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 Amendment
The Amendment filed 09/04/2026 has been entered. Claims 1-12 and 14-20 remain pending in the application. Claims 1-7 and 15-20 are withdrawn.
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.
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.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Jaklenec et al. (JAKLENEC, ANA ET AL., "High Throughput Layer-by-Layer Films for Extracting Film Forming Parameters and Modulating Film Interactions with Cells", ACS Appl. Mater. Interfaces, Dec 29, 2015, pgs. 2255-2261, Vol. 8, DOI: 10.1021/acsami.5b11081; cited in the IDS filed 10/15/2021) in view of Peterson et al. (US 20170166884 A1; effectively filed 12/15/2015).
Regarding claim 8, Jaklenec teaches a multiwell plate comprising wells (abstract and Fig. 1 teaches a 96 well-plate comprising wells), wherein a bottom surface of m wells is coated by a polyelectrolyte multilayer film (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches the bottom surfaces of the wells are coated with a film of multiple layers of a polyelectrolyte),
wherein the polyelectrolyte multilayer film coats only the bottom surface of the m wells and a portion of a wall of each of them wells corresponding to the thickness of the multilayer film of said well (Fig. 1 shows the polyelectrolyte multilayer film coating only the bottom surface and a portion of a well of each well, which corresponds to the thickness of the film),
wherein m is an integer from 2 to the number of wells of the multiwell plate (Fig. 1, teaches coating of 96 wells, i.e. m is the number of wells),
the polyelectrolyte multilayer film comprising n layer pairs, n is an integer from 1 to 2000 (Fig. 1 shows at least two pairs of layers; Fig. 2 teaches up to 55 bilayers, i.e. layer pairs), and each layer pair comprising a layer of a first polyelectrolyte PE1 (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH) and a layer of a second polyelectrolyte PE2 of opposite charge (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA),
wherein the first polyelectrolyte PE1 is either a cationic polymer comprising amino groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH), or an anionic polymer (interpreted as not required due to the “or” statement),
wherein the second polyelectrolyte PE2 is a cationic polymer comprising amino groups when PE1 is an anionic polymer (interpreted as not required due to the “or” statement), or PE2 is an anionic polymer when PE1 is a cationic polymer comprising amino groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA);
wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction (page 2256, right column, last paragraph teaches the methods exhibited uniform and smooth buildup of layers; page 2257, right column, first full paragraph teaches the center of the films exhibit homogenous thicknesses; Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches identical preparation of each well of the well plate; page 2260, section “Profilometer Measurements” teaches surface profilometer were on random points of the films; therefore, the area of the center of the film of the respective well would have a coefficient of variation CV, as calculated by the claimed equations, of its mean thickness of about 0%, i.e. less than 20.3%, since each well is identically produced with uniform, smooth, and homogenous films), and
wherein the anionic polymer comprises carboxylic groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA; wherein, PAA structurally includes carboxylic groups).
Jaklenec fails to teach: the polyelectrolyte multilayer film is cross-linked via amide bonds or derivatives thereof formed from the carboxylic groups and the amino groups of the polyelectrolyte multilayer film.
Jaklenec teaches it has been shown that PAH-PAA films have layers that are ionically cross-linked, wherein the more tightly packed the layers are, cell attachment increased (page 2259, right column, first full paragraph).
