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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 04/02/2026 has been entered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
The previous claim objections to claim 1 are withdrawn in light of the amendments.
Claim Rejections - 35 USC § 112
The previous 35 U.S.C. § 112(a) rejection to claim 4 is withdrawn in light of the amendments.
Some of the previous 35 U.S.C. § 112(b) rejections are withdrawn in light of the amendments, the remaining rejections are reiterated below.
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 and 3-4 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.
Regarding claim 1, in lines 12-13, the phrase “the first pores” is recited. There is insufficient antecedent basis for this limitation in the claim. The limitation should be amended to “the plurality of first pores”.
Regarding claim 1, in line 13, the phrase “the second pores” is recited. There is insufficient antecedent basis for this limitation in the claim. The limitation should be amended to “the plurality of second pores”.
Regarding claim 3, in lines 1-2, the phrase “The porous microwell of claim 1, wherein a plurality of the porous microwells are located in the region formed by the penetrating part” describes an invention with the preamble “The porous microwell” (from independent claim 1’s preamble “A porous microwell”), but then claims “a plurality of the porous microwells” within the same invention’s claim set. This claim language incurs:
an antecedent basis issue; and,
widening the metes and bounds or scope of the independent claim.
Regarding point 1, to clarify, claim 3 recites limitation “the porous microwells” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Regarding point 2, to clarify, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “wherein a plurality of the porous microwells are located in the region formed by the penetrating part”, and the claim also recites “The porous microwell of claim 1” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because the first limitation belongs to the singular porous microwell of claim 1, and the second limitation belongs to the singular porous microwell of claim 1 comprising a plurality of the porous microwells of claim 1. The first limitation is narrower than the second limitation, causing the widening of the metes and bounds of the claims.
Regarding the dependent claims 3-4, these claims are rejected for the same reason as the base claim upon which they depend.
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.
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 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Martin (US 20170218321) (previously cited) in view of Gaudette (US 20110142804) (newly cited) and Leong (US 20100093093) (newly cited).
Regarding claim 1, Martin discloses a porous microwell (paragraph [0039]; Fig. 3A-3D), comprising:
a cell culture surface (paragraph [0039]) for culturing three-dimensional cell spheroids (paragraph [0039]), comprising a plurality of first pores (paragraph [0039] “a porous membrane 420”), and having a connection part (paragraph [0039] “the substrate having an array of microwells 410 is porous”) surrounding the cell culture surface (paragraph [0039]) with a plurality of second pores (paragraph [0041] “porous material or a gas permeable material”);
wherein the porous microwell (paragraph [0039]; Fig. 3A-3D) is located with the connection part (paragraph [0039] “the substrate having an array of microwells 410 is porous”) within a region defined by a penetrating part of a cell culture vessel (paragraph [0036]; Fig. 3A-3D, element 110 “sidewalls”) when viewed from a top (Fig. 3A-3D) or bottom side (Fig. 3A-3D), and is indented in a downward direction (Fig. 3A-3D),
wherein the cell culture surface (paragraph [0039]) forms a membrane (paragraph [0039] “a porous membrane 420”) with the connection part (paragraph [0039] “the substrate having an array of microwells 410 is porous”), where the membrane is formed from a plurality of intertwined polymer fibers (paragraphs [0025]-[0026] and [0029]; also, this would have been either inherent or expected with a porous membrane comprising a porous polymer, which constitutes a plurality of polymer fibers),
wherein the plurality of first pores and the plurality of second pores are formed in a region between the plurality of intertwined polymer fibers (paragraphs [0025]-[0026] and [0039]; also, this would have been either inherent or expected with a porous membrane and/or a porous substrate comprising a porous polymer, which constitutes a plurality of polymer fibers).
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Martin, Annotated Fig. 1A
Martin does not disclose:
the cell culture surface has a thickness thinner than the connection part, and
a first porosity formed by the first pores is greater than a second porosity formed by the second pores.
Regarding feature 1, the limitation “the cell culture surface has a thickness thinner than the connection part” is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the thickness of the microwell to be less than the thickness of the connection part in order to promote more fluid transfer through the microwell so that the proper nutrients can more easily flow to the cells and the cellular wastes could be removed more easily.
Nevertheless, if it is deemed that prior art is required to sustain the rejection, Gaudette discloses a cell culture surface (Fig. 15) having a thickness that can be in the variable range of 10-150 μm. (paragraph [0060], “The thickness of the nanofibrous scaffold can also be adjusted as needed. The thickness can be 10-150 μm. … Thickness can be a range of these parameters”).
In the analogous art of the multiwell plates, it would have been obvious to one skilled in the art before the effective filing date to modify the thickness of a scaffold (culture surface) of modified Martin to be adjusted or variable as needed as in Gaudette in order to have a thicker portion near the connecting region so that cells cannot pass through the connection region, and a thinner portion near the cell culture region so that the proper nutrients can more easily flow to the cells and the cellular wastes could be removed more easily.
