DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of 1-5, 8-11, 15-29, 35, and 37-39 in the reply filed on 11/25/25 is acknowledged.
Claims 46-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (kit), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/25/25.
Claim Status
Claims 1-5, 8-11, 15-29, 35, and 37-39 are pending and are examined. Claims 46-49 are withdrawn and are not examined.
Claim Objections
Claim 16 is objected to because of the following informalities: “0. I mm” should be “0.1 mm”. 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.
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.
Claims 1, 2, 3, 4, 5, 8, 9, 10, 11, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 38, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Terbrueggen (US Pub 2016/0045187), in view of Klapproth (US Pub 2017/0218356).
Regarding Claim 1, Terbrueggen teaches a method comprising:
(a) receiving into a facility one or a plurality of closed containers ([0219] at the manufacturing facility site before shipping the device to an end user.), each container comprising (A device for collecting and stabilizing a biological sample, the device comprising:
(a) a housing comprising an open end portion, an closed end portion, and an interior space. See Claim 1; Figs. 1A-D, housing 102).
(i) a cap comprising an applicator attached thereto and disposed in the container (a collector removably engagable with the open end portion of the housing and capable of sealingly closing the open end portion of the housing. See Claim 1., Figs. 2A-3D seal 116),
(ii) solid beads adapted for cell disruption ([0278] In accordance with one aspect of the invention, the probes can possess detectable labels (e.g. fluorescent labels, electrochemical labels, magnetic beads, nanoparticles, biotin, etc.) to aid in the identification, purification, quantification or detection of the ligated oligonucleotide product. The probes may also optionally include in their structure: anchoring oligonucleotide sequences designed for subsequent capture on a solid support (microarrays, microbeads, nanoparticles), molecule handles that promote the concentration or manipulation of the ligated product (magnetic particles, oligonucleotide coding sequences), and promoter sequences to facilitate subsequent secondary amplification of the ligated product via an enzyme like a DNA or RNA polymerase.),
(iii) an aqueous liquid comprising one or more nucleic acid preservatives, and (iv) a sample comprising cells ([0275] The buffers of the invention may further include any additional components known in the art, particularly components known in the art to be of use in reactions involving nucleic acids. Additional components may include without limitation: adjuvants, diluents, binders, stabilizers, salts (including NaCl and MgCl2), lipophilic solvents, preservatives, or the like.);
Terbrueggen is silent to (b) subjecting material in the received container to mechanical agitation sufficient to lyse cells, to provide a container comprising a cell homogenate; and (c) providing the cell homogenate to a liquid handling system, wherein the liquid handling system processes the sample, wherein processing comprises isolating nucleic acid from the cell homogenate.
Klapproth teaches in the related art of extracting nucleaic acids. [0090] After placing the sample in the bead beating tube, the tube is subject to agitation to mechanically lyse the cells. Lysis can be achieved by a common laboratory vortexer or a homogenizer. While processing time in a vortexer is 3-10 times longer than that in a specialty homogenizer, vortexing works for easily disrupted cells and is inexpensive. [0093] After cell lysis, the fluid sample is separated from the beads, for instance by removing the liquid sample from the sample tube by means of a pipette or the like, leaving behind the beads, which deposit on the bottom of the sample tube. [0094] Impurities that might interfere with analysis of the extracted DNA can be removed, for example by precipitation of the impurities by known methods such as with ammonium acetate or using a commercial kit. [0095] The nucleic acid can be recovered and washed and optionally further purified. Recovery and/or purification of nucleic acid can be carried out using routine methods such as by precipitation with isopropanol or using a commercial kit or an automated instrument. [0096] The analysis of a sample for the presence of nucleic acids of interest (such as bacterial or fungal DNA) can be performed using any nucleic acid analysis method including, but not limited to amplification technologies.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the steps of (b) subjecting material in the received container to mechanical agitation sufficient to lyse cells, to provide a container comprising a cell homogenate; and (c) providing the cell homogenate to a liquid handling system, wherein the liquid handling system processes the sample, wherein processing comprises isolating nucleic acid from the cell homogenate, as taught by Klapproth, to the method of Terbrueggen, to allow for disrupting cells, recovery and purification of nucleic acids in an inexpensive manner, as taught by Terbrueggen, in [0090] and [0095].
Regarding Claim 2, modified Terbrueggen teaches the method of claim 1, wherein subjecting the material in the received container does not comprise transferring some or all of the sample from the received container to another, different, container ([0192] transfer reactions).
Regarding Claim 3, Terbrueggen teaches the method of claim 1, wherein the container has a capacity of no more than about 3 ml ([0284] 1.7 mL microfuge tube).
Regarding Claim 4, modified Terbrueggen teaches the method of claim 1, wherein the container comprises a bead beating tube compatible with commercially available bead beating instruments ([0089] As an initial step in nucleic acid preparation, a sample is placed into a bead beating tube for bead beating. The bead beating step can utilize a bead beating system of the disclosure or a standard bead beating system.).
