DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, presently claims 1-6, 18, 22-27, 31, 36, and 38, in the reply filed on 6/08/2026 is acknowledged.
Claims 51, 53, 54, and 59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/08/2026.
Claims 1-6, 18, 22-27, 31, 36, and 38 are under consideration on the merits.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-6, 18, 22-26, 31, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dang et al. (WO 2020/204829; provided in the IDS dated 4/29/2024).
Dang teaches a method of making a device comprising a gelatin methacrylate (GelMA) hydrogel matrix, a first chamber in the hydrogel matrix, the hydrogel matrix being derived from a prepolymer and the first chamber being perfusable, and a waffle-like mold the method comprising: blocking a first portion of a pre-polymerization solution with a first photomask, the pre- polymerization solution comprising the prepolymer, such that the pre-polymerization solution comprises an exposed portion and a first blocked portion; and irradiating the exposed portion of the pre-polymerization solution and the first photomask with ultraviolet radiation for 19 seconds, the first photomask being substantially opaque to the electromagnetic radiation; wherein the prepolymer within the exposed portion of pre-polymerization solution photopolymerizes to form the hydrogel matrix and the prepolymer within the first blocked portion does not photopolymerize and forms the first chamber, removing the photomask, and rinsing the hydrogel (Examples 7 and 8, and Fig. 12 with each square microwell each being a chamber capable of perfusion), anticipating claims 1, 3-6, 31, and claim 36. Dang teaches further adding alginate and BaCl2 as a crosslinker of alginate (Example 7), anticipating claim 18 and the embodiment of alginate as an additional component of claim 22, the embodiment of alginate as a monomer, prepolymer, and chemical agent of claim 23, and the embodiment of alginate as a natural or biological prepolymer for claim 24, and the embodiment of a hydrogel derived from collagen (i.e. gelatin) for claim 25, and claim 26.
Claims 1, 3-6, 18, 22-24, 26, 31, and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iwase et al. (Journal of Robotics and Mechatronics (2013), 25(4), 682-689; provided in the IDS dated 12/10/2015).
Iwase teaches a method of making a device comprising a propylene glycol alginate (PGA) and sodium alginate (NaA) hydrogel matrix, a first chamber in the hydrogel matrix, the hydrogel matrix being derived from a prepolymer and the first chamber being perfusable, and a lattice-like mold the method comprising: blocking a first portion of a pre-polymerization solution with a first photomask, the pre- polymerization solution comprising the prepolymer, such that the pre-polymerization solution comprises an exposed portion and a first blocked portion; and irradiating the exposed portion of the pre-polymerization solution and the first photomask with ultraviolet radiation, the first photomask being substantially opaque to the electromagnetic radiation; wherein the prepolymer within the exposed portion of pre-polymerization solution photopolymerizes to form the hydrogel matrix and the prepolymer within the first blocked portion does not photopolymerize and forms the first chamber, removing the photomask, and rinsing the hydrogel (subheading 2.3 and Fig. 2 and Fig. 3, with each square microwell each being a chamber capable of perfusion), anticipating claims 1, 3-5, and 31, the embodiment of PGA as a synthetic hydrogel of claim 6, the embodiment of alginate as an additional component of claim 22, the embodiment of alginate as a monomer, prepolymer, and chemical agent of claim 23, and the embodiment of alginate as a natural or biological prepolymer for claim 24, and claim 26. Iwase teaches further adding CaCl2 as a crosslinker of alginate (subheading 2.3), anticipating claim 18. Iwase teaches that the lattice-shaped chambers retain at least 50% of their shape after two days of culturing with mammalian cells (Fig. 6 and subheading 3.3), anticipating the embodiment of at least 50% shape fidelity of claim 38.
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.
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 1-6, 18, 22-26, 31, 36, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Dang et al. (WO 2020/204829; provided in the IDS dated 4/29/2024). in view of Hribar et al. (US 2018/0011408; Reference A).
