DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/11/2026 has been entered.
Claim Status
As of the Final Office Action mailed 3/11/2026, claims 1-4, 6, 8-12, 14-15, 17-21, 23-29, and 31-35 were pending and claims 17-21, 23-29, and 31-33 were withdrawn for being drawn to nonelected invention.
In Applicant's Response filed on 9/11/2026, claim 1 was amended.
As such, claims 1-4, 6, 8-12, 14-15, 17-21, 23-29, and 31-35 are pending and claims 1-4, 6, 8-12, 14-15, and 34-35 have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
Claim Rejections - 35 USC § 112(b) – New Ground of Rejection
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 6, 8-12, 14-15, and 34-35 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites, inter alia, “A microfabricated device comprising an intact and functional miniature tissue for high-throughput screening of modulators of biological tissue activity comprising at least two biocompatible posts and a substrate to which the posts are attached . . . wherein each post has a constant diameter from post base to post top, the curve being located at a height between the post base and the post top and having the same diameter as a remainder of the post, such that the curve retains the tissue strip at said height and so force of tissue contraction is derived from displacement of the top of the curved post according to classical beam bending theory”. This limitation is replete with narrative language. A suggested claim amendment would be e.g., “A microfabricated device comprising: at least two biocompatible posts and a substrate to which the at least two biocompatible posts are attached; wherein the distance separating the at least two biocompatible posts is at least 0.5 mm; wherein each of the at least two biocompatible posts comprise an elastomeric material, a force sensor, and a curve; wherein a tissue strip is tethered between the at least two biocompatible posts; wherein each of the at least two biocompatible posts has a constant diameter from post base to post top; wherein a post curvature of the at least two biocompatible posts retains the tissue strip at a specific height on each of the at least two biocompatible posts; and wherein the tissue strip comprises a composition comprising cells of at least one force-generating cell type and one extracellular matrix cell type.”
The term “miniature” in claim 1 is a relative term which renders the claim indefinite. The term “miniature” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The “functional tissue” as claimed is rendered indefinite by the use of the term “miniature”. Thus, the claim is indefinite.
The term “classical beam bending theory” in claim 1 is a relative term which renders the claim indefinite. The term “beam bending theory” changes over time, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is indefinite.
The term “suitable” in claim 1 is a relative term which renders the claim indefinite. The term “suitable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is indefinite.
Claims 2-4, 6, 8-12, 14-15, and 34-35 are included in these rejections for being dependent on indefinite claim 1.
Claim Rejections - 35 USC § 103 - Modified
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(s) 1-4, 6, 8-12, 14-15, and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (US 20140220555 A1, 8 April 2014; previously cited) in view of Thavandiran et al (US 20150313704 A1, 6 December 2013; previously cited).
Please note, that as stated above, “classical beam bending theory” is a relative term. As such, the teachings of the references below is interpreted to meet such theory absent evidence to the contrary.
Regarding claim 1, Chen teaches a method for generating cardiac microtissues and a microfabricated platform containing microwells and a suspension of cells that polymerize to form a matrix and anchor to microcantilevers (i.e., posts) to form a band of microtissue that span across the microcantilevers (p. 1, para 0010).
Regarding claim 1, 3-4, 6, and 8, Chen continues to teach that the cells which will make up the suspension of cells and form the microtissue can be human iPSC-derived cardiomyocytes and also include human cells such as fibroblasts (i.e., cell of extracellular matrix) and cardiac myocytes (i.e., human ventricular cardiomyocytes) (p. 1, para 0011).
Chen continues to teach that the contractile function of the band of microtissue can also be measured by electrically stimulating the band and the platform can be imaged over time to acquire image data (p. 2, para 0012 and 0013). The static and dynamic force that is exerted on the microcantilevers can be measured over time (para 0013).
Regarding claim 1, 2, and 14, Chen continues to teach that the imaging device and processor is used to determining the displacement of the microcantilevers and electrodes within the platform can be used to apply electrical stimulation (p. 2, para 0017 and 0018).
Chen continues to teach that the number of cantilevers can be, for example, two (p. 4, para 0046). Each cantilever can include a cap to prevent the tissues from becoming dislodged from the posts and further anchor the microtissue (p. 4, para 0048).
Regarding claims 1, 9-10, and 34, Chen teaches that the microcantilevers and substrates (microwells and ridges) can be made of rubber-like materials with elastic properties such as PDMS or other silicone-based polymers like polyurethanes (p. 4, para 0051).
Regarding claim 11 and 12, Chen teaches that the substrate can be cast on thin slab of PDMS (p. 5, para 0060).
Chen does not teach:
Each post has a constant diameter from post base to post top, the curve being located at a height between the post base and the post top and having the same diameter as a remainder of the post, such that the curve retains the tissue strip at said height.
Regarding (i), Thavandiran teaches a microfabrication platform for forming a tissue construct that includes a stabilizing feature for stabilizing the position of the tissue construct during its formation at an intermediate location between said substrate and a distal end of a retaining structure (i.e., post) (see claim 1 of Thavandiran).
