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 .
Status of the Claims
Claims 7 and 9-21 are pending.
Claim 7, 15-16, 18, and 21 are newly amended.
Claim 21 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/05/2025.
Claims 7 and 9-20 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejections under 35 USC 102 or 35 USC 103 are maintained but modified to address the claims as amended as discussed below. The rejections under 35 USC 102 or 35 USC 103 incorporate Hampton Research (LM Agarose, 2021) and Elzanowska et al. (Molecular Oncology, 2021) as evidentiary references.
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 7, 9, 10-12, 14, and 19 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Engelward et al. (US20200109362A1, 2020, previously cited) as evidenced by Hampton Research (LM Agarose, 2021), Elzanowska et al. (Molecular Oncology, 2021), and University of San Diego (Techniques in Molecular Biology, available online 2016, previously cited).
In regards to claims 7 and 12, Engelward discloses compositions for monitoring (screening) cells (Abstract; claims 1, 18, 45; paragraph [0091]). Engelward discloses that the composition can be embodied as a kit (paragraph [0238]).
In regards to kit being “for screening a target cell, the target cell being suitable for secreting a target molecule”, this is an intended use of the preamble and the claim neither requires a cell nor a target molecule. The only structure implied by this intended use is that the kit is suitable for supporting a target cell that can secrete a target molecule. Thus, a prior art structure capable of performing the intended use meets the claim (see MPEP 2111.02).
Additionally, it is noted that neither the claims nor specification defines the terms “target cell” or “target molecule”. Therefore, giving the term their broadest reasonable interpretation, they have been interpreted as referred to any cell and any molecule that may be secreted from the cell.
Turning to the art, since Engelward discloses that the invention can be used for metabolic detection assays (paragraph [0003]), demonstrates that cells can survive and express proteins (paragraphs [0194—196]), and broadly discloses that the invention is suitable for a wide breadth of cell types including human cells and bacterial cells (paragraphs [0020-0022, 0082]; claim 27), all of which are known to secrete molecules such are proteins (e.g., signaling peptides) or even DNA (see as evidenced by Elzanowska, 2. The presence and origins of cell-free DNA in the circulation, 1702; 3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), the kit of Engelward is suitable for this intended use.
Continuing, Engelward discloses that the composition (a kit) comprises a hydrogel (paragraphs [0006, 0018]; e.g., normal melting point agarose, claims 4, 52, or low melting point agarose, claims 20-21 and 47).
Engelward also discloses that the composition comprises a fluorescent dye (claims 1, 30, and 55; paragraph [0038), which is a type of well-known signaling molecule (see also instant specification, paragraphs [0047-0048]).
Engelward also discloses that the composition comprises a cell culture (biological) chip (claims 1 and 18; paragraphs [0016, 0049; Figs. 3 and 4).
In regards to the chip, Engelward discloses that the chip comprises a matrix material (claim 2; paragraphs [0093]); that the chip comprises culture chamber (microwell) formed on an opening configured on a surface of the matrix to define the culture chamber (Fig. 3A); and that the microwells can be configured to culture a single cell (paragraphs [0047, 0080, 0090]; Fig 1).
In regards to the chamber configured under a condition suitable for secreting a targeting molecules, as discussed above, the claims do not require secreted target molecules.
Additionally, as discussed above, since Engelward discloses that the invention can be used for metabolic detection assays (paragraph [0003]), demonstrates that cells can survive and express proteins (paragraphs [0194—196]), broadly discloses that the invention is suitable for a wide breadth of cell types including human cells and bacterial cells (paragraphs [0020-0022, 0082]; claim 27), all of which are known to secrete molecules such are proteins (e.g., signaling peptides) or even DNA (see as evidenced by Elzanowska, 2. The presence and origins of cell-free DNA in the circulation, 1702; 3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), and explicitly discloses that the microwells can be configured to culture a single cell (paragraphs [0047, 0080, 0090]; Fig 1), the culture chamber as disclosed by Engelward is considered to be suitable for culturing a candidate single cell for secreting a target molecule.
