Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 23, 2026 has been entered.
DETAILED ACTION
Claims 1, 3, 9, 16-24, 28 and 56-59 are pending and under examination.
The rejection of claims 2 and 8 are withdrawn in light of the cancellation of the claims in the amendment filed 1/23/2026.
Priority
This application is a 371 of PCT/US2017/060345 filed on November 7, 2017,
which claims benefit of U.S. Provisional Application 62/418,762 filed on November 7,
2016. The effective filing date of the current application is November 7, 2016.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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, 3, 16-18, 55 and 58-59 are rejected under 35 U.S.C. 103 as being unpatentable over Jem (US patent 6,455,287, issued on September 24, 2002; previously cited) in view of Gautsch et al. (US Patent 6,706,498, issued on March 16, 2004; previously cited), Yu et al. (“Nucleic acid extraction, oligonucleotide probes and PCR methods”. 2005. In: Makkar, H.P., McSweeney, C.S. (eds) Methods in Gut Microbial Ecology for Ruminants. Springer, Dordrecht; previously cited) and Fujii et al. (“Potential use of the astaxanthin-producing microalga, Monoraphidium sp.GK12, as a functional aquafeed for prawns”, Journal of Applied Phycology, 2010, Vol. 22, pp.363-369; previously cited). The rejection of claim 58 is further evidenced by Manicone et al. (“An overview of zirconia ceramics: basic properties and clinical applications”, Journal of Dentistry, 2007 Nov., Vol. 35, Issue 11, pp.918-826; previously cited).
Regarding claims 1 and 59, Jem teaches mechanical disruption of bacterial cells for plasmid recovery (relevant to nucleic acid isolation) (title). Jem teaches A type KDL pilot scale bead mill from Glen Mills Inc., for bead mill experiments (description column 10, lines 23-25). Jem teaches pumping a cell suspension at high or low flow rate with a Masterflex peristaltic pump (relevant to (a) disposing a sample into a sample container) (description column 10, lines 25-27). Jem teaches a bead chamber filled with approximately 1170 cc of 0.5mm dry glass beads (chamber volume is 1.4L) (relevant to wherein each sample container comprises the sample and a plurality of beads) (description column 10, lines 27-29), which is 84% by volume.
Jem teaches that agitation was either at low speed (1910 rpm) or high speed (3400 rpm) (relevant to disrupting microbial cells and viruses) (description column 10, lines 29-31). Jem further teaches a method of first passing liquid containing plasmid-containing bacterial cells (relevant to disposing the sample) through a bead mill containing beads of about 0.1mm to about 1mm in diameter, at an agitation speed of about 1,000 to 2,500 rpm (relevant to (b) applying a mechanical force to the sample container, wherein each sample container comprises the sample and a bead or plurality of beads) (description column 5, lines 42-46). Jem teaches the cell suspension was pumped through a horizontal grinding chamber filled about 80 to 85% with microspheres (beads) (relevant to wherein the first beads are substantially spherical) (description, column 14, lines 18-20). Jem further teaches wherein the beads are about 0.25 mm to about 0.75 mm (relevant to wherein the first beads comprise an average diameter of between 0.25 and 0.77 mm) (column 18, Claim 11). Jem teaches that bacteria typically require smaller beads, typically about 0.1mm diameter, while yeast cells require slightly larger beads, about 0.5mm in diameter (description col. 14, lines 6-8). Jem teaches that glass beads are a typical medium for grinding cells, although ceramic or stainless steel beads are also used (relevant to the bead is composed of a ceramic) (description column 14, lines 4-5).
Jem does not teach a plurality of samples; an array of sample containers; wherein the plurality of samples comprise at least two different species of biological agents each selected from bacterial cells and fungal cells; a plurality of second beads; wherein the first and second beads are in a ratio of 1:1; or loading the sample container at 40-60% by volume.
