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 .
The amendment to the claims filed on 5/20/2026 does not comply with the requirements of 37 CFR 1.121(c) because the claims are not properly marked-up. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states (emphasis added):
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
As noted above, the amendment under consideration herein fails to comply with 37 CFR 1.121. Thus, the amendment could be considered non-responsive. In the interest of compact prosecution, the amendment at issue will not be considered non-responsive, however, any future responses failing to comply with 37 CFR 1.121 will be held non-responsive and will not be considered.
Claims 1-21, of record 5/20/2026, are pending and subject to prosecution. Claims 10-21 remain withdrawn. Claims 1, 5, and 9 are amended.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The applicant’s argument is not found persuasive. The trademarks/tradenames in the specification are not adequately identified by generic terminology. The objection is maintained.
RE: Rejection of claim 9 under 35 U.S.C. 101:
The amendment to claim 9 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 1-6 and 9 under 35 U.S.C. 102(a)(1) over Ando et al. (In Vitro Cellular and Developmental Biology, 1991), evidenced by Schneeberger et al. (American Journal of Physiology – Lung Cellular and Molecular Physiology, 1992) and further evidenced by Corning (Product data sheet, 2023):
RE: Rejection of claims 1-7 and 9 under 35 U.S.C. 103 over Ando et al. (In Vitro Cellular and Developmental Biology, 1991), evidenced by Schneeberger et al. (American Journal of Physiology – Lung Cellular and Molecular Physiology, 1992) and further evidenced by Corning (Product data sheet, 2023).
RE: Rejection of claims 1-9 under 35 U.S.C. 103 over Ando et al. (In Vitro Cellular and Developmental Biology, 1991), evidenced by Schneeberger et al. (American Journal of Physiology – Lung Cellular and Molecular Physiology, 1992) and further evidenced by Corning (Product data sheet, 2023), further in view of Masters et al. (Nature Protocols, 2007):
The amendment to claim 1 to exclude pre-treatment of the bottom support liquid with an extracellular matrix protein is effective to obviate the rejections. The rejections are withdrawn.
New/Maintained Objections/Rejections
Specification
The use of the terms 3M, Novec, Fluorinert, TECCEM, Fluoronox, Pluronic, and Millicell, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, 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.
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, 6, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pilarek et al. (Biotechnology Letters, 2013), evidenced by Perez White et al. (Journal of Cell Science, 2017) and Corning (Product data sheet, 2023), of record.
Regarding claims 1-2, 6, and 9: Pilarek et al. teach the culture of adherent A431 cells on an interface formed between immiscible liquid phases (See Abstract). The aqueous phase comprised DMEM (which reads on “a culture medium”), and the bottom hydrophobic phase comprised perfluorodecalin (which reads on “the bottom support liquid has a higher density than the culture medium, and is not miscible with the culture medium”, “the bottom support liquid is not pretreated with an extracellular matrix protein prior to inoculation of the adherent cells”, and “fluoroalkane compounds”) (See Abstract and page 1388, col. 2, 2). The cells formed a confluent monolayer (which reads on “membranous cell sheet” and “non-stratified, undifferentiated, harvestable monolayer sheet”) after 4-5 days (See page 1389, col. 2, ¶2).
Pilarek et al. do not expressly teach the cells as forming tight junction structures. However, Perez White et al. teach that A431 cells express the tight junction protein occludin and tight junction-associated protein afadin, which localize to cell-cell junctions (See fig. S4), thereby reading on “a tight junction structure”. Micrographs of the cells in 2D culture show a hexagonally close-packed configuration of substantially spherical cells (See fig. S4A-B).
Regarding claim 4: Following the discussion of claims 1-2, 6, and 9, Pilarek et al. teach that 2 ml perfluorodecalin was added per well of a 24-well plate (See page 1388, col. 2, ¶2). Corning et al. teach an approximate growth area of 1.9 cm for each well of a 24-well plate (See Product data sheet, page 2). The amount of perfluorodecalin corresponds to approximately 1.05 ml/cm2 (which reads on “an amount greater than 0.08 mL/cm2”).
Claims 1, 4-7, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frampton et al. (Advanced Functional Materials, 2015), evidenced by Zhang et al. (Journal of Inflammation Research, 2021), Yuki et al. (Journal of Immunology, 2011), and Stevenson et al. (Journal of Cell Science, 1994).
