DETAILED ACTION
Response to Amendment
Applicant’s responses to the office action filed on December 10, 2025 and February 24, 2026 have been entered. The claims pending in this application are claims 1, 7-16, and 18-20 wherein claims 8-10, 15, and 16 have been withdrawn due to the restriction requirement mailed on June 10, 2025. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on December 10, 2025 and February 24, 2026. Claims 1, 7, 11-14, and 18-20 will be examined.
Drawings
New Figures 1A to 1C and 2 submitted on December 10, 2025 have been accepted by the office.
Specification
The substituted specification submitted on December 10, 2025 has been entered.
The disclosure is objected to because of the following informality: although New Figures 1A to 1C oshow sshowshshow that Figures 1A, 1B, and 1C correspond to SEQ ID No. 1, SEQ ID Nos. 2 and 3, and SEQ ID No:4 respectively, there are no nucleotide sequences in Figures 1A to 1C or Brief Description Of Figures related to Figures 1A to 1C does not describe SEQ ID Nos: 1-4 either.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informality: “G-quadruplex Hemin” in last line should be “the G-quadruplex Hemin DNAzyme”.
Claim 7 is objected to because of the following informality: “activity of the G-quadruplex Hemin DNAzyme substrate is detected by” should be “the catalytic activity of the G-quadruplex Hemin DNAzyme is a peroxidase activity and the peroxidase activity is measured by detecting a peroxidase substrate by”.
Claim 12 is objected to because of the following informalities: (1) no period should appear after the label of each step, e.g., “a.” should be --a)--; (2) “G-quadruplex Hemin” in the end of (ii) should be “the G-quadruplex Hemin DNAzyme”; and (3) “said detection nanostructures” in (iii) should be “said nucleic acid nanostructure”.
Claim 18 is objected to because of the following informality: “G-quadruplex Hemin” should be “G-quadruplex Hemin DNAzyme”.
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.
New Matter
Claim 12 is 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A limitation “(ii) the composition comprising at least one DNA polymerase enzyme; and a catalytic nucleic acid nanostructure comprising a G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure and is elongated in the presence of the polymerase, wherein the elongation inhibits catalytic activity of G-quadruplex Hemin, attached at a second location” is added to dependent claim 12 in the amendment filed on February 24, 2026. Although original claim 3 describes that “the stimulus responsive element comprises a polymerase-responsive element that inhibits the DNAzyme/ RNAzyme activity in the presence of polymerase” and original claim 12 describes “(ii) catalytic nucleic acid nanostructure of any one of claims 3 to 7, attached at a second location”, nowhere in the specification describes such limitation recited in claim 12 since original claims 3 and 12 only describe that the catalytic nucleic acid nanostructure is attached to a second location. Furthermore, in applicant’s remarks filed on February 24, 2026, applicant does not indicate which parts in the specification support above claim limitation recited in claim 12.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
Written Description
Claims 18-20 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 written description requirement. The claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is referred to the interim guidelines on written description published on December 21, 1999 in the Federal Register at Volume 64, Number 244, pp.71427-71440.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1117. The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed”. Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The specification provides adequate written description for: (1) a G-quadruplex Hemin DNAzyme consisting of Hemin and SEQ ID NO:1; (2) a polymerase-responsive element consisting of SEQ ID NO:10; and (3) a catalytic nucleic acid nanostructure consisting of Hemin and SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 (see paragraphs [0104] and [0105], Table 1 of US 2023/0159990 A1, which is US publication of this instant case). However, the specification fails to adequately describe: (1) the G-quadruplex Hemin DNAzyme comprises a nucleic acid sequence set forth in SEQ ID NO: 1; (2) the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) the catalytic nucleic acid nanostructure comprises a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. The claimed inventions as a whole are not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which are not conventional in the art as of Applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics (as it relates to the claimed inventions as a whole) such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998).
