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
Applicant’s arguments with respect to the rejections of claims 1-8, 10-11, 14-17, and 21-26 under 35 U.S.C. 103 filed 7/15/2026 have been considered but are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
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 1-7, 10-12, 14-17, 19, and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Nawroth et al. (US 2021/0062129 A1) (hereinafter referred to as Nawroth, previously presented) in view of Y. S. Zhang, C. Zhu, Y. Xia, Inverse Opal Scaffolds and Their Biomedical Applications, Adv. Mater. 2017 (hereinafter referred to as Zhang, see PTO-892).
Regarding claim 1, Nawroth discloses a lung model apparatus (abstract, “lung-on-chip”), comprising:
an elastic hydrogel ([0199] teaches that hydrogel can be inside a membrane; Fig. 1B, membrane 208; [0519], “a membrane can be a hydrogel or a gel comprising an extracellular matrix polymer, and/or a biopolymer or biocompatible material”) disposed within a housing ([0573] discloses a round PDMS chamber loaded with hydrogel to form stroma); and
a pressure chamber disposed within the housing and adjacent to the hydrogel, the pressure chamber coupled to the hydrogel such that changes in pressure within the pressure chamber cause deformation of the hydrogel ([0207], “within the circular chamber both stroma and epithelium undergo mechanical stretching…hollow vacuum chambers on either sides of the stromal compartment…The vacuum chambers were specifically designed to generate a deformation”; [0573], “The two curved shaped hollow chambers (4) are used to generate a cyclic deformation of the PDMS chamber that transfers to the hydrogel”).
Nawroth is silent to the hydrogel forming a plurality of sacs.
However, Zhang in the art of biomimetics teaches that it is well known in the art to form a hydrogel with an inverse opal scaffold, i.e., a plurality of sacs, in a microfluidic device to mimic the structure of pulmonary alveoli (p. 13, col. 1).
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 hydrogel of Nawroth such that it forms a plurality of sacs to mimic the structure of pulmonary alveoli, as taught by Zhang.
Regarding claim 2, the prior art combination teaches the apparatus of claim 1.
Zhang of the prior art combination discloses wherein each sac of the plurality of sacs comprises an open space within the hydrogel (p. 2, col. 1, “Inverse opals, or inverted colloidal crystals, refer to a class of porous structures that possess an ordered array of uniform pores with dimensions on the nano- and micrometer scale”; Fig. 1 shows exemplary inverse opal structures).
Regarding claim 3, the prior art combination teaches the apparatus of claim 2
Zhang of the prior art combination discloses wherein a subset of the plurality of sacs of the hydrogel are interconnected by one or more openings in the hydrogel between adjacent sacs (p. 4, col. 2, “The surface pore size refers to the size of the circular openings on the surface of a scaffold”; Fig. 2 shows that the sacs are interconnected by openings).
Regarding claim 4, the prior art combination discloses the apparatus of claim 1.
Nawroth of the prior art combination discloses the apparatus further comprising a fluidic chamber disposed within the housing ([0572], “The platform consists of a top microfluidic channel 200 μm×600 μm with variable geometry, a bottom spiraled shaped microfluidic channel 400 μm×600 μm, a circular chamber surrounded by two curved shaped hollow chambers on either sides of the central stromal chamber and separated by a porous flexible PDMS membrane”) and adjacent to the hydrogel ([0572]-[0573] disclose that the hydrogel is adjacent to microfluidic channels (i.e., fluidic chamber)).
Regarding claim 5, the prior art combination teaches the apparatus of claim 4.
Nawroth of the prior art combination discloses wherein the fluidic chamber comprises a plurality of fluidic channels ([0572], “The platform consists of a top microfluidic channel 200 μm×600 μm with variable geometry, a bottom spiraled shaped microfluidic channel 400 μm×600 μm, a circular chamber surrounded by two curved shaped hollow chambers on either sides of the central stromal chamber and separated by a porous flexible PDMS membrane”) adjacent to the hydrogel ([0572]-[0573] disclose that the hydrogel is adjacent to microfluidic channels (i.e., fluidic chamber)).
Regarding claim 6, the prior art combination teaches the apparatus of claim 5.
Nawroth of the prior art combination discloses wherein the fluidic channels comprise culture media ([0572], “Channels are used to perfuse the tissue with culture media, blood or other fluids”).
Regarding claim 7, the prior art combination teaches the apparatus of claim 1.
