ADETAILED 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 Rejections - 35 USC § 112
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 1-3 and 5-18 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 recites the limitation "the first end face". There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the second end face". There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the diameter of the spheroid". There is insufficient antecedent basis for this limitation in the 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.
Claim(s) 1-3, 5-9,11, and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Makino et al. (US 2021/0123012).
Regarding claim 1 Makino discloses a cell culture device comprising at least one microwell comprising a top portion including a top opening for introducing cells, a bottom portion for cultivating said cells and a side wall joining said top portion to said bottom portion for guiding cells from said top opening to said bottom portion, characterized in that said top portion and said side wall are integral and made of a first material non-adhesive to cells and said bottom portion is made of a second material adhesive to cells. (See Makino Abstract and Figs. 4-5 and [0109]-[0111] wherein a cell culture device comprises a microwell with a top portion for introducing cells and a bottom portion for cultivating cells with a sidewall joining the two. The top portion and sidewall are integrally formed in one layer and are made of a first material non-adherent to cells and the bottom portion is formed in a layer made of a second material adhesive to cells.)
Makino also discloses wherein said side wall is an inclined surface which connects the first end face to the second end face in order to guide cells deposited on said inclined surface substantially towards a coplanar level of the second end face by gravity so that the cells adhere to the bottom portion thus allowing their culture in order to form a spheroid, (See Makino Figs. 4-5 wherein the sidewall is inclined from top face to bottom face to guide cells by gravity to the bottom portion to form a spheroid.)
Makino also discloses wherein the bottom portion is comprised within a circular shape and wherein the diameter of said circular shape is smaller than the diameter of the spheroid.(See Makino [0043] wherein the bottom portion is comprised within a circular shape and has diameters which may be smaller than a spheroid diameter, i.e. spheroids range in diameter from about 50 to 2000 microns which is greater than the 10-1000 microns of the bottom portion .)
Furthermore it is noted that limitations directed to cell settling, spheroid formation, and spheroid diameter are directed to intended uses and materials worked on by the device which do not define structural elements which differentiate the claimed invention from the cited prior art. See MPEP 2114 and 2115.
Regarding claim 2 Makino discloses all the claim limitations as set forth above as well as the device wherein said top portion is a first end face of said microwell, said microwell comprises a second end face opposite to said first end face, which second end face comprises a bottom opening, and said bottom portion is formed by a base made of said second material with said second end face resting on said base. (See Makino Figs. 4-5 and [0109]-[0111] wherein the top portion is a first open end face and a second end face is placed on a base, i.e. substrate, layer made of the second material.)
Regarding claim 3 Makino discloses all the claim limitations as set forth above as well as the device wherein said bottom opening is arranged above said bottom portion in an overlapping manner. (See Makino Figs. 4-5 and [0109]-[0111] wherein the bottom opening overlaps above the bottom portion.)
Regarding claim 5 Makino discloses all the claim limitations as set forth above as well as the device wherein said bottom portion comprises a layer of functionalized extracellular matrix protein. (See Makino [0061] wherein the bottom portion is coated with a functionalized extracellular matrix protein, i.e. collagen.)
Regarding claim 6 Makino discloses all the claim limitations as set forth above as well as the device wherein said first material is chosen in the group consisting of polyethylene glycol, a polyurethane polymer, polyamides, polyvinyl alcohol, polyethylene oxide, polypropylene oxides, polyethylene glycol, polypropylene glycol, polytetralethylene oxide, polyvinylpyrrolidone, polyacrylamide, polyhydroxyethyl acrylate, polyhydroxyethyl methacrylate, and mixtures thereof, PDMS and silicone-based materials. (See Makino [0111] where the first material includes those described.)
Regarding claim 7 Makino discloses all the claim limitations as set forth above as well as the device wherein said second material is glass. (See Makino [0111] wherein the substrate is formed from glass, i.e. the second material is glass.)
Regarding claim 8 Makino discloses all the claim limitations as set forth above as well as the device wherein a plurality of microwells microwells are arranged together in a seeding well. (See Makino Abstract and [0129] wherein a cell culture sheet, i.e. a seeding well, comprises a plurality of microwells arranged together.)
