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 .
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, 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.
Claim(s) 1 and 8-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (“Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions”, 2016, from IDS) in view of Occhetta et al. (“Fabrication of 3D cell-laden hydrogel microstructures through photo-mold patterning”, 2013.
Regarding claim 1 Li et al. discloses a system and kit for applying mechanical stimuli to a hydrogel-based construct or culturing a cell or tissue embedded in a hydrogel-based construct, comprising: a hydrogel-based construct, wherein the hydrogel-based construct comprises a main body and at least one arm extending from the main body with cells embedded therein and carrying magnetic beads at a free end of the arm; The arm anchored at an anchoring point to a constrained layer. (See Li Abstract and Figs 1-2 wherein a hydrogel-based construct has a main body and arms extending therefrom with cells embedded therein. The arms have magnetic particles, i.e. beads, at the free end thereof.) and a magnetic attraction force-producing device configured to cyclically apply magnetic attraction force to the magnetic beads at the free end of the arm. (See Li Abstract and Figs. 1-2 wherein a magnet mounted on a stage is provided to move relative to the hydrogel-based construct and cyclically apply magnetic attractive force to the magnetic beads.)
Li et al. discloses utilizing photolithography and providing masks to form the device and not molds with concaves.
Occhetta et al. discloses a device and method for forming hydrogel constructs having cells embedded therein wherein a mold for forming and shaping the hydrogel construct is provided with concaves conforming the desired shape of the hydrogel construct. (See Occhetta Abstract Pg. 1-2 Introduction, and Fig. 1 wherein a mold having concaves conforming to the shape of the cell embedded hydro-gel construct to be formed is provided.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide a mold having concaves conforming to the shape of the hydrogel construct to be formed as described by Occhetta et al. in the system of Li et al. because such molds allow the use of low cost alternatives to photolithography techniques and improve cell viability in such constructs as would be desirable in the system of Li et al.
It is noted that the mold of modified Li has the predetermined size and scale and is such that it is loaded with hydrogel, cells, and magnetic beads to form the device as described by Li.
Additionally assuming arguendo with respect to the shape of the mold it is noted that one of ordinary skill in the art at the time of invention would recognize a mold is to be shaped having concaves conforming to the dimensions of all parts of the device to be formed and such a modification would have required a mere change in shape of the mold concaves to fit the hydrogel-based construct which would have been obvious to one of ordinary skill in the art at the time of filing because the change in configuration of shape of a device is obvious absent persuasive evidence that the particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
Assuming arguendo with respect to the magnetic particles being in the shape of a bead it is noted that such a modification would have required a mere change in shape of the particle in order to optimize placement within the hydrogel and because the change in configuration of shape of a device is obvious absent persuasive evidence that the particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
Regarding claim 8-9 modified Li discloses all the claim limitations as set forth above as well as the device wherein the mold is formed of polydimethylsiloxane (PDMS). (See Occhetta Abstract and Fig. 1 wherein the molds are formed from PDMS.)
Regarding claim 10 modified Li discloses all the claim limitations as set forth above as well as the device wherein the main body concave and/or the arm concave has the same shape and effect as a mold that is formed using a soft-lithography method and/or 3D printing.
It is noted that such limitations are directed to methods of production and is a product-by-process claim. The examiner notes that the determination of patentability is determined by the recited structure of the apparatus and not by a method of making said structure. A claim containing a recitation with respect to the manner in which a claimed apparatus is made does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim.