Peterson teaches a cell culture device comprising a polymer surface configured for incubating cells, a polyelectrolyte multilayer (PEM), and the PEM comprising one or more bi-layers of oppositely charged polyelectrolytes (abstract). Peterson teaches the PEM can include a combination of positively and negatively charged polyelectrolyte layers (paragraph [0045]), the polyelectrolytes can include PAH and PAA (paragraph [0048]). Peterson teaches a method of producing crosslinked polyelectrolyte multilayer films which proves to be stabilized and therefore can withstand numerous physical, chemical and biological stresses (paragraph [0063]); the method including forming amide bonds between complementary reactive groups to give rise to a cross-linked PEM film (paragraph [0063]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polyelectrolyte multilayer film of Jaklenec to incorporate Jaklenec’s teachings of cross-linked layers and tightly packing the layers (page 2259, right column, first full paragraph) and Peterson’s teachings of crosslinked polyelectrolyte multilayer films that formed from amide bonds (paragraphs [0045],[0048],[0063]) to provide: the polyelectrolyte multilayer film is cross-linked via amide bonds or derivatives thereof formed from the carboxylic groups and the amino groups of the polyelectrolyte multilayer film. Doing so would have a reasonable expectation of successfully improving crosslinking of the film for improved stability to withstand numerous physical, chemical and biological stresses as taught by Peterson (paragraph [0063]).
Regarding claim 9, Jaklenec further teaches wherein the anionic polymer is selected from the group consisting of poly(acrylic) acid, poly(methacrylic) acid,poly(glutamic) acid, polyuronic acid, glycosaminoglycans, poly(aspartic acid) and Polystyrene sulfonate, any combination of polyamino-acids in D and/or L forms, and mixtures thereof (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA, i.e. poly(acrylic) acid).
Regarding claim 10, Jaklenec further teaches wherein the cationic polymer comprising amino group is selected from the group consisting of poly(lysine), poly(diallydimethylammonium chloride), poly(allylamine), poly(ethylene)imine, chitosan, polyarginine, Poly(ornithine), polyhistidine, poly(mannosamine), polyallylamine hydrochloride, any combination of polyamino acids in D and/or L forms, and mixtures thereof (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH, i.e. polyallylamine hydrochloride).
Claims 11-12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Jaklenec in view of Peterson as applied to claim 8 above, and further in view of Rubner et al. (US 20050191430 A1; cited in the IDS filed 10/15/2021).
Regarding claim 11, while Jaklenec teaches the film includes polyallylamine hydrochloride (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH), modified Jaklenec fails to teach: wherein the polyelectrolyte multilayer film is a poly(L-lysine)/hyaluronan sodium film, a polystyrene sulfonate/polyallylamine hydrochloride film, a poly(L-lysine)/poly(L-glutamic acid) film or a chitosan/poly(L-glutamic acid) film.
Rubner teaches a multiwell plate comprising wells (paragraph [0083], “cell plates”; paragraph [0019], “multiwell plates”; wherein cell plates and multiwell plates comprise wells), wherein a bottom surface of m wells is coated by a polyelectrolyte multilayer film (paragraph [0008] teaches coating a surface with layers of polyelectrolytes; paragraphs [0118]-[0119] teaches polyelectrolyte multilayer thin films were deposited on multiwell plates, which is interpreted as at least the bottom surface of at least one well of the multiwell plate being coated by a polyelectrolyte multilayer thin film). Rubner teaches the polyelectrolyte multilayer thin films includes PAH and a polyanionic polymer of PAA or SPS, i.e. polystyrene sulfonate (paragraph [0119]). Rubner teaches PAH/SPS films were cytophilic (paragraph [0048]).
Since Rubner teaches both PAA and polystyrene sulfonate are known anionic polymers for polyelectrolyte multilayer films and their functions were known in the art, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sheet of modified the PAH/PAA polyelectrolyte multilayer film of modified Jaklenec to substitute one known element (Jaklenec’s PAA anionic polymer) with another known element (Rubner’s polystyrene sulfonate anionic polymer) to provide: wherein the polyelectrolyte multilayer film is a polystyrene sulfonate/polyallylamine hydrochloride film, and the results of the substitution (i.e. a polyelectrolyte multilayer film that is cytophilic) would have been predictable. See MPEP 2143(I)(B).
Regarding claim 12, modified Jaklenec fails to teach: the multiwell plate according to claim 8, further comprising a layer of a third polyelectrolyte PE3 deposited on the top of the polyelectrolyte multilayer film, wherein the third polyelectrolyte PE3 is linked to at least a peptide, and the third polyelectrolyte PE3 is a cationic polymer comprising amino groups when the second polyelectrolyte PE2 is an anionic polymer, or the third polyelectrolyte PE3 is an anionic polymer when the second polyelectrolyte PE2 is a cationic polymer comprising amino groups.
