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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 4-5, 7, 9, 11-17, and 19-24 in the reply filed on 11/14/2025 is acknowledged.
Claims 1-3 and 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/14/2025.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/21/2023, 10/17/2023, 05/21/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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.
Claims 4, 12, 16, 19-20, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cho et al. (US Patent Application Publication 2014/0273223) (already of record).
Regarding claim 4, Cho et al. discloses a microphysiological system (Abstract, para. 82), comprising a microfluidic chip (para. 14), comprising:
a planar surface (101) (para. 37) (Fig. 1, sheet 1 of 18);
a first channel (“low height” channel) (201) formed on the planar surface (Abstract, para. 37) (Fig. 2, sheet 2 of 18) and having a first volume defined by a first width, a first height, and a first length (Abstract, para. 61) (Figs. 1-2, sheets 1-2 of 18), the first channel extending in a first direction (Fig. 1, sheet 1 of 18); and
a second channel (high height channel, e.g., channel 200 in Fig. 1 and 10, sheets 1 and 12 of 18; channel 203 in Fig. 12, sheet 14 of 18) (Abstract, para. 40) formed on the planar surface adjacent to the first channel (para. 36-37) (e.g., Fig. 2, sheet 2 of 18), the second channel having a second volume defined by a second width, a second height, and a second length (Abstract) (Figs. 1-2, sheets 1-2 of 18), the second channel extending in the first direction (Fig. 1, sheet 1 of 18), the second height being greater than the first height (para. 36-40) (Fig. 2, sheet 2 of 18);
wherein the first channel is in fluid communication with the second channel through a first opening that extends along at least a portion of the first length wherein the first opening extends from the planar surface to the first height (para. 36, 43-50) (Figs. 2, 4, sheets 2, 4 of 28); and
wherein the first height and the second height are selected such that surface tension of a liquid added to either the first channel or the second channel provides a non-physical microfluidic barrier that selectively limits passage of the liquid through the first opening (para. 40, 53); and
an extracellular matrix (401) (called scaffold; reads on an extracellular matrix as it provides a 3-dimensional scaffold for cell growth therein and is made of extracellular matrix materials such as collagen) (para. 43-45) for use within the first channel (201) (para. 43), wherein a side wall of the extracellular matrix when added to the first channel and gelled extends across the first opening and forms a further barrier between the first channel and the second channel (para. 43) (Fig. 4, sheet 4 of 18).
Regarding claim 12, Cho et al. discloses first cells in the extracellular matrix in the first channel (201) (para. 63-65, 84, 90).
Regarding claim 16, Cho et al. discloses wherein the extracellular matrix comprises a hydrogel (para. 86).
Regarding claim 19, Cho et al. discloses wherein the system further comprises:
a first media within the second channel (200) (para. 84);
a third channel formed on the planar surface adjacent to the first channel (see “second lowest height” channel comprising cells 501, adjacent to “low height” channel comprising cells 500, Fig. 10, sheet 12 of 18), wherein the third channel has a third volume defined by a third width, a third height, and a third length (para. 84) (Fig. 10, sheet 12 of 18),
wherein the third channel extends in the first direction (Figs. 10-11, sheets 12-13 of 18), and wherein the third height is greater than the first height (para. 84) (Fig. 10, sheet 12 of 18),
wherein the third channel is in fluid communication with the first channel through a second opening that extends along at least a portion of the first length, wherein the second opening extends from the planar surface to the first height (para. 84, 87) (Fig. 10, sheet 12 of 18); and
wherein the first height and the third height are selected such that surface tension of a liquid added to the first channel or the third channel provides a non-physical microfluidic barrier that selectively limits passage of the liquid through the second opening (para. 40, 84, 87); and
a second media confined within the third channel (para. 84, 87) (Fig. 10, sheet 12 of 18).
Regarding claim 20, Cho et al. discloses wherein the third height (height of channel comprising cells 501) is less than the second height (height of channel 200) (para. 84, 87) (Fig. 10, sheet 12 of 18), and the system further comprises a second extracellular matrix confined within the third volume of the third channel (para. 84, 87).
Regarding claim 24, Cho et al. discloses wherein the extracellular matrix is added to the first channel in liquid form and is then gelled (para. 87).
Claim Rejections - 35 USC § 103
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 5, 7, 9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US Patent Application Publication 2014/0273223) (already of record) in view of Uwamori et al. (Integration of neurogenesis and angiogenesis models for constructing a neurovascular tissue).
