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
Claims 1-2, and 5-20 are currently pending. Claims 3-4 are canceled. Claims 1, 5-12 and 14 are amended.
Claims 10-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim.
Claims 1-2 and 5-9 are examined on their merits.
Information Disclosure Statement
The Information Disclosure Statement filed 2/6/2026 has been reviewed.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Rejections Withdrawn
Claim Rejections - 35 USC § 112(b)
In light of the amendments to the claims the rejection of claims 5-9 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention is withdrawn.
Claim Rejections - 35 USC § 103
In light of the amendments to the claims the rejection of claims 1-9 under 35 U.S.C. 103 as being unpatentable over Wu et al. WO 2019/028166 (2/7/2019) (6/25/2025 IDS) in view of de Rutte et al. Massively parallel Encapsulation of Single Cells with Structured Microparticles and Secretion-based Flow Sorting, bioRxiv, 11 March 2020, pp 1-23, XP055921908 (3/11/2020)(6/25/2025 IDS) and Niemeyer et al. EP 3590885 (1/8/2020) is withdrawn.
New Rejections
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-2 and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. WO 2019/028166 (2/7/2019) (6/25/2025 IDS) in view of de Rutte et al. Massively parallel Encapsulation of Single Cells with Structured Microparticles and Secretion-based Flow Sorting, bioRxiv, 11 March 2020, pp 1-23, XP055921908 (3/11/2020)(6/25/2025 IDS), Niemeyer et al. EP 3590885 (1/8/2020) and Buehler et al. US 2002/0035167 (3/21/2002).
Wu et al. teach hydrogel beads which are made of a hydrogel polymer and a genetic material which can be a cell, wherein the bead has multiple pores that allow diffusion of a reagent through the bead while retaining the genetic material. (See [0004]). The diameter of the bead can be from about 2 to about 100 micrometers in diameter. (See [0084]). The bead is a particle that has a plurality of micropores as called for in instant claim 2.
Wu teaches that the pore size of the hydrogel can be engineered to allow the diffusion of enzymes and smaller size primers (less than 50 base pairs) while retaining larger nucleic acids (greater than 300 base pairs). (See [0035]). Wu teaches that the pore size can be finely tuned by varying the ratio of the concentration of the polymer to the concentration of crosslinker. (See [0030]). Wu teaches that cells that are 2 micrometers in diameter can be captured. (See [0037]). Since cells that are 2 micrometers in diameter can be captured within the particle, the pore size and open interior volume must be at least about a micron as called for in instant claim 1.
Wu teaches an embodiment in which the encapsulated nucleic acids can be sequenced within the hydrogel beads. The sequencing can be sequencing by synthesis. (See [0055-56]). Wu teaches that in the methods of sequencing by synthesis, a primer may be used. (See [0077]).
Wu does not teach antibodies that are covalently linked to the particle, and Wu does not expressly teach that the particles have a nanoporous structure in the mesh of cross-linked polymers. Wu also does not teach polymers of acrylamide and bisacrylamide, These deficiencies are made up for with the teachings of Rutte et al, Niemeyer et al and Buehler et al.
Rutte et al. (Rutte) teaches the fabrication of structured hydrogel microparticles containing cavities. (See Figure 1 and page 4). The structured hydrogel microparticles containing cavities are further functionalized with an antibody or biotinylated antibody for cell adhesion. Antibodies are called for in instant claim 5. Biotin is covalently linked to the particle as called for in instant claim 9. (See page 4, first paragraph and Figure S1G).
Cells are then introduced to particles. (See Figure 3). Rutte teaches that its approach, which it terms “dropicles” are able to capture circulating cells within the cavities of the microparticles, so that the secretions of the cell can be further analyzed. (See page 3, second paragraph). Circulating cells are called for in instant claim 7 and they are a target capture moiety as called for in claim 6. The secretions of the cell are further analyzed through cell lysis. Cell lysis is called for in instant claim 8.
Rutte teaches that its approach, which uses cavity-containing hydrogel microparticles to perform functional single-cell secretion analysis and sorting using only commonly accessible lab infrastructure. (See Abstract). The microparticles act as a solid support which facilitates cell attachment, templates formation of uniform aqueous compartments which prevent cross-talk between cells, and captures secreted proteins. This reads on the aqueous liquid permeating the interior of the micropores which allows analytes in the fluid to access the reagent as called for in instant claim 1. Rutte notes that microparticles are easily distributed and used, democratizing access to high-throughput functional cell screening. (See Abstract).
Niemeyer et al. (Niemeyer) teaches a composite material comprising DNA hydrogel and silica nanoparticles. (See Abstract). It is a DNA polymer material with designed properties including adhesiveness, stiffness and plasticity. By incorporating silica nanoparticles into the DNA hydrogel, the mechanical stiffness and elastic properties can be improved. The composite material is mechanically stable and has a porous structure such that the three-dimensional structures allow the diffusion of chemical and biological substances through the wall of the structures.
