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 .
Detailed Action
This action is in response to the papers filed on December 11th, 2023. Claims 1-14 are currently pending. Claims 1, 6, 10 and 14 are independent claims.
Therefore, claims 1-14 are under examination to which the following grounds of rejection are applicable.
Priority
The instant application is a continuation of International Patent Application No. PCT/JP2022/023371 filed on June 9th, 2022. This application claims priority to foreign application JP 2020-139260, filed on June 11th, 2021. Note that Applicants have failed to provide of a certified translation required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
The earliest possible priority for the instant application is June 11th, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on December 11 2023, February 28 2024, September 24 2025, were filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification Objection
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.
Claim Objections
Claims 1, 6 ,7 and 8 are objected to because of the following informalities:
Claim 1 contains multiple limitation that recite duplicative language. The phrase “maintenance process of maintaining a liquid” recite the same concept of maintenance without a distinct structural or procedural limitation. It is recommended to omit “a maintenance process of” in line 2 from the claim.
Claim 1 is also objected for lack of clarity as the recited “cell-aggregate maintaining method” blurs the distinction between a method and a tangible product. It is recommended to rewrite the pre-amble as “A method of maintaining a plurality of cell aggregates”
Claim 6 contains multiple limitation that recite duplicative language. The phrase “a culturing process of culturing cells” recite the same concept of culturing without a distinct structural or procedural limitation. It is recommended to omit “a culturing process of” in line 2 from the claim.
Claim 6 is also objected for lack of clarity as the recited “cell-aggregate producing method” blurs the distinction between a method and a tangible product. It is recommended to rewrite the pre-amble as “A method of producing a plurality of cell aggregates”
Claim 7 contains a limitation that recites duplicative language. The phrase “concentration process of concentrating the cell” recites the same concept of concentrating cells without a distinct structural or procedural limitation. It is recommended to omit “a concentration process of” in line 1 from the claim.
Claim 8 contains a limitation that recites duplicative language. The phrase “fractionation process of fractionating the cell” recites the same concept of concentrating cells without a distinct structural or procedural limitation. It is recommended to omit “a concentration process” from the claim.
Claims 1 and 6 recite the acronym “mPa•s” but it is not defined in the claim. An acronym should be defined the first time it appears in an independent claim or in the group of claims under the independent claim. For the purposes of compact prosecution, “mPa•s” will be interpreted as millipascal-seconds.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite in its recitation of the phrase “culture temperature of the cells”. There is not a proper antecedent basis for “cells” as the claims only recite cell aggregates. Claim 1 is also indefinite in its recitation of the phrase “at which the liquid is not frozen”, as liquids can have various freezing points.
Claim 2 is indefinite in its recitation of the phrase “the temperature”, as it is unclear if the limitation is directed to the temperature of the liquid or the temperature of the culture temperature discussed in claim 1.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
In the present instance, claim 2 recites the broad recitation “2°C or higher ”, and the claim also recites specific types of temperatures such as 22°C which is the narrower statement of the range/limitation. Moreover, claim 4 recites the broad recitation “50um or more ”, and the claim also recites specific types of diameters such as 1,000uM which is the narrower statement of the range/limitation.
Claim 7 is indefinite in it recitation of “concentration process of concentrating the cell aggregates” . The phrase " concentrating the cell aggregates " is not defined by the claim. ”. The specification does not provide any closed definition as to what is meant by “concentrating the cell aggregates”. Although it is acknowledged the specification some conditions are considered by applicant to result in " concentrating the cell aggregates” , e.g, “After collecting the cell aggregates and removing the excess medium” (para [0047]) “reduce the sedimentation rate of a large amount of concentrated aggregates “ or (para [0122])“the volume of the liquid containing cell aggregates is reduced” (para [0144]), these are merely exemplary and non-limiting. The metes and bounds of the claims are unclear particularly since concentrating the cell aggregates would vary depending on the method and conditions used to concentrate a cell aggregate. As such, the metes and bounds of the claims cannot be determined.