Regarding claim 5, Cho et al. discloses the microfluidic chip comprising the first opening between the first channel and the second channel, as set forth above, and further discloses wherein the device is configured mimic a cell environment within the body (para. 82), such as a disease microenvironment (para. 87). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to an epithelial barrier arranged in the first opening between the first channel and the second channel.
Uwamori et al. discloses a microfluidic chip (Abstract, Fig. 1) configured to mimic the brain microenvironment for the development of treatments for brain disorders (Abstract, p. 1 para. 1), the chip comprising a first channel, a second channel, and an opening between the first channel and the second channel (p. 10 para. 2-3) (Fig. 1, p. 2), wherein a gel is constrained within the first channel by surface tension forces (p. 10 para. 3). The chip further comprises a barrier formed by brain microvascular endothelial cells (reads on an epithelial barrier, consistent with Applicant’s specification) arranged in the opening between the first channel and the second channel (p. 1 para. 1, p. 9 para. 3-p. 10 para. 4) (Fig. 1, p. 2; Fig. 3, p. 4). Uwamori et al. discloses that this configuration provides a model of the blood brain barrier which is experimentally valuable for developing brain treatments (Abstract, p. 1 para. 1-p. 2 para. 2).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the microfluidic chip disclosed by Cho et al. to comprise an epithelial barrier arranged in the first opening between the first channel and the second channel, by providing a barrier comprising brain microvascular endothelial cells, as taught by Uwamori et al., in order to enhance the experimental utility of the system by enabling it to model the blood brain barrier for the development of brain treatments.
Regarding claim 7, Cho et al. in view of Uwamori et al. teaches wherein the epithelial barrier comprises endothelial cells, as set forth above.
Regarding claim 9, Cho et al. in view of Uwamori et al. teaches wherein the epithelial barrier comprises brain microvascular endothelial cells, as set forth above.
Regarding claim 11, Cho et al. discloses the microfluidic chip comprising the first channel having extracellular matrix therein and the second channel, as set forth above. Cho et al. further discloses wherein the second channel (high height channel) comprises cells therein (para. 89-90). Additionally, Cho et al. discloses wherein the chip is configured to mimic a cell environment within the body (para. 82), such as a disease microenvironment (para. 87). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to the system comprising pericytes in the second channel.
Uwamori et al. discloses a microfluidic chip (Abstract, Fig. 1) configured to mimic the brain microenvironment for the development of treatments for brain disorders (Abstract, p. 1 para. 1), the chip comprising a first channel, a second channel, and an opening between the first channel and the second channel (p. 10 para. 2-3) (Fig. 1, p. 2), wherein an extracellular matrix gel is constrained within the first channel by surface tension forces (p. 9 para. 4-p. 10 para. 3). Pericytes are provided within the second channel (p. 2 para. 2, p. 9 para. 6-p. 10 para. 3) (Fig. 3, p. 4) to accurately model the brain microenvironment (p. 1 para. 1).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the microfluidic chip disclosed by Cho et al. to comprise pericytes in the second channel, as taught by Uwamori et al., in order to enhance the experimental utility of the system by enabling it to model the blood brain barrier for the development of brain treatments.
Claims 13-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US Patent Application Publication 2014/0273223) (already of record) in view of Kim et al. (US Patent Application Publication 2021/0171889) (already of record).
Regarding claim 13, Cho et al. discloses the first cells in the extracellular matrix, as set forth above. Cho et al. further discloses wherein the chip is configured to mimic a cell environment within the body (para. 82). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to the first cells being neural cells.
Kim et al. discloses a microfluidic chip for modeling a cell environment within the body (para. 9), the chip comprising a gel channel configured to confine a gel therein owing to a height difference between the gel channel and channels adjacent thereto (para. 124, 139). The gel channel comprises an extracellular matrix gel having astrocytes (neural cells) provided therein (para. 120-123, 142); thus, the chip provides an accurate model of the brain microenvironment for the evaluation of new drug efficacy and toxicity (Abstract, para. 4, 14).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Cho et al. such that the first cells are astrocytes (neural cells), based on the teachings of Kim et al., as the skilled artisan would have been motivated to configured the system so as to model a brain microenvironment for new drug development in order to enhance the experimental utility of the device.
Regarding claim 14, Cho et al. in view of Kim et al. teaches wherein the neural cells comprise astrocytes, as set forth above.
Regarding claim 15, Cho et al. discloses the first cells in the extracellular matrix, as set forth above. Cho et al. further discloses wherein the chip is configured to mimic a cell environment within the body (para. 82). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to wherein the first cells are cardiac cells, skeletal muscle cells, hepatic cells, renal cells, bone cells, skin cells, esophageal cells, intestinal cells, gastric cells, colon cells, lung cells, or pancreatic cells.
