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 .
DETAILED ACTION
Application status
In response to the previous Office action, a non-Final rejection (mailed on 12/11/2025), Applicants filed a response and amendment received on 06/10/2026. Said amendment amended Claim 15. Thus, Claims 1-18 are at issue and present for examination.
It is noted by the Examiner that Claims 19-20 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention in the previous Office actions, a non-Final rejection (mailed on 12/11/2025).
Objections to the Specification – MAINTAINED
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 25, line 3. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. It is noted by the Examiner that the ‘marked-up’ version of the amendment to specification still shows the hyperlink. However, the ‘clean’ version of the amendment to specification is free of the noted hyperlink. The Examiner suggests submitting new amendment without the discrepancy between ‘marked-up’ version and ‘clean’ version.
The sequence listing, filed in computer readable form (.txt or .xml) on XXX, has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2) ST.25 and 37 C.F.R. § 1.831(b) ST.26. However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.821 through 1.825 ST.25 and 1.831-1.839 ST.26.
The following Figures/parts of the specification contain sequences that contain four or more specifically defined amino acids or ten or more specifically defined nucleotides without any corresponding SEQ ID NO:.
See particularly pages 14, 34-36, 42 and 44 of the specification containing amino acid/nucleic acid sequences, and therefore, those sequences should be represented by proper sequence identifier numbers.
If the noted sequences are not in a sequence listing as filed, Applicants must provide (1) an updated copy of the sequence listing containing the requisite sequences in computer readable form (CRF), (2) an amendment directing its entry into the specification, (3) a statement that no new matter has been added and (4) an amendment to the specification to identify each of the identified sequences by SEQ ID NO:, and (5) an incorporation by reference statement with the date of creation, sequence file name and size in bytes. – See also MPEP 2422.
Appropriate correction is required.
Claim Objections – WITHDRAWN
The previous objection of Claim 15 for the recitation of “the 3'-blocked nucleoside triphosphate is blocked a group selected from” is withdrawn by virtue of Applicants’ amendment.
Claim Rejections - 35 U.S.C. § 102 – MAINTAINED
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.
(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.
The previous rejection of Claims 1-18 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Milton et al. (WO 2019/224544 A1, published 11/28/2019, see IDS) is maintained.
The instant claims are drawn to a method of nucleic acid synthesis, wherein the method comprises the steps of: (al) providing a solid support comprising particles coated with a pre-polymerised material, wherein the pre-polymerised material comprises a co-polymer to which an initiator oligonucleotide is to be attached, wherein the co-polymer is a co-polymer of one or more first co-monomer(s) selected from acrylamide, methacrylamide, N- methylacrylamide, N,N'-dimethylacrylamide, N-(hydroxylmethyl)acrylamide, N- (hydroxyethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, hydroxyethyl methacrylate and N-vinyl pyrrolidinone and a second co-monomer which attaches to the initiator; (a2) coupling an initiator oligonucleotide to said co-polymer to form a solid-supported initiator oligonucleotide; (b) adding a 3'-blocked nucleoside triphosphate to said initiator oligonucleotide in the presence of a terminal deoxynucleotidyl transferase (TdT) enzyme or modified terminal deoxynucleotidyl transferase (TdT) enzyme; (c) cleaving the blocking group from the 3'-blocked nucleoside triphosphate in the presence of a cleaving agent; and (d) repeating steps (b) and (c) to synthesize an extended nucleic acid.
Milton et al. teach/discloses a method for nucleic acid synthesis (page 22, lines 24-30; claims 1-6, 40, 41, 51, 52, 68, 71; examples 10, 11, 13), providing a solid support such as silica-coated surface, a plurality of magnetic beads or other particles (page 89-90, line 25 - page 90, line 70; page 99, lines 1-3, 20-22) which is coated with a copolymer of acrylamide (first co-monomer) and N-(5-bromoacetamidyl-pentyl) acrylamide (BRAPA; second co-monomer, see below chemical structure which meets the limitation of Applicants’ claims 5-8), which attaches to oligonucleotides via the second co-monomer, further wherein a 3'-blocked nucleoside triphosphate is added in the presence of a TdT enzyme and subsequently the blocking group removed and the chain extension repeated, thereby anticipating claims 1-8, 13-14 and 17.
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Claim 9 is included in this rejection because Milton et al. teach that the initiator oligonucleotide is coupled via a phosphorothioate moiety (see Figure 40a on page 337).
Claim 10 is included in this rejection because Milton et al. teach that the initiator oligonucleotide is coupled via click chemistry between an azide and an alkyne (see page 69).
Claim 11 is included in this rejection because Milton et al. teach that the extended nucleic acid is detached from the solid support (see claim 61 of Milton et al. on page 271).
Claim 12 is included in this rejection because Milton et al. teach that the initiator contains a uracil moiety and nucleic acid is detached by removing the uracil base and cleaving the abasic site (see page 20, lines 19-29).
Claim 15 is included in this rejection because Milton et al. teach 3’-blocked nucleoside triphosphate comprising 3’-blocking group including 3’-O-azidomethyl (see under “Reversible blocking groups” on pages 75-81).
Claim 16 is included in this rejection because Milton et al. teach the cleaving agent, tris(2-carboxyethyl)phosphine (TCEP) (see page 117, line 30).
Claim 18 is included in this rejection because Milton et al. teach that the pre-polymerisation is carried out for at least 90 minutes prior to exposure to the surface being coated (see pages 238-239 under “Fabrication of a bromoacetyl functionalised thin polyacrylamide surface”).
For the reasons provided herein, teachings of Milton et al. anticipate Applicants’ claims 1-18.
Applicants’ Arguments:
Applicant respectfully submits that the presently claimed invention is partly based on a technique that requires particles coated with a pre-polymerized material. The specification, for example, recited as follows (page 12 lines 20-24): "Where the coating is applied to an existing surface, the surface coating can be applied as a pre-polymerized polymer mixture of the first and second co-monomers. Alternatively the surface coating can be applied to the solid support during polymerization of the first and second co-monomers."
Claim 1 and claims dependent therefrom, have also recited and required pre-polymerization. See step (al) in claim 1. Also see claim 19(i).
Milton, however, fails to teach or disclose the use of or the benefits of using pre- polymerized material, but instead uses in-situ polymerization by applying to the solid support during polymerization of the first and second co-monomers. Thus, the current disclosure is novel over Milton.
Examiner’s Explanations:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Contrary to Applicants’ allegation, Milton et al. teach that the pre-polymerization is carried out for at least 90 minutes prior to exposure to the surface being coated (see pages 238-239 under “Fabrication of a bromoacetyl functionalized thin polyacrylamide surface”), which directly rebut Applicants’ arguments. The Examiner notes that this point was already discussed in the previous office action for claim 18 (see above). For the reasons provided herein and in the previous office action, teachings of Milton et al. anticipate Applicants’ claims 1-18.
Conclusion
Claims 1-18 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
THIS ACTION IS MADE FINAL. 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 extension fee 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 JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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