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 .
Election/Restrictions
Applicant’s election without traverse of the particular species that are: (I) ligation characterized in that the first oligonucleotide is ligated directly or via an oligonucleotide bridge (relevant to claim 6) and (II) providing a DNA strand by a padlock workflow (relevant to claim 12) in the reply filed on 05/08/2026 is acknowledged.
Claims 8-10 (drawn to non-elected methods of providing an oligonucleotide) and claims 11 and 13 (draw n to non-elected methods of providing a DNA strand) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/08/2026.
Claim Objections
Claim 12 is objected to because of the following informalities:
The claim has a period in the middle of the text of the claim, at the end of 4 of the claim (i.e.: “and ligation.”).
The term “Circular” as recited in line 3 of the claim, and the term “Oligonucleotide” as recited in line 5 of the claim, each being with an unnecessary capitalized letter.
Appropriate correction is required.
Objections to the Specification and Drawings
The disclosure is objected to because of the following informalities:
The specification provides several instances of the abbreviation “TECP” (e.g.: para 0011 on p.3; para 0022 on p.6) where the abbreviation “TCEP” (i.e.: for tris(2-carboxyethyl)phosphine ) is likely intended.
Appropriate correction is required.
Similarly, the drawings are objected to because Fig. 4 provides the abbreviation “TECP” where “TCEP” is likely intended.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 2 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The rejection of claim 2 for lack of an adequate written description of the claimed subject matter in the application as originally filed is relevant in to the claim as it generically encompasses any progenitor of any reagent (i.e.: the structures encompassed by the claim are broad) in combination with the required particular functionalities of being able to be cleaved with light to provide a reagent that cleaves a blocking group from a nucleotide. The claim encompasses any cleaving agent, and progenitors thereof, that cleave by any mechanism; in this regard it is noted that such cleavage can be effected by different mechanisms (and thus via different reagents) including but not limited to enzymatic cleavage, chemical cleavage, oxidative cleavage. The application as filed discloses only a single agent that is a progenitor of a cleaving reagent that is activated by irradiation with light; the application discloses Cy5-TCEP that is irradiated to form free TCEP which cleaves a blocking group via nucleophilic attack, cleavage and hydrolysis. But such a particular teaching is not informative to the skilled artisan as to any other progenitors of cleaving reagents that are suitable for use in the method as claimed. A disclosure that some particular reagent meets the functional limitations of the claim is not itself a description of any other reagents that may be encompassed by the claim. This finding is emphasized in Ex Parte Kubin (No. 2007-0819, Bd. Pat. App. & Int. May 31, 2007), wherein it is stated that:
“Although there is often significant overlap” between the enablement and written description requirements, “they are nonetheless independent of each other.” University of Rochester, 358 F.3d at 921, 69 USPQ2d at 1891. An “invention may be enabled even though it has not been described.” Id. Such is the situation here. While we conclude one skilled in the art would have been able to make and use the full scope of claim 73 through routine experimentation, we find Appellants did not describe the invention of claim 73 sufficiently to show they had possession of the claimed genus of nucleic acids. See, e.g., Noelle v. Lederman, 355 F.3d 1343, 1348, 69 USPQ2d 1508, 1513 (Fed. Cir. 2004) (“invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed”). Thereby, a showing of how to potentially identify sequence that might be used in the claimed methods is not sufficient to establish that Applicants were in possession of the invention as broadly encompassed by the rejected claim.
Thereby, a showing of a particular progenitor of a specific cleavage reagent that might be used in the claimed methods is not sufficient to establish that Applicants were in possession of the invention as broadly encompassed by the rejected claim.
Claim Rejections - 35 USC § 112 - Indefiniteness
Where the limitations of claims 6, 7 and 12 are unclear, as detailed below, the Examiner was not able to make a comparison between the claimed methods and the related prior art for consideration of patentability under 35 USC 102 an103.
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 6, 7 and 12 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.
Claims 5-7 are unclear over recitation of the limitation “the overhang of the first strand is provided at its 5’-end with a first oligonucleotide”, as recited in claim 5 from which claims 6 and 7 depend, because it is unclear what is intended to be required with regard to providing an oligonucleotide. It is unclear if the limitation intends to require that “first oligonucleotide” is hybridized to nucleotides at the 5’ portion of the first strand (e.g.: forming a duplex), or if “provided at its 5’-end” is intended to require that the oligonucleotide is joined (e.g.: ligated to) the 5’-end of the first strand.
Claim 6 is unclear over recitation of the limitation “the first oligonucleotide is ligated … to the 3' end of the first strand thereby forming a circle”, because there appears to be a step or element that is omitted from the claimed method. Where the claim is directed to a first strand and a first oligonucleotide, the step of ligating the oligonucleotide to the 3’-end of the first strand does not appear to be sufficient to form a circle. Ligating two oligonucleotides together, as recited in the claim, does not result in a circle.
