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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/30/2025 has been entered.
Claim Rejections - 35 USC § 102
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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-6, 8-14, 16 & 19-35 is/are rejected under 35 U.S.C. 102(a1/a2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Miklas et al. (US 2016/0282338).
Regarding claim 1, Miklas et al. teach: 1. A system comprising:
(a) a first-stage screening apparatus comprising:
(i) a biocompatible gel (e.g., Matrigel) comprising cardiomyocytes (¶ 0046, 0636);
(ii) a biocompatible support apparatus (see e.g., PDMS ¶ 0110, ¶ 0583 for example) capable of suspending the biocompatible gel, wherein the biocompatible gel and the biocompatible support apparatus form a cardiac tissue strip (see ¶ 0002, 0010, 0018-0026+, 110; see also Figs. 1-3, 29, 34-40, 51-61+, Example 1 ¶ 0583-0584 & Example 4 ¶ 0792);
(iii) a first detection device (e.g., Olympus MVX-10 microscope ¶ 0606+, confocal microscope (Olympus IX81) or an upright confocal microscope (Zeiss LSM 510) ¶ 0687, or SEM (Hitachi S-3400 N) ¶ 0688, transmission electron microscope (Hitachi H-7000) ¶ 0605; see also i.e., Liquid chromatography coupled with tandem mass spectrometric detection (LC/MS/MS) can be used as an analytical method to monitor early absorption, distribution, metabolism and elimination testing. ¶ 0547; Hybrid quadrupole-time-of-flight (Q-TOF) LC/MS/MS systems can also be used for the characterization of metabolite profiles. The configuration of Q-TOF results in high sensitivity in mass resolution and mass accuracy in a variety of scan modes. ¶ 0549; Liquid chromatography coupled with nuclear magnetic resonance spectroscopy (LC-NMR) provides a way of confirming absolute molecular configurations. A linear ion-trap mass spectrometer possesses significantly enhanced production-scanning capabilities, while retaining all of the scan functions of a triple quadrupole MS. The ultra-high resolution and sensitivity of Fourier transform ion-cyclotron resonance MS (FI-ICRMS) can be useful for the analysis and characterization of biological mixtures. Data processing and interpretation software packages also enable efficient identification and quantification of metabolites using the tissue-engineered devices of the present invention. ¶ 0550) capable of detecting movement of the biocompatible gel (see i.e., The scaffold elements are preferably deflectable, deformable, bendable, or the like, which are further configured to allow the measurement of contractile forces exerted by the tissue strand on the scaffold elements. ¶ 0022; see also ¶ 0491, 0692, 0700, 0727, 0750, 0919 for example) in response to treatment with a test compound (see ¶ 0050, 0052, 0054, 0491, 0692, 0700, 0727, 0750, 0919 for example, and (b) (ii) below); and
(iv) an electrical power source (e.g., electrical stimulator) capable of applying an electrical pacing stimulus to the biocompatible gel (see i.e., the bioreactor can be further configured to include electrodes configured to generate an electric field across the channel of the bioreactor. The direction of the electric field can be in any direction, but preferably in a direction that is parallel or perpendicular to the longitudinal axis of the tissue strand that forms along the length of the perfusable luminal element. ¶ 0020; As shown in FIG. 36, the microwells may be configured with two electrodes (at the terminal ends of the microchannel) for stimulating cardiac cells. ¶ 0728; see also ¶ 0025, 0029, 0748, 0898+ for example); and
(b) a second-stage screening apparatus comprising:
(i) at least one organoid module comprising at least one organoid cartridge (e.g., AngioChip ¶ 0109+; dual-well bioreactor ¶ 0133+), wherein the organoid cartridge comprises a media inlet, a media outlet (see below), and at least one wall compatible with an external detection device (see i.e., SEM images in Fig. 51/¶ 0109, SEM images in Fig. 58/¶ 0116-0117, and the human whole blood perfusion through an inlet and an outlet of the endothelialized AngioChip network in Fig. 58G/ ¶ 0116; see also Fig. 74/¶ 0133, Fig. 29/¶ 0680 for example), wherein the organoid cartridge comprises a three-dimensional cardiac organoid (see i.e., the various tissue systems of the disclosure are comprised of cardiac tissue, liver tissue, kidney tissue, cartilage tissue, skin, bone marrow tissue, or combinations of such tissues. In particular embodiments, the three-dimensional tissue system comprises cardiac tissue. ¶ 0018; see also ¶ 0002, 0010, 0018-0020, 0029, 0031+ for example) comprising a lumen on the inside of the organoid (see i.e., the disclosure relates to a bioreactor system for growing a tissue culture, e.g., a three dimensional tissue strand. The bioreactor system includes a well or channel suitable for seeding cells and a perfusable scaffold with one or more lumens and which is supported or suspended over the well or channel, e.g., along the longitudinal axis of the well or channel. Once cells