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 .
Status of the Application
Claims 19-38 are pending.
Claims 1-18 are canceled.
Claims 19-38 are new.
Claims 23-26 and 32-35 are withdrawn
Claims 19-22, 27-31, and 36-38 have been examined on the merits.
Applicant’s election without traverse of Group I, claims 19-22 and 27-38, drawn to a method of using inorganic particles, filed on 04/06/2026 in response to the restriction requirement set forth in the prior office action, is acknowledged.
Claims 23-26 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant’s election without traverse of the species of swellable layered silicate in response to the species requirement set forth in the prior office action is acknowledged.
Claims 32-35 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Specification
The specification is objected, because the use of the term “mica”, which is a trade name or a mark used in commerce, has been noted in this application (see paras 0013-0015 and 0024-0025 of the instant specification). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trade marks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Priority
This application, U.S. Application number 17/910629, is a national stage entry of International Application Number PCT/JP2021/011128, filed on 03/18/2021, which claims for foreign priority to JAPAN 2020-049062 filed on 03/19/2020 under 35 U.S.C. 119 (a)-(d).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/09/2022, 04/17/2024, 09/20/2024, 11/15/2024, 12/16/2024, 02/04/2025, 05/08/2025, and 06/26/2025 is acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97., and have been considered by the examiner.
Drawings
The drawings submitted on 09/09/2022 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Rejections - 35 USC § 112(b), or 112, Second Paragraph
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 19-22 and 29-31 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 pre-AIA the applicant regards as the invention.
Claim 19 recites in the preamble the use of inorganic particles having adsorbability as a spheroid formation promoter. But, since the claim does not set forth any active steps involved in the method/process, it is unclear what specific method/process Applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966). Furthermore, this method claim requires an essential step to culture cells so as to allow the inorganic particles to achieve the goal of acting as a spheroid formation promoter, as stated in the claim's preamble as well as in the specification of the instant application. However, the claim does not recite any step for culturing cells or any limitations about cell culture. In the absence of this essential step, it is unclear how the action of promoting spheroid formation is achieved and whether the recited inorganic particles act as a promoter for forming spheroids of cultured cells or other different materials.
Claims 22 and 31 recites the limitation “mica” to describe a particular material, i.e. a swellable layered silicate. It is noted that the recited mica is a trademark. Per MPEP 2173.05(u), if the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Given that different formulations can be prepared under the same trademark name and products under certain trademark names may be discontinued commercially, the metes and bounds set forth by this trademark term are not clear.
Claims 20 and 29 are indefinite due to the recitation of “inorganic particles are particles composed of … magnesium oxide-aluminum oxide solid solution”. It is noted that the “inorganic particles” specifically defined in the claims are solid particles, whereas the recited “magnesium oxide-aluminum oxide solid solution” is in the liquid form. It is unclear how the purely solid inorganic particles can be composed of a liquid solution. For the purpose of examination, the “magnesium oxide-aluminum oxide solid solution” is interpreted as “magnesium oxide-aluminum oxide”.
Claims 21 and 30 describe that inorganic particles have a property of adsorbing 10 mg – 500 mg of bovine serum albumin (BSA) per 1 mg of the inorganic particles. However, neither the claim nor the specification specifically defines any standard conditions for carrying out a BSA adsorption assay for determining BSA adsorption. It is noted that adsorption assay conditions affect an amount of BSA adsorbed to inorganic particles, and an amount of BSA adsorbed by a specific inorganic particle is varied based on specific assay conditions such as BSA concentrations, a weight ratio of inorganic particles vs. BSA, temperatures, pH, and buffer solutions. As such, 10 mg – 500 mg of BSA may be adsorbed by 1 mg of inorganic particles under one assay condition, but not under another assay condition, even though the same inorganic particles are used in the assays. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the metes and boundary of the “inorganic particles” described in the claims.
The remaining claims are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 102
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.
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.
Claims 19 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Whitehead et. al. (Adv. Biosys. 2019, 1900141, pages 1-9, cited in IDS).
This is a rejection of the GENERIC claims with respect to the specie of inorganic particles.
Whitehead et. al. teach a method for promoting the formation of spheroids having osteogenic phenotype, comprising: mixing human mesenchymal stem cells with hydroxyapatite particles (i.e. inorganic particles having adsorbability) with adsorbed BMP-2 (as an osteoinductive cue) in a culture medium to obtain a mixture; and culturing the cells in the mixture in microwell plates to thereby form spheroids (abstract; page 7/right col/para 2 – page 8/left col/para 1). Whitehead et. al. further teach that formation of spheroids having osteogenic phenotype is promoted by hydroxyapatite particles with adsorbed BMP-2 (i.e. BMP-2 loaded HA), compared to formation of spheroids without using BMP-2 loaded HA (abstract, page 7/conclusion/lines 1-3). Given that the inorganic particles with adsorbed BMP-2 used in the method of Whitehead et. al. promote the formation of osteogenic spheroids, the teachings of Whitehead et. al. read on the claim 19.
