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 .
Applicant's amendment and response received on 03/16/2026 has been entered.
Claims 1-26 are currently pending. Claims 1, 3, 5, 8, 13, 16, 21, 25, 26 are amended. Claims 1, 16, and 21 are independent claims.
Therefore, claims 1-26 are examined on their merits to which the following grounds of rejection are applicable.
Priority
Applicant's claim for the benefit of a prior-filed application PRO 63/390,501 filed 07/19/2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Thus, the earliest possible priority for the instant application is 07/19/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/17/2026 was filed after the mailing date of the current office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Withdrawn Objections in response to Applicants’ arguments
Claim Objections
In view of Applicants’ amendment of claims 1 and 21, the objection of
claims 1 and 21 has been withdrawn. Applicant’s argument with regard to a withdrawn objection are moot.
Withdrawn Rejections in response to Applicants’ arguments
35 USC § 112(b)
In view of Applicants’ amendment of claims 1, 3, 5, 8, 13, 16, 21, 25, 26, the rejection of claims 1-26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn. Applicant’s argument with regard to a withdrawn rejection are moot.
Withdrawn Rejections in response to Applicants’ arguments
35 USC § 103
In view of Applicants’ amendment of claims 1, 13, 16, and 21, the rejection of
claims 1-26 under 35 U.S.C. 103 as being unpatentable over Tiemeijer et al (Front Bioeng Biotechnol. 2022; page 1-19; as cited in IDS), Martinez et al (Macromol Biosci. 2012; page 946-951), Pertoft et al (US Patent Application Pub. 20040038356 A1), OptiPrep (Density Gradient Media. page 1-9; as cited in IDS) Tasoglu et al (Nat Commun. 2014; page 1-11), CryoPro Hampton Research (downloaded on 12/5/25; page 1-7), Tao et al (Mater Sci Eng C Mater Biol Appl. 2021; page 1-9; as cited in IDS), and Brooks et al (ACS Biomater Sci Eng. 2018; page 707-718) has been withdrawn as amended claims have changed the scope of the invention.
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 in response to Applicants’ Amendments
Claim Interpretation
The term “bulk”, as recited in claim 1, 16, and 21, is interpreted as a method which can yield more than one hydrogel particle. This interpretation is made in light of the specification which only mentions the term “bulk” as “bulk aqueous phase emulsification” and “bulk two-phase oil-water suspensions” in para 0032. This interpretation is further detailed below:
Applicant’s remarks on page 12 state alleged support for the phrase “bulk method” as recited in para 0032, 0034, and 0042. Applicant’s remarks on page 12 state "For downstream applications and efficacy of the cargo, the suspension media must then be thoroughly removed from the hydrogel. The suspension media removal step of prior technologies has prevented scaling and widespread use of the bulk two-phase oil-water suspensions." Id. To overcome these drawbacks, the Application as filed teaches mixing the hydrogel (see id., at para. [0042]), and removing the suspension media from the hydrogel suspension media mixture in steps 141 to 147 (see id., at paras. [0047] to [0058]). As mentioned above, In para 0032 of the specification, it recites “microparticles may be prepared by bulk aqueous phase emulsification” as background information to the invention and “The suspension media removal step of prior technologies has prevented scaling and widespread use of the bulk two-phase oil-water suspensions”. A Google® search of the phrase “bulk aqueous phase emulsion”, indicates that the phrase can pertain to bulk dispersal of microfluidics drops to create smaller droplets which, for example, can be a fifty-microliter sample (as described in Sukovich et al reference) and there is no clear definition from Google Search as to the term “bulk two-phase oil-water suspensions”. Therefore, examiner interprets “bulk” to include yielding more than one hydrogel particle.
The term “container” as recited in claim 1, 2, 8, and 16 is interpreted as a device that holds materials. The specification describes the container as “holding combined hydrogel materials” (para 0042).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1-26 are newly rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. This is a new rejection necessitated by amendment of the claims in the response filed 03/16/2026.
Claim 1, 16, and 21 are vague and indefinite in the recitation of “a bulk method for generating hydrogel particles”. It is unknown what constitutes being “bulk”. The specification does not disclose the meaning of the phrase “bulk”. As such the metes and bounds of the claim are indefinite.
Claim 7-10, recites the limitation " agitating". There is insufficient antecedent basis for this limitation in the claim.
