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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/6/2026 has been entered.
Response to Arguments
The arguments filed 2/6/2026 have been fully considered and are partially persuasive.
Regarding claim 1, Applicant argues that the amended claim specifies the method is specifically directed towards creating flow-defined heterogeneity by selecting the precursor solution, the method of infiltration, and controlling the inlet flow rate. Applicant argues that Hasan does not describe the claimed limitations because Hasan’s concentric needles do not create flow-defined heterogeneity or disclose a method of providing for flow-defined heterogeneity. Examiner disagrees. The term “flow-defined heterogeneity” is not specified enough in claim 1 to overcome the Hasan reference. Hasan describes concentric needles or tubes made of different types of hydrogels. These hydrogels are made from flowing different solutions into different inlets. This meets the broadest reasonable interpretation of flow-defined heterogeneity as claimed in claim 1. Since Hasan also selects the precursor solutions and controls the method of infiltrating the solutions and also exhibits flow-defined heterogeneity, Hasan is controlling the heterogeneity via these choices. Hasan does not explicitly mention a flow rate but the polymers are inherently injected at some flow rate.
Hasan does differ, however, from the claimed limitations with respect to dependents claims such as 22-23 and 25. In these claims, the heterogeneity of the hydrogel is more specifically defined with respect to the flow rates or the infiltration methods. Claim 22 specifically links the flow rate to having different regions of different sizes in the hydrogel. This is not taught by the cited references. Claims 23 and 25 specify that there is a secondary region within the main hydrogel region. This differs from Hasan because Hasan describes concentric tubes or cylinders, not a secondary region within the main region. With respect to these claims, the basis of the arguments are convincing and these claims are indicated as containing allowable subject matter, see below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-10. 13-14, and 20-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Knopf (US 2020/0062877) modified by Hasan (A multilayered microfluidic blood vessel-like structure. Biomed Microdevices 17, 88 (2015). See NPL copy previously provided.)
Regarding claim 1, Knopf meets the claimed, A method for generating three-dimensional (3D) hydrogels, (Knopf Example 7 [0343]-[0346] describes making hydrogels) the method comprising: generating a fluidic mold; (Knopf [0343] describes 3D printing a microfluidic mold) wherein the fluidic mold comprises at least one inlet, (Knopf [0344] describes adding a solution to a mold, therefore the mold necessarily has an inlet) infiltrating the fluidic mold with a precursor solution; (Knopf [0344] describes adding a PVA solvent mixture) gelatinizing the precursor solution; (Knopf [0344] describes the process of forming a hydrogel from the solvent mixture) and degrading the fluidic mold in a degradation solution to release a 3D hydrogel (Knopf [0344]-[0345] describes soaking the molds in water to dissolve them.)
Knopf describes inlets but not necessarily inlets where the material flows into the mold to provide heterogeneity and does not meet the claimed, wherein the precursor solution flows into the fluidic mold via the at least one inlet providing for flow-defined heterogeneity to a 3D hydrogel and wherein the flow-defined heterogeneity of the 3D hydrogel is achieved using a programmed infiltration by (1) selecting of the precursor solution, (2) selecting of a method of infiltration, and (3) controlling an inlet flow rate associated with the precursor solution.
Analogous in the field of hydrogel molding, Hasan meets the claimed, wherein the fluidic mold comprises at least one inlet, (Hasan Section 2.5 and Figure 1 show multiple inlets on the mold, the ends of the concentric needles) wherein the precursor solution flows into the fluidic mold via the at least one inlet providing for flow-defined heterogeneity to a 3D hydrogel (Hasan Section 2.5 describes multiple solutions are added to the inlets of the mold, the multiple solutions would provide some degree of flow heterogeneity) and wherein the flow-defined heterogeneity of the 3D hydrogel is achieved using a programmed infiltration by (1) selecting of the precursor solution, (2) selecting of a method of infiltration, and (3) controlling an inlet flow rate associated with the precursor solution (Hasan Section 2.5 describes selecting solutions and adding the solutions via the inlets. The flow rate of the solution is necessarily controlled when the solutions are added.)
It would have been obvious to a person of ordinary skill in the art before the filing date to combine the method of Knopf with the inlets and providing for flow heterogeneity as described in Hasan in order to provide different solutions having different functions to create a tri0layered architecture, see Hasan Section 1.