In this instant case, the G-quadruplex Hemin recited claim 18 is read as a G-quadruplex Hemin DNAzyme comprising the nucleic acid sequence from SEQ ID NO:1 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO:1, the polymerase-responsive element recited in claim 19 is read as a polymerase-responsive element comprising the nucleic acid sequence of SEQ ID NO: 10 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO:10, and the catalytic nucleic acid nanostructure recited in claim 20 is read as a catalytic nucleic acid nanostructure comprising the nucleic acid sequence from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. Since the specification does not describe that any kind of nucleic acid sequence which has SEQ ID NO: 1 but is longer than SEQ ID NO:1 can be used as a G-quadruplex of a G-quadruplex Hemin, any kind of nucleic acid sequence which has SEQ ID NO: 10 but is longer than SEQ ID NO:10 can be used as a polymerase-response element, and any kind of nucleic acid sequence which has SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 but is longer than SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9, claims 18-20 encompass numerous unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures that miss from the disclosure and it is unclear whether these numerous unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures still have the same functions of a G-quadruplex Hemin DNAzyme consisting of Hemin and SEQ ID NO:1, a polymerase-responsive element consisting of SEQ ID NO:10, and a catalytic nucleic acid nanostructure consisting of Hemin and SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. Therefore, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
With limited disclosure provided by the specification, the skilled artisan cannot envision all unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of identifying it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Scope of Enablement
Claims 1, 7, 11-14, and 18-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase wherein 5’ of the polymerase-responsive element is ligated to 3’ of G-quadruplex of the G-quadruplex Hemin DNAzyme and the polymerase-responsive element is elongated in the presence of the DNA polymerase in order to destroy the peroxidase-like activity of the G-quadruplex-hemin DNAzyme, does not reasonably provide enablement for (1) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19, wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a composition and a device comprising the composition. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 1 and 7 encompass a composition comprising: at least one DNA polymerase enzyme; and a catalytic nucleic acid nanostructure comprising a G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure and is elongated in the presence of the polymerase wherein the elongation inhibits catalytic activity of G-quadruplex Hemin DNAzyme. Claim 18 further limits claim 1 and requires that the G-quadruplex Hemin comprises the nucleic acid sequence of SEQ ID NO: 1. Claim 19 further limits claim 18 and requires that the polymerase-responsive element comprises the nucleic acid sequence of SEQ ID NO: 10. Claim 20 further limits claim 1 and requires that the catalytic nucleic acid nanostructure comprises the nucleic acid sequence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. Claims 11-14 encompass
a device comprising the composition of claim 1 immobilized on a surface.
Working Examples
The specification provides 5 examples (see pages 5-7 of US 2023/0159990 A1, which is US publication of this instant case). However, the specification provides no working example for (1) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19 wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10;
and (3) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although the specification provides 5 examples (see pages 5-7 of US 2023/0159990 A1, which is US publication of this instant case). However, the specification provides no working example for (1) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19 wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) inhibiting peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to (1) inhibit peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19 wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) inhibit peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) inhibit peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether (1) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19 wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element can be inhibited using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20.
First, since the specification teaches that “[I]n one example, we developed three-dimensional DNA structures to incorporate G-quadruplex Hemin DNAzyme (SEQ ID NO: 1), which has peroxidase activity” and “[T]he inventors further designed and optimized the incorporation of a polymerase activity-responsive element to the nanostructures (SEQ ID NOs: 4 to 9). The created nanostructures thus contain both binding site for polymerase activity as well as intrinsic catalytic domains (SEQ ID NO: 2 and 3, SEQ ID NOs: 4 to 9), and are responsive to polymerase activity to change their catalytic peroxidase activity. Specifically, the responsive element provides a substrate for the polymerase activity, thereby unfolding and destroying the catalytic activity. While secondary and higher order DNA structures are known to inhibit polymerase activity [Nelms, B. L. and Labosky, P. A. Scientific Reports 1: 106 (2011)], we showed that, in the absence of the polymerase activity-responsive element, the designed nanostructure does not interfere with polymerase activity. After the incorporation of a polymerase activity-responsive element, in the absence of the polymerase activity, the catalytic activity of the nanostructure is preserved. In the presence of polymerase activity, the catalytic activity of the nanostructure is destroyed (FIG. 1). Of the polymerase-responsive elements tested, the best design had an internal hairpin structure, which we hypothesize can increase the stability of the polymerase responsive element through self-priming (FIG. 1) (SEQ ID No: 10). The inventors further optimized the design and position of the responsive element, with respect to the catalytic domain, by adjusting the length of the responsive element 5′ overhang to make the nanostructure highly responsive to polymerase activity. In the optimized design (SEQ ID NO: 4), polymerase elongation of a few bases was sufficient to completely destroy the catalytic activity; as any decrease in catalytic activity results in an exponential signal decrease, the designed nanostructure becomes highly sensitive to polymerase activity (FIG. 2)” (see paragraphs [0104] and [0105], Figures 1A to 1C and 2, and Table 1), the specification clearly indicate that peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase wherein 5’ of the polymerase-responsive element is ligated to 3’ of G-quadruplex of the G-quadruplex Hemin DNAzyme and a DNA polymerase elongation of the polymerase-responsive element of the catalytic nucleic acid nanostructure destroys the peroxidase-like activity of the G-quadruplex-hemin DNAzyme and the scope of claims 1, 7, 11-14, and 18-20 is much broader than the teachings of the specification. Since claim 1 does not require that 5’ of the polymerase-responsive element is ligated to 3’ of G-quadruplex of the G-quadruplex Hemin DNAzyme and it is known that a DNA polymerase reads the existing template strand in 3’ to 5’ direction (see page 2 of “DNA polymerase” from Wikipedia), if 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme, 3’ end of the polymerase-responsive element of the catalytic nucleic acid nanostructure cannot be elongated in the presence of a DNA polymerase such that the peroxidase-like activity of the G-quadruplex-hemin DNAzyme can be destroyed by a DNA polymerase elongation of the polymerase-responsive element of the catalytic nucleic acid nanostructure and the peroxidase-like activity of the G-quadruplex-hemin DNAzyme cannot be inhibited. Furthermore, since claim 1 does not require that 5’ of the polymerase-responsive element is ligated to 3’ of G-quadruplex of the G-quadruplex Hemin DNAzyme and the specification and available arts do not teach that peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase wherein the polymerase-responsive element is hybridized to G-quadruplex of the G-quadruplex Hemin DNAzyme, if the polymerase-responsive element is hybridized to G-quadruplex of the G-quadruplex Hemin DNAzyme in the catalytic nucleic acid nanostructure, it is unpredictable how peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, and 11-14.