Claims 1-15 are rejected insofar as they depend from claim 1, Claims 17-20 are rejected insofar as they depend on claim 16 and claims 22-26 are rejected insofar as they depend on claim 21
Claim Rejections - 35 USC § 103
Claim 1-26 are newly rejected under 35 U.S.C. 103 as being unpatentable over Tiemeijer et al (Front Bioeng Biotechnol. 2022; page 1-19; as cited in IDS), Pertoft et al (US Patent Application Pub. 20040038356 A1), OptiPrep (Density Gradient Media. page 1-9; as cited in IDS), Tasoglu et al (Nat Commun. 2014; page 1-11), and CryoPro Hampton Research (downloaded on 12/5/25; page 1-7). This is a new rejection necessitated by amendment of the claims in the response filed 03/16/2026.
Regarding claim 1, 3, 4, 12, 15, 16, and 21 Tiemeijer teaches microfluidic devices for forming hydrogel particles “production of hydrogel droplet microfluidics are poly(ethylene glycol) (PEG), poly(acrylic acid), poly(vinyl alcohol) (PVA), poly(acrylamide” (Page 5, Synthetic polymers), droplet-based approaches have a main advantage for being high-throughput (page 4, left col, para1), “Alterations of these polymers can be used to provide useful cross-linking approaches such as photopolymerization as demonstrated in PEG and PVA” (Page 5, synthetic polymers) and “Calcium–chelator complexes are mixed with alginate solutions where the high chelator affinity prevents direct gelation. By decreasing pH, calcium is released which allows cross-linking” (Page 4, natural hydrogels)), “The dispersed phase is a water-based cell suspension” (Page 2, left column), “photopolymerization as demonstrated in PEG” (Page 5, Synthetic Hydrogels), Figure 6 (page 11)), and droplets can be “tuned to contain multiple cells or approach single-cell encapsulation” and producing highly homogenized droplet sizes occurs inside a device (i.e. a container) (page 2, right col, Microfluidics, para 2), rendering obvious combining hydrogel materials in a container, mixing to form suspension, polymerizing to form hydrogel particles, and the hydrogel particles having encapsulated cargo
The examiner is interpreting “high-throughput” as “bulk” because it describes making more than one particle.
Tiemeijer does not teach adding a density adjusting material and a cargo-compatible solution; centrifuging the hydrogel particles; forming a three-phase solution, wherein the three-phase solution comprises the density adjusting material settled between the hydrogel particles in the cargo-compatible solution and the suspension media; and retrieving the hydrogel particles lacking the suspension media.
However, Pertoft teaches a method of purification of biological particles, such as antigen core particles, using flotation ultracentrifugation on a density gradient. More specifically, the sample is placed on top of a preformed density gradient, which is then centrifuged, causing forced separation, to allow for collection of the sample in the top layer while contaminants (i.e. suspension media) etc have migrated to the lower layers of the gradient (Para 005) and the steps include placing a solution of low density on top of the mixture (i.e. cargo-compatible solution) such that the sample float to the low density solution (Para 0010-0014). Pertoft teaches that the method can be “adapted to separate different cell types, such as X- and Y-sperm cells, from each other in a sample on the basis of their buoyant density, shape, permeability, movement, and/or viscosity in a density gradient medium by centrifugation” (para 00250).
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to use the teachings of combining hydrogel materials resulting in cargo-encapsulated hydrogel particles in a suspension media from Tiemeijer and teachings from Pertoft for separation of substances by adding a density adjusting material to a substance mixture (i.e. hydrogel particles in a suspension media) and centrifuging to result in a method of cargo-encapsulated hydrogel particle generation and suspension media removal. Collected hydrogel particles in suspension media, as taught by Tiemeijer, can be subjected to Pertoft’s method for substance separation resulting in hydrogel particles that lack suspension media. One would be motivated to combine these teachings because downstream use of the hydrogel particles can require suspension media removal and density gradient-centrifugation methods are known to be used for purification/washing/separation experiments to separate desirable substances from contaminants, such as suspension media. 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 combined teachings of Tiemeijer and Pertoft, do not disclose adding a cargo-compatible solution wherein the cargo-compatible solution comprises a cargo-compatible surfactant (claim 4 and 12), shaking the container until the hydrogel material are mixed (claim 16), and polymerizing via UV light (claim 21).