In regards to a “signal screening layer” the specification does not not define this term, but only gives examples, and states, “According to an embodiment of the present disclosure, the signal screening layer is arranged in a matrix material of the culture chamber; the signal screening layer is arranged in a culture medium; the signal screening layer comprises at least one kind of antibodies or probes; the signal screening layer is formed from a hydrogel; or a mechanical strength of the matrix material is higher than a mechanical strength of the signal screening layer” (paragraph [0045]).
Therefore, a “signal screening layer” is any layer that is at least a hydrogel that comprises a probe (a screening molecule).
As disclosed by Engelward, a cell loaded in a microwell can be layered with low melting point agarose (a hydrogel, claims 20, 21, 45 and 47; paragraphs [0018-0019, 0039]). As further disclosed by Engelward these layers can comprise the fluorescent dye (the signaling molecule, claims 30 and 55).
While Engelward discloses that the fluorescent dye is for detecting DNA (claim 1, paragraph [0005], etc.), as evidenced by Elzanowska as above, it is well attested that DNA is found in at least secreted bodies such as microvessels, apoptotic bodies, or exosomes (3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), and therefore, a DNA fluorescent dye is still a signaling molecule for specific recognition of a (secreted) target molecule as broadly claimed.
In regards to the mechanical properties of the signal screening layer, as above, Engelward discloses that this layer comprises low melting point agarose (a hydrogel, claims 20, 21, 45 and 47; paragraphs [0018-0019, 0039]), while microwells themselves are normal melting point agarose (claims 4 and 52). As evidenced by Hampton Research, low melting point agarose has lower gel strength (thus, a lower mechanical property) compared to standard (normal) melting point agarose (Material Description, p1).
In regards to the equilibrium swelling ratio, it is noted that this is a property of all hydrogels and refers to the change of volume in the hydrogel when immersed in a fluid, as is measured as the ratio of the hydrogel’s swollen mass to its dry mass.
While Engelward is silent as to the equilibrium swelling ratio of the matrix material, in arriving at this property, it is noted that the instant specification states that an agarose gel liquid with a concentration of 0.5% to 1.2% will result in a swelling ratio of 1.25 to 1.75 (instant paragraph [0137]).
To this end, in specific embodiments, Engelward discloses that in specific embodiments, 1% normal melting point agarose is used as the matrix material (paragraph [0094]).
Thus, as the instant specification indicates that agarose at a concentration of 0.5% to 1.2% will result in a swelling ratio of 1.25 to 1.75, and as the centration of 1% agarose, as disclosed by Engelward lies within this range, the matrix material as disclosed by Engelward appears to in fact have a swelling ratio that overlaps with the range of 1.25 to 1.75, absent evidence to the contrary.
In regards to claim 9, Engelward discloses that in specific embodiments the matrix is normal melting point agarose (paragraph [0094]), which as evidenced by University of San Diego, has a gelling temperature (a solid liquid phase transition temperature) of 34-42°C (Types of Agarose, p2), which overlaps with the range as in claim 9.
In regards to claims 10 and 11, Applicant should note that the product of claim 7 does not require cells and does not require method steps. Furthermore, claims 10 and 11 themselves are not directed to culturing methods, but rather describe properties of the biological culture chip as in claim 7, if a method step of contacting the chips were to occur.
Furthermore, this appears to be a property of the substrate itself. Specifically, the claims indicate that a biological chip as in claim 7 would have the property of forming a concave area (with a depth of not less than 5% of a diameter of a cell) between the matrix and a cell if culturing step were performed.
According to MPEP 2112, “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Id.
In the instant case, because Engelward discloses the biological culture chip kit as discussed above, it would be expected to have the properties as in claim 10 and 11 if a culturing step were performed, absent evidence to the contrary.
In regards to claim 14, Engelward discloses that the matrix can comprise collagen (paragraph [0019]).
In regards to claim 19, in regards to a “positioning marker”, this term is not specifically defined in the specification, and the specification broadly states “The form of the positioning marker is not particularly limited.” Additionally, the phrase does not have a specific definition in the. Therefore, giving the terms its broadest reasonable interpretation in view of the specification and the art, a “positioning marker” has been interpreted as any mark that establishes a position on the matrix. In this regards, Engelward discloses that matrix comprises microwells, with walls, which establish the location of the microwell on the matrix (Fig. 1), and are therefore positioning markers as defined above.
