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 .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites “wherein, in a case where a cell sheet is formed on the upper surface of the gas permeable membrane, a space above the gas permeable membrane is in a seal state in which gas does not pass through” is confusing and indefinite. The wherein clause does not identify the boundary or path through which gas is allegedly prevented from passing. This phrase can be read in at least three materially different ways:
(i) no gas passes between the upper space and ambient atmosphere;
(ii) no gas passes through the gas-permeable membrane into or out of the upper space; or
(iii) no gas passes through the cell sheet that completes the boundary.
The first interpretation is consistent with a gas-tight lid, the second directly conflicts with 'gas permeable,' and the third makes scope depend on an unrecited permeability property of a biological sheet.
Furthermore, the conditional phrase, 'in a case where a cell sheet is formed, ' compounds the uncertainty in apparatus claim 1. It is unclear whether the device must possess structure capable of producing the sealed state, whether the cell sheet is a required component of the claimed apparatus, or whether the limitation applies only after an unclaimed future use. The specification states that the space is defined by the cell sheet, insert, first member, and second member (US 2024/0302353 A 1, para. [0037] as published), but does not resolve which interfaces must prohibit which gases or to what degree.
Because claims 2-13 directly or indirectly incorporate claim 1, the same ambiguity prevents a person of ordinary skill from determining their boundaries. Applicant may overcome this rejection by positively identifying the boundary and permitted gas-transfer path, and by reciting the required structural state without the conditional 'in a case where' formulation.
Note: any amendment should preserve written-description support and should clarify whether 'sealed' means gas-tight. Substantially gas-tight, or a specified leakage/permeability threshold.
Claim 13 depends on claim 7 which depends on claim 1. Claim 13 repeats the same structure of cell culture device recited in claim 1. Thus, it is unclear if the cell culture device in claim 13 is referring to the same device in claim 1. This is confusing and indefinite. Also, applicant should refrain from compound claiming (13 depends on claim 7 which depends on claim 1) for clarity.
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 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) 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):
(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). The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f), 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). The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f), 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) 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) 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) 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:
“member for holding” in claim 1 has been interpreted as corresponding to the first member /insert receiver 17 as commensurate with the structures in the specification or structural equivalents;
b. “a structure for regulating a gas concentration” is construed to include a cover or plug whose seal or structural equivalents.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) 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) applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) (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).
In the patentability analysis of apparatus claims 1-6, aspects or limitations the examiner interprets as functional/process/intended use language and/or elements that are not positively recited as part of the claimed apparatus have been generally italicized whereas aspects interpreted as positively recited structural components are normally bolded. The bold font and italics are shown when the structure and function are initially introduced though not necessarily repeated, particularly in dependent claims. The examiner applies this formatting for both the examiner and applicant’s convenience. However, absent the referenced typestyles, the patentability analysis will still be clear regarding which limitations the examiner interprets as structural versus functional/process/intended use and/or not positively recited structure(s). Also, note that it has been held that recitations in which an element is "adapted to/for", “configured to/for”, “positionable”, “moveable/immovable”, etc., only requires the ability to so perform (i.e., functional/process/intended use). Again, functional/process/intended use recitation(s) and/or element(s) not positively recited as part of the apparatus do not constitute a limitation in any patentable sense with respect to the prior art. Please note these recitations have not been ignored by the examiner. All of the recitation(s) in applicant’s claims 1-6 have been considered by the examiner and afforded the appropriate amount of patentable weight. In certain instances, during prosecution, the examiner’s current interpretation(s) regarding the patentable weight of these limitation(s) might change based on the facts of the case.
The examiners below patentability analysis provides one or more interpretations and claim mappings of the claimed structures and steps although other interpretations may be possible. In the patentability analysis, the Office applies the broadest reasonable interpretation (BRI) consistent with the specification and specific limitations from the specification have not been read into the claims.
See MPEP at least §2111.02, 2173.01 I 2114, and 2173.05(g).
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 1-5 and 7-13 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Allbritton et al., (WO 2019/222333- hereinafter “Allbritton”), see corresponding US 2021/0087515 for citations below.