Regarding claim 2, Knopf meets the claimed, The method of claim 1, wherein the fluidic mold is generated using a 3D printing process (Knopf [0343] describes 3D printing a microfluidic mold.)
Regarding claim 3, Knopf meets the claimed, The method of claim 2, wherein the 3D printing process is 3D stereolithography (Knopf [0343] describes SLA, stereolithography.)
Regarding claim 4, the embodiment in Knopf Example 7 uses a variety of compositions for the sacrificial mold but does not explicitly describe ABS. Knopf does disclose ABS in order embodiments and meets the claimed, The method of claim 2, wherein the 3D printing process utilizes acrylonitrile butadiene styrene (ABS) resin (Knopf [0237] describes the sacrificial molds can be made of ABS.)
The courts have held that substituting one known prior art element for another according to known methods to yield predictable results would have been obvious to a person of ordinary skill in the art before the filing date, see MPEP §2143. It would have been obvious to a person of ordinary skill in the art before the filing date to substitute the compositions used for the mold as described in Example 7 with another composition such as ABS as described in the other portions of Knopf with a reasonable expectation of successfully creating a mold, see Knopf [0237] and [0343].
Regarding claim 5, Knopf meets the claimed, The method of claim 1 further comprising pretreating the fluidic mold with a surfactant prior to infiltration (Knopf [0343] describes post-print cleaning as described in examples 1-3 which includes cleaning using a number of solvents [0327] including acetone, diethyl ether, ethanol, ethyl acetate, etc.)
Regarding claim 6, Knopf meets the claimed, The method of claim 1, wherein the selecting of the precursor solution for the flow-defined heterogeneity of the 3D hydrogel comprises selecting a natural or synthetic solution (Knopf [0344] describes creating the solution therefore the solution is synthetic.)
Regarding claim 7, Knopf does not disclose a doped pre-polymer solution for the hydrogel and does not meet the claimed, The method of claim 1, wherein the precursor solution is doped using nanomaterials or biomolecules.
Hasan also described the formation of hydrogels on microfluidic molds and meets the claimed, The method of claim 1, wherein the precursor solution is doped using nanomaterials or biomolecules (Hasan 2.5 describes a fibroblast cell laden pre-polymer solution.)
It would have been obvious to a person of ordinary skill in the art before the filing date to substitute or combine the solvent mixture described in Hasan with the fibroblast laden pre-polymer solution as described in Hasan in order to provide blood vessel capillary-like structures, see Hasan Section 1.
Regarding claim 8, Knopf meets the claimed, The method of claim 1, wherein the degradation solution is a water-miscible solvent (Knopf [0344] describes water, [0216] describes other aqueous solvents.)
Regarding claim 9, Knopf Example 7 does not explicitly meet the claimed, The method of claim 1, wherein degrading the fluidic mold further comprises adjusting a temperature associated with the degradation of the fluidic mold to minimize concentration of the degradation solution or exposure time to the degradation solution, however Knopf discloses elsewhere that the temperature affects the dissolution of the mold. Knopf [0216] describes the dissolution can be controlled by adjusting the temperature.
It would have been obvious to a person of ordinary skill in the art before the filing date to combine the process disclosed in Knopf Example 7 with the step of controlling the temperature as described in Knopf [0216] in order to control the degradation of the mold, see Knopf [0216].
Regarding claim 10, Knopf does not explicitly meet the claimed, The method of claim 1, wherein the 3D hydrogel is released with minimal to no change to the 3D hydrogel's basic physical behavior, however, Knopf [0244] describes dissolving the sacrificial mold to leave to hydrogel and [0015] describes the reagents used during dissolution should not be incompatible with physical properties of the object being molded (hydrogel) that would lead to undesired behaviors. Therefore, it would have been obvious to a person of ordinary skill in the art before the filing date to remove the hydrogel from the sacrificial mold without altering the behavior of the hydrogel, see Knopf [0015].
Regarding claim 13, Knopf meets the claimed, The method of claim 1, wherein the fluidic mold further comprises at least one outlet (Knopf [0236] describes the microfluidic sacrificial mold has inlets and outlets.)
Knopf does not describe the method of adding the solution as and wherein the selecting of the method of infiltration for flow-defined heterogeneity of the 3D hydrogel comprises selecting a diffusion method of infiltration where the precursor solution enters via the at least one inlet and exits via the least one outlet.