Regarding feature 2, Martin does not disclose a first porosity formed by the first pores is greater than a second porosity formed by the second pores.
Leong discloses a first porosity formed by first pores is greater than a second porosity formed by second pores (inherent to two different porosities found in paragraphs [0063], [0066]-[0067], and [0094]-[0095]).
In the analogous art of culture containers, it would have been obvious to one skilled in the art before the effective filing date to modify the first and second porosity of Martin’s microwells with the first and second porosity of Leong’s pores in order to allow for the optimization of pore size for different cell culture-specific applications – e.g., neovascularization, fibroblast ingrowth, hepatocyte ingrowth, skin regeneration, etc. (Leong, paragraph [0094]).
Additionally, regarding the phrase “a cell culture surface for culturing three-dimensional cell spheroids”, this limitation is an intended use of the invention. The manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Martin would be fully capable of operating in this manner given the cell culture surface above.
Regarding claim 3, Martin discloses wherein a plurality of the porous microwells (paragraph [0039]; Fig. 3A-3D) are located in the region formed by the penetrating part (paragraph [0036]; Fig. 3A-3D, element 110 “sidewalls”).
Martin does not disclose a plurality of the porous microwells according to claim 1.
Modified Martin teaches the porous microwell according to claim 1 (see rejection to claim 1).
Additionally, if it is deemed that the limitation “a plurality of the porous microwell according to claim 1” is not taught by modified Martin, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the porous microwell of claim 1 as taught by modified Martin with a plurality of porous microwells of claim 1 in order to create a multi-well plate for the use of growing multiple cell spheroids under optionally different environmental conditions and/or under replicate conditions to optimize the results for cell growth, in one device.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Martin (US 20170218321) (previously cited) in view of Gaudette (US 20110142804) (newly cited) and Leong (US 20100093093) (newly cited) as applied to claim 1, as evidenced by McCutcheon (“Influence of concentrative and dilutive internal concentration polarization on flux behavior in forward osmosis”) (previously cited).
Regarding claim 4, Martin discloses wherein, when a fluid flows vertically (paragraph [0080] “fluid communication”) through the porous microwell (paragraph [0039]; Fig. 3A-3D) from an upper side (Annotated Fig. 1A) to a lower side (Annotated Fig. 1A) within an accommodating space of a cell culture vessel (paragraph [0023]; Annotated Fig. 1A, element 150 “a reservoir or a well”), and the surface of the porous microwell (paragraph [0039]; Fig. 3A-3D).
Martin does not disclose a flow concentration phenomenon occurs around a surface of the porous microwell.
However, this phenomenon is inherent to a flow with particles through a filter, and is known as “concentration polarization”, as evidenced by McCutcheon (see pg. 239 under “3.1 Concentrative and dilutive external concentration polarization”, specifically “Water permeates this layer leaving the solute behind in higher concentrations”).
Additionally, regarding the limitation “a flow concentration phenomenon occurs around a surface of the porous microwell” the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Martin would be fully capable of operating in this manner given the porous microwell, an accommodating space of a cell culture vessel, and fluid communication of modified Martin.
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
(DE-202006017853) (machine translation) (newly cited) – This invention describes a synthetic thermoplastic insert for a microtiter plate for the cultivation of different cells (see Fig. 3, below).
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(DE-202006017853), Fig. 3
Béduer (US 20190336649) (newly cited) – This invention describes a 3D scaffold that has various porosities (paragraphs [0107]-[0108]).
Kim (US 20030040033) (newly cited) – This invention describes spin-coating (paragraph [0050]) the structure of microwells within a macro-well (abstract).
Corning. “Transwell Permeable Supports.” (newly cited) – This non-patent literature describes cell culture Transwell inserts for multiwell plates.
Response to Arguments
Applicant’s arguments, see pg. 9 of 15, filed 04/02/2026, with respect to the rejection of claim 1 under 35 U.S.C. § 103 have been fully considered and are partially persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made under 35 U.S.C. § 103 in view of Martin (US 20170218321) (previously cited) in view of Gaudette (US 20110142804) (newly cited) and Leong (US 20100093093) (newly cited).
Regarding the Applicant arguments, pg. 4 of 15, the claim objections have been withdrawn in light of the amendments.
Regarding the Applicant arguments, pgs. 4-6 of 15, the 35 U.S.C. § 112(a) rejection is withdrawn in light of the amendments to align with the expression “a fluid concentration phenomenon” as originally filed. The fluid concentration phenomenon is both a functional limitation and an intended use or manner of operation of the invention, as the flow of fluid vertically downwards through the porous microwell is a manner of operation of the device.