Nawroth of the prior art combination discloses the apparatus further comprising a plurality of cells associated with the hydrogel ([0209] discloses epithelial cells and fibroblasts are embedded with the hydrogel).
Regarding claim 10, the prior art combination teaches the apparatus of claim 7.
Nawroth of the prior art combination discloses wherein the plurality of cells is embedded within the hydrogel ([0209] discloses epithelial cells and fibroblasts are embedded with the hydrogel).
Regarding claim 11, the prior art combination teaches the apparatus of claim 10.
Nawroth of the prior art combination discloses wherein the plurality of cells embedded within the hydrogel comprise endothelial cells ([0209] discloses epithelial cells and fibroblasts are embedded with the hydrogel).
Regarding claim 12, the prior art combination teaches the apparatus of claim 1.
Zhang of the prior art combination teaches it is known in the art to form a hydrogel forming a plurality of sacs comprising GelMA (p. 11, col. 1-2, spanning paragraph discusses GelMA). Zhang teaches that GelMA is a suitable material for culturing cells (Fig. 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to form the hydrogel comprising a low-stiffness biomaterial comprising GelMA, as Zhang teaches that such material is known in the art to be suitable for culturing cells.
Regarding claim 14, the prior art combination teaches the apparatus of claim 11.
Nawroth of the prior art combination discloses wherein the pressure chamber is configured to generate negative pressure, wherein the negative pressure causes the hydrogel to expand in at least one dimension ([0207], “vacuum chambers were specifically designed to generate a deformation liner proportional to the intensity of the applied suction (negative pressure)”).
Regarding claim 15, the prior art combination teaches the apparatus of claim 14.
Nawroth of the prior art combination discloses wherein the pressure chamber is configured to generate negative pressure in a cyclic manner ([0209], “A cyclic suction (negative pressure) cycle of 0.2 Hz at 50 kPa was applied”).
Regarding claim 16, the prior art combination teaches the apparatus of claim 1.
Nawroth of the prior art combination discloses wherein the pressure chamber is a first pressure chamber, and wherein the apparatus further comprises a second pressure chamber disposed within the housing, wherein the first and second pressure chambers are coupled ([0208], “two curved shaped hollow vacuum chambers were incorporated into an open top fluidic device, located on both sides of the stromal compartment”) to opposite sides of the hydrogel ([0573] discloses that stromal compartment comprises hydrogel).
Regarding claim 17, the prior art combination teaches the apparatus of claim 16.
Nawroth of the prior art combination discloses wherein each of the first and second pressure chambers is configured to generate negative pressure ([0207], “two curved shaped hollow vacuum chambers…The vacuum chambers were specifically designed to generate a deformation liner proportional to the intensity of the applied suction (negative pressure)”),
wherein the negative pressure in the first and second pressure chambers causes the hydrogel to expand in at least one dimension ([0207], “A module produced in house allowed to produce suction cycle of 0.2 Hz which generated in turn a cyclic stretching/relaxation cycles of 5 seconds on the adherent epithelial cell monolayer and on the fibroblasts embedded into the collagen I hydrogel scaffold…are used to mimic breathing by stretching the membrane 1840”), and wherein the first and second pressure chambers are configured to generate negative pressure in a cyclic manner ([0209], “A cyclic suction (negative pressure) cycle of 0.2 Hz at 50 kPa was applied”).
Regarding claim 19, the prior art combination teaches the apparatus of claim 1.
Zhang of the prior art combination discloses wherein the plurality of sacs comprises an inverse opal structure, as set forth above.
The limitation “wherein the inverse opal structure is formed from a plurality of beads assembled into a lattice” is drawn to the method of making the inverse opal structure. It has been held that the patentability of product-by-process claims is based on the product itself (MPEP § 2113 I). Nonetheless, Zhang discloses the claimed process of manufacturing the inverse opal structure (p. 2-3, section 2.1).
Regarding claim 21, the prior art combination discloses the apparatus of claim 1.
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Nawroth of the prior art combination discloses wherein the housing comprises a planar support structure having an opening therein (Fig. 2D shows opening therein – see annotated figures below), wherein the pressure chamber is disposed within the housing adjacent to the opening (Fig. 2D shows pressure chambers adjacent to opening), and wherein the hydrogel is disposed within the opening in contact with the pressure chamber ([0207]-[0208]).
Regarding claim 22, the prior art combination teaches the apparatus of claim 21.