Niemeyer teaches that in a preferred embodiment, the mesh size is estimated to be bigger than 100 nm and smaller than 500 nm, as determined by the 200 nm tracer particles freely moving inside the hydrogel mesh structure, while the 500 nm tracer particles are restrained inside the hydrogel mesh structure. This range of mesh size bigger than 100 nm and less than 500 nm overlaps with the mesh size of at least about 200 nm is called for in instant claim 1. Since the 200 nm tracer particles are moving freely inside the hydrogel mesh structure, there is open interior volume in the hydrogel mesh as called for in instant claim 1. There is also a nanoporous structure in the mesh as called for in instant claim 1.
Buehler et al. (Buehler) teach polyacrylamide hydrogels which are made from prepolymers and polyacrylamide reactive polymers. (See Abstract). Buehler also teaches a method that provides greater control of polyacrylamide pore size and crosslink density, allowing for the preparation of a polyacrylamide hydrogel appropriate for use with DNA. (See Abstract). Buehler teaches that polyacrylamide hydrogels are especially employed as molecular sieves for the separation of biologic moieties. (See [0003]). Buehler teaches that polyacrylamide is particularly flexible and adaptable for specified uses. (See [0002]). Buehler teaches a method of making the hydrogels that uses a solution of acrylamide and bisacrylamide crosslinker. (See [0003]). Crosslinked polymers comprising acrylamide and bisacrylamide are called for in instant claim 1.
One of ordinary skill in the art before the earliest effective filing date of the invention making the Wu hydrogel beads with multiple micropores that can capture cells that are 2 micrometers in diameter would also have a nanoporous structure with a mesh size that is bigger than 100 nm and smaller than 500 nm and functionalize the cavities with a biotinylated antibody in order to adhere 200 nm cells that can access the inside of the hydrogel mesh structure as taught by Rutte and Niemeyer. This would allow for the democratization of access to high-throughput functional cell screening.
One of ordinary skill in the art before the earliest effective filing date of the invention making the Wu hydrogel beads with multiple micropores that can capture cells that are 2 micrometers in diameter would use acrylamide and bisacrylamide crosslinker taught by Buehler in order to have a polymer and crosslinker that is flexible and adaptable to a variety of biologic specified uses and tunable pore sizes as taught by Buehler.
Response to Remarks
Applicants’ arguments of January 8, 2026 have been fully considered and are found to be mostly unpersuasive as described further below.
§112 Rejections
Applicants assert that their amendments to the claims have addressed the indefiniteness rejections.
Response
In light of the amendments to the claims, the indefiniteness rejections are withdrawn above.
Obviousness Rejections
Applicants argue that the obviousness rejection relies on conclusory logic and hindsight because features from the cited art were recited without a reason for why a person of ordinary skill in the art would be motivated to combined them. Additionally, Applicants assert that no advantage was articulated in modifying the hydrogel beads of Wu with the features of de Rutte and/or Niemeyer, given the differences in the particle materials among the cited references.
Response
Applicants’ arguments are not found to be persuasive. However, in light of the amendments to the claims, the rejections have been withdrawn above and new rejections applied.
Applicants’ arguments are not found to be persuasive because the obviousness rejection does not rely in conclusory logic and hindsight.
Respectfully, Applicants’ assertion that hindsight has been employed in making the obviousness rejections is incorrect and unpersuasive. Hindsight has not been used in making any obviousness rejections; this is evident in that all of the claimed elements are taught or suggested in the prior art references themselves and so is the motivation to combine them. Since both the teaching of the components and the motivation to use it is found in the prior art references themselves, the rejection relies on only knowledge from the prior art references themselves.
As stated in the rejection one of ordinary skill in the art before the earliest effective filing date of the invention making the Wu hydrogel beads with multiple micropores that can capture cells that are 2 micrometers in diameter would also have a nanoporous structure with a mesh size that is bigger than 100 nm and smaller than 500 nm and functionalize the cavities with a biotinylated antibody in order to adhere 200 nm cells that can access the inside of the hydrogel mesh structure as taught by Rutte and Niemeyer. This would allow for the democratization of access to high-throughput functional cell screening. The motivation would be to have easier, cheaper access to high-throughput cell screening. The references teach that this is a stated goal of their inventions: easier access to high-throughput screening. Lower cost and being able to achieve high throughput screening more easily is a highly motivating reason to combine teachings.
Similarly, Buehler teaches that acrylamide and bisacrylamide crosslinker are a polymer and crosslinker that allow for good control of the pore size and crosslink density. This is a powerful motivation because persons of ordinary skill in the art are able to control these features so that they can adapt them to meet their objectives in their research. Varying crosslink density can affect the properties of the hydrogel and make it adaptable to suit varying research needs. Flexibility is sought after and makes a system or hydrogel more desirable for use in research.
The references themselves speak to a desire for this flexibility. Wu states at [0023] that it is to be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.
Conclusion
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 SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
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/SARAH CHICKOS/
Examiner, Art Unit 1619
/SARAH ALAWADI/Primary Examiner, Art Unit 1619