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 .
Claims 1-20 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed February 06, 2024 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - 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:
Amend the Sequence Listing Incorporation by Reference paragraph at page 1 of the
specification. It is noted the Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 12,000 bytes, whereas the ASCII text file itself lists the size as 12,368 bytes.
Specification
The use of the term NovaSeq™ 6000, HiSeq™ 2000, MiniSeq® and MiSeq™ (see Page 31, [0129], Tables 7-8, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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.
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 1-6 and 9-20 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.
In claim 1, the terms “a first nucleotide single strand” and “a first nucleotide single strand segment” in lines 3 and 6 are unclear and confusing. It is unclear as to if these are the same nucleotide single strand regions or if they are different single strands in different locations?
In claim 1, the terms “the first nucleotide single strand segment including at least one random base”, in lines 8-9 is unclear and confusing. It is unclear as to where the random bases should be located; is this any single strand region?
Claims 2-6 and 9-20 depend from claim 1 and are therefor included in this rejection.
In claim 2, the terms “the first nucleotide single strand segment including at least one random base”, in lines 1-2 and 4, is unclear and confusing. It is unclear as to where the random bases should be located; is this any single strand region?
In claim 3, the terms “the first nucleotide single strand segment including at least one random base”, in lines 1-2 and 4, is unclear and confusing. It is unclear as to where the random bases should be located; is this any single strand region?
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.
Claims 1-2, 4-9 and 17-19 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Wu et al. (People’s Republic of China Application Publication CN 108300716, published July 20, 2018), cited on the IDS filed February 06, 2024.
Regarding claim 1, Wu teaches an adapter comprising at least one first sub-adapter, wherein each first sub-adapter includes, a first nucleotide single strand and a second nucleotide single strand, the first nucleotide single strand being complementarily paired with the second nucleotide single strand as well as a first nucleotide single strand segment (i.e. joint component Abstract, Page 6, Seventh Paragraph and Fig. 2). Wu teaches the first nucleotide single strand segment being ligated to an end of the first nucleotide single strand or an end of the second nucleotide single strand (Page 3, Eleventh-Twelfth Paragraphs and Page 7, Fourth Paragraph). Wu teaches using the joint elements (adapters) for multiplex targeted sequencing library construction (Page 6, Seventh—Eighth Paragraph). Wu teaches at least on adenine (A) base (Page 7, Fourteenth Paragraph and Page 11, Eleventh Paragraph). Wu teaches using random and/or fixed bases (Page 3, Fourth Paragraph). Wu teaches a first nucleotide single strand segment including at least one random base and at least one adenine (A) base, and each random base being any one of an A base, a cytosine (C) base, a guanine (G) base and a thymine (T) base (Page 3, Seventh Paragraph and Page 6, Fifth Paragraph).
Regarding claim 2, Wu teaches the first nucleotide single strand segment includes a plurality of random bases and at least one A base, and the plurality of random bases are arranged consecutively and/or the first nucleotide single strand segment includes a plurality of A bases and at least one random base, and the plurality of A bases are arranged consecutively (Page 3, Seventh Paragraph and Page 6, Fifth Paragraph).
Regarding claim 4, Wu teaches the first nucleotide single strand segment includes three random bases and one A base (Page 3, Seventh Paragraph and Page 6, Fifth Paragraph).
Regarding claim 5, Wu teaches the adapter comprises a plurality of first sub-adapters and among the plurality of first sub-adapters, at least two first sub-adapters are different in that random bases and A bases of respective first nucleotide single strand segments are arranged in different orders (Page 3, Seventh—Eighth Paragraph and Page 6, Fifth Paragraph).
