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 .
Claim Interpretation
Claims 1 and 2 state that a kidney organoid is cultured in a collagenous three-dimensional matrix comprising a decellularized kidney extracellular matrix and that the matrix is collagenous. Claims 6 and 7 further narrow the scope of claims 1 and 2 by stating that the decellularized kidney extracellular matrix increases the expression of one or more genes selected from AQP1, E-cadherin, PKD1, VEGF, a podocyte marker, NPHS1, SYNPH, or WT1 and that the collagenous three-dimensional matrix of claim 2 is a hydrogel. The specification further discloses that an exemplary embodiment of the present invention may use a hydrogel as the collagenous three-dimensional matrix. (Pg 4, lines 18-19) Therefore, any collagenous three-dimensional matrix that is a hydrogel or a decellularized kidney extracellular matrix will be interpreted as satisfying the requirements of the claims.
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.
Claims 1-7, 11, and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Yanagawa et al. (US 2016/0361466 A1) in view of Takasato et al. (Generation of kidney organoids from human pluripotent stem cells, 2016) as evidenced by Simian et al. (Organoids: A historical perspective of thinking in three dimensions, 2017), Park et al. (Angiogenesis induction using organoid-tissue modules: A platform for modular vessel construction, 2025), and Herbert et al. (Molecular control of endothelial cell behaviour during blood vessel morphogenesis, 2011)
Regarding Claims 1, 2, and 13: Takasato teaches a method of development for a kidney organoid that comprises both a monolayer culture and 3D culture to facilitate self-organizing of the organoid, seeded from hPSCs. (Pg 1681, Abstract) Takasato further specifies generation of a “successful” organoid, as defined by the organoid comprising segmented nephrons, collecting duct, renal interstitum, and endothelium which were generated from both human ESC and iPSC lines. (Pg 1690, Anticipated Results) This reads on the method of production of a kidney organoid comprising a nephron-like structure. Takasato fails to disclose use of a kidney ECM.
Yanagawa teaches an embodiment of the invention in which the ECM from either adult or embryonic kidneys may be used in the liquid hydrogel to stimulate differentiation and branching. Yanagawa further states that collagen I may be used. (0081) Furthermore, Yanagawa states clearly that “all or any portion” of the hydrogel can comprise adult or embryonic kidney ECM. (0063) This reads on the use of a collagenous three-dimensional matrix comprising a decellularized kidney ECM. In addition to this, Yanagawa teaches that the organoid can be incubated with VEGF for 3 hours prior to implantation (0084), which will trigger angiogenesis as evidenced by Herbert (discussed below). In addition, Yanagawa discloses an example of the invention in which an embryonic kidney organoid is developed in the claimed mold system as described above and transplanted into a mammalian subject for further development. (0087) A person skilled in the art would be motivated to transplant the kidney organoid of Takasato into a mammalian subject as taught by Yanagawa due to Yanagawa teaching the act of implantation will further develop the organoid. (0087)
As evidenced by Simian, the very act of culturing an organoid in three dimensions is what triggers the maturation of an organoid in culture. Specifically, Simian states that “functional differentiation is dependent on 3D architecture”. (Pg 31, How do we define organoids and 3D cultures?) In addition, Herbert et al. teaches that exposure to VEGF stimulates angiogenic sprouting via a signaling cascade, leading to angiogenesis within an organoid. (pg 554, VEGF stimulates angiogenic sprouting)
Lastly, after establishing via Simian that three dimensional culture is essential for functional differentiation, Park teaches that endothelial organoids in culture, when compared to cells in two dimensional culture, express significantly higher levels of VEGF simply by virtue of being cultured in a 3D environment. (Pg 7, Results)
As such, following the culture method as taught by the combined teachings of Takasato and Yanagawa, it is inherent as evidenced by Park, Simian, and Herbert that the resulting organoid would further develop into a mature kidney organoid which expressed increased amounts of VEGF.
Regarding Claims 3 and 14: Takasato teaches that the kidney organoids of the invention are generated from human pluripotent stem cells. (Pg 1681, Introduction) Furthermore, Yanagawa discloses an embodiment of the invention in which the cells used to create the kidney organoid are derived from induced pluripotent stem cells (iPSCs). (0069)
Regarding Claims 4 and 15: Yanagawa discloses an embodiment of the invention in which decellularized embryonic or adult mammalian kidneys may be used as a component of the extracellular matrix. (0063)
Regarding Claims 5-6, and 16-17: Yanagawa discloses an embodiment of the invention in which the embryonic kidney organoid is prepared for vascularization prior to implantation by incubating the organoid with vascular endothelial growth factor (VEGF). (0084) This reads on the claimed method of the decellularized kidney organoid promoting angiogenesis or vascular maturation and increasing VEGF expression.
