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 .
Applicant’s amendment and response filed on 3/12/2026 have been received and entered into the case. Claims 9-11 have been canceled. Claims 1-8 and 12-20 are pending, Claims 2-8, 12 and 15-20 have been withdrawn, and Claims 1, 13 and 14 have been considered on the merits. All arguments have been fully considered.
Withdrawn Rejections
Rejections of Claims 1, 13 and 14 under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Ingber et al (US 2020/0231938 A1; 7/23/2020.) are withdrawn in view of applicant’s amendments.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 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 of this title, 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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Hee et al (Stem Cell Research. 2018;28:165-171.) in view of Cho et al (US 2019/0390149 A1; 12/26/2019.).
The instant claims recite a method for producing a two-dimensional small intestinal organoid having a villus structure, the method comprising: culturing a cell derived from a small intestinal epithelium in an extracellular matrix to obtain a three-dimensional small intestinal organoid; dispersing the three-dimensional small intestinal organoid in one to several cells and monolayer culturing on the extracellular matrix to obtain a two-dimensional small intestinal organoid; and further culturing the two-dimensional small intestinal organoid while letting a culture medium of the two-dimensional small intestinal organoid to flow by shaking a cell culture vessel on a shaker so that the two-dimensional small intestinal organoid forms a villus structure.
Hee teaches a method for generating confluent intestinal cell monolayers from single-cell suspensions (Abstract), comprising culturing a cell derived from a small intestinal epithelium in an extracellular matrix to obtain a three-dimensional small intestinal organoid (p.166 col left – para 2); and dispersing the three-dimensional small intestinal organoid in one to several cells and monolayer culturing on the extracellular matrix to obtain a two-dimensional small intestinal organoid (p.166 col left – para 3); wherein large numbers of villin-positive cells in villus tips and throughout the 2D monolayer indicated the presence of mature absorptive enterocytes, moreover, microvilli, which are characteristic of mature enterocytes, were seen on the apical membrane of cells in the 2D monolayers (p.167 col right – last para, p.168 col left – first para).
Hee does not teach the method comprises further culturing the two-dimensional small intestinal organoid while letting a culture medium of the two-dimensional small intestinal organoid to flow by shaking a cell culture vessel on a shaker (claim 1).
However, Hee does teach the method comprises 2D monolayer organoid cultures, wherein the 2D organoid forms a villus structure. Cho teaches an organoid culture system comprising a shaker (para 0019), wherein the shaker is capable of imparting a dynamic flow to a culture medium by causing a culture device to make a motion at a constant cycle (para 0087), the culture medium in the device can make a reciprocating motion in a chamber at a constant cycle, and an environment in which the organoid can be stably cultured can be established (para 0091). The organoid culture system can simply form a fluid flow using the shaker, and is excellent in usability and expandability (para 0099-0100).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to shake a cell culture vessel on a shaker, since Hee discloses a method comprises 2D monolayer organoid cultures, wherein the 2D organoid forms a villus structure, and Cho discloses an organoid culture system comprises a shaker that is capable of imparting a dynamic flow to a culture medium to establish an environment in which the organoid can be stably cultured. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to shake a cell culture vessel on a shaker, with a reasonable expectation for successfully generating confluent intestinal cell monolayers from single-cell suspensions.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Hee et al (Stem Cell Research. 2018;28:165-171.) in view of Cho et al (US 2019/0390149 A1; 12/26/2019.) as applied to claim 1 above, further in view of Dedhia et al (Gastroenterology. 2016;150(5):1098-1112.).
References cited above do not teach the method wherein the cell is derived from a patient with a small intestinal dysfunction or a small intestinal disease (claim 13), or from a normal small intestine (claim 14).
Dedhia teaches organoid models of human gastrointestinal development and disease (Title), wherein patient-specific organoids can be used to study mechanisms of diseases, organoids generated from normal and tumor specimens can be used to characterize the events that occur during transformation, growth, and progression of malignancies, and organoids generated from patient biopsies could be used to regenerate intestinal tissues for patients with disorders such as short bowel syndrome or IBD and avoid the adverse effects of immune rejection or immune suppression (p.15 para 4).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate cells derived from a patient with a small intestinal dysfunction or a small intestinal disease, or from a normal small intestine, since Hee and Dedhia both disclose intestinal organoid cultures, and Dedhia discloses that patient-derived small intestinal cells and normal small intestine cells in intestinal organoid cultures offer personalized medicine capabilities, disease modeling, and the ability to study cell-specific functions. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate cells derived from a patient with a small intestinal dysfunction or a small intestinal disease, or from a normal small intestine, with a reasonable expectation for successfully generating confluent intestinal cell monolayers from single-cell suspensions.
Response to Arguments
Applicant argues that Ingber does not disclose the two-dimensional small intestinal organoid is cultured while letting a culture medium of the two-dimensional small intestinal organoid to flow by shaking a cell culture vessel on a shaker, and that in Ingber, organoids are not excessively dissociated into single cells. However, these arguments are moot since those rejections are withdrawn in view of applicant’s amendments.
Conclusion
No claims are 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 mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759
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