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 .
DETAILED ACTION
This action is in response to papers filed on August 18, 2026.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 1, 2026 has been entered.
Claims 1-13, 16, 18, 20, 23 and 25 are currently pending. Claim 1 has been amended and claim 15 has been canceled by Applicants’ amendment filed on 08/18/2026. No claims were newly added. Applicants’ previous election of Group 1 directed to a three-dimensional cell culture medium, e.g., claims 1-13, 14-16, 18 and 20 was previously acknowledged. Claims 23 and 25 were previously withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to non-elected invention, there being no allowable generic or linking claim. Claims 5 and 6, 7-13 were previously withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to non-elected species, there being no allowable generic or linking claim. Note that claims 7-12 were previously withdrawn from further consideration as they are dependent on claim 6 and claim 13 was previously withdrawn from consideration as it is dependent on claim 5. The restriction requirement was previously made FINAL.
Therefore, claims 1-4, 16, 18 and 20 are under examination to which the following grounds of rejection are applicable.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/US21/19922, filed on 02/26/2021 . This application has claims priority to PRO 62/983,056 filed 02/28/2020.
Thus, the earliest possible priority for the instant application is February 28, 2020.
Response to Arguments
Withdrawn Objections/Rejections in Response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
In view of Applicants’ amendment filed on August, 18, 2026, the rejection of claims 1-4, 16, 18 and 20 under USC § 103 as being obvious over O’Bryan (Published 26 February 2019, ACS Appl. Bio Mater, IDS filed on 8/28/2022 ) are withdrawn ), in view of Canning et al. (Published on March 9 2016, Macromolecules 2016, 49, 6, 1985–2001) es evidenced by Lin et al. (Published: 2006. Journal of Membrane Science, vol. 276, no. 1-2, 1 May 2006, pp. 145–161) has been withdrawn.
In view of Applicants’ amendment filed on August, 18, 2026, the rejection of claims 1, 4 and 20 under USC § 103 as being obvious over O’Bryan (Published 26 February 2019, ACS Appl. Bio Mater, IDS filed on 8/28/2022 ) are withdrawn ), in view of Canning et al. (Published on March 9 2016, Macromolecules 2016, 49, 6, 1985–2001) es evidenced by Lin et al. (Published: 2006. Journal of Membrane Science, vol. 276, no. 1-2, 1 May 2006, pp. 145–161) has been withdrawn.
Applicants have amended claim 1 to introduce the limitations of claim 15 which was not rejected under USC § 103 as being obvious over O’Bryan.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to any argument pertaining to a new or maintained rejection can be found below.
New Rejections Necessitated by the Amendments filed August 18, 2026
Claim Objections
Claim 1 is objection to for its recitation of the phrase “wherein a ratio” in line 10, as it is the incorrect definitive article providing proper antecedent basis to the claim. The claim should be amended to recite “wherein the ratio of PEGa and PEGda ”. Appropriate correction is required.
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.
Claim(s) 1-3, 16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over O’Bryan (Published 26 February 2019, ACS Appl. Bio Mater, IDS filed on 8/28/2022 ), in view of Canning et al. (Published on March 9 2016, Macromolecules 2016, 49, 6, 1985–2001)(ref. of record) and Sagle et al. (Published: 2009. PEG-based hydrogel membrane coatings. Polymer. 2009 Jan 28;50(3):756-766). This is a new rejection necessitated by the amendments filed August 18, 2026.
Regarding claim 1, O’Bryan teaches a three-dimensional culture system comprising microgel particles (pp. 1509, Abstract); and a liquid cell culture medium, wherein they particles have a radius that is 4.76 ± 1.49 μm for MAA microgels, 5.17 ± 1.94 μm for qDMAEMA microgels, and 5.21 ± 2.14 μm for the CBMA microgels (pp. 1511, col 2, para 3). Further, O’Bryan teaches a percentage of polymer network (pp. S-4, “Small amplitude oscillatory frequency sweeps of polyelectrolyte microgels swollen in MEGM cell growth media at 4 wt % polymer”).
