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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 11, 2023 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claim 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of copending Application No. 16501730 (reference application) (‘730 application herein). Although the claims at issue are not identical, they are not patentably distinct from each other because while the language of the claims of the ‘730 Application and the instant claims are not word for word the same, both sets of claims encompass the same type of method and cover the same subject matter. Compare claims 2-6 of the instant claims and the claims of the ‘730 application, where the same dependent limitations are included, which include streptavidin coated magnetic beads (see claim 2 of each claim set), origami tails (see claims 4-5 of both claim sets) and particular length of primer (see claim 6 of each claim set).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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.
Claim(s) 1-3, 6, 9, 15-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dapprich et al. (US Patent 9,103,827; August 2015) in view of Lowery Jr et al. (US PgPub 20120100546; April 2012).
With regard to claim 1, Dapprich teaches a method for capturing a long polynucleotide comprising a DNA target segment from a population of polynucleotide molecules, the method comprising:
providing a mixture comprising the population of the polynucleotide molecules, capture molecules comprising one or more polynucleotide primers and/or biotinylated nucleotides, and a buffered liquid medium (example 2, Figure 2, where primers are extended with biotinylated nucleotides);
denaturing the polynucleotide molecules in the mixture so as to create single stranded portions of the polynucleotide molecules which can be accessible to the one or more polynucleotide primers (example 2, Figure 2, where primers are extended with biotinylated nucleotides and where primer extension includes denaturation, hybridization and extension);
hybridizing the one or more capture molecules to the polynucleotide comprising the DNA target segment (example 2, Figure 2, where primers are extended with biotinylated nucleotides and where primer extension includes denaturation, hybridization and extension);
adding streptavidin-labeled magnetic beads to the mixture;
using a magnetic field to move the streptavidin-labeled magnetic beads relative to the buffered liquid medium as a means for increasing binding of the biotinylated nucleotides of the capture molecules to the streptavidin-labeled magnetic beads (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads);
and using the magnetic field to collect the streptavidin-labeled magnetic beads so as to capture the polynucleotide comprising the DNA target segment which is bound to the streptavidin- labeled magnetic beads (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads).
With regard to claim 2, Dapprich teaches a method according to claim 1, wherein the winding of the biotinylated nucleotides of the capture molecules onto the streptavidin-labeled magnetic beads lessens entanglement of the captured long polynucleotide with the population of polynucleotides so as to avoid an increase in off-target capture during capturing of the polynucleotide comprising the DNA target segment from a population of polynucleotide molecules (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads).
With regard to claim 3, Dapprich teaches a method according to claim 1, wherein the one or more polynucleotide primers are capable of binding to the same polynucleotide strand or to two or more separate polynucleotide strands (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads).
With regard to claim 6, Dapprich teaches a method according to claim 1, wherein the polynucleotide primer has a length of between about 15 to about 30 DNA bases and polynucleotide primers designed to hybridize to adjacent DNA target segments are spaced at a distance of between about 1 to about 20 kilobases, to pull down the polynucleotide comprising the DNA target segment from a population of polynucleotide molecules (Example 8, where the primer sequence is given and the primer is 20 nt in length).
With regard to claim 9, Dapprich teaches a method according to claim 1, wherein the polynucleotide primer has a number of nucleotide bases selected from the group consisting of 5 bases, 6 bases, 7 bases, 8 bases, 9 bases, 10 bases, 15 bases, 16 bases, 17 bases, 18 bases, 19 bases, 20 bases, 21 bases, 22 bases, 23 bases, 24 bases, 25 bases, 26 bases, 27 bases; 28 bases, 29 bases, 30 bases, 31[[q]] bases, 32 bases, 33 bases, 34 bases, 35 bases, 36 base, 37 bases, 38 bases, 39 base, 40 bases, 41 base, 42 bases, 43 bases, 44 bases, 45 bases, 46 bases, 47 bases, 48 bases, 49, bases, 50 bases and any combination thereof (Example 8, where the primer sequence is given and the primer is 20 nt in length).
