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 Claims
The amendment filed 7/8/2026 has been entered. Claims 1 and 3-19 remain pending in the application; and claims 2 and 20 have been cancelled. Applicant’s amendments to the claims have overcome each objection and 112(b) rejection previously set forth in the Non-Final Office Action mailed 3/2/2026.
Drawings
The drawings were objected to as failing to comply with 37 CFR 1.84(p)(5) because they did not include the following reference sign(s) mentioned in the description: "platform 100" (paras. 0017, 0041); “upper sub-chambers” 10-2, 10-3, 10-4 (para. 0044); “upper sub-chambers” 20-2, 20-3, 20-4 (para. 0044). Corrected drawing sheets and amendments to the specification were received 7/8/2026. Accordingly these objections to the drawings have been withdrawn.
The drawings were objected to as failing to comply with 37 CFR 1.84(p)(4) because reference characters “10-1” and “10” had both been used to designate the upper sub-chamber (paras. 0031, 0044, 0045); reference characters “15-1” and “15” had both been used to designate the culture substrate ridge (paras. 0044, 0045); reference characters "16-1" and "16" had both been used to designate the separating member (para. 0022); reference characters “20-1” and “20” had been used to designate the sub-chamber (paras. 0022, 0029, 0030, 0044, 0045). Corrected drawing sheets and amendments to the specification were received 7/8/2026. Accordingly, the objections to the drawings have been withdrawn.
The drawings were objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “T1” had been used to designate both the first tube and the second tube (para. 0025). Corrected drawing sheets and amendments to the specification were received 7/8/2026. Accordingly, the objections to the drawings have been withdrawn.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “20-1” has been used to designate both lower sub-chamber and upper sub-chamber (para. 0044, lines 6-7 “upper sub-chamber 20-1”). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The abstract of the disclosure was objected to because "In accordance with various embodiments of the disclosed subject matter" is a phrase which can be implied and the abstract was less than 50 words. A corrected abstract of the disclosure was received 7/8/2026. Accordingly, the objection to the abstract of the disclosure has been withdrawn.
The use of the terms Matrigel (para. 0021), Formlabs Form2 SLA 3D printing system (para. 0055), and Formlabs Clear Resin (para. 0055), which are trade names or marks used in commerce, has been noted in this application. Amendments to the specification were received 7/8/2026. Accordingly, these objections to the specification have been withdrawn.
The disclosure was objected to because it was recommended that "This application claims benefit to U.S. provisional application 63/423,689, filed November 8, 2022, said application incorporated herein by reference." be added on page 1 after the title. Amendments to the specification were received 7/8/2026. Accordingly, this objection to the specification has been withdrawn.
The disclosure is objected to because of the following informalities: paragraph [0001.1] appears to be improperly labeled; i.
Appropriate correction is required.
Response to Arguments
Applicant’s arguments filed 7/8/2026 have been considered but they are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
Applicant argues on p. 10 of Remarks that Mackowiak et al.’s lid would render the combination of Singh and Mackowiak et al. unable to perform its intended function. This is not persuasive, as it has been held that a determination of obviousness based on teachings from multiple references does not require an actual, physical substitution of elements; the criterion being not whether the references could be physically combined but whether the claim inventions are rendered obvious by the teachings of the prior art as a whole; rather, the test for obviousness is what the combined teachings of those references would have suggested to those of ordinary skill in the art (MPEP § 2145 III). Mackowiak et al. discloses an inset with protrusions that sits on top of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10), and this would suggest to one of ordinary skill in the art that a cover with protrusions would be an advantageous structure to include in a fluidic culture apparatus to allow a second population of cells to be cultured with the first set of cells. Therefore, one of ordinary skill in the art would be motivated to include a lid comprising protrusions based on the teachings of Mackowiak et al.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8, 15-16, and 19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 8, 15-16, and 19 do not contain a reference to a claim previously set forth, but instead contain a reference to a cancelled claim (claim 2). For the purpose of examination on the merits, the Examiner is interpreting claims 8, 15-16, and 19 as if dependent on claim 1, of which claims 8, 15-16, and 19 specify a further limitation of the subject matter (a lid) claimed. Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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.
Claims 1, 3-8, and 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Singh (WO 2023/036942 A1) (already of record) in view of Mackowiak et al. (US 2019/0249126 A1) (already of record).