However, Tasoglu teaches (i) a density gradient liquid to increase the density of solution enabling gels to float on the surface of the reservoir and (ii) surfactant Tween-80 to decrease the surface tension and drag forces on gels (page 2, Results Fabrication of magnetoceptive materials) and Pyrolytic graphite-embedded PEGDMA hydrogel was prepared by adding 90% (w/v) pyrolytic graphite powder into 20% (w/v) PEGDMA prepolymer solution, and vortexing for 1min (page 10, left column, last para). Tasoglu also teaches photopolymerization (Page 5, Synthetic Hydrogels), Figure 6 (page 11) UVtriggered cross-linking” (page 5, 2nd column, first para).
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to modify the teachings Tiemeijer and Pertoft according to the teachings from Tasoglu. One would be motivated to combine these teachings because shaking/mixing materials and removal of suspension media from hydrogel encapsulation processing is routine and well known in the art and density gradient methods and surfactants are known to be used for purification/washing/separation experiments. 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 combined teachings of Tiemeijer, Peroft, and Tasoglu do not teach a robotic arm, an automated liquid handling system, and automated mixing mechanical mixing device (claim 21).
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to use automation (e.g. automated liquid handling system, robotic arm, automated mechanical mixing device). Providing mechanical or automated approaches to replace manual labor would accomplish the same result of generating cargo-encapsulated hydrogels. Motivation to do so would be to increase efficiency and throughput of making hydrogels.
Regarding claim 2 and 22, the combined teachings of Tiemeijer and Pertoft render obvious claim 1 and 21.
The combined teachings of Tiemeijer and Pertoft do not teach mixing the hydrogel materials comprises: 1) accelerating a container holding the hydrogel materials in a first direction, 2) decelerating the container to a stop, 3) accelerating the container in a second direction opposite the first direction back to an initial position, and 4) repeating steps 1-3 a plurality of times.
Tasoglu teaches "Pyrolytic graphite-embedded PEGDMA hydrogel was prepared by adding 90% (w/v) pyrolytic graphite powder into 20% (w/v) PEGDMA prepolymer solution, and vortexing for 1min". (page 10, left column, last para). Examiner notes that vortexing causes acceleration of a container which can be stopped and accelerated in an opposite direction.
It would have been obvious to mix hydrogel material by using a vortex into a direction and then an opposite direction in order to combine the hydrogel material with a reasonable expectation of success. Repeating the mixing several times would a matter of routine optimization for one of ordinary skill in the art to facilitate effective mixing to form a hydrogel-suspension media mixture with a reasonable expectation of success.
Regarding claim 5, the combined teachings of Tiemeijer and Peroft, render obvious claim 1. Moreover, Tiemeijer teaches “For washing, on-chip designs have been proposed to get microgels from the oil phase into the water phase. Passive methods use the interfacial tension of the water–oil droplets to allow microgels to merge into a parallel flowing extraction aqueous phase. More active approaches use filtering or slow infusion of the aqueous phase” (Page 6, column 1, Recovery of Microgels)), rendering obvious washing the hydrogel particles on a filter and resuspending the hydrogel particles in a storage solution as required in claim 5.
Regarding claim 6, the combined teachings of Tiemeijer and Pertoft, render obvious claims 1 and 5.
The combined teachings of Tiemeijer and Pertoft, do not disclose resuspending the hydrogel particles in a mixture of suspension media and storage solution, and repeating the steps of washing the hydrogel particles and resuspending the hydrogel particles in a mixture of suspension media and storage solution having progressively higher ratios of storage solution to gradually resuspend the hydrogel particles in the storage solution in a stepwise manner.
However, CryoPro Hampton Research teaches “Incrementally increase the concentration and/or alter composition of the cryoprotectant (storage solution) serially, 5 to 10%” (Page 2, first para).
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to modify the teachings Tiemeijer and Pertoft according to the teachings of CryoPro Hampton Research to resuspend the hydrogel particles in a mixture of suspension media and storage solution having progressively higher ratios of storage solution to ensure limited carryover of residual media ending up in the final storage solution with a reasonable expectation of success. Stepwise washing/repeated washing of materials to get progressively higher ratios of storage solution is routine and well known in the art. 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.
Regarding claim 7, 9, 10, 17, and 23 the combined teachings of Tiemeijer , Peroft, and CryoPro Hampton Research render obvious claim 1, 16, and 22.