The teachings of Dang are relied upon in rejecting claims 1, 3-6, 18, 22-24, 26, 31, and 36 as anticipated under 35 U.S.C. § 102. The waffle-like mold and subsequent microtissue pattern of Dang as relied upon above reads in-part on the second chamber being perfusable and fluidly independent in the hydrogel matrix of claim 2 (e.g. each square microwell being a chamber). Dang further teaches changing the designs of the photomasks to yield various micropatterns with aligned arrays of either square or circular microwells (Example 7 and Fig. 13), reading in-part the second photomask of claim 2. Dang further teaches loading the device with microtissues consisting of INS-1E cells (i.e. a insulin-secreting cell line) (Example 7), reading in-part on claim 2.
Regarding claim 2, Dang does not teach the embodiment of a second and successive photomask. Regarding claim 38, Dang does not the teach a storage modulus of greater than 0 Pa to 5,000 Pa.
Hribar teaches an apparatus for reproducibly fabricating hydrogel-based organ and tumor models inside multi-well plates (Abstract) and methods of use thereof ([0061]). Hribar teaches the device comprises a holder allowing for successive photomasks to generate a hydrogel construct with varying different shape and/or diameter ([0013], [0047], [0055]-[0056], Fig. 1C, and Fig. 4A-B), reading on claim 2. Hribar teaches that spatial patterning of chemically and crosslinkable materials with a broad range of material properties (e.g., stiffness and composition) enables a more realistic extracellular matrix for downstream cellular assays ([0066]), reading on βclaim 2. Hribar teaches that tumor-cell containing hydrogel(s) having a stiffness range from 1 Pa to 100,000 kPa, 10 Pa to 100 kPa ([0052]), reading on that embodiment of claim 38.
Regarding claim 2, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the second photomask of Hribar to the methods of Dang. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dang and Hribar are directed towards making a patterned hydrogel matrix comprising cells. The skilled artisan would have been motivated to do so because Hribar teaches that spatial patterning of chemically and crosslinkable materials with a broad range of material properties (e.g., stiffness and composition) enables a more realistic extracellular matrix for downstream cellular assays, and so the addition would predictably improve upon the device made by Dang.
Regarding claim 38, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. Furthermore, where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)In this case, a narrower embodiment of the claimed storage modulus (e.g. stiffness) is taught by Hribar as being result-effective and particularly advantageous for tumor cells. Thus, the burden is shifted back to establish criticality of the claimed storage modulus range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 1, 3-6, 18, 22-27, 31, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Dang et al. (WO 2020/204829; provided in the IDS dated 4/29/2024) in view of Jeon et al. (Advanced Materials (2013), 25, 6366-6372; Reference U).
The teachings of Dang are relied upon in rejecting claims 1, 3-6, 18, 22-24, 26, 31, and 36 as anticipated under 35 U.S.C. § 102. Dang further teaches loading the hydrogel composition with mesenchymal pluripotent stem cells (claim 26), reading in-part on claim 27.
Regarding claim 27, Dang does not teach any chemical and/or therapeutic agent having a gradient across the hydrogel matrix.
Jeon teaches an alginate hydrogel having an RGD peptide gradient and comprising mesenchymal stem cells (MSCs) , wherein the MSCs have a higher cell number in regions of higher RGD concentration and which is advantageous to examine whether having such spatial control over cell-biomaterial interactions could result in gradient changes in cell responses like cell number, alignment and migration (the paragraph spanning pages 6368-6369 and Fig. 3A; detailed methods at page 6370, right column, paragraph starting “Fabrication and characterization of gradient hydrogels with covalently coupled RGD-containing peptides:”), reading on claim 27.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the RGD peptides as a gradient of Jeon to the hydrogel and methods of Dang. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dang and Jeon are directed towards making either a spatially- or chemically- patterned hydrogel matrix comprising mesenchymal stem cells, respectively. The skilled artisan would have been motivated to do so because Jeon teaches that the addition would be predictably advantageous to spatially control cell-biomaterial interactions and further examine whether having such spatial control over cell-biomaterial interactions could result in gradient changes in cell responses like cell number, alignment and migration, thus improving upon the methods of Dang and the downstream application of Dang’s hydrogel device.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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