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 .
Response to Arguments and Amendments
Regarding Applicant’s request to withdraw the restriction requirement (pg. 8 of Remarks dated 9/4/2026), there is still a lack of unity of invention because the common matter of the independent claims is well known and the remaining subject matter of each claim differs from that of the others without there being any unifying novel inventive concept common to all (MPEP § 1850 II).
The interpretation of “measurement unit” in claim 14 and “control unit” in claim 15 under 35 U.S.C. 112(f) is withdrawn in light of the claim amendments dated 9/4/2026.
The claim amendments dated 9/4/2026 have overcome the rejection under 35 U.S.C. 112(b) presented in the prior Office Action.
Applicant’s arguments with respect to rejected claims 1-4, 8-12, and 15 under 35 U.S.C. 103 filed 9/4/2026 have been considered but are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“a measurer configured to measure a potential between the first electrode and the second electrode, thereby determining a permeability of the modelled blood labyrinth barrier” in claim 14, lines 1-3.
Note: Examiner is interpreting the noted limitation under 35 U.S.C. 112(f) because the term “measurer” does not provide sufficient structure.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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, 9-12, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Alcon et al. (US 2016/0326477 A1) (hereinafter referred to as Fernandez-Alcon, previously presented) in view of Takezawa (WO 2018/003858 A1) (English machine translation provided, see PTO-892) and Xiaorui Shi, Pathophysiology of the cochlear intrastrial fluid-blood barrier (review) (hereinafter referred to as Shi, see PTO-892).
Regarding claim 1, Fernandez-Alcon discloses a device, comprising:
a first fluid channel (Fig. 3G, first central microchannel 312 – see figure below);
a second fluid channel (Fig. 3G, second central microchannel 314);
and a membrane separating the first and second fluid channels (Fig. 3G, membrane 320 separates each channel), a first cover sheet (Fig. 3H, sealing layer 301 – see figure below), a second cover sheet (Fig. 3H, sealing layer 307)
wherein the membrane has a luminal side in the first fluid channel and an abluminal side in the second fluid channel (Fig. 3G, membrane has a side facing each channel),
wherein endothelial cells are attached to the luminal side of the membrane ([0074], cells of a first type adhered a first side of the membrane; [0475], endothelial cells can be co-cultured on one side of the membrane),
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wherein pericytes are attached to the abluminal side of the membrane ([0074], cells of a second type adhered to a second side of the membrane; [0475], pericytes cells can be co-cultured on one side of the membrane).
Fernandez-Alcon teaches a first lamination layer having at least one first opening (Fig. 3H, 303), wherein the first medical tape adheres at the first cover sheet, thereby forming the first fluid channel ([0103]; Fig. 3H); and a second lamination layer having at least one second opening portion (Fig. 3H, 305), wherein the second medical tape adheres at the second cover sheet, thereby forming the second fluid channel ([0103]; Fig. 3H). Moreover, Fernandez-Alcon teaches that at least one of the lamination layers can include an optically clear adhesive layer ([0103]).
Fernandez-Alcon does not explicitly disclose wherein the first lamination layer and second lamination layer are a first medical tape, a second medical tape.
However, Takezawa in the analogous art of organ chip systems teaches it is known in the art to use double-sided medical tape as adhesive layers ([0076]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute Fernandez-Alcon’s lamination layers for Takezawa’s medical tape because it would serve the same purpose of binding the layers and membrane together. It has been held that it is prima facie obvious to substitute equivalents known for the same purpose (MPEP § 2144.06).
The prior art combination discussed above does not explicitly disclose wherein perivascular macrophage-type melanocytes are arranged in the second fluid channel.
However, Shi in the analogous art of the study in vitro cell models teaches that in vitro models of the BLB co-culturing endothelial cells (ECs) on one side of a transwell membrane and perivascular macrophage-type melanocytes (PVM/Ms) on the other is known in the art (Fig. 5). Moreover, Shi teaches that the structure of the BLB includes pericytes (PCs) on an abluminal side of a membrane (Fig. 1A; pg. 53, section 2, “Extensively branched strial PCs tightly embrace the abluminal strial capillary wall”), ECs on a luminal side of a membrane (Fig. 1A), and PVM/Ms opposite the vascular channel (Figs. 1A and 3D).
Shi teaches that in vitro cell line-based blood barrier models are well known in the art (p. 59, first column, second paragraph) and are important for determining interaction between vascular blood barrier cells and testing potential drug candidates, as well as providing insight (p. 59, second column, second paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art combination device to co-culture ECs, PCs, and PVM/Ms in the manner claimed for the purpose of accurately mimicking the anatomical BLB. The ordinarily skilled artisan would be motivated to investigate signaling interactions between ECs, PCs, and PVM/Ms in an environment similar to that of an anatomical BLB.
The limitation “for modelling a blood labyrinth barrier of a human ear” is merely a recitation of a purpose or intended use of the invention and has been given an appropriate patentable weight (MPEP § 2111.02 II).
