose or suggest the use of such particles in combination with a plurality of smaller particles. This also applies to paragraphs [0317] to [0319] of NARVA specifically cited in the Office Action (see middle of page 9)” and paragraphs [0317] of Narva et al., “discloses neither the size of the used tungsten beads, nor a non-spherical shape, and NARVA throughout as explained is silent on the use of non-spherical solid disrupting particles. Accordingly, one of ordinary skill in the art would not have been motivated to modify KEMP in view of NARVA to arrive at the instantly claimed methods with a reasonable likelihood of success. This is especially the case in view of the teaching in KEMP that ‘not all mechanical lysis methodologies perform equally. The type of bead (matrices) used to homogenize the sample and the type of homogenization device are major contributors to bias [in nucleic acid purification]’ (see paragraph [0008] of KEMP, emphasis added). Second, as discussed in Applicant’s previous submission, the presently claimed methods efficiently release microbial nucleic acids from microorganisms in various plant samples, resulting in not only overall high yield but also high amount of microbial nucleic acids compared to prior art methods, such as methods using the combination of small beads of 0.1 mm and 0.5 mm in diameters as disclosed in KEMP and a method using a combination of beads of 0.1 mm and 0.5 mm in diameters with spherical stainless-steel beads of approximate 2.4 mm in diameter. Such superior properties of the instantly claimed methods have not been taught or suggested in the newly cited reference NARVE. Thus, the instantly claimed methods are unexpectedly superior to those in the cited references (both the new cited NARVE and the previously cited references) and not obvious”.
These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection.
First, although applicant argues that “the claims as currently amended in the present application are not obvious in view of the cited references. Specifically, one of ordinary skill in the art would not have been motivated to modify KEMP in view of NARVA as asserted in the Office Action to arrive at the methods currently claimed in the present application with a reasonable expectation of success”, “[K]EMP fails to disclose a combination of beads wherein the first type has a size of 0.5 mm and a first shape (and/or material), and the second type has a size of 0.1 mm and a second shape (and/or material) different from the first shape”, and “[N]ARVA is silent on the use of non-spherical solid disrupting particles (let alone having a size of 1.5 mm or more for disrupting a plant sample). Thus, similar to KEMP, NARVA also fails to disclose or suggest the use of such particles in combination with a plurality of smaller particles. NARVA is silent on the use of non-spherical solid disrupting particles (let alone having a size of 1.5 mm or more for disrupting a plant sample). Thus, similar to KEMP, NARVA also fails to disclose or suggest the use of such particles in combination with a plurality of smaller particles”, the rejection on claim 1 is not dependent on either Kemp et al., or Narva et al., alone but is based on a combination of Kemp et al., and Narva et al.. Since Kemp et al., teach that “[T]he plurality of beads may be made of plastic, glass, ceramic, mineral, metal and/or any other suitable materials. In certain embodiments, the beads may be made of non-magnetic materials. In certain embodiments, the beads are rotationally symmetric about at least one axis (e.g., spherical, rounded, oval, elliptic, egg-shaped, and droplet-shaped particles). In other embodiments, the beads have polyhedron shapes. In some embodiments, the beads are irregularly shaped particles. For example, the beads can be glass, ceramic, silicon (e.g., fumed silica or pyrogenic silica, colloidal silica, silica gel), metal, steel, tungsten carbide, garnet, sand, or sapphire beads” and “[T]he beads of different sizes allows for the efficient lysis of the samples. In particular embodiments, the beads comprise a mixture of beads of 0.1 mm and 0.5 mm diameter beads, such as at a ratio of 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 or 2:1, 3:1, 4:1, 5:1, 6:1 by volume. Other mixtures and ratios are contemplated and may be preferred depending on the types of beads used. For instance, a single large steel ball mixed with a plurality of 0.1 mm and 0.5 mm beads to help break down large materials such as tissues. In addition, 2.0-5.0 mm beads maybe used to help break down tissues (e.g. insect, plant, animal). Further 2.0 mm and 0.1 mm represents a preferred embodiment as it is ideal for the disruption of infectious disease carrying vectors (e.g. insects) and the organism they harbor maybe a tough to lyse gram positive bacteria or yeast” (see paragraphs [0070] and [0072]) while Narva et al., have successfully disrupted tissue samples using three tungsten beads and isolated RNA from the tissue samples (see paragraphs [0317] to [0319]), one having ordinary skill in the art would have been motivated to performed the methods recited in claims 1-4, 7, and 10 by mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles wherein a first type of the at least two types of solid disrupting particles are one or more non-spherical disrupting particles (ie., polyhedron shapes) having a size of 1.5 mm to 15 mm wherein the first type and the second type of solid disrupting particles differ from each other in shape and/or material and wherein the first type has at least discontinuity that is an edge, and the second type (ie., spherical shaped beads) is provided by a plurality of particles that are substantially spherical, the surface of the first type of the at least two types of solid disrupting particles contains a first part and a second part, whereby the first part and the second part meet by forming an edge, the first type of the at least two types of solid disrupting particles has a shape selected from a cone, a cylinder, a cube, a triangle, a rectangle, a ballcone and a satellite, the first type of the at least two types of solid disrupting particles is a single solid disrupting particle, and said mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles is performed sequentially or simultaneously in view of the prior arts of Kemp et al., and Narva et al.. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 1-4, 7, and 10 by mechanically disrupting the plant sample in a liquid lysis composition using at least two types of solid disrupting particles formed by mixing the first type of the at least two types of solid disrupting particles (eg., 2-5 mm polyhedron shape beads) and the second type of the at least two types of solid disrupting particles (eg., 0.1 and 0.5 mm spherical beads) taught by Kemp et al., in view of the prior arts of Kemp et al., and Narva et al., in order to help break a plant sample from a root.
Second, although applicant argues that “the presently claimed methods efficiently release microbial nucleic acids from microorganisms in various plant samples, resulting in not only overall high yield but also high amount of microbial nucleic acids compared to prior art methods, such as methods using the combination of small beads of 0.1 mm and 0.5 mm in diameters as disclosed in KEMP and a method using a combination of beads of 0.1 mm and 0.5 mm in diameters with spherical stainless-steel beads of approximate 2.4 mm in diameter”, applicant has not provided evidence to show that, comparing with other methods, when the at least two types of solid disrupting particles recited in claim 1 are used to release microbial nucleic acids from microorganisms in a plant sample, not only overall high yield but also high amount of microbial nucleic acids can be produced.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph.D., whose telephone number is (571)272-0746. The examiner can normally be reached on Monday-Friday from 9 A.M. to 5 P.M.
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/FRANK W LU/Primary Examiner, Art Unit 1683 November 17, 2025