Claim 9 is indefinite in its recitation of the term “substantially free”, as the term is a relative term that fails to provide clear metes and bounds for the scope of the claim. It is unclear to what degree does a liquid become “substantially free”.
Claim 11 is indefinite in its recitation of “the temperature” in line 2. There is not proper antecedent bases for “the temperature” in the claim.
Claim 12 and 13 are indefinite in its recitation of the term “the cell” as both claims are directed to the cell aggregate of independent claim 10, therefore lacking proper antecedent basis. It is recommended to amend the claims to “The cell aggregate further comprises undifferentiated cells” and “The cell aggregate further comprises nephron progenitor cells” to overcome the lack of antecedent basis.
Claim Rejections - 35 USC § 112: Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14 are rejected under 35 U.S.C. l 12(a) or 35 U.S.C. 112 (preAIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
M.P.E.P. § 2163 recites, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406." Further, the written description inquiry is limited to that which is contained within the four corners of the specification, not the extent to which the skilled artisan, given his or her knowledge of the art, would have considered it to expand with only routine experimentation. See Ariad Pharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane); see also id. At 1352 ("[I]t is the specification itself that must demonstrate possession. A description that merely renders the invention obvious does not satisfy the requirement.").
Claim 1 is drawn to a maintenance process comprising of a liquid containing of a cell aggregate containing a plurality of cell aggregates and a viscosity modifier at a temperature lower than a culture temperature of the cells, wherein a viscosity of the liquid at 4°C is 0.8 mPa·s to 25 mPa· s.
The claimed “viscosity modifier” can be broadly but reasonably interpreted as comprising a genus of substances that modulates the viscosity of a liquid, specifically the liquid medium suspending the cell aggregates as described in the instant application to result in a a viscosity of the liquid at 4°C is 0.8 mPa·s to 25 mPa· s. There is no structure to function correlation for the claimed genus of viscosity modifiers that would reasonably result in the suspension and maintenance of a plurality of cell aggregates in a liquid medium wherein a viscosity of the liquid at 4°C is 0.8 mPa·s to 25 mPa·s.
Although the specification discloses working examples using methylcellulose where mouse embryo-derived nephron progenitor cell aggregates after maintaining at 4° C. for 24 hours in a medium containing 0.6% methylcellulose (para [0034]) of the published application. Moreover, the Specification teaches that it can be added at a concentration of 0.1% by mass to 1.0% by mass based on the entire solution. Alternatively, the viscosity modifier can be added such that the viscosity of the solution is 0.8 mPa.Math.s to 25 mPa.Math.s (JIS Z8803) at 4° C. (para [0049]). The Specification is silent about other “viscosity modifier” as recited in claim 1. Though there is preferred embodiments directed to the viscosity modifier being gellan gum, there are no working examples containing molecular weights, and/or ratios. Therefore, the disclosure does not reasonably convey to a skilled artisan that the inventors were in possession of the full scope of the claimed genus of viscosity modifiers capable of maintaining a plurality of cell aggregates at a viscosity the liquid at 4°C is 0.8 mPa·s to 25 mPa·s.
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Leung et al. (Published: 2015. Biomater. Sci.,3, 336-344) teaches that different viscosity modifiers—despite being at the same viscosity—can affect spheroid circularity and compactness (page 341-342, “Conversely, these macromolecule additives may interfere with spheroid formation, in a cell-type dependent manner, as noted when they are present in HEK293 spheroid culture. Specifically, even though all HEK293 cultures resulted in the formation of spheroids regardless of additives, each hanging drop culture with either PEG or DEX supplements resulted in the formation of multiple spheroids”; Figure 3). Furthermore, Leung discusses that the multi-spheroids caused by these viscosity modifiers can influence swelling and the aggregation of cells (page 342, “Such factors may be crowding or “swelling” effects which could produce localization of ECM proteins). Additionally, Leung discuses that “these phenomena have been demonstrated to result in mechanisms that should induce particle and cellular aggregation when using certain macromolecules as additives” (page 342). Given this, the prior art establishes that different viscosity modifiers can results in different outcomes for cell aggregates, depending on the modifier identity.