Hasan meets the claimed, and wherein the selecting of the method of infiltration for flow-defined heterogeneity of the 3D hydrogel comprises selecting a diffusion method of infiltration where the precursor solution enters via the at least one inlet and exits via the least one outlet. (Hasan Section 2.5 describes at least one HUVEC pre-cursor solution is flowed through an inlet and out an outlet of the microfluidic mold.)
It would have been obvious to a person of ordinary skill in the art before the filing date to substitute the method of adding the hydrogel solution into the mold as described in Knopf with the method of flowing the precursor solution through the inlet and outlet as described in Hasan in order to form a monolayer of the cells on the wall, see Hasan Section 2.5.
Regarding claim 14, Knopf meets the claimed, the selecting of the precursor solution for flow-defined heterogeneity of the 3D hydrogel comprises selecting a first precursor solution and a second precursor solution (Knopf [0344] describes adding multiple different hydrogel materials to the molds).
Kopf only describes one inlet where material flows into the mold and does not meet the claimed, The method of claim 1, wherein at least one inlet comprises a first inlet and a second inlet.
Hasan meets the claimed, The method of claim 1, wherein the at least one inlet comprises a first inlet and a second inlet (Hasan Figure 1 shows the media is pipetted in at the ends of the needles, the space at the ends of the needles being the inlets).
It would have been obvious to a person of ordinary skill in the art before the filing date to combine the method of Knopf with the multiple inlets as described in Hasan in order to provide different solutions having different functions to create a tri0layered architecture, see Hasan Section 1.
Regarding claim 19, Knopf meets the claimed, The method of claim 1, wherein the 3D hydrogel is programmed for function including motion/mechanics, temperature/light interactivity, or gradient behavior (Knopf [0343] describes a microfluidic mold meaning the hydrogel molded therein is programmed for microfluidic motion/mechanics.)
Regarding claim 20, Knopf meets the claimed, The method of claim 1, wherein the 3D hydrogel is multi-material and (Knopf [0344] describes multiple materials) multi- functional, (Knopf [0250] describe multiple functions of the microfluidic device made by the hydrogel in Example 7).
Regarding claim 21, Kopf meets the claimed, The method of claim 14, wherein the selecting of the method of infiltration for flow-defined heterogeneity of the 3D hydrogel comprises selecting a co-flow method of infiltration, (Knopf [0344] describes adding multiple different hydrogel materials to the molds).
Knopf does not describe that the second precursor is added wherein the co-flow method includes co-flowing the first precursor solution via the first inlet and the second precursor solution via the second inlet.
Hasan meets the claimed, wherein the co-flow method includes co-flowing the first precursor solution via the first inlet and the second precursor solution via the second inlet. (Hasan Section 2.5 and Figure 1 show the different solutions are pipetted in to different locations at different inlets.)
It would have been obvious to a person of ordinary skill in the art before the filing date to combine the method of Knopf with the multiple materials being added through multiple inlets as described in Hasan in order to provide different solutions having different functions to create a tri0layered architecture, see Hasan Section 1.
Regarding claim 24, Kopf does not describe a third solution and does not meet the claimed, The method of claim 14, wherein the selecting of the precursor solution for flow-defined heterogeneity of the 3D hydrogel comprises further selecting a third precursor solution.
Hasan further meets the claimed, The method of claim 14, wherein the selecting of the precursor solution for flow-defined heterogeneity of the 3D hydrogel comprises further selecting a third precursor solution (Hasan Section 2.5 describes the HUVEC cells are added in the same area that the second pre-polymer solution was added.) It would have been obvious to a person of ordinary skill in the art before the filing date to combine the method of Knopf with the step of adding the third solution in the second inlet as described in Hasan in order to add additional monolayer of HUVEC media on the inner surface, see Hasan Section 2.5
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Liu (US 2010/0056740)
Regarding claim 11, Knopf does not disclose the claimed materials and does not meet the claimed, The method of claim 1, wherein the selecting of the precursor solution for flow-defined heterogeneity of the 3D hydrogel comprises selecting polyacrylamide (PAAm), poly(n-isopropylacrylamide) (PNIPAAm), or calcium alginate (Ca-ALG).
