DETAILED ACTION
Reopen prosecution
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on March 27, 2026 has been entered and the allowance mailed on December 30, 2025 has been withdrawn in view of claims 1-20 filed on November 21, 2025. Claims 1-20 will be examined.
Claim Objections
Claim 2 is objected to because of the following informality: “a polymer core” should be “a polymer core in said conjugated polymer-nucleotide composition”.
Claim 5 is objected to because of the following informality: “antigen-binding fragment thereof” should be “an antigen-binding fragment thereof”.
Claim 8 is objected to because of the following informality: “at 3’ carbon” should be “at its 3’ carbon”.
Claim 12 is objected to because of the following informality: “(a)” should be “step (a)”.
Claim 13 or 14 is objected to because of the following informality: “said amplifying” should be “the amplifying step”.
Claim 15 is objected to because of the following informalities: (1) “(b) and (c)” should be “steps (b) and (c)”; and (2) “coupled to” should be deleted.
Claim 16 is objected to because of the following informality: “said deblocking” should be “the deblocking step”.
Claim 17 is objected to because of the following informality: “said extending” should be “the extending step”.
Claim 18 is objected to because of the following informality: “a plurality of said second nucleobases comprising said second blocking group coupled thereto” should be “said second nucleobase comprising said second blocking group”.
Claim 19 is objected to because of the following informality: “said plurality of said second nucleobases comprises a plurality of types of nucleobases” should be “said second nucleobase is”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Enablement
Claims 1-20 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court considered the issue of enablement in molecular biology. The Court summarized eight factors to
be considered in a determination of “undue experimentation”. These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims. The Court also stated that although the level of skill in molecular biology is high, results of experiments in molecular biology are unpredictable.
To begin, there is no direction or guidance to show that identity of a nucleotide at N+1 position of a primed nucleic acid sequence can be determined using the methods recited in claims 1-20. While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether identity of a nucleotide at N+1 position of a primed nucleic acid sequence can be determined using the methods recited in claims 1-20.
Since the specification shows that “[T]he ternary complex has longer persistence time when the nucleotide on the polymer-nucleotide conjugate is complementary to the target nucleic acid than when a non-complementary nucleotide. The ternary complex also has longer persistence time when the nucleotide on the polymer-nucleotide conjugate is complementary to the target nucleic acid than a complementary nucleotide that is not conjugated or tethered. For example, in some embodiments, said ternary complexes may have a persistence time of less than 1 s, greater than 1 s, greater than 2 s, greater than 3 s, greater than 5 s, greater than 10 s, greater than 15 s, greater than 20 s, greater than 30 s, greater than 60 s, greater than 120 s, greater than 360 s, greater than 3600 s, or more, or for a time lying within a range defined by any two or more of these values” and “[T]he persistence time can be measured, for example, by observing the onset and/or duration of a binding complex, such as by observing a signal from a labeled component of the binding complex. For example, a labeled nucleotide or a labeled reagent comprising one or more nucleotides may be present in a binding complex, thus allowing the signal from the label to be detected during the persistence time of the binding complex” (see paragraphs [0098] and [0099] of US 2021/0247389 A1, which is US Publication of this instant case), the specification clearly indicates that a stable ternary complex can be formed between a nucleotide moiety of a conjugated polymer-nucleotide composition and a nucleotide at N position of a primed nucleic acid sequence when said nucleotide moiety of said conjugated polymer-nucleotide composition is complementary to said nucleotide at N position of said primed nucleic acid sequence and said primed nucleic acid sequence is brought into contact with said conjugated polymer-nucleotide composition. Since a stable ternary complex is formed between a nucleotide moiety of a conjugated polymer-nucleotide composition and a nucleotide at N position (ie., not N+1 position) of a primed nucleic acid sequence when said nucleotide moiety of said conjugated polymer-nucleotide composition is complementary to said nucleotide at N position of said primed nucleic acid sequence and said primed nucleic acid sequence is brought into contact with said conjugated polymer-nucleotide composition, bringing said primed nucleic acid sequence into contact with a conjugated polymer-nucleotide composition in step (b) of claim 1 cannot form a stable ternary complex between a nucleotide moiety of said conjugated polymer-nucleotide composition and a nucleotide at N+1 position of said primed nucleic acid sequence such that it is unpredictable how said identity of said nucleotide at said N+1 position of said primed nucleic acid sequence can be determined by detecting said stable ternary complex as recited in claims 1-20.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. The undue experimentation at least includes to test whether identity of a nucleotide at N+1 position of a primed nucleic acid sequence can be determined using the methods recited in claims 1-20.
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 1-20 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 1 is rejected as vague and indefinite because step (a) does not make sense. Does step (a) mean providing a primed nucleic acid sequence comprising a nucleobase, wherein said nucleobase is located on N position of said primed nucleic acid sequence and comprises a blocking group? Furthermore, since a stable ternary complex is formed between a nucleotide moiety of a conjugated polymer-nucleotide composition and a nucleotide at N position (ie., not N+1 position) of a primed nucleic acid sequence when said nucleotide moiety of said conjugated polymer-nucleotide composition is complementary to said nucleotide at N position of said primed nucleic acid sequence and said primed nucleic acid sequence is brought into contact with said conjugated polymer-nucleotide composition, bringing said primed nucleic acid sequence into contact with a conjugated polymer-nucleotide composition in step (b) cannot form a stable ternary complex between a nucleotide moiety of said conjugated polymer-nucleotide composition and a nucleotide at N+1 position of said primed nucleic acid sequence. In addition, since the preamble of the claim is directed to a method of determining an identity of a nucleotide in any kind of nucleic acid sequence while step (c) is used for determining said identity of said nucleotide at said N+1 position of said primed nucleic acid sequence, the preamble and step (c) of the claim do not correspond from each other. Please clarify.
Conclusion
No claim is allowed.
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/FRANK W LU/Primary Examiner, Art Unit 1683 August 21, 2026
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