Therefore, Engelward anticipates the invention as claimed.
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 17 is rejected under 35 U.S.C. 103 as being unpatentable over Engelward et al. (US20200109362A1, 2020, previously cited) as evidenced by Hampton Research (LM Agarose, 2021) and Elzanowska et al. (Molecular Oncology, 2021).
Engelward anticipates claim 1 as discussed above.
In regards to claim 17, Engelward teaches that the biological culture chip microwells can have diameters between 10-20 µm paragraph [0094]), which overlaps with the range as in claim 17 (see MPEP 2144.06(I)).
Additionally, Engelward teaches that the biological culture chip microwells can have depths of approximately 40 µm (paragraph [0094]), which is at least close (see MPEP 2144.05, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).
Furthermore, a person of ordinary skill in the art could have arrived at a depth of approximately 35 µm as in claim 17, and the disclosure does not point to a criticality in this amount.
According to MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) .
In the instant case, because Engelward teaches that the wells are tunable (paragraph [0094]), a person of ordinary skill in the art could have arrived at a depth of approximately 35 µm by routine optimization with predictable results and a reasonable expectation of success.
Therefore, Engelward renders obvious the invention as claimed.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Engelward et al. (US20200109362A1, 2020, previously cited) in view of Blau et al. (US20120177611A1, 2012, on IDS 01/19/2023, previously cited) as evidenced by Hampton Research (LM Agarose, 2021) and Elzanowska et al. (Molecular Oncology, 2021).
Engelward anticipates claim 7 as discussed above.
In regards to claim 13, it is noted that the phrase “corresponding to a biocompatible material” has been interpreted to mean that the cytokine is in contact with a biocompatible material. Furthermore, a “biocompatible material” has been interpreted as anything that biologically compatible with the material.
While as above, Engelward that the matrix can comprise agar or collagen (paragraphs [0019, 0094]), which is a biocompatible materials, Engelward does not explicitly teach that the matrix further comprises a cytokine.
However, a person of ordinary skill in the art would have been motivated to add a cytokine to the matrix because Blau teaches that biomolecules, including cytokines, can be added to hydrogels in order to mimic a native microenvironment of a cell (Abstract; claims 24 and 27; paragraphs [0090-0091]). They would have been specifically motivated to add a cytokine, as taught by Blau, in order to enhance proliferation or to induce an exit to quiescence (paragraphs [0090-0091]). Furthermore, because Blau teaches that hydrogels can comprise cytokines (claims 24 and 27), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Engelward and Blau renders the invention unpatentable as claimed.
Claims 15-16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Engelward et al. (US20200109362A1, 2020, previously cited) in view of Tsukamoto et al. (Electronics and Communications in Japan, 2018, previously cited) as evidenced by Hampton Research (LM Agarose, 2021) and Elzanowska et al. (Molecular Oncology, 2021).
Engelward anticipates claim 7 as discussed above.
In regards to claims 15 and 16, Engelward does not explicitly teach that the diameter of the opening of the culture chamber is smaller than a diameter of a bottom portion of the culture chamber (i.e., an incline-tapered microwell).
However, a person of ordinary skill in the would have been motivated to fabricate an inverse-tapered microwell because Tsukamoto teaches that incline-tapered microwells are better at trapping single cells than vertical well (Abstract, p45; Fig. 1, p46).
In specific embodiments, Tsukamoto teaches that this result was obtained when the opening diameter is 50 µm (D2 which has a radius (R2) of 25), with a tapered angle (slant angle) of 30°, and a depth (h) of 30 µm (table 1,p 47). This results in a frustum with a second diameter (larger bottom diameter, D1) of about 153.92 µm (R1 = R2 + (h/tan(s)) = 25 + (30/tan(30°)) = 76.96 x 2 = D1 = 153.92 µm). This is a percentage of about 32.5% which overlaps with the range as in claim 16.