Regarding claim 1, Singh discloses an apparatus (cell culture apparatus 100), comprising: a base (cell culture plate 102), having a top surface and a bottom surface and having formed therein a plurality of open top chambers (cell culture modules 106, first chamber 206) and at least a first fluidics circuit (first flow channel 210, second flow channel 212); each open top chamber being divided into respective upper (first (apical or top) chamber 206) and lower sub-chambers (second (basal or bottom) chamber 208) by a respective chamber separating membrane (membrane 214; p. 16, lines 25-26 “The membrane 214 has through pores (see FIG. 2C) and is arranged between the first chamber 206 and the second chamber 208 such that the first chamber 206 and the second chamber 208 are in flow communication with each other via the through pores of the membrane 214”; abstract “The apical and basal chambers are separated by a porous membrane”), wherein the upper and lower sub-chambers are defined by interior surfaces configured to allow organ culture substrates to be secured thereto (abstract “cultivate cells of the same or different types on the basal surface of the porous membranes in the cell culture module”); the first fluidics circuit configured to support a first fluid flow between a first port (first culture medium reservoir 202, inlet 216) on the base and second port (second culture medium reservoir 204, inlet 220) on the base, the fluidics circuit being further configured to support a fluid flow through a lower sub-chamber of at least one of the plurality of open top chambers (p. 17, lines 14-16 “The first and second flow channels 210 and 212 are microchannels providing the passage of the culture medium between the first and second culture medium reservoirs 202 and 204 through the second chamber 208”).
Singh does not disclose a lid, having a top surface and a bottom surface, the bottom surface having formed thereon a plurality of protrusions, each protrusion configured to mate with a corresponding upper sub-chamber of the plurality of open top chambers. However, Mackowiak et al. discloses an inset with protrusions that sits on top of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10). It would have been obvious to a person of ordinary skill in the art to use the Mackowiak et al. configuration of an inset with protrusions that sits on top of a culture plate in Singh’s device with a reasonable expectation that it would allow a second population of cells to be cultured in the wells of a culture plate. This method for improving Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Mackowiak et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Singh and Mackowiak et al. to obtain the invention as specified in claim 1.
Regarding claim 3, Singh discloses an apparatus wherein the first fluidics circuit is further configured to support a fluid flow through a lower sub-chamber of at least a second one of the plurality of open top chambers (p. 15, lines 22-26).
Regarding claim 4, Singh discloses an apparatus the base having formed therein a second fluidics circuit configured to support a second fluid flow between a bottom port on the base in fluid communication with a lower sub-chamber and a top port on the base in fluid communication with a respective upper sub-chamber (p. 15, lines 22-26).
Regarding claim 5, Singh discloses an apparatus wherein each of the plurality of open top chambers have associated with it a respective second fluidics circuit for supporting a respective second fluid flow therethrough (p. 14, lines 16-17; p. 15, lines 22-25).
Regarding claim 6, Singh discloses an apparatus wherein the base forms therein a third fluidics circuit configured to support a third fluid flow between a port on the base in fluid communication with an upper sub-chamber and a top port protruding through the top surface of the base convey thereby a portion of the first fluid flow (p. 14, lines 16-17; p. 15, lines 22-25).
Regarding claim 7, Singh discloses a cell culture apparatus, but does not disclose a lid, having a top surface and a bottom surface, the bottom surface having formed thereon a plurality of protrusions, each protrusion configured to mate with a corresponding upper sub-chamber of the plurality of open top chambers; the lid having formed therein a recess configured to allow passage therethrough of a top port protruding through the top surface of the base. However, Mackowiak et al. discloses an inset with protrusions that sits on top of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10). It would have been obvious to a person of ordinary skill in the art to use the Mackowiak et al. configuration of an inset with protrusions that sits on top of a culture plate in Singh’s device with a reasonable expectation that it would allow a second population of cells to be cultured in the wells of a culture plate. This method for improving Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Mackowiak et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Singh and Mackowiak et al. to obtain the invention as specified in claim 7.
Regarding claim 8, it has been held that 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 art product was made by a different process (MPEP § 2113 I). Therefore, the cell culture apparatus disclosed by Singh would anticipate the 3D printed apparatus of the claimed invention even though both were made by a different process.
Regarding claim 10, Singh discloses an apparatus wherein each chamber separating membrane is capable of isolating at least some target cells harbored in the respective sub-chambers separated thereby. Regarding the limitation “configured to isolate at least some target cells harbored in the respective sub-chambers separated thereby”, it has been held that a claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim (MPEP § 2114 II). Therefore, the apparatus disclosed by Singh would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to have a membrane that separates chambers and allow cells to be cultivated on it (abstract) and would be structurally capable of isolating cells in the respective sub-chambers absent clear evidence otherwise.
Regarding claim 11, Singh discloses an apparatus wherein interior chamber surfaces are configured to allow organ culture substrates to be secured thereto (abstract “cultivate cells of the same or different types on the basal surface of the porous membranes in the cell culture module”).
Regarding claim 12, it has been held that 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 art product was made by a different process (MPEP § 2113 I). Therefore, the cell culture apparatus disclosed by Singh would anticipate the 3D printed apparatus of the claimed invention even though both were made by a different process.
Regarding claim 13, Singh discloses an apparatus wherein interior chamber surfaces treated to promote adhesion and growth of organ culture substrates are configured to allow organ culture substrates to be secured thereto (p. 13, lines 1-10; p. 3, line 16 “the cells in the culture medium to cause the cells to bond”).
Regarding claim 14, Singh discloses an apparatus wherein at least one of the sub-chambers includes a growth matrix associated with a desired organ culture (p. 10, lines 12-13 “the culture medium comprises human brain vascular endothelial cells and said another culture medium comprises human astrocytes”).