Jaklenec teaches polyelectrolyte multilayer films of up to 55 bilayers (Fig. 2).
Rubner teaches a layer of a third polyelectrolyte PE3 deposited on the top of the polyelectrolyte multilayer film (paragraph [0119] teaches the substrate was immersed in PAH, and then PAA, PMA or SPS, and then the procedure is repeated until the desired number of layers was assembled, thus at least three total layers are present; i.e. PAH is the third polyelectrolyte added on top of the PAA, PMA, or SPS during the first repeated procedure), and the third polyelectrolyte PE3 is a cationic polymer comprising amino groups when the second polyelectrolyte PE2 is an anionic polymer (paragraph [0008] teaches a first polymer is a cationic polyelectrolytes; paragraph [0119], “PAH”). Rubner teaches the capability to present on bio-inert multilayers a variety of cell-adhesive biomolecules, e.g., fibronectin or the RGD (arginine-glycine-aspartic acid) amino acid sequence, i.e. peptide, via several different approaches should also expand the versatility of polyelectrolyte multilayers for bio-interface material (paragraph [0043]). Rubner teaches it should be quite facile to chemically modify the functional of PAA, PMA, or PAH to tether specific cell-adhesion proteins, such as RGD to enable controlled binding of cells (paragraph [0043]). Rubner teaches micropatterning of cell-adhesive and -resistant features on a surface should provide opportunities for making cellular networks and arrays as well as biosensors and multilayers could then easily be created to fabricate conformal coatings with highly tailored structural features as well as predictable, favorable interactions with living cells. (paragraph [0043]). Rubner teaches chemical groups of the multilayers possess a rich density of reactivity sites for further biochemical ligand modification, such as for tethering of RGD or other peptide sequences in order to selectively attract cells (paragraph [0057]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified multiwell plate of modified Jaklenec to incorporate Jaklenec’s teachings of multiple bilayers (Figs. 1-2) and Rubner’s teachings a third polyelectrolyte (paragraph [0119]) and teachings of tethering RGD or other peptide sequences to the polyelectrolyte multilayers (paragraphs [0043],[0057]) to provide: the multiwell plate according to claim 8, further comprising a layer of a third polyelectrolyte PE3 deposited on the top of the polyelectrolyte multilayer film, wherein the third polyelectrolyte PE3 is linked to at least a peptide, and the third polyelectrolyte PE3 is a cationic polymer comprising amino groups when the second polyelectrolyte PE2 is an anionic polymer, or the third polyelectrolyte PE3 is an anionic polymer when the second polyelectrolyte PE2 is a cationic polymer comprising amino groups. Doing so would have a reasonable expectation of successfully providing desired numbers of layer pairs and improving controlled binding of cells and improving tailoring of the multiwell plate as taught by Rubner (paragraphs [0043],[0057]).
Regarding claim 14, modified Jaklenec fails to teach: wherein a protein is incorporated on and inside the cross-linked polyelectrolyte multilayer film.
Rubner teaches coupling cell-binding proteins to a PEO-rich surface is a popular way in which to prepare hybrid coatings with cell-resistant and cell-adherent domain (paragraph [0005]). Rubner teaches the capability to present on bio-inert multilayers a variety of cell-adhesive biomolecules, e.g., fibronectin or the RGD (arginine-glycine-aspartic acid) amino acid sequence via several different approaches should also expand the versatility of polyelectrolyte multilayers for bio-interface material (paragraph [0043]). Rubner teaches it should be quite facile to chemically modify the functional of PAA, PMA, or PAH to tether specific cell-adhesion proteins to enable controlled binding of cells (paragraph [0043]). Rubner teaches PAH/PAA multilayers absorbing proteins (paragraph [0101] teaches multilayers absorbing lysosomes, i.e. protein incorporated inside the multilayer film). Rubner teaches performing in vitro cell studies to test multilayers ability to adhere to proteins (paragraph [0101]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cross-linked polyelectrolyte multilayer film of modified Jaklenec to incorporate the teachings of coupling cell-binding proteins to a surface and testing for adsorption of proteins of Rubner (paragraphs [0005],[0043],[0101]) to provide wherein a protein is incorporated on and inside the cross-linked polyelectrolyte multilayer film. Doing so would have a reasonable expectation of successfully improving controlled binding of cells and improving tailoring of the multiwell plate as taught by Rubner (paragraphs [0043]). Furthermore, doing so would improve the ability to analyze the ability of the multilayer film to adsorb proteins as taught by Rubner (paragraph [0101]).