Claim 7 is unclear over recitation of the limitation “the first oligonucleotide is hybridized with the corresponding nucleotides” because there is not antecedent basis for any “corresponding nucleotides”. It is unclear what the hybridization target of the “first oligonucleotide” is intended to be.
Claim 12 is unclear over recitation of the limitation “characterized in that the DNA strand is provided by” because the claim depends from claim 1 where claim 1 recites “a first and a second strand”. There is no antecedent basis for any “DNA strand”. Furthermore it is unclear which strand (i.e.: the first or the second) may be intended by the singular “strand” in the recitation of “the DNA strand”.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, and 3-5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nguyen et al (US PG Pub 20210301615, effectively filed 05/01/2020).
Relevant to the limitations of claims 1 and 3, Nguyen et al teaches methods of adding a distinct polynucleotide sequence (i.e.: a barcode) to a polynucleotide comprising a first and second strand where the first strand comprises a 5’-end overhang with universal bases and the second strand has a recessed 3’-end, where the recessed 3’-end of the second strand is provided with a nucleotide with a blocking group, and the blocking group is removed by irradiation with light (e.g.: (e.g.: Fig 2; para 0046; para 0066).
Relevant to claim 4, Nguyen et al provides a depiction of a universal template (i.e.: the first strand) attached via its 3’-end to a solid support (e.g.: Fig 2), teaches that the template may be attached to the solid support via a functionalized linker (e.g. para 0072), and teaches that nucleotides added by a polymerase are not added to the 3’-end of the template, thus providing that the 3’-end of the template is blocked by attachment to the solid surface.
Relevant to claim 5, Nguyen et al teaches that an oligonucleotide is hybridized to the 5’-end of the first strand (e.g. Fig 2C).
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.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen et al (US PG Pub 20210301615, effectively filed 05/01/2020) in view of Guo et al (2008) and Vaughn et al (2013) (citation 16 on the IDS of 09/06/2024).
Relevant to the limitations of claims 1 and 3, Nguyen et al teaches methods of adding a distinct polynucleotide sequence (i.e.: a barcode) to a polynucleotide comprising a first and second strand where the first strand comprises a 5’-end overhang with universal bases and the second strand has a recessed 3’-end, where the recessed 3’-end of the second strand is provided with a nucleotide with a blocking group, and the blocking group is removed by irradiation with light (e.g.: (e.g.: Fig 2; para 0046; para 0066).
Relevant to claim 4, Nguyen et al provides a depiction of a universal template (i.e.: the first strand) attached via its 3’-end to a solid support (e.g.: Fig 2), teaches that the template may be attached to the solid support via a functionalized linker (e.g. para 0072), and teaches that nucleotides added by a polymerase are not added to the 3’-end of the template, thus providing that the 3’-end of the template is blocked by attachment to the solid surface.
Relevant to claim 5, Nguyen et al teaches that an oligonucleotide is hybridized to the 5’-end of the first strand (e.g. Fig 2C).
Nguyen et al does not teach removal of a blocking group by irradiation of a progenitor of a cleaving reagent to provide a cleaving reagent, as recited in claim 2. However, a cleaving reagent to remove blocking groups was known in the prior art and is taught by Guo et al, and the production of the cleaving reagent of Guo et al by irradiation of a progenitor of the cleaving reagent was known in the prior art and is taught by Vaughn et al.
Guo et al teaches the removal of nucleotide blocking azidomethyl moiety using tris(2-carboxyethyl)phosphine (TCEP) for regenerating the 3′-OH group to allow a subsequent cycle of nucleotide incorporation (Fig S2). Vaughan et al teaches that in a covalent adduct of TCEP-Cy5, TCEP can be can be separated from Cy5 via irradiation with light (e.g. Figure 1).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to provide TCEP as a cleaving agent (as taught by Guo et al) to remove a blocking agent from a nucleotide incorporated by the methods of Nguyen et al. The skilled artisan would have been motivated to use TCEP based on the expressed teachings of Nguyen et al that 3′-O-azidomethyl is an exemplary blocking group suitable for use in the methods of Nugyen et al (e.g.: para 0045; para 0080), and the expressed teaching of Gou et al that TCEP completely cleaves the 3’-O-azidomethyl group with high efficiency (e.g.: p.9147, left col). The skilled artisan would have been motivated to provide TCEP by irradiation of the TCEP-Cy5 adduct, as taught by Vaughan et al based on the expressed teachings of Vaughan et al that such methods allow for high-resolution photoreversible quenching (i.e.: separation of TCEP) of Cy 5 in the TCEP-Cy5 adduct, and the expressed teachings of Nguyen et al that polynucleotides with different sequences can be created in parallel by selectively deblocking protected nucleotides at only specific locations on the surface of the solid substrate.
Conclusion
No claim is allowed
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Li et al (2013) teaches methods comprising the addition of nucleotides that are templated by universal bases.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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, Anne Gussow can be reached at 571-272-6047. 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.
Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights