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, 7, 10, 14, 20, 23, 40-42, 71, 87-89, 92 and 145-150 are currently pending. Applicant previously cancels claims 2-6, 8-9, 11-13, 15-19, 21-22, 24-39, 43-70, 72-86, 90-91, 93-144 and 151-154. Claims 87-89, 92 and 145-150 are withdrawn as being drawn to a nonelected group. Claims 1, 7, 10, 14, 20, 23, 40-42 and 71 are currently under examination.
Election/Restrictions
Applicant’s election without traverse of Group I: claims 1, 7, 10, 14, 20, 23, 40-42 and 71 drawn to a method for counting nucleic acid molecules in a sample in the reply filed on October 22, 2025 is acknowledged.
Claims 87-89, 92 and 145-150 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 October 22, 2025.
Information Disclosure Statement
The Information Disclosure Statement filed October 22, 2025 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/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:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
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.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Claim Rejections - 35 USC § 112
Claim 42 is 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 42 recites the limitation "the SS" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 7, 10, 14, 20, 23, 40-42 and 71 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions (i.e., product of nature, a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Every claimed invention must be examined to determine whether the claimed invention complies with 35 U.S.C. 101, particularly whether the claimed invention falls within a 35 U.S.C. 101 judicial exception of non-patentable subject matter (e.g., an abstract idea, law of nature, natural phenomenon, natural product etc.). Phenomena of nature, though just discovered, natural products, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work. See MPEP 2106. As per the “2019 Revised Subject Matter Eligibility Guidance” (Federal Register Vol. 84, No. 4, available 01-07-2019), claims drawn to a process, machine, manufacture or composition of matter are further analyzed according to a two-part process to determine if A) the claim(s) is/are “directed to” a judicial exception because the claims(s) recite(s) a judicial exception (i.e. prong one) that is not integrated into a practical application (i.e. prong two) and, if so, if B) the claim(s) provide(s) an inventive concept, i.e. recite(s) additional elements that amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES
Claims 1, 7, 10, 14, 20, 23, 40-42 and 71 are directed to one of the statutory classes. Claims 1, 7, 10, 14, 20, 23, 40-42 and 71 are directed to a method for counting nucleic acid molecules of a sample (Process).
Step 2A, Prong One — Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Claims 1, 7, 10, 14, 20, 23, 40-42 and 71 recite the abstract ideas of receiving and processing data using mental steps and mathematical concepts. Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection (see MPEP 2106.04). Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). The instant claims are directed to methods for "aligning", "identifying" and “counting” where mental processes including observation, evaluation, and opinion are abstract ideas used in the acts of "aligning", “counting” and "identifying" present in the claim. In particular, these abstract ideas include:
• Counting nucleic acids (mental process, human mind is capable of receiving data).
• Aligning reads to a reference sequence (mental process of receiving and evaluating information as well as determining a mathematical quantity).
• Identifying a number of template nucleic acid molecules present in the sample (mental process of receiving and evaluating information as well as determining a mathematical quantity).
Therefore, the claims recite elements that constitute one or more judicial exceptions.
Step 2A, Prong Two — Does the Claim Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. However, absent are any additional elements recited in the claim beyond the judicial exceptions which integrate the exception into a practical application of the exception. The “integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
The claim analysis continues with identifying additional elements beyond the judicial exceptions that might evidence integration of the judicial exceptions into a practical application. The steps or elements in addition to the judicial exceptions are: “obtaining a sample”, “randomly truncating said plurality of template nucleic acid molecules”, “forming a plurality of second strand cDNA molecules from said plurality of template nucleic acid molecules”, “amplifying at least a portion of said plurality of truncated nucleic acid molecules to produce a plurality of amplified nucleic acid molecules” and “sequencing at least a portion of said plurality of amplified nucleic acid molecules to produce a plurality of sequencing reads”, which is not indicative of integration into practical application. These steps, recited at a high level of generality, comprise routine data gathering, which is considered an insignificant extra-solution activity. This data gathering is required for using the judicial exceptions. (See MPEP 2106.05(g)). There are no further/additional steps which applies either the identified judicial exception into practical application. Thus, a careful evaluation of the claim as a whole fails to reveal the practical application of the judicial exception to, e.g., effect an improvement to the functioning of a computer or other technology/technical field, effect a particular treatment or prophylaxis for a disease or medical treatment, implement a particular machine that is integral to the claim, or effect a transformation or reduction of a particular article to a different state or thing, or to apply the judicial exception in another meaningful way beyond generally linking its use to a particular technological environment. Accordingly, the claims do not integrate the judicial exception(s) into a practical application and is therefore directed to a judicial exception.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to “significantly more” than the judicial exception(s) itself. The claims as a whole are analyzed to determine whether any additional element/step, or combination of additional elements/steps, in addition to the identified judicial exception(s) is sufficient to ensure that the claim amounts to “significantly more” than the exception(s).