In an alternative interpretation of claim 8, claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Jaklenec et al. (JAKLENEC, ANA ET AL., "High Throughput Layer-by-Layer Films for Extracting Film Forming Parameters and Modulating Film Interactions with Cells", ACS Appl. Mater. Interfaces, Dec 29, 2015, pgs. 2255-2261, Vol. 8, DOI: 10.1021/acsami.5b11081; cited in the IDS filed 10/15/2021) in view of Peterson et al. (US 20170166884 A1; effectively filed 12/15/2015), Rubner et al. (US 20050191430 A1; cited in the IDS filed 10/15/2021) and Lea et al. (US 20080131600 A1). In this alternative interpretation, Jaklenec is interpreted as failing to teach: “wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction”.
Regarding claim 8, Jaklenec teaches a multiwell plate comprising wells (abstract and Fig. 1 teaches a 96 well-plate comprising wells), wherein a bottom surface of m wells is coated by a polyelectrolyte multilayer film (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches the bottom surfaces of the wells are coated with a film of multiple layers of a polyelectrolyte),
wherein the polyelectrolyte multilayer film coats only the bottom surface of the m wells and a portion of a wall of each of them wells corresponding to the thickness of the multilayer film of said well (Fig. 1 shows the polyelectrolyte multilayer film coating only the bottom surface and a portion of a well of each well, which corresponds to the thickness of the film),
wherein m is an integer from 2 to the number of wells of the multiwell plate (Fig. 1, teaches coating of 96 wells, i.e. m is the number of wells),
the polyelectrolyte multilayer film comprising n layer pairs, n is an integer from 1 to 2000 (Fig. 1 shows at least two pairs of layers; Fig. 2 teaches up to 55 bilayers, i.e. layer pairs), and each layer pair comprising a layer of a first polyelectrolyte PE1 (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH) and a layer of a second polyelectrolyte PE2 of opposite charge (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA),
wherein the first polyelectrolyte PE1 is either a cationic polymer comprising amino groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches a cationic polyelectrolyte, PAH), or an anionic polymer (interpreted as not required due to the “or” statement),
wherein the second polyelectrolyte PE2 is a cationic polymer comprising amino groups when PE1 is an anionic polymer (interpreted as not required due to the “or” statement), or PE2 is an anionic polymer when PE1 is a cationic polymer comprising amino groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA); and
wherein the anionic polymer comprises carboxylic groups (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches an anionic polyelectrolyte, PAA; wherein, PAA structurally includes carboxylic groups).
Jaklenec fails to teach: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction; and the polyelectrolyte multilayer film is cross-linked via amide bonds or derivatives thereof formed from the carboxylic groups and the amino groups of the polyelectrolyte multilayer film.
Jaklenec teaches it has been shown that PAH-PAA films have layers that are ionically cross-linked, wherein the more tightly packed the layers are, cell attachment increased (page 2259, right column, first full paragraph).
