Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Nucleotide and/or Amino Acid Sequence Disclosures
2. 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/PatentLegalFramework), 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:
A. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification and the claims are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
Amendments to claims including sequence ID modifiers, and
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Election/Restrictions
3. Applicant’s election without traverse of Group I, claims 1-7, in the reply filed on 29 July 2025 is acknowledged.
Claim Objections
4. Claims 3 and 5 are objected to because of the following informalities: Claim 3 has a tick mark at the bottom left of the claim, and claim 5 has an extraneous period after the word “follows” in line 2 of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. Claims 1-7 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.
A. Claim 1 recites the terms “Y-shaped reverse linker” and “high GC clamp linker,” however, neither the applicant’s specification nor the existing claim language provide a limiting definition for these terms. For example, what is a Y-shaped reverse linker “reversed” from? What is a “high” GC clamp linker? What is it “high” compared to? What is required for it to be a clamp or a linker? This language makes the metes and bounds of this claim unclear, and therefore the claim is indefinite. For the purpose of prosecution, this claim is being interpreted as though any Y-shaped linker is a “reverse” Y-shaped linker, compared to a linker comprising the “reversed” sequence. Additionally, a high GC clamp linker is being interpreted as though any sequence that “clamps” something (e.g., hybridizes to a target) and “links” something (e.g., connects one thing to another) satisfies these claim limitations.
B. Claim 2 recites the phrase “said Y-shaped reverse linker sequence is reverse complementary to a normal Y-shaped linker sequence.” The sequence of a normal Y-shaped reverse is not defined in the specification or the claims, and therefore this claim is indefinite. Without any further limiting definition a Y-shaped reverse linker sequence is being interpreted as the reverse of any possible normal Y-shaped linker sequence for which it is the reverse complement of. Additionally, this claim recites the phrases “Y-shaped reverse linker sequence” and “has the following sequence.” The claim then provides 2 sequences, and it is unclear within the existing claim language whether the Y-shaped reverse adapter has both sequences or one of the two sequences.
C. Claim 5 recites the term “end closed,” however this is not a routine term used in the art. Therefore this claim is indefinite. For the purpose of prosecution, this is being interpreted as though the 5' and 3' ends of sequence 2 are blocked. Additionally, there is not proper antecedent basis for the phrase “said GC clamp sequences” in claim 1’s recitation of “a high GC clamp linker.”
D. Claim 4 recites the phrase “the sequence at the P7 end of the Y-shaped reverse linker.” There is not sufficient antecedent basis in claim 1 for this limitation.
E. Claims 2-3 and 5-7 are further rejected as being dependent on a previously rejected claim.
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
8. Claims 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al (Titration-free massively parallel pyrosequencing using trace amounts of starting material, Nucleic Acids Research, 38, 13, e137, published 30 April 2010) in view of Knierim et al (Systematic comparison of three methods for fragmentation of long-range PCR products for next generation sequencing, PLoS ONE, 6, 11, e28240, published 30 November 2011).
Zheng teaches extracting a sample of gDNA (pg. 3 column 1 ¶ 1), nebulizing the gDNA (i.e., fragmenting; pg. 3 column 1 ¶ 1), end polishing the DNA (i.e., filling ends of the gDNA) and dA extension (pg. 3 column 2 ¶ 2 and FIG 1). Zheng teaches ligating to the dA-tailed gDNA fragments a Y-adapter (i.e., a linker combination) comprising a Y-shaped region and a high GC duplex region that links the Y-shape region to the gDNA (i.e., a high GC clamp linker; Adapter Y, supplementary table 1). Zheng teaches that this product is quantified (i.e., screened; pg. 4 column 1 ¶ 5 and column 2 ¶ 1) to obtain a sequencing library.
Zheng does not specifically teach that the gDNA is fragmented by enzyme cleavage.
However, Knierim teaches that nebulization and enzymatic fragmentation are “equal with only minor differences” and that a fragmentation method is chosen based on lab facilities and experimental design (abstract).
It would have been obvious to one having ordinary skill in the art to have simply substituted the nebulization fragmentation taught by Zheng with the enzymatic fragmentation taught by Knierim to arrive at the instantly claimed invention with a reasonable expectation of success. The ordinary artisan would have been motivated to make this substitution because Knierim specifically teaches that these fragmentation methods are equivalent (abstract). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in the fragmentation of DNA for sequencing library preparation.
Regarding claim 7, Zheng teaches that the library is sequenced on using Roche 454 titanium sequencing, a patterned flow-through technology wherein sequencing reagents are flowed over a patterned picotiter plate in a flow cell.
Conclusion
9. No claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN ELLIS YOUNG whose telephone number is (703)756-5397. The examiner can normally be reached M-F 0730 - 1700.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN ELLIS YOUNG/Examiner, Art Unit 1684
/JULIET C SWITZER/Primary Examiner, Art Unit 1682