Kim et al. discloses a microfluidic chip for modeling a cell environment within the body (para. 9), the chip comprising a gel channel configured to confine a gel therein owing to a height difference between the gel channel and channels adjacent thereto (para. 124, 139). The gel channel comprises an extracellular matrix gel having cardiac cells provided therein (para. 120-121, 142); thus, the chip provides an accurate model of the heart microenvironment for the development of new drugs (Abstract, para. 132).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Cho et al. such that the first cells are cardiac cells, based on the teachings of Kim et al., as the skilled artisan would have been motivated to configured the system so as to model a heart microenvironment for new drug development in order to enhance the experimental utility of the device.
Regarding claim 17, Cho et al. discloses wherein the extracellular matrix comprises a hydrogel, as set forth above. Cho et al. further discloses wherein the chip is configured to mimic a cell environment within the body (para. 82). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to the hydrogel comprising basement membrane extract.
Kim et al. discloses a microfluidic chip for modeling a cell environment within the body (para. 9), the chip comprising a gel channel configured to confine a gel therein owing to a height difference between the gel channel and channels adjacent thereto (para. 124, 139). The gel channel comprises an extracellular matrix gel having cells provided therein (para. 120-121, 142), wherein the extracellular matrix comprises a hydrogel “preferably” comprising basement membrane extract gel (para. 123).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the hydrogel disclosed by Cho et al. to comprise basement membrane extract, based on the teachings of Kim et al., as the skilled artisan would have been motivated to select a material recognized to be preferable for modeling a cell microenvironment of the body.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (US Patent Application Publication 2014/0273223) (already of record) in view of Cho et al. (US Patent Application Publication 2021/0348098) (hereinafter “Cho et al. ‘098”).
Regarding claim 21, Cho et al. discloses the gelled extracellular matrix in the first channel and the second channel, as set forth above. Cho et al. further discloses wherein the chip is configured to mimic a cell environment within the body (para. 82). Cho et al. discloses wherein the device can be applied to “various cells” (para. 16).
Cho et al. is silent as to wherein the microphysiological system is a vascularized tissue model, wherein the gelled extracellular matrix in the first channel comprises first cells, and the second channel contains endothelial cells and pericyte cells in a liquid medium.
Cho et al. ‘098 discloses a microfluidic chip (Abstract) (Figs. 1a-1b, sheet 1 of 33) comprising a first channel (central channel) comprising a gelled matrix including first cells (para. 95, 119, 158, 174), and a second channel containing endothelial cells and pericyte cells in a liquid medium (para. 115, 148, 158, 174); thus, the chip provides a vascularized tissue model which has experimental utility in demonstrating the vascular permeability of drugs (para. 12, 31).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Cho et al. such that the gelled extracellular matrix comprises first cells, and the second channel contains endothelial cells and pericyte cells in a liquid medium, based on the teachings of Cho et al. ‘098, as the skilled artisan would have been motivated to configured the system so as to model a vascular microenvironment for new drug development in order to enhance the experimental utility of the device.
Regarding claim 22, Cho et al. in view of Cho et al. ‘098 teaches the vascularized tissue model including the first cells, as set forth above, and Cho et al. ‘098 further teaches wherein the model is a blood brain barrier model (Abstract) wherein the first cells are neural cells including astrocytes (para. 110). Cho et al. ‘098 discloses that astrocytes play an important role in modeling the blood brain barrier (para. 9).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the system taught by Cho et al. such that the vascularized tissue model is a blood brain barrier model wherein the first cells are neural cells including astrocytes, based on the teachings of Cho et al. ‘098, in order to improve the accuracy of the model for drug development.
Regarding claim 23, Cho et al. in view of Cho et al. ‘098 teaches the vascularized tissue model including the first cells, as set forth above, and Cho et al. ‘098 further teaches wherein the first cells are liver cells (para. 174), thereby allowing multi-organ modeling to enhance the utility of the chip (para. 97, 191, 199).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the system taught by Cho et al. such that the first cells are liver cells, based on the teachings of Cho et al. ‘098, in order to enhance the experimental utility of the model by providing multi-organ modeling.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Wang et al. (A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice) is directed to a microfluidic chip for modeling the microenvironment of a kidney comprising first and second channels wherein a height different between the channels causes surface tension to constrain a gel within the first channel.
Conclusion
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799