Pertoft teaches repeating the same round of mixing (i.e agitation) and centrifugation as a stepwise method (para 0008) and the round of steps, including adding density adjusting material, can be repeated (para 0017), rendering obvious repeating the steps of agitating the three-phase solution and centrifuging the three-phase solution a plurality of times and adding additional density adjusting material following the steps of agitating and centrifuging, and agitating comprises mechanical agitation. Furthermore, it is noted that repeating rounds of mixing and centrifugation constitutes routine optimization on the part of an artisan of ordinary skill. The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983).
Regarding claim 8, the combined teachings of Tiemeijer and Pertoft render obvious claims 1 and 7.
The combined teachings do not disclose adding the hydrogel materials to a substantially transparent container such that the steps of agitating the three-phase solution and centrifuging the three-phase solution a plurality of times are repeated until hydrogel/suspension media clumps are substantially broken apart based on a visual inspection through the substantially transparent container.
It would have been prima fascie obvious to one of ordinary skill in the art to centrifuge the hydrogel-suspension media mixture repeat the agitation and centrifugation steps until hydrogel/suspension media clumps are substantially broken apart based on a visual inspection through the substantially transparent container. One would be motivated to do so to ensure that the hydrogel/suspension clumps were broken apart as clumps would impede further use of the hydrogels and this would best be achieved through visualization through a transparent container.
Regarding claim 11, 13, and 18, the combined teachings of Tiemeijer and Pertoft render obvious claim 1 and 16. Moreover, Pertoft teaches the density medium should be high density of >1.3 g/mL (para 0019), rendering obvious wherein a density of the density adjusting material is from 1.2 g/mL to 1.4 g/mL and about 1.3 g/mL.
The combined teachings of Tiemeijer and Pertoft do not teach the density adjusting material comprises iodixanol (claim 13).
However, OptiPrep teaches “Density gradient medium for the isolation of viruses, organelles, macromolecules, or cells is a stertile endotoxin tested solution of 60% iodixanol in water with a density of 1.32 g/ml” (page 2, left column).
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to modify the teachings Tiemeijer and Pertoft according to the teachings of OptiPrep to have a density adjusting material comprising iodixanol. One would be motivated in order to have the correct density adjusting material for proper separation of the hydrogel particles and have a reasonable expectation of success.
Regarding claim 14, the combined teachings of Tiemeijer and Pertoft render obvious claim 1. Moreover, Peroft teaches centrifuging 1 to 5 minutes at 10,000 x g” (Page 12, General exemplifying non-limiting description), rendering obvious centrifuging at 7000 RPM for 3 minutes as required in claim 14. Moreover, it is noted that
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since the prior art teaches that the concentration of the gases for the preservation can vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the biotech art.
Regarding claim 19 and 20, the combined teachings of Tiemeijer, Pertoft, and Tasoglu render obvious claims 16.
The combined teachings of Tiemeijer, Pertoft, and Tasoglu do not teach the upper phase once collected comprises a yield of between 0.1 gram and 1 gram of hydrogel particles (claim 19) and the cargo suspension comprises viable cells and the upper phase once collected comprises cell viability of about 93% (claim 20).
Regarding the recitations of “wherein the upper phase comprises a yield of between 0.1 gram and 1 gram of hydrogels” and “the cargo suspension comprises viable cells and the upper phase once collected comprises cell viability of about 93%”, do not provide an active step, and appears to be an inherent effect of the methodology of claim 16. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Regarding claim 24, the combined teachings of Tiemeijer, Pertoft, and Tasoglu render obvious claims 21.
The combined teachings of Tiemeijer, Peroft, and Tasoglu do not teach a preparing the cargo suspension prior to mixing the hydrogel materials, comprising the steps of: growing mammalian cells in a bioreactor until a desired cell number is reached; harvesting the mammalian cells from the bioreactor via an automated centrifuge system; and adjusting a cell concentration of the mammalian cells to a desired cell concentration via the automated liquid handling system.
Growing mammalian cells in a bioreactor, harvesting via an automated centrifuge system and automated liquid handling device would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to use since it provides a replacement to manual labor and would accomplish to increase the yield of hydrogel particles having encapsulated cargo. Motivation to do so would be to increase efficiency and throughput of preparing the cargo suspension (i.e. cells).