Thus, the prior art and the specification fails to provide support for the full scope of the claims, and does not provide reasonable possession of all viscosity modifiers such that when added to a liquid containing a plurality of the cell aggregates, the viscosity of the solution is 0.8 mPa·s to 25 mPa·s.
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—2, 4-10, 12 and 14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Hayasashi et al. (Published: 2016. EP Pub. EP3098300A1; Cited in IDS filed September 24th 2025).
Regarding claim 1, Hayasashi discloses a cell aggregate maintaining method (para [0001], “The present invention relates to a medium composition for culturing animal and plant cells and/or tissues particularly in a three dimensional or suspended state”; para [0130], “Using the preservation or transportation method of the present invention, cells and tissues can be maintained in a suspended state”); comprising a maintenance process of maintaining a liquid containing a plurality of the cell aggregates and a viscosity modifier (para [0130], “Using the preservation or transportation method of the present invention, cells and tissues can be maintained in a suspended state”, para [0133], “The obtained suspension (10 ml) of spheres {diameter 100 - 200 μm) was centrifuged (200G, for 5 min) to allow for sphere sedimentation, and the supernatant was removed to give a) sphere suspension (1.0 ml). Successively, the deacylated gellan gum-containing medium prepared above was placed in a 1.5 ml Eppendorf tube 35 by 1.0 ml, and a Hela cell sphere suspension (10 μ,L) was further added. The cell aggregate was dispersed by tapping, incubated at 37°C, and the dispersion state of the cells for 1 hr later was visually observed.”, Table 1). Hayasashi also teaches that the liquid containing the plurality of cell aggregates and the viscosity modifier is lower than a culture temperature of the cells, at which the liquid is not frozen (para [0126], "A decrease in the viability of cell or tissue during preservation or transport can be avoided when the temperature is low. However, to prevent freezing of cells or tissues, they are generally preserved or transported at a temperature exceeding the melting point of the medium composition of the present invention. Therefore, the temperature during preservation or transport is generally maintained at -5 - 42°C, preferably 1 - 37°C, more preferably 4 - 32°C, further preferably 18 - 30°C."); and that the viscosity of the liqu
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id at 4°C is 0.8 mPa·s to 25 mPa·s (Claim 2, “The medium composition of [1], having a viscosity of not more than 8 mPa·s.”; para [0246], “Cellulose nanofiber (PNC) prepared in Production Example 2 and 1 mass %(w/v) aqueous solution of K-carageenan (GENUGEL WR-80-J, manufactured by SANSHO Co., Ltd.: Car) produced in the same manner as in Example 5 were used…The above-mentioned medium free of the substrates and suspending Macaca fascicularis primary hepatocytes was dispensed. The above-mentioned operation was performed with 2 lots. Successively, this tube was transported while being stood still for 2 days in cold storage {about 4°C). Trypan Blue reagent (manufactured by Life Technologies, Inc.) was used for the cell suspension transported for 2 days in cold storage conditions, and the survival rate of the cells in the suspension was measured.” ).
Regarding claim 2, Hayasashi discloses that the temperature of the liquid is 2°C or higher and 22°C or lower, (para [0126], “A decrease in the viability of cell or tissue during preservation or transport can be avoided when the temperature is low. However, to prevent freezing of cells or tissues, they are generally preserved or transported at a temperature exceeding the melting point of the medium composition of the present invention. Therefore, the temperature during preservation or transport is generally maintained at -5 - 42°C, preferably 1 - 37°C, more preferably 4 - 32°C, further preferably 18 - 30°C”).