Regarding claim 1, Allbritton teaches a cell culture device comprising:
a plate (corresponds to microtiter plate 10) having a concave portion (corresponds to reservoir 120) for accommodating a culture medium (see Figs. 1A-1F; paras. [0182], [0187] et seq.);
a cell accommodating container having a gas permeable membrane (reads on luminal reservoir/container 140 positioned within basal reservoir 120, with bottom wall 170 formed as a porous, semipermeable, or oxygen-permeable membrane supporting a collagen scaffold and epithelial cells (Figs. 1A-1F and 14A-14C; paras. [0183], [0187], [0252], [0272], [0282] et seq.);
a first member for holding the cell accommodating container (reads on basal reservoir 120 together with basal flange 126 and the cooperating support-arm receiving relationship. Support arms 156 of luminal container 140 contact flange 126 to support and hold luminal container 140 within basal reservoir 120, while keyed features maintain its spacing (Figs. 1A-1F; paras [0182] et seq. Basal reservoir 120 and its flange are distinct from microtiter plate 10 in the illustrated assembly and perform the same insert-holding function as the claimed first member);
a second member having a structure for regulating a gas concentration in an upper space of the cell accommodating container, (reads on removable cover 260 and its port/channel 266, plug 268, tubing, and gas-supply arrangement. Gas of an adjusted composition can be supplied through a cover port to establish or regulate a gas gradient, and the port can then be sealed (see Figs. 1D-1F; paras. [0146]-[0149], [0189] et seq.);
wherein, in a case where a cell sheet is formed on an upper surface of the gas permeable membrane, a space above the gas permeable membrane is in a sealed state in which gas does not pass through- not required for reasons delineated above, but Allbritton teaches epithelial monolayer supported above porous bottom wall 170 and the upper luminal region bounded by luminal reservoir 140 and installed cover 160/260. The cover, plug, gasket, walls, and sealed port form a gas barrier that prevents gas exchange with the environment, while the cell layer and permeable support permit the intended basal-to-luminal oxygen gradient (Figs. 1A-1F, 2A-8C, and 14A-14C; paras. [0181], [0184], [0189]-[0191], [0252]-[0254], [0258], [0272], [0281]-[0282], [0295] et seq).
Regarding claim 2, Allbritton teaches wherein the cell accommodating container is attachable and detachable (reads on luminal container 140 being separately positioned within basal reservoir 120, with support arms 156 resting on flange 126 rather than being formed as a unitary part of the basal reservoir (see Figs. 1B, 1E, 1F, and 14A-14C; paras. [0182]-[0183], [0252]-[0254], [0282]).
Regarding claim 3, Allbritton teaches wherein the space above the gas permeable membrane is allowed to be accessed by removing the second member (reads on cover 160/260 being removably installed, including by threaded engagement, so that removal of the cover opens the luminal reservoir and provides access to the
upper surface of the cell support (Figs. 1A-1F; paras. [0181], [0189]-[0190]).
Regarding claim 4, Allbritton teaches wherein the structure for regulating the gas concentration in the upper space of the cell accommodating container is a structure for holding an oxygen scavenger and/or a structure for supplying gas having an adjusted concentration (reads cover port, tubing, and gas supply for introducing gas having an adjusted composition into the luminal reservoir to generate or regulate the gas gradient (Figs. 1D-1F; paras. [0146]-[0149], [0189] et seq.) Because this claim presents alternatives "and/or" the adjusted-gas-supply structure satisfies the limitation. Allbritton need not show an oxygen-scavenger holder.
Regarding claim 5, Allbritton teaches wherein the second member has a structure for measuring the gas concentration in the upper space (reads on release port 266 extending through cover 260 and receiving a gas sensor, including an oxygen sensor or needle probe, for measuring oxygen saturation in the luminal reservoir while the port is sealed around the sensor (Figs. 1D-1F; para [0189] et seq.)
Regarding claim 7, Allbritton teaches a cell culture method comprising:
culturing cells on the gas permeable membrane in a state in which the cells form a cell sheet, using the cell culture device according to claim 1 (reads on culturing primary human colonic epithelial cells on the porous-membrane cassette and collagen support until a confluent monolayer is formed, followed by installation of the plug/cover to establish luminal hypoxia, Figs. 2A-8C and 14A-14c, paras. [0252]-[0258], [0272], [0282] et seq.) Allbritton teaches a thin collagen or Matrigel coating on the porous membrane, which does not remove the cells from being cultured "on" the membrane under the broadest reasonable interpretation (see para [0276] et seq.)
Regarding claim 8, Allbritton further teaches the cells are intestinal epithelial cells (reads on primary human colon or colonic epithelial cells forming the monolayer (paras. [0257]-[0258], [0282], [0296] et seq.)
Regarding claim 9, Allbritton further teaches wherein bacteria are co-cultured on the cell sheet (reads on inoculating C. difficile onto the luminal side of the human colonic epithelial monolayer and co-culturing the bacteria with the epithelial cell sheet under the oxygen gradient (paras. [0264], [0303] et seq.)
Regarding claim 10, Allbritton teaches wherein the bacteria are bacteria capable of inhabiting a human intestine reads on C. difficile, a colon pathogen associated with disruption of human gut microbiota and colonic infection, cultured on the luminal side of human colonic epithelial cells (para. [0303] et seq.). Allbritton identifies the common probiotic intestinal organism Bifidobacterium adolescentis (para. [0310] et seq.)
Regarding claim 11, Allbritton teaches the cells are cultured in aerobic conditions, and the bacteria are cultured in anaerobic conditions (reads on maintaining an oxygenated basal reservoir for the intestinal epithelial cells while the sealed luminal compartment is hypoxic or anaerobic and supports obligate anaerobic bacteria (paras. [0258] et seq.)
Regarding claim 12, Allbritton teaches wherein a response of intestinal epithelial cells or bacteria is evaluated by co-culturing the intestinal epithelial cells and the bacteria (reads on evaluating bacterial CFU and growth and epithelial responses including IL-8 secretion, ZO-1 organization, tight-junction integrity, TEER, morphology, viability, proliferation, differentiation, and barrier function during co-culture (paras. [0296] et seq.)