Regarding claims 1, 6-7, and 9: Frampton et al. teach the formation of epithelial cell constructs using an aqueous two-phase system (See Abstract). MCF10A cells, A549 cells, MDCK cells, and primary human keratinocytes (which read on “adherent cells”) in polyethylene glycol media (which read on “culture medium”) were inoculated onto a dextran solution (which reads on “the bottom support liquid has a higher density than the culture medium, and is not miscible with the culture medium” and “the bottom support liquid is not pretreated with an extracellular matrix protein prior to inoculation of the adherent cells”), and the cells settled at the interface of the phases (See fig. 1). After 24 h incubation at 37°C (which reads on “at the temperature of 35-39°C for 1-28 days”), planar tissue constructs (which read on “a membranous cell sheet”) formed (See page 1698, col. 1, full ¶4). Frampton et al. depict the cells as being substantially spherical and cohering to form a hexagonally close-packed sheet (See fig. 1b-c).
Frampton et al. do not expressly teach the cells as forming tight junctions. However, A549 cells (See Zhang et al., page 5804, col. 1, full ¶1 and fig. 4), human keratinocytes (See Yuki et al., Abstract and fig. 5), and MDCK cells (See Stevenson et al., Abstract and fig. 4-6 and 8) all form tight junctions in monolayer culture.
Regarding claims 45: Following the discussion of claims 1, 6-7, and 9, Frampton et al. teach that 500 µl of the dextran solution and 1 × 106 cells in PEG-medium were added to a microcentrifuge tube wherein the area of the biphasic interface was calculated to be approximately 66.5 mm2 (See page 1695, col. 2, full ¶1 and page 1698, col. 1, full ¶4). Therefore, the amount of support phase liquid was greater than 0.75 ml/cm2 (owing to the narrowing of the tube bottom) (which reads on ‘an amount greater than 0.08 mL/cm2”), and the cell concentration was 1.5 × 106 cells/cm2 (which reads on “a concentration of 1×106 -2×106 pcs/cm2”).
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 1-4, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Pilarek et al. (Biotechnology Letters, 2013), evidenced by Perez White et al. (Journal of Cell Science, 2017) and Corning (Product data sheet, 2023), of record, in view of Hanga et al. (Journal of Chemical Technology and Biotechnology, 2017).
The teachings of Pilarek et al., Perez White et al., and Corning are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 3: Following the discussion of claims 1-2, 4, 6, and 9, Pilarek et al., evidenced by Perez White et al. and Corning, teach a method of culturing adherent cells comprising tight junction structures at a liquid-liquid interface but do not teach the hydrophobic phase as a fluorinated oil.
Hanga et al. teach the culture of adherent hMSCs at the interface formed between DMEM and Fluorinert FC-40 (which reads on “fluorinated oil”) (See Abstract and page 1578, col. 2, full ¶1-3).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Pilarek et al., evidenced by Perez White et al. and Corning, to substitute Fluorinert FC-40, as taught by Hanga et al., in place of perfluorodecalin for culturing adherent cells at a liquid-liquid interface. Substitution of one known element for another known element is considered to be prima facie obvious, absent a showing that the substitution yields more than predictable results. See MPEP 2143(I)(B).
Claims 1 and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Frampton et al. (Advanced Functional Materials, 2015), evidenced by Zhang et al. (Journal of Inflammation Research, 2021), Yuki et al. (Journal of Immunology, 2011), and Stevenson et al. (Journal of Cell Science, 1994), in view of Masters et al. (Nature Protocols, 2007), of record.
The teachings of Frampton et al., Zhang et al., Yuki et al., and Stevenson et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 8: Following the discussion of claims 1, 4-7, and 9, Frampton et al., evidenced by Zhang et al., Yuki et al., and Stevenson et al., teach a method of culturing adherent cells comprising tight junction structures at a liquid-liquid interface but do not teach replacement of the culture medium every 10-15 h or replacement of 70-90% of the spent medium.
Masters et al. provide an overview of cell culture protocols and teach that frequency of changing media depends on cell line and medium used and that medium changes must be related to cell health and any experiments (See page 2278, col. 2, full ¶3-4).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Frampton et al., evidenced by Zhang et al., Yuki et al., and Stevenson et al., to comprise the claimed medium change, because Masters et al. indicate that the timing and nature of media changes are result-effective variables (See page 2278, col. 2, full ¶3-4), and therefore ripe for optimization. See MPEP 2144.05(II)(B).
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
Prosecution Insights