Nawroth of the prior art combination discloses wherein the pressure chamber is a first pressure chamber, and wherein the apparatus further comprises a second pressure chamber disposed within the housing adjacent to the opening ([0208], “two curved shaped hollow vacuum chambers were incorporated into an open top fluidic device, located on both sides of the stromal compartment”),
wherein the second pressure chamber is disposed on an opposite side of the opening from the first pressure chamber (Fig. 2D shows second pressure chamber on the opposite side of the opening from the first pressure chamber), and
wherein the first and second pressure chambers are coupled to opposite sides of the hydrogel ([0207], “two curved shaped hollow vacuum chambers on either sides of the stromal compartment”).
Regarding claim 23, the prior art combination teaches the apparatus of claim 22.
Nawroth of the prior art combination discloses wherein each of the first and second pressure chambers is configured to generate negative pressure ([0207], “two curved shaped hollow vacuum chambers…The vacuum chambers were specifically designed to generate a deformation liner proportional to the intensity of the applied suction (negative pressure)”), wherein the negative pressure in the first and second pressure chambers causes the hydrogel to expand in at least one dimension ([0207], “A module produced in house allowed to produce suction cycle of 0.2 Hz which generated in turn a cyclic stretching/relaxation cycles of 5 seconds on the adherent epithelial cell monolayer and on the fibroblasts embedded into the collagen I hydrogel scaffold…are used to mimic breathing by stretching the membrane 1840”).
Regarding claim 24, the prior art combination teaches the apparatus of claim 23.
Nawroth of the prior art combination discloses wherein the first and second pressure chambers are configured to generate negative pressure in a cyclic manner ([0209], “A cyclic suction (negative pressure) cycle of 0.2 Hz at 50 kPa was applied”).
Regarding claim 25, the prior art combination teaches the apparatus of claim 24.
Nawroth of the prior art combination discloses wherein the fluidic chamber comprises a plurality of fluidic channels ([0572], “The platform consists of a top microfluidic channel 200 μm×600 μm with variable geometry, a bottom spiraled shaped microfluidic channel 400 μm×600 μm, a circular chamber surrounded by two curved shaped hollow chambers on either sides of the central stromal chamber and separated by a porous flexible PDMS membrane”) adjacent to the hydrogel ([0572]-[0573] disclose that the hydrogel is adjacent to microfluidic channels (i.e., fluidic chamber)).
Regarding claim 26, the prior art combination teaches the apparatus of claim 25.
Nawroth of the prior art combination discloses wherein each of the first and second pressure chambers comprise pressure tubing coupled thereto, wherein the pressure tubing is coupled to a pressure source ([0542], “In operation, one or more pressure tubes (not shown) connected to an external force source (e.g., pressure source) can provide positive or negative pressure to the device”),
wherein and the fluidic chamber comprises fluid tubing coupled thereto, wherein the fluid tubing is coupled to a fluid source ([0544], “As with the first outer body portion or first structure 204 described above, one or more fluid tubes connected to a fluid source can be coupled to the aperture 219 to provide fluid to the device 200 via port 218”),
wherein the pressure source is configured to provide at least one of negative pressure or positive pressure to the pressure chamber ([0542], “external force source (e.g., pressure source) can provide positive or negative pressure to the device”), and
wherein the fluid source is configured to circulate culture media through the plurality of fluidic channels ([0572], “Channels are used to perfuse the tissue with culture media, blood or other fluids”).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Nawroth and Zhang as applied to claim 7 above, and further in view of Knudsen, L., Ochs, M. The micromechanics of lung alveoli: structure and function of surfactant and tissue components. Histochem Cell Biol 150, 661–676 (2018). (hereinafter referred to as Knudsen, see PTO-892).
Regarding claim 8, the prior art combination teaches the apparatus of claim 7.
The prior art combination is silent to the plurality of cells adhered to the surfaces of the plurality of sacs.
However, Knudsen in the art of lung alveoli teaches the structure of alveoli has cells adhered to a cell matrix (p. 666-667 spanning column).
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 apparatus such that the plurality of cells is adhered to the surfaces of the plurality of sacs to better mimic the anatomy of natural alveoli.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Huang et al., Reversed-engineered human alveolar lung-on-a-chip model, Proc. Natl. Acad. Sci. discloses a human alveolar lung-on-a-chip model.
Douville et al., Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model, Lab Chip discloses a microfluidic alveolar model.
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.
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/A.J.C./ Examiner, Art Unit 1799
/William H. Beisner/ Primary Examiner, Art Unit 1799
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