DETAILED ACTION
The present application is a domestic application filed 06 December 2023, which claims priority to US Provisional Application No. 63/386,765, filed 09 December 2022.
The preliminary amendment filed 16 June 2026 is acknowledged. Claims 1-14 are pending in the current application and are examined on the merits herein.
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
Applicants’ election without traverse of Group I, claims 1-9 in the reply filed on 16 June 2026 is acknowledged.
Canceled claims 15, 25, 28, 30, 38, 42, 44, 51 and 53 (Groups IV-XII) remain withdrawn.
Applicant requested that Groups II and III be rejoined once the Group I claims are found allowable.
The claims of Group I were found to be free of prior art. Thus, Groups II and III are hereby rejoined.
Closest Prior Art
Lelieveldt et al. (Organic & Biomolecular Chemistry, 2019, vol. 17, pp. 8816-8821, cited in PTO-892) teach the use of vinylboronic acids (VBAs) as biorthogonal protecting group for doxorubicin (DOX), (abstract). Lelieveldt et al. teach vinyl ethers, with or without a boron ester will react with a tetrazine, to release 4-hydroxybenzyl alcohol 1 (see figure 2):
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Lelieveldt et al. teach conjugating DOX, via the C3’-NH2 of the carbohydrate moiety of DOX:
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(see fig. 3). The protected DOX was cytotoxic towards HeLa cells in the presence of 10 µM of tetrazine, in an almost similar toxicity level as free DOX demonstrating the protecting group could be cleaved in vitro to release the DOX active agent (p.8819-8820).
Li et al. (WO 2017/185026, cited in PTO-892) teach
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, wherein R2 is a nucleobase, and R1 is a reversible blocking group selected from the group consisting of allenyl, cyanoethyl, cyanoethenyl, formaldehyde oximyl, acrylaldehyde oximyl, propionaldehyde oximyl, and cyanoethenaldehyde. However, Li et al. do not expressly disclose the use of tetrazine to remove the blocking group at the C3’-position.
While the self-immolative protecting groups as claimed were known before the effective filing date of the claimed invention, as taught by Lelieveldt et al., their use as protecting groups for nucleosides and nucleotides as claimed were not known. Additionally, Lelieveldt et al. teach the use of the vinyl arylene group as a DOX prodrug. While the present claims are drawn towards the use of the 3’-blocking group for synthesizing optionally labeled oligo/polynucleotides.
There is no teaching, suggestion or motivation in the prior art to modify a nucleoside or nucleotide of Li et al. to contain a vinyl arylene protecting group at the C3’-hydroxy position as claimed. Additionally, there is no teaching, suggestion or motivation to use the vinyl arylene group as part of a method for synthesizing oligo/polynucleotides.
Claim Objections
Claims 8 and 10 are objected to because of the following informalities:
The recitation “or nucleotide is nucleotide having” in line 2 of claim 8 would read better if it recited “or nucleotide is a nucleotide having”.
The recitation “copy polynucleotide complementary” is not standard terminology in the art. Specifically, the term “copy” appears to be redundant. It is respectfully suggested each instance of “copy” be deleted. For clarity, the term “copy polynucleotide strand” in (b) and (c) of claim 10 could be replaced with “complementary polynucleotide strand”. Appropriate correction is required.
The recitation “(a) incorporating a nucleotide claim 8” in claim 10, line 3 should be amended to recite “(a) incorporating a nucleotide of claim 8”.
Claim Rejections - 35 USC § 112(b)
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 7, 10 and 12-14 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.
Claim 7 recites a structure having a variable L, which is not defined in claim 6 or claim 1. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The recitation “the target” in claim 10, line 4 lacks antecedent basis. The rejection can be overcome by reciting “a target”.
The following is a suggestion (not a requirement). While claim 10 includes the subject matter of claim 8, which includes the subject matter of claim 1, it would be beneficial to provide clearer antecedent reference or definition of the 3’ blocking group.
The recitation “the oligonucleotide” in claim 12, line 3 lacks antecedent basis, which renders the claim and dependent claim 13 herein indefinite. The rejection can be overcome by reciting “an oligonucleotide”.
The recitation “unsubstituted or substituted variants thereof” in claim 14, renders the claim herein indefinite. The term “variants” is not defined in the present Specification.
The term “variant” could include substituted or unsubstituted compounds that are structurally related the claimed tetrazine reagent. However, the same parent tetrazine compound is not necessarily present in a variant thereof. One of ordinary skill in the art would not know the metes and bounds of the compounds encompassed by claim 14.
Conclusion
Claims 8 and 10 are objected. Claims 7, 10 and 12-14 are rejected.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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