Peterson teaches a cell culture device comprising a polymer surface configured for incubating cells, a polyelectrolyte multilayer (PEM), and the PEM comprising one or more bi-layers of oppositely charged polyelectrolytes (abstract). Peterson teaches the PEM can include a combination of positively and negatively charged polyelectrolyte layers (paragraph [0045]), the polyelectrolytes can include PAH and PAA (paragraph [0048]). Peterson teaches a method of producing crosslinked polyelectrolyte multilayer films which proves to be stabilized and therefore can withstand numerous physical, chemical and biological stresses (paragraph [0063]); the method including forming amide bonds between complementary reactive groups to give rise to a cross-linked PEM film (paragraph [0063]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polyelectrolyte multilayer film of Jaklenec to incorporate Jaklenec’s teachings of cross-linked layers and tightly packing the layers (page 2259, right column, first full paragraph) and Peterson’s teachings of crosslinked polyelectrolyte multilayer films that formed from amide bonds (paragraphs [0045],[0048],[0063]) to provide: the polyelectrolyte multilayer film is cross-linked via amide bonds or derivatives thereof formed from the carboxylic groups and the amino groups of the polyelectrolyte multilayer film. Doing so would have a reasonable expectation of successfully improving crosslinking of the film for improved stability to withstand numerous physical, chemical and biological stresses as taught by Peterson (paragraph [0063]).
Modified Jaklenec fails to teach: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction.
Jaklenec teaches the methods exhibited uniform and smooth buildup of layers (page 2256, right column, last paragraph) and the center of the films exhibit homogenous thicknesses (page 2257, right column, first full paragraph). Jaklenec teaches identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”). Jaklenec teaches surface profilometer were on random points of the films (page 2260, section “Profilometer Measurements” teaches).
Rubner teaches films exhibit homogenous, well-mixed surfaces (paragraph [0092]) and layer thicknesses do not vary by more than 10% (paragraph [0094], table 2).
Lea teaches a method for preparing a substrate coated support for use in micro-array devices, wherein the method produces a substrate coated membrane in which the thickness is uniform across the entire coated surface (abstract). Lea teaches known issues in the art of uneven film thicknesses across a surface (paragraphs [0006]-[0008]). Lea teaches spot density plots, confirm the substrate coating planarity, essentially a linearly changing thickness measure, i.e. an even coating thickness (paragraph [0051]). Lea teaches that the variance in signal response at different locations on the surface of the support will be very low, surface responses measuring up to 25% variance and coating planarity measures of up to 25% variance would be acceptable (paragraph [0041]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polyelectrolyte multilayer film of modified Jaklenec to incorporate Jaklenec’s teachings of uniform and smooth layers and films with homogenous thicknesses (page 2256, right column, last paragraph; page 2257, right column, first full paragraph) and identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”), Rubner’s teachings of films exhibiting homogenous, well-mixed surfaces (paragraph [0092]) and layer thicknesses do not vary by more than 10% (paragraph [0094], table 2), and Lea’s teachings of a uniform thickness coating of a membrane across a surface (abstract; paragraphs [0006], [0008], [0051], [0041]) to provide: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction. Doing so would have a reasonable expectation of successfully improving uniformity, smoothness, and homogeneity of the film of each well as desired by Jaklenec.
Response to Arguments
Applicant’s arguments, see page 8, filed 09/04/2026, with respect to the claim objections and rejections under 35 U.S.C. 112(b), have been fully considered and are persuasive. The claim objections and rejections under 35 U.S.C. 112(b) of 06/04/2026 have been withdrawn.
Applicant's arguments, see pages 8-9, filed 09/04/2026, with respect to the claim rejections under 35 U.S.C. 103, specifically regarding claim 8, have been fully considered but they are not persuasive. Note that the Non-Final Rejection filed 06/04/2026 referred to “Jaklenex”, which was a typographical mistake. Herein, Jaklenex is now referred to as Jaklenec.
In response to applicant’s arguments that Jaklenec and Peterson does not teach or render obvious “the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%” and since Jaklenec is silent to any kind of homogeneity between wells (Remarks, pages 8-9), the examiner disagrees.