Regarding claim 2, the prior art combination teaches the device according to claim 1, wherein the membrane has a permeability allowing a chemical transport between the first fluid channel and the second fluid channel (Fernandez-Alcon: [0314]).
Regarding claim 3, the prior art combination teaches the device according to claim 1, wherein the luminal side of the membrane is coated with collagen and/or the abluminal side of the membrane is coated with fibrinogen (Fernandez-Alcon: [0278]).
Regarding claim 4, the prior art combination teaches the device according to claim 1, comprising a first inlet and a first outlet (Fig. 3A, inlet and outlet 334 and 336) configured to perfuse a first culture medium through the first fluid channel ([0163] and [0457]-[0460]), and a second inlet and a second outlet configured to perfuse a second culture medium through the second fluid channel ([0163] and [0457]-[0460]).
Regarding claim 9, the prior art combination teaches the device according to claim 1, wherein each of the first medical tape and the second medical tape comprises an acrylic-based adhesive ([0076], 3M product number 1524 is acrylic-based).
Regarding claim 10, the prior art combination teaches the device according to claim 1.
The prior art combination as discussed above does not disclose wherein each of the first cover sheet and the second cover sheet comprises glass and/or polycarbonate.
However, Fernandez-Alcon teaches in different embodiments the device can use glass or polycarbonate to enable uniform pressure distribution throughout the device ([0127]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art device to use glass or polycarbonate for each of the first cover sheet and the second cover sheet to enable uniform pressure distribution and allow a user to monitor the culture.
Regarding claim 11, the prior art combination teaches the device according to claim 4, wherein the first fluid channel comprises a first main portion in an elongated form (Fernandez-Alcon: Fig. 3A, first central microchannel 312; Fig. 3B, top channel of central channel 310 – see annotated figure below), and a first incoming portion connected with the first inlet and a first outgoing portion connected with the first outlet (Fernandez-Alcon: Fig. 3B, first incoming and first outgoing portion shown, inlet 334 and outlet 336), and
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wherein the second fluid channel comprises a second main portion in an elongated form (Fernandez-Alcon: Fig. 3A, second central microchannel 314; Fig. 3B, bottom channel of central channel 310), and a second incoming portion connected with the second inlet and a second outgoing portion connected with the second outlet (Fernandez-Alcon: Fig. 3B, second incoming portion and second outgoing portion shown, inlet 330 and outlet 332).
Regarding claim 12, the prior art combination teaches the device according to claim 11, wherein the first incoming portion does not overlap with the second incoming portion in a direction perpendicular to the first medical tape, and the second incoming portion does not overlap with the first main portion in the direction perpendicular to the second medical tape, and
wherein the first outgoing portion does not overlap with the second outgoing portion in the direction perpendicular to the first medical tape, and the second outgoing portion does not overlap with the first main portion in the direction perpendicular to the second medical tape (Fernandez-Alcon: Fig. 3A-3B shows that all features do not cross a plane defined by the membrane, which meets all the limitations set forth).
Regarding claim 15, the prior art combination teaches the device according to claim 1, comprising a controller configured to control a pressure applied to the device ([0163] discloses a central processing unit to control flow of fluid through the device, i.e., fluid pressure).
The limitation “for simulating a disease such as inflammation and Meniere's disease using the blood labyrinth barrier modelled by the device” is directed toward the intended manner of operating the claimed controller and does not differentiate the claimed structure from the prior art structure because all structural limitations are taught in the prior art (MPEP § 2114 II). The prior art central processing unit would be fully capable of achieving every claimed intended use because it can control fluid flow through the device.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Alcon, Takezawa, and Shi as applied to claim 4 above, and further in view of Karasiewicz-Mendez et al. (US 2018/0298328 A1) (hereinafter referred to as Karasiewicz-Mendez, previously presented).
Regarding claim 5, the prior art combination teaches the device according to claim 4.
Fernandez-Alcon of the prior art combination teaches that the formulation of cell culture media can vary with individual cell types because cell types can require a unique combination and concentrations of nutrients and/or supplements ([0457]).
The prior art combination discussed above does not explicitly disclose the first culture medium as claimed in claim 5.
However, Karasiewicz-Mendez in the art of cell culturing teaches it is known in the art that cell culture mediums can include endothelial basal medium ([0335]), fetal bovine serum ([0222]), epidermal growth factor ([0224]), basic fibroblast growth factor ([0224]), insulin-like growth factor ([0224]), vascular endothelial growth factor ([0224]), ascorbic acid ([0222], [0232]), hydrocortisone ([0222]), and penicillin/streptomycin ([0224]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the prior art combination to further comprise a first culture medium as claimed in claim 5 for the purpose of facilitating growth and stimulation of cells, as taught by Karasiewicz-Mendez. The ordinarily skilled artisan would be motivated to use ingredients known to successfully culture cells.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Alcon, Takezawa, Shi, and Karasiewicz-Mendez as applied to claim 5 above, and further in view of Zhang et al., Culture media-based selection of endothelial cells, pericytes, and perivascular-resident macrophage-like melanocytes from the young mouse vestibular system, Hearing Research, Elsevier Science Publishers, vol. 345, pp. 10-22, January 11, 2017. (hereinafter referred to as Zhang, previously presented).
