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 .
Claims 1-20 are pending and will be examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 10, 2014 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3-5, 7-8 and 11-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Drmanac et al. (US Patent 9,228,228 B2; January 2016).
With regard to claim 1, Drmanac teaches a method for amplifying a plurality of different nucleic acid populations in a single reaction mixture, comprising:
providing a single reaction mixture including a first and a second population of nucleic acids, wherein the first population of nucleic acids contain a first primer binding sequence and the second population of nucleic acids contain a second primer binding sequence, and wherein the first and second primer binding sequences are different;
a first plurality of beads including a first capture sequence that can bind to the first primer binding sequence; a second plurality of beads including a second capture sequence that can bind to the second primer binding sequence, wherein the first and second capture sequences are different (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62); and
b) amplifying, within the single reaction mixture, one or more nucleic acids from the first population to form a first amplified population, and one or more nucleic acids from the second population to form a second amplified population, wherein the first amplified population is bound to one or more beads of the first type and the second amplified population is bound to one or more beads of the second type (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 3, Drmanac teaches a method of claim 1, wherein the amplifying in step (b) include PCR, isothermal, rolling circle, or emulsion based amplification (col. 27, line 41 to col. 28, line 16, where emulsion PCR and water-in-oil emulsions are described; Fig 11, where the method of emulsion PCR is depicted).
With regard to claim 4, Drmanac teaches a method of claim 3, wherein the emulsion based amplification includes water-in-oil emulsions (col. 27, line 41 to col. 28, line 16, where emulsion PCR and water-in-oil emulsions are described; Fig 11, where the method of emulsion PCR is depicted).
With regard to claim 5, Drmanac teaches a method of claim 1, wherein the first amplified population is covalently bound to one or more beads of the first type (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 6, Drmanac teaches a method of claim 1, wherein the second amplified population is bound to one or more beads of the second type (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 7, Drmanac teaches a method of claim 1, wherein the single reaction mixture further includes at least two, three, four, five, six, seven, eight, nine, ten, or more types of beads, each type of bead including a different type of primer binding sequence (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 8, Drmanac teaches a method of claim 1, further comprising sequencing one or more nucleic acids of the first amplified population and one or more nucleic acids from the second amplified population in parallel (col. 39 and 42, where sequencing is described).
With regard to claim 11, Drmanac teaches a method of claim 1, wherein the first and second primer binding sequences are present in about the same concentration (col. 18, “methods of amplification” heading, where the details of amplification are described).
With regard to claim 12, Drmanac teaches a method of claim 1, wherein the amplifying in step
(b) includes hybridizing at least one target sequence from the first population to a first primer binding sequence on the first type of beads; and the forming the second amplified population includes hybridizing at least one target sequence from the second population to a second primer binding sequence on the second type of beads (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 13, Drmanac teaches a method of claim 1, further including extending one or more first and second primer binding sequence in a template-dependent fashion (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
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) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (US Patent 9,228,228 B2; January 2016) as applied over claims 1-5, 7-8 and 11-13 and further in view of Gao et al. (US PgPub 20100112558 A1; May 2010).
With regard to claim 9, Gao teaches a method of claim 8, wherein the sequencing includes detection of one or more nucleotide incorporation byproducts (paragraph 15, where samples are sequenced).
With regard to claim 10, Gao teaches a method of claim 8, wherein the sequencing includes detecting hydrogen ions or pyrophosphate (paragraph 15, where samples are sequenced).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have extended the teachings of Drmanac to include the steps of sequencing and emulsion amplification as taught by Gao to arrive at the claimed invention with a reasonable expectation for success. As taught by Gao, “The present invention provides methods for sequencing specific regions in whole genome DNA or transcriptome RNA samples to obtain high quality quantitative measurements in a single reaction. This enables routine performance of large-scale studies of human genetics (SNP, CGH, Chip-on-Chip, methylation, etc.) and gene expression (coding mRNA or noncoding RNA) related to population, sex, age, disease, environmental exposure, etc. The probe bead-based assays of the present invention can be performed at significantly reduced costs, and on a much larger scale than prior art methods.” (paragraph 15). Therefore, one of ordinary skill in the art at the time the invention was made would have been motivated to have extended the teachings of Drmanac to include the steps of sequencing and emulsion amplification as taught by Gao to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 2, 14-19 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (US Patent 9,228,228 B2; January 2016) as applied over claims 1, 3-5, 7-8 and 11-13 and further in view of Leng et al. (Lab Chip, 2010, 10:2841-2843).