Regarding claim 25, the combined teachings of Tiemeijer, Pertoft, and Tasoglu render obvious claims 21.
The combined teachings of Tiemeijer, Peroft, and Tasoglu do not teach washing the hydrogel particles via the liquid handling system.
Using a liquid handling system would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to use since it provides a replacement to manual labor cost and to reduce time and would accomplish the same result washing the hydrogel particles. Motivation to do so would be to increase efficiency and throughput of making hydrogel particles.
Regarding claim 26, the combined teachings of Tiemeijer, Pertoft, and Tasoglu render obvious claims 21.
The combined teachings of Tiemeijer, Peroft, and Tasoglu do not teach observing hydrogel particles having encapsulated cargo via an automated microscope to ensure encapsulation and no clumping of particles.
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to examine hydrogel particles via an automated microscope to ensure correct encapsulation and substantially no clumping of particles for a more accurate evaluation of hydrogel particles produced from the hydrogel mixture. One would be motivated to do so as to ensure the outcome of performing the method was successful.
Response to Applicants’ Arguments as they apply to rejection of claims 1-26 under 35 USC § 103 as it relates to the teachings of Tiemeijer, Martinez, and Pertoft
Applicant's arguments filed 03/16/2026 have been fully considered but have not
been found persuasive in overcoming the rejection for reasons of record as discussed in
detail below.
On page 5-9 of Remarks filed by applicant on 3/16/2026, applicant argues that a prima facie case of obviousness has not been established because 1) the proposed modifications of Martinez, which teaches a microfluidic technique to encapsulate cells in an alginate hydrogel from double emulsion templates, by the teachings of Peroft, which teaches separation methods of biological particles, such as antigen core particles and serum proteins, using ultracentrifugation on a density gradient, render Martinez’s method unsatisfactory for its intended purpose; 2) the ultracentrifugation method of FR 256126, as cited in Pertoft, and the colloidal density gradient by Pertoft would change the principle of operation of using double emulsion and self-separation of alginate drop as recited by Martinez; and 3) the methods of Pertoft and FR 2561356 are substantially different than what is recited in claim 1 and the examiner has failed to explain how the method of Pertoft could move suspension media from hydrogel particles as recited by amended claim 1, therefore a convincing line of reasoning has not been provided without impermissible hindsight.
Regarding argument 1, examiner has withdrawn 103 rejection using Martinez reference and presents a new 103 rejection without the Martinez reference, therefore applicant’s argument related to Martinez reference is moot. The reference Pertoft teaches using phase separation with a density gradient material to isolate substances of interest in a sample. While examiner acknowledges Applicant’s remark that Pertoft teaches their method not be suitable for separation of more delicate biological structures, such as cells, Pertoft does disclose that the method can be “adapted to separate different cell types, such as X- and Y-sperm cells, from each other in a sample on the basis of their buoyant density, shape, permeability, movement, and/or viscosity in a density gradient medium by centrifugation” (para 0025). Moreover, the density adjusting material disclosed by Pertoft can be 1.120 g/mL (para 0035) and up to 1.5 g/mL (para 004), which reads on claim 11 of the instant application which recites the density adjusting material is from 1.2 g/mL to 1.4 g/mL. Furthermore, Pertoft teaches a method of separating desirable substances in a solution (i.e. hydrogel particles in a cargo-compatible solution) from undesirable substances (i.e. suspension media) using a density-gradient material. Therefore, Pertoft teaching a separation method can be adapted for cells and the density adjusting material used falls within the range of density recited in the instant application, one of ordinary skill in the art would be motivated to use the teachings of Pertoft to arrive at a hydrogel generation method with suspension media removal.
Regarding argument 2, applicant is directed to examiners rebuttal to argument 1 above, specifically in regards to the withdrawn rejection pertaining to Martinez reference, therefore applicant’s argument related to Martinez reference is moot.
Regarding argument 3, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Pertoft teaches a method of purification of biological particles using flotation ultracentrifugation on a density gradient and the sample is placed on top of the gradient, which is centrifuged to allow for collection of sample in the top while contaminants have migrated to the lower level of the gradient and that this method can be used for cells. Moreover, as previously mentioned, Pertoft uses a density adjusting material with the same density as the instant application. Therefore, Pertoft teaches that one could use a method which employs density gradient material to separate desirable substances from undesirable substances (i.e. suspension media from hydrogel particles). Overall, since Pertoft teaches a method of separation using density gradient material and there is need to remove/separate suspension media from hydrogel particles when generating hydrogel particles, there is teaching, suggestion, and motivation to use the Pertoft teaching for such application.
