Prosecution Insights
Last updated: April 19, 2026
Application No. 17/794,320

METHODS OF NUCLEIC ACID SYNTHESIS

Non-Final OA §102
Filed
Jul 21, 2022
Examiner
LEE, JAE W
Art Unit
1656
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Nuclera Ltd.
OA Round
1 (Non-Final)
66%
Grant Probability
Favorable
1-2
OA Rounds
3y 0m
To Grant
99%
With Interview

Examiner Intelligence

Grants 66% — above average
66%
Career Allow Rate
270 granted / 412 resolved
+5.5% vs TC avg
Strong +38% interview lift
Without
With
+38.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 0m
Avg Prosecution
26 currently pending
Career history
438
Total Applications
across all art units

Statute-Specific Performance

§101
4.1%
-35.9% vs TC avg
§103
28.6%
-11.4% vs TC avg
§102
25.3%
-14.7% vs TC avg
§112
31.9%
-8.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 412 resolved cases

Office Action

§102
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 Claims 1-20 are pending in this application. Priority The instant application is the 371 national stage entry of PCT/BG2021/050154, filed on 01/22/2021. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application UNITED KINGDOM GB2000902.3 filed on 01/22/2020 and UNITED KINGDOM GB2013102.5 filed on 08/21/2020. Election Applicant's election with traverse of Group I, Claims 1-18, and species elections: first co-monomer: acrylamide; pre-polymerised material: acrylamide; second co-monomer containing a reactive moiety: haloacetamide; and 3’block group: 3’-aminooxy, in the response filed on 09/26/2025, is acknowledged. Applicants argue that there is no additional search burden to search all claims. Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. There would be a serious search and examination burden if restriction were not required because [1] the prior art applicable to one invention would not likely be applicable to another invention; and [2] the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph, i.e., method of nucleic synthesis vs. product kit claims. Claims 19-20 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention. For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final. Information Disclosure Statement The information disclosure statement (IDS) submitted on 07/21/2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Objections to the Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 25, line 2; and page 25, line 6. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825; Applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990). To be in compliance, Applicants should identify nucleotide sequences of at least 10 nucleotides and amino acid sequences of at least 4 amino acids in the specification by a proper sequence identifier, i.e., “SEQ ID NO:” (see MPEP 2422.01). If these sequences have not been listed in the computer readable form and paper copy of the sequence listing, applicant must provide an initial computer readable form (CRF) copy of the “Sequence Listing”, an initial paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, and a statement that the content of the paper and CRF copies are the same and, where applicable, include no new matter as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.821(b) or 1.825(d). See particularly pages 13, 28-36, 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 Claim 15 is objected to because of the following informalities: Claim 15 recites “the 3'-blocked nucleoside triphosphate is blocked a group selected from” which can be substantially improved with respect to grammar. In the interest of advancing prosecution, the Examiner interpreted the phrase as “the 3'-blocked nucleoside triphosphate comprises a blocking group selected from”. Appropriate correction is required. Claim Rejections - 35 U.S.C. § 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. (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 1-18 are rejected 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). 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. PNG media_image1.png 223 823 media_image1.png Greyscale 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. 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. The instant Office action is non-final. 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. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /JAE W LEE/ Examiner, Art Unit 1656 /SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
Read full office action

Prosecution Timeline

Jul 21, 2022
Application Filed
Dec 09, 2025
Non-Final Rejection — §102 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
66%
Grant Probability
99%
With Interview (+38.5%)
3y 0m
Median Time to Grant
Low
PTA Risk
Based on 412 resolved cases by this examiner. Grant probability derived from career allow rate.

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