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
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/JP2022/000564 (filed 01/11/2022). Additionally, the application claims priority to Japanese application JP2021-002203 (filed 01/08/2021). A copy of the foreign priority document is present in the application file.
Election/Restrictions
Applicant’s election without traverse of Group II (Claims 11-22), drawn to a method for culturing and expanding nephron progenitor cells, in the reply filed on 02/10/2026 is acknowledged. Claims 1-8 and 23-24 are withdrawn from consideration, as being directed to a non-elected invention. Claims 11-22 have been examined on the merits.
Claim Interpretation
Claims 17-21 use product-by-process language. Product-by-process claims are considered only in so far as the process of production affects the final product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant case, the process of production involves differentiating pluripotent stem cells to nephron progenitor cells, this is understood to require the final product to comprise nephron progenitor cells.
Specifically, claims 17 and 18 require nephron progenitor cells induced from pluripotent stem cells that are iPS cells. These limitations do not further limit the nephron progenitors. Thus, the final nephron progenitor cells of claims 17 and 18 comprise any nephron progenitor cells.
Claims 19-21 require the nephron progenitor cells to be produced by a method comprising steps (i)-(iv) listed in claim 19. The specification teaches steps (i)-(iv) are a method for producing nephron progenitor cells disclosed in Sueta (WO2018216743A1) (See: Specification pg. 66, ln 23 – pg. 68, ln3). Sueta discloses producing nephron progenitors expressing OSR1, HOX11, WT1, SIX2, and SALL1. Thus, the nephron progenitors of claims 19-21 are understood to comprise nephron progenitor cells expressing OSR1, HOX11, WT1, SIX2, and SALL1.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 17 and 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 17 and 18 use product-by-process language which does not further define the nephron progenitors of claim 11 (See claim interpretation section above). Thus, claims 17 and 18 do not recite an active step in the claimed method for culturing and expanding nephron progenitor cells and do not further limit claim 11.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 11, 12, 16-18, and 22 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Nishinakamura (WO201710448a1) (cited in IDS filed 08/18/2023).
Nishinakamura teaches a method or culturing and amplifying nephron progenitor cells in a medium comprising a Wnt agonist, FGF, LIF, BMP, a ROCK inhibitor, and notch inhibitors (See English translation, pg. 3, second paragraph). The Wnt agonist is a GSK-3ß inhibitor, preferably CHIR-99021 and the FGF is selected from the group consisting of FGF1, FGF2, FGF9 or FGF20 (See English translation, pg. 3, second paragraph). The optimum culture conditions of Nishinakamura comprise culturing SIX2 positive nephron progenitors in CDBLY medium (CHIR99021, DAPT, BMP2, LIF, Y27632) supplemented with FGF2 or FGF9 (See pg. 4, first paragraph and pg. 11, Example 6). The cells are cultured in a continuous subculture of SIX2 positive cells (See pg. 3, last paragraph – pg. 4, first paragraph). In Example 6, Nishinakamura discloses a method of producing nephron progenitors from human iPS cells. The nephron progenitors produced in Example 6 are subsequently cultured in CDBLY + FGF9 medium (See pg. 11 Example 6). The nephron progenitors in the culture method of Nishinakamura are positive for SIX2, PAX2, SALL1, WT1, and OSR1 (See Pg. 5, Example 5). Nishinakamura further discloses a method for producing three-dimensional nephron structures comprising steps of culturing nephron progenitors in CDBLY +FGF9 medium then further culturing the cells with spinal cord to form the three-dimensional structures comprising glomeruli (See Pg. 10, Example 3).
Regarding claim 11, 17, and 18: Nishinakamura teaches a method of culturing and amplifying nephron progenitors (reads on culturing and expanding) in CDBLY +FGF9 medium which comprises CHIR99021 (reads on GSK-3ß inhibitor) and Y27632 (reads on ROCK inhibitor).
Regarding claim 12: Following the discussion of claim 1 above, Nishinakamura teaches culturing the nephron progenitors in a continuous subculture of SIX2 positive cells which reads on the method includes subculturing of nephron progenitor cells.
Regarding claims 16-18: Following the discussion of claim 1 above, Nishinakamura discloses culturing nephron progenitors produced from human iPS cells which reads on the nephron progenitors are human nephron progenitor cells and the nephron progenitors are induced from iPS cells.