The eligibility analysis proceeds with identifying any additional elements or limitations, separate from the judicial exceptions, that might potentially render the claims directed to a judicial exception patent eligible. To render the claims patent- eligible, these elements must comprise meaningful limitations that add to or transform the judicial exception to the effect that it amounts to significantly more than the natural correlation or abstract idea itself - i.e. provide an “inventive concept’. The elements that are in addition to the judicial exception comprise: obtaining a sample, randomly truncating said plurality of template nucleic acid molecules, forming a plurality of second strand cDNA molecules from said plurality of template nucleic acid molecules, amplifying at least a portion of said plurality of truncated nucleic acid molecules to produce a plurality of amplified nucleic acid molecules and sequencing at least a portion of said plurality of amplified nucleic acid molecules to produce a plurality of sequencing reads. When considered separately and in combination, these elements do not add significantly more to the judicial exception. These steps are well-understood, routine and conventional activities in the field. For example, Fodor et al. (U.S. Patent Application Publication US 2019/0100798 A1, published April 04, 2019), cited on the IDS filed October 22, 2025, discloses obtaining a sample, randomly truncating said plurality of template nucleic acid molecules, forming a plurality of second strand cDNA molecules from said plurality of template nucleic acid molecules, amplifying at least a portion of said plurality of truncated nucleic acid molecules to produce a plurality of amplified nucleic acid molecules and sequencing at least a portion of said plurality of amplified nucleic acid molecules to produce a plurality of sequencing reads. The claims recite an abstract idea with additional elements. Because these elements are not inventive concepts, the claims do not integrate the abstract idea into a practical application. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Accordingly, the claims do not qualify as patent-eligible subject matter.
For further information, please see the latest revision of MPEP 2104-2106 {Patent Subject Matter Eligibility Under 35 U.S.C. 101}, including MPEP 2106.04 {Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception} and 2106.05 {Eligibility Step 2B: Whether a Claim Amounts to Significantly More}, as well as the guidance on Subject Matter Eligibility, including the 2019 Guidance issued Jan. 7, 2019, and the October 2019 Update, provided on the USPTO website at https:/Awww.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter- eligibility.
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.
(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, 7, 10, 14, 40 and 71 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Fodor et al. (U.S. Patent Application Publication US 2019/0100798 A1, published April 04, 2019), cited on the IDS filed October 22, 2025.
Regarding claim 1, Fodor teaches a method for counting nucleic acid molecules of a sample (Page 2, [0013]). Fodor teaches obtaining a sample comprising a plurality of template nucleic acid molecules (Page 2, [0013], Page 7, [0081] and Pages 7-8, [0085]). Fodor teaches randomly truncating said plurality of template nucleic acid molecules at a truncation base position within said plurality of template nucleic acid molecules, and said truncating comprises performing a random selection of said truncation base position among a plurality of base positions of said template nucleic acid molecule, thereby producing a plurality of truncated nucleic acid molecules (Page 14, [0141]). Fodor teaches said plurality of template nucleic acid molecules comprises cDNA molecules (Pages 7-8, [0085], Page , [0130] and Claim 28). Fodor teaches truncating comprises making a copy of at least a portion of said plurality of template nucleic acid molecules, forming a plurality of second strand cDNA molecules from said plurality of template nucleic acid molecules, and said truncation base positions are preserved in said plurality of second strand cDNA molecules (Page 13, [0130], Page 14, [0135], Page 14, [0141] and Fig. 6). Fodor teaches amplifying at least a portion of said plurality of truncated nucleic acid molecules to produce a plurality of amplified nucleic acid molecules and said truncation base positions are preserved in said amplified nucleic acid molecules (Page 18, [0174]). Fodor teaches sequencing at least a portion of said plurality of amplified nucleic acid molecules to produce a plurality of sequencing reads and each of said plurality of sequencing reads comprises a truncation location corresponding to said truncation base position of said corresponding amplified nucleic acid molecule (Page 18, [0174] and Page 14, [0141]). Fodor teaches aligning at least a portion of said plurality of sequencing reads to a reference sequence, thereby producing a plurality of aligned sequencing reads (Page 20, [0190]-[0191] and Claim 12). Fodor teaches identifying a number of template nucleic acid molecules present in said sample using truncation locations of said plurality of aligned sequencing reads (Page 14, [0141] and Page 18, [0174]).
