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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/4/2025 has been entered.
Claim Rejections - 35 USC § 112
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 7 is 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.
Claim 7 recites the limitation "the electromagnet". There is insufficient antecedent basis for this limitation in the claim.
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; (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.
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; (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 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.)
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).
Response to Arguments
Applicant's arguments filed 12/4/2025 have been fully considered but they are not persuasive.
Applicant argues that “The primary reference Li teaches adjustment of magnetic force by controlling magnet movement via a displacement stage to simulate different biomechanical conditions, and this adjustment taught by Li is a one-time sustained strain operation (see Li page 2, left column, 1st paragraph and right column 2nd paragraph) rather than a dynamic, cyclical process, so one of the distinguishing features of the amended claim 1 resides in the device providing controllable cyclical tensile strain to the cell or tissue that is embedded in the arm of the hydrogel-based construct.”
It is noted that the system of Li does in fact disclose cyclic application of controlled magnetic force and not just a single application. See Li Pg. 2 2nd paragraph which states “magnetic loading was applied to each sample 10h per day”. The devices and cells are cultured for multiple days and thus the magnetic force is cycled on on off to apply such a force each day. Furthermore even assuming arguendo with respect to such features it is noted that such limitations are directed to intended uses of the claimed device. The device of Li is fully capable of being cycled in a controlled manner if one so wished and there is no claimed structural difference between the magnetic attraction force device claimed and the prior art.
Applicant also argues that “ Occhetta and Lee fail to rescue the deficiency of Li. None of the cited references teaches a system with such a structure which may make the cells and/or tissues embedded in hydrogel to achieve 10-45% elongation under cyclical tensile strain as claimed by the amended claim 1. For example, Lee taught: 1) deflection of a cantilever so that the cantilever is deflected out of plane; 2) the cells were seeded on extracellular matrix (ECM) protein (e.g., fibronectin fibril) rather than embedded in hydrogel (see Lee Figs.5A-5C; paragraphs [0052] and [0080]). Furthermore, Lee suggests the use of ECM protein and also appears to teach away from using hydrogel (see Lee paragraphs [0009], [0049], and [0052]). It is improper to combine references where the references teach away from their combination. In re Grasselli, 713 F.2d 731, 743, 218 USPQ 769, 779 (Fed. Cir. 1983). Overall, the cited references do not teach all the claim limitations. Thus, the amended claims 1 and 15 are non-obvious over the cited references. The other claims are also non-obvious over the cited references at least for the same reason. Withdrawal of the rejection is appropriate and respectfully requested. “
It is noted that Lee is not utilized to reject the claims and as such applicant’s arguments with respect to such a reference are moot.
Conclusion
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