Regarding Claim 5, Terbrueggen teaches the method of claim 1, wherein the container comprises a plastic, wherein the plastic comprises polypropylene ([0025] polypropylene).
Regarding Claim 8, Terbrueggen teaches the method of claim 1, wherein the container is a screw top container ([0053] screw).
Regarding Claim 9, modified Terbrueggen teaches the method of claim 1, wherein the applicator has a paddle or spoon-shaped end ([0196] Figs. 1A-1D the collector 106 includes an absorbent member 118 for collecting the biological sample.).
Regarding Claim 10, modified Terbrueggen teaches the method of claim 1, wherein the applicator has a stick shape ([0196] Figs. 1A-1D the collector 106 includes an absorbent member 118 for collecting the biological sample.).
Regarding Claim 11, modified Terbrueggen teaches the method of claim 1, wherein the applicator has a volume between about 10 L and 100 L, or between about 20 L and about 50 L (the applicator would be capable of having a volume between about 10 L and 100 L, or between about 20 L and about 50 L).
Regarding Claim 15, modified Terbrueggen teaches the method of claim 1, wherein the solid beads comprise zirconium, a glassy or stainless steel ([0191] In Claim 20, the beads comprise mineral beads, ceramic beads, glass beads, metal beads, or a combination thereof. [0192] In Claim 21, the beads comprise zirconium beads, zircon beads, zirconia beads, quartz beads, aluminum oxide beads, silicon carbide beads, ceramic beads, silicon dioxide glass beads, stainless steel beads, chrome steel beads, or a combination thereof.).
Regarding Claim 16, modified Terbrueggen teaches the method of claim 1, wherein the solid beads have a diameter between about 0.1 mm and about 2 mm, or wherein the solid beads have a diameter of about 0.5 mm or about 1 mm ([0077] the beads will range from 50 μm to 3 mm in diameter.).
Regarding Claim 17, modified Terbrueggen teaches the method of claim 1, wherein each container comprises an identifier, that differentiates containers comprising samples from different sources (identifier see barcode in Fig. 11, 1102).
Regarding Claim 18, modified Terbrueggen teaches the method of claim 1, wherein the nucleic acid preservative comprises an RNA preservative or a DNA preservative ([0275] preservatives).
Regarding Claim 19, modified Terbrueggen teaches the method of claim 1, wherein the preservative preserves both RNA and DNA at room temperature for at least two weeks ([0275] preservatives, the preservatives would preserve RNA and DNA at room temperature for at least two weeks).
Regarding Claim 20, Terbrueggen teaches the method of claim 1, wherein the sample comprises a fecal sample, saliva sample, a vaginal sample, or a blood sample ([0002] collecting and stabilizing blood or other bodily fluids from a user's fingertip, earlobe, heel or other locations.).
Regarding Claim 21, Terbrueggen teaches the method of claim 1, wherein the one or a plurality of closed containers received is at least any of 10, 25, 50, 90, 150, or 300 closed containers (TABLE-US-00008 TABLE 8 400-001 Tubes (BCT) DxCollect DirectMix A Contains S-probes).
Regarding Claim 22, modified Terbrueggen teaches the method of claim 1, wherein the closed containers are received from each of a plurality of different remote locations ( more particularly, for collecting and stabilizing blood or other bodily fluids from other locations.).
Regarding Claim 23, modified Terbrueggen teaches the method of claim 1, wherein receiving comprises receiving, in a single package, a plurality of the closed containers, wherein, (A) at least one of the containers is subjected to the agitation and processing; and (B) at least one of the other containers is received into storage ([0011] Various other aspects of the present invention provide methods to use the novel devices and kits to collect and stabilize biological samples. In some embodiments, a method of the present invention includes (i) collecting a biological sample using the collector and (ii) inserting the collector into the housing. In some embodiments, the method further includes (iii) transporting or shipping the collector along with the housing to a receiver such as a testing lab for subsequent processing. [0090] After placing the sample in the bead beating tube, the tube is subject to agitation to mechanically lyse the cells.).
Regarding Claim 24, modified Terbrueggen teaches the method of claim 1, further comprising, before agitating, replacing the cap comprising an applicator with a cap that does not comprise an applicator (see Figs. 6A-6D).
Regarding Claim 25, modified Terbrueggen teaches the method of claim 1, wherein agitation comprises bead beating ([0089] As an initial step in nucleic acid preparation, a sample is placed into a bead beating tube for bead beating tube. The bead beating tube step can utilize a bead beating tube system of the disclosure or a standard bead beating tube system).
Regarding Claim 26, modified Terbrueggen teaches the method of claim 1, wherein the cell homogenate is provided to the liquid handling system in the same container ([0022] Bead beating is a homogenization process used to lyse cells in order to release their contents, including their nucleic acids (DNA and RNA). Samples are placed in tubes with the appropriate grinding beads and subjected to high energy mixing. The samples are then typically centrifuged and the lysate recovered from above the beads.).