With regard to claim 17, Drmanac teaches a method of amplifying a first target sequence from a first population of target nucleic acids and a first target sequence from a second population of target nucleic acids comprising:
(a) providing a single reaction mixture having a plurality of a first type of beads including first capture primers; a plurality of a second type of beads including second capture primers,wherein the first and second capture primers are different; a first population of target nucleic acids, wherein the first population includes at least one target nucleic acid that binds to a first fusion primer; a first fusion primer that includes a portion complementary to the first capture primers; a second population of target nucleic acids, wherein the second population includes at least one target nucleic acid that binds to a second fusion primer; a second fusion primer that includes a portion complementary to the second capture primers (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62);
(b) forming a population of the first target sequence from the first population of target nucleic acids on the first type of beads using the first fusion primer; and
(c) forming a population of the first target sequence from the second population of target nucleic acids on the second type of beads using the second fusion primer (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 18, Drmanac teaches a method of claim 17, wherein the single reaction mixture further includes at least two, three, four, five, six, seven, eight, nine, ten, or more types of beads, each type of bead including a different type of primer binding sequence (see Fig 11, for example, where emulsion PCR is depicted; see also col. 3, lines 38-55, where the primers on beads and the amplification is described; see also col 27-28, where one bead per site or well and emulsion PCR is described; see also col. 43, lines 28-62).
With regard to claim 19, Drmanac teaches a method of claim 17, wherein the forming in step (b) include PCR, isothermal, rolling circle, or emulsion based amplification (col. 27, line 41 to col. 28, line 16, where emulsion PCR and water-in-oil emulsions are described).
With regard to claim 20, Drmanac teaches a method of claim 19, wherein the emulsion based amplification includes water-in-oil emulsions (col. 27, line 41 to col. 28, line 16, where emulsion PCR and water-in-oil emulsions are described).
Regarding claims 2, 14-19, while Drmanac teaches the method of amplification, Drmanac does not specifically teach the amplification is substantially monoclonal.
With regard to claim 2, Leng teaches a method of claim 1, wherein the first amplified population, the second amplified population, or both, are substantially monoclonal (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets).
With regard to claim 14, Leng teaches a method of claim 1, wherein the first amplified population is substantially monoclonal (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets).
With regard to claim 15, Leng teaches a method of claim 1, wherein the second amplified population is substantially monoclonal (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets).
With regard to claim 16, Leng teaches a method of claim 1, wherein the first amplified population, the second amplified population, or both, are substantially monoclonal (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets).
With regard to claim 17, Leng teaches substantially monoclonal amplification and (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets); and
(c) forming a substantially monoclonal population of the first target sequence (Abstract, Scheme 1, p 2842, where amplification products monoclonality is preserved in agarose droplets).
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 Drmanac to include the monoclonal amplification as taught by Leng to arrive at the claimed invention with a reasonable expectation for success. Drmanac teaches “The need for low-cost high-throughput sequencing and resequencing has led to the development of several new approaches that employ parallel analysis of many target DNA fragments simultaneously, e.g., Use of water/buffer-in-oil emulsions to carry out enzymatic reactions is well known in the art, particularly carrying out PCRs, e.g., as disclosed by Drmanac et al., Scienta Yugoslavica, 16(1-2): 97-107 (1990)” (col. 1 line 28-34). Leng teaches “The role of agarose in the aqueous phase is to serve as a capturing matrix to replace conventional primer functionalized microbeads to preserve the monoclonal nature of the DNA product in each droplet” (p 2842, col. 1). Leng also teaches “after PCR amplification, the solution form of the agarose droplet can be switched to the solid gel phase by simply cooling the solution below gelling point. Once solidified, agarose beads will remain solid unless the temperature rises above 56 _C. As a result, DNA products amplified in the droplet will retain their monoclonality even after the oil phase is removed. The clonal beads can be used for downstream sequencing or genotyping applications” (p 2842, col. 1). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Drmanac to include the monoclonal amplification as taught by Leng 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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