Regarding claim 22: Nishinakamura teaches a method of culturing and amplifying nephron progenitors in CDBLY +FGF9 medium which comprises CHIR99021 and Y27632 (reads on culturing and expanding nephron progenitors according to claim 11). Nishinakamura teaches further culturing the nephron progenitors cultured in CDBLY +FGF9 medium with spinal cord to produce three-dimensional nephron cultures which comprise glomeruli (reads on a step of differentiating the cultured and expanded nephron progenitor cells into renal organoids).
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.
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 11, 12, and 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Nishinakamura (WO2017010448A1) in view of Sueta (WO2018216743A1) (cited in IDS filed 08/18/2023).
The teachings of Nishinakamura are set forth above.
Nishinakamura anticipates claims 11, 12, 16-18, and 22.
Regarding claims 19-21: Nishinakamura teaches a method of culturing and amplifying nephron progenitors in CDBLY +FGF9 medium which comprises CHIR99021 and Y27632 (reads on culturing and expanding nephron progenitors according to claim 17). The nephron progenitor cells used in the culture method of Nishinakamura express SIX2, PAX2, SALL1, WT1, and OSR1 (See claim interpretation section above).
The differentiation method of claims 19-21 produces nephron progenitor cells that are HOX11, WT1, SIX2, and SALL1 positive.
Nishinakamura does not disclose culture progenitors which are positive for HOX11.
Sueta discloses a method of differentiating iPS cells to nephron progenitors comprising steps (i)-(vi) of the instant application. The cells produced by the method are positive for HOX11, WT1, SIX2, and SALL1.
Given that Nishinakamura teaches a method for culturing nephron progenitors produced by iPS cells and Sueta discloses a method for differentiating iPS cells to nephron progenitors, it would have been prima facie obvious to substitute the nephron progenitors of Nishinakamura with the nephron progenitors of Sueta in the culture method of Nishinakamura. One would have expected the nephron progenitors of Sueta to work equivocally with the nephron progenitors of Nishinakamura in the culture method of Nishinakamura because the cells of Sueta are nephron progenitors and Nishinakamura teaches a method for culturing nephron progenitors. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Claims 11-18 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Nishinakamura (WO2017010448A1) in view of Morizane (Nature Protocols, 2017) and Oxburgh (US9752115B2).
The teachings of Nishinakamura are set forth above.
Nishinakamura anticipates claims 11, 12, 16-18, and 22.
Regarding claim 13: Nishinakamura discloses a method of culturing nephron progenitors in CDBLY+FGF9 medium which reads on culturing nephron progenitor cells in the medium according to claim 1.
Nishinakamura does not disclose the cells are cultured for 30 to 60 hours.
Morizane teaches a method of producing kidney organoids from IPS cells with an intermediate step of differentiating the cells to nephron progenitor cells (See pg. 15, Steps 21 – 23 A). The intermediate step comprises culturing nephron progenitor cells for 2 days. Morizane further teaches the cells should be fed every 2-3 days (reads on culturing 30 to 60 hours) or sooner if the medium becomes yellow.
Given that Nishinakamura teaches a method of culturing nephron progenitors and Morizane teaches culture medium used for culturing nephron progenitors should be changed every 2-3 days or when medium becomes yellow, it would have been prima facie obvious to optimize the length of time for which the cells or Nishinakamura are cultured in CDBLY +FGF9 medium and arrive at the claimed time of 30-60 hours through routine experimentation in order to prevent the medium from becoming yellow. Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II).
Additionally, Nishinakamura does not teach further culturing the nephron progenitors in medium comprising FGF9 and a GSK-3ß inhibitor but not comprising a ROCK inhibitor.
Oxburgh teaches that without ROCK inhibition, cells form clumps and begin to differentiate See Col. 3, lns 5-12).
Morizane teaches culturing nephron progenitor cells in medium comprising CHIR99021 and FGF9 results in differentiation of the nephron progenitors to kidney organoids and renal vesicle structures (See steps 23A i-iv).
Given that Nishinakamura discloses a method of culturing nephron progenitor cells, Oxburgh teaches ROCK inhibition prevents nephron progenitors from differentiating, and Morizane teaches nephron progenitors can be differentiated to kidney organoids and renal vesicle structures in medium comprising CHIR99021 and FGF9, it would have been prima facie obvious to further culture the cells of Nishinakamura in a medium comprising CHIR99021 and FGF9, but not comprising a ROCK inhibitor, in order to further differentiate the nephron progenitors to kidney organoids and renal vesicle structures. One would have been motivated to add a step of culturing in medium comprising CHIR99021 and FGF9 but not comprising ROCK inhibitor to the culture method of Nishinakamura in order to further differentiate the nephron progenitors. There is a reasonable expectation of success because Morizane teaches a method of differentiating nephron progenitor cells in a medium comprising CHIR99021 and FGF9 but not comprising ROCK inhibitor.