However, Gautsch teaches methods for isolating DNA from natural cellular sources or other sources containing these materials (title, column 1, lines 5-10). Gautsch teaches methods of tissue or cell disruption in which the tissues and/or cell walls are fractured by specified forces created by the reciprocal motion producing the mechanical energy in a container with the tissue and liquid medium, thereby releasing the DNA from the tissue and into the medium (description column 2, lines 7-13). Gautsch further teaches methods of using tissue and/or cell wall fracturing particles in the disruptive media in a closed container (description column 2, lines 14-16). Gautsch teaches a BEAD BEATER bead mill manufactured by BioSpec Products for use with up to eight specimen vessels at one time (relevant to (a) disposing a plurality of samples into an array of sample containers) (description column 4, line 64 – column 5, line 1). Gautsch teaches the size of the particle also may vary depending on tissue type and scale of process, although particularly preferred are particles of from about 0.1 mm to about 2.0 cm (description, column 14, lines 47-49). Gautsch teaches that if the container further contains particles to aid the mechanical lysis, the total volume of the closed tube is about 1/3 particles, 1/3 tissue/buffer, and about 1/3 air space, which is about 33% bead loading by volume (description column 13, lines 39-42).
Yu teaches that bacteria, fungi and protozoa, present in rumen and gastrointestinal (GI) tracts, interact with feed, with each other, and with their host animals, resulting in a complex symbiotic microbiota (relevant to wherein the plurality of samples each comprise at least two different species of biological agents selected from bacterial cells, fungal cells and protozoans) (p.1, 1st paragraph). Yu teaches that ruminal and GI tract microbial communities are complex and contain numerous hard-to-lyse microorganisms (p.3, Direct DNA extraction). Yu teaches that community DNA is often extracted directly from digesta samples without cell isolation, using enzyme-chemical or mechano-chemical lysis (p.3, Direct DNA extraction). Yu further teaches that mechano-chemical lysis, especially bead beating in the presence of a detergent, is most commonly used due to its robustness and high efficiency in cell lysis (p.3, Direct DNA extraction).
Fujii teaches freeze-dried Monoraphidium sp. GK12 cells (30 mg) were suspended in 500 μL of distilled water containing 50 mg of 0.5-mm glass beads and 50mg of 0.1-mm zirconia silica beads, and were ground for 30 s using a Mini Bead Beater-8 (Biospec, USA) (relevant to wherein the first beads comprise an average diameter of 0.5mm; wherein the second beads comprise an average diameter of 0.1mm; and wherein the first and second beads are in a ratio of 1:1; relevant to claim 59: wherein the first and second beads are in a ratio of 1:1) (p.364, 2nd column Water-soluble vitamin analysis).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the Bead Beater bead mill using up to 8 specimen vessels taught by Gautsch for the KDL bead mill in the method taught by Jem to arrive at the claimed invention, because it would be a simple substitution of one known bead mill instrument for another. Both Jem and Gautsch teach methods of isolating DNA from cells using mechanical forces produced by particles. One of ordinary skill would reasonably expect that this simple substitution of one known instrument capable of handling up to 8 samples at a time for another known instrument that could only handle 1 sample at a time would predictably result advantageously in being able to process a plurality of samples.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the single size of bead taught by Jem with a mixture of different sized beads as taught by Yu in a 1:1 ratio taught by Fujii in the method of Jem to arrive at the claimed invention. Both Jem and Yu teach the use of bead mills to extract nucleic acids from a sample. One of ordinary skill in the art would have found it beneficial to use two different sizes of beads as taught by Yu to extract nucleic acids from a mixed sample of bacteria, fungi and protozoa taught by Yu, because Jem teaches that bacteria typically require a smaller bead of about 0.1mm while yeast require slightly larger beads about 0.5mm in diameter. One of ordinary skill would reasonably expect that mixing two sizes of beads in the bead mill would predictably result in extracting and isolating nucleic acids from bacterial cells, fungal cells and protozoa simultaneously, because Jem teaches different sized beads are used for different cell samples, Yu teaches DNA extraction using a mix of 0.1mm and 0.5mm beads, and it was known in the art at the time of invention that cells could be disrupted with a mixture of beads having diameters of 0.5mm and 0.1mm in a ratio of 1:1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Jem to use samples comprising at least two different species of biological agents such as bacterial cells, fungal cells and protozoans as taught by Yu, because Yu teaches that GI tracts contain a complex symbiota of bacteria, fungi and protozoa. Both Jem and Yu teach the isolation of nucleic acids from biological agents. One of ordinary skill would reasonably expect that substituting a sample comprising two different species as taught by Yu for a sample comprising one species taught by Jem would predictably result in being able to isolate nucleic acids from both biological agents such that the resulting amount of genetic material from each of the biological agents within the sample is extracted in proportion to the prevalence of each of the given biological agents in the sample, because it would amount to a simple substitution of one known sample for another, and it was known in the art at the time of invention that a sample comprising bacterial cells, fungal cells and protozoa could be used to successfully isolate nucleic acid material.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the volume of beads loaded in the chamber to arrive at the 40-60% by volume of the sample container, because Gautsch teaches a bead chamber filled about 33% and Jem teaches a bead chamber filled about 84%. One of ordinary skill would reasonably expect that reducing the volume of beads loaded into the sample container would predictably result in determining an optimum volume ratio of beads and sample within the sample container.