Regarding claim 13, Allbritton teaches a cell culture method comprising:
wherein the cells are cultured by installing a cell culture device in a CO2 gas incubator or in a multi-gas incubator (reads on culturing all human cells in a CO2 incubator at 37 C and incubating the aerobic and oxygen-gradient co-culture samples in the CO2 incubator at 37 C (paras. [0258] et seq.)
wherein the cell culture device comprises a plate having a concave portion for accommodating a culture medium; a cell accommodating container having a gas permeable membrane; a first member for holding the cell accommodating container; and a second member having a structure for regulating a gas concentration in an upper space of the cell accommodating container (reads on microtiter plate 10, basal reservoir 120, luminal container 140 with porous bottom wall 170, the flange 126/support-arm 156 holding relationship, and removable ported cover 260 for the reasons and citations provided above for claim 1).
wherein, in a case where a cell sheet is formed on an upper surface of the gas permeable membrane, a space above the gas permeable membrane is in a sealed state in which gas does not pass through (reads on the confluent intestinal epithelial monolayer and the luminal space substantially sealed against outside gas exchange by the installed cover, plug, walls, gasket, and sealed port, while oxygen reaches the cells from the basal side through the permeable support (paras. [0181] et seq. and Figs. 1A-1F and 8A-8C).
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Allbritton in view of Sato et al. (WO 2020/235206 A1; corresponding US 2022/0220427 A1; hereinafter "Sato"). Paragraph citations below are to the corresponding U.S. publication.
Regarding claim 6, Allbritton teaches the cell culture device according to claim 1 (see the reasons and citations provided above for claim 1). Allbritton does not explicitly tach an oxygen scavenger. In the related art of cell culture devices, Sato teaches an oxygen scavenger analogous epithelial-cell culture container. Sato teaches an upper container 110, an airtightly fitted lid 120, a lower container 140, a membrane 113, and an oxygen-scavenger portion in the lid or upper container configured to hold an oxygen scavenger. The scavenger absorbs or removes oxygen from the upper container so that the upper space rapidly becomes anaerobic without a nitrogen chamber. Sato identifies iron-oxidation and organic oxygen scavengers as suitable examples, (see Fig. 1; paras. [0043]-[0045], and [0136]).
Accordingly, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the oxygen scavenger of Sato in the sealed hypoxic cell-culture device in Allbritton, as an alternative or
supplemental means for reducing residual luminal oxygen since the references address the same problem in the same field. That is, maintaining epithelial cells from the basal side while creating an anaerobic upper or luminal compartment suitable for anaerobic intestinal bacteria. Sato expressly teaches that the scavenger makes the upper compartment anaerobic quickly and avoids the need for a nitrogen chamber (Sato- paras. [0043]-[0045], [0134]-[0139]). Allbritton independently acknowledges that an anaerobic gas-generating sachet can create an anaerobic, CO2-rich environment in a closed container without an external gas supply (para. [0103]). Supplying Sato's disclosed scavenger with Allbritton's compatible device as the claimed kit would therefore have predictably accelerated or supplemented oxygen removal and
ensured that the consumable needed for that disclosed mode of operation was available with the culture device.
Citations to art
In the above citations to documents in the art, an effort has been made to specifically cite representative passages, however rejections are in reference to the entirety of each document relied upon. Other passages, not specifically cited, may apply as well.
Pertinent Prior Art
The following prior art is hereby made of record. Although the prior art is relied upon, the examiner considers the listed prior art relevant to the applicant’s invention and may be relied upon in a future prior art rejection or as general background information related to applicant’s field of endeavor.
Li et al., (US 2010/0047907) teach tissue culture plates with permeable tissue culture plate inserts therein, which provides the tissue culture plates with apical chamber and a basolateral chambers, wherein cells are deposited on the permeable tissue culture inserts and essentially all of tissue culture medium has been removed from the apical chambers of the tissue culture plates and the basolateral chambers of the tissue culture plates contain a solidifiable form of cell culture medium. Also described are cells that can be deposited and grown on the described tissue culture inserts, methods for transporting a tissue culture plate with a permeable tissue culture plate insert therein on which cells are deposited. Also described is a kit for transporting the tissue culture plates described above, and corresponding methods of use.
Oliver et al., (US 2018/0346867) teach a low-oxygen system is directed to culturing a diverse microbiome and includes an anaerobic chamber and at least one microfluidic device removably inserted in the anaerobic chamber. The microfluidic device includes a first microchannel in which a first level of oxygen is maintained, and a second microchannel in which a second level of oxygen is maintained, the second level of oxygen having a greater oxygen concentration than the first level of oxygen. The microfluidic device further includes a membrane located at an interface region between the first microchannel and the second microchannel, the membrane further having a plurality of pores via which oxygen flows from the second microchannel to the first microchannel to form an oxygen gradient in the first microchannel. The system further includes a culture system provided in the first microchannel and including oxygen-sensitive anaerobic bacteria.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to P. Kathryn Wright whose telephone number is (571)272-2374. The examiner can normally be reached between 9:30am-7pm EST.
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E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
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/P. Kathryn Wright/Primary Examiner, Art Unit 1798
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