Regarding claim 6, the prior art combination teaches the device according to claim 5.
The prior art combination discussed above does not explicitly disclose or teach the second culture medium as claimed in claim 6.
However, Zhang in the analogous art culturing endothelial cells, pericytes, and perivascular-resident macrophage-like melanocytes teaches it is known in the art to use culture media including a combination of Dulbecco's modified eagle's medium, fetal bovine serum, pericyte growth supplement, pigment epithelium-derived factor, and penicillin/streptomycin solution (pg. 11, section 2.3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the claimed culture medium in the device taught by the prior art combination because it is appropriate for endothelial cells, pericytes, and perivascular-resident macrophage-like melanocytes, as taught by Zhang.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Alcon, Takezawa, Shi, and Karasiewicz-Mendez as applied to claim 5 above, and as evidenced by Atzler et al. (US 2022/0127553 A1) (hereinafter referred to as Atzler, previously presented).
Regarding claim 7, the prior art combination teaches the device according to claim 5.
The prior art combination does not explicitly disclose or teach the second culture medium as claimed in claim 7.
However, Zhang teaches use of a culture media including a combination of medium 254CF plus calcium chloride (pg. 11, section 2.3), fetal bovine serum (pg. 11, section 2.3), human melanocyte growth supplement (pg. 11, section 2.3), basic fibroblast growth factor (pg. 14, section 2.12), insulin-like growth factor (pg. 14, section 2.12) and gentamicin/amphotericin B (pg. 11, section 2.3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use insulin in place of insulin-like growth factor because insulin and insulin-like growth factor are both usable as growth factors, as evidenced by Atzler in the art of culturing cells ([0053]). It has been held that it is prima facie obvious to substitute equivalents known for the same purpose (MPEP § 2144.06).
Further, Karasiewicz-Mendez teaches it is known in the art of culturing to use hydrocortisone in cell culture media as an immunosuppressive or immunomodulatory agent ([0068]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use hydrocortisone in a culture media to suppress or modulate the immune response of the cells cultured.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use culture medium as claimed in the device taught by the prior art because it would facilitate cell growth and control the immune response of the cells being cultured, as taught by the prior art combination.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Alcon, Takezawa, and Shi as applied to claim 1 above, and further in view of Ingber (US 2018/0298317 A1) (hereinafter referred to as Ingber, previously presented).
Regarding claims 13-14, the prior art combination teaches the device according to claim 1.
The prior art combination does not disclose or teach a first electrode or second electrode as claimed in claim 13.
However, Ingber discloses a system comprising a first channel, second channel and membrane disposed between the channels (abstract; Fig. 1) for cell culturing and biomimetics (abstract; [0010]). Ingber further discloses wherein the system comprises one or more sensors for measuring a potential across the membrane to determine permeability ([0181], lines 16-24). The one or more sensors are taught to be capable of being integrated with the device for culturing ([0181], lines 24-26).
The claimed measurer is interpreted under 35 U.S.C. 112(f) (see Claim Interpretation section above). The corresponding prior art elements perform the functions specified in the claim, are not precluded by any explicit definition provided in the specification for an equivalent, and are an equivalent of the means- (or step-) plus-function limitation. Examiner finds that the prior art sensors are equivalent to the limitation of note because of at least one of the following reasons:
The prior art element performs the identical function specified in the claim in substantially the same way, and produces substantially the same results as the corresponding element disclosed in the specification.
A person of ordinary skill in the art would have recognized the interchangeability of the element shown in the prior art for the corresponding element disclosed in the specification.
There are insubstantial differences between the prior art element and the corresponding element disclosed in the specification.
In particular, the prior art elements perform the identical function specified in the claim in substantially the same way, and produces substantially the same results as the corresponding element disclosed in the specification. Therefore, the one or more sensors is prima facie equivalent to the claimed measurer (MPEP § 2183).
As for the location of the electrodes, it has been held that rearrangement of parts is unpatentable because the shifting of parts would not modify the operation of the device (MPEP § 2144.04 VI). The one or more sensors of Ingber would predictably be capable of measuring a potential across the membrane to determine permeability regardless of placement with respect to a first channel or a second channel.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate one or more sensors to measure a potential across the membrane and determine permeability.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Ponomarenko (US 2016/0369221 A1) drawn to a device for in vitro complex living tissue reconstruction.
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 ADRIAN J CARREON whose telephone number is (571)272-6818. The examiner can normally be reached Monday - Friday 8:30 AM - 5 PM.
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/A.J.C./Examiner, Art Unit 1799
/William H. Beisner/Primary Examiner, Art Unit 1799