Regarding claim 11 modified Li discloses all the claim limitations as set forth above as well as the device wherein the hydrogel-based construct is formed from a material selected from the group consisting of Gelatin Methacryloyl (GelMA), collagen, poly(ethylene glycol) diacrylate (PEGDA), methacrylated hyaluronic acid (MeHA), methacrylated chondroitin sulfate, methacrylamide chitosan (MAC), Methacrylated alginate, methacrylate and lysine functionalized dextran (Dex-MA-Ly), methacrylated gellan gum, methacrylated glycol chitosan (MeGC), Poly(ethylene oxide) (PEO), and/or poly(ethylene glycol) (PEG). (See Li Page 2 wherein the hydrogel is GelMA)
Regarding claim 12 modified Li discloses all the claim limitations as set forth above as well as the device wherein the system is for culturing the cells, tissues, or a combination of cells and tissues embedded in the hydrogel-based construct. (See Li Abstract wherein the device is for culturing cells embedded in the hydrogel-based construct)
Regarding claim 13 modified Li discloses all the claim limitations as set forth above as well as the device wherein the cell or tissue is embedded in the arm of the hydrogel-based construct. (See Li Pg. 2 wherein cells are mixed with the hydrogel which forms the arm and thus are embedded therein.)
Regarding claim 14 modified Li discloses the system wherein various cells are tested but does not specify all types of cells which may be utilized in the device.
Occhetta discloses a system comprising a hydrogel with cells embedded therein for the purposes of growing and testing said cells wherein said cells comprise a bone marrow derived stem cell (BMSC). (See Occhetta Abstract and Pg. 3 where BMSCs are grown and tested in a molded hydrogel.)
It would have been obvious to one of ordinary skill in the art at the time of filing to embed BMSC cells in the hydrogel for testing of Li as described by Occhetta because such cells are known to be grown in hydrogel constructs such as those described by Li and such cells represent and area of study and the use thereof in the device of Li would have been desirable for said study and one would have had a reasonable expectation of success in studying such cells in the device of Li.
Claim 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (“Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions”, 2016, from IDS) and further in view of Lee et al. (US 2021/0040427).
Regarding claim 15 Li et al. discloses a system for applying mechanical stimuli to a hydrogel-based construct or culturing a cell or tissue embedded in a hydrogel-based construct, comprising: a hydrogel-based construct, wherein the hydrogel-based construct comprises a main body and at least one arm extending from the main body and carrying magnetic beads at a free end of the arm; The arm anchored at an anchoring point to a constrained layer(See Li Abstract and Figs 1-2 wherein a hydrogel-based constrict has a main body and arms extending therefrom. The arms have magnetic particles, i.e. beads, at the free end thereof.) and a magnetic attraction force-producing device configured to cyclically apply magnetic attraction force to the magnetic beads at the free end of the arm. (See Li Abstract and Figs. 1-2 wherein a magnet mounted on a stage is provided to move relative to the hydrogel-based construct and cyclically apply magnetic attractive force to the magnetic beads.)
Assuming arguendo with respect to the magnetic particles being in the shape of a bead it is noted that such a modification would have required a mere change in shape of the particle in order to optimize placement within the hydrogel and because the change in configuration of shape of a device is obvious absent persuasive evidence that the particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
In regards to the electromagnet causing 10-45% elongation under tensile strain it is noted that Li appears to disclose such elongation of the hydrogel based construct. (See Fig. 2d where the hydrogel based construct elongates by at least 10% when provided with magnetic attractive force based on the scale image.)
Furthermore it is noted that limitations directed to cyclical activating and deactivating as well as elongation of the hydrogel under tensile strain it is noted that such limitations are directed to intended uses of the claimed device which do not define structural elements which differentiate the claimed invention from the cited prior art as the cited prior art is fully capable of cycling the magnet by moving it and producing such elongation by adjusting magnet distance and/or strength. See MPEP 2114 and 2115.
Claims 2-4, 6-7, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (“Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions”, 2016, from IDS) in view of Occhetta et al. (“Fabrication of 3D cell-laden hydrogel microstructures through photo-mold patterning”, 2013) as applied to claims above and further in view of Liu et al. (CN 110484444)
Regarding claims 2 modified Li discloses all the claim limitations as set forth above as well as the device wherein the magnet is moved relative to the hydrogel-based construct but does disclose the specific magnet or actuation of the magnet.