Regarding claim 4, Hayasashi teaches that the diameter of the cell aggregate is 50 μm or more and 1,000 μm or less (para [0119], “The particle size of the plant cell aggregate during culture is 3 mm to 40 mm, preferably 3 mm to 20 mm, more preferably 5 mm to 15 mm. As used herein, the "particle size" means a diameter when, for example, the plant cell aggregate has a spherical shape, a major axis when it has an ellipse spherical shape, and the maximum length possible when it has other shape.”)
Regarding claim 5, Hayasashi teaches that the cell aggregate is a cell aggregate of undifferentiated cells (para [0118], “As a method for standing culture of plant-derived cells and/or tissues, callus, which is an undifferentiated plant cell aggregate, can be cultivated.”)
Regarding claim 6, 10 and 14 Hayasashi teaches the cell-aggregate producing method, comprising a culturing the cells results in a plurality of cell aggregates (para [0243], “As a result, cell aggregate mass (sphere) was merely dispersed in a medium condition using deacylated gellan gum, whereas spheres and cells were proliferated in cluster of grapes in a medium condition using chitin nanofiber.”); and cooling the liquid (para [0126]), wherein a viscosity of the liquid at 4°C is 0.8 mPa·s to 25 mPa·s (para [0246], “Cellulose nanofiber (PNC) prepared in Production Example 2 and 1 mass %(w/v) aqueous solution of K-carageenan (GENUGEL WR-80-J, manufactured by SANSHO Co., Ltd.: Car) produced in the same manner as in Example 5 were used…The above-mentioned medium free of the substrates and suspending Macaca fascicularis primary hepatocytes was dispensed. The above-mentioned operation was performed with 2 lots. Successively, this tube was transported while being stood still for 2 days in cold storage {about 4°C). Trypan Blue reagent (manufactured by Life Technologies, Inc.) was used for the cell suspension transported for 2 days in cold storage conditions, and the survival rate of the cells in the suspension was measured.” ).
Regarding claim 7, Hayasashi teaches a concentration process of concentrating the cell aggregates in the liquid, (para [0106], “The cells and/or tissues cultured by this method can be collected by performing centrifugation and filtration treatment while the cells and/or tissues are embedded in the carrier after the culture”).
Regarding claim 8, Haysashi teaches the fractionating the cell aggregates by diameter (para [0106], “The number of cells that can be cultured on a bead-like carrier is not particularly limited, and can be freely selected according to the bead size. For example, 5 million cells can be embedded in a bead-like carrier with a diameter of about 2000 μ,m. …. The cells and/or tissues cultured by this method can be collected by performing centrifugation and filtration treatment while the cells and/or tissues are embedded in the carrier after the culture. In this 10 case, centrifugation and filtration treatment may be performed after adding the liquid medium used. For example, unlimitatively, the gravitational acceleration (G) of centrifugation is 1 00G to 400G, and the size of the pore of the filter used for the filtration treatment is 10 μ,m to 100 μ,m”.
Regarding claim 9, Hayasashi teaches that the culture medium and the liquid are substantially free of a cell cycle inhibitor (para [0144], “Using this microcarrier suspension, DMEM medium (containing 10% (v/v) fetal bovine serum, 20 ml) containing 120 mg of Cytodex (registered trade mark) 1 and 4000000 HepG2 cells was prepared”).
Regarding claim 12, Hayasashi teaches that the cell aggregate is a cell aggregate of undifferentiated cells (para [0118], “As a method for standing culture of plant-derived cells and/or tissues, callus, which is an undifferentiated plant cell aggregate, can be cultivated.”)
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.
Claims 3, 11 and 13 are rejected under 35 U.S.C. 103 as rendered obvious in view of Hayasashi et al. (Published: 2016. EP Pub. EP3098300A1; Cited in IDS filed September 24th 2025.).