Analogous in the field of hydrogels, Liu [0009] discloses prior art which uses microfluidic networks made of a calcium alginate hydrogel and meets the claimed, The method of claim 1, wherein the selecting of the precursor solution for flow-defined heterogeneity of the 3D hydrogel comprises selecting polyacrylamide (PAAm), poly(n-isopropylacrylamide) (PNIPAAm), or calcium alginate (Ca-ALG).
It would have been obvious to a person of ordinary skill in the art before the filing date to substitute the materials of Knopf with the calcium alginate of Liu in order to provide biocompatible properties to the microfluidic device.
Allowable Subject Matter
Claims 22-23 and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 22, neither Knopf nor Hasan meet the claimed, The method of claim 21, wherein the controlling the inlet flow rate for flow- defined heterogeneity of the 3D hydrogel comprises co-flowing the first precursor solution via the first inlet at a first inlet flow rate and the second precursor solution via the second inlet at a second inlet flow rate, wherein the difference in the first and second inlet flow rates create hydrogel regions of different sizes within the 3D hydrogel. Knopf does not disclose a relationship between the flow rate and the size of the hydrogel. Additionally, although Hasan discloses multiple precursor solutions and creating different areas having different hydrogels, Hasan also does not disclose multiple different flow rates or the relationship between flow rate and the size of the hydrogel. Neither Knopf nor Hasan describe creating different regions of different sizes within the same 3D hydrogel.
Regarding claim 23, neither Knopf nor Hasan meet the claimed, wherein the flow of the first precursor solution via the first inlet creates a main hydrogel region within the 3D hydrogel and the sequential flow of the second precursor solution via the second inlet creates a secondary hydrogel region within the main hydrogel region.
Hasan Section 2.5 describes a sequential flow method where the first pre-polymer is added to an annular gap between the needle and capillary first and then a second step of adding the second pre-polymer solution where the previous needle was. By this disclosure, Hasan describes the first half of the claim, The method of claim 14, wherein the selecting of the method of infiltration for flow-defined heterogeneity of the 3D hydrogel comprises selecting a sequential flow method of infiltration, wherein the sequential flow method includes flowing the first precursor solution via the first inlet and then sequentially flowing the second precursor solution via the second inlet.
Hasan does not describe creating a main hydrogel region and a secondary hydrogel region within the main hydrogel region. As per Hasan Figure 1, the pre-polymers do create two different regions within the product but these regions are in the shape of concentric tubes or cylinders. Claim 23 refers to the sequential flow of the second precursor solution via the second inlet creates a secondary hydrogel region within the main hydrogel region meaning the secondary region should be within the first region, not merely concentric to it. Therefore, Hasan does not meet the claimed wherein the flow of the first precursor solution via the first inlet creates a main hydrogel region within the 3D hydrogel and the sequential flow of the second precursor solution via the second inlet creates a secondary hydrogel region within the main hydrogel region. Claim 23 contains allowable subject matter. Examiner notes that claim 23 specifies a sequential flow style using two precursor solutions and two inlets which may conflict with other claims using different flow styles such as 21-22 and 25.
Similarly with respect to claim 25, The method of claim 24, wherein the selecting of the method of infiltration for flow-defined heterogeneity of the 3D hydrogel comprises selecting a consecutive flow method of infiltration, wherein the consecutive flow method includes: flowing the first precursor solution via the first inlet; flowing the second precursor solution via the second inlet; and consecutive flowing the third precursor solution via the second inlet; and wherein the first precursor solution creates a primary hydrogel region within the 3D hydrogel, the second precursor solution creates a first secondary hydrogel region within the 3D hydrogel, and the third precursor solution creates a second secondary hydrogel region within the 3D hydrogel, the claim requires three precursors being flowed into two different inlets. While Hasan teaches three precursors, Hasan does not describe wherein the first precursor solution creates a primary hydrogel region within the 3D hydrogel, the second precursor solution creates a first secondary hydrogel region within the 3D hydrogel, and the third precursor solution creates a second secondary hydrogel region within the 3D hydrogel. As described previously, the hydrogels in Hasan are concentric cylinders rather than one main hydrogel area with a plurality of regions within that main hydrogel. Therefore, claim 25 is allowable. Examiner notes that claim 25 specifies a consecutive flow style using two precursor solutions and two inlets which may conflict with other claims using different flow styles such as 21-22 and 23.
Conclusion
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/V.B./Examiner, Art Unit 1744
/XIAO S ZHAO/Supervisory Patent Examiner, Art Unit 1744