Thavandiran continues to teach that the post can be any geometric shape so long as it performs the function of tethering the construct during contraction (para 132). This shows that the choice in post shape is a matter of routine experimentation using standard laboratory techniques available to one of ordinary skill at the time of filing to determine optimal post shape(s) that maintain tissue tethering function at a particular height during contraction.
Thavandiran continues to teach that it may be important to localize or stabilize the location of each tissue construct on a given microcantilever relative the each associated microwell base in order to provide a measure of the force exerted due to contraction that is consistent for all tissue constructs (para 156). The stabilizing feature may be formed as a cap or other structure located at a distal end of a given retaining structure. The stabilizing feature may be provided at an intermediate location between the base of the microwell and the distal end of the retaining structure (para 158).
Thavandiran continues to teach that the cantilever post diameters range from 50 μm to 300 μm, depending on the extent of deflection desired (para 171).
Regarding claim 15, Thavandiran teaches that the tissue constructs are point stimulated using a bipolar electrode and tissue beating was recorded (p. 23, para 0306).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a microfabricated device as taught by Chen, where the post contains a curve and the tissue is point stimulated by a bipolar electrode as taught by Thavandiran, to arrive at the instantly claimed invention. As Thavandiran shows that a curve can be put in the retaining feature (i.e., post) of a device to grow and measure forces on cardiac microtissue and that the post can be any shape so long as the tethering function remains, one of ordinary skill would have been motivated to simply substitute one known element [the capped post of Chen] for another [curved post of any shape as taught by Thavandiran] to obtain the predictable result of advantageously stabilizing and localizing the tissue construct during and after contraction and ensure consistent force measuring as taught by the prior art.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
On p. 7-10 of Remarks, Applicant argues, in sum, that neither Chen nor Thavandiran disclose a post of constant diameter from base to top and having a curve of the same diameter. Applicant argues Thavandiran stating that “the retaining structures may take on other geometrical shapes, so long as they are suitable for retaining the tissue construct during its contraction, and such that the retaining structures are provided such that tension is applied within the tissue construct during the remodeling process” (para 132) is a generic statement, not constrained, and is not a disclosure of the specific structure claimed. Applicant argues that various paragraphs of the specification show that the design of the post geometry was challenging, making it inconsistent with the allegation that the instantly claimed post would have been obtained by routine experimentation.
While Applicant’s arguments have been fully considered, they are not persuasive. Thavandiran teaches the stabilizing feature may be formed as a cap or other structure located at a distal end or at an intermediate location between the base of the microwell and the distal end of the retaining structure. Chen and Thavandiran contemplate various configurations of the retaining structures. While Applicant argues that Thavandiran’s teaching is generic regarding geometric shapes, this does not motivate the ordinary artisan away from combining Chen and Thavandiran. Rather, one of ordinary skill would have readily understood that they would not be limited to these specific embodiments enumerated, especially in view of Thavandiran stating that “the retaining structures may take on other geometrical shapes, so long as they are suitable for retaining the tissue construct during its contraction, and such that the retaining structures are provided such that tension is applied within the tissue construct during the remodeling process” (para 132). Accordingly, Thavandiran teaches to the ordinary artisan that a broad number of shapes/arrangements are applicable to the retaining structure. Thus, Applicant’s argument is not persuasive. Please note that this response to arguments also applies to the rejection of claim 35 below.
Claim(s) 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al in view of Thavandiran et al as applied to claims 1-4, 6, 8-12, 14-15, and 34 above, and further in view of McDevitt et al (J. Biomed. Mater. Res., 1 Sept 2003; 66a:586-595; previously cited).
The teachings of Chen and Thavandiran were recited in the above 35 U.S.C. 103 rejection as applied to claim 1 of which claim 35 depend. The teachings will not be repeated here.
Neither Chen nor Thavandiran teach that the substrate is thin polyurethane, thin-layer polyethylene, or thin-layer polyacrylamide.
McDevitt teaches the examination of spatially organized cardiomyocyte cultures on biodegradable, elastomeric polyurethane films (abstract). Over the course of 4 weeks, the integrity of the cardiomyocyte patterns on the thin films was retained and highly aligned monolayers of patterned cardiomyocytes were able to contract the thin, solvent-cast polyurethane films (p. 594, para 1). This suggests that the combination of cardiomyocyte organization and the mechanical properties of elastomeric scaffold materials, such as the biodegradable polyurethane, may lead to significantly enhanced functional properties such as directionally oriented contractile forces (same para).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a microfabricated device as taught by Chen and Thavandiran in combination, where the substrate is made of thin-layer polyurethane as taught by McDevitt, to arrive at the instantly claimed invention. As McDevitt shows the organization of cardiomyocytes on thin, solvent cast polyurethane, one of ordinary skill would have been motivated to simply substitute one known element [PDMS or polyurethane substrate of Chen] for another [thin, solvent-cast polyurethane of McDevitt] to obtain the predictable result of advantageously enhancing the functional properties of the seeded cardiomyocytes as taught by the prior art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Miklas et al (US20160282338A1, 10/30/2014; published 9/292016), which describes devices for making and using three-dimensional biological tissues that accurately mimic native physiology.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
/G.R./Examiner, Art Unit 1632
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