Regarding the claim 21, the adsorption of bovine serum albumin is directed to an inherent property of the inorganic particles recited in the claim. The inorganic particles having adsorbability taught by Whitehead et. al. have the same structure as that of the claimed inorganic particles. In the absence of evidence to the contrary, it is presumed that products having substantially the same structure have substantially the same properties. Thus, the inorganic particles of Whitehead et. al. meet the limitation in the claim.
Therefore, in view of the teachings of Whitehead et. al., the method of Claims 19 and 21 is anticipated by the method of Whitehead et. al.
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 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.
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.
Claims 19, 21, 27-28, 30, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Whitehead et. al. (Adv. Biosys. 2019, 1900141, pages 1-9, cited in IDS).
This is a rejection of the GENERIC claims with respect to the specie of inorganic particles.
The teachings of Whitehead et. al. are described above.
Regarding the claim 27, the method of Whitehead et. al. is slightly different from the claimed method, specifically, in that Whitehead et. al. teach resuspending the pellet of a known number of cells, not a cell suspension, in a liquid medium dispersed of HA inorganic particles (with adsorbed BMP-2) to obtain a HA-cell mixture in which HA inorganic particles are dispersed with homogeneity (page 7, right col, last 3 lines). However, how to mix the cells with the inorganic particles to obtained the HA-cell mixture in the method of Whitehead et. al. is an obvious design choice. It would have been obvious to one of ordinary skill in the art to resuspend/mix a suspension of the cells in/with the liquid medium dispersed of HA inorganic particles to obtain the HA-cell mixture in the method of Whitehead et. al. for promoting the spheroid formation, because this mixing process also generates a HA-cell mixture in which HA inorganic particles are dispersed with homogeneity.
Regarding the claims 36 and 37, Whitehead et. al. teach cells are human mesenchymal stem cells, as indicated above.
Regarding the claim 38, Whitehead et. al. teach culturing the cells are cultured in a culture microplate to form a spheroid, as indicated above.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 19-22, 27-30, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Yuko et al. (JP 2019163212 A, published on 09/26/2019, cited in IDS, a machine-translated English version is attached), as evidenced by Whitehead et. al. (Adv. Biosys. 2019, 1900141, pages 1-9, cited in IDS).
Yuko et al. teach a spheroid-formation accelerator (i.e. a spheroid-formation promoter) derived from a protein raw material of fish species, which promotes spheroid formation after being simply added to a culture medium of animal cells (e.g. pluripotent stem cells, iPS cells); and Yuko et al. also teach a method of using water-insoluble inorganic particles as a powdered adsorbent for concentrating and/or purifying the spheroid-formation promoter (i.e. a target protein) from the protein raw material, which comprises mixing the inorganic particles and the protein raw material for adsorbing the target protein, thereby obtaining water-insoluble inorganic particles with adsorbed target protein (i.e. spheroid-formation promoter), while impurities are remained in liquid solution (abstract; paras 0001-0003, 0015-0016, 0021-0024, and 0026-0027; Example 1; Claim 4). In the Example 1 (paras 0020-0026), Yuko et al. tested various different water-insoluble powdered candidate substances to find adsorbents effective at adsorbing the target protein through determining whether the remained liquid solution still has any target protein with spheroid-formation promoting activity. Yuko et al. concluded that the inorganic particles of aluminum silicate, aluminum oxide, diatomaceous earth, hydrotalcite, allophane, and montmorillonite are adsorbents suitable for effectively adsorbing the target protein (i.e. spheroid-formation promoter) from the protein raw material (para 0026). Furthermore, Yuko et al. continued to teach directly using a powder form of adsorbents with adsorbed target protein (spheroid-formation promoter), when culturing animal cells, for promoting formation of three-dimensional culture/spheroids (para 0027/lines 1-3).
In view of that Yuko et al. teach using a powdered adsorbent with adsorbed target protein (spheroid-formation promoter) for promoting spheroid formation and that water-insoluble inorganic powdered adsorbents are suitable for the adsorbing the target protein, it would have been obvious to one of ordinary skill in the art to use water-insoluble inorganic particles with adsorbed target protein as a spheroid-formation promoter for promoting spheroid formation when culturing animal cells to form a spheroid. Thus, the teachings of Yuko et al. render the claim 19 to be obvious.