Regarding Claim 27, modified Terbrueggen teaches the method of claim 1, wherein the cell homogenate is provided to the liquid handling system in a different container ([0091] Many homogenizers suitable for bead beating are commercially available and can be used with the beat beating systems of the disclosure.).
Regarding Claim 38, modified Terbrueggen teaches the method of claim 1.
Modified Terbrueggen is silent to a liquid handling system operates in an 8x12 tube format.
An 8x12 tube format is standard for a laboratory apparatus of for testing multiple biological samples simultaneously.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used an 8x12 tube format for the liquid handling system in the method of modified Terbrueggen to allow for simultaneously analyzing of multiple biological samples.
Regarding Claim 39, modified Terbrueggen teaches the method of claim 1, further comprising, before receiving, transmitting one or a plurality of sample collection kits to each of one or a plurality of locations remote from the facility, wherein each sample collection kit comprises (i) a container, (ii) a cap comprising an applicator attached thereto, (iii) an aqueous solution, and (iv) solid beads adapted for cell disruption (Fig. 6, tube, cap, applicator, [0278] , the probes can possess detectable labels (e.g. fluorescent labels, electrochemical labels, magnetic beads, nanoparticles, biotin, etc.) to aid in the identification, purification, quantification or detection of the ligated oligonucleotide product.).
Claims 28, 29, 35, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Terbrueggen (US Pub 2016/0045187), in view of Klapproth (US Pub 2017/0218356), and further in view of Wang (US Pub 2016/0017320).
Regarding Claims 28, 29, 35, and 37, modified Terbrueggen is silent to the method of claim 1.
Modified Terbrueggen is silent to wherein processing comprises preparing a DNA library or an RNA library from nucleic acid in the sample, processing comprises: (1) isolating RNA from the sample; and (2) converting the isolated RNA into adapter-tagged cDNA, wherein processing comprises:(1) isolating DNA from the sample; (2) performing end repair on the isolated DNA; and(3) ligating adapters comprising oligonucleotide primer binding sites to the end repaired DNA to produce adapter tagged DNA, comprising: (d) preparing, from the isolated nucleic acid, an adapter tagged library; (e) amplifying the adapter tagged library; and(f) sequencing the amplified, adapter tagged library.
Wang teaches in the related art of nucleic acids. [0066] Thus, sequencing adapters generated from oligonucleotides in one set (“Set A”) may be used to generate a sequencing library for DNA fragments of one sample (“Sample A”), and sequencing adapters generated from oligonucleotides in another set (“Set B”) may be used to generate a sequencing library for DNA fragments of another sample (“Sample B”). [0160] The cDNA molecules may also be first fragmented, the resulting fragments may be then end-repaired, and optionally single or multiple nucleotides may be added to the 3′ termini of the end-repaired cDNA fragments before being ligated to sequencing adapters. [0161] [0161] Methods for fragmenting DNA molecules, end-repairing of DNA fragments, adding 3′-overhangs to end-repaired DNA fragments, and ligating adapters to blunt-ended DNA fragments or to DNA fragments with 3′-overhangs (e.g., modified DNA molecules or fragments having adenines added to their 3′ ends) are known in the art and may be used in generating sequencing libraries. [0163] A schematic representation of generating a sequencing library of DNA or cDNA molecules or fragments using sequencing adapters having a semi-random barcode sequence (as well as subsequent sequencing) is shown in FIG. 7. [0172] The kit comprises sequencing adapters or sets of sequencing adapters that comprise semi-random barcode sequences as provided herein, and may further comprise one or more of the following additional components: a DNA ligase (e.g., T4 DNA ligase and E. coli DNA ligase), a ligation buffer, an end-repair enzyme mix (e.g., an enzyme mix containing T4 DNA polymerase coupled with Klenow DNA Polymerase and T4 Polynucleotide kinase), an end-repair buffer. [0176] the same sequencing adapter is attached (e.g., ligated) to both ends of each cDNA molecule. In other embodiments, two different sequencing adapter are attached (e.g., ligated) to the two ends of each cDNA molecule. The ds sequencing adapter(s) used in this method do not need to contain a semi-random barcode sequence because the semi-random barcode sequence is present in the reverse transcription primer and thus already incorporated into the cDNAs prior to being ligated to the sequencing adapters.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the steps of processing comprises preparing a DNA library or an RNA library from nucleic acid in the sample, processing comprises: (1) isolating RNA from the sample; and (2) converting the isolated RNA into adapter-tagged cDNA, wherein processing comprises:(1) isolating DNA from the sample; (2) performing end repair on the isolated DNA; and(3) ligating adapters comprising oligonucleotide primer binding sites to the end repaired DNA to produce adapter tagged DNA, comprising: (d) preparing, from the isolated nucleic acid, an adapter tagged library; (e) amplifying the adapter tagged library; and(f) sequencing the amplified, adapter tagged library, as taught by Wang, to the method, as taught by Modified Terbrueggen, to allow for nucleic acid sequencing and preparing sequencing adapters and sequencing libraries, as taught by Wang, in the Abstract, and [0003].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798