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 .
DETAILED ACTION
The Response of 26 Jan. 2026 has been entered.
Claims 1-20 are currently pending.
Election/Restrictions
Applicant’s election without traverse of the species of a site on the base for attachment of a primary polynucleotide as the species of primary modification, a TdT of SEQ ID 1 as the species of polymerase, an azide-cyclooctyne bond as the species of bond for the primary polynucleotide and an azide-cyclooctyne bond as the species of bond for the secondary polynucleotide in the reply filed on 26 Jan. 2026 is acknowledged. In the interest of compact prosecution, the species election requirement for species of polymerases is hereby withdrawn.
Claims 12 and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 26 Jan. 2026.
Claims 1-11 and 14-20 are considered here with respect to the elected species.
Claim Rejections - 35 USC § 112(a) (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.
Claim 3 is rejected under 35 U.S.C. 112(a) 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.
Claim 3 recites a TdT that is at least 80% identical to SEQ ID 1. SEQ ID 1 is a 504-amino acid polypeptide, and the claimed 80% identity allows for 100 nonidentical residues at any point in the sequence. Thus, claim 3 recites a large genus of variant TdT polypeptides.
To show possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus, which in the case of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties (MPEP 2163). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species sufficient to show the applicant was in possession of the claimed genus; A "representative number of species" means that the species which are adequately described are representative of the entire genus (MPEP 2163).
The instant specification discloses only the sequence of SEQ ID 1 (Published Spec. US20220333146, [0081]). The specification does not provide any additional sequences capable of incorporating modified bases into a DNA strand as set forth in the claimed method that could be considered a representative number of species. The specification also fails to provide any structure-function relationship or other teachings/guidance that would allow one of ordinary skill to identify variants within the claimed genus (e.g., which portions of the enzyme can be modified and/or which portions are responsible for the claimed functionality). Thus, the instant specification does not evidence possession of a method of making a branched DNA polymer by incorporating modified bases into a DNA strand using a TdT enzyme having at least 80% identity to SEQ ID 1 for the entire scope of the claimed genus (see MPEP 2163 - A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed).
Claim Rejections - 35 USC § 112(b) (indefiniteness)
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.
Claims 2-7 are rejected under 35 U.S.C. 112(b) 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.
Claims 2 and 6 recite the limitation "the polymerase" in claim 1. There is insufficient antecedent basis for this limitation in the claim, making it unclear how the polymerase limits the method of claim 1.
Claim Rejections - 35 USC § 102
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.
Claims 1, 5-7, 14 and 15 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Marciel et al., Macromolecules 48.5 (2015): 1296-1303.
Regarding claims 1, 6, 14 and 15, Marciel teaches a method of preparing a branched DNA polynucleotide, comprising: adding a plurality of modified nucleoside triphosphates to a ssDNA chain in a template-directed manner via DNA polymerase, wherein the modified nucleosides comprise a base having a dibenzocyclooctyl (DBCO) group; and contacting the synthesized DNA strand with a DNA polynucleotide strand (i.e. primary polynucleotide) comprising a terminal azide group such that the DBCO and azide groups form an azide-cyclooctyne covalent bond via click chemistry, thereby forming a branched DNA polymer (under RESULTS AND DISCUSSION; Fig. 1).
Regarding claims 5 and 7, Marciel teaches 53-nucleotide DNA strand with two modified nucleosides at positions 18 and 36 to which branch polynucleotides are attached, giving a ratio of 1:26.5 of modified nucleosides to unmodified nucleosides (p. 1300, 1st full ¶ to p. 1301, 2nd full ¶). Marciel also teaches a 50-nucleotide strand having branches at positions 1, 7, 13, 19 and 25, giving a 1:10 ratio (p. 1301, right col., 1st full ¶).
Claim Rejections - 35 USC § 103
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, 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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Marciel, as applied to claims 1, 5-7, 14 and 15, in view of Winz et al., Nucleic acids research 43.17 (2015): e110-e110 (cited in IDS of 26 Aug. 2022).
Claim 2 differs from Marciel, as applied to claims 1, 5-7, 14 and 15, in that: the nucleotides are added via a terminal deoxynucleotidyl transferase (TdT).
Winz teaches a method substantially similar to Marciel in which modified nucleosides are incorporated into a DNA polynucleotide, wherein the modified nucleosides comprise an alkyne (such as DBCO, as in Marciel) or an azide for click chemistry coupling, e.g. formation of an azide-cyclooctyne bond (Fig. 1 and related text; p. 4, 1st full ¶ to p. 5, last ¶). Winz teaches that the modified nucleosides are added using TdT (p. 2, under Tailing reactions with TdT; p. 4-5, under Many different modified nucleotides are incorporated by TdT with varying efficiencies). Winz teaches that "TdT can be employe to incorporate a diverse range of modified nucleotides that contain ‘clickable’ moieties, namely alkynes, azides, DIBAC or norbornene attached at various positions" (1st ¶, under DISCUSSION). Winz further teaches that the synthesized DNA comprising modified nucleosides is "amenable not only to internal attachment of different labels, but also to branching" (p. 8, 2nd to last ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Marciel to prepare a branched DNA polynucleotide by incorporating modified bases into a DNA strand comprising click chemistry moieties capable of bonding with other modified DNA strands comprising complementary moieties wherein the modified nucleosides are added using TdT as taught by Winz because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use TdT to incorporate modified nucleosides in the method of Marciel in order to add such modified nucleosides in a template-independent manner (e.g., where sequence specificity is unimportant and/or where a template is not available). Using TdT to incorporate modified nucleosides in the method of Marciel would have led to predictable results with a reasonable expectation of success because Winz teaches that TdT can be used to incorporate a wide range of click chemistry moieties, including azide and cyclooctyne moieties, and that the DNA comprising such modified nucleosides is amenable to branching, as taught by Marciel.
