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 .
Priority
This application is a CON of 16/937,225 (07/23/2020, now US11242522);
16/937,225 is a CON of 16/246,195 (01/11/2019, now US10731150);
16/246,195 is a DIV of 15/738,104 (12/19/2017 ABN);
15/738,104 is a 371 of PCT/GB2016/051883 (06/23/2016);
which claims foreign priority to UNITED KINGDOM 1511050.5 (06/23/2015).
Status
Claims 47-54 are pending.
Rejections not reiterated in this office action are withdrawn.
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 47-52 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (WO2014145820).
Regarding claim 47, Drmanac teaches a method of sequencing and analysis of long DNA fragments (Abstract; claim 1; [0014]: “Multiple Tagging of Individual Long DNA Fragments (referred to herein by the abbreviation Multiple Tagging, or MT).”). Drmanac teaches preparing a nucleic acid sample for sequencing ([0015]: “sequencing a target nucleic acid by: (a) combining in a single reaction vessel (i) a plurality of long fragments of the target nucleic acid, and (ii) a population of polynucleotides, wherein each polynucleotide comprises a tag and a majority of the polynucleotides comprise a different tag; (b) introducing Into a majority of the long fragments tag-containing sequences from said population of polynucleotides to produced tagged long fragments, wherein each of the tagged long fragments comprises a plurality of the tag-containing sequences at a selected average spacing, and each tag-containing sequence comprises a tag; and (c) producing a plurality of subfragments from each tagged long fragment, wherein each subfragment comprises one or more tags.”). Drmanac also teaches the use of the prepared sample to sequence the sample and process the reads and assemble into the sequence of the target nucleic acid ([0015]: “Such methods are suitable for preparing a target nucleic acid for nucleic acid sequencing, and may comprise sequencing the subfragments to produce a plurality of sequence reads; assigning a majority of the sequence read to corresponding long fragments; and assembling the sequence reads to produce an assembled sequence of the target nucleic acid.”).
Drmanac does not specifically describe claim 47’s “first, second and third” aspects of target nucleic acids or corresponding barcode regions. However, Drmanac does teaches
MT (multiple tagging of individual long DNA fragments) can be performed using
clonal barcodes including those prepared by synthesis. By "clonal" is meant tags or
barcodes containing (i.e., comprising) the same sequence and physically associated
with each other (rather than separate and free to diffuse in solution) such that a source
of clonal tags can be associated with a single long DNA fragment. The result is that a
plurality of identifiable clonal tags or barcodes may be associated with one DNA
fragment and not with others. The clonal tags or barcodes may be kept together in the
form of concatemers, dendrimers, or on a carrier such as a polymer (e.g., DNA
fragment) or micro-size beads. The terms "particle" and "source of clonal barcodes"
refer to a delivery system for multiple copies of a tag sequence ([0115]-[0120]; [0074]: “In principle, each fragment may have introduced into it multiple copies of one unique tag - a fragment-specific tag - or a unique pattern of insertion of multiple tags - a fragment-specific tag pattern.”). Accordingly, Drmanac teaches the use of "a clonal barcode" to label DNA fragments so that it can be inferred from the sequencing result that the sub-sequence is generated from the same original long DNA sequence. Drmanac further discloses using the tags to build contigs to guide de novo assembly, and discloses the sequencing method in which sequence
reads are assembled using matched adjacent barcodes to build long reads ([0138]-[0141]). As a result, one of ordinary skill in the art of sequencing would have known the barcode regions uniquely identify each of the barcode molecules, and those skilled in the art readily considered using the same principle to arrive at the claimed invention with a reasonable expectation of success. Thus, claim 47 is prima facie obvious.
Regarding claim 48 wherein the barcode regions uniquely identify the target, Drmanac teaches this as an advantage ([0087]: “The advantages of MT include: A practically unlimited number of Individual DNA fragments can be uniquely tagged, providing maximal information for de novo assembly, for example.”).
Regarding claim 49 wherein the multimeric barcode molecule comprises at least 5 regions, Drmanac teaches multiple barcode segments allowing for combinatorial designs allowing for a large repertoire that may be needed depending on the target sequences ([0124]-[0128]) which one of ordinary skill in the art would consider utilizing at least 5 such segments and arrive at the claimed invention.
Regarding claim 50 specifying the number of barcode molecules, as with claim 49, Drmanac teaches a design to allow for sufficient unique number of tags and provides an example of 65,000 ([0127]) which one of ordinary skill in the art would consider in design to cover the targets and arrive at the claimed invention.
Regarding claim 51, Drmanac teaches the barcodes may have a unique pattern of multiple tags corresponding to at least 2 barcodes that are different to at least 1 other barcode
([0074]: “In principle, each fragment may have introduced into it multiple copies of one unique tag - a fragment-specific tag - or a unique pattern of insertion of multiple tags - a fragment-specific tag pattern.”).
Claims 53-54 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (WO2014145820) as applied to claims 47-52 above and further in view of Anderson et al. (US20130005585).
Regarding claims 53-54, Drmanac teaches the target nucleic acids are from a cell or tissue (claim 13; [0022]-[0023]; [0220]-[0222]), but is not specifically teach FFPE or an individual cell.
Anderson is in the same field of endeavor of nucleic acid sequencing and teaches preparation of target nucleic acids from FFPE samples ([0073]; [0380]; claim 145) as well as from single cells ([0111]-[0116]; [00380]; Figs 19-24). One of ordinary skill in the art would have been aware of these well-known nucleic acid sample preparations routinely used in sequencing of target nucleic acids and combined the teaching with that of Drmanac and arrive at the claimed invention with a reasonable expectation of success. Thus, the claims are prima facie obvious.
