DETAILED ACTION
In application filed on 11/29/2023, Claims 1-14 are pending. The claim set submitted on 02/13/2024 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-7 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/30/2023 and 07/26/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Species I in the reply filed on 06/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 8-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 06/23/2026.
Species I, Claims 1-7 are considered on the merits below.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “a passivation component the polymeric hydrogel” in lines 5-6 of the Claim. It appears that this limitation should be recited as “a passivation component attached to the polymeric hydrogel”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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 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 1-2 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Ren et al. (US20200129974A1).
Regarding Claim 1, Ren teaches a flow cell (See Abstract…patterned flow cell substrate), comprising:
a substrate (referred to as patterned substrate [Para 0118; Fig. 3A, ref. 12]) including depressions (referred to as depressions [Para 0118; Fig. 3A, ref. 14]) separated (See Figs. 3A-D for ‘separated’; See Para 0004…the depressions are separated by interstitial regions) by interstitial regions (referred to as interstitial regions [Para 0118; Fig. 3A, ref. 16]);
a polymeric hydrogel (‘hydrogel’) positioned within each of the depressions (See Para 0004…grafting a primer to the functionalized coating layer to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer);
a primer set (‘primer’) attached to the polymeric hydrogel (See Abstract…. A primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions. A hydrogel is applied on at least the grafted functionalized coating layer.); and
a passivation component (referred to as a silane or a silane derivative [Para 0012]; See Para 0072… the terms “silane” and “silane derivative” can include mixtures of different silane and/or silane derivative compounds) attached to (in light of the objection of Claim 1 above; ‘applying’) the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions).
The limitations “one of: a passivation component attached to the interstitial regions, or respective passivation components attached to each of the interstitial regions and the polymeric hydrogel” are viewed as optional limitations/alternative limitations and thus not required by the claim. As a result, claims are given the appropriate weight by the Examiner; wherein
or the passivation component (referred to as a silane or a silane derivative [Para 0012]; See Para 0072… the terms “silane” and “silane derivative” can include mixtures of different silane and/or silane derivative compounds) is exclusively attached to (‘applying’) the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions) and includes i) a second linker (See Para 0074…suitable linkers) selected from the group consisting of alkylene, poly(ethyleneglycol), poly(meth)acrylate, polyacrylamide, pentaerythritol, and combinations thereof, and a second end group selected from the group consisting of a poly(ethylene glycol) end group when the linker is poly(meth)acrylate, polyacrylamide, pentaerythritol, and combinations thereof, a zwitterionic end group, a hydroxyl end group, a carboxylic acid end group, a sulfonic acid end group, a positively chargeable end group, an alkoxy end group, an anionic polymer end group, and an amphoteric polymer end group (See Para 0074…The unsaturated moiety can be covalently attached either directly to the silicon atoms of the silane or silane derivative, or indirectly attached via linkers. Examples of suitable linkers include optionally substituted alkylenes (e.g., bivalent saturated aliphatic radicals (such as ethylene)…).
The limitation “or ii) a dibenzocyclooctyne-functionalized passivation agent” is viewed as “optional.
Further the limitations “the passivation component is exclusively attached to the interstitial regions and includes i) a silane, siloxane, or alkoxy silane small molecule with an alkoxy, hydroxyl, carboxylic acid, or perfluorinated end group, or ii) a first linker selected from the group consisting of alkylene, poly(ethylene glycol), poly(meth)acrylic acid, polyacrylamide, poly(2-hydroxyl ethyl (meth)acrylate), and poly(2-hydroxypropyl (meth)acrylamide) and a first end group selected from the group consisting of phosphate, phosphonate, a zwitterionic end group and an amphoteric polymer end group; or the respective passivation components are attached to each of the interstitial regions and to the polymeric hydrogel, the respective passivation component attached to the interstitial regions includes i) a silane, siloxane, or alkoxy silane small molecule with an alkoxy, hydroxyl, carboxylic acid, or perfluorinated end group, or ii) a third linker selected from the group consisting of alkylene, poly(ethylene glycol), poly(meth)acrylic acid, polyacrylamide, poly(2-hydroxyl ethyl (meth)acrylate), and poly(2-hydroxypropyl (meth)acrylamide) and a third end group selected from the group consisting of a zwitterionic end group and an amphoteric polymer end group, and the respective passivation component attached to the polymeric hydrogel includes i) a fourth linker selected from the group consisting of alkylene, poly(ethylene glycol), poly(meth)acrylate, polyacrylamide, and pentaerythritol, and combinations thereof, and a fourth end group selected from the group consisting of a poly(ethylene glycol) end group when the linker is poly(meth)acrylate, polyacrylamide, or pentaerythritol, a zwitterionic end group, a hydroxyl end group, a carboxylic acid end group, a sulfonic acid end group, a positively chargeable end group, an alkoxy end group, an anionic polymer end group, and an amphoteric polymer end group, or ii) a dibenzocyclooctyne-functionalized passivation agent.” are viewed as optional and thus not required by the claims.