Regarding claim 3, Jem teaches the cell suspension was pumped through a horizontal grinding chamber filled about 80 to 85% with microspheres (beads) (relevant to substantially spherical) (description, column 14, lines 18-20). Jem further teaches a bead mill containing beads of about 0.1mm to about 1mm in diameter (relevant to beads of different sizes and comprising an average diameter of between 0.01 and 1.0mm) (description column 5, lines 44-45).
Regarding claims 16-18, Jem does not teach a mechanical force comprising subjecting the sample container to vertical or orbital oscillation.
Gautsch teaches a method involving the application of controlled oscillatory mechanical energy to the sample for short periods of time of about 5 to 60 seconds to lyse the sample and release the components from the sample, followed by standard isolation methods (abstract). Gautsch further teaches several specimen containing vessel receivers on the holder disc and showing further a tilting of the vessel holder in a position denoting the vertical extremes of the vertical oscillating movement to which it is subjected during apparatus operation (description column 2, lines 48-52 and Figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select orbital oscillations in place of vertical oscillation conditions taught by Gautsch in the method of mechanical disruption taught by Jem to arrive at the claimed invention. Gautsch teaches bead-beater systems that use oscillation to physically disrupt samples. One of ordinary skill in the art would have reasonably expected that substituting orbital oscillations as the mechanical force in the method of Jem would predictably result in unbiased release of nucleic acids, because Gautsch teaches oscillation forces are effective in disrupting cells.
Regarding claim 58, Jem teaches a bead chamber filled with approximately 1170 cc of 0.5mm dry glass beads (chamber volume is 1.4L) (description column 10, lines 27-29), which is 84% by volume. Jem teaches that glass beads are a typical medium for grinding cells, although ceramic or stainless steel beads are also used (relevant to the bead is composed of a ceramic) (description column 14, lines 4-5).
Jem does not teach wherein the plurality of beads are loaded in the sample container at 40-60% by volume.
Gautsch teaches that if the container further contains particles to aid the mechanical lysis, the total volume of the closed tube is about 1/3 particles, 1/3 tissue/buffer, and about 1/3 air space (description column 13, lines 39-42). Jem and Gautsch do not teach wherein the plurality of beads comprises beads of different sizes, wherein the beads of different sizes comprise beads that are 0.5mm and beads that are 0.1mm in diameter.
Yu teaches direct DNA extraction using Zirconia beads (0.1 and 0.5mm in diameter) (relevant to wherein the beads of different sizes comprise beads that are 0.5mm and beads that are 0.1 mm in diameter) (p.83, Materials). As evidenced by Manicone et al., Zirconia is a ceramic material (abstract), thus Yu teaches “wherein the beads are composed of a ceramic”.
Jem, Yu and Fujii do not teach a mechanical force comprising subjecting the sample container to oscillation.
