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 .
Applicant previously cancels claims 1-117. Claims 118-137 are currently pending. Claims 135-137 are withdrawn as being drawn to a nonelected species. Claims 118-134 are under examination.
Election/Restrictions
Applicant's election without traverse of Group I, claims 118-134, drawn to a method of preparing a library of nucleic acids in the reply filed on December 22, 2025 is acknowledged.
Claims 135-137 are withdrawn from further consideration to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 22, 2025, and is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements filed October 14, 2022; December 19, 2024; and March 20, 2025 have 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 2.1 Kilobytes, whereas the ASCII text file itself lists the size as 2,141 bytes.
Specification
The use of the term USER®, Tween® 20, (see, Page 9, [0093], Page 38, [0209], Page 40, [0215] and [0217] and Page 50, [0238]), which are trade names or marks used in commerce, has been noted in this application. The terms 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.
Claim 124-131 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 124 recites the limitation "the second locus primers" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 125-131 depend from claim 124 and are therefore included in this rejection.
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.
Claims 118-134 are rejected under 35 U.S.C. 103 as being unpatentable by Zhang et al. (WIPO International Application Publication WO 2017/176896 A1, published October 12, 2017), cited on the IDS filed October 14, 2022, in view of Shoemaker et al. (U.S. Patent Application Publication US 2008/0171364 A1, published July 17, 2008).
Regarding claim 118, Zhang teaches method of normalizing a nucleic acid library comprising target nucleic acids (Abstract). Zhang teaches obtaining a substrate having a normalizing amount of capture probes attached thereto (Page 20, [0071], Page 60, [0163]-[0165] and Pages 63-64, [0174]-[0175]). Zhang teaches the capture probes comprise first amplification sites (Page 53, [0142], Page 55, [0149] and Pages 63-64, [0174]-[0175]). Zhang teaches hybridizing a plurality of target nucleic acids to the capture probes (Page 20, [0071], Page 52, [0141], Page 60 [0163]-[0165] and Page 71, [0195]). Zhang teaches extending the capture probes to obtain extended probes (Page 60-61, [0163]-[0166], Page 63, [0173] and Pages 71-72, [0195]-[0196]). Zhang teaches the extended probes comprise second amplification sites (Page 53, [0141], Page 55, [0149], Page 60-61, [0163]-[0166], Page 63, [0173] and Pages 71-72, [0195]-[0196]). Zhang teaches amplifying the extended probes by hybridizing extension primers to the second amplification sites (Pages 5-6, [0016], Page 18, [0066] and Page 42, [0114]). Zhang teaches the amplification is performed such that substantially all the capture probes are extended, thereby obtaining a normalizing amount of amplified target nucleic acids (Pages 20-21, [0073], Pages 54-55, [0148], Page 61, [0167], Figures 2-3, and Example 12). Zhang the first amplification sites and the extension primers are incapable of or are essentially incapable of hybridizing to one another (Pages 20-21, [0073] and Pages 54-55, [0148]-[0149]). Zhang teaches that the reaction conditions (e.g., incubation time, P7 and/or P5 primer concentration, and reaction components) can be selected such that all available primers immobilized on the capture beads are extended into amplicons, (e.g., the reaction is allowed to run to saturation and may be designed by user’s choice Pages 20-21, [0073]).
Regarding claim 119, Zhang teaches the first amplification site and extension primers as discussed above. Zhang teaches the first amplification sites comprise modified nucleotides that inhibit hybridization with the extension primers (Page 63, [0174]).
Regarding claim 120, Zhang teaches the extension primers are in solution (Page 17, [0062]).
Regarding claim 121, Zhang teaches the capture probes comprise first indexes or first sequencing primer sites (Page 60, [0162]-[0163], Page 63, [0173] and Page 88, [0249]).
Regarding claim 122, Zhang teaches the capture probes comprise first locus specific primers (Page 17, [0062], Page 50, [0133] and Pages 52-53, [0141]-[0142]).
Regarding claim 123, Zhang teaches the plurality of target nucleic acids hybridize to the first locus specific primers (Page 15, [0039]-[0041], Pages 42-43, [0114]-[0116] and Page 50, [0133]).
Regarding claim 124, Zhang teaches extending the capture probes comprises ligating the first locus specific primers to the second locus specific primers (Pages 4-5, [0013], Page 17, [0062], Pages 20-21, [0073], Page 38, [0101], Page 50, [0133], Page 52, [0138] and Page 53, [0143]).
Regarding claim 125, Zhang teaches extending the capture probes comprises hybridizing second locus specific primers to the target nucleic acids and ligating the first locus specific primers to the second locus specific primers (Pages 4-5, [0013], Page 17, [0062], Pages 20-21, [0073], Page 38, [0101], Page 50, [0133], Page 52, [0138] and Page 53, [0143]).