Response to Arguments as they apply to rejection of claims 2-15, 22, 23 under 35 USC § 103 as they applied to Tasoglu, CryoPro Hampton Research, and OptiPrep
Applicant's arguments filed 03/16/2026 have been fully considered but have not
been found persuasive in overcoming the rejection for reasons of record as discussed in
detail below.
On page 9-11 of Remarks filed by applicant on 3/16/2026, applicant argues that 1) Tasoglu teaches vortexing which is not appropriate for the claimed invention which is directed to a mixing step that intentionally avoids vortexing, 2) Tiemijer teaches on-chip designs for washing and the present application is not compatible with microfluidics devices or on-chip designs, 3) CryoPro Hampton Research reference is not related to the claimed invention.
Regarding argument 1, while examiner acknowledges that the specification recites avoidance of vortexing, the specification also recites in para 0043 that the mechanical agitation must not be in a non-vertical manner. The process of vortexing is defined as a flow of fluid around an axis line (Wikipedia, page 1, first paragraph, downloaded 4/30/26) in which the flow can occur in a vertical manner. Moreover, claim 2 and 22 recites the term “comprising” indicating other aspects of mixing are included in the claim. And finally, para 0054 in the specification recites that the mechanical agitation can occur with a mechanical mixing device which can be a Scientific Industries GENIE G560 Vortex-Genie 2. Additionally, examiner points out that claims do not recite the limitation of NO vortexing. It is noted that the features upon which applicant relies (i.e., no vortexing) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, examiner presents similar 103 rejection combining Tasoglu art which teaches vortexing for mixing of hydrogel materials.
Regarding argument 2, while applicant acknowledges applicant’s remarks pertaining to Tiemeijer teaching washing for microfluidic devices, examiner directs applicant to Tiemeijer teaching that recovering microgels (i.e. hydrogel particles) is achieved through techniques such as washing which can performed either on-chip or in bulk after droplet collection (page 5, right column, recovery of microgels). Hence, the concept of washing hydrogels from a microfluidics system, wherein the washing which can be achieved on a filter, and resuspending in a storage solution, is applicable in the instantly claimed invention as the amended claims recite “bulk” method.
Regarding argument 3, examiner directs applicant to office action filed 12/16/2026 on page 12 which recites the teachings of CryoPro Hampton Research for teachings incrementally increasing a concentration of a cryoprotectant, which is a type of a storage solution as recited in claim 6. While examiner acknowledges that the teachings of CryoPro Hampton Research pertain to biological macromolecular crystals and not hydrogel particles, the CryoPro does teach repeating the process of washing with higher concentrations of solutions to gradually resuspend a substance in a storage solution in a stepwise manner and the concept would be obvious in combination with Tasoglu and Tiemeijer. It appears that applicant’s arguments are against the references individually and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).Thus, CryoPro Hampton Research renders obvious claim 6 when combined with the teachings of Tasoglu and Tiemeijer.
Response to Arguments as they apply to rejection of claims 17-20 under 35 USC § 103 as they applied to OptiPrep, Tao, and Brooks
On page 12-13 of Remarks filed by applicant on 3/16/2026, applicant argues that a prima facie case of obviousness has not been established because Optiprep, Tao, and Brooks do not teach what is recited in claims 17-20 and one would to be motivated to modify the teachings of Tiemeijer, Pertoft, and Tasoglue based on Brooks teachings.
Examiner has withdrawn the 103-rejection using Tao and Brooks reference and presents a new 103 rejection without the Tao and Brooks reference for claims 17-20, therefore applicant’s argument related to Tao and Brooks reference is moot.
35 USC § 112 (a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new rejection necessitated by amendment of the claims in the response filed 03/16/2026.
Claim 1, 16, and 21 are directed to a bulk method for generating hydrogel particles having encapsulated cargo and removing suspension media from the particles comprising hydrogel materials, wherein the hydrogel materials comprise a polymer, a linker, a cargo suspension, and a suspension media in a container and wherein removing the suspension media comprises adding a density adjusting material and a cargo-compatible solution which is centrifuged, therefore the hydrogel particles can be retrieved without the suspension media. Moreover, claim 16 and 21 are directed to the cargo-compatible solution includes a cargo-compatible surfactant.