Regarding claim 7, Fodor teaches processing at least a portion of said amplified nucleic acid molecules to produce a sequencing library and said truncation base positions are preserved in said sequencing library (Page 18, [0174, Page 14, [0141] and Pages 16-17, [0159]).
Regarding claim 10, Fodor teaches the sample comprises one or more barcoded beads and the template nucleic acid molecules are cDNA molecules attached to said barcoded beads (Page 1, [0009], Page 2, [0013], Page 7, [0078], Pages 7-8, [0085], Page 8, [0091], Page 12, [0116], Page 25, [0221] and Claim 28). Fodor teaches the cDNA molecules are obtained by reverse transcription of RNA molecules that are released from cellular single cell samples (Pages 7-8, [0085], Pages 1-2, [0011], Page 11, [0110] and [0113], and Claim 29).
Regarding claim 14, Fodor teaches contacting said plurality of template nucleic acid molecules with a plurality of second strand primers (Page 13, [0130], Page 14, [0135], Page 14, [0141] and Fig. 6). Fodor teaches each of said plurality of second strand primers comprises a 5' universal primer sequence and a 3' sequence complementary to a sequence of said template nucleic acid molecules, and wherein said 3' sequence comprises a random sequence (Page 1, [0013], Page 13, [0130], Page 14, [0135], Page 14, [0141] and Fig. 6). Fodor teaches extending said plurality of second strand primers to produce said plurality of second strand cDNA molecules (Page 13, [0130] and Page 14, [0135]).
Regarding claim 40, Fodor teaches a PCR amplification that re-establishes directionality of said sequencing library (Page 4, [0054], Pages 4-5, [0058]-[0059], Page 7, [0081], Page 13, [0128], Page 14, [0141], Page 18, [0174], Page 22, [0199]-[0200], Page 23, [0201] and Fig. 6)
Regarding claim 71, Fodor teaches sequencing comprises obtaining a first sequencing read and a second sequencing read (Pages 20-21, [0190]-[0193] and Claims 11-15). Fodor teaches the sample barcode is captured in said first sequencing read and wherein said truncation location corresponding to said truncation base position is captured in said second read (Page 2, [0013]-[0014], Page 10, [0103], Page 14, [0141] and Pages 20-21, [0190]-[0193]).
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.
Claims 20, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Fodor et al. (U.S. Patent Application Publication US 2019/0100798 A1, published April 04, 2019), cited on the IDS filed October 22, 2025, as applied to claims 1, 7, 10, 14, 40 and 71 above, and in view of Brown et al. (WIPO International Application Publication WO 2016/040524 A1, published March 17, 2016).
Regarding claim 20, Fodor teaches second strand primers as discussed above.
Regarding claim 41, Fodor teaches the sequencing library as discussed above.
Regarding claim 42, Fodor teaches the nucleic acid molecules and second strand primer as discussed above.
Fodor does not explicitly teach said second strand primers comprise a sided sequence (SS), and said SS comprises 5 to 9 bases. Fodor does not teach or suggest said sequencing library comprises known sided sequences (SS) on a 3' and a 5' side of nucleic acid molecules of said sequencing library, and the 3' and 5' SS defines the 3' and 5' direction of the sequencing library respectively. Fodor does not teach or suggest said 3' SS is a copy of the SS in the nucleic acid molecules, and said 5' SS is a copy of the SS in the second strand primer.