Regarding claim 126, Zhang teaches the second locus specific primers comprise the second amplification sites, second indexes, and/or second sequencing primer sites (Pages 4-5, [0013], Page 9, [0023], Page 17, [0062], Pages 20-21, [0073], Page 38, [0101], Page 50, [0133], Page 52, [0138] and Page 53, [0143]).
Regarding claim 127, Zhang teaches hybridizing extension oligonucleotides to the second locus specific primers and extending the second locus specific primers with sequences complementary to the extension oligonucleotides by polymerase extension (Pages 4-5, [0013], Page 17, [0062], Pages 20-21, [0073], Page 38, [0101], Page 50, [0133], Page 52, [0138], Page 53, [0143], Page 57, [0152] and Page 58, [0155]).
Regarding claim 128, Zhang teaches the extension oligonucleotides comprise sites complementary to the second amplification sites, complementary to second indexes, or complementary to second sequencing primer sites (Pages 4-5, [0013] and Page 88, [0248]).
Regarding claim 129, Zhang teaches the target nucleic acids comprise sites complementary to the second amplification sites, and the extending comprises polymerase extension of the first locus specific primers with sequences complementary to the target nucleic acids (Pages 4-5, [0013], Page 17, [0062], Pages 20-21, [0073], Page 38, [0101], Page 50, [0133], Page 52, [0138], Page 53, [0143], Page 57, [0152] and Page 58, [0155]).
Regarding claim 130, Zhang teaches preparing the target nucleic acids by adding adaptors to an end of the target nucleic acids (Page 38, [0101], Page 52, [0138], Pages 52-53, [0141]-[0142] and Claim 16). Zhang teaches the adaptors comprise sites complementary to the second amplification sites (Page 88, [0248]).
Regarding claim 131, Zhang teaches adding adaptors comprises a tagmentation reaction (Pages 4-5, [0013], Page 52, [0138] and Pages 52-53, [0141]-[0142]).
Regarding claim 132, Zhang teaches the substrate comprises a plurality of beads, and/or a flow cell (Pages 3-4, [0011] and Pages 6-7, [0018]).
Regarding claim 133, Zhang teaches the amplification is performed under conditions such that the normalizing amount of capture probes limits the amount of amplification products (Pages 5-6, [0016], Page 9, [0023] and Example 4).
Regarding claim 134, Zhang teaches sequencing the amplified target nucleic acids (Pages 91-92, [0257]-[0258]).
Zhang does not explicitly teach or suggest the amount of the extension primers is equal to or greater than the normalizing amount of capture probes. Zhang does not teach or suggest the first amplification site lack types of nucleotides complementary to one another and each extension primer lack at least one type of nucleotide selected from adenine (A), cytosine (C), guanine (G), and thymine (T).
Shoemaker teaches method and compositions for amplification and capture of nucleic acid sequences using capture probes and extended primers (Title and Abstract). Shoemaker teaches exponentially amplifying the extended primers and adding a single capture probe, therefore teaching the amount of extension primers is greater than the amount of capture probes (Page 1, [0005]). Shoemaker teaches the amplification site lack types of nucleotides complementary to one another and each extension primer lack at least one type of nucleotide selected from adenine (A), cytosine (C), guanine (G), and thymine (T) (Abstract, Page 1, [0005] and Page 3, [0033]). Shoemaker teaches using a specifically designed non-complementary oligonucleotides and extension primers lacking at least one type of nucleotide which would allow for the reaction to be strategically terminated prior to generation of any significant amount of negative reaction products, with little or no loss of generation of the positive reaction product and therefore the accuracy of detection of the actual presence of one or more nucleic acid sequences would be enhanced (Page 1, [0005], Page 3, [0033] and Page 4, [0038]).
As a common field of endeavor both Zhang and Shoemaker disclose using methods and compositions comprising capture probes and extension primers.
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 Zhang, with the teachings of Shoemaker, having the amount of the extension primers be equal to or greater than amount of capture probes and having the first amplification site lack types of nucleotides complementary to one another and each extension primer lack at least one type of nucleotide selected from adenine (A), cytosine (C), guanine (G), and thymine (T). Using a specifically designed non-complementary oligonucleotides and extension primers lacking at least one type of nucleotide which would allow for the reaction to be strategically terminated prior to generation of any significant amount of negative reaction products, with little or no loss of generation of the positive reaction product and therefore the accuracy of detection of the actual presence of one or more nucleic acid sequences would be enhanced as taught by Shoemaker (Page 1, [0005], Page 3, [0033] and Page 4, [0038]). Additionally, there is a reasonable expectation of success to use the amount Shoemaker’s capture probes and extension primer’s in the systems of Zhang (where the amount of the extension primers is equal or greater that the amount of capture probes) because Zhang discloses the reaction conditions including reaction components and concentrations may be chosen and designed by the user.
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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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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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684