Regarding the Applicant arguments, pg. 6 of 15, the 35 U.S.C. § 112(b) rejections are partially withdrawn. The remaining rejections are put forth above, regarding the use of the terms “the first pores” and “the second pores” of claim 1, as well as the widening scope of claim 3 in comparison to parent claim 1. Claim 4 is rejected by virtue of its dependency on claim 1.
Regarding the Applicant arguments, pgs. 7-8 of 15, features of claim 1 are summarized by the Applicant.
Regarding the Applicant arguments, pg. 8 of 15, Applicant alleges that primary reference Martin does not disclose a single fiber membrane microwell with lateral thickness / porosity gradients. However, the arguments are not commensurate in scope with the claim limitations.
Claim 1 is currently amended as follows:
A porous microwell, comprising:
a cell culture surface for culturing three-dimensional cell spheroids, comprising a plurality of first pores, and having a connection part surrounding the cell culture surface with a plurality of second pores;
wherein the porous microwell is located with the connection part within a region defined by a penetrating part of a cell culture vessel when viewed from a top or bottom side, and is indented in a downward direction,
wherein the cell culture surface forms a membrane with the connection part, where the membrane is formed from a plurality of intertwined polymer fibers, and the cell culture surface has a thickness thinner than the connection part, and
wherein the plurality of first pores and the plurality of second pores are formed in a region between the plurality of intertwined polymer fibers, and a first porosity formed by the first pores is greater than a second porosity formed by the second pores.
The claim does not recite the following argued limitations:
a single, laterally engineered fiber membrane
porosity gradients
Regarding feature 1, the limitations “the cell culture surface forms a membrane with the connection part” and “a plurality of intertwined polymer fibers” are the closest limitations to the argued feature. Regarding “the cell culture surface forms a membrane with the connection part”, Martin discloses that the cell culture surface (paragraph [0039]) forms a membrane (paragraph [0039] “a porous membrane 420”) with the connection part (paragraph [0039] “the substrate having an array of microwells 410 is porous”). Regarding “a plurality of intertwined polymer fibers”, Martin discloses a woven polymer membrane (paragraphs [0025]-[0026] and [0029]). A woven polymer membrane inherently discloses intertwined polymer fibers.
Regarding argued feature 2, porosity gradients, the closest limitations to this argued feature are “a cell culture surface … comprising a plurality of first pores”, “a connection part surrounding the cell culture surface with a plurality of second pores”, and “a first porosity formed by the first pores is greater than a second porosity formed by the second pores”. Although modified Martin was argued previously to contain these limitations, Applicant arguments are persuasive regarding the secondary reference Gottardi.
Regarding the Applicant arguments, pgs. 9 to 11 of 15, Gottardi’s invention does not have the same design of a microwell insert as the instant invention. Therefore, although Gottardi is in the field of endeavor of cell culture plates and qualifies as analogous prior art, the design of the porous membranes of Gottardi is not pertinent to the instant invention in light of the Applicant arguments.
Regarding the Applicant arguments, pg. 11 of 15, Martin discloses the idea of microwells within a well insert (see Figs. 3A-3D). Regarding feature 1 of claim 1, the differences in thicknesses between the connecting part and the cell culture surface is considered obvious in terms of size / proportion of the singular membrane. Nevertheless, newly cited reference Gaudette discloses that different thicknesses can be accomplished by varying the electrospinning method of manufacture (paragraphs [0006]-[0007] and [0060]).
Additionally, regarding Applicant arguments, pg. 12 of 15, the thickness of a membrane being related to its fluid transfer is an obvious design choice. As restated from the previous Office Action:
It would have been obvious to one skilled in the art before the effective filing date to modify the thickness of the microwell to be less than the thickness of the connection part in order to promote more fluid transfer through the microwell so that the proper nutrients can more easily flow to the cells and the cellular wastes could be removed more easily.
Previous Office Action
Regarding feature 2 of claim 1, the difference between the larger first porosity and the smaller second porosity is not found in Gottardi given the context of the claim environment. However, newly cited reference Leong describes different porosities manufactured by electrospinning (paragraphs [0007] and [0094]). Additionally, the woven polymer membranes of one of the embodiments of Martin (see paragraph [0029]) would read upon an intertwined polymer membrane.
Regarding Applicant arguments, pg. 13 of 15, the manner in which a product is manufactured does not pertain to its patentability. The argument that the invention is formed by an embossing process that stretches the fiber membrane is moot. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” MPEP § 2113.
Regarding Applicant arguments, pg. 13 of 15, in response to Applicant’s argument that the examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN G ESPERON whose telephone number is 571-272-9807, and whose fax number is 571-273-8464. The examiner can normally be reached 9 am - 6 pm Monday through Thursday, and 9 am - 6 pm every other Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at 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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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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