O'Bryan does not explicitly teach the microgel particles as charge-neutral or substantially spherical or within the same embodiment.
However, O’Bryan further discusses the modification of the hydrogel composition to be charge neutral to reduce deformities within the microgel particles (pp. 1512 col 2 para 2, "Neutral hydrogels swell to an equilibrium concentration in which the driving osmotic pressure (pi) generated from the random motion of the polymer chains is balanced" ; pp. 1516 col 1 para 1, "In contrast, simple polyelectrolyte scaling laws do not capture the rheological behavior of zwitterionic microgels. Instead, zwitterionic microgels exhibit a plateau in rheological properties in the high-salt limit. This unique behavior may be advantageous when swelling microgels in salt-rich solvents, such as cell growth media. However, interactions between the zwitterionic microgels and biological zwitterionic molecules, including amino acids and proteins, may result in unforeseen changes in rheological properties beyond the scope of this work. Further development of charge-neutral microgels may circumvent these interactions, providing opportunities for further biomaterial applications using microgels").
A skilled artisan would have been motivated to utilize charge-neutral microgels to circumvent altered rheological properties of microgel particles. Therefore, it would be obvious for one skilled in the art to incorporate charge-neutral microgels to prevent unwarranted changes in rheological properties as contemplated by O’Bryan with a reasonable expectation of success.
However, O’Bryan does not explicitly teach that the charge-neutral microgel particles comprise a crosslinked polymer network comprises poly(ethylene qlycol) methyl ether acrylate (PEGa) and poly(ethylene qlycol) diacrylate (PEGda), wherein a ratio of PEGa to PEGda is about 80:20, and wherein the 3D cell culture medium comprises about 10 wt% to about 25 wt% crosslinked polymer network.
Canning et al. teaches non-ionic microgels particles comprise a crosslinked polymer network of poly(ethylene glycol) methyl ether acrylate and poly(ethylene glycol) diacrylate, (pp. 1989, “Similarly, RAFT aqueous emulsion polymerization has been used to produce non-ionic, anionic, or cationic spheres.”; pp. 1991, “RAFT CTA can be used to confer pH-responsive behavior on ostensibly non-ionic diblock copolymers while requiring minimal amounts of added base or acid.”; page 1989, col 2 para 3 bridging into page 1990 col 1 para 1, “Chain extension of a poly(ethylene glycol) (PEG)-based macro- CTA with 2-methoxyethyl acrylate (MEA), PEG methyl ether acrylate, and a small amount of PEG diacrylate (PEGDA) cross-linker produced spherical nanogels, whose dimensions decreased almost linearly as the solution temperature was increased from 20 to 60 °C”).
It would be obvious to substitute the charged-microgels of O’Bryan with the charge-neutral microgels of Canning, because PEG-based acrylates are well known in the art to be neutral and hydrophilic monomers. The incorporation of PEGa and PEGda would result in a chemically inert gel that would not respond to any charged stimuli, representing a predictable design choice that a skilled artisan would to produce a neutral microgel. Furthermore, O’Bryan mentions the use of charge-neutral microgels to overcome the unforeseen changes in rheological properties (pg 1516 col 1 para 1,”Further development of charge-neutral microgels may circumvent these interactions, providing opportunities for further biomaterial applications using microgels.”). So, a skilled artisan in the art would have been motivated to utilize PEGa and PEGda as they are known to produce charge neutral microgels and prevent any change in rheological characteristics of the gel. Further, it would have been obvious to optimize aspects of the charge-neutral microgel based on influential considerations of the design, such as modifying ratios of PEGa and PEGda, processing conditions, pH of culture medium, to achieve the claimed range of 10% to 25% wt polymer network within a 3D culture medium.
However, O’Bryan and Canning fail to teach wherein ratio of PEGa to PEGda is about 80:20, and wherein the 3D cell culture medium comprises about 10 wt% to about 25 wt% crosslinked polymer network, or that the charge-neutral microgel particles have a permeability of 0.1 µm2 to 10000 µm2. Moreover, O’Bryan emphasizes that cell performance is dependent on chemical composition (pp. 1510, col 2 para 1).