With regards to claim 1, 6 and 10, Hayasashi et al teaches the method for producing cell aggregates and the obtained cell aggregates render obvious the claimed product, as iterated in the 102 rejection the content of which is incorporated herein, in its entirety.
Regarding claim 3, Hayasahi teaches the maintenance process to be 2 hours our longer (para [0129], “as long as the cells or tissues can be maintained in a viable state in the medium composition of the present invention. It is generally not less than 1 hr, within 10 days, preferably 1 - 8 days, more preferably 1 - 3 days. During the preservation or transport period, the cells or tissues are preferably maintained in a suspension stand state in the medium composition”).
It would have been obvious for one of ordinary skill in the art to optimize maintenance process based on influential considerations in the design of the method such as increasing the maintenance to longer than 2 hours to preserve cells or tissues.
Regarding claim 11, Hayasashi et al teach that fresh Macaca fascicularis primary
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hepatocytes liquid comprising Cellulose nanofiber (PNC) has a cell viability (e.g, survival rate ) of more than 62% in cold storage (about 4°C) the for 24 hours (Table 64), however, Hayasashi fails to explicitly teach that the cell viability would be over 70%.
It would have been obvious for one of ordinary skill in the art to optimize the cell aggregate and liquid medium based on influential considerations in the design of the medium such as short or long culture, additives or viscose modifiers and confluency to result at the desired 70% viability.
The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421.
MPEP 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount.
***
Claim 13 is rejected under 35 U.S.C. 103 as rendered obvious in view of Hayasashi et al. (Published: 2016. EP Pub. EP3098300A1; Cited in IDS filed September 24th 2025.) as applied to claims 6 and 10 above, in further view of Li et al. (Published 2016. 3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors,Cell Stem Cell. 2016 Oct 06; 19(4): 516-529. Cited in IDS filed December 11th, 2023).
With regards to claim 6 and 10, the teachings of the method for producing cell aggregates and the obtained cell aggregates render obvious the claimed product, as iterated in the 102 rejection the content of which is incorporated herein, in its entirety. Moreover, Hayasashi teaches that the cell aggregates can contain human kidney cells (para [0165], “Human embryonic kidney cell line HEK293 was suspended in EMEM medium containing 10% (v/v) fetal bovine serum at 250000 cells/ml, 34 2/4/2026 13:50:32 Page 35 of 85 EP 3 098 300 A1 and this suspension (10 ml) was plated on EZ SPHEREand cultured for 2 days in a CO2 incubator (5% CO2). A suspension (10 ml) of the spheres {diameter 100 - 200 μ,m) of HEK293 cells obtained here was centrifuged (200G, for 5 min) to allow for sphere sedimentation, the supernatant was removed and the sphere was suspended in 1 ml.”).
However, Hayasashi fails to explicitly teach cell aggregates made of nephron progenitor cells.
Li teaches a cell aggregate using nephron progenitor cells (page 4, “Thus, to better preserve the native microenvironment, we cultured sorted Six2-GFP+ NPCs in 3D aggregates.). Li teaches that nephron progenitor cells “generate all of the nephrons of the mammalian kidney during development” (Abstract, page 1). Hayasashi also teaches that 3D culture conditions of nephron progenitor cells “support long-term expansion of primary mouse and human fetal NPCs as well as NPCs derived from human induced pluripotent stem cells (iPSCs). Expanded NPCs maintain genomic stability, molecular homogeneity, and nephrogenic potential in vitro, ex vivo, and in vivo.” (Abstract).
It would have been obvious to a skilled artisan to substitute the cell aggregate containing human kidney cells with nephron progenitor cells because they were well-known in the art as a predictable and alternative cell source when desiring a cell with differentiation potency, as discussed in the instant claims. Such substitution would have been expected to achieve predictable results in forming nephron progenitor cells aggregates. Additionally, a skilled artisan would be motivated to incorporate nephron progenitor cells within the cell aggregate maintenance process as it would allow the long-term expansion of NPCs for downstream purposes.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
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/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634