Regarding claim 15, Singh discloses a cell culture apparatus, but does not disclose a lid wherein at least one of said lid protrusions is configured to extend into and substantially seal a corresponding upper sub-chamber. However, Mackowiak et al. discloses an inset that protrudes into the wells of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10). It would have been obvious to a person of ordinary skill in the art to use the Mackowiak et al. configuration of an inset that protrudes into the wells of a culture plate in Singh’s device with a reasonable expectation that it would allow a second population of cells to be cultured in the wells of a culture plate. This method for improving Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Mackowiak et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Singh and Mackowiak et al. to obtain the invention as specified in claim 15.
Regarding claim 16, Singh discloses an apparatus wherein said base comprises four open top chambers (Fig. 1 cell culture plate 102 comprises multiple cell culture modules), but does not disclose a lid comprising four corresponding protrusions. However, Mackowiak et al. discloses an inset with protrusions that sits on top of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10). It would have been obvious to a person of ordinary skill in the art to use the Mackowiak et al. configuration of an inset with protrusions that sits on top of a culture plate in Singh’s device with a reasonable expectation that it would allow a second population of cells to be cultured in the wells of a culture plate. This method for improving Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Mackowiak et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Singh and Mackowiak et al. to obtain the invention as specified in claim 16.
Regarding claim 17, Singh discloses an apparatus wherein said base comprises four open top chambers (Fig. 1 cell culture plate 102 comprises multiple cell culture modules) but does not disclose a lid comprising four corresponding protrusions. However, Mackowiak et al. discloses an inset with protrusions that sits on top of a culture plate to allow a second population of cells to be cultured in the wells of a culture plate (abstract; Fig. 6 well insert 10). It would have been obvious to a person of ordinary skill in the art to use the Mackowiak et al. configuration of an inset with protrusions that sits on top of a culture plate in Singh’s device with a reasonable expectation that it would allow a second population of cells to be cultured in the wells of a culture plate. This method for improving Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Mackowiak et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Singh and Mackowiak et al. to obtain the invention as specified in claim 17.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Singh (WO 2023/036942 A1) (already of record) in view of Mackowiak et al. (US 2019/0249126 A1) (already of record) as applied to claim 1 above, and further in view of Sbrana et al. (WO 2015/044813 A1) (already of record).
Regarding claim 9, Singh discloses an apparatus wherein the base comprises four chambers defined therein (Fig. 1 cell culture plate 102 comprises multiple cell culture modules), but does not disclose wherein the base comprises a cylindrical component. However, Sbrana et al. teaches that a support for cell cultures having a cylindrical body is known in the art (Fig. 1). Though modified Singh does not explicitly teach a cylindrical apparatus, it would have been obvious to a person of ordinary skill in the art to use a cylindrical-shaped apparatus because the substitution of one known element for another would have predictably resulted in an apparatus that supports cell cultures, with reasonable expectation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the teachings of modified Singh with the teachings of Sbrana et al. to obtain the invention as specified in claim 9.
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Singh (WO 2023/036942 A1) (already of record) in view of Mackowiak et al. (US 2019/0249126 A1) (already of record) as applied to claim 1 above, and further in view of Klausner et al. (US 2024/0368508 A1) (already of record).
Regarding claim 18, Singh discloses a cell culture apparatus, but does not disclose wherein the apparatus comprises a first apparatus and the top surface of the lid of the first apparatus is configured to cooperate with a bottom surface of a base of a second apparatus such that the first and second apparatus may be combined into a stacked apparatus. However, Klausner et al. discloses stackable multi-well culture plates (abstract; Fig. 10) which allows crosstalk between physiological systems (para. 0002). It would have been obvious to a person of ordinary skill in the art to use the Klausner et al. configuration of stackable culture plates in modified Singh’s device with a reasonable expectation that it would allow crosstalk between physiological systems. This method for improving modified Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Klausner et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Singh and Klausner et al. to obtain the invention as specified in claim 18.
Regarding claim 19, modified Singh discloses a cell culture apparatus comprising a lid, but does not disclose wherein the apparatus comprises a first apparatus and the top surface of the lid of the first apparatus is configured to cooperate with a bottom surface of a base of a second apparatus such that the first and second apparatus may be combined into a stacked apparatus; wherein each upper sub-chamber of the first apparatus is in fluid communication with a respective lower sub-chamber of the second apparatus. However, Klausner et al. discloses stackable multi-well culture plates (abstract; Fig. 10) which allows crosstalk between physiological systems (para. 0002). It would have been obvious to a person of ordinary skill in the art to use the Klausner et al. configuration of stackable culture plates in modified Singh’s device with a reasonable expectation that it would allow crosstalk between physiological systems. This method for improving modified Singh’s device was within the ability of one of ordinary skill in the art based on the teachings of Klausner et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Singh and Klausner et al. to obtain the invention as specified in claim 19.
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 ASHLEY LOPEZLIRA whose telephone number is (703)756-5517. The examiner can normally be reached Mon - Fri: 8:30-5:00.
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
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