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 filed September 25, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. Non-patent literature document #2, titled “Characterization of bacteriophage T3DNA Ligase” has been improperly uploaded. Therefore, it has been placed in the application file, but the information referred to therein has not been considered.
Claim Objections
Claim 70 is objected to because of the following informality: in the next to last line, a comma is required between “fifth strand” and “sixth strand”. 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 3, 25, 27, and 30 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.
Claim 3 is indefinite in regards to the usage of “about” in relation to nucleic acid size, specifically “about 24 bases”, “about 4 bases”, “about 1 base”, and “about 5 bases.” The specification defines “about” as ±10%. However, as nucleotide length can only be expressed in discrete whole numbers, application of this definition of “about” to “[24, 4, 1, 5] base(2)” does not provide clear objective boundaries as to the scope of the claim. For example, “about 24 bases” could encompass 22-26 or 21-27 bases depending on how ±10% is rounded. Furthermore, with the recitations of “about [4, 1, 5] base(s)”, it is unclear if the claim is bound by the exact recited number, or also by the closet adjacent integers (i.e. 4 or 3-5). Thus, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the claim.
Claim 25 is indefinite in regards to the terminology “enzyme units.” This metric is not defined by the specification and, while “enzyme unit” appears to be commonly used within the art, the definition of the term can vary. For example, for a T4 DNA Ligase, Qiagen defines enzyme unit as “the amount of DNA Ligase required to join 50% of 100ng of DNA fragments with cohesive termini in 50uL 1X DNA Ligase Buffer following a 30 minute incubation at 23oC,” whereas New England BioLabs defines enzyme unit as “the amount of enzyme required to give 50% ligation of 6ug of Lambda-HindIII DNA in 30 minutes at 16oC in a total reaction volume of 20uL” (QIAGEN and New England BioLabs product specification sheets). As the definition of “enzyme unit” depends on the manufacturer of the enzyme, the exact meaning cannot be discerned absent that information.
Claims 27 and 30 contain the trademarks/trade names:
Kapa HiFi DNA Polymerase (Roche)
NEB Q5 DNA Polymerase (NEB)
PrimeStar GXL DNA Polymerase (Takara)
High Fidelity DNA Polymerase (Qiagen)
Kapa HiFi Hot Start DNA Polymerase (Roche)
NEB Q5 Hot Start DNA Polymerase (NEB)
PrimeStar GXL Hot Start DNA Polymerase (Takara)
High Fidelity Hot Start DNA Polymerase (Qiagen)
Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademarks/trade names are used to identify/describe polymerases and, accordingly, the identification/description is indefinite.
Allowable Subject Matter
Claims 1, 2, 11, 20, 21, 23, 24, 26, 28, 29, 31, 32, 33, 35, 37, 39, 69, and 71 are allowable.
Claim 70 (and 71 by virtue of its dependency) would be allowable if rewritten or amended to overcome the objection set forth in this office action.
Claims 3, 25, 27, and 30 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
The following is a statement of reasons for the indication of allowable subject matter:
The instant application describes a method of ligation-coupled PCR in which a first indexing primer is ligated to a partially double stranded DNA substrate, followed by subsequent rounds of PCR amplification (reminiscent of asymmetric amplification), all of which is performed in a single, closed tube. The first round of amplification uses the second indexing primer, the second round uses the first indexing primer, and the third round uses both primers. This is made possible through manipulation of cycle parameters to control which aspects of the reaction mix are active at a given stage.
Lazinski (US 2015/0203887 A1) teaches a method for producing a double-stranded nucleic acid in which a homopolymer exists at each 3` end. Although the first embodiment described is similar in structure to the DNA substrate of the instant application (see below), the second and fourth portions of the molecules contain only one common sequence (Lazinski [0006-0010]) whereas the instant application requires two. Furthermore, although additional embodiments disclose the addition of a second common sequence, they are described as being located on the 5` ends of the molecule (Lazinski [0012, 0014-0018]), rather than further 3` to the first common sequence as is required by the instant application. It is for this reason that the examiner disagrees with the decisions of previously issued office actions available on Global Dossier, and makes the determination that Lazinski does not anticipate, nor make obvious, the instant application.
PNG
media_image1.png
300
582
media_image1.png
Greyscale
Makarov (US 10316357 B2, herein referred to as Makarov 1) discloses a method for generating a partially double stranded DNA molecule with two 3` overhangs. Figures 40-42 depict this process, with part of figure 42 annotated below for exemplarily purposes. In the method, forward and reverse primers are constructed to each contain a target-specific sequence, a degenerate sequence (first common sequence), and a universal sequence (second common sequence). After PCR amplification, an appropriate enzyme is then selected to degrade the compliment of the universal sequence resulting in a partially double stranded DNA substrate akin to that of the instant application.
PNG
media_image2.png
370
1405
media_image2.png
Greyscale
Therefore, Makarov 1 teaches the limitations of claim 1(i). However, the adapters used by Makarov 1 in further analysis steps do not contain both common sequences and additional examples show that the adapters are non-complementary with each other. These features mean that the adapters of Makarov 1 do not read on the indexing primers of the instant application. Furthermore, Makarov 1 does not teach the asymmetrical amplification of the substrate performed by the instant amplification after ligation.
Makarov (WO 201804857 A2, herein referred to as Makarov 2) discloses a method for normalizing the concentration of a next generation sequencing (NGS) library. In one embodiment, this method requires the ligation of a probe to a DNA substrate, which imparts nuclease resistance to the ligated fraction of the DNA library. The non-ligated fraction is digested. This results in a remaining fraction that is equivalent in concentration to that of the probe used for ligation. Therefore, if the probe is used in quantities that are rate-limiting, the concentration of the library will be equivalent to the concentration of the probe (Makarov 2, [0013]). Makarov 2 does not, however, teach the partially double-stranded DNA substrate, the indexing primers, or the ligation and asymmetrical amplification of the substrate as required by the instant application.
Therefore, any of the listed references could be considered the closest prior art, but the claims of the instant application are not obvious over them.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kara N Kovach whose telephone number is (571)272-8134. The examiner can normally be reached Monday - Friday, 9am - 3pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at (571) 272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.N.K./Examiner, Art Unit 1681
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681