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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/10/23, 3/7/24, and 4/21/25 has been considered by the examiner.
Election/Restrictions
Claims 16-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1/23/26.
Applicant's election with traverse of claims 16-21 in the reply filed on 1/23/26 is acknowledged. The traversal is on the ground(s) that the hydrogel forms cages on page 10 of applicant’s remarks 1/23/26 which is in contrast to Ramachandran Iyer.
This is not found persuasive because Ramachandran Iyer teaches In some embodiments, the method includes rehydrating (e.g., adding water) the shrunken hydrogel features, wherein the shrunken hydrogel features are located in the wells. Rehydrating shrunken hydrogel features can be accomplished by any method described herein. Rehydrating a shrunken hydrogel feature in the well can cause the shrunken hydrogel feature to expand. In some embodiments, the shrunken hydrogel feature expands to fill the well. In some embodiments, the shrunken hydrogel feature expands in a z direction, such that the feature expands out of the unenclosed (i.e. open) end of the well. The exposed area of the rehydrated feature can create a patterned hydrogel array (e.g., a well array). The examiner notes the expanded and contracted forms of the hydrogel as taught by Ramachandran Iyer.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-15 are pending and are examined. Claims 16-21 are withdrawn and are not examined.
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 /3invention is not identically disclosed as set forth in section 102, if the differences bet/ween 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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Ramachandran Iyer (WO 2020/123309) in view of Aizenberg (WO 2013/067525).
Regarding Claim 1, Ramachandran Iyer teaches a microfluidic device (FIG. 14A and 14B are schematics illustrating expanded FIG. 14A and side views FIG. 14B of an electrophoretic transfer system configured to direct transcript analytes toward a spatially-barcoded capture probe array. FIG. 15 is a schematic illustrating an exemplary workflow protocol utilizing an electrophoretic transfer system.) comprising:
a first wall (1401) comprising a first substrate on which a plurality of closed patterns is grafted, a second wall (1403), facing the first wall, comprising a second substrate,
a plurality of nucleic acids grafted either on the first substrate or on the second substrate, wherein each nucleic acid comprises a barcode that encodes the position of the nucleic acid on said first or second substrate (barcoded capture probe array 1404, 1405, and the spatially-barcoded capture probe array 1404, 1405 is sandwiched between the sample 1402),
Ramachandran Iyer is silent to at least the plurality of closed patterns or the second substrate is made of an actuatable hydrogel which is swellable between a retracted state and a swollen state in which the closed patterns and the second substrate come into contact.
Aizenberg teaches in the related art of hydrogels. As illustrated in FIG. 27A, a SMARTS system 2700 can include microstructures 2710, an upper reaction layer 2701 and a lower hydrogel layer 2703. The tips 2704 of the microstructures are decorated, for example, with a catalyst and extend above the reaction layer. Thus, no reaction takes place in the inactivated state. Upon activation, hydrogel in the hydrogel layer contracts and the microstructures are bent so that the catalyst tips now contact the reactive layer and a chemical reaction ensues, as is illustrated in FIG. 27B. As noted above, a self-regulatory homeostatic system can be developed when the reaction produces a signal that triggers the swelling of the hydrogel.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added at least the plurality of closed patterns or the second substrate is made of an actuatable hydrogel which is swellable between a retracted state and a swollen state in which the closed patterns and the second substrate come into contact, as taught by Aizenberg, to the device of Ramachandran Iyer, to produce a chemo-mechano-chemical (C1-M-C2) system capable of volume change in response to an environmental stimulus (as taught by Aizenberg, in the Abstract).
Regarding Claim 2, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein the actuatable swellable hydrogel is a temperature-responsive swellable hydrogel (In some embodiments, the hydrogel bead or hydrogel bead array undergoes an alteration in temperature (e.g., an alteration from about 37 °C, 38 °C, 39 °C, 40 °C, 41 °C, 42 °C, 43 °C, 56 °C, 57 °C, 58 °C, 59 °C 60 °C, 61 °C, 62 °C, 63 °C, 64 °C, 65 °C, 66 °C, 67 °C, 68 °C, 69 °C, 70°C, or higher, or any temperature alteration encompassed within these ranges) to form a shrunken hydrogel bead or shrunken hydrogel bead array.).