Sagle explores the different fundamental relationships between copolymer structure and hydrogel properties (pp. 757, col 1, para 2). Moreover, Sagle reveals that crosslinking density, and concentration of polymers influenced water permeability (pp. 756, Abstract). Sagle also teaches that the highest water volume fraction when a copolymer was achieved with 80 mol% PEGA and 20 mol% of PEGDA (pp. 756, Abstract and Figure 7).
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It would have been obvious to modify the charge-neutral microgel of Canning and O’Bryan, to use the ratio of PEG methyl ethyl acrylate and PEG diacrylate taught by Sagle, as it was found to influence permeability and diffusivity of PEGa/PEGda materials. Moreover, a person with ordinary skill in the art would have been motivated to use the specific ratio of PEGa (80 mol%) to PEGda (20 mol%), as discussed in Sagle, as it displayed the highest water volume fraction. Further, a skilled artisan would have optimized certain ratios of PEGa to PEGda as Sagle discusses that characteristics such as permeability are known to be dependent on varying concentrations of comonomer content, and optimizing such concentrations would subsequently affect cell performance as taught by O’Bryan (pp. 1510, col 2 para 1). The specific /absolute permeability of 10 wt% to about 25 wt% is intrinsic to the crosslinked polymer matrix, absent any evidence to the contrary. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421.
MPEP § 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount.
Regarding claim 2, the combined teachings of Sagle, O’Bryan and Canning render obvious the claimed methodology of claim 1. Moreover, O’Bryan teaches microgels with a surface roughness, relative to a perfect spherical surface (Figure 1A, See attached; pp. 1514 col 1, “As the polymer concentration of the microgels increases above the jamming concentration, individual microgel particles will deform without osmotically driven deswelling, resulting in volume fractions in excess of the random close packing limit of hard spheres”).
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Regarding claim 3, the combined teachings of Sagle, O’Bryan and Canning render obvious the claimed methodology of claim 1. Moreover , O'Bryan teaches the microgels to have a polymer concertation of 4 wt% (pg 1511 col 1 para 1-2, "Microgels for cell culturing are swollen in MEGM cell growth media to a final polymer concentration of 4 wt% ... ").
Regarding claim 16, the combined teachings of Lin, O’Bryan and Canning render obvious the claimed methodology of claim 1. Further, O’Bryan discloses that yield stress of microgels is influenced by the environment in which the microgels are cultivated in (pp. 1513, “Similar to the yield stress of microgels, the elastic shear modulus decreases with increasing concentrations of calcium chloride.”). O’Bryan also teaches that changes in salt concentration affects yield stress, measured in Pascals (Figure 4B, D, and F).
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It would have been obvious for a skilled artisan to optimize aspects of the microgel, such as polymer identity, concentration, processing conditions, etc. to achieve a yield stress within the claimed range of the instant application. As yield stress is known to depend on the composition, structure of the polymer network, and the environment in which it is suspended as taught by O’Bryan, a skilled artisan would have recognized that yield stress is a result-effective variable that would have constituted routine optimization of polymer concentrations, salt concentrations within the environment, etc. Applicants must provide evidence demonstrating that the claimed yield stress range is critical or yields unexpected results (See MPEP 2144.05).
Regarding claim 18, O’Bryan renders obvious the 3D cell culture medium according to claim 1, wherein the concentration of the microgel particles is from 0.05% to 1.0% by weight (Results and Discussion, pg 1511 col 2 para 7 bridging into pg 1512 col 1 para 1, “We find the jamming concentrations of the microgels to be 0.3, 0.45, and 0.9 wt % for microgel particles containing 17 mol % of MAA, qDMAEMA, and CBMA, respectively"), falling within the scope of concentration of microgel particles is from 0.05% to 1.0% by weight.