With regard to claim 15, Dapprich teaches a method according to claim 1, wherein the buffered liquid medium is a buffer MBSA which comprises an aqueous solution comprising 10 mM Tris pH 7.5, 2 mM EDTA, 0.2% Tween-20, 1 M NaCl, 5 pg/ml BSA, 1.25 mg/ml Nestle Carnation dried milk, and 1 mg/ml glycine, wherein the polynucleotide molecules can be selected from the group consisting of a DNA sample, a genomic DNA sample, a plasmid DNA sample, an amplified DNA sample, a cDNA, a mitochondrial nucleotide sample, an oligonucleotide sample, an oligo-peptide nucleic acid (PNA) sample, an oligo-LNA, and any combination thereof, and wherein the polynucleotide molecules may be obtained from a human, a mammal, a plant, a bacteria, an archaea, a fungi, a viruses, a single biological cell, a biological tissue, a biological organ, and any combination thereof, wherein each of the magnetic beads have a diameter of about one micron and the rotation of each magnetic bead is at least one winding turn to increase the binding and winding of the biotinylated nucleotides of the capture molecules around the magnetic bead, wherein the long polynucleotide is from about 10 kb to about 5 Mb in length, or a combination thereof (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads).
With regard to claim 16, Dapprich teaches a method according to claim 1, wherein a nucleotide linker is selected from the group consisting of AcryditeTMACRYDITETM acrylic phosphoramidite-based nucleotide linker, Adenylation, Azide NHS ester, Digoxigenin NHS Ester, Cholesterol-TEG, I- LinkerTMI-LINKERTM covalent attachment linker, biotin, streptavidin, and any combination thereof (Example 2 and 4 and Fig 2, where the biotin labeled extended primers are captured with streptavidin coated magnetic beads).
With regard to claim 18, Dapprich teaches a kit, comprising:
streptavidin-labeled magnetic beads; polynucleotide primers comprising nucleotides and/or biotinylated nucleotides; and a polymerase enzyme (example 2, Figure 2, where primers are extended with biotinylated nucleotides).
With regard to claim 19, Dapprich teaches a kit according to claim 18, further comprising a buffered liquid medium (example 2, Figure 2, where primers are extended with biotinylated nucleotides).
Regarding claims 1, 7 and 20, while Dapprich teaches many steps of the method, Dapprich does not specifically teach the step of rotation of the magnetic field.
With regard to claim 1, Lowery Jr teaches using either a rotation of the magnetic field relative to the mixture or a rotation of the mixture relative to the magnetic field for causing a streptavidin-labeled magnetic bead rotation in the buffered liquid medium as a means for performing the steps of increasing the binding of the biotinylated nucleotides of the capture molecules to the streptavidin-labeled magnetic beads and increasing the winding of the biotinylated nucleotides of the capture molecules onto and around the streptavidin-labeled magnetic beads, so as to increase the probability of capturing a long polynucleotide comprising the DNA target segment, wherein the long polynucleotide is at least 10 kb, and so as to increase the probability of preventing damage to the long polynucleotide comprising the DNA target segment (p 4, paragraph 13-15; Figure 26 legend, Example 16, where long oligonucleotides are captured on the magnetic particle surface, specifically, p. 54, paragraph 443).
With regard to claim 7, Lowery Jr teaches a method of claim 1, where the step of using either a rotation of the magnetic field relative to the mixture or a rotation of the mixture relative to the magnetic field for causing 104a streptavidin-labeled magnetic bead rotation in the buffered liquid medium comprises a streptavidin-labeled structure (p 4, paragraph 13-15; Figure 26 legend).
With regard to claim 20, Lowery Jr teaches a kit according to claim 18, further comprising a rotating magnetic field (p 4, paragraph 13-15; Figure 26 legend).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Dapprich to include the rotating magnetic field as taught by Lowery, Jr to arrive at the claimed invention with a reasonable expectation for success. Both Dapprich and Lowery Jr are focused on methods which incorporate magnetic beads and streptavidin and biotin label interactions for the capture and agglomeration of large macromolecules. Lowery Jr devotes some time to the specific issue of magnetic field rotation and notes that their method is first focused on “specific agglomeration of magnetic particles in a liquid sample by (i) providing a liquid sample including one or more analytes and the magnetic particles, wherein the magnetic particles have binding moieties on their surfaces, the binding moieties operative to alter the specific aggregation of the magnetic particles in the presence of the one or more analytes or a multivalent binding agent; (ii) applying a magnetic field gradient to the liquid sample for a time sufficient to cause concentration of the magnetic particles in a first portion of the liquid sample; (iii) following step (ii), agitating the liquid sample; and (iv) repeating step (ii). In certain embodiments, step (iii) includes vortexing the liquid sample” (p 4, paragraph 14). Further, the method “features a method for assisting the specific agglomeration of magnetic particles in a liquid sample by (i) providing a liquid sample including one or more analytes and the magnetic particles, wherein the magnetic particles have binding moieties on their surfaces, the binding moieties operative to alter the specific aggregation of the magnetic particles in the presence of the one or more analytes or a multivalent binding agent; and (ii) exposing the liquid sample to a gradient magnetic field and rotating the gradient magnetic field about the sample, or rotating the sample within the gradient magnetic field” (p 4, paragraph 15). Finally, regarding the topic of capture and protection of longer oligos, Lowery, Jr teaches “modification to this procedure could include hybridization of a particle bound capture probe flanking the hybridization of a biotinylated probe. When a perfectly complementary duplex is formed via hybridization of the particle bound probe, the ligase would covalently bind the biotin probe to the magnetic particle. Again repeated rounds of heat denaturation followed by annealing and ligation should yield a high proportion of long biotinylated oligos on the magnetic particle surface. A wash to remove any free probe would be conducted followed by the addition of a second streptavidin labeled superparamagnetic particle. Agglomeration would ensue only if the biotinylated probes were ligated onto the surface of first particle” (p 54, Example 16, paragraph 443). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Dapprich to include the rotating magnetic field as taught by Lowery, Jr to arrive at the claimed invention with a reasonable expectation for success.