Gautsch teaches a method involving the application of controlled oscillatory mechanical energy to the sample for short periods of time of about 5 to 60 seconds to lyse the sample and release the components from the sample, followed by standard isolation methods (abstract). Gautsch further teaches several specimen containing vessel receivers on the holder disc and showing further a tilting of the vessel holder in a position denoting the vertical extremes of the vertical oscillating movement to which it is subjected during apparatus operation (description column 2, lines 48-52 and Figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the volume of beads loaded in the chamber to arrive at the 40-60% by volume of the sample container, because Gautsch teaches a bead chamber filled about 33% and Jem teaches a bead chamber filled about 84%. One of ordinary skill would reasonably expect that reducing the volume of beads loaded into the sample container would predictably result in determining an optimum volume ratio of beads and sample within the sample container.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the single size glass bead taught by Jem with a mixture of different sized ceramic beads as taught by Yu and Fujii in the method of Jem to arrive at the claimed invention. Both Jem and Yu teach the use of inert beads in bead mills to extract nucleic acids from a sample. One of ordinary skill in the art would have found it beneficial to use two different sizes of beads as taught by Yu to extract nucleic acids from a mixed sample of bacteria, fungi and protozoa taught by Yu using the ratio of Fujii, because Jem teaches that bacteria typically require a smaller bead of about 0.1mm while yeast require slightly larger beads about 0.5mm in diameter. One of ordinary skill would reasonably expect that mixing two sizes of beads in the bead mill would predictably result in extracting and isolating nucleic acids from bacterial cells and yeast cells simultaneously, because Jem teaches that bacteria typically require a smaller bead of about 0.1mm while yeast require slightly larger beads about 0.5mm in diameter. One of ordinary skill would reasonably expect that substituting ceramic beads taught by Yu for the glass beads taught by Jem would predictably result in isolating nucleic acids from a sample, because it would have amounted to a simple substitution of one known bead material for another, and it was known in the art at the time of invention that glass beads and ceramic beads could be used in a bead mill for nucleic acid isolation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select orbital oscillations in place of vertical oscillation conditions taught by Gautsch in the method of mechanical disruption taught by Jem to arrive at the claimed invention. Gautsch teaches bead-beater systems that use oscillation to physically disrupt samples. One of ordinary skill in the art would have reasonably expected that substituting orbital oscillations as the mechanical force in the method of Jem would predictably result in unbiased release of nucleic acids, because Gautsch teaches oscillation forces are effective in disrupting cells.
Claims 19-20, 22-24 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Jem (US patent 6,455,287, issued on September 24, 2002; previously cited) in view of Gautsch et al. (US Patent 6,706,498, issued on March 16, 2004; previously cited), Yu et al. (“Nucleic acid extraction, oligonucleotide probes and PCR methods”. 2005. In: Makkar, H.P., McSweeney, C.S. (eds) Methods in Gut Microbial Ecology for Ruminants. Springer, Dordrecht; previously cited) and Fujii et al. (“Potential use of the astaxanthin-producing microalga, Monoraphidium sp.GK12, as a functional aquafeed for prawns”, Journal of Applied Phycology, 2010, Vol. 22, pp.363-369; previously cited) as applied to claim 1 above, and further in view of Carrera et al. (US Patent Publication 2013/0272087 A1, published on October 17, 2013; previously cited).
The teachings of Jem, Gautsch, Yu and Fujii are discussed above.
Regarding claims 19-20 and 24, Jem, Gautsch, Yu and Fujii do not teach a bashing magnet.
However, Carrera teaches a fluidically integrated magnetic bead beater (title). Carrera teaches a system for at least one of homogenization and lysis of a sample including one or more walls forming an enclosed chamber, a permanent magnet within the enclosed chamber (relevant to a bashing magnet), a magnet guide (relevant to a drive magnet), and one or more magnets located outside the chamber (abstract). Carrera further teaches that lobes 302 provide adequate space around magnetic beater 214 for liquid and beads to move while magnetic beater 214 traverses enclosed chamber 212 (description p.4, paragraph 0053). Carrera teaches a method of lysing the sample within the chamber via the movement of the permanent magnet and the plurality of beads (description p.2, paragraph 0013). Carrera teaches that the method further includes laterally guiding the movement of the permanent magnet between a first position and a second position within the chamber, and further includes homogenizing the sample within the chamber via the movement of the permanent magnet (description p.1, paragraph 0010). Carrera teaches that the magnetic field generated by the one or more magnets (relevant to a drive magnet) induces a force upon a permanent magnet (relevant to a bashing magnet) having a positive pole and a negative pole (description p.1, paragraph 0012). Carrera further teaches that the induced force causes the permanent magnet to move (relevant to using a drive magnet to move the bashing magnet) (description p.1, paragraph 0012). Carrera teaches that mechanical methods of disruption have a number of advantages, including employing a one-step process, generally very rapid, are amenable to automation, and have the ability to disrupt solid specimens such as bone, where the analyte(s) of interest may not be made obtainable without mechanical homogenization (description p.1, paragraph 0007).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the magnetic bead beater having cylindrical magnet as taught by Carrera for the bead beater taught by Gautsch using the method of Jem in view of Gautsch, Yu and Fujii to arrive at the claimed invention. One of ordinary skill in the art would have found it beneficial to use a magnetic bead beater as taught by Carrera because Carrera teaches that mechanical methods of disruption have a number of advantages. One of ordinary skill would have been motivated to use the magnetic bead beater taught by Carrera in place of the bead beater taught by Gautsch because using a magnet allows control over the lateral movement of the magnet to homogenize the sample, which would be beneficial for obtaining more complete cell disruption.