Regarding claim 6, Wu teaches the adapter comprises four first sub-adapters, and four first nucleotide single strand segments of the four first sub- adapters are different in that random bases and A bases of respective first nucleotide single strand segments are arranged in different orders (Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 7, Wu teaches at least one second sub-adapter, wherein each second sub-adapter includes a third nucleotide single strand and a fourth nucleotide single strand, the third nucleotide single strand being complementarily paired with the fourth nucleotide single strand and a second nucleotide single strand segment (Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4). Wu teaches the second nucleotide single strand segment being ligated to an end of the third nucleotide single strand or an end of the fourth nucleotide single strand, the second nucleotide single strand segment including at least one random base, each random base being any one of an A base, a C base, a G base and a T base (Page 3, Eleventh-Twelfth Paragraphs, Page 7, Fourth Paragraph, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 8, Wu teaches the second nucleotide single stranded segment includes four random bases Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 9, Wu teaches an adapter ligation reagent, comprising: the adapters according to claim 1 (see Claim 1 above and Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9 and Page 9, Thirteenth Paragraph).
Regarding claim 17,Wu teach a method for sequencing a gene (Page 3, Eleventh Paragraph and Page 7, First Paragraph, ). Wu teaches performing gene sequencing on DNA obtained by using the method for constructing the DNA library according to claim 19 (see claim 19 below).
Regarding claim 18, Wu teaches at least one second sub-adapter, wherein each second sub-adapter includes a third nucleotide single strand and a fourth nucleotide single strand, the third nucleotide single strand being complementarily paired with the fourth nucleotide single strand and a second nucleotide single strand segment (Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4). Wu teaches the second nucleotide single strand segment being ligated to an end of the third nucleotide single strand or an end of the fourth nucleotide single strand, the second nucleotide single strand segment including at least one random base, each random base being any one of an A base, a C base, a G base and a T base (Page 3, Eleventh-Twelfth Paragraphs, Page 7, Fourth Paragraph, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 19, (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9, Page 9, Thirteenth Paragraph and Figs. 1-2 and 4). Wu teaches a unique molecular tag and molecule label each UMI being located on the fifth nucleotide single strand or the sixth nucleotide single strand (i.e., at least one UMI; Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4). Wu teaches the adapter ligation reagent further includes a third sub-adapter, the third sub-adapter includes a fifth nucleotide single strand and a sixth nucleotide single strand, the fifth nucleotide single strand being complementarily paired with the sixth nucleotide single strand (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9, Page 9, Thirteenth Paragraph and Figs. 1-2 and 4). Wu teaches a unique molecular tag and molecule label each UMI being located on the fifth nucleotide single strand or the sixth nucleotide single strand (i.e., at least one UMI; Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
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.
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 3 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (People’s Republic of China Application Publication CN 108300716, published July 20, 2018), cited on the IDS filed February 06, 2024, as applied to claims 1-2, 4-9 and 17-19 above, in view of Gnerre et al. (U.S. Patent Application Publication US 2016/0319345 A1, published November 03, 2016), cited on the IDS filed February 06, 2024.
Regarding claim 3, Wu teaches the first nucleotide single strand segment includes a plurality of random bases and at least one A base as discussed above.
Wu does not teach or suggest one or more A bases of the at least one A base are disposed between two random bases of the plurality of random bases or the first nucleotide single strand segment includes a plurality of A bases and at least one random base, and one or more random bases of the at least one random base are disposed between two A bases of the plurality of A bases.
Gnerre teaches methods for sequencing a gene (Page 7, [0084]-[0085] and Page 8, [0090]). Gnerre teaches UMIs located on single stranded are regions of double stranded adapters and the UMIs may include random bases (Page 1, [0003]-[0006], Page 14, [0145]-[0146]). Gnerre teaches the adapter may have a single strand region including and overhang with at least 2 random bases on each side of an A base (Page 3, [0024]). Gnerre teaches using these adapters with UMIs can allow one to determine which strand of DNA fragments reads are derived from as well as reducing errors in the determined sequences (Page 3, [0025] and Page 9, [0100]).