Regarding Claim 2, Ren teaches that the passivation component (referred to as a silane or a silane derivative [Para 0012]; See Para 0072… the terms “silane” and “silane derivative” can include mixtures of different silane and/or silane derivative compounds) is exclusively attached to (‘applying’) the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions); and the second linker (See Para 0074…suitable linkers) further includes an alkyne-containing functional group or an alkene- containing functional group attached to the polymeric hydrogel (See Para 0074…Examples of suitable linkers include optionally substituted alkylenes (e.g., bivalent saturated aliphatic radicals (such as ethylene); Under BRI, Alkylenes (more commonly known as alkenes) contain at least one carbon-carbon double bond ( C=C )).
Claim 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (US20200129974A1) in view of Stawicki et al. ("Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins." Scientific Reports 11.1 (2021): 19921.).
Regarding Claim 3, Ren teaches wherein: the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions) includes terminal azide groups (See Para 0058… the functionalized coating layer includes an azide/azido functional group that can react with an alkyne functional group. In an example, the functionalized coating layer is poly(N-(5-azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM).) ; and the passivation component referred to as a silane or a silane derivative [Para 0012]; See Para 0072… the terms “silane” and “silane derivative” can include mixtures of different silane and/or silane derivative compounds).
Ren does not teach that the passivation component is selected from the group consisting ofdibenzocyclooctyne- poly(ethylene glycol)-carboxylic acid, norbornene-poly(ethylene glycol)-carboxylic acid, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-carboxylic acid, dibenzocyclooctyne- poly(ethylene glycol)-amine, norbornene-poly(ethylene glycol)-amine, bicyclo[6.1.0]non-4-yne- poly(ethylene glycol)-amine, dibenzocyclooctyne-poly(ethylene glycol)-hydroxyl, norbornene- poly(ethylene glycol)-hydroxyl, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-hydroxyl, dibenzocyclooctyne-poly(ethylene glycol)-sulfonic acid, norbornene-poly(ethylene glycol)- sulfonic acid, and bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-sulfonic acid.
In the analogous art of modular fluorescent nanoparticle dna probes for detection of peptides and proteins, Stawicki teaches that the passivation component (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer) is selected from the group consisting of dibenzocyclooctyne- poly(ethylene glycol)-carboxylic acid, norbornene-poly(ethylene glycol)-carboxylic acid, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-carboxylic acid, dibenzocyclooctyne- poly(ethylene glycol)-amine, norbornene-poly(ethylene glycol)-amine, bicyclo[6.1.0]non-4-yne- poly(ethylene glycol)-amine, dibenzocyclooctyne-poly(ethylene glycol)-hydroxyl, norbornene- poly(ethylene glycol)-hydroxyl, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-hydroxyl, dibenzocyclooctyne-poly(ethylene glycol)-sulfonic acid, norbornene-poly(ethylene glycol)- sulfonic acid, and bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-sulfonic acid (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer); See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer; See Page 12… the carboxylate modified polystyrene particles are generated by copolymerizing a carboxylic acid-containing monomer with styrene , thereby teaching “dibenzocyclooctyne- poly(ethylene glycol)-carboxylic acid”.
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 flow cell of Ren to include that the passivation component is selected from the group consisting ofdibenzocyclooctyne- poly(ethylene glycol)-carboxylic acid, norbornene-poly(ethylene glycol)-carboxylic acid, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-carboxylic acid, dibenzocyclooctyne- poly(ethylene glycol)-amine, norbornene-poly(ethylene glycol)-amine, bicyclo[6.1.0]non-4-yne- poly(ethylene glycol)-amine, dibenzocyclooctyne-poly(ethylene glycol)-hydroxyl, norbornene- poly(ethylene glycol)-hydroxyl, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-hydroxyl, dibenzocyclooctyne-poly(ethylene glycol)-sulfonic acid, norbornene-poly(ethylene glycol)- sulfonic acid, and bicyclo[6.1.0]non-4-yne-poly(ethylene glycol)-sulfonic acid, as taught by Stawicki, for the benefit of directly conjugating a DBCO-modified aptamer to the PEG-azide layer (Stawicki, Page 8), allowing for the provision of a protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments (Stawicki, Abstract).
Regarding Claim 5, Ren teaches wherein: the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions) includes terminal azide groups (See Para 0058… the functionalized coating layer includes an azide/azido functional group that can react with an alkyne functional group. In an example, the functionalized coating layer is poly(N-(5-azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM).).
