DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election of “triazole” as the linker species (for covalently coupling the tag to the terminal phosphate of the nucleotide) and further election of the “triazole” sub-species recited in claim 43, as well as election of “oligonucleotide” as the tag species, in the reply filed on 6/22/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
3. Claims 34, 36-40, 42-44 and 46-56 are pending in the application. Claim 44 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 34, 36-40, 42-43 and 46-56 are currently under examination.
Specification
4. The disclosure is objected to because of the following informalities: paragraph [0055] of the specification states that “Figure 1 shows a tag attached to the terminal phosphate of a nucleotide”, however Figure 1 was not included in the list of drawings as filed on 7/1/2022.
Appropriate correction is required.
Claim Objections
5. Claims 53 and 56 are objected to because of the following informalities:
Claim 53, line 3: “a C3-alkyl to C12-alkyl spacers” should be changed to “[[a]] one of C3-alkyl to C12-alkyl spacers” for more clarity.
Claim 56, line 3: “a C3-alkyl to C12-alkyl spacers” should be changed to “[[a]] one of C3-alkyl to C12-alkyl spacers” for more clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 49-50 are rejected 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.
(1). Claim 49, which depends from claim 34, recites the limitation “the oligonucleotide” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Since claim 48 recites “an oligonucleotide” (see line 3), claim 49 may be amended to depend from claim 48 (instead of claim 34) to overcome this rejection.
(2). Claim 50, which depends from claim 34, recites the limitation “the oligonucleotide” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Since claim 48 recites “an oligonucleotide” (see line 3), claim 50 may be amended to depend from claim 48 (instead of claim 34) to overcome this rejection.
Claim Rejections - 35 USC § 102
8. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
9. 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.
10. Claims 34, 36-38, 40, 46, 48-51 and 54 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Ju et al. (US 2013/0264207 A1).
Regarding claims 34 and 36
Ju et al. teach, throughout the whole document and particularly paragraphs [0008]-[0013], a method for determining the nucleotide sequence of a single-stranded nucleic acid (e.g., DNA) comprising: (a) contacting the single-stranded nucleic acid (e.g., DNA), wherein the single-stranded nucleic acid is in an electrolyte solution which is in contact with a nanopore in a membrane and wherein the single-stranded nucleic acid has a primer hybridized to a portion thereof, with a nucleic acid polymerase (e.g., DNA polymerase) and at least four tagged nucleotides under conditions permitting the nucleic acid polymerase to catalyze incorporation of one of the tagged nucleotides into the primer if it is complementary to the nucleotide residue of the single-stranded nucleic acid which is immediately 5' to a nucleotide residue of the single-stranded nucleic acid hybridized to the 3' terminal nucleotide residue of the primer, so as to form a nucleic acid extension product, wherein each of the at least four tagged nucleotides comprises a poly-phosphate moiety having a terminal phosphate, a base which is adenine, guanine, cytosine, thymine, or uracil, or a derivative of each thereof, and a tag covalently coupled to the terminal phosphate of the nucleotide by a triazole, a 1,2- diazine, a disulfide, a secondary amine (e.g., –NH–. Since X is covalently coupling the terminal phosphate to the tag (see the structure of the tagged nucleotide as shown in paragraph [0009]), a secondary amine linkage (i.e., –NH–) is formed when X is NH (see paragraph [0010]).), a hydrazone, a thio-acetamide, or a maleimide-thioadduct (see Figure 16, which suggests that the tagged nucleotide may be produced by reacting a tag with a maleimide group with a thiol group from the terminal phosphate), wherein (i) the type of base in each tagged nucleotide is different from the type of base in each of the other three tagged nucleotides, and (ii) either the number of phosphates in the poly-phosphate moiety of each tagged nucleotide is different from the number of phosphates in the poly-phosphate moiety of the other three tagged nucleotides, or the number of phosphates in the poly-phosphate moiety of each tagged nucleotide is the same and the type of tag on each tagged nucleotide is different from the type of tag on each of the other three tagged nucleotides, wherein incorporation of the tagged nucleotide results in release of a polyphosphate having the tag attached thereto (see paragraphs [0009]-[0010]); (b) determining which tagged nucleotide has been incorporated into the primer to form a nucleic acid extension product in step (a) by applying a voltage across the membrane and measuring an electronic change across the nanopore resulting from the polyphosphate having the tag attached thereto generated in step (a) entering into, becoming positioned in, and/or translocating through the nanopore, wherein the electronic change is different for each different number of phosphates in the poly-phosphate moiety, or for each different type of tag, as appropriate, thereby identifying the nucleotide residue in the single-stranded nucleic acid complementary to the incorporated tagged nucleotide (see paragraph [0011]); and (c) iteratively performing steps (a) and (b) for each nucleotide residue of the single-stranded nucleic acid being sequenced, wherein in each iteration of step (a) the tagged nucleotide is incorporated into the nucleic acid extension product resulting from the previous iteration of step (a) if it is complementary to the nucleotide residue of the single-stranded nucleic acid which is immediately 5' to a nucleotide residue of the single-stranded nucleic acid hybridized to the 3' terminal nucleotide residue of the nucleic acid extension product, thereby determining the nucleotide sequence of the single-stranded nucleic acid (see paragraphs [0012]-[0013]).
Regarding claim 37
The method according to Ju et al., wherein the number of phosphates in the poly-phosphate moiety of each tagged nucleotide is the same and the type of tag on each tagged nucleotide is different from the type of tag on each of the other three tagged nucleotides (see paragraph [0010]).