Regarding Claim 3, modified Ramachandran Iyer teaches the microfluidic device according to claim 2, wherein the temperature- responsive hydrogel has a critical solution temperature ranging from 4°C to 98°C, preferably from 20°C to 50°C, more preferably from 25°C to 40°C (In some embodiments, the hydrogel bead or hydrogel bead array undergoes an alteration in temperature (e.g., an alteration from about 37 °C, 38 °C, 39 °C, 40 °C, 41 °C, 42 °C, 43 °C, 56 °C, 57 °C, 58 °C, 59 °C 60 °C, 61 °C, 62 °C, 63 °C, 64 °C, 65 °C, 66 °C, 67 °C, 68 °C, 69 °C, 70°C, or higher, or any temperature alteration encompassed within these ranges) to form a shrunken hydrogel bead or shrunken hydrogel bead array.).
Regarding Claim 4, modified Ramachandran Iyer teaches the microfluidic device according to claim 3, wherein the critical solution temperature is a lower critical solution temperature above which the temperature- responsive hydrogel is in the retracted state and below which the temperature-responsive hydrogel is in the swollen state (In some embodiments, the hydrogel bead or hydrogel bead array undergoes an alteration in temperature (e.g., an alteration from about 37 °C, 38 °C, 39 °C, 40 °C, 41 °C, 42 °C, 43 °C, 56 °C, 57 °C, 58 °C, 59 °C 60 °C, 61 °C, 62 °C, 63 °C, 64 °C, 65 °C, 66 °C, 67 °C, 68 °C, 69 °C, 70°C, or higher, or any temperature alteration encompassed within these ranges) to form a shrunken hydrogel bead or shrunken hydrogel bead array.).
Regarding Claim 5, modified Ramachandran Iyer teaches the microfluidic device according to claim 3, wherein the critical solution temperature is an upper critical solution temperature above which the temperature- responsive hydrogel is in the swollen state and below which the temperature-responsive hydrogel is in the retracted state (In some embodiments, the hydrogel bead or hydrogel bead array undergoes an alteration in temperature (e.g., an alteration from about 37 °C, 38 °C, 39 °C, 40 °C, 41 °C, 42 °C, 43 °C, 56 °C, 57 °C, 58 °C, 59 °C 60 °C, 61 °C, 62 °C, 63 °C, 64 °C, 65 °C, 66 °C, 67 °C, 68 °C, 69 °C, 70°C, or higher, or any temperature alteration encompassed within these ranges) to form a shrunken hydrogel bead or shrunken hydrogel bead array.).
Regarding Claim 6, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein the polymer matrix of the hydrogel comprises, preferably consists of, a thermo-responsive polymer chosen from homopolymers, copolymers and terpolymers of acrylic acid, alkyl (meth)acrylates, alkyl (meth)acrylamides, oligoethylene (meth)acrylates, sulfobetaines (meth)acrylates and N-acryloyl glycinamide and any mixtures thereof, preferably chosen from homopolymers copolymers and terpolymers of alkyl (meth)acrylamides and any mixtures thereof, more preferably the polymer is poly(N-Isopropylacrylamide) (Non-limiting examples of photo-crosslinkable polymer precursors include polyethylene (glycol) diacrylate (PEGDA), gelatin-methacryloyl (GelMA), and methacrylated hyaluronic acid (MeHA). In some embodiments, a photo-crosslinkable polymer precursor comprises polyethylene (glycol) diacrylate (PEGDA), gelatin-methacryloyl (GelMA), methacrylated hyaluronic acid (MeHA), or a combination thereof. In some embodiments, a photo-crosslinkable polymer precursor (e.g., PAZAM) can be covalently linked (e.g., cross-linked) to a substrate.)
Regarding Claim 7, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, further comprising at least one inlet and at least one outlet permitting respectively the introduction or the removal of reactants into the device (Fig. 22A a fluid inlet 2218. Fluid outlet 2220).
Regarding Claim 8, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein the first substrate and the second substrate are independently made in a material chosen from: silicon, quartz, glass, polydimethylsiloxane, thermoplastics such as cyclic olefin copolymers and polycarbonates, preferably from glass and polydimethylsiloxane (Exemplary substrates include, but are not limited to, glass, modified and/or functionalized glass, hydrogels, films, membranes, plastics (including e.g., acrylics, polystyrene, copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, Teflon™, cyclic olefins, polyimides etc.).)