Brown teaches nucleic acid library preparation and cDNA second strand synthesis using oligo(dT) priming (Abstract, Pages 12-13, [0021], Page 35, [00113], Page 72, [00277] and Pages 86-87, [00323]). Brown teaches counting/quantifying nucleic acids/reads (Page 22, [0045]-[0046] and Pages 86-87, [00323]). Brown teaches randomly truncating (fragmenting) nucleic acids, tagging, amplifying and sequencing the fragments (Pages 1-2, [0005], Pages 17-18, [0027], Page 26, [0071] and Pages 26-27, [0074]). Brown teaches barcoding the fragments, which is used to identify the source of the sample (Page 26, [0071], Pages 26-27, [0074] and Pages 27-28, [0078]). Brown teaches aligning a plurality of sequence reads to a reference sequence (Page 75, [00287]). Brown teaches using second strand primers (Pages 48-49, [00170], Page 69, [00264] and Page 103, [00381]). Brown teaches the second strand primers comprise a side sequence (e.g., B adapter, Pages 48-49, [00170], Page 69, [00264] and Page 103, [00381]). Brown teaches the adapters (sided sequences) are known sequences that flank a sample sequence (3’ and 5’) and that the known sequence (adapters) may be designed by user’s choice (Page 27, [0077] and Pages 32-33, [00105]). Brown teaches complementary oligos to the adapters at each end of the library molecule (e.g., Known 3’SS and 5’ SS, Page 120, [00491]). Brown teaches 3' SS is a copy of the SS in the nucleic acid molecules, and said 5' SS is a copy of the SS in the second strand primer (Page 38, [00128], Page 44, [00149] and Page 50, [00176]). Brown teaches using these methods requires fewer processing steps, removes expensive and cumbersome aspects of the library generation workflow and is done at a reduced cost (Pages 32-33, [00104]-[00106]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Fodor with the teachings of Brown to use a sequencing library comprises known sided sequences (SS) on a 3' and a 5' side of nucleic acid molecules of said sequencing library, and the 3' and 5' SS defines the 3' and 5' direction of the sequencing library respectively as well as said 3' SS is a copy of the SS in the nucleic acid molecules, and said 5' SS is a copy of the SS in the second strand primer. Using these methods requires fewer processing steps, removes expensive and cumbersome aspects of the library generation workflow and is done at a reduced cost as taught by Brown (Pages 32-33, [00104]-[00106]).
Additionally, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the second primers of Fodor with the second primers of Brown, designing the SS of the second primers to be 5-9 bases because Brown teaches that the adapters (sided sequences) may be designed by user’s choice (Page 27, [0077]). Additionally, It would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to modify the method of Hogrefe by substituting the forward and reverse primers as taught by Short because it has been held that the simple substitution of one known element for another to obtain predictable results is obvious. In re Fout, 213 USPQ 532 (CCPA 1982), In re O'Farrell, 7 USPQ2d 1673 (Fed. Cir. 1988). Simply substituting the primers of Hogrefe with primers of Short would obtain predictable results because both Fodor and brown teach methods using second strand primers, and the second strand primers of Brown are well suited for the system of Fodor.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Fodor et al. (U.S. Patent Application Publication US 2019/0100798 A1, published April 04, 2019), cited on the IDS filed October 22, 2025, as applied to claims 1, 7, 10, 14, 40 and 71 above, and in view of Fu et al. (WIPO International Application Publication WO 2013/130674 A1, published September 06, 2013).
Regarding claim 23, Fodor teaches template nucleic acid molecules, a universal primer sequence, a sample barcode, a poly(dT) sequence, and a sequence that is complementary to a sequence of a target nucleic acid as discussed above.
Fodor does not explicitly teach or suggest the template nucleic acid molecules comprise, in 5' to 3' direction, a universal primer sequence, a sided sequence (SS), a sample barcode, a poly(dT) sequence, and a sequence that is complementary to a sequence of a target nucleic acid.
Fu teaches randomly fragmenting nucleic acids and tagging the fragments with a barcode (Page 35, [00181]). Fu teaches cDNA second strand synthesis and second strand primers (Page 81, [00340], Page 98, [00441] and Page 97, [00439]). Fu teaches the template nucleic acid molecules comprise, in 5' to 3' direction, a universal primer sequence, a sided sequence (SS) (Known Flanking sequence), a sample barcode (unique identifier), a poly(dT) sequence, and a sequence that is complementary to a sequence of a target nucleic acid (target specific region) (Page 31, [00167], Page 34, [00179] and Page 35, [00181]. Fu teaches using these methods may reduce or prevent unintended incorporation of oligonucleotide tags during PCR amplifications as well as improve sequencing of the stochastically labeled molecules and reduce/prevent sequencing errors (Pages 68-69, [00294]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Fodor with the teachings of Fu, to use the template nucleic acid molecules comprising, in 5' to 3' direction, a universal primer sequence, a sided sequence (SS), a sample barcode, a poly(dT) sequence, and a sequence that is complementary to a sequence of a target nucleic acid. Using these methods would allow for reduced or preventing unintended incorporation of oligonucleotide tags during PCR amplifications as well as improve sequencing of stochastically labeled molecules and reduce/prevent sequencing errors as taught by Fu (Pages 68-69, [00294]).
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.
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 571-272-28765. 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