Furthermore, because teaches methods for making incline-tapered microwell (Fabrication of Micro-Inclined Well Array, p46-47) and because Engelward and Tsukamoto are in the same technical field of fabricating microwells for culturing cells, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 18, in specific embodiments Engelward teaches that microwells can be spaced approximately 240 µm apart, but also that any distance between wells is fully scalable (paragraph [0094]).
While larger, a person of ordinary skill in the art could have arrived at a spacing of 10 to 100 µm by routine optimization and the disclosure does not point to a criticality in this range.
According to MPEP 2144.05(II)(A), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) .
In the instant case, because Engelward teaches that any distance between wells is fully scalable (paragraph [0094]), and because as taught by Tsukamoto, it was known in the art that wells could be fabricated with distances of about 50 µm (Fig. 4, p47), a person of ordinary skill in the art could have arrived at a spacing as in claim 18, by routine optimization with predictable results and a reasonable expectation of success.
Therefore, Engelward and Tsukamoto renders the invention unpatentable as claimed.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Engelward et al. (US20200109362A1, 2020, previously cited) in view of Blau et al. (US20120177611A1, 2012, on IDS 01/19/2023, previously cited) as evidenced by Hampton Research (LM Agarose, 2021) and Elzanowska et al. (Molecular Oncology, 2021) as applied to claims 7 and 13 above, and further in view of Horwitz et al. (Molecular Immunology, 1990, previously cited) and Collins et al. (Veterinary Immunology and Immunopathy, 1995, previously cited).
In regards to claim 20, Engelward teaches that the biological culture chip can comprise cells (claims 1 and 45) (which are thus are biocompatible materials).
Engelward also teaches that biological culture chip can comprise growth modifying compounds (factors) (paragraph [0032]).
Engelward does not explicitly teach that IL2 is configured on the inner surface of the microwell or that the biocompatible material is B cells, specifically,
However, a person of ordinary skill in the art would have been motivated to configure IL2 on the inner surface of the microwell because Horwitz teaches that immobilized IL-2 prevents free lateral diffusion and internalization of bound IL2 receptors while still permitting specific binding of cells and immobilized ligands (Abstract, p1041).
Furthermore, because Horwitz teaches methods for immobilizing IL-2 onto cell culture surfaces (Preparation of membranes, p1042) and because as above, Engelward also teaches that biological culture chip can comprise growth modifying compounds (factors) (paragraph [0032]), of which IL-2 is a type, it could have been done with predictable results and a reasonable expectation of success.
In regards to B cells, a person of ordinary skill in the art would have been motivated to use B cells as a biocompatible material because as taught by Collins, IL-2 promotes proliferation of activated B cells (Abstract, p142).
Furthermore, because Collins teaches that B cells can be supplemented with IL-2 in microwells (Reagents, p143), and because as above, Engelward teaches that the biological culture chip can comprise cells (claims 1 and 45), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Engelward, Blau, Horwitz, and Collins renders the invention unpatentable as claimed.
Response to Arguments
Applicant argues that the prior art does not anticipate or render obvious the claimed invention (Remarks, p6). Specifically, Applicant argues that Engelward does not teach the features of the claims as newly amended (Remarks, p6).
Specifically, Applicant argues that a soft matrix is not necessary for the chip of Engelward as the microwells can be semi-solid or solid matrix (Remarks, p7). Additionally, Applicant argues that Engelward only mentions that 1% agarose can be used as a matrix material (see paragraph [0094]), but does not require a soft matrix (Remarks, p7).
Applicant argues that Engelward is not intended to screen and isolate single cells (Remarks, p7).
Applicant argues that Engelward involves pressing agarose into a PDMS mold to form micropores, then loading cells, and then covering with low-melting-point agarose, culturing cells to form microcolonies, but does not require a “signal screening layer” (Remarks, p7).
Applicant argues that Engelward does not investigate the properties of the matrix, and the Engelward chip has no special requirements for the equilibrium swelling rate of the matrix (Remarks, p7).
Applicant’s arguments filed 02/02/2026 have been fully considered but are not found persuasive.
In regards to claim 7 as newly amended, as discussed above Engelward discloses compositions for monitoring (screening) cells (Abstract; claims 1, 18, 45; paragraph [0091]). Engelward discloses that the composition can be embodied as a kit (paragraph [0238]).