Ren does not teach that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the amphoteric polymer end group; and the amphoteric polymer end group includes both a carboxylic acid functional group and an amine functional group.
In the analogous art of modular fluorescent nanoparticle dna probes for detection of peptides and proteins, Stawicki teaches that that the second linker (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer, thereby teaching “second linker”) is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer); See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer, thereby teaching “poly(ethylene glycol)-dibenzocyclooctyne”; the second end group (‘covalent attachment of amine-PEG-azide to carboxylated particles’) is the amphoteric polymer end group (‘covalent attachment of amine-PEG-azide to carboxylated particles’); and the amphoteric polymer end group (‘covalent attachment of amine-PEG-azide to carboxylated particles’) includes both a carboxylic acid functional group and an amine functional group (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Fig. 1…Figure 1. Fluorescent nanoparticle probe fabrication and DNA aptamer probe attachment. (A) Carboxylate-modified nanoparticle labels are PEGylated for passivation and click chemistry modification using a combination of mPEG-amine and amine-PEG-azide and NHS/EDC chemistry).
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 flow cell of Ren to include that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the amphoteric polymer end group; and the amphoteric polymer end group includes both a carboxylic acid functional group and an amine functional group, as taught by Stawicki, for the benefit of directly conjugating a DBCO-modified aptamer to the PEG-azide layer (Stawicki, Page 8), allowing for the provision of a protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments (Stawicki, Abstract).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (US20200129974A1) in view of Stawicki et al. ("Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins." Scientific Reports 11.1 (2021): 19921.) as applied to claim 2 above, and further in view of Mao et al. ("Biology-oriented design strategies of AIE theranostic probes." Matter 4.2 (2021): 350-376).
Regarding Claim 4, Ren teaches wherein: the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions) includes terminal azide groups (See Para 0058… the functionalized coating layer includes an azide/azido functional group that can react with an alkyne functional group. In an example, the functionalized coating layer is poly(N-(5-azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM).)
Ren does not teach that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether.
In the analogous art of modular fluorescent nanoparticle dna probes for detection of peptides and proteins, Stawicki teaches that that the second linker (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer, therebyb teaching “second linker”) is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer); See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer, thereby teaching “poly(ethylene glycol)-dibenzocyclooctyne”.
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 flow cell of Ren to include that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine, as taught by Stawicki, for the benefit of directly conjugating a DBCO-modified aptamer to the PEG-azide layer (Stawicki, Page 8), allowing for the provision of a protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments (Stawicki, Abstract).
The combination of Ren and Stawicki does not explicitly teach that the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine.
In the analogous art of biology-oriented design strategies of aie theranostic probes, Mao teaches that the second end group (See Page 360… a zwitterionic sulfobetaine) is the zwitterionic end group (See Page 360… a zwitterionic sulfobetaine); and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine (See Page 360… a zwitterionic sulfobetaine).
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 flow cell of Ren and Stawicki to include that the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine, as taught by Mao for the benefit of constructing selective antibacterial AIE probes (Mao, Page 360), allowing for the provision of improved designs of theranostic materials, which will also broaden the potential applications of AIEgens (Mao, Page 351).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (US20200129974A1) in view of Stawicki et al. ("Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins." Scientific Reports 11.1 (2021): 19921.) as applied to claim 2 above, and further in view of Bolívar-Monsalve et al. ("Engineering bioactive synthetic polymers for biomedical applications: A review with emphasis on tissue engineering and controlled release." Materials Advances 2.14 (2021): 4447-4478.).
Regarding Claim 6, Ren teaches wherein: the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions) includes terminal azide groups (See Para 0058… the functionalized coating layer includes an azide/azido functional group that can react with an alkyne functional group. In an example, the functionalized coating layer is poly(N-(5-azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM).)
Ren does not teach that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether.
In the analogous art of modular fluorescent nanoparticle dna probes for detection of peptides and proteins, Stawicki teaches that the second linker (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer, thereby teaching “second linker”) is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer); See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer, thereby teaching “poly(ethylene glycol)-dibenzocyclooctyne”.
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 flow cell of Ren to include that the second linker is poly(ethylene glycol)-dibenzocyclooctyne, poly(ethylene glycol)- norbornene, bicyclo[6.1.0]non-4-yne-poly(ethylene glycol), or bicyclo[6.1.0]non-4-yne- poly(ethylene glycol) methyl ether; the second end group is the zwitterionic end group; and the zwitterionic end group is selected from the group consisting of phosphocholine, a sulfobetaine, and a carboxybetaine, as taught by Stawicki, for the benefit of directly conjugating a DBCO-modified aptamer to the PEG-azide layer (Stawicki, Page 8), allowing for the provision of a protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments (Stawicki, Abstract).