Regarding Claim 9, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein the plurality of closed patterns is made of the actuatable swellable hydrogel and the second substrate is made of a non-swellable material (The swelling of the beads can be accomplished by various swelling methods. In some embodiments, swelling is reversible (e.g., by subjecting beads to conditions that promote de swelling). In some embodiments, the de- swelling of the beads is accomplished, for instance, by transferring the beads in a thermodynamically unfavorable solvent, subjecting the beads to lower or higher temperatures, subjecting the beads to a lower or higher ion concentration, and/or adding or removing an electric field. The de- swelling of the beads can be accomplished by various de- swelling methods. In some embodiments, de- swelling is reversible).
Regarding Claim 10, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein the second substrate is made of the actuatable swellable hydrogel and the closed patterns are made of a non- swellable material (The swelling of the beads can be accomplished by various swelling methods. In some embodiments, swelling is reversible (e.g., by subjecting beads to conditions that promote de swelling). In some embodiments, the de- swelling of the beads is accomplished, for instance, by transferring the beads in a thermodynamically unfavorable solvent, subjecting the beads to lower or higher temperatures, subjecting the beads to a lower or higher ion concentration, and/or adding or removing an electric field. The de- swelling of the beads can be accomplished by various de- swelling methods. In some embodiments, de- swelling is reversible).
Regarding Claim 11, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein a plurality of ligands is grafted on the first substrate and/or on the second substrate (In such cases, the reactive functional groups can facilitate conjugation to ligands and/or surfaces.).
Regarding Claim 12, modified Ramachandran teaches the microfluidic device according to claim 1, wherein a plurality of ligands conjugated with a nucleic acid is associated by hybridization to at least part of the grafted nucleic acids (In such cases, the reactive functional groups can facilitate conjugation to ligands and/or surfaces. In some embodiments, a molecule (e.g., a nucleic acid molecule) having a barcode (e.g., a spatial barcode) can include thiol modifiers that are designed to react with a broad array of activated accepting groups (e.g., maleimide and gold microspheres). For example, a molecule (e.g., a nucleic acid molecule) having a barcode (e.g., a spatial barcode) having thiol modifiers can interact with a maleimide-conjugated peptide thereby resulting in labelling of the peptide.).
Regarding Claim 13, modified Ramachandran Iyer teaches the microfluidic device according to claim 11, wherein each ligand is independently chosen from the group consisting of antibodies, fragments of antibody, lectins, and aptamers (Suitable substances that can be used to coat or functionalize the substrate include, but are not limited to, lectins, poly-lysine, antibodies, and polysaccharides.).
Regarding Claim 14, modified Ramachandran Iyer teaches the microfluidic device according to claim 1, wherein nucleic acids sharing the same barcode have a plurality of sequences (See section 4. Polymersomes. In some embodiments of any of the spatial analysis methods described herein, capture of a biological analyte by a molecule (e.g., a nucleic acid molecule) having a barcode (e.g., a spatial barcode) and a capture domain is facilitated by a polymersome. In some embodiments, a molecule (e.g., a nucleic acid molecule) having a barcode (e.g., a spatial barcode) and a capture domain is contained in the polymersome, and the molecule (e.g., a nucleic acid molecule) having a barcode (e.g., a spatial barcode) and a capture domain uses the polymersome to get access to analytes inside the cell. A “polymersome” as referred to herein is an artificial vesicle.).
Regarding Claim 15, modified Ramachandran Iyer teaches he microfluidic device according to claim 1, wherein nucleic acids comprise one or any combinations of the following sequences:1) a restriction site or a photocleavable site for nucleic acid release (In some embodiments, the cleavage domain includes a sequence that is recognized by one or more enzymes capable of cleaving a nucleic acid molecule, e.g., capable of breaking the phosphodiester linkage between two or more nucleotides. A bond can be cleavable via other nucleic acid molecule targeting enzymes, such as restriction enzymes (e.g., restriction endonucleases)) 2) a sequence complementary to an amplification primer for further amplification 3) a T7 RNA polymerase promoter sequence for in vitro transcription (T7 DNA polymerase enzymes.) 4) a hybridization site, a ligation site or a recombination site, for nucleic acid labeling (Template switching oligonucleotides can include a hybridization region and a template region. The hybridization region can include any sequence capable of hybridizing to the target.), and 5) a sequence of randomized nucleotide residues that function as a unique molecular identifier (The capture probe can include a capture domain. The capture probe can include a universal molecular identifier (UMI) and a cleavage domain.).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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