DETAILED ACTION
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 .
Status of claims / Response to Amendment
This office action is in response to an amendment filed on July 17, 2026.
Claims 1-26 were previously pending. Applicant amended claims 1, 4, 8, 10-14, 16-19, 21-25; cancelled claims 5-7, 9, 15 and 20; added new claims 27-30.
Claims 1-4, 8, 10-14, 16-19, 21-30 are currently pending, with claims 3, 10-14, 16-19, 21-26 and 28-30 withdrawn. Claims 1-2, 4, 8 and 27 are under consideration.
All of the previously presented rejections have been withdrawn as being obviated by the amendment of the claims, which introduces new combinations of elements that were not previously considered in the prior rejection (e.g., the amended claim 1 now requires "a linkage selected from the group consisting of: a reaction product of an amine and an n-hydroxysuccinimide (NHS) ester, a vicinal diol, an azidoalkyl ether, an allyl ether, a t-butyl ester, an oligonucleotide, a peptide, a Diels-Alder conjugation, an ester linkage, a saccharide, a coumarin group, a nitrobenzene group, a guest-host interaction, and a multi-valent protein interaction," which was not presented in prior claims and not considered in the prior office action.)
Thus, the scope of the claims has been changed in a manner that were not considered in the previous rejections.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Priority
The priority date of the instant claims 1-2, 4, 8 and 27 is November 21, 2022, filling date of the US provisional application NO. 63/427,018.
Claim Objections
Claim 27 is objected to because of the following informalities:
In claim 27, "reversable " should read "reversible" for consistency within the claim.
Claim Interpretation – Updated in view of Amendment1
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
Claim 1 recites the term "hydrogel," which is defined by the specification as follows:
"As used herein, a “hydrogel” refers to a three-dimensional polymer network structure that includes polymer chains and is at least partially hydrophilic and contains water within spaces between the polymer chains. A hydrogel may include any suitable combination of hydrophilic, hydrophobic, and/or amphiphilic polymer(s), so long as the overall polymer network is hydrophilic and contains water within spaces between the polymer chains. Hydrogels include chemical hydrogels in which both the bonding to form the polymer chains, and any cross-linking between the polymer chains, is covalent; such cross-linking during hydrogel formation may be irreversible, as distinguished from the present reversible cross-linking which is performed after the hydrogel is formed. In some cases, the chemical hydrogel may include, or may consist essentially of, brush-like structures of polymer chains attached to a surface, substantially without physical or covalent crosslinks between polymer chains, or alternatively polymer chains with multiple attachment points to a surface, resulting in loops, but also lacking interchain crosslinks. Hydrogels also include physical hydrogels in which the bonding to form the polymer chains, and any cross-linking within the polymer chains, is not covalent. Nonlimiting examples of physical hydrogels include agarose and alginate." ([0052])
Claim 1 recites the term "polymer chains," which is defined by the specification as follows:
"As used herein, the “polymer chain” of a hydrogel is intended to mean those portions of the hydrogel that are polymerized with one another during the polymerization process. Polymer chains may be cross-linked to form the hydrogel. For example, cross-linkers may be added during or after the polymerization process that forms the polymer chains. Additionally, or alternatively, in some examples the polymer chains may be deposited on a substrate surface that includes functional groups to which functional groups of the polymer chains become coupled. The polymer chains may be coupled to the surface, e.g., via reactions between the functional groups of the polymer chains and the functional groups at the surface, and such coupling may cross-link the polymer chains to form the hydrogel. Such cross-linking may cause the polymer chains to covalently or non-covalently attach to one another, or may occur as a result of chain entanglement during polymerization and/or attachment to a surface. As provided herein, polymer chains also or alternatively may be reversibly cross-linked after the hydrogel is formed, e.g., using functional groups in a manner such as described in greater detail below."([0053])
For the purpose of applying prior art, claim 1 recites:
"first functional groups coupled to the polymer chains";
"amplification primers coupled to the polymer chains via the first functional groups" ; and
"second functional groups coupled to the polymer chains."
The application's disclosure does not expressly define the terms "couple" or "coupled."
Under BRI and in light of the specification, "A coupled to B" is interpreted to mean that A is physically associated with B, either directly or indirectly, through covalent or non-covalent interactions.
This interpretation is consistent with the specification. For example, Fig. 1 illustrates amplification primers covalently coupled to hydrogel polymers, while also being indirectly coupled to a substrate that is in physical contact with the hydrogel (see also [0056-0057]). See also the definition of amplification primers as being couple to the substrate:
"[a]n “amplification primer” is intended to mean a primer that is coupled to the substrate." ([0036])
New Grounds of Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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.
Claims 1-2, 4, 8 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over
Khurana (WO2021108499A1 - On-flow cell three-dimensional polymer structures; Published 2021-06-03; cited as Foreign Patent Document #C05 in IDS filed on 04/18/2024), in view of
Wolfel (Wolfel et al., "Post-synthesis modification of hydrogels. Total and partial rupture of crosslinks: Formation of aldehyde groups and re-crosslinking of cleaved hydrogels." Polymer 116 (2017): 251-260.), as evidenced by
Wang (Wang et al. "Dissolvable polyacrylamide beads for high‐throughput droplet DNA barcoding." Advanced Science 7.8 (2020): 1903463.)
A) Khurana teaches methods for making an on-flow cell, three- dimensional hydrogel matrix, comprising amplification primers embedded within the hydrogel matrix ([00071]-[0073]; Fig. 20-21; [000321]; [00346]-[00347] for examples).