As a common field of endeavor both Wu and Gnerre disclose methods for sequencing a gene using adapters.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teaching of Wu with the teachings of Gnerre to use UMIs located on single stranded are regions of double stranded adapters and the UMIs may include random bases and the adapter may have a single strand region including and overhang with at least 2 random bases on each side of an A base. Using these adapters would allow for one to determine which strand of DNA fragments reads are derived from as well as reducing errors in the determined sequences as taught by Gnerre (Page 3, [0025] and Page 9, [0100]).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (People’s Republic of China Application Publication CN 108300716, published July 20, 2018), cited on the IDS filed February 06, 2024, as applied to claims 1-2, 4-9 and 17-19 above, in view of Ahern (“Biochemical, Reagents Kits Offer Scientists Good Return On Investment” The Scientist, Vol. 9, Issue 15, published July 24, 1995).
Regarding claim 10, Wu teaches the adapter ligation reagent of claim 9, including the adapters of claim 1 as discussed above.
Although Wu teaches all of the components of a kit and an adapter ligation reagent, Wu does not teach or suggest explicitly a kit comprising the adapter ligation reagent.
Ahern teaches investigators can purchase a kit that supplies all of the necessary reagents for a particular research application and even provides them with detailed instructions to follow (Page 5, Paragraph 3).
It would have been prima facie obvious to one of ordinary skill in the art before the
effective filing date of the claimed invention to include the adapter ligation reagent as taught by
Wu, within a kit, as taught by Ahern, because a kit is merely a collection of parts. Ahern
teaches Rather than buying individual chemicals, investigators can instead purchase a kit that
supplies all of the necessary reagents for a particular research application and even provides
them with detailed instructions to follow, as well as buying premade reagents and kits allows researchers to save time and is an added convenience as taught by Ahern (Page 5, Paragraph 3).
Claims 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (People’s Republic of China Application Publication CN 108300716, published July 20, 2018), cited on the IDS filed February 06, 2024 and Ahern (“Biochemical, Reagents Kits Offer Scientists Good Return On Investment” The Scientist, Vol. 9, Issue 15, published July 24, 1995), as applied to claim 10 above, in view of Gnerre et al. (U.S. Patent Application Publication US 2016/0319345 A1, published November 03, 2016), cited on the IDS filed February 06, 2024.
Regarding claim 11, Wu teaches a third sub-adapter, wherein the third sub-adapter includes a fifth nucleotide single strand and a sixth nucleotide single strand, the fifth nucleotide single strand being complementarily paired with the sixth nucleotide single strand (Fig. 4). Wu teaches a unique molecular tag and molecule label (i.e., UMIs; Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4). Wu teaches at least one unique molecular identifier (UMI), each UMI being located on the fifth nucleotide single strand or the sixth nucleotide single strand (Figs. 1-2 and 4).
Regarding claim 12, Wu teaches the UMI includes at least one random base, each random base being any one of an A base, a C base, a G base and a T base (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 13, Wu teaches the at least one random base includes at least six random bases (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 14, Wu teaches the at least one UMI includes one UMI, and the UMI is located on the fifth nucleotide single strand (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4).
Regarding claim 15, Wu teaches the fifth nucleotide single strand is a forward strand, and the sixth nucleotide single strand is a reverse strand (Fig. 4). Wu teaches the fifth nucleotide single strand includes a sequencing primer sequence and an amplification primer sequence (Page 4, First Paragraph, Page 7, First Paragraph, Page 9, Fifth-Sixth Paragraph, Table 2 and Fig. 4)
Wu does not teach or suggest the UMI located on the fifth nucleotide single strand is located between the sequencing primer sequence and the amplification primer sequence, and the sequencing primer sequence is combined with bases of the sixth nucleotide single strand through complementary base pairing.