Regarding Claims 7 and 18: Yanagawa discloses an embodiment of the invention in which the kidney mold device is made from a hydrogel. (0009)
Regarding Claim 11: Yanagawa discloses an embodiment of the invention in which the embryonic kidney organoid suspended in collagen with the extracellular matrix of embryonic or adult kidneys and implanted into a mammalian subject. (0013)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Takasato of the generation of fully formed kidney organoids with the teachings of Yanagawa of use of adult or embryonic kidney ECM hydrogel scaffolds to create a fully formed kidney organoid and then embed it in a hydrogel scaffold. One would have been motivated and had a reasonable expectation of success at doing so based on the teachings of Yanagawa, who detail that use of adult or embryonic kidney ECM encourages branching and development of kidney organoids.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Yanagawa et al. (US 2016/0361466 A1) as evidenced by Nagalakshmi et al. (The ureteric bud epithelium: Morphogenesis and roles in metanephric kidney patterning, 2016) in view of Van den Berg et al. (Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo, 2018) as evidenced by Simian et al. (Organoids: A historical perspective of thinking in three dimensions, 2017), Park et al. (Angiogenesis induction using organoid-tissue modules: A platform for modular vessel construction, 2025), and Herbert et al. (Molecular control of endothelial cell behaviour during blood vessel morphogenesis, 2011)
The teachings of Yanagawa and Nagalakshmi are disclosed above. Yanagawa fails to teach transplantation of the organoid into the renal subcapsular space of an animal and that the transplanted kidney recruits the cells of its host and is connected to the blood vessels of the animal.
Regarding Claim 8: Van den Berg teaches a method of transplantation of renal organoids into the renal subcapsular space of mice. (Pg 752, 2nd and 3rd paragraph)
Regarding Claim 9: Van den Berg reports that host-derived murine endothelial cells were recruited into the transplanted hiPSC-derived organoid after transplantation into the host animal. (Pg 756, Kidney Organoids Become Functionally Vascularized upon Transplantation In Vivo, Pg 757, Fig 3)
Regarding Claim 10: Van der Berg teaches that the implanted kidney organoids incorporate themselves into the vascular system of the host animal as shown by the combined presence of human CD31+ endothelial cells and murine MECA-32+ cells in the organoids, showing both host and donor contributions to the vascular network. (Pg 756-758, Kidney Organoids Become Functionally Vascularized upon Transplantation In Vivo, Pg 759, Fig 4)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the renal transplantation into the subcapsular space as taught by Van den Berg with the embryonic kidney organoid as taught by Yanagawa to create a functioning renal organoid that after transplantation, recruits endothelial cells from the host animal and that is connected to the blood vessels of the host animal. One would have been motivated to do so and had a reasonable expectation of success based on the teachings of Van der Berg, who states that renal organoids, when transplanted into the subcapsular space of an animal, show that host endothelial cells were recruited and present within the organoid (as evidenced by MECA-32+ staining) and that host-derived renal vasculature functionally connected to the transplanted organoid.
Response to Arguments
Applicant's arguments filed 02/18/2026 have been fully considered but they are not persuasive. Applicant’s primary argument is that Takasato fails to generate a completed and mature kidney organoid. However, the combined teachings of Takasato and Yanagawa read on the method of claims 1, 2, and 13 (the amended claims in the claimset dated 02/18/2026) and as the method of the claims themselves have not changed or been amended, the result of having a generated kidney organoid with a glomerulus-like structure which has been infiltrated by vascular structures expressing one or more genes selected from VEGF, NPHS1, SYNPO, or WT1 is the inherent result of said culturing method. To further reinforce this result, new sources Park, Simian, and Herbert have been added in as evidence for the following teachings, all of which are discussed in the main body of the rejection above: Simian teaches that functional differentiation is dependent on 3D architecture and that by virtue of being cultured in three dimensions, organoids will continue to mature and functionally develop. Herbert teaches that exposure to VEGF stimulates angiogenic sprouting via a signaling cascade, leading to angiogenesis within an organoid. Lastly, Park teaches that endothelial cells in 3D culture compared to 2D culture express significantly higher levels of VEGF.
Applicant further argues that Yanagawa fails to provide a maturation environment. However, Yanagawa teaches exposure of the organoid to VEGF and as discussed above, there is evidence in the art to support the teaching that exposure to VEGF will cause angiogenesis, which will inherently cause the production of higher levels of VEGF via a positive feedback loop. Therefore, when the teachings of Takasato and Yanagawa are taken in context together, it is inherent that culturing organoids in a 3D environment with VEGF exposure will create an environment in which a vascularized kidney organoid will functionally mature.
Lastly, Applicant further argues that neither Takasato nor Yanagawa provide through their combined teachings the application of a kidney-derived ECM matrix to a fully developed kidney organoid. However, as discussed above, the method step of claims 1, 2, and 13 itself has not changed. Therefore, it is still inherent that a person skilled in the art would arrive at the end product of a fully generated kidney organoid following the same method steps outlined in the combined teachings of Takasato and Yanagawa. Furthermore, there is evidence in the art to support this via the previously discussed teachings of Simian, Herbert, and Park.
As such, the 35 U.S.C. 103 rejections under Takasato and Yanagawa of claims 1-7, 11, and 13-18 are upheld. As claims 8-10, rejected under the combined teachings of Yanagawa, Nagalakshmi, and Van den Berg were not discussed in the Remarks dated 02/18/2026, the respective rejections for claims 8-10 are upheld as well.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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