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 .
The amended claims dated 3/31/2023 are under consideration.
Priority
This application is a continuation of US 16/077,295 (filed 8/10/2018), which is a 371 national stage entry of PCT/US2017/020297 (filed 3/1/2017), which claims benefit of US provisional 62/301,967 (filed 3/1/2016).
Priority to US provisional 62/301,967 is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency #1- This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because Fig. 20 includes sequences identified with a SEQ ID NO, but no Sequence Listing is provided.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specific deficiency #2 - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The use of terms that are trade names or marks used in commerce, such as NextSeq®, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities: in para. 34, the specification states “nuclei acid” rather than “nucleic acid”; and in para. 54, the specification states “adaptors” rather than “adapters”.
Appropriate correction is required.
Claim Objections
Claim 86 is objected to because of the following informalities: in line 1 the claim recites “nucleic acid target” rather than “a nucleic acid target”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 102, 103 and 106 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 102, the claim states “the plurality of barcodes is produced by direct synthesis, or clonal amplification”. It is unclear what additional structural elements, if any, are imposed by this description of how the barcodes were produced.
Furthermore, it is unclear if the claim is intended to require an active method step of “producing the plurality of barcodes by direct synthesis, or clonal amplification”.
Claim 103 depends from claim 102 and is rejected for the same reason.
Regarding claim 103, it is unclear what additional structural elements, if any, are imposed by the description of how the barcodes were produced using one of the recited clonal amplification processes.
Furthermore, it is unclear if the claim is intended to require an active method step of “producing the plurality of barcodes” by using one of the recited processes.
Regarding claim 106, the claim recites “the handle sequence is used as a binding site for amplification, hybridization, annealing, and/or ligation”. It is unclear if the claim requires an active method step of “using the handle sequence as a binding site for amplification, hybridization, annealing, and/or ligation.
Furthermore, it is unclear what additional structural elements, if any, are imposed by this description of an intended use.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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) 86-100 and 102-106 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gormley (US 2014/0194324 A1).
Claim 86 is drawn to a method requiring parts (a), (b), (c) and (d). MPEP 2111.01(II) states it is improper to read a specific order of steps into method claims where, as a matter of logic or grammar, the language of the method claims did not impose a specific order on the performance of the method steps, and the specification did not directly or implicitly require a particular order. Here nothing imposes any specific order on the recited steps.
Regarding claims 86, 96 and 106, Gormley teaches contacting a nucleic acid target with a transpososome comprising a transposable DNA and a transposase (Fig. 1a, 2a, 3a, etc.). Gormley teaches the elements of the active step and as a consequence forms a “transpososome-nucleic acid complex”.
Gormley teaches providing a plurality of barcoded microparticles and a plurality of “blank microparticle” not having a barcode (para. 109). The barcode on the bead comprises a “barcode sequence” or index and a handle flanking the index on each side, e.g. P5 primer, P7 primer, Read 1 seq primer, ME, etc.) (Fig. 9, Fig. 13).
Gormley teaches attaching a barcode to the transposable DNA through ligation, hybridization, etc. (Fig. 9, 10, 13).
Gormley teaches removing the transposase from the transpososome-nucleic acid complex (Fig. 4a, 6b, 7, 18a). Gormley teaches the elements of the active step and as a consequence fragments “the nucleic acid target, to produce a barcode tagged fragment”.
Regarding claim 87, Gormley teaches one barcode per bead (para. 112) that is unique to the bead (para. 120).
Regarding claim 88, Gormley teaches an ME handle sequence that is complementary to the ME sequence of a transposable DNA (Fig. 5a, 10).
The ME sequences are hybridized to immobilize the transpososome and to attach the barcode to the transposable DNA.
Regarding claims 89 and 98, Gormley teaches a “linker” or splint oligonucleotide that is single-stranded and complementary to the sequence on the bead and to the transposable DNA and hybridizing the linker to each (Fig. 5b).
Regarding claim 90, Gormley teaches denaturing the barcode tagged fragment and releasing it from the barcoded bead via cleavage or PCR (Fig. 15; para. 32 and 121).
Regarding claim 91, Gormley teaches repairing a gap formed during the transposition reaction (para. 64, 136).
Regarding claims 92-95, Gormley teaches the use of a Tn5 transposase and its corresponding Tn5 transposable DNA (para. 44-45).
Regarding claim 97, Gormley teaches releasing the repaired nucleic acid via a strand displacement extension reaction (para. 136 and Fig. 15).
Regarding claim 99, Gormley teaches removing the transpososome using heat and PBI (para. 136). See also, para. 39.
Regarding claim 100, Gormley teaches using primers that recognize a tag or tag domain in the transposable DNA (para. 49, 65, 78).
Regarding claim 102, the claim describes how the barcodes were produced but does not require any additional active method steps. The description of how the barcodes were produced does not distinguish them from those of Gormley. Gormley anticipates claim 102 for the same reason it anticipates claim 86.
Regarding claim 103, the claim describes how the barcodes were produced but does not require any additional active method steps. The description of how the barcodes were produced does not distinguish them from those of Gormley. Gormley anticipates claim 103 for the same reason it anticipates claim 86.
Regarding claim 104 and 105, Gormley teaches barcodes with a length of 6-8 bases (para. 119) or a tag domain of 10 or 20 bp (para. 49).
It is noted that the full bread of claim 105 broadly encompasses a 9 base sequence. Thus, Gormley anticipates that full scope of claim 105.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 101 is rejected under 35 U.S.C. 103 as being unpatentable over Gormley (US 2014/0194324 A1) as applied to Claims 86, 90 and 100 above and in view of Robins (US 2016/0024493 A1).
Regarding claim 101, the teachings of Gormley with respect to Claims 86, 90 and 100 have been described above and are incorporated herein.
While Gormley does not teach all of claim 101, Gormley uses primers with P5 and/or P7 adapter sequences corresponding to ‘a first set of primers’.
Robins teaches creating a sequencing library by a method which
“starts with anticoagulated blood (1), separates PBMCs on a Ficoll gradient (2), aliquots even numbers of cells into the wells of a 96-well plate (3), isolates RNA in a 96-well plate (4), synthesizes cDNA (5), amplifies TCRA sequences with gene-specific PCR primers (6), amplifies TCRB sequences with gene-specific PCR primers (7), runs a nested PCR to add sequencing adaptors and well-specific barcodes to TCRA sequences (8), runs a nested PCR to add sequencing adaptors and well-specific barcodes to TCRA sequences (9), and combines amplicons to create a sequencing library (10)” (see para. 253 and Fig. 10).
It would have been obvious to one having ordinary skill in the art at the time of the invention to modify the method of Gormley (after releasing bead attached target nucleic acids for amplification) as explained above, to: i) form a library of amplicons with use of primers with P5 and/or P7 adapter sequences (as taught by Gormley) which have at least a portion of one or more the barcode sequences to selectively amplify molecules released from one or more beads, and ii) perform a second amplification that selectively amplifies gene sequences using “gene-specific PCR primers” (which are “nested” within the amplicons) as taught by Robins, with the reasonable expectation of successfully expanding the method to produce a library for sequencing gene sequences without surprising or unexpected results.
Additional rationales for the above modifications are provided by the skilled person’s recognition of the changes as simple combining of prior art elements according to known methods to yield predictable results; and simple use of known techniques (of Robins) to improve a similar method in the same way.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682