Regarding the mixing step recited in the claim 27, Yuko et al. teach when culturing the animal cells, simply adding the spheroid-formation promoter to the culture medium and mixing it with animal cells to obtain a mixture for promoting spheroid formation (paras 0002/last 4 lines, 0024/lines 5-6). Given that Yuko et al. teach using a powdered adsorbent with adsorbed target protein as a spheroid-formation promoter, it would have been obvious to mix a cell suspension and a dispersion of inorganic particles with adsorbed target protein in a culture medium to obtain a mixture of the cells and inorganic particles, and then to culture the cells in the mixture in the method suggested by Yuko et al. for promoting spheroid formation, thus arriving the claimed method of the claim 27.
Regarding the claim 28, the spheroid-formation promoter of Yuko et al. promotes spheroid formation. It would be expected that the spheroid formation is promoted in the presence of the inorganic particles with adsorbed target protein, compared to a negative control in which no spheroid-formation promoter is used.
Regarding the inorganic particles defined in the claims 20, 22, and 29, Yuko et al. teach the water-insoluble inorganic particles are silicate, specifically: montmorillonite, thus meeting the claimed limitations.
Regarding the claims 21 and 30, the adsorption of bovine serum albumin is directed to an inherent property of the inorganic particles recited in the claims. The inorganic particles having adsorbability taught by Yuko et al. have the same structure as that of the claimed inorganic particles. In the absence of evidence to the contrary, it is presumed that products having substantially the same structure have substantially the same properties. Thus, the inorganic particles of Yuko et al. meet the limitation in the claims.
Regarding the claims 36 and 37, Yuko et al. teach the cells are animal cells or specifically human liver cells HepG2 (paras 0002 and 0024), thus, meeting the limitations in the claims.
Regarding the claim 38, it is a common practice in the art to use a culture plate to culture cells, as evidenced by Whitehead et al. (whose teachings are described above). Thus, the teachings of Yuko et al. render the claim to be obvious.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 19-22, 27-31, and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Yuko et al. (JP 2019163212 A, published on 09/26/2019, cited in IDS, a machine-translated English version is attached), as applied to the claims 19-22, 27-30, and 36-38, further in view of Whitehead et. al. (Adv. Biosys. 2019, 1900141, pages 1-9, cited in IDS).
The teachings of Yuko et al. and Whitehead et. al. are described above.
Whitehead et. al. further teach that lower concentration of HA inorganic particles with adsorbed BMP-2 exhibited the greatest increase in gene expression and activity as well as the highest percentage of retained calcium for induction of the formation of osteogenic spheroids (page 7, Conclusion), and they specifically choosing the lower concentrations of 0.1 mg/ml, i.e. 0.01 w/v% (g/ml); 0.5 mg/ml, i.e. 0.05 w/v% (g/ml); and 1 mg/ml, i.e. 0.1 w/v% (g/ml) as the solid content concentrations in the HA-cell mixture (page 2/the para spanning both cols, Figs. 1 and 3), all of which read on the claimed range of 0.0003 – 0.333 w/v%.
Regarding the claim 31, Yuko et al. are silent about a solid content/concentration of silicate in the mixture. However, it would have been obvious to include montmorillonite silicate in the mixture at a concentration in the range of 0.0003 – 0.333 w/v% in the method suggested by Yuko et al. for promoting the spheroid formation for the following reasons. First, the claim 31 does not recite any unit to limit the claimed concentration range 0.0003 – 0.333 w/v%, and the recited concentrations can have any w/v units, such as g/ml, g/liter, mg/ml, mg/liter, microgram/ml, and microgram/liter. As such, the claimed concentration range has an extremely broad scope and it does not meaningfully limit the amount of silicate used in the claimed method. Second, it is well known in the art that an inorganic particle concentration in a mixture of cells and inorganic particles affects formation and phenotype of spheroids; and that concentrations in the claimed range promote the formation of spheroid with desired phenotype, as supported by Whitehead et. al. Furthermore, it is considered that a concentration of silicate/montmorillonite in the mixture used in the method suggested by Yuko et al. can be readily modified by routine optimization for promoting the spheroid formation; and routine optimization is not patentable even though it results in significant improvement over the prior art (see MPEP 2144.05). Thus, the concentration range recited in the claim 31 would have been obvious over the teachings of the cited prior art, in the absence of evidence to support it is critical.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656
Prosecution Insights