Claims 4-5 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dapprich et al. (US Patent 9,103,827; August 2015) in view of Lowery Jr et al. (US PgPub 20120100546; April 2012) as applied over claims 1-3, 6, 9, 15-20 in view of Han et al. (Nature Nanotechnology, 2010, vol. 5, p. 712-717).
With regard to claim 4, Han teaches a method of claim 1, wherein two different polynucleotide primers have two complementary origami tails which are capable of binding to each other, so as to result into the condensation of two separate DNA target segments which are located on at least one polynucleotide strand and which are hybridized to two different polynucleotide primers (p. 716, col. 1, Fig 3b, where toehold single stranded tails are included as part of DNA origami structures, where 3' tails are in orange, 5' tails are in green and displacement strands are in red).
With regard to claim 5, Han teaches a method of claim 1, wherein a polynucleotide may comprise two origami tails and may be capable of binding to at least two different DNA target segments so as to result into the condensation of two different DNA target segments which are located on at least one polynucleotide strand (p. 716, col. 1, Fig 3b, where toehold single stranded tails are included as part of DNA origami structures, where 3' tails are in orange, 5' tails are in green and displacement strands are in red).
With regard to claim 8, Han teaches a method of claim 1, wherein condensation of at least one polynucleotide is effected by a condensation reagent or moiety selected from the group consisting of: DNA origami tails, DNA origami oligonucleotides, origami oligonucleotides comprising modified nucleotides, Cot-1 DNA, oligonucleotides comprising Cot-1, SINE, LINE, transposon or other types of repeat sequences, heterochromatin protein 1 (HP 1), HP 1 a (wild-type, nPhos-HP 1 a, and HP 1 a (BPM)), HP 1 p3, histones, spermidine, spermine, ethanol, streptavidin-labeled magnetic bead, streptavidin-labeled structure, cobalt(III) hexaamine ion [Co(NH3)6]3+ or any combination thereof (p. 716, col. 1, Fig 3b, where toehold single stranded tails are included as part of DNA origami structures, where 3' tails are in orange, 5' tails are in green and displacement strands are in red).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Dapprich and Lowery Jr to include origami tails within the oligonucleotide structures as taught by Han to arrive at the claimed invention with a reasonable expectation for success. Han teaches “we show that DNA origami3 can be used to assemble a Mobius strip, a topological ribbon-like structure that has only one side4–6. In addition, we show that the DNA Mo¨bius strip can be reconfigured through strand displacement7 to create topological objects such as supercoiled ring and catenane structures. This DNA fold-and-cut strategy, analogous to Japanese kirigami8, may be used to create and reconfigure programmable topological structures that are unprecedented in molecular engineering” (Abstract). Han also teaches “The recent development of DNA origami3, a method that uses short DNA oligos as staples to fold single-stranded genomic DNA scaffolds into geometrically defined two- (ref. 3) and three-dimensional nanoarchitectures17–21, has opened up great opportunities for directed assembly of chemical and biomolecular species with exquisite positional control” (p. 712, col. 1).Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Dapprich and Lowery Jr to include origami tails within the oligonucleotide structures as taught by Han to arrive at the claimed invention with a reasonable expectation for success.
Claims 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over Dapprich et al. (US Patent 9,103,827; August 2015) in view of Lowery Jr et al. (US PgPub 20120100546; April 2012) as applied over claims 1-3, 6-9, 12 and 17-20 in view of Litos et al. (Anal. Chem, 2007, 79, p. 395-402).