Second, as shown in above description rejection, the G-quadruplex Hemin recited claim 18 is read as a G-quadruplex Hemin comprising the nucleic acid sequence from SEQ ID NO:1 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO:1, the polymerase-responsive element recited in claim 19 is read as a polymerase-responsive element comprising the nucleic acid sequence of SEQ ID NO: 10 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO:10, and the catalytic nucleic acid nanostructure recited in claim 20 is read as a catalytic nucleic acid nanostructure comprising the nucleic acid sequence from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 wherein the nucleic acid sequence can be equal to or longer than SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. Since the specification does not describe that any kind of nucleic acid sequence which has SEQ ID NO: 1 but is longer than SEQ ID NO:1 can be used as a G-quadruplex of a G-quadruplex Hemin, any kind of nucleic acid sequence which has SEQ ID NO: 10 but is longer than SEQ ID NO:10 can be used as a polymerase-response element, and any kind of nucleic acid sequence which has SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 but is longer than SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9, claims 18-20 encompass numerous unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures that miss from the disclosure and it is unclear whether these numerous unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures still have the same functions of a G-quadruplex Hemin DNAzyme consisting of Hemin and SEQ ID NO:1, a polymerase-responsive element consisting of SEQ ID NO:10, and a catalytic nucleic acid nanostructure consisting of Hemin and SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. Without knowing the information of these unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures in the specification, a skilled artisan does not know how to make these unknown and unidentified G-quadruplex Hemin DNAzymes, polymerase-responsive elements, and catalytic nucleic acid nanostructures recited in claims 18-20 such that peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure cannot be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10 and peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element cannot be inhibited using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 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. These undue experimentation at least includes to test whether (1) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 1, 7, 11-14, 18, and 19 wherein 3’ of the polymerase-responsive element is ligated to 5’ of G-quadruplex of the G-quadruplex Hemin DNAzyme or the polymerase-responsive element hybridizes to G-quadruplex of the G-quadruplex Hemin DNAzyme; (2) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element which comprises an internal hairpin structure can be inhibited using a composition comprising the catalytic nucleic acid nanostructure and at least one DNA polymerase as recited in claims 18 and 19 wherein the G-quadruplex Hemin comprises a nucleic acid sequence set forth in SEQ ID NO: 1 and the polymerase-responsive element comprises the nucleic acid sequence set forth in SEQ ID NO: 10; and (3) peroxidase-like activity of a G-quadruplex-hemin DNAzyme in a catalytic nucleic acid nanostructure formed by the G-quadruplex Hemin DNAzyme and a polymerase-responsive element can be inhibited using a composition comprising the catalytic nucleic acid nanostructure comprising a nucleic acid sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9 and at least one DNA polymerase as recited in claim 20.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
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.
Claim 12 is 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 12 recites the limitation “the sample” in (a) of the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “a sample” in claims 1 and 11. Please clarify.
Response to Arguments
Applicant’s arguments with respect to claims 1, 2, 4-7, 11-14, and 17 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowed.
Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center. The faxing of such papers must conform with the notices published in the Official Gazette, 1096 OG 30 (November 15, 1988), 1156 OG 61 (November 16, 1993), and 1157 OG 94 (December 28, 1993)(See 37 CAR § 1.6(d)). The CM Fax Center number is (571)273-8300.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph.D., whose telephone number is (571)272-0746. The examiner can normally be reached on Monday-Friday from 9 A.M. to 5 P.M.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Dr. Anne Gussow, Ph.D., can be reached on (571)272-6047.
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.
/FRANK W LU/Primary Examiner, Art Unit 1683
May 28, 2026
Prosecution Insights