Gnerre teaches methods for sequencing a gene (Page 7, [0084]-[0085] and Page 8, [0090]). Gnerre teaches UMIs located on single stranded are regions of double stranded adapters and the UMIs may include random bases (Page 1, [0003]-[0006], Page 14, [0145]-[0146]). Gnerre teaches the adapter may have a single strand region including and overhang with at least 2 random bases on each side of an A base (Page 3, [0024]). Gnerre teaches adapters with UMIs on the fifth and sixth single stranded regions (Fig. 1B-2D). Gnerre teaches the UMI located on the fifth nucleotide single strand is located between the sequencing primer sequence and the amplification primer sequence, and the sequencing primer sequence is combined with bases of the sixth nucleotide single strand through complementary base pairing (Fig. 1B-2D). Gnerre teaches using these adapters with UMIs can allow one to determine which strand of DNA fragments reads are derived from as well as reducing errors in the determined sequences (Page 3, [0025] and Page 9, [0100]).
Claims 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (People’s Republic of China Application Publication CN 108300716, published July 20, 2018), cited on the IDS filed February 06, 2024, as applied to claims 1-2, 4-9 and 17-19 above, in view of Troll et al. (“A ligation-based single-stranded library preparation method to analyze cell-free DNA and synthetic oligos” BMC Genomics. 20(1):1023, published December 27, 2019).
Regarding claim 16, Wu teaches method for constructing a deoxyribonucleic acid (DNA) library (Abstract and Page 8, Seventh Paragraph). Wu teaches using physical or chemical methods to break the DNA sample (i.e., degraded DNA sample; Page 7, Ninth Paragraph). Wu teaches using the adapter ligation reagent according to claim 9 to make the adapters at least one first sub-adapter and the at least one second sub-adapter of the adapter ligation reagent react with the single-stranded DNA to obtain adapter ligation products (see Claims 1 and 9 above and Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9 and Page 9, Thirteenth Paragraph). Wu teaches purifying and enriching the adapter ligation products to obtain the DNA library (Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9, Page 9, Thirteenth Paragraph, Page 10, Sixth Paragraph, Page 8, Second Paragraph, and Page 11, First Paragraph).
Regarding claim 20, Wu teaches the adapter ligation reagent further includes a third sub-adapter, the third sub-adapter includes a fifth nucleotide single strand and a sixth nucleotide single strand, the fifth nucleotide single strand being complementarily paired with the sixth nucleotide single strand (Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9, Page 9, Thirteenth Paragraph and Figs. 1-2 and 4). Wu teaches a unique molecular tag and molecule label each UMI being located on the fifth nucleotide single strand or the sixth nucleotide single strand (i.e., at least one UMI; Abstract, Page 3, Seventh—Eighth Paragraph, Page 6, Fifth Paragraph and Figs. 1-2 and 4). Wu teaches using the adapter ligation reagent, to make the at least one first sub-adapter, the at least one second sub-adapter and the third sub-adapter of the adapter ligation reagent react with the single-stranded DNA to obtain the adapter ligation products (see Claims 1 and 9 above and Page 8, First Paragraph, Page 3, Eleventh-Twelfth Paragraph, Page 4, Paragraph 9 and Page 9, Thirteenth Paragraph)..
Wu does not teach or suggest melting the degraded DNA to form single-stranded DNA.
Troll teaches a ligation based single stranded library preparation method (Abstract and Title). Troll teaches uniquely designed adapters with two single strand sub-adapters that are complementarily paired with a single strand overhang containing at least 6 random bases (Figs. 1 and 3). Troll teaches the adapters are used with sample indexing (comparable to using UMIs; Page 11, Left Column, Last Paragraph). Troll teaches the template DNA is degraded by heat (melting). Troll teaches degrading the DNA in this manner renders all DNA template molecules to be uniformly single stranded to allow for the ligation reaction to continue downstream for library construction (Page 2, Right Column, Last Paragraph—Page 3, Left Column Second Paragraph and Fig. 1).
As common field of endeavor both Wu and Troll disclose methods for sequencing library construction using ligation.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Wu with the teachings of Troll to degrade the template DNA using heat (melting). Degrading the DNA in this manner renders all DNA template molecules to be uniformly single stranded which allows for the ligation reaction to continue downstream for library construction as taught by Troll (Page 2, Right Column, Last Paragraph—Page 3, Left Column Second Paragraph and Fig. 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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