Response to Remarks - 35 USC § 103
Applicant argues that Drmanac fails to teach every element of claim 47, including a multimeric barcode molecule with at least three barcode regions.
Drmanac teaches an equivalent “clonal barcode” which comprises multiple barcode regions in a DNA fragment ([0080]: (emphasis added) “As is detailed below, "clonal barcodes" refers to a plurality of barcodes or tags that have a common sequence and which are physically associated with each other (rather than physically separate and, for example, free to diffuse in solution). In this approach, a source of clonal tags can be associated with a single long DNA fragment. The result is that a plurality of identifiable clonal tags or barcodes may be associated with one DNA fragment and not with others. The clonal tags or barcodes may be kept together in the form of, without limitation, concatemers, dendrimers, or on a carrier such as a polymer (e.g., DNA fragment)”).
Applicant argues that Drmanac does not teach methods of sequencing the co-localized target nucleic acids from a sample.
This is not persuasive as Drmanac teaches sequence analysis of multiple co-localized DNA ([0102]: “in one approach, a small amount of DNA (e.g., from 10 cells) is tagged in a single container. Clonal tags are Interacted with DNA in a small volume to give high probability that almost a!! long DNA fragments will find a clonal barcode”) where the analysis comprises the same grouping process according to the tags (claim 1: “A method for sequence analysis of a target nucleic acid … producing tagged long fragments, wherein each tagged long fragment comprises target nucleic acid sequence and multiple interspersed tag sequences, wherein the multiple interspersed tag sequences In an individual tagged long fragment may be the same or different … producing from each tagged long fragment a plurality of tagged subfragments, wherein the tagged subfragments each comprise one or more tag sequences; (d) obtaining sequence of individual tagged subfragments, wherein the obtained sequence includes target nucleic acid sequence and at least one tag sequence; (e) combining sequences obtained In (d) to produce assembled sequence(s) of the target nucleic acid, wherein the combining comprises (i) determining that sequences obtained in (d) originated from the same long DNA fragment if said sequences comprise the same tag sequence and/or (ii) identifying pairs of sequences as being adjacent sequences in the target nucleic acid if the pair comprise the same tag sequence.”).
Drmanac also teaches the use of the prepared sample to sequence the sample and process the reads and assemble into the sequence of the target nucleic acid ([0015]: “Such methods are suitable for preparing a target nucleic acid for nucleic acid sequencing, and may comprise sequencing the subfragments to produce a plurality of sequence reads; assigning a majority of the sequence read to corresponding long fragments; and assembling the sequence reads to produce an assembled sequence of the target nucleic acid.”).
Applicant also argues that Anderson also fails to render the claims obvious because the primers of Anderson comprise a single barcode region which would not be traceable back to a single parent molecule.
This argument is not persuasive because Anderson is cited as in the same field of endeavor of nucleic acid sequencing and further teaches preparation of target nucleic acids from FFPE samples ([0073]; [0380]; claim 145) as well as from single cells ([0111]-[0116]; [00380]; Figs 19-24). One of ordinary skill in the art would have known that the techniques relating to FFPE samples would have been combinable with Drmanac and they would have had a reasonable expectation of success.
Double Patenting
Claims 47-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11242522 in view of Drmanac et al. (WO2014145820) and Anderson et al. (US20130005585). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of generating a synthetic long read which comprises substantially the same steps as the instant claims. Thus, in view of the secondary references as detailed in the 35 USC 103 rejection supra and incorporated herein, one of ordinary skill in the art would had a reasonable expectation of success in arriving at the instantly claimed invention.
Claims 47-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10731150 in view of Drmanac et al. (WO2014145820) and Anderson et al. (US20130005585). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of generating a synthetic long read which comprises substantially the same steps as the instant claims. Thus, in view of the secondary references as detailed in the 35 USC 103 rejection supra and incorporated herein, one of ordinary skill in the art would had a reasonable expectation of success in arriving at the instantly claimed invention.
Response to Remarks - Double Patenting
Applicant argues that the instant claims are patentably distinct from the claims of the ‘522 and ‘150 at least in view of the deficiencies of Drmanac and Anderson as in the response to the rejections under 35 USC 103.
This argument is not persuasive both because of the response in the 35 USC 103 rejection supra and because the claims of the patents are to the same steps and one of ordinary skill in the art practicing the claims of the patents would anticipate or render obvious the instant claims.
For example, in the ‘522 patent the claim 1 primarily differs by the following (marked up relative to instant claim 47) (and similarly in the ‘150 patent):
47. (New) A method of sequencing co-localized target nucleic acids comprising the steps of: …
such that one of ordinary skill in the art would have recognized that the sequencing method steps are essentially the same, including preparing … , sequencing … , processing … and would be applicable to any nucleic acids present including co-localized targets. Furthermore, Drmanac teaches sequencing of co-localized target nucleic acids in the same manner ([0015] “Methods are provided in this disclosure for sequencing a target nucleic acid by: (a) combining in a single reaction vessel (i) a plurality of long fragments of the target nucleic acid”) and one of ordinary skill in the art would have considered routine utilizing the same technique to prepare a long-read target or co-localized targets and arrived at the claimed invention with a reasonable expectation of success.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626