The claims broadly encompass any density adjusting material, any cargo-compatible solution, and any cargo-compatible surfactant for use in generating hydrogel particles with suspension media removal. Thus, the claims are directed to a large genus any density adjusting material, any cargo-compatible solution, and any cargo-compatible surfactant for use in generating hydrogel particles with suspension media removal.
There is not structure/function correlation for the claimed genus of density adjusting materials, cargo-compatible solutions, and cargo-compatible surfactants used in methods for generating hydrogel particles and suspension media removal as claimed. Rather, the only structure/function correlation present is use of the density adjusting material Opti-prep (para 0075), the cargo-compatible surfactant pluronic F68 surfactant (para 0073), and the cargo-compatible solution PBS and DMEM (para 0060 and 0069). Thus, the specification only teaches use of the density adjusting material Opti-prep, the cargo-compatible surfactant pluronic F68 surfactant, and the cargo-compatible solution PBS and DMEM. Moreover, the specification does not disclose the density adjusting material, cargo-compatible solution, and cargo-compatible surfactant used in data shown by Fig 3, 4, and 5, further indicating lack of structure/function for using the density adjusting material, cargo-compatible solution, and cargo-compatible surfactant recited by the methods and, thus, lack of possession of the claimed invention.
The specification does not provide guidance or data related to use of any other density adjusting material, cargo-compatible solution, and cargo-compatible surfactant other than Opti-prep, DMEM and PBS, and F86, respectively. It does not disclose if the method would be capable of generating hydrogel particles having encapsulated cargo and removal of the suspension media when using any density adjusting material, cargo-compatible solution, and cargo-compatible surfactant nor does the specification disclose if they would give the same result as using Opti-prep, DMEM and PBS, and F86, respectively. Therefore, it is unclear if the disclosed method will provide the same function as the disclosed invention.
Applicant were referred to the guidelines for Written Description Requirement
published January 5, 2001 in the Federal Register, Vol.66, No.4, pp.1099-1110 (see
http://www.uspto.gov). The disclosure of a single species is rarely, if ever, sufficient to
describe a broad genus, particularly when the specification fails to describe the features
of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue
Pharma L. P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000). The possession may
be shown by actual reduction to practice, clear depiction of the invention in a detailed
drawing, or by describing the invention with sufficient relevant identifying characteristics
(as it relates to the claimed invention as a whole) such that a person skilled in the art
Would recognize that the inventor had possession of the claimed invention. See, e.g.,
Pfaff v. WellsElectronics, Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,
1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai
Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991).
The “written description” requirement may be satisfied by using such descriptive
means as words, structures, figures, diagrams, formulas, etc., that fully set forth the
claimed invention. See Noelle v. Lederman, 355 F.3d 1343, 1349, 69 USPQ2d 1508,
1514 (Fed. Cir. 2004) and Lockwood v. American Airlines, Inc., 107 F.3d at 1572, 41
U.S.P.Q.2d at 1966. A definition by function alone “does not suffice” to sufficiently describe a coding sequence “because it is only an indication of what the gene does,
rather than what it is.” Regents of the University of California v. Eli Lilly & Co., 119 F.3 at
1568, 43 USPQ2d at 1406 (Fed. Cir. 1997) (discussing Amgen Inc. v. Chugai
Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016 (Fed. Cir. 1991)). In Fiers v.
Ravel, 984 F.2d at 1169-71, 25 U.S.P.Q.2d at 1605-06 (1993), the CAFC found that “a
mere wish or plan for obtaining the claimed chemical invention” is not sufficient to
describe a chemical invention (discussed in Eli Lilly at 1404).
In the instant application, the only method disclosed is for a method of generating hydrogel particles having encapsulated cargo and removing suspension media comprising adding the density adjusting material Opti-prep, the cargo-compatible surfactant pluronic F68 surfactant, and the cargo-compatible solution PBS and DMEM. Therefore, the limited disclosure in the specification is not deemed sufficient to reasonably convey to one skilled in the art that the applicants were in possessions of the huge genera recited in the claims at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genera.
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.
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/JULIANA IRENE CANDELARIA/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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