DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of group I comprising claims 1 – 3, 5, 16, 18 – 22, 24 – 28 and 36 – 43 in the reply filed on 1/13/2026 is acknowledged. Claims 29 – 32 and 34 were canceled by Applicant.
Note Regarding Prior Art
Examiner cites particular sections, columns, line numbers, paragraphs and figures, in the references as applied to the claims below for the convenience of the Applicant. Although the specified citations are representative of the teachings in the art and are applied to the specific limitations within the individual claim, other passages and figures may apply as well. It is respectfully requested that, in preparing responses, the Applicant fully consider the references in their entirety as potentially teaching all or part of the claimed invention, as well as the context of the passage as taught by the prior art or disclosed by the examiner.
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.
Claim(s) 1, 20, 21, 24 – 27, 38, 39, 42 and 43 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Arai et al. (US 2005/0208465 A1; hereinafter “Arai”).
Regarding claim 1, Arai teaches throughout the publication a method for preparing a three-dimensional polymerized matrix, comprising:
a) delivering a matrix-forming material (e.g., a mixture of 0.01 g of yeast (particle size: about 6 µm) and 8 ml of a 2 % aqueous solution of methylcellulose; paragraph 57) in a space between a surface of a first planar substrate and a surface of a second planar substrate (e.g., the top and bottom transparent electrodes; paragraph 50; figure 7), wherein:
a biological sample is immobilized on the surface of the first planar substrate, wherein the biological sample is a fixed biological sample (after selecting a target material, the transparent electrode in the vicinity of the target material was irradiated with the focused laser. The transparent electrode in the area exposed was heated, and the methyl cellulose in the area was gelled while entrapping the target material; paragraphs 20, 50 and 59; figures 7 and 8),
the space is at least partially enclosed by a spacer between the first planar substrate and the second planar substrate (e.g., the top polymer or glass portion is structurally equivalent to the recited spacer which functions to hold the top and bottom transparent electrodes in place as shown in figure 7), and
the spacer is non-integral to the first planar substrate or the second planar substrate (e.g., the top polymer or glass portion is structurally equivalent to the recited spacer which functions to hold the top and bottom transparent electrodes in place as shown in figure 7, and is structurally separate or non-integral to the top and bottom transparent electrodes); and
b) forming the three-dimensional polymerized matrix from the matrix-forming material in the space (after selecting a target material, the transparent electrode in the vicinity of the target material was irradiated with the focused laser. The transparent electrode in the area exposed was heated, and the methyl cellulose in the area was gelled while entrapping the target material; paragraphs 50 and 59; figures 7 and 8), wherein the three-dimensional polymerized matrix with the biological sample embedded therein has an average thickness between about 5 µm and about 200 µm (e.g., a mixture of 0.01 g of yeast (particle size: about 6 µm) and 8 ml of a 2 % aqueous solution of methylcellulose; paragraph 57) in a space between a surface of a first planar substrate and a surface of a second planar substrate (a transparent substrate; paragraph 50). Since the yeast particle size is about 6 µm, the average thickness would be at least 6 µm; see also paragraph 28; Ari further teaches that the micromaterials prepared can comprise a biological sample comprising cells, and have a target material size of about several nm and 200 µm; paragraph 28).
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Regarding claim 20, Arai teaches the method of claim 1, further comprising clearing the biological sample embedded within the three-dimensional polymerized matrix (e.g., Ari teaches the step wherein the target material was extracted using a recovery flow; paragraph 68; claim 1).
Regarding claim 21, Arai teaches the method of claim 1, wherein the biological sample is a tissue slice between about 1 µm and about 50 µm in thickness (the micromaterials prepared can comprise a biological sample comprising cells, which implicitly includes tissue samples, and have a target material size of about several nm and 200 µm; paragraph 28).
Regarding claim 24, Arai teaches the method of claim 1, wherein the three-dimensional polymerized matrix is formed by subjecting the matrix-forming material to polymerization (paragraphs 15 and 32).