In regards to kit being “for screening a target cell, the target cell being suitable for secreting a target molecule”, this is an intended use of the preamble and the claim neither requires a cell nor a target molecule. The only structure implied by this intended use is that the kit is suitable for supporting a target cell that can secrete a target molecule. Thus, a prior art structure capable of performing the intended use meets the claim (see MPEP 2111.02).
Additionally, it is noted that neither the claims nor specification defines the terms “target cell” or “target molecule”. Therefore, giving the term their broadest reasonable interpretation, they have been interpreted as referred to any cell and any molecule that may be secreted from the cell.
Turning to the art, since Engelward discloses that the invention can be used for metabolic detection assays (paragraph [0003]), demonstrates that cells can survive and express proteins (paragraphs [0194—196]), and broadly discloses that the invention is suitable for a wide breadth of cell types including human cells and bacterial cells (paragraphs [0020-0022, 0082]; claim 27), all of which are known to secrete molecules such are proteins (e.g., signaling peptides) or even DNA (see as evidenced by Elzanowska, 2. The presence and origins of cell-free DNA in the circulation, 1702; 3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), the kit of Engelward is suitable for this intended use.
Continuing, Engelward discloses that the composition (a kit) comprises a hydrogel (paragraphs [0006, 0018]; e.g., normal melting point agarose, claims 4, 52, or low melting point agarose, claims 20-21 and 47).
Engelward also discloses that the composition comprises a fluorescent dye (claims 1, 30, and 55; paragraph [0038), which is a type of well-known signaling molecule (see also instant specification, paragraphs [0047-0048]).
Engelward also discloses that the composition comprises a cell culture (biological) chip (claims 1 and 18; paragraphs [0016, 0049; Figs. 3 and 4).
In regards to the chip, Engelward discloses that the chip comprises a matrix material (claim 2; paragraphs [0093]); that the chip comprises culture chamber (microwell) formed on an opening configured on a surface of the matrix to define the culture chamber (Fig. 3A); and that the microwells can be configured to culture a single cell (paragraphs [0047, 0080, 0090]; Fig 1).
In regards to the chamber configured under a condition suitable for secreting a targeting molecules, as discussed above, the claims do not require secreted target molecules.
Additionally, as discussed above, since Engelward discloses that the invention can be used for metabolic detection assays (paragraph [0003]), demonstrates that cells can survive and express proteins (paragraphs [0194—196]), broadly discloses that the invention is suitable for a wide breadth of cell types including human cells and bacterial cells (paragraphs [0020-0022, 0082]; claim 27), all of which are known to secrete molecules such are proteins (e.g., signaling peptides) or even DNA (see as evidenced by Elzanowska, 2. The presence and origins of cell-free DNA in the circulation, 1702; 3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), and explicitly discloses that the microwells can be configured to culture a single cell (paragraphs [0047, 0080, 0090]; Fig 1), the culture chamber as disclosed by Engelward is considered to be suitable for culturing a candidate single cell for secreting a target molecule.
In regards to a “signal screening layer” the specification does not not define this term, but only gives examples, and states, “According to an embodiment of the present disclosure, the signal screening layer is arranged in a matrix material of the culture chamber; the signal screening layer is arranged in a culture medium; the signal screening layer comprises at least one kind of antibodies or probes; the signal screening layer is formed from a hydrogel; or a mechanical strength of the matrix material is higher than a mechanical strength of the signal screening layer” (paragraph [0045]).
Therefore, a “signal screening layer” is any layer that is at least a hydrogel that comprises a probe (a screening molecule).
As disclosed by Engelward, a cell loaded in a microwell can be layered with low melting point agarose (a hydrogel, claims 20, 21, 45 and 47; paragraphs [0018-0019, 0039]). As further disclosed by Engelward these layers can comprise the fluorescent dye (the signaling molecule, claims 30 and 55).