Regarding claims 22-23, Jem, Gautsch, Yu and Fujii do not teach wherein the bashing magnet and edge of the sample container comprise a gap of 0.7 to 1.2 mm or 0.9 to 1.1 mm.
Carrera teaches that the volume existing around the magnetic beater 214 within the enclosed chamber 212 is 1mL though other volumes may be considered as well (description p.4, paragraph 0053). Carrera further teaches that the geometry of the chamber walls includes lobes 302 and ridges 204 that act as magnet guides (description p.4, paragraph 0051). Carrera teaches that lobes 302 provide adequate space around magnetic beater 214 for liquid and beads to move while magnetic beater 214 traverses the enclosed chamber 212 (description p.4, paragraph 0053). Carrera further teaches that the curvature and general size of lobes 302 may be chosen so as to reduce any dead volume within enclosed chamber 212 (description p.4, paragraph 0053).
Carrera does not explicitly teach a gap of 0.7 to 1.2 mm or 0.9 to 1.1 mm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the gap between the bashing magnet and the edge of the sample container based on the gap volume taught by Carrera to arrive at a gap between 0.9 to 1.1 mm with reasonable expectation of success, by adjusting the curvature and size of the lobes taught by Carrera to obtain a gap distance within the desired range. The results would have been predictable to one of ordinary skill in the art because the function of the volume around the magnetic beater and the effect on dead volume reduction in the chamber was known at the time of invention.
Regarding claim 28, Jem, Gautsch, Yu and Fujii do not teach wherein the drive magnet to bashing magnet pulling force ratio is from 8:1 to 10:1.
Carrera teaches a method of introducing a sample into an enclosed chamber and actuating one or more magnets located outside the chamber (description p.1, paragraph 0011). Carrera teaches that the magnetic field generated by the one or more magnets induces a force upon a permanent magnet disposed within the chamber, the permanent magnet having a positive pole and a negative pole (description p.1, paragraph 0011). Carrera teaches that the induced force caused the permanent magnet to move, and further includes laterally guiding the movement of the permanent magnet between a first position and a second position (description p.1, paragraph 0011).
Carrera does not explicitly teach a magnet pulling force ratio is from 8:1 to 10:1.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the force generated by the permanent magnet as taught by Carrera to identify optimum pulling force ratios to obtain the magnet pulling force ratio desired with reasonable expectation of success, by adjusting the field generated by the one or more magnets. The results would have been predictable to one of ordinary skill in the art because the function of magnetic field and the magnet pulling force was known in the art at the time of invention.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Jem (US patent 6,455,287, issued on September 24, 2002; previously cited) in view of Gautsch et al. (US Patent 6,706,498, issued on March 16, 2004; previously cited), Yu et al. (“Nucleic acid extraction, oligonucleotide probes and PCR methods”. 2005. In: Makkar, H.P., McSweeney, C.S. (eds) Methods in Gut Microbial Ecology for Ruminants. Springer, Dordrecht; previously cited) and Fujii et al. (“Potential use of the astaxanthin-producing microalga, Monoraphidium sp.GK12, as a functional aquafeed for prawns”, Journal of Applied Phycology, 2010, Vol. 22, pp.363-369; previously cited) as applied to claim 1 above, and further in view of Carrera et al. (US Patent Publication 2013/0272087 A1, published on October 17, 2013; previously cited) and Jovanovich et al. (WO 2010/141921 A1, published on December 9, 2010; previously cited).
The teachings of Jem, Gautsch, Yu and Fujii are discussed above.
Regarding claim 21, Jem, Gautsch, Yu and Fujii do not teach wherein the bashing magnet is a rectangular bar.
Carrera teaches that the permanent magnet may have a substantially cylindrical shape (description, paragraph 0056).
Carrera does not teach that the magnet is a rectangular bar.