Regarding claim 25, Arai teaches the method of claim 24, wherein the polymerization is initiated by adding a polymerization-inducing catalyst or UV light (laser irradiation; paragraphs 50 and 59).
Regarding claim 26, Arai teaches the method of claim 1, wherein the matrix-forming material comprises polyacrylamide, cellulose, or cross-linked polyethylene glycol (paragraphs 15 and 59).
Regarding claim 27, Arai teaches the method of claim 1, wherein the surface of the first planar substrate or the second planar substrate has a recessed cavity (e.g., a vessel is considered structurally equivalent to a recessed cavity; paragraph 27).
Regarding claim 38, Arai teaches the method of claim 1, wherein the biological sample is a tissue slice between about 5 µm and about 35 µm in thickness (the micromaterials prepared can comprise a biological sample comprising cells, which implicitly includes tissue samples, and have a target material size of about several nm and 200 µm; paragraph 28).
Regarding claim 39, Arai teaches the method of claim 1, wherein the three-dimensional polymerized matrix with the biological sample embedded therein has an average thickness between about 10 µm and about 100 µm (the micromaterials prepared can comprise a biological sample comprising cells, which implicitly includes tissue samples, and have a target material size of about several nm and 200 µm; paragraph 28; claim 9).
Regarding claim 42, Arai teaches the method of claim 1, further comprising clearing the biological sample embedded in the three-dimensional polymerized matrix (e.g., Ari teaches the step wherein the target material was extracted using a recovery flow; paragraph 68; claim 1).
Regarding claim 43, Arai teaches the method of claim 42, wherein the clearing is performed for less than about 60 minutes (e.g., Ari teaches the step wherein the target material was extracted using a recovery flow; paragraph 68; claim 1; the method using the disclosed microchip can be a high speed recovery (e.g., paragraphs 46 and 60), so it is considered implicit that a clearing or recovery step would be performed for less than about 60 minutes).
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.
Claim(s) 2, 3, 36, 40 and 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arai et al. (US 2005/0208465 A1; hereinafter “Arai”) in view of Albrecht et al. (US 2019/0078985 A1; hereinafter “Albrecht”).
Regarding claim 2, Arai does not specifically teach the method of claim 1, further comprising c) removing the spacer from the first planar substrate or the second substrate.
However, the immobilization of biological samples embedded in hydrogels between glass slides with 100 µm tape spacers is well known in the art as evidenced by Albrecht (e.g., paragraphs 83, 114 and 116). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the step of removing the spacer from the first planar substrate or the second substrate in order to recover the sample for analysis.
Regarding claim 3, Albrecht teaches wherein the spacer is an adhesive tape having a thickness of about 100 µm (e.g., paragraphs 83, 114 and 116).
Regarding claim 36, Arai and Albrecht do not further teach the method of claim 1, wherein the spacer is an adhesive tape having a thickness of between about 10 µm and 20 µm.
Albrecht does teach related sample analysis methods wherein the use of an adhesive tape as a spacer having a thickness of about 100 µm (e.g., paragraphs 83, 114 and 116). Changing the thickness of the adhesive tape would have been within the ambit of a person of ordinary skill in the art depending on the size of the sample and the channel dimensions of the microchip. The rationale to support an obviousness rejection under 35 U.S.C. 103 may rely on logic and sound scientific principle (see MPEP § 2144.02). The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success (see MPEP § 2143.02). Furthermore, the combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein the spacer is an adhesive tape having a thickness of between about 10 µm and 20 µm.
Regarding claim 40, Arai does not specifically teach the method of claim 1, further comprising (i) applying the spacer to the surface of the second planar substrate which is downward facing or applying the spacer to the surface of the first planar substrate which is upward facing, and (ii) bringing the first planar substrate and the second planar substrate together to form the space.
