DETAILED ACTION
This action is in reply to papers filed 7/7/2026. Claims 1-23 are pending with claims 1-16 and 19 -23 examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20200399613A1, Published 12/24/2020.
Withdrawn Rejection
The 103 (a) rejection of claims 1-16 and 19-21 as being of unpatentable over Rossen et al. (PgPub US20180042970A1, Published 2/15/2018), Ingber et al. (PgPub US20140093905A1, Published 4/3/2014) and Takebe et al. (US20170067014A1, Published 3/9/2017) is withdrawn. Note that the rejection is withdrawn in view of amendments made to independent claim 1.
New Rejection Necessitated by Amendments
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.
Claim(s) 1-16 and 19-23 are newly rejected under 35 U.S.C. 103 as being unpatentable over Rossen et al. (PgPub US20180042970A1, Published 2/15/2018), Komada et al. (JP2011172533A, Published 9/8/2011) and Takebe et al. (US20170067014A1, Published 3/9/2017).
Claim interpretation: In the absence of a definition in the as-filed specification, the phrase ‘obverse and reverse sides’ are interpreted as set forth: According to Merriam-Webster, the obverse is the "heads" side and the reverse is the opposite or "tails" side.
Rossen et al. is drawn to spheroid microtissues that can mimic native tissue-like structure and function, spheroid production methods that are high-throughput, suitable for efficient production, maintainable over long-term culture, and/or offer repeatable control over size distribution (Abstract).
Regarding claim 1, claim 15 and claim 16, Rossen teaches a method of fusing cell masses (Pg. 10, para. 107), comprising seeding cell masses (Pg. 11, para. 119) on a collagen membrane coated plane (as in claim 20 and claim 21) (Pg. 10, para. 107), capable of cell adhesion (Pg. 15,para. 148) and culturing the cell masses on a surface of the cell mass-seeded plane, thereby fusing the cell masses, wherein the cell masses are spheroids (as in claim 19). Rossen teaches the spheroids were previously formed in a culture vessel having a non-cell adhesive plane (Pg. 14, para. 141) (as in claim 11, in-part). As shown in Fig. 28C, the area occupied by the cell masses is more than 40% (as in claim 2). Also of note, Rossen teaches the cell masses comprises vascular cells and mesenchymal cells at a ratio of 1: 1 (as in claim 4 and claim 5) (Pg. 4, para. 40). Rossen demonstrate the microtissues can be reliably formed with controlled sizes and spatial architectures, and can self-organize into a macrotissue in which elements of the final architecture (such as branching lengths) of the new vascular network (as in claim 6, claim 12 , in-part and claim 16, in-part) can also be controlled (Pg. 17,para. 157). Rossen teaches the vascular network comprises blood vessels (as in claim 13) (Pg. 6, para. 57). Rossen also teaches varying the size of spheroids before allowing them to aggregate into tissues can provide control of the resulting vasculature. Rossen teaches their methods are highly scalable. For example, the methods may be used to produce up to half-a-billion cells, which would be enough to form a 10 mm×10 mm×1 mm tissue in vitro (as in claim 23) (Pg. 7,para. 67).
However, Rossen fails to teach a culture medium is fed from both the obverse and reverse sides of the plane (as further in claims 1, 15 and 16) and wherein said medium from both sides are identical (claim 22).
Before the effective filing date of the claimed invention, Komada et al. taught a cell culture carrier substrate having a porous structure part, wherein a through-hole is formed in the porous structure and wherein the substrate is placed in a cell culture tank having at least an inlet port and an outlet port for a fluid. (Abstract). Komada teaches culturing can be carried out whereby cell seeded substrates are disposed in a cell culture tank, but nutrients and oxygen are applied to cells that are engrafted on the inner wall surface of the through-hole. In order to supply without delay, Komada teaches the cell culture support substrate is not placed on the bottom surface of the cell culture tank, and is cultured in a suspended state in the tank, or while being stirred in the suspended state in the tank (as further in claim 1, as in claim 15, claim 16 and claim 22) (paragraph bridging Pg. 11 and 12). Komada teaches this allows the spheroids to form without causing central necrosis (Pg. 12, para. 3).
However, neither Rossen nor Komada teach the cell mass is an organ bud (as in claim 7).
Takebe et al. teach a platform technology which recapitulates interactions among organ cells, vascular cells and mesenchymal cells (as in claim 3 and claim 8) that are essential for early processes of organogenesis, to thereby induce 3D organ primordia (starting material for organs) and enable generation of vascularized functional organs (Abstract). In one embodiment, Takebe teaches the organ bud is a liver bud (as in claim 7, as further in claim 11, claim 12 and claim 14) (Pg. 7,para. 94; Pgs. 7-8,para. 105). Takebe teaches an advantageous cell count ratio between the organ cells, mesenchymal cells and vascular cells is 10:1-3:0.1-7 (as in claim 8, claim 9 and claim 10) (Pgs. 5-6,para. 84). Takebe teaches a great number of organs essentially require that reconstitution associated with other organs be realized in order to exhibit their functions; e.g., in liver, reconstitution of junctions with bile duct (as in claim 14) and pancreatic duct and connection to duodenum is essential for exhibiting its function (Pg. 7, para. 95). According to the present invention, Takebe teaches a cell condensate which recapitulates interactions with other organs is prepared.
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Rossen et al., wherein Rossen examined the ability of the spheroids to form a macro-tissue in vitro, namely, creating a larger tissue from smaller tissues units comprising distinct cell types, with the teachings of Komada et al., wherein Komada teaches a method of culturing spheroids such that necrosis is not formed in the center of said spheroids, with the teachings of Takebe et al., wherein Takebe teaches a platform technology which recapitulates interactions among organ cells, vascular cells and mesenchymal cells, with a reasonable expectation of arriving at the claimed invention.
That is, one of ordinary skill in the art would have found it prima facie obvious to combine micro-tissues of organ cells, micro-tissues of vascular cells and micro-tissues of mesenchymal cells into a larger macro-tissue, as set for in Takebe, in order to mimic native tissue-like structure, as set forth in Rossen. Further, and as noted in Komada et al., the skilled artisan would have found it prima facie obvious to culture the macro-tissue using the method of Komada in order to provide sufficient microtissue such that central necrosis is not induced.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious
Applicant’s Arguments/ Response to Arguments
Arguments drawn to Ingber et al. are not addressed as the reference is not currently cited in this office action. With respect to Applicant’s argument regarding “unexpected results”, arguments are not found persuasive. This is because arguments of counsel cannot substitute for factual evidence.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is 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 extension fee 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 date of this final action.
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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