Jaklenec teaches: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction (page 2256, right column, last paragraph teaches the methods exhibited uniform and smooth buildup of layers; page 2257, right column, first full paragraph teaches the center of the films exhibit homogenous thicknesses; Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches identical preparation of each well of the well plate; page 2260, section “Profilometer Measurements” teaches surface profilometer were on random points of the films; therefore, the area of the center of the film of the respective well would have a coefficient of variation CV, as calculated by the claimed equations, of its mean thickness of about 0%, i.e. less than 20.3%, since each well is identically produced with uniform, smooth, and homogenous films). Since Jaklenec teaches the methods exhibited uniform and smooth buildup of layers (page 2256, right column, last paragraph), the center of the films exhibit homogenous thicknesses (page 2257, right column, first full paragraph), identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”), and surface profilometer were on random points of the films (page 2260, section “Profilometer Measurements”), Jaklenec’s polyelectrolyte multilayer film (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches the bottom surfaces of the wells are coated with a film of multiple layers of a polyelectrolyte) would have a coefficient of variation CV, as calculated by the claimed equations, of its mean thickness of about 0%, i.e. less than 20.3%, since each well is identically produced with uniform, smooth, and homogenous films.
In response to applicant’s arguments regarding the alternative rejection of claim 8 that Jaklenec and Lea does not teach or render obvious “the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%” and since Lea describes a variance of up to 25%, but does not teach a CV for a multi-well plate or evaluation of CV between wells (Remarks, page 9), the examiner disagrees. Note that the alternative rejection of claim 8 included Rubner within the rejection (Non-Final Rejection filed 06/04/2026, pages 12-17), but the header had a typographical mistake and did not include Rubner et al. (US 20050191430 A1; cited in the IDS filed 10/15/2021). The header of the alternative rejection of claim 8 has been updated to include Rubner et al. (US 20050191430 A1; cited in the IDS filed 10/15/2021).
The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Jaklenec provides teachings and suggestions of: methods exhibited uniform and smooth buildup of layers (page 2256, right column, last paragraph); identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”); the center of the films exhibit homogenous thicknesses (page 2257, right column, first full paragraph); and surface profilometer were on random points of the films (page 2260, section “Profilometer Measurements” teaches). Rubner provides teachings of films that exhibit homogenous, well-mixed surfaces (paragraph [0092]) and layer thicknesses do not vary by more than 10% (paragraph [0094], table 2). Lea provides teachings of a uniform thickness coating of a membrane across a surface (abstract; paragraphs [0006], [0008], [0051], [0041]).
It would have been obvious to one of ordinary skill in the art to have modified the polyelectrolyte multilayer film of modified Jaklenec to incorporate Jaklenec’s teachings of uniform and smooth layers and films with homogenous thicknesses (page 2256, right column, last paragraph; page 2257, right column, first full paragraph) and identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”), Rubner’s teachings of films exhibiting homogenous, well-mixed surfaces (paragraph [0092]) and layer thicknesses do not vary by more than 10% (paragraph [0094], table 2), and Lea’s teachings of a uniform thickness coating of a membrane across a surface (abstract; paragraphs [0006], [0008], [0051], [0041]) to provide: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction. Doing so would have a reasonable expectation of successfully improving uniformity, smoothness, and homogeneity of the film of each well as desired by Jaklenec.
Therefore, there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art to have modified Jaklenec in view of Rubner and Lea to provide the claimed CV, i.e. the wells have polyelectrolyte multilayer films with homogenous thicknesses within each well and between wells as claimed.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., Remarks, page 9, first full paragraph, “determination of CV”; Remarks, page 9, second full paragraph, “evaluation of CV between wells”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Note that the claim does not claim a method or process of calculating and determining the CV using the claimed equations.
In response to applicant’s arguments that uniformity of film thickness within a single well is not the same as uniformity of film thickness among multiple wells as recited in claim 8 and therefore the prior art does not teach claim 8 (Remarks, page 9, third full paragraph), the examiner disagrees.
