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 .
Priority
This application was filed June 7, 2021, and is a 371 application of PCT/JP2021/021478 filed on June 7, 2021, which claims benefit to the foreign application JP2020-099128 filed on June 8, 2020.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-10) in the reply filed on September 9, 2025, is acknowledged.
Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 9, 2025.
Claim Status
Currently, claims 1-10 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 13, 2023, July 19, 2024, and January 7, 2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper”. Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains three embedded hyperlinks (e.g. https://www.nejm.org/doi/pdf/10.1056/NEJMra1806175,https://www.nature.com/articles/s41568-018-0007-6 and http://www.amsbio.com/brochures/organoid-culture-handbook.pdf), located in para. 19, page 18. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2 and 4 is objected to because of the following informalities: grammatically incorrect.
Claim 2 appears to be missing an indefinite article before the word time. It is suggested to use the word “a” before the word “time” in the claim.
Claim 4 recites “wherein a matrix in which the organoid and/or the cells constituting an organ is embedded is immobilized in the chamber in a state suspended from a breathable membrane.” Suggestion for claim 4 is having the word “that” or an “and is” between the phrase “is embedded is immobilized” , and the word “and is” in line 2 between “in the chamber in a state” of the claim.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claims 1 and 2 recite the phrase “in such a manner as to” which is interpreted as not involving invoking 35 U.S.C. 112(f), because the term “manner” is not a sufficient term or generic placeholder that is used as a substitute for the term “means” or “step”. Although the phrase “such a manner as” is a non-structural term having no specific structural meaning for performing the claimed function, the word “manner” implies a process that could be changed, whereas the term “means” implies a specific actionable step. Further, the phase “as to” does not comprise a clear transitional phrase. Therefore, claims 1 and 2 are interpreted as not invoking 35 U.S.C. 112(f).
Claims 8-10 recite the term “Drug,” and the specification defines the term “drug” as “not especially limited as long as it can be used as an active ingredient of a medicament” (see e.g. page 44).
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, and 3-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mosig et al., (US2017/0226457A1, published 2017, cited IDS 7/19/2024).
Regarding claim 1 and 3-4, Mosig discloses a culture method for culturing an organoid and/or cells constituting an organ (see e.g. claims 1-4, fig. 1-3 and 10) immobilized, wherein a state embedded in a matrix (see e.g. page 6, para. 103, figs. 1-3 and 10), and chamber with a culture fluid perfused (see e.g. para. 31-35), wherein the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber (see e.g. para. 31-35 and 103, figs. 1-3 and 10). Further, Mosig discloses wherein the organoid is embedded and immobilized in the chamber and is in a state suspended from a breathable membrane (i.e. porous)(see e.g. claims 1, 3-4 and 14-16 paras. 14-16, 22-23, 28-39, 50, 89-90 and 103, figs. 1-3, 5-6, and 10).
Regarding claim 5, Mosig wherein the organoid has a vascular structure, and/or the cells constituting an organ coexists with vascular cells (i.e. human intestinal microvascular endothelial cells)(see e.g. para. 103, fig. 10).
Regarding claim 6, Mosig wherein the organoid is a liver (see e.g. para. 27, 55-60).
In conclusion, the prior art of Mosig anticipates the instant claims.
Claims 1, and 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deplano et al., (US2014/0030762 A1, published 2014, cited IDS 3/13/2023),
Regarding claim 1 and 3-4, Deplano discloses a culture method for culturing an organoid and/or cells constituting an organ immobilized (see e.g. para. 42, 47, pages 2, 6-8, fig. 1, 4 and 6), wherein a state embedded in a matrix (see e.g. page 2, fig. 6), and chamber with a culture fluid perfused (see e.g. pages 1-2 and 4), wherein the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber (see e.g. page 1, and 5, para. 96). Further, Deplano discloses wherein the organoid is embedded and immobilized in the chamber and is in a state suspended from a breathable membrane (i.e. porous)(see e.g. page 2, para. 19-23, fig. 1, 4 and 6 ).
In conclusion, the prior art of Deplano anticipates the instant claims.
Claims 1, 3, and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sekiya et al., (JP2020-010683A, Tokyo Women’s Medical University, published 2020, cited IDS 3/13/2023).
Regarding claim 1 and 3, Sekiya discloses a culture method for culturing an organoid and/or cells (see e.g. claim 1, paras. 1-2 and 14-15) constituting an organ (i.e. tissue) immobilized in a chamber with a culture fluid perfused (i.e. porous membrane)(see e.g. para. 6-8), wherein the culture fluid is perfused in such a manner as to generate a turbulent flow in the chamber (see e.g. para. 7-8, and 32-33). Sekiya discloses wherein the organoid is immobilized in a state embedded in a matrix (i.e. porous membrane)(see e.g. para. 6-8). Further, Sekiya discloses a state of suspension from a breathable membrane (i.e. porous)(see e.g. paras. 12-14).
Regarding claim 5, Sekiya discloses wherein the organoid has a vascular structure (i.e. kidney organoid)(see e.g. para. 57).
Regarding claim 6, Sekiya discloses wherein the organoid is a kidney organoid and the organ is liver or kidney (see e.g. paras. 12-16).
Regarding claim 7, Sekiya discloses a production method for producing a conformational organ (i.e. three-dimensional tissue), comprising a step of performing the culture method according to claim 1 (see e.g. abstract, whole document).
In conclusion, the prior art of Sekiya anticipates the instant claims.
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Sekiya et al., (JP2020-010683A, Tokyo Women’s Medical University, published 2020, cited IDS 3/13/2023, hereinafter as Sekiya), as applied to claims 1, 3, and 5-7 above, and further in view of Hof, Björn, et al. (science 327.5972: 1491-1494, published 2010), and Homan, Kimberly A., et al. (Nature methods 16.3: 255-262, published 2019, cited IDS 3/13/2023).