Liu et al. disclose a device for applying stimuli to cell constructs wherein a magnetic attraction force-producing device is a rail slider comprising: a rail, a permanent magnet/electromagnet disposed on the rail, and a platform disposed on the rail for holding the cell construct, wherein at least one of the permanent magnets/electromagnet and the platform is configured to cyclically move towards the other, thereby cyclically applying magnetic attraction force to the cell construct. (See Liu Abstract, Fig. 2b wherein a cell contract 3 is held on a platform 21 connected to a screw rail 64 and a magnet platform 6 holding permanent magnet 61 are provided on said rail to move relative to the cell construct and apply magnetic force thereto.)
It would have been obvious to one of ordinary skill in the art to provide a magnet attraction force-producing device as described by Liu in the system of modified Li because such a device allows the controlled and automatic application of magnetic force as would be desirable in the system of modified Li.
Regarding claims 7 and 30 modified Li discloses all the claim limitations as set forth above as well as a magnet and a platform for holding the hydrogel-based constructs and also discloses that the magnet may be an electromagnet (See Lui Abstract and [0090]-[0093] wherein the magnet 61 may be an electromagnet)
Lui does not specifically disclose a controller configured to cyclically activate and deactivate the magnet and apply magnetic force but it is noted that such a modification would have required merely automating a manual process, i.e. activating and deactivating an electromagnet, which would have been obvious to one of ordinary skill in the art at the time of filing to reduce manual labor and because since it has been held that broadly providing a mechanical or automatic means to replace manual activity which has accomplished the same result involves only routine skill in the art. In re Venner, 120 USPQ 192 (CCPA 1958); In re Rundell, 9 USPQ 220 (CCPA 1931).
Regarding claims 3-4 and 6 modified Li discloses all the claim limitations as set forth above as well as the device wherein the rail slider further comprises a controller configured to control an operation parameter of the rail slider wherein the operation parameter of the controller configured to control the rail slider is a minimal distance between the permanent magnet and the free end of the arm when at least one of the permanent magnets and the platform moves towards the other, a moving speed of the permanent magnet and/or the platform, or a cycle period. (See Liu Figs. 1a and 3a-3b wherein a controller, i.e. stepper motor 65, controls the speed, distance, and cycle period of the permanent magnet.)
Response to Arguments
Applicant's arguments filed 5/20/2026 have been fully considered but they are not persuasive.
Applicant argues that “Li et al fails to disclose essential limitations of amended claim 1. For example, Li et al does not disclose the following features as a whole:
(i) a mold for loading components including hydrogel, cells, and magnetic beads, and shaping the hydrogel-based construct to a predetermined size and scale;
(ii) a mold having a main body concave and an arm concave;
(iii) cells or tissues embedded inside the arm of the hydrogel construct;
(iv) the hydrogel anchored to an anchoring point;
(v) controllable cyclic tensile strain provided by programmed cyclic magnetic actuation; and
(vi) 10-45% elongation under tensile strain that directly deforms the embedded cells.”
In regards to (i) and (ii) is noted that Li was not cited to have the claimed mold but additional art was relied upon for such features.
In regards to (iii) the examiner specifically pointed out where Li discloses cells embedded in the hydrogel. Li discloses in Fig. 1 and elsewhere that a hydrogel GelMa layer “encapsulates” cells and such encapsulated cells are embedded in the said hydrogel which encapsulates them. Furthermore such limitations are related to intended uses of the device as the claims are merely directed to a mold which may for such an embedded cell hydrogel and the claims do not require the hydrogel having such cells.
In regards to (iv) the examiner specifically pointed out that Li teaches the arms anchored to an anchoring point, i.e. a constrained layer as shown in Fig. 1.
In regards to (v) the examiner specifically pointed out where a controlled the cyclic strain was applied and the claims do not require “programmed cyclic magnetic actuation” and such a specific structure and arguments relating thereto are not commensurate in scope with the claim language.