Jovanovich teaches a system that can process a raw biological sample, perform a biochemical reaction and provide an analysis readout (abstract). Jovanovich teaches that the system can extract DNA from a swab, amplify STR loci from the DNA, and analyze the amplified loci and STR markers in the sample (abstract). Jovanovich teaches a MagMill or magnetically driven lysis or homogenizing device for efficient lysis of Bacillus and other spores, as well as vegetative cells (description, paragraph 00406). Jovanovich further teaches that the magnet 2002 contained within the sample-containing vessel can have any shape, for example the magnet can have a bar, spherical, cylindrical, rectangular, oval, hexagonal or propeller shape (description, paragraph 00406).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a rectangular bar magnet for the bashing magnet shape, because it would amount to a simple substitution of a rectangular bar shape as taught by Jovanovich for the cylindrical shape taught by Carrera. The results would have been predictable to one of ordinary skill in the art because Jovanovich teaches that the magnet can have any shape including cylindrical or rectangular, and the function of the bashing magnet was known at the time of invention. One skilled in the art would reasonably expect that changing the physical shape of the magnet would predictably result in the magnet functioning as intended.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Jem (US patent 6,455,287, issued on September 24, 2002; previously cited) in view of Gautsch et al. (US Patent 6,706,498, issued on March 16, 2004; previously cited), Yu et al. (“Nucleic acid extraction, oligonucleotide probes and PCR methods”. 2005. In: Makkar, H.P., McSweeney, C.S. (eds) Methods in Gut Microbial Ecology for Ruminants. Springer, Dordrecht; previously cited) and Fujii et al. (“Potential use of the astaxanthin-producing microalga, Monoraphidium sp.GK12, as a functional aquafeed for prawns”, Journal of Applied Phycology, 2010, Vol. 22, pp.363-369; previously cited) as applied to claim 1 above, and further in view of Dudley et al. (WO 2014/059370 A1, published on April 17, 2014; previously cited).
The teachings of Jem, Gautsch, Yu and Fujii are discussed above.
Regarding claim 9, Jem, Gautsch, Yu and Fujii do not teach wherein the sample containers are in a 96-well format.
However, Dudley teaches an improved high throughput system for genetic studies (title). Dudley teaches methods of high-throughput genetics by enabling the generation and genotyping of large numbers of progeny that are isolated, genotyped, and maintained as individuals that allows the sister spore relationships of all four meiotic products to be recovered (description p.3, paragraph 0007). Dudley teaches yeast cell genomic DNA isolation in 96-well format using the ZR 96 Fungal/Bacterial DNA Kit™ (ZymoResearch) (description p.16, paragraph 0044). Dudley teaches that yeast cells were pelleted and transferred to the kit’s ZR lysis rack, containing 0.5mm beads, and the racks were processed at 1300 rpm for 2 min in a 96-well block bead beater (Geno/Grinder® 2010, SPEC Sample Prep.) (description p.16, paragraph 0044).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the 96-well block bead grinder taught by Dudley for the single-chamber bead grinder taught by Jem, because Dudley teaches that using a high-throughput machine is beneficial for improving genetic material for studies. One of ordinary skill in the art would have found it reasonably expect that using a 96-well block bead grinder in order to rapidly process multiple samples in the same amount of time would predictably result in nucleic acid isolated from a plurality of samples.
Claims 56 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Jem (US patent 6,455,287, issued on September 24, 2002; previously cited) in view of Gautsch et al. (US Patent 6,706,498, issued on March 16, 2004; previously cited), Yu et al. (“Nucleic acid extraction, oligonucleotide probes and PCR methods”. 2005. In: Makkar, H.P., McSweeney, C.S. (eds) Methods in Gut Microbial Ecology for Ruminants. Springer, Dordrecht; previously cited) and Fujii et al. (“Potential use of the astaxanthin-producing microalga, Monoraphidium sp.GK12, as a functional aquafeed for prawns”, Journal of Applied Phycology, 2010, Vol. 22, pp.363-369; previously cited) as applied to claim 1 above, and further in view of Kido et al. (“A novel, compact disk-like centrifugal microfluidics system for cell lysis and sample homogenization”, Colloids and Surfaces B, 2007, Vol. 58, pp.44-51; previously cited) and Hosney et al. (“In Vitro Validation of Clearing Clogged Vessels using Microrobots”, 2016 6th IEEE International Conference on Biomedical Robotics and Biomechatronics (BioRob), Singapore, 2016, pp. 272-277; previously cited).
The teachings of Jem, Gautsch, Yu and Fujii are discussed above.
Regarding claims 56 and 57, Jem, Gautsch, Yu and Fujii do not teach wherein the lateral oscillation has an offset of 15-25 mm.