With regard to claim 10, Litos teaches a method according to claim 1, wherein the polymerase enzyme is selected from the group consisting of 029 DNA polymerase, BST 2.0 polymerase, and a combination thereof (p. 397, col. 1 “reagents” and col. 2 “primer extension reaction”, where primer extension reactions included biotin-dUTP for detection of SNPs and including DNA polymerase, primers and buffer, and where the primer extension reaction includes cycling temperatures as described in col. 2 which includes annealing and extension of the primers).
With regard to claim 11, Litos teaches a method according to claim 10, wherein the 029 polymerase is used at temperature of between 40oC.-50° C (p. 397, col. 1 “reagents” and col. 2 “primer extension reaction”, where primer extension reactions included biotin-dUTP for detection of SNPs and including DNA polymerase, primers and buffer, and where the primer extension reaction includes cycling temperatures as described in col. 2 which includes annealing and extension of the primers).
With regard to claim 12, Litos teaches a method according to claim 1, wherein a temperature range during the hybridization to specific genomic regions of interest is selected from the group consisting of 20° C. to 90° C., 25° C. to 80° C., 30° C. to 70° C., 35° C. to 65° C., 40° C. to 60° C., 45° C. to 65° C., 45° C. to 60° C., 50° C. to 60° C., 55° C. to 65° C., 55° C. to 60° C., and any combination thereof (p. 397, col. 1 “reagents” and col. 2 “primer extension reaction”, where primer extension reactions included biotin-dUTP for detection of SNPs and including DNA polymerase, primers and buffer, and where the primer extension reaction includes cycling temperatures as described in col. 2 which includes annealing and extension of the primers, and where the annealing occurs at 65oC).
With regard to claim 13, Litos teaches a method according to claim 1, further comprising using non-extendable blocking oligonucleotides which is longer or has a higher Guanosine and Cytosine content than the polynucleotide primer which is used (p. 396, col. 1, where primer extension is carried out in the presence of ddNTPs).
With regard to claim 14, Litos teaches a method according to claim 1, further comprising performing a pre- extension with terminating nucleotides which are dideoxynucleotides triphosphates selected from the group consisting of ddATP, ddTTP, ddCTP, ddGTP, and any combination thereof so as to repair a strand break and terminate free 3'-polynucleotide ends so as to reduce off-target capture (p. 396, col. 1, where primer extension is carried out in the presence of ddNTPs).
With regard to claim 15, Litos teaches a method according to claim 1[[ ]], further comprising using a nucleotide base selected from the group consisting of a 5' Bromo dU, a 5' 2-Aminopurine, a 3' 2- Aminopurine, a 5' 2,6-Diaminopurine (2-Amino-dA), a 3' 2,6-Diaminopurine (2-Amino-dA), a 5' deoxyUridine, a 3' deoxyUridine, an Inverted DT, an Inverted Dideoxy-T, a Dideoxy-C, a 5- Methyl dC, a deoxylnosine, a Super T, a Super G, Locked Nucleic Acids (LNA's), a 5- Nitroindole, a 2'-O-Methyl RNA Bases, a Hydroxmethyl dC, an Iso-dG, an Iso-dC, a 5' Fluoro C, a 5' Fluoro U, a 5' Fluoro A, a 5' Fluoro G, a 5' 2-MethoxyEthoxy A, a 5' 2-MethoxyEthoxy MeC, a 5' 2-MethoxyEthoxy G, a 5' 2-MethoxyEthoxy T, a 3' Fluoro C, a 3' Fluoro U, a 3' Fluoro A, a 3' Fluoro G, a 3' 2-MethoxyEthoxy A, a 3' 2-MethoxyEthoxy MeC, a 3' 2- MethoxyEthoxy G, a 3' 2-MethoxyEthoxy T, and a combination thereof (p. 397, col. 1 “reagents” and col. 2 “primer extension reaction”, where primer extension reactions included biotin-dUTP for detection of SNPs and including DNA polymerase, primers and buffer, and where the primer extension reaction includes cycling temperatures as described in col. 2 which includes annealing and extension of the primers).
Further, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Dapprich and Lowery Jr to include the streptavidin coated magnetic beads as taught by Litos to arrive at the claimed invention with a reasonable expectation for success. Litos is focused on capture of nucleic acids using biotin-streptavidin interaction. Litos teaches “The described PEXT-dipstick assay is rapid and highly accurate; it does not require specialized instrumentation or highly trained technical personnel. It is appropriate for a diagnostic laboratory where a few selected SNP markers are examined per patient with a low cost per assay” (Abstract). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Litos to include the streptavidin coated magnetic beads as taught by Briggs to arrive at the claimed invention with a reasonable expectation for success.
Conclusion
No claims are allowed. All claims stand rejected.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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