Regarding claim 9 Makino discloses all the claim limitations as set forth above as well as the device wherein said seeding well is arranged in a microwell.(See Makino [0129] wherein a seeding well, i.e. cell culture sheet, is arranged in another cell culture vessel, i.e. a dish, which may be a microwell/macrowell.)
Regarding claim 11 Makino discloses all the claim limitations as set forth above as well as the device wherein the microwell is shaped in the form of a funnel. (See Makino Fig. 4 wherein the microwells are shaped in the form of a funnel, i.e. tapered walls.)
Regarding claim 18 Makino discloses all the claim limitations as set forth above as well as the device wherein the bottom portion is circular. (See Makino [0043] wherein the bottom portion is a circle.)
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.
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.
Claim(s) 10,12, and 15-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Makino et al. (US 2021/0123012) as applied to claims above.
Regarding claim 10 Makino discloses all the claim limitations as set forth above as well as the device comprising a plurality of macrowells in which at least a seeding well is arranged. (See Makino [0129] wherein a seeding well, i.e. cell culture sheet, is arranged in another cell culture vessel, i.e. a dish, which may be a macrowell.)
Makino does not specifically disclose a plurality of macrowells however it is noted that such a modification would have required a mere duplication of parts which would have been obvious to one of ordinary skill in the art in order to increase amounts of cells grown and because mere duplication of parts has no patentable significance unless a new and unexpected result is produced. In re Harza, 124 USPQ 378, 380 (CCPA 1960). Further, it has been held that mere duplication of the essential working parts of a device involves only routine skill in the art. St. Regis Paper Co. v. Bemis Co., 193 USPQ 8.
Regarding claim 12 Makino discloses all the claim limitations as set forth above as well as a method for cultivating spheroids, comprising the step of introducing cells and medium into a microwell of a device according to claim 1, letting the cells sediment to the bottom of said microwell by gravity and cultivating the cells in order to enable said cells to aggregate into spheroids. (See Makino Abstract Figs. 4-5 and rejection of claims above wherein cells settle by gravity into the microwells to form spheroids therein.)
Makino does not specifically disclose the amount of time in which the cells are cultured it is noted that as the cost of operation and level of cell growth are variables that can be modified, among others, by adjusting said culture time, with said cost and cell growth both increasing as the culture time is increased, the precise culture time would have been considered a result effective variable by one having ordinary skill in the art at the time the invention was made. As such, without showing unexpected results, the claimed culture time cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the culture time in the method of Makino to obtain the desired balance between the cost and cell growth. (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding claim 15 Makino discloses all the claim limitations as set forth above as well as the device wherein the top opening presents a diameter between 10 and 1000 μm the bottom portion presenting a diameter in a range from 10 microns to 300 μm, and a distance from the bottom portion to the top opening being 10-1000 μm.
In regards to the specific diameters and distances claimed it would have been obvious to one of ordinary skill in the art at the time of invention to have selected the overlapping portion of the ranges disclosed by the reference because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. In re Malagari, 182 USPQ 549.
Regarding claims 16-17 Makino discloses all the claim limitations as set forth above as well as the device wherein the bottom portion may have a variety of shapes but does not specifically disclose the bottom portion is hexagonal or wherein the bottom portion is orthogonal.
It is noted that it would have required a mere change of shape to provide a bottom portion which is hexagonal or orthogonal in the device of Makino which would have been obvious to one of ordinary skill in the art at the time of filing because Makino recognizes that the shape of the bottom portion may be optimized according to use and because the change in configuration of shape of a device is obvious absent persuasive evidence that the particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
Claim 13 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Makino et al. (US 2021/0123012) as applied to claims above, and further in view of Martin et al. (US 2017/0218321).
Regarding claim 13 Makino discloses all the claim limitations as set forth above but does not specifically disclose adding cells of a different type to the spheroids.
Martin discloses a method of forming spheroids wherein said spheroids are formed from more than one cell type and requires adding cells of more than one type to the spheroids. (See Martin Abstract and [0063] wherein cells of more than one type are added to spheroids.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide cells of a different type to the spheroids of Makino as described by Martin in order to grow spheroids of a desirable nature as would be desirable in the method of Makino.