The teachings of Sekiya apply here as indicated above.
Regarding claim 2, Sekiya discloses wherein the culture fluid is “perfused at a pump flow rate of 10μL/min which changes in ureteric bud tissue and induced tubular structure within renal organoids due to perfusion”(see e.g. para. 12, fig. 9), corresponding to the claim limitation wherein the culture fluid is perfused in such a manner as to have a time of transition from a laminar flow to a turbulent flow, and a time of generation of a turbulent flow.
Sekiya does not explicitly state a time of transition from a turbulent flow to a laminar flow in the chamber.
However, the prior art of Hof discloses that during intermediate flow rates when a control strategy (e.g. perturbations, i.e. pulse in a flow) is activated, there is an immediate collapse of turbulence, and the flow relaminarizes (turbulent flow transition to laminar flow) (see e.g. abstract, page 1491 and 1492).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods as taught by Sekiya and have the transition of turbulent to laminar flow (i.e. relaminarization) as taught by Hof because Hof discloses that the turbulent and laminar states are dynamically connected and can be controlled (see e.g. abstract, page 1491 and 1492). Additionally, a person of ordinary skill in the art would have done so because the prior art of Homan discloses that vascularized kidney organoids cultured under flow had more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression compared with that in static controls (see e.g. abstract). Further, Homan discloses that the ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studies of kidney development, disease, and regeneration (abstract). A person of ordinary skill in the art would have a reasonable expectation of success because Sekiya and Homan both disclose methods for culturing kidney organoids, as discussed above. Additionally, Sekiya discloses that “whether the fluid is laminar or turbulent can be predicted by calculating the Reynolds number” (See e.g. para. 32-35). Thus, providing a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. in vitro cell culture methods) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Sekiya et al., (JP2020-010683A, Tokyo Women’s Medical University, published 2020, cited IDS 3/13/2023, hereinafter as Sekiya), as applied to claims 1, 3, and 5-7 above, and further in view of Bertram et al., (US10,077,442B2, published 2018), and Sabaawy et al., (WO2019/006127A1, published 2019).
Claim Interpretation: The specification discloses that the term “drug” is not especially limited as long as it acts on the organoid or the like, or it is used for analyzing whether or not it acts and can be selected in accordance with the purpose (see Specification, page 44). Therefore, the term drug will be given its broadest reasonable interpretation.
The teachings of Sekiya apply here as indicated above.
Regarding claims 8 and 9, Sekiya discloses that the organoids are to be applied to drug discoveries (see e.g. para. 2).
Sekiya is silent regarding the culture fluid containing a drug (i.e. gelatin)(see spec. page 44), the drug being for treatment of a disease involving ischemia, and a medicinal effect evaluation.
However, the prior art of Bertram discloses bioactive renal cell populations (e.g. organ structure)(col. 21, 41) wherein the cultured fluid contains gelatin (i.e. drug) and formed particles from crosslinked, lyophilized sponges (see e.g. table 15.3, fig. 12, 19-26, Examples 1 and 15). Further, Bertram discloses an invention and methods for therapeutic treatment and prophylactic or preventative measures for kidney disease (i.e. disease involving ischemia)(see e.g. col. 8-9, and 21). Additionally, Bertram discloses methods for assessing the bioactive renal cell population where the “gelatin particles were nearly completely resorbed, and less giant cell reaction was observed than in tissues that received HA particles”(see e.g. fig. 19, col. 77-80, Example 15).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Sekiya and incorporate a culture fluid containing a drug as taught by Bertram because Sekiya discloses that organoid methods are to be used for drug discoveries which include evaluating drugs. Thus, it would have been obvious to combine prior art elements according to known methods to yield predictable results. Furthermore, incorporating a culture fluid containing a drug would have led to predictable results with a reasonable expectation of success because both Sekiya and Bertram disclose methods relating to Kidney studies. Additionally, Bertram discloses that regenerative medicine technologies may provide next-generation therapeutic options for chronic kidney disease (see e.g. col. 2). Furthermore, an artisan of ordinary skill in the art of (i.e. in vitro renal cell populations) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 10, as discussed above, Sekiya discloses that the organoids are to be applied to drug discoveries (see e.g. para. 2). Further, Bertram discloses methods for assessing the bioactive renal cell population wherein the “gelatin particles were nearly completely resorbed, and less giant cell reaction was observed than in tissues that received hyaluronic acid (HA) particles”(see e.g. fig. 19, col. 77-80, Example 15).
Sekiya and Bertram do not explicitly state a medicinal effect evaluation.
However, the prior art of Sabaawy discloses examining the toxicity of agents targeting renal organoids (see e.g. para. 21, Example 1), corresponding to the claim limitation of a medicinal effect evaluation.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Sekiya and incorporate a medicinal effect evaluation as taught by Sabaawy because Sekiya discloses that organoid methods are to be used for drug discoveries which include performing a medicinal effect evaluation on drugs. A person of ordinary skill in the art would have done so because Sabaawy discloses that “kidney organoids represent powerful models of the human organ for future applications, including renal regeneration, nephrotoxicity screening, disease modelling and as a source of cells for personalized therapy for not only renal cell carcinoma but also other renal disorders (see e.g. para. 52). Thus, it would have been obvious to combine prior art elements according to known methods to yield predictable results. Furthermore, incorporating a culture fluid containing a drug and a medicinal effect evaluation would have led to predictable results with a reasonable expectation of success because both Sekiya and Sabaawy disclose methods regarding kidney organoids. Furthermore, an artisan of ordinary skill in the art of (i.e. organoid methods) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631