While Engelward discloses that the fluorescent dye is for detecting DNA (claim 1, paragraph [0005], etc.), as evidenced by Elzanowska as above, it is well attested that DNA is found in at least secreted bodies such as microvessels, apoptotic bodies, or exosomes (3.1. DNA in microvesicles and apoptotic bodies; 3.2. DNA in exosomes, p1703-1704), and therefore, a DNA fluorescent dye is still a signaling molecule for specific recognition of a (secreted) target molecule as broadly claimed.
In regards to the mechanical properties of the signal screening layer, as above, Engelward discloses that this layer comprises low melting point agarose (a hydrogel, claims 20, 21, 45 and 47; paragraphs [0018-0019, 0039]), while microwells themselves are normal melting point agarose (claims 4 and 52). As evidenced by Hampton Research, low melting point agarose has lower gel strength (thus, a lower mechanical property) compared to standard (normal) melting point agarose (Material Description, p1).
In regards to the equilibrium swelling ratio, it is noted that this is a property of all hydrogels and refers to the change of volume in the hydrogel when immersed in a fluid, as is measured as the ratio of the hydrogel’s swollen mass to its dry mass.
While Engelward is silent as to the equilibrium swelling ratio of the matrix material, in arriving at this property, it is noted that the instant specification states that an agarose gel liquid with a concentration of 0.5% to 1.2% will result in a swelling ratio of 1.25 to 1.75 (instant paragraph [0137]).
To this end, in specific embodiments, Engelward discloses that in specific embodiments, 1% normal melting point agarose is used as the matrix material (paragraph [0094]).
Thus, as the instant specification indicates that agarose at a concentration of 0.5% to 1.2% will result in a swelling ratio of 1.25 to 1.75, and as the centration of 1% agarose, as disclosed by Engelward lies within this range, the matrix material as disclosed by Engelward appears to in fact have a swelling ratio that overlaps with the range of 1.25 to 1.75, absent evidence to the contrary.
Applicant argues that the invention is not obvious in view of Engelward (Remarks, p6). In particular, Applicant argues that the soft matrix of the claimed invention improves survival rate, etc. (Remarks, p6).
Applicant argues that the chip (kit) of Engelward is used for rapid and sensitive assessment of cell proliferation and toxicity (see, paragraph [0005] (Remarks, p7).
Applicant’s arguments filed 02/02/2026 have been fully considered but are not found persuasive.
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., improved survival rates; or specific uses such as those distinguishable from measuring and monitoring proliferation or toxicity) 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).
Applicant argues that there are unexpected results (Remarks, p7-9). Specifically, Applicant argues that the instant invention unexpectedly discovered that the specific equilibrium swelling ratio of the matrix material has a significant impact on the biological activity and function of cells when culturing single cells (Remarks, p7). In particular, Applicant argues that with the soft matrix chip of the present application, the cell survival rate can reach 98.7%, which is significantly higher than the cell survival rate (56.4%) using a hard matrix chip (Remarks, p8). Applicant also argues that when the equilibrium swelling ratio is maintained between 1.25 and 1.75, the cell alignment efficiency reaches 95.10%, and the cell signal discrimination accuracy reaches 85.60% (Remarks, p8). Furthermore, Applicant argues that when the equilibrium swelling ratio is greater than 1.75, the cell signal discrimination accuracy was relatively good, but the cell alignment efficiency is significantly reduced (Remarks, p8). Therefore, Applicant argues that maintaining the equilibrium expansion ratio between 1.25 and 1.75 can further improve the biological activity of cells during cell culture, making it easier for cells to perform their biological functions (such as antibody and factor secretion) and facilitating accurate detection (Remarks, p8-9).
Applicant’s arguments filed 02/02/2026 have been fully considered but are not found persuasive.
In regards to Applicant’s allegations of unexpected results, whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (see MPEP 716.02(d)).
In the instant case, the claims do not require any specific result and are drawn only to a composition.
Applicant argues that the dependent claims are patentable over the cited reference by virtue of their own separately claimed subject matter and also for depending from patentable independent claim 7 (Remarks, p9).
Applicant’s arguments filed 02/02/2026 have been fully considered but are not found persuasive because at least claim 7 is anticipated by Engelward as discussed in depth above.
Conclusion
No claims are allowed.
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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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631