***
Claims 1, 4 and 20 are newly rejected under 35 U.S.C. 103 as being unpatentable over over O’Bryan (Published 26 February 2019, ACS Appl. Bio Mater, IDS filed on 8/28/2022 ), in view of Canning et al. (Published on March 9 2016, Macromolecules 2016, 49, 6, 1985–2001)(ref. of record) and Sagle et al. (Published: 2009. PEG-based hydrogel membrane coatings. Polymer. 2009 Jan 28;50(3):756-766), as applied to claims 1-3, 16, and 18, and in further view of Weaver et al. (US 20190321797 A1, IDS filed on 08/26/2022). This is a new rejection necessitated by the amendments filed August 18, 2026.
With regard to instant claim 1, the combined teachings the 3D cell culture medium in O’Bryan, Canning and Sagle render obvious the claimed product, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, the combined teachings fail to teach teaches a pore space formed between adjacent charge-neutral microgel particles is from 50 nm to 10 um as recited in claim 4.
Weaver teaches a pore space formed between adjacent charge-neutral microgel particles is from 50 nm to 10 um (Claim 10, “ the stabilized scaffold comprising pores having a median diameter of about 10 μm to about 35 μm). Further, Weaver teaches that microporous gel systems provide prevention and treatment for infections (para 0005, “In some instances, microporous gel systems disclosed herein provide for prevention and treatment of infections via antimicrobial activity.”). Moreover, Weaver teaches that the microporous scaffolds comprising the nanoparticles provides several rates at which a therapeutic agent can be administered (para 0093).
It would have been obvious to modify the charge-neutral microgels of O’Bryan to have a porous structure as taught by Weaver, as the system can aid in treating infections. Further, it would have been obvious to optimize the porosity diameter based on influential considerations of the design of the 3D cell culture medium, such as controlling the rate at which therapeutic agents are administered into the medium, as described in Weaver (para 0093). Moreover, the pore space formed between microgel particles is 10 µm, which is within the limitation of claim 4.
Regarding claim 20, the combined teachings of O’Bryan, Canning, Sagle and Weaver render obvious the claimed methodology. Moreover, Weaver discusses that the microgel scaffold can comprise a therapeutic agent such as an antibiotic (Abstract).
Response to Arguments as they pertain to O’Bryan et al. and Canning et al.
Beginning on page 5 of the remarks filed August 18, 2026, Applicants’ essentially argue the following:
Applicants assert that the Office Action has not provided an articulated rationale with an explanation of why it would have been routine optimization to arrive at the claimed features and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range. MPEP 2144.05(11)(B) states that only result effective variables can be optimized.
In response, the arguments are considered but deemed unpersuasive for reasons listed:
Regarding 1), the applicant’s arguments regarding routine-optimization are found not persuasive. The claimed parameters (e.g. permeability and yield stress) are result of the PEGa to PEGda which is about 80:20 and is disclosed by the prior art of Sagle et al. (Published: 2009. PEG-based hydrogel membrane coatings. Polymer. 2009 Jan 28;50(3):756-766). The applicant is on record as stating that the ordinary artisan would have had no reason to expect that specific/absolute permeability is not an intrinsic property of the matrix (Page 6 of applicants’ remarks). Therefore, any variation on the ratio PEGa to PEGda would result in inherent changes in specific/absolute permeability. Specifically, when altering the concentration of PEGa:PEGda to about 80:20 as discussed in Sagle, a person with ordinary skill in the art would recognize that the structure of the matrix will change, and subsequently produce a specific permeability outlined within claim 1. This is supported by O’Bryan (2019) statements “The yield stress of microgel packs may be tuned through changes in either the polymer charge density of the microgels or in the overall polymer concentration. As we increase the polymer charge density at a fixed polymer concentration, the yield stress increases” (pp. 1512, col 1, para 2). Thus, O’Bryan reveals that yield stress is a result-effective parameter that is influenced by tuning concentrations/ratio of polymers. Moreover, Sagle teaches that crosslinking density, and molar ratio of PEGa-PEGda comonomers can be modified to increase water permeability (hydraulic permeability) (Sagle, Abstract). Therefore, a person with skill in the art would have been motivated to optimize concentrations of PEGa and PEGda to achieve a desired permeability within the claimed range, as Applicant states on the record that modifications of polymer concentrations would inherently result in a change in permeability.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
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/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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