Regarding claim 38
The method according to Ju et al., wherein each tag comprises nucleotides, oligonucleotides, peptides, polyethylene glycol (PEG), oligo-saccharides, carbohydrates, peptide nucleic acids (PNA), vinyl polymers, other water-soluble polymers or any combination thereof (see paragraphs [0077]-[0078]; Figures 16 and 19).
Regarding claim 40
The method according to Ju et al., wherein each poly-phosphate moiety comprises at least 3 phosphates, or from 4 to 6 phosphates (see paragraphs [0009]-[0010]).
Regarding claim 46
The method according to Ju et al., wherein each tagged nucleotide comprises a cyanine dye moiety in a linker connecting the tag to the nucleotide (see paragraph [0389]). Since the tagged nucleotide meets all the structural limitations required by the tagged nucleotide used in the instantly claimed method, it would inherently possess all the corresponding characteristics, such as having “an improved rate of capture by a polymerase compared to a tagged nucleotide without a cyanine dye moiety” as recited in the claim.
Regarding claim 48
The method according to Ju et al., wherein the poly-phosphate moiety is at the 5'-position of the nucleotide (see paragraph [0009]), or wherein the tag comprises an oligonucleotide (see paragraphs [0077]-[0080], [0117] and [0380]; Figure 8).
Regarding claim 49
The method according to Ju et al., wherein the oligonucleotide of the tag comprises at least 7 monomer units, or at least 30 monomer units (see paragraphs [0079]-[0083]).
Regarding claim 50
The method according to Ju et al., wherein the oligonucleotide comprises an unnatural nucleotide, wherein the unnatural nucleotide comprises a group selected from the group consisting of an L- nucleotide, a 2', 5'-linkage, an -D-nucleotide, a non-naturally occurring internucleotide linkage, a non-naturally-occurring base, a non-naturally occurring sugar moiety, and any combination thereof, or the unnatural nucleotide comprises a non-naturally occurring base selected from the group consisting of nitropyrrole, nitroindole, nebularine, zebularine, benzene, and benzene derivatives, or the unnatural nucleotide comprises a non-naturally occurring internucleotide linkage selected from the group consisting of a phosphotriester, phosphorothioate, methylphosphonate, boronophosphate, phosphoramidate, and a morpholino moiety (see paragraphs [0077]-[0083] and [0304]).
Regarding claim 51
The method according to Ju et al., wherein the 5'-end of the oligonucleotide is covalently coupled to the terminal phosphate of a poly-phosphate moiety (see Figure 8b; paragraphs [0117] and [0380]).
Regarding claim 54
The method according to Ju et al., wherein the 3'-end of the oligonucleotide is covalently coupled to the terminal phosphate of a poly-phosphate moiety (see paragraphs [0077]-[0080], [0117] and [0380]; Figure 8a).
Claim Rejections - 35 USC § 103
11. 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 of this title, 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.
12. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
13. Claims 34, 36-40, 42-43, 46, 48-51 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Ju et al. (US 2013/0264207 A1) as applied to claims 34, 36-38, 40, 46, 48-51 and 54 above, and further in view of Hardin et al. (US 2011/0165652 A1).
Ju et al. teach the method of claims 34, 36-38, 40, 46, 48-51 and 54 as discussed above. Although Ju et al. generally teach that various reactive or functional groups, including azide and alkyne, may be used in the coupling of the tag to the terminal phosphate (see paragraph [0383]; Table 1; Figure 16), Ju et al. do not specifically disclose the species of tag coupling to the terminal phosphate by a “triazole”, wherein each triazole is formed by a reaction between an azide and an alkyne, and wherein each triazole has the structure as recited in instant claim 43.
However, Hardin et al. teach that triazole “click” chemistry may be used for synthesizing such tagged nucleotides, wherein each triazole is formed by a reaction between an azide and an alkyne, and wherein each triazole has the structure as recited in instant claim 43 (see paragraphs [0016] and [0205]-[0209]; Figures 4 and 61). Hardin et al. further teach that the triazole “click” chemistry-based coupling approach offers many advantages, such as the coupling reaction being modular, wide in scope, high yielding, creating only inoffensive by-products (that can be removed without chromatography), being stereospecific, simple to perform, and requiring benign or easily removed solvent (see paragraph [0205]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to use triazole “click” chemistry-based coupling approach, as taught by Hardin et al., in the method of Ju et al. for the coupling of the tag to the terminal phosphate, because: (1) Ju et al. generally envisioned the use of azide and alkyne functional reactive groups for the coupling of the tag to the terminal phosphate (see paragraph [0383]; Table 1; Figure 16); (2) the triazole “click” chemistry-based coupling approach would offer many advantages, such as the coupling reaction being modular, wide in scope, high yielding, creating only inoffensive by-products (that can be removed without chromatography), being stereospecific, simple to perform, and requiring benign or easily removed solvent (see Hardin et al., paragraph [0205]). Given the teachings of the prior art and the level of the ordinary skilled artisan at the time of the application’s effective filling date, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Allowable Subject Matter
14. Claims 47, 52-53 and 55-56 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
15. No claim is currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAIJIANG ZHANG whose telephone number is (571)272-5207. The examiner can normally be reached Monday - Friday, 8:30 am - 5 pm.
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, Heather Calamita can be reached at 571-272-2876. 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.
/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
Prosecution Insights