Regarding claim 1, Khurana teaches a hydrogel on a substrate (FIG. 2A; [00161] polymer (e.g., hydrogel) structures on a flow cell; FIG. 20-21, hydrogel beads on a glass slide) , comprising:
a three-dimensional network of polymer chains ([0071]-[0073] three- dimensional sequencing matrix, wherein the permeable three-dimensional matrix is a hydrogel; [00111]);
first functional groups coupled to the polymer chains ([000192] FIG. 20 depicts the copolymerization of acrylamide and acrydite-modified oligos into large polyacrylamide beads; see also [00348] biotinylated oligos coupled to hydrogel via streptavidin );
amplification primers coupled to the polymer chains via the first functional groups ([0071], “embedding oligonucleotides within a permeable three-dimensional matrix, wherein the oligonucleotides facilitate nucleic acid fragment clonal amplification” ); and
second functional groups coupled to the polymer chains and reversibly cross-linking the polymer chains to one another ([000346]-[000347] reversible hydrogel structures formed using UV-mediated co-polymerization of acrylamide, crosslinker, and PAZAM, the crosslinker forms covalent bonds with the acrylamide via UV crosslinking, see Wang, Fig. 1; [000123] wherein the monomer is acrylamide, the crosslinker is N,N'-Bis(acryloyl)cystamine (BACy)).
Khurana teaches its hydrogel matrix structures are reversible, and cleavable ([000177] FIG. 6 is a flow chart depicting an example implementation of a method for making reversible, permeable three-dimensional polymer structures on a flow cell; [00346] functionalized reversible hydrogel structures were formed within a channel on a flow cell by utilizing poly(N-(5- azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM) into which azide moieties have been incorporated; and the azide-alkyne click reaction; [00265]).
Khurana teaches cleaving hydrogel features from flow cell can be done using heat or chemical cleavage of the crosslinker. For example, incubating acrylamide hydrogel structures comprising N,N'-Bis(acryloyl)cystamine (BACy) crosslinker with a reducing agent, such as DTT, cleaves the structures by reducing the disulfide bonds in the hydrogel crosslinker to thiols, thereby permitting the hydrogel to be washed out of flow cell ([00274] lines 15-24; [000123]).
Although Khurana does not explicitly teach the claimed specific linkages, such as a vicinal diol linkage, this feature is obvious in view of Wolfel.
Wolfel teaches reversible hydrogel formation using N, N′-diallyltartramide (DAT) as a crosslinker. DAT possesses a vicinal diol linkage and it can be selectively cleaved by reaction with periodate, obtaining aldehydes as products. The treatment of the gels crosslinked with DAT leads to complete digestion of the material, obtaining a liquid as a product. (Abstract; Fig. 3)
Wolfel further teaches advantages of its hydrogel with DAT crosslinker, including capability of re-forming new hydrogels, and yielding polymers having aldehyde groups, thereby allowing the flexibility of attaching a variety of molecules or to functionalize diverse synthetic polymers (p. 259, right-hand col., lines 20-26).
Accordingly, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it prima facie obvious to substitute Wolfel's DAT crosslinker, cleavable by periodate, for the BACy crosslinker taught in Khurana’s method, cleavable by a reducing agent. As both crosslinkers function to form reversible hydrogel matrix with acrylamide monomers, such a modification represents a simple substitution of one known element for another to obtain predictable results, see MPEP §2143.
This substitution is a predictable use of known hydrogel crosslinkers within the same context – formation of reversibly crosslinked hydrogels -- with no unexpected change in function or result. Since Khurana and Wolfel both use reversible crosslinkers to form hydrogels which can then be turned into a liquid form using corresponding cleaving agents, using the DAT crosslinker and its cleaving agent from Wolfel in the context of Khurana’s method of forming reversible hydrogel matrix on a flow cell would not alter the method’s fundamental operation but would utilize a variant of the same approach, yielding the same predictable result of forming a reversible hydrogel matrix on a given substrate.
B) Regarding claim 2, Khurana teaches the first and second functional groups are of different types than one another (Fig. 20, FIG. 20 depicts the copolymerization of acrylamide and acrydite-modified oligos oligos; [000123] wherein the monomer is acrylamide, the crosslinker is N,N'-Bis(acryloyl)cystamine (BACy), comprising amine group ).
Regarding claim 4, Khurana teaches wherein the first functional group is azide ( [000321] azide-alkyne click reaction).
Regarding claim 8, it recites:
"The hydrogel of claim 1, wherein the t-butyl ester linkage is reversible using an acid."
This limitation is obvious in view of the combined teachings of Khurana and Wolfel because it does not further distinguish the claimed device having a vicinal diol linkage from the prior art.
Base claim 1 recites a hydrogel comprising a linkage selected from a Markush group that includes a vicinal diol and a t-butyl ester. Thus, vicinal diol and t-butyl ester are alternatives.
Claim 8 merely describes t-butyl ester linkage. However, it does not require the linkage to be t-butyl ester.
Therefore, a hydrogel comprising vicinal diol linkage, as taught by the combined teachings of Khurana and Wolfel, remains within the scope of claim 8.
Regarding claim 27, Wolfel teaches vicinal diol linkage is reversable using periodate (Abstract).
Conclusion
Claim 27 is objected to; claims 1-2, 4, 8 and 27 are rejected. No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 Prior interpretation for “reversibly cross-linking” removed in view of amended claim 1, identifying specific reversible linkages in Markush group.
