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 .
Application Status
This action is written in response to applicant’s correspondence received on 05/15/2026. Claims 1-20 are currently pending. Claims 13-16, 20 are withdrawn from prosecution as being drawn to nonelected subject matter. Accordingly, claims 1-12, 17-19 are examined herein. The restriction requirement mailed on 03/17/2026 is still deemed proper.
Election/Restrictions
Claims 13-16, 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Applicant's elected Group I without traverse in the reply filed on 05/15/2026. Accordingly, claims 1-12, 17-19 are examined herein. The restriction requirement mailed on 03/17/2026 is still deemed proper.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered, e.g. NPLs listed on Page 3, ¶[0009].
Priority
This application is a 371 of PCT/EP2022/058814 filed on 04/01/2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in EP21305428 on 04/02/2021.
Drawings
The drawing is objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG.”.
In the current case, the view number for Fig. 1 and Fig. 2 are preceded by the word "Fig." instead of the capitalized abbreviation "FIG.".
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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. For example, on page 37, line 11. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term “Sigma”, “New England Biolabs”, “Bio-Rad”, “Typhoon”, “GE Life Sciences”, “Biotium”, “TECAN” on pages 29-30, “Dynabeads” on page 9, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 10 is objected to because of the following informalities: the recitation “claim_7” should not include the “_” character. Appropriate correction is required.
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.
Claims 1, 3-12, and 19 are 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The independent claim 1 directs to an extremely broad genus of “polyC oligonucleotides” comprised in the reaction mixture, with no specified requirement regarding how these “polyC oligonucleotides” exist within said reaction mixture, i.e. it encompasses a broad range of positional relationship between the “polyC oligonucleotides” and the polynucleotide being synthesized. In another word, there is no structural limitation on the form of presence for the “polyC oligonucleotides”.
The specification teaches embodiments wherein the “polyC oligonucleotides” are components of the initiator tethered to a solid synthesis support, or are in free form in the reaction mixture solution (Page 2, ¶[0004]). Only one example, however, is presented with the claimed limitation “polyC oligonucleotides” comprised in the initiator (Page 32, ¶[0074]). Since the form of presence of “polyC oligonucleotides” in the context of Template-independent Enzymatic Oligonucleotide Synthesis (TiEOS) is free of the art, there is no pre-existing knowledge regarding how the “polyC oligonucleotides” would perform in preventing G4 structure formation during TiEOS given that the interactions between the “polyC oligonucleotides” with the elongating G4-prone polynucleotide being synthesized are entirely unknown, thereby unpredictable and highly variant. The single example of “polyC oligonucleotide”-comprising initiator does not sufficiently represent the full scope of the genus as claimed.
Regarding the state of the art, To prevent secondary structure formation during TiEOS, Efcavitch (US20180274001A1, published on 09/27/2018; Citated on IDS filed on 05/15/2026) teaches the incorporation of alternative strategies of either setting “an elevated temperature when a thermostable DNA polymerase is used” or “base-pair-inhibiting moieties” to “prevent formation of hairpin or other secondary structures of the nascent oligonucleotide due to base-pairing between self-complementary regions during synthesis” (¶[0020]) for the purpose of “insuring high yield enzymatic synthesis of long oligonucleotides” (¶[0059], last line). Although not specifically pointing out G4 structures, “hairpin or other secondary structures” encompasses G4 structures under BRI. Efcavitch further teaches that “The removable base-pair-inhibiting moiety may be linked via N6 of adenine, N2 of guanine, or N4 of cytosine” (¶[0014], lines 12-14). Since G-quadruplexes require the formation of Hoogsteen base paring via hydrogen bonds between each pair of guanines involving the N1, N7, N2 and O6 atoms, as evidenced by Fay (J Mol Biol. 2017 Jul 7;429(14):2127-2147; Page 2127, Introduction, lines 12-18), some embodiments of Efcavitch’s “base-pair-inhibiting moiety” inherently disrupt G4 structure formation.
Efcavitch does not specifically teach “synthesizing a polynucleotide having a predetermined sequence capable of forming a G4 structure” or “wherein the reaction mixture for elongating the initiator or the elongated fragment comprise polyC oligonucleotides capable of forming duplexes with regions of the polynucleotide”. Hence, the closest art in the field can not be relied upon to predict the outcome of various embodiments of how “polyC oligonucleotides” would perform with each distinct form of presence within the broad genus as claimed.
The disclosure of insufficient species of a broad genus, the high degree of variation in the art, and the failure to disclose correlation between structure in the specification and the claimed function led to the determination that claim 1 is overly broad with insufficient evidence of possession at the time of filing to one skilled in the art. Thus, claim 1 does not meet the written description requirement, and the specification demonstrates a clear lack of possession of the full genus as claimed.
Claims 3-12, and 19 are also rejected for depending from the rejected claim 1 and failing to remedy the lack of written description therein.
Allowable Subject Matter
Claims 2, 17 and 18 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
Claims 2, 17 and 18 describe specific methods of template-independent enzymatic synthesis of a polynucleotide having a predetermine sequence capable of forming a G4 structure, wherein an initiator comprises polyC oligonucleotides capable of forming duplexes with regions of the polynucleotide, wherein a claimed synthesis support further comprises said polyC oligonucleotides attached thereto, and wherein said polynucleotide is a DNA and wherein a claimed template-independent polymerase is a terminal deoxynucleotidyltransferase (TdT) or variant thereof. These that are fully described in the specification (Page 12, ¶[0030]; Page 17, ¶[0043]; Page 32, ¶[0074]). There is one working example disclosed in the specification demonstrating that representative variant of an initiator comprising the claimed “polyC oligonucleotides” meets the limitation as claimed (Page 32, ¶[0074]).
The closest prior art is Efcavitch (US20180274001A1, published on 09/27/2018; Citated on IDS filed on 05/15/2026). The prior art teaches a template-independent enzymatic synthesis of polynucleotide using DNA polymerase theta and describes “hairpin or other secondary structures” encompasses G4 structures under BRI. Efcavitch does not specifically teach “synthesizing a polynucleotide having a predetermined sequence capable of forming a G4 structure” or “wherein the reaction mixture for elongating the initiator or the elongated fragment comprise polyC oligonucleotides capable of forming duplexes with regions of the polynucleotide”. Efcavitch also does not teach further limitations such as: the method of claim 2, wherein an initiator comprises polyC oligonucleotides capable of forming duplexes with regions of the polynucleotide, wherein a claimed synthesis support further comprises said polyC oligonucleotides attached thereto, and wherein said polynucleotide is a DNA and wherein a claimed template-independent polymerase is a TdT or variant thereof. Thus, the claimed inventions are free of prior art.
Claims 2, 17 and 18 remedy the lack of written description in claim 1 upon which they depend. Therefore, claims 2, 17 and 18 are allowable.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled "Comments on Statement of Reasons for Allowance".
Conclusion
Claims 2, 17 and 18 are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Delphinus D. Yu whose telephone number (571) 272-1576. The examiner can normally be reached Mon-Thr 7:30am to 4:30pm Fri 10am to 2pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil P Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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