As discussed above regarding Jaklenec, since Jaklenec teaches the methods exhibited uniform and smooth buildup of layers (page 2256, right column, last paragraph), the center of the films exhibit homogenous thicknesses (page 2257, right column, first full paragraph), identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”), and surface profilometer were on random points of the films (page 2260, section “Profilometer Measurements”), Jaklenec’s polyelectrolyte multilayer film (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis” teaches the bottom surfaces of the wells are coated with a film of multiple layers of a polyelectrolyte) would have a coefficient of variation CV, as calculated by the claimed equations, of its mean thickness of about 0%, i.e. less than 20.3%, since each well is identically produced with uniform, smooth, and homogenous films. I.e. Jaklenec’s wells that are identically produced each with homogenous thicknesses teaches the claimed uniformity of film thickness among multiple wells, and therefore Jaklenec teaches the polyelectrolyte multilayer film has a coefficient of variation CV, as calculated by the claimed equations, of its mean thickness of about 0%, i.e. less than 20.3%.
Furthermore, regarding Jaklenec and Lea, it would have been obvious to one of ordinary skill in the art to have modified the polyelectrolyte multilayer film of modified Jaklenec to incorporate Jaklenec’s teachings of uniform and smooth layers and films with homogenous thicknesses (page 2256, right column, last paragraph; page 2257, right column, first full paragraph) and identical preparation of each well of the well plate (Fig. 1 and page 2260, section “Layer-by-Layer Synthesis”), Rubner’s teachings of films exhibiting homogenous, well-mixed surfaces (paragraph [0092]) and layer thicknesses do not vary by more than 10% (paragraph [0094], table 2), and Lea’s teachings of a uniform thickness coating of a membrane across a surface (abstract; paragraphs [0006], [0008], [0051], [0041]) to provide: wherein the polyelectrolyte multilayer film has a coefficient of variation CV of its mean thickness less than or equal to 20.3%, and wherein CV =(SD/hMEAN)x100, SD being the standard deviation (see equation in claim 1), hN, hW, hC, hE and hS are respectively, film thicknesses determined at North, West, Center, East, South positions inside each well, wherein the Center position is the center of a respective well, the East and West positions are opposite poles of the respective well along an X direction and the North and South positions are opposite poles of the respective well along a Y direction orthogonal to the X direction. Doing so would have a reasonable expectation of successfully improving uniformity, smoothness, and homogeneity of the film of each well as desired by Jaklenec.
Therefore, there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art to have modified Jaklenec in view of Rubner and Lea to provide the claimed CV, i.e. the wells have polyelectrolyte multilayer films with homogenous thicknesses within each well and between wells as claimed.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Tian et al. (US 20180141263 A1; effectively filed 04/24/2015; cited in the OA filed 08/14/2025) teaches microplates (abstract). Tian teaches microplates are be formed so that the shape/geometry of each well is substantially the same and/or the batch to batch variation less between microplates; variation between wells within a plate or among different batches of plates may be minimized (i.e., wall thickness between wells of the same microplate and wells of different batches of microplates exhibit high homogeneity); for example, the CV value between wells of the same microplate and between batches of microplates may range from about 3% to about 5% (paragraph [0027]). Tian teaches a uniform thickness ensures that wells have a consistent wall thickness, and the CV value can be between about 3% to about 5%, however in some instances, it can be about 3% or less (paragraph [0030]).
Lichtenberg et al. (US 20180187136 A1; effectively filed 07/01/2015) teaches devices for cultivation of cells (abstract; paragraph [0001]) including multiwells (Fig. 1). Lichtenberg teaches the bottom of the at least one well is provided by a layer having an essentially homogeneous thickness of between about 100 μm to about 250 μm, preferably a homogeneous thickness of about 180 μm (paragraph [0037]). Lichtenberg teaches the bottom of at least one well is manufactured in form of a film or disk that has an essentially homogeneous thickness (paragraph [0073]). Lichtenberg teaches as the array of wells (52) is essentially identical to the array of wells within the multiwell plate (1), each of the wells (52) is aligned with a well (2) of the multiwell plate (paragraph [0126]).
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 HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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