However, the immobilization of biological samples embedded in hydrogels between glass slides with 100 µm tape spacers is well known in the art as evidenced by Albrecht (e.g., paragraphs 83, 114 and 116). Applying the spacer tape to either planar substrate in constructing the apparatus would have been within the ambit of a person of ordinary skill in the art. The rationale to support an obviousness rejection under 35 U.S.C. 103 may rely on logic and sound scientific principle (see MPEP § 2144.02). The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success (see MPEP § 2143.02). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the step of removing the spacer from the first planar substrate or the second substrate in order to recover the sample for analysis. Furthermore, regarding claim 41, it would have been obvious to a person of ordinary skill in the art to further provide the step of removing the second planar substrate or the spacer from the first planar substrate after forming the three-dimensional polymerized matrix in order to recover the sample for further analysis.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arai et al. (US 2005/0208465 A1; hereinafter “Arai”) in view of Rockel et al. (US 2017/0241911 A1; hereinafter “Rockel”).
Regarding claim 16, Arai does not specifically teach the method of claim 1, wherein the first planar substrate comprises a coating with or is functionalized with one or more substances to facilitate attachment of the biological sample to the surface of the first planar substrate.
However, the immobilization of biological samples into functionalized surfaces for analysis is well known in the art as evidenced by Rockel (e.g., paragraph 52). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein the first planar substrate comprises a coating with or is functionalized with one or more substances to facilitate attachment of the biological sample to the surface of the first planar substrate.
Claim(s) 18 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arai et al. (US 2005/0208465 A1; hereinafter “Arai”) in view of Nolan et al. (US 2014/0099637 A1; hereinafter “Nolan”).
Regarding claim 18, Arai does not specifically teach the method of claim 1, further comprising permeabilizing the biological sample prior to the delivering step.
However, the immobilization and permeabilization of biological samples prior to analysis is well known in the art as evidenced by Nolan (e.g., paragraphs 46 and 52 – 55). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the step of permeabilizing the biological sample prior to the delivering step.
Regarding claim 19, Arai does not specifically teach the method of claim 1, further comprising cross-linking the biological sample embedded within the three-dimensional polymerized matrix.
However, the immobilization and fixation or cross-linking of biological samples prior to analysis is well known in the art as evidenced by Nolan (e.g., paragraphs 47 – 51). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide the step of cross-linking the biological sample embedded within the three-dimensional polymerized matrix.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arai et al. (US 2005/0208465 A1; hereinafter “Arai”) in view of Chee (US 2011/0245111 A1; hereinafter “Chee”).
Regarding claim 28, Arai does not specifically teach the method of claim 1, wherein the surface of the first planar substrate or the second planar substrate comprises one or more positional markers or one or more fiducial markers.
However, the use of positional markers on slides or substrates containing samples for enabling effective reagent delivery to the sample and analysis is well known in the art as evidenced by Chee (e.g., paragraph 83). The combination of familiar elements is likely to be obvious when it does no more than yield predictable results (see MPEP § 2143, A.). Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to provide wherein the surface of the first planar substrate or the second planar substrate comprises one or more positional markers or one or more fiducial markers.
Allowable Subject Matter
Claims 5, 22, and 37 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 5, the cited prior art neither teaches nor fairly suggests the method of claim 1, wherein the spacer comprises a plurality of monodisperse microparticles.
Regarding claim 22, the cited prior art neither teaches nor fairly suggests the method of claim 1, wherein the matrix-forming material comprises a plurality of fluorescent beads, and wherein the thickness of the three-dimensional polymerized matrix is measured by imaging the fluorescent beads, optionally wherein the fluorescent beads have an average diameter of about 0.2 µm.
Regarding claim 37, the cited prior art neither teaches nor fairly suggests the method of claim 1, wherein the spacer comprises a plurality of monodisperse microparticles having an average diameter of between about 10 µm and 50 µm.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Chen et al. (US 2023/0013775 A1) is a related application that discloses methods for sample transfer and analysis.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN J. SINES whose telephone number is (571)272-1263. The examiner can normally be reached 9 AM-5 PM EST M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRIAN J. SINES
Primary Patent Examiner
Art Unit 1796
/BRIAN J. SINES/Primary Examiner, Art Unit 1796
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