The combination of Ren and Stawicki does not explicitly teach that the second end group is the anionic polymer end group; and the anionic polymer end group is poly(meth) acrylic acid.
In the analogous of engineering bioactive synthetic polymers for biomedical applications: a review with emphasis on tissue engineering and controlled release, Bolivar-Monsalve teaches that the second end group (See Table 1-2…PMMA) is the anionic polymer end group(See Table 1-2…PMMA); and the anionic polymer end group (See Table 1-2…PMMA) is poly(meth) acrylic acid (See Table 1-2…PMMA).
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 flow cell of Ren and Stawicki to include that the second end group is the anionic polymer end group; and the anionic polymer end group is poly(meth) acrylic acid, as taught by Bolivar-Monsalve, for the benefit of evaluating different functionalization strategies to enhance the suitability of SyPs as cellular scaffolds for different emergent biomedical purposes (Bolivar-Monsalve, Introduction), allowing for SyPs functionalization to impart antimicrobial or conductive character and to engineer actuators for tissue engineering applications (Bolivar-Monsalve, Abstract).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (US20200129974A1) in view of Stawicki et al. ("Modular fluorescent nanoparticle DNA probes for detection of peptides and proteins." Scientific Reports 11.1 (2021): 19921.) and further in view of Brown et al. (US20180274026A1).
Regarding Claim 7, Ren teaches that the passivation component (referred to as a silane or a silane derivative [Para 0012]; See Para 0072… the terms “silane” and “silane derivative” can include mixtures of different silane and/or silane derivative compounds) is exclusively attached to (‘applying’) the polymeric hydrogel (See Para 0012…grafting a primer to the functionalized coating layer in the silanized depressions to form a grafted functionalized coating layer in the depressions; and applying a hydrogel on the grafted functionalized coating layer in the depressions).
Ren does not teach that the passivation component includes the dibenzocyclooctyne-functionalized passivation agent; and the dibenzocyclooctyne-functionalized passivation agent is selected from the group consisting of dibenzocyclooctyne-acid, dibenzocyclooctyne-amine, and dibenzocyclooctyne- sulfo-amine.
In the analogous art of modular fluorescent nanoparticle dna probes for detection of peptides and proteins, Stawicki teaches that the passivation component (See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer) includes the dibenzocyclooctyne-functionalized passivation agent (See Abstract… Particle passivation was achieved by covalent attachment of amine-PEG-azide to carboxylated particles; See Page 2, Results… The handle consists of a 3′ dibenzocyclooctyne (DBCO) for conjugation to the PEG layer); See Page 6… we evaluated a more traditional attachment approach by directly conjugating a DBCO-modified aptamer to the PEG-azide layer).
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 flow cell of Ren to include the dibenzocyclooctyne-functionalized passivation agent; and the dibenzocyclooctyne-functionalized passivation agent is selected from the group consisting of dibenzocyclooctyne-acid, dibenzocyclooctyne-amine, and dibenzocyclooctyne- sulfo-amine. as taught by Stawicki, for the benefit of directly conjugating a DBCO-modified aptamer to the PEG-azide layer (Stawicki, Page 8), allowing for the provision of a protocol for preparation of nanoparticle probes relies solely on commercially available reagents and common equipment, breaking down the barriers to use nanoparticles in biological experiments (Stawicki, Abstract).
The combination of Ren and Stawicki does not explicitly teach that the dibenzocyclooctyne-functionalized passivation agent is selected from the group consisting of dibenzocyclooctyne-acid, dibenzocyclooctyne-amine, and dibenzocyclooctyne- sulfo-amine.
In the analogous art of substrates comprising dual-functional polymer layered surfaces with binary surface chemistry. Methods of preparing these substrates by using nano-imprinting lithography processes are also disclosed, Brown teaches that the dibenzocyclooctyne-functionalized passivation agent See Para 0112… dibenzocyclooctynes (MO) functionalized amine) is selected from the group consisting of dibenzocyclooctyne-acid, dibenzocyclooctyne-amine, and dibenzocyclooctyne- sulfo-amine (See Para 0112… dibenzocyclooctynes (MO) functionalized amine).
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 flow cell of Ren and Stawicki to include that the dibenzocyclooctyne-functionalized passivation agent is selected from the group consisting of dibenzocyclooctyne-acid, dibenzocyclooctyne-amine, and dibenzocyclooctyne- sulfo-amine, as taught by Brown for the benefit of providing strained ring moiety to the polymer, which can subsequently undergoing catalyst-free ring strain promoted click reaction with a tetrazine functionalized oligos to graft the primers to surface (Brown, Para 0112), allowing for the use of substrates as flow cells, nanofluidic or microfluidic devices for biological molecules analysis (Brown, Abstract).
Conclusion
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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