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Marciel in view of Winz, as applied to claim 2, further in view of US12209266 to Nirantar et al. (effectively filed 12 May 2020).
Claims 3-4 differ from Marciel in view of Winz, as applied to claim 2, in that: the TdT is at least 80% identical to SEQ ID 1 (claim 3); and the TdT comprises SEQ ID 1 (claim 4).
Nirantar teaches a method comprising using TdT to incorporate modified bases into a ssDNA polynucleotide, wherein the modified bases comprise click chemistry moieties such as azide or cyclooctyne moieties (col. 1, line 43 to col. 7, line 16). SEQ ID 15 of Nirantar is 100% identical to SEQ ID 1 (col. 12, line 60 to col. 13, line 4). Nirantar teaches that the method can be used to make branched DNA polymers (col. 1, line 43 to col. 7, line 16).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Marciel in view of Winz to form a branched DNA polynucleotide, wherein the TdT used to incorporate the modified nucleosides is that of Nirantar because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Using the TdT of Nirantar to in the method of Marciel in view of Winz would have led to predictable results with a reasonable expectation of success because Nirantar teaches that the TdT can be used to incorporate modified nucleosides comprising click chemistry moieties of the same type use in Marciel in view of Winz, and can be used to generate branched DNA polynucleotides of the same type made by the method of Marciel in view of Winz.
Claims 8-11 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Marciel and/or Marciel in view of Winz, as applied to claims 1, 2, 5-7, 14 and 15, and further in view of US20120059173 to Monteiro et al.
Claims 8-11 and 16-20 differ from Marciel and/or Winz, as applied to claims 1, 2, 5-7, 14 and 15, in that: the primary polynucleotide branches further comprise a secondary modification comprising a site for attachment of a secondary polynucleotide (claim 8); the site if for covalent attachment (claims 9, 16; elected species = azide-cyclooctyne bond); and the method further comprises attaching the secondary polynucleotide (claims 10, 11, 17-20).
Monteiro teaches method of making multiply branched dendritic DNA polynucleotides, comprising a forming a first main chain polynucleotide comprising one or more click chemistry moieties, binding one or more branch polymers (primary polynucleotides) to the main chain wherein the branch polynucleotides further comprise additional click chemistry moieties that bind further branch polynucleotides (secondary polynucleotides), and binding the secondary polynucleotides to the branched chain ([0014]-[0072]; [0094]-[0180]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Marciel to prepare a branched DNA polynucleotide wherein primary polynucleotide branches are connected to a main chain via click chemistry wherein the primary polynucleotides comprise additional click chemistry moieties which are used to attach additional secondary polynucleotides to the primary polynucleotides as taught by Monteiro because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to attach additional secondary polynucleotide branches off the primary polynucleotide branches of Marciel because Monteiro teaches that highly branched dendrimer polymers have numerous applications in research and industry (Monteiro, [0008]). Attaching additional secondary polynucleotide branches off the primary polynucleotide branches of Marciel would have led to predictable results with a reasonable expectation of success because Monteiro teaches that the same click chemistry reactions taught by Marciel can be used to form dendritic polymers, and Winz teaches a variety of click chemistry moieties that can be incorporated into modified bases (e.g., Winz, Fig. 1). Moreover, making a dendritic polymer using the method of Marciel and/or Winz would have simply required repeating the steps of Marciel and/or Winz to form multiple branches (e.g., first making several series of polynucleotide strands, each comprising different click chemistry moieties, using the method of Marciel and/or Winz, and then assembling the polynucleotides stepwise as taught by Monteiro).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2 and 7-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 12209266 in view of Winz and/or Monteiro, as applied above. The '266 claims recite a method wherein a TdT is used to incorporate modified bases comprising click chemistry moieties into a ssDNA, wherein the bases can be used to covalently attach accessory oligonucleotides ('266, claims 1-24, esp. claims 16-18). The '266 claims further recite the ratios of modified to unmodified nucleosides in instant claim 5 ('266, claim 13). The '266 claims differ from the claimed method in that the click chemistry bonds are azide-cyclooctyne (elected species); and the primary/accessory polynucleotides comprise additional click chemistry moieties which are used to attach additional secondary polynucleotides to the primary/accessory polynucleotides. Marcel teaches the incorporation of azide-cyclooctyne click chemistry moieties using TdT in a manner similar to that of the '266 claims, and suggests that the DNA comprising such modified nucleosides can be used to make branched polymers (see above). Moreover, Monteiro teaches assembly of multiple layers of branches to form dendritic DNA polymers using click chemistry (see above). As such, it would have been obvious to carry out the method of the '266 claims wherein the click chemistry bond is an azide-cyclooctyne bond and wherein the method is used to form multiply branched dendritic polymers.
Conclusion
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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