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 Claims 135-137 remain withdrawn as being drawn to a nonelected invention. Claims 118-134 are under examination. Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is Final.
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 118-134 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. This is a new rejection as necessitated by amendments.
Claim 118 is vague and indefinite for the following reasons:
Claim 118 recites the limitation "the same type of nucleotide" in lines 15 and 18. There is insufficient antecedent basis for this limitation in the claim.
Claims 119-134 depend from claim 118 and are therefore included in this rejection.
Claim 119 is considered vague and indefinite for the following reasons:
Claim 119 recites the limitation "the same type of nucleotide" in lines 5 and 10. There is insufficient antecedent basis for this limitation in the claim.
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), previously cited in the January 23, 2026 Office Action, and further in view of Wang et al. (U.S. Patent Application Publication US 2018/0148775 A1, published May 31, 2018). This is a new rejection as necessitated by amendments.
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 and the extension primers each lack the same types of nucleotide.
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 lacking at least one type 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]).
Wang teaches a method of amplifying a segment of a target nucleic acid comprising contacting a sample comprising a target nucleic acid with forward and reverse primers and conducting an amplification reaction wherein an amplified segment (site) of the target nucleic acid is formed by extension of the forward and reverse primers with the target nucleic acid serving as a template (Page 2, [0009]). Wang teaches using capture probes (Page 11, [0121]). Wang teaches a first amplification site and the extension primers each lack the same type of nucleotide (e.g., the primers are underrepresented in one or more of the four standard nucleotide types, the underrepresented nucleotide type(s) being the same in the primers, and the amplified segment; Page 2, [0009]). Wang teaches using the extension primer and amplification site lacking the same type of nucleotide allows for substantially suppressing primer dimers as well as unwanted side reaction amplification products and improving hybridization efficiency (Page 2, [0009], Page 3, [0016] and Page 24, [0243]).
As a common field of endeavor Zhang, Shoemaker and Wang all 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 lacking 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.
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 and Shoemaker with the teachings of Wang, to use a first amplification site and extension primers each lacking a same type of nucleotide. This would allow for substantially suppressing primer dimers as well as unwanted side reaction amplification products and improving hybridization efficiency as taught by Wang (Page 2, [0009], Page 3, [0016] and Page 24, [0243]).
Response to Arguments
Applicant’s arguments and amendments filed April 21, 2026, with respect to the rejections under U.S.C. § 112(b) have been fully considered and are persuasive. Therefore, these rejections have been withdrawn.
Applicant’s arguments and amendments filed April 21, 2026, with respect to the rejections under U.S.C. § 103 have been fully considered and are persuasive. Therefore, these rejections have been withdrawn.
However, upon further consideration, new rejections under 35 U.S.C. § 112(b) and 103 are made in view of applicant’s amendments.
As discussed above, newly cited Wang discloses a first amplification site and the extension primers each lack the same type of nucleotide (e.g., the primers are underrepresented in one or more of the four standard nucleotide types, the underrepresented nucleotide type(s) being the same in the primers, and the amplified segment). Using the extension primer and amplification site lacking the same type of nucleotide allows for substantially suppressing primer dimers as well as unwanted side reaction amplification products and improving hybridization efficiency as taught by Wang (Page 2, [0009], Page 3, [0016] and Page 24, [0243]).
Therefore, for all these reasons and those listed above, Zhang in view of Shoemaker and further in view of Wang are deemed to render the instant invention obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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, 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.
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.
/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
Prosecution Insights