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 .
2. This action is in response to the papers filed January 7, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Claims 1, 3-23 are currently pending.
Claims 11-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 24, 2025.
Claim Rejections - 35 USC § 103
3. 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.
4. Claims 1, 5, 8, 9, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Roesler (US 2010/0248991 Pub 9/30/2010) in view of Heron (WO 2019/150134 Pub 8/8/2019 Filed 2/4/2019) and Zhang (Polymers 2018 10, 1044).
Regarding Claim 1 Roesler teaches a method comprising: a) providing a plurality of beads, characterized in that each bead comprises at least one pair of sequence specific amplification primers, further characterized in that at least one of said primers is bound to the bead via a cleavable linker, b) capturing the nucleic acid molecules of interest from a sample, c) clonally isolating said plurality of beads, d) cleaving said at least one primer, e) clonally amplifying said nucleic acid thereby creating multiple amplification products, and f) analyzing said amplification products (para 0122-0128).
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Roesler teaches that an overview is shown in FIG. 1: A sample is subjected to a population of beads comprising a pair of amplification primers, one of which is photo-cleavable (steps a, b). Clonal amplification is achieved by means of performing an emulsion PCR (steps c, d, e). Subsequently, the amplification products are becoming analyzed (step f). Roesler further teaches that primers comprising the azide groups can be attached to aklyne groups on the surface of beads (Table 1). Roesler teaches maleimide groups on the surface of beads (para 0084). Thus Roesler teaches a method of synthesizing a copy of a nucleic acid template on a solid support comprising the steps of: (a) immobilizing a linker on the solid support; (b) attaching an oligonucleotide primer to the linker, wherein the oligonucleotide primer comprises a nucleic acid sequence complementary to a portion of the 3' end of the nucleic acid template; (c) providing a reaction mixture comprising the nucleic acid template, a nucleic acid polymerase, nucleotide substrates or analogs thereof, a suitable buffer, and, optionally, one or more additives, wherein the nucleic acid template specifically hybridizes to the oligonucleotide primer; and (d) performing a primer extension reaction to produce the copy of the nucleic acid template.
Regarding Claim 5 Roesler teaches a method wherein the nucleic acid template is cDNA (Example 6).
Regarding Claim 9 Roesler discloses linkers having cleavable moieties (para 0123).
Regarding Claim 10 Roesler teaches a method wherein the solid support is a bead (para 0122).
Roesler does not teach a method wherein the linker comprises a first end proximal to the solid support and a second end distal to the solid support, wherein the first end is coupled to a maleimide moiety and the second end is coupled to an alkyne moiety, and wherein the maleimide moiety is crosslinked to the solid support (clm 1). Roesler does not teach a method wherein the 5' end of the oligonucleotide primer is coupled to an azide moiety, and wherein the azide moiety reacts with the alkyne moiety to form a triazole moiety (clm 1). Roesler does not teach a method wherein the linker further comprises a spacer arm interposed between the first end and the second end, wherein the spacer arm comprises one or more monomers of ethylene glycol (clm 8).
However Heron discloses alkyne-PEG-maleimide linkers. Heron teaches that one end of the linker is attached to a substrate (page 97, lines 19-23). Heron discloses DNA sequences can be modified with azide groups (page 95, lines 8-14). Heron discloses examples of click chemistry including where azide groups react with alkyne groups to form triazole (page 94, lines 6-20).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Roesler by using a linker comprising alkyne-PEG-maleimide to attach the primer to the bead as suggested by Heron. As disclosed by Heron bifunctional alkyne-PEG-maleimide linkers were well known in art as were nucleic acids modified with azide groups, and the click chemistry reaction between alkyne and azide groups. The claim would have been obvious because the substitution of one type of linker (the linker of Roesler) for another (the alkyne-PEG-maleimide of Heron) would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The combined references do not teach a method wherein the maleimide moiety is crosslinked to the solid substrate by a catalyst free photo-initiated proton abstraction reaction, wherein the catalyst free photo-initiated proton abstraction reaction comprises treatment with UV light (clm 1).
However Zhang discloses hydrogen abstraction reactions for the grafting of maleimides to polyethylene by UV radiation (page 3). Zhang does not disclose the use of a catalyst, thus the method is being interpreted as a catalyst free photo-initiated proton abstraction reaction.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Roesler and Heron by crosslinking using a catalyst free photo-initiated proton abstraction reaction comprising UV light as suggested by Zhang. One of skill in the art would have been motivated to use the methodology since as demonstrated by Zhang this was a known method in the art for crosslinking and the skilled artisan would have been motivated to use crosslinking methods that work.
5. Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Roesler (US 2010/0248991 Pub 9/30/2010) in view of Heron (WO 2019/150134 Pub 8/8/2019 Filed 2/4/2019) and Zhang (Polymers 2018 10, 1044) as applied to claim 1 above and in further view of Vargeese (US Patent 6,020,206)
The teachings of Roesler, Heron, and Zhang are presented above.
The combined references do not teach a method wherein the solid substrate is comprised of polyolefin (clm 3). The combined references do not teach a method wherein the polyolefin is a cyclic olefin copolymer (COC) or a polypropylene (clm 4).
However Vargeese teaches maleimide derivatized polypropylene beads (Example 25).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Roesler, Heron, and Zhang by using polypropylene beads as the solid support as suggested by Vargeese. One of skill in the art would have been motivated use polypropylene beads because Vargeese teaches that they can be functionalized with maleimide and the linker comprises a maleimide moiety.
6. Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Roesler (US 2010/0248991 Pub 9/30/2010) in view of Heron (WO 2019/150134 Pub 8/8/2019 Filed 2/4/2019) and Zhang (Polymers 2018 10, 1044) as applied to claims 1 and 5 and in further view of Kokoris (US 2009/0035777 Pub 2/5/2009)
The teachings of Roesler, Heron, and Zhang are presented above.
The combined references do not teach a method wherein the DNA template is an expandable polymer that comprises a strand of non- natural nucleotide analogs, and wherein the each of the non-natural nucleotide analogs is operably linked to the adjacent non-natural nucleotide analog by a phosphoramidate ester bond (clm 6). The combined references do not teach a method wherein the expandable polymer is an Xpandomer (clm 7).
However Kokoris discloses expandomers (abstract).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Roesler, Heron, and Zhang by using an Xpandomer as the DNA template. One of skill in the art would have been motivated to use an Xpandomer particularly since Kokoris teaches that Xpandomers preserve the original genetic information of a target nucleic acid, while also increasing linear separation of the individual elements of the sequence data and that this overcomes the spatial resolution challenges presented by existing high throughput nucleic acid sequencing techniques (para 0019).
Response To Arguments
7. In the response the Applicants traversed the rejections made under 35 USC 103. The Applicants state that they have amended the claims to overcome the previously made rejections. The Applicants state that the claims as amended now require a method wherein the maleimide moiety is crosslinked to the solid support by a catalyst-free photo-initiated proton abstraction reaction, wherein the catalyst-free photo-initiated proton abstraction reaction comprises treatment with UV light. They argue that the prior arts cited in the previous Office action do not anticipate or render obvious the claims as amended.
This argument has been fully considered. It is noted that the rejection have been modified to address the claims as amended. The prior art of Zhang is now being relied upon to teach a method wherein a maleimide moiety is crosslinked to the solid support by a catalyst-free photo-initiated proton abstraction reaction, wherein the catalyst-free photo-initiated proton abstraction reaction comprises treatment with UV light.
8. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682
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