Regarding claims 14 Makino discloses all the claim limitations as set forth above as well as the device configured for automated image acquisition, wherein all the materials of the cell culture device are substantially optically transparent with respect to the visible light, (See Makino [0111] wherein the substrate is transparent, i.e. optically clear with respect to visible light also materials listed for the substrate include those with are transparent to visible light. )
The device is thus configured for automated image acquisition and such limitations are directed to intended uses of the claimed device which do not define structural elements which differentiate the device from the cited prior art. See MPEP 2114 and 2115.
Makino also discloses the device may have numerous shapes but does not specifically disclose the sidewall having first top and second bottom portions with inclinations and the first portion having a steeper inclination angle. does not specifically
Martin discloses a device for forming spheroids comprising a microwell with a top opening a bottom portion and a sidewall joining the two wherein the side wall comprising at least a first portion and a second portion presenting a first inclination angle and a second inclination angle respectively, the second portion being located next to the bottom portion of the at least one microwell, the first inclination angle being steeper than the second inclination angle with respect to the vertical of the side wall. (See Martin Fig. 1A wherein a microwell comprises a top opening 101, a bottom portion 120 and a sidewall with a first portion 110 having a greater inclination angle than a second portion 115.)
It would have been obvious to one of ordinary skill in the art at the time of filing to provide a sidewall with first and second portions as described by Martin in the device of Makino because such shaped sidewalls encourage seeded cells to aggregate and form spheroids without binding to the sidewall as would be desirable in the device of Makino.
Furthermore It is noted that such a modification would have required a mere change of shape of the sidewall which would have been obvious to one of ordinary skill in the art at the time of filing because Makino recognizes that the shape of sidewall may be optimized according to use and because the change in configuration of shape of a device is obvious absent persuasive evidence that the particular configuration is significant. In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966).
Response to Arguments
Applicant's arguments filed 11/18/2025 have been fully considered but they are not persuasive.
Applicant argues “nothing discloses or suggests (neither in Makino nor in any other cited prior art) that the diameter of the bottom portion is smaller than the diameter of the formed spheroid. As amended, claim 1 now requires that "the diameter of said circular shape is smaller than the diameter of the spheroid." Therefore, subject matter of Claim 1 is new.”
It is noted that Makino discloses bottom portions having a diameter from 10 to 1000 microns which is less than a diameter of a spheroid which ranges to diameters greater than this. Limitations directed to the spheroid and diameter thereof are intended uses and materials worked on by the device which do not structurally differentiate the claimed invention from the cited art.
Applicant also argues “In addition, Makino does not disclose that its device is adapted or configured for automated image acquisition. Makino merely mentions that image-analysis software can be used to measure the diameter of the spheroid (paragraph [0134]). However, there is no teaching about the automatization of the image-analysis software. In particular, Makino provides no indication that the device can perform multiple steps or operations autonomously, without requiring continuous human intervention, in contrast to subject matter of Claim 1.
Moreover, Makino does not disclose that all the materials of the device are optically transparent to the visible light. (See Makino [0111] wherein the substrate is transparent, i.e. optically clear with respect to visible light also materials listed for the substrate are those with are transparent to visible light.)
Further, Makino only reveals continuous side wall from top to bottom whereas subject matter of Claim 1 requires at least two inclination angles. “
Applicant’s arguments with respect to the specific automated image analysis types envisioned are not commensurate in scope with the claimed invention. The device of Makino is fully capable of being used in automated image analysis devices/software if one so wished and is thus so configured.
Furthermore Makino does in fact disclose the device being formed from materials which are optically transparent to visible light.
In regards to the shape of the sidewall it is noted that additional art and rational were utilized to reject such limitations and applicant’s arguments with respect to such are moot.
Applicant finally argues that “Also, Makino discloses a top opening diameter of 500 pm and a bottom portion diameter of 300 pm. These values differ from those of the subject matter of claim 15, which specifies 600 pm for the top opening and 120 ±10pm for the bottom portion. Moreover, the distance from the bottom portion to the top opening in D1 is 275 pm, compared to 600 pm in claim 15.”
It is noted that Makino specifically notes that the opening diameter, bottom portion diameter, and depth are subject to modification according to use and discloses ranges of values which include the claimed ranges. In regards to the specific diameters and distances claimed it would have been obvious to one of ordinary skill in the art at the time of invention to have selected the overlapping portion of the ranges disclosed by the reference because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. In re Malagari, 182 USPQ 549.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONATHAN M HURST/ Primary Examiner, Art Unit 1799