DETAILED ACTION
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.
Maintained Rejections
Applicant’s arguments regarding the rejection of record of claims 1-4, 6, 8-12, 14-15, and 34 under 35 U.S.C. 103 as being unpatentable over Chen et al (US 20140220555 A1, 8 April 2014) in view of Thavandiran et al (US 20150313704 A1, 6 Dec 2013) have been fully considered but are not persuasive. Thus, the rejection has been maintained and recast below to account for Applicant’s amendment to claim 1. Response to arguments will follow the rejection.
Applicant’s arguments regarding the rejection of record of claims 35 under 35 U.S.C. 103 as being unpatentable over Chen et al (US 20140220555 A1, 8 April 2014) in view of Thavandiran et al (US 20150313704 A1, 6 Dec 2013) and further in view of McDevitt et al (J. Biomed. Mater. Res., 1 Sept 2003; 66a:586-595) have been fully considered but are not persuasive. Thus, the rejection has been maintained and recast below. Response to arguments will follow the rejection.
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) 1-4, 6, 8-12, 14-15, and 34 remain 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 this rejection has been recast and updated in view of the newly added limitations of claim 1.
Chen discloses 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). 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) (“wherein the tissue strip comprises a composition comprising cells of at least one force-generating cell type and one extracellular matrix type” as in instant claim 1 in-part; “wherein the force-generating cell type is a cardiac muscle cell type, a fibroblast cell type” as in instant claim 3; “wherein the force-generating cell is a stem cell-derived cell type or a myocyte cell type” as in instant claim 4; “wherein the myocyte is a cardiomyocyte” as in instant claim 6; “wherein the cardiomyocyte is a human ventricular cardiomyocyte” as in instant claim 8). 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) (“force sensor” as in instant claim 1 in-part). 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) (“wherein the microfabricated device is suitable for monitoring tissue strip position over time in situ” as in instant claim 1 in-part; “wherein the device is further suitable for imaging tissue strip position or movement over time by an imaging modality or imaging system” as in instant claim 2; “a recording device to monitor tissue strip position or to detect movement of a tissue strip” as in instant claim 14). The number of cantilevers can be, for example, two (p. 4, para 0046) (“at least two biocompatible posts” as in instant claim 1 in-part). 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) (“a feature for tethering a tissue strip” as in instant claim 1 in-part). The separation distance between the cantilevers can be 1 mm or 5mm (p. 4, para 0050) (“wherein the distance separating at least two posts is at least 0.5 mm” as in instant claim 1 in-part). The reference further discloses that the microcantilevers (including the posts and caps) and substrates (“substrate to which the posts are attached” as in instant claim 1 in-part) (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) (“wherein each post comprises an elastomeric material” as in instant claim 1 in-part; “wherein the elastomeric material is silicone” as in instant claim 9; “wherein the silicone is polydimethylsiloxane” as in instant claim 10; “wherein the elastomeric material is polyurethane” as in instant claim 34). The substrate can be cast on thin slab of PDMS (p. 5, para 0060) (“wherein the substrate is thin-layer silicone” as in instant claim 11; “wherein the thin-layer silicone is thin-layer polydimethylsiloxane” as in instant claim 12).
The difference between the teachings of Chen and the invention as instantly claimed is that it does not teach that there is a curve in the post or that the post curvature is designed to retain the tissue strip at a specific height on the post, without altering post diameter so force of tissue contraction is derived from displacement of the top of the curved post according to classical beam bending theory (related to claim 1 in-part). It also does not teach that the device contains two unipolar electrodes for field stimulation, a bipolar micro-electrode for point contact stimulation, or a micro-cannula for contacting a tissue strip with an electrical stimulus or a modulator of a biological tissue activity (related to claim 15).
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). The stabilizing feature is a groove (i.e., a curve in the post) or a protuberance (see claim 2 of Thavandiran and Fig. 20 for groove labeled ‘440’) (“a curve for tethering a tissue strip in each post” as in instant claim 1 in-part). Although Thavandiran does not show that both posts contain a groove, one of ordinary skill would reasonably put a curve in both posts since it is shown that a curve can be put in one post. The tissue constructs are point stimulated using a bipolar electrode and tissue beating was recorded (p. 23, para 0306) (“a bipolar microelectrode for point contact stimulation” as in instant claim 15). The reference teaches that the groove stabilizes and localizes the tissue construct during and after the contraction (p. 9, para 0155) in order to provide a measure of the force exerted due to contraction that is consistent for all tissue constructs (p. 9, para 0156). Finally, Thavandiran teaches 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. This reads on “wherein post curvature is designed to retain the tissue strip at a specific height on the post, without altering post diameter so force of tissue contraction is derived from displacement of the top of the curved post according to classical beam bending theory” as in instant claim 1 in-part.
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 groove/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 of 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, in sum, argues (p. 8-13 of Remarks) that neither Chen nor Thavandiran teach all of the elements of claim 1 (specifically, the design of the posts without altering the post diameter). Applicant also argues that Thavandiran does not disclose that the curved portions serves the same purpose as the device of claim 1 nor does it teach or suggest that a curve in the design of the post that has the same diameter from base to top such that there would be no motivation to combine Thavandiran with Chen to arrive at the instant invention of claim 1.
In response, the examiner disagrees. First, the examiner notes that the claimed “wherein post curvature is designed to retain the tissue strip at a specific height on the post, without altering post diameter from post base to post top so force of tissue contraction is derived from displacement of the top of the curved post according to classical beam bending theory” is an intended use/result of the post itself. Generally, intended results do not impart patentable weight. Even if, arguendo, this limitation were to be interpreted as a potentially patentable limitation, none of the cited references criticize/discredit the use of a post that maintains a diameter from post base to top. The examples that Applicant relies upon from the respective references are preferred embodiments. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) (see MPEP 2123(II).
"A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness ... of the claims at issue." In re Corkill, 771 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985). However, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (see MPEP § 716.02(a)). The examiner again notes that Thavandiran also states that the post can be any geometric shape so long as it performs the function of tethering the construct during contraction (para 132), showing 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. Thus, Applicant’s arguments are not persuasive and the rejection is maintained.
Claim(s) 35 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) 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.
The difference between the teachings of Chen and Thavandiran in combination and the invention as instantly claimed is that they do not 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.
Response to Arguments
Applicant’s arguments regarding instant claim 35 are drawn to whether McDevitt cures the purported deficits of Chen and Thavandiran regarding the posts of the instant invention. As previously stated, Chen and Thavandiran render obvious the instant invention of claims 1-4, 6, 8-12, 14-15, and 34 as described above. Applicant has not, however, provided any arguments challenging the specific teachings of cited reference McDevitt as it relates to the substrate of the instantly claimed microfabricated device. Applicant has not attempted to distinguish the use of thin-layer polyurethane as a biodegradable substrate for cardiomyocytes as taught by McDevitt and the instantly claimed invention of claim 35. Thus, the rejection is maintained.
Conclusion
No claim is 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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/G.R./Examiner, Art Unit 1632 /KARA D JOHNSON/Primary Examiner, Art Unit 1632