In regards to (vi) the claims are directed to a system which does not yet have a hydrogel construct but instead has a mold for forming such construct and thus the magnetic atraction device of Li is fully capable of providing such elongation under tensile strength of a construct which may be hypothetically formed using the mold.
In general applicant’s arguments are related to the hypothetical construct which may be formed and acted upon and not to the claims which merely require a mold which may form a construct which may be elongated using cyclic magnetic force.
Applicant also argues “Occhetta et al fails to cure the deficiencies of Li et al and provides no teaching or suggestion to arrive at the instantly claimed invention. Occhetta et al is directed solely to hydrogel fabrication using photo-mold patterning. Occhetta et al does not disclose magnetic actuation, cyclic tensile loading, a main-body-and-arm structure, cells embedded in an arm, cyclic mechanical stimulation, or a mold configured to load hydrogel, cells, and magnetic beads together. Occhetta et al is irrelevant to mechanical actuation and provides no motivation to combine with Li et al.”
It is noted that Occhetta was cited to show the use of providing molds for forming hydrogel shapes having cells and that such is obvious because it reduces costs. Occhetta was not cited to show the specific hydrogel construct formed and thus such arguments are not persuasive.
In response to applicant's arguments against the references individually, 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).
Applicant also argues in reference to claim 15 that “Li et al does not disclose the following features as a whole:
(i) cells embedded inside the arm;
(ii) the hydrogel anchored to an anchoring point;
(iii) controllable cyclic tensile strain of 10-45%; and
(iv) elongation of the arm to deform embedded cells.”
In regards to (i) the examiner specifically pointed out where Li teaches cells embedded in the arm. Li discloses in Fig. 1 and elsewhere that a hydrogel GelMa layer “encapsulates” cells and such encapsulated cells are embedded in the said hydrogel which encapsulates them.
In regards to (ii) the he examiner specifically pointed out that Li teaches the arms anchored to an anchoring point, i.e. a constrained layer as shown in Fig. 1.
In regards to (iii) and (iv) the examiner specifically pointed out that Li in Fig. 2d where the hydrogel based construct elongates by at least 10% when provided with magnetic attractive force based on the scale image. The examiner also explicitly noted why such limitations, i.e. deformation and elongation, are directed to intended uses of the device and why the device is so fully capable. The applicant provides no argument explaining why the examiner is in error but mere argues such isn’t taught.
Applicant alos argues “Lee et al is fundamentally different and teaches away from the present invention,
because Lee et al relates to a magnetically actuated cantilever bending device for 2D cell culture and uses out-of-plane bending, not tensile stretching. Lee et al involves cells seeded on a surface instead of being embedded in 3D hydrogel. Lee et al explicitly prefers ECM coatings and teaches away from bulk hydrogels. Lee et al does not disclose one or more of the features such as a main- body-and-arm construct, anchored hydrogel, and 10-45% tensile strain.
Combination of Li et al and Lee et al fails to establish obviousness. Even if combined, Li et al and Lee et al do not disclose all the recited features as a whole, including the integrated system with an anchored hydrogel construct, cells embedded in the arm, and magnetically controlled cyclic tensile strain of 10-45%.
The cited references, singly or combined, do not teach all the claim limitations. Withdrawal of the rejection is appropriate and respectfully requested.
It is noted that Lee was not relied on for any teachings argued by applicant and as such arguments related to the teachings of Lee are moot. Additionally the examiner explained that elongation and deformation as well as the amounts thereof are related to intended uses of the device which do not structurally differentiate the claimed invention from the cited prior art. The applicant has provided no explanation as to why the examiner’s interpretation of the art and assertions are in error but merely states the art does not explicitly teach such features. As such without further explanation as to why the examiner’ citations and interpretation of the art are specifically in error the arguments are not persuasive.
Conclusion
THIS ACTION IS MADE FINAL. 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 JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONATHAN M HURST/ Primary Examiner, Art Unit 1799
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