Regarding claim 14: Following the discussion of claims 1 and 13 above, Nishinakamura, Oxburgh, and Morizane teach a method of culturing nephron progenitors according to claim 13 to produce kidney organoids.
Nishinakamura further teaches a method of producing three-dimensional nephron structures (reads on kidney organoids) from nephron progenitors comprising steps of passaging the cells every 3-4 days (See English translation, pg. 10, Example 4).
Oxburgh further teaches including a ROCK inhibitor in culture medium increases survival during plating (See Table 1).
Given that Nishinakamura, Oxburgh, and Morizane teach a method of producing kidney organoids in medium comprising CHIR99021 (reads on a GSK-3ß inhibitor) and FGF9, Nishinakamura teaches cells should be passaged every 3-4 days (reads on subculturing) during differentiation to kidney organoids, and Oxburgh teaches ROCK inhibitors increase survival during plating, it would have been prima facie obvious to passage the cells in medium comprising CHIR99021, FGF9, and a ROCK inhibitor in order to increase cell survival during passaging of the cells. One would have been motivated to use medium comprising CHIR99021, FGF9, and a ROCK inhibitor while replating the cells after passaging because Oxburgh teaches ROCK inhibitors increase survival during plating and CHIR99021 and FGF9 are used in medium for culturing kidney organoids. There is a reasonable expectation of success because Nishinakamura and Morizane disclose culturing nephron progenitors and differentiating the nephron progenitors in medium comprising CHIR99021 and FGF9 and Oxburgh teaches including ROCK inhibitors in culture medium increases survival.
Regarding claim 15: Following the discussion of claims 1, 13, and 14 above, Nishinakamura, Oxburgh, and Morizane teach a method of culturing nephron progenitors according to claim 14 to produce kidney organoids.
Nishinakamura does not disclose the cells from step (C) for 30 to 60 hours.
Morizane teaches a method of producing kidney organoids from IPS cells with an intermediate step of differentiating the cells to nephron progenitor cells (See pg. 15, Steps 21 – 23 A). The intermediate step comprises culturing nephron progenitor cells for 2 days. Morizane further teaches the cells should be fed every 2-3 days (reads on culturing 30 to 60 hours) or sooner if the medium becomes yellow.
Given that Nishinakamura teaches a method of culturing nephron progenitors and Morizane teaches culture medium used for culturing nephron progenitors should be changed every 2-3 days or when medium becomes yellow, it would have been prima facie obvious to optimize the length of time for which the cells or Nishinakamura are cultured in CDBLY +FGF9 medium and arrive at the claimed time of 30-60 hours through routine experimentation in order to prevent the medium from becoming yellow. Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II).
Additionally, Nishinakamura does not teach further culturing the cells obtained in step (D) in medium comprising FGF9 and a GSK-3ß inhibitor but not comprising a ROCK inhibitor.
Oxburgh teaches that without ROCK inhibition, cells form clumps and begin to differentiate See Col. 3, lns 5-12).
Morizane teaches culturing nephron progenitor cells in medium comprising CHIR99021 and FGF9 results in differentiation of the nephron progenitors to kidney organoids and renal vesicle structures (See steps 23A i-iv).
Given that Nishinakamura discloses a method of culturing nephron progenitor cells, Oxburgh teaches ROCK inhibition prevents nephron progenitors from differentiating, and Morizane teaches nephron progenitors can be differentiated to kidney organoids and renal vesicle structures in medium comprising CHIR99021 and FGF9, it would have been prima facie obvious to further culture the cells of Nishinakamura in a medium comprising CHIR99021 and FGF9, but not comprising a ROCK inhibitor, in order to further differentiate the cells. One would have been motivated to add a step of culturing in medium comprising CHIR99021 and FGF9 but not comprising ROCK inhibitor to the culture method of Nishinakamura in order to further differentiate the nephron progenitors. There is a reasonable expectation of success because Morizane teaches a method of differentiating nephron progenitor cells in a medium comprising CHIR99021 and FGF9 but not comprising ROCK inhibitor.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633