However, Kido teaches that the most efficient and elegant method of mechanical cell lysis is bead-beating (p.45, 2nd column – 1st full paragraph). Kido teaches the instrumentation of bead-beating technology includes vortex-like shakers, linear motion shakers such as mixer-mills (lateral oscillation) and orbital shakers (orbital oscillation) (p.45, 2nd column – 2nd full paragraph).
Hosney teaches mechanical grinding of blood clots using helical microbots that are steered under the influence of rotating magnetic fields (abstract). Hosney teaches that an offset of 15mm exerts an additional magnetic force to assist the grinding (abstract). Hosney teaches that non-zero offset between the helical microrobot and the dipole field provides an additional pulling magnetic force and a decrease in the exerted magnetic torque (p.274, 1st column - top paragraph). Hosney further teaches examining the effect of offsets ranging from 0 mm to 40 mm to study the effect of the offset on the drilling time (p.274, 1st column – top paragraph). Hosney teaches that
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Jem in view of Gautsch, Yu and Fujii to replace the vertical oscillation taught by Gautsch with lateral oscillation taught by Kido, because Kido teaches that mechanical cell lysis can be accomplished through linear motion shakers and orbital shakers. One of ordinary skill would reasonably expect that substituting lateral oscillation for vertical oscillation would predictably result in cell lysis, because it would amount to a simple substitution of one known oscillation for another, and the use of lateral, vertical and orbital motions for mechanical cell lysis were known in the art at the time of invention.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further select lateral oscillation with an offset of 15mm, because Hosney teaches that an offset of 15mm exerts an additional magnetic force to assist the grinding. One of ordinary skill in the art would have found it beneficial to have a 15mm offset, because Hosney teaches that a non-zero offset provides an additional pulling magnetic force and a decrease in the exerted magnetic torque.
Response to Arguments
Regarding the rejection of claims 1, 3, 16-18, 55 and 58-59: Applicant argues that the optimal bead volume is not an obvious parameter, and the data show that it has a substantial impact on yield (See Remarks dated 1/23/26, p.6 last paragraph). Applicant argues that as shown in instant FIG. 18B, bead volumes of approximately 40-60% produce markedly higher average yields compared to significantly higher fill levels, confirming that bead volume is a critical variable affecting performance (See Remarks dated 1/23/26, p.6 last paragraph).
Applicant argues that Jem does not teach or suggest any advantage to the use of ceramic beads like the instant claimed method provides, citing [0131] from the specification and stating the DNA recovery was nearly 100% using ceramic beads and lower using other bead types (See Remarks dated 1/23/26, p.7 last paragraph).
Applicant's arguments filed January 23, 2026 have been fully considered but they are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., average yield of DNA based on bead volume; DNA yield based on bead material i.e. ceramic beads over other materials) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Jem teaches the claimed method steps of disposing a sample into a sample container; sample containers comprising the sample and a plurality of beads; agitating the sample and passing the sample through a bead mill containing beads; and using beads of different sizes, as required by the instant claims. Gautsch teaches filling the container about 1/3 particles, which is a 33% volume and not significantly different from 40%. Fujii teaches using two differently sized beads at a 1:1 ratio, using a mixture of 50mg of 0.5mm glass beads and 50mg of 0.1mm zirconia silica beads. The amount of DNA extraction is a desired result of practicing the claimed method of disposing a plurality of samples into an array of sample containers and applying a mechanical force to the sample containers.
Regarding the rejection of claims 19-20, 22-24 and 28: Applicant argues that Carrera does not cure the deficiencies of Jem, Gautsch, Yu and Fujii as discussed above, and requests the rejection to be withdrawn.
Applicant’s arguments are not found persuasive for the reasons stated above.
Regarding the rejection of claim 21: Applicant argues that Jovanovich and Carrera do not cure the deficiencies of Jem, Gautsch, Yu and Fujii as discussed above.
Applicant’s arguments are not found persuasive for the reasons stated above.
Regarding the rejection of claim 9: Applicant argues that Dudley does not cure the deficiencies of Jem, Gautsch, Yu and Fujii as discussed above.
Applicant’s arguments are not found persuasive for the reasons stated above.
Regarding the rejection of claims 56 and 57: Applicant argues that Kido and Hosney do not cure the deficiencies of Jem, Gautsch, Yu and Fujii as discussed above.
Applicant’s arguments are not found persuasive for the reasons stated above.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/DEEPA MISHRA/Examiner, Art Unit 1657