are seeded into the well or channel, along with optional suitable growth media, growth factors, and other nutrients suitable for the culture of the cells, the cells grow to form a tissue strand that surrounds and/or integrates with the perfusable scaffold. In use, nutrients and growth factors, as well as test agents (e.g., drugs, proteins, toxins etc.) may be delivered to the tissue strand via the perfusable lumen which is integrated with a means for delivering such materials (e.g., a reservoir element connected to the lumen via a tube or vessel). In addition, the bioreactor system may also include in various embodiments a passage that exits from the perfusable lumen, e.g., a drain or otherwise terminal reservoir that allows waste and otherwise metabolic products to diffuse from the tissue strand into the perfusable lumen and out through to the terminal reservoir. In various embodiments involving cardiac cells (or other electrically-stimulated cells) ¶ 0020; the invention relates to a bioreactor system for growing a three-dimensional tissue comprising a three-dimensional branched tissue scaffold or matrix having one or more luminal passageways (e.g., mimicking a vascularized three-dimensional tissue structure) integrated therein. The three-dimensional scaffold or matrix may contain a first portion or region for growing seeded cells and a second portion or region for providing interconnected channels that pass through or are integrated with the first portion. Preferably, the interconnected channels are perfusable with respect to the first portion and may be configured to mimic a biological vasculature. The first portion can contain one or more open regions or chambers, thereby providing an open network of chambers for growing cells and/or tissues. The three-dimensional scaffold or matrix may also contain pores or open connections between all of the components. For example, open pores or connections can be positioned between the open network of chambers for growing cells. In addition, open pores or connections can be positioned or integrated with the one or more luminal passageways. The open pores or connections facilitate movement of cells, media, growth factors, nutrients, and waste through the bioreactor system. ¶ 0025; see also ¶ 0026, 0029) where fluid may pass and capable of measuring contractile response of the three-dimensional cardiac organoid (these limitations do not impart structure. However, Miklas et al. teach: a bioreactor system for growing a tissue culture, e.g., a three-dimensional tissue strand, that is suitable for measuring contractile forces. ¶ 0021; The scaffold elements are preferably deflectable, deformable, bendable, or the like, which are further configured to allow the measurement of contractile forces exerted by the tissue strand on the scaffold elements. ¶ 0022; see also ¶ 0027, 0727 for example);
(ii) a mirror arrangement comprising at least one pyramidal mirror (e.g., Olympus MVX-10 ¶ 0606+, see the pyramid shape of mirror units shown in P3 of the provided NPL. Since Miklas et al. filed a provisional application 61/897276 on 10/30/2013, it is presumed that the NPL was available prior to this date; see also ¶ 0776) capable of monitoring of an inotropic effect of the test compound on the cardiac organoid in the organoid cartridge (see i.e., any suitable experimental drug or pharmacologic test agent may be tested by the three-dimensional systems of the invention, including opioid analgesics, anti-inflammatory drugs such as antihistamines and non-steroidal anti-inflammatory drugs (NSAIDs), diuretics such as carbonic anhydrase inhibitors, loop diuretics, high-ceiling diuretics, thiazide and thiazide-like agents, and potassium-sparing diuretics, agents that impinge on the renal and cardiovascular systems such as angiotensin converting enzyme inhibitors, cardiac drugs such as organic nitrates, calcium channel blockers, sympatholytic agents, vasodilators, beta-adrenergic receptor agonists and antagonists, .alpha.-adrenergic receptor agonists and antagonists, cardiac glycosides, anti-arrhythmic drugs, agents that affect hyperlipoproteinemias such as 3-hydroxymethylglutaryl-coenzyme A (HMG-CoA) inhibitors, anti-neoplastic agents such as alkylating agents, antimetabolites, natural products, antibiotics, and other drugs, immunomodulators, anti-diabetic agents, and anti-microbial agents such as antibacterial agents, antiviral agents, antifungal agents, antiprotozoal agents, and antihelminthic agents. ¶ 0033; Using methods of the invention, various doses of individual test agents and combinations of test agents will be screened in panels comprised of tissues having diverse genetic backgrounds to determine the pharmacogenetic toxicity profile of the test agents. For example, multiple doses of, or combinations with, test agents will be screened for toxic effects specific to one or more genetic backgrounds. Toxic effects to be screened for genetic variance include, but are not limited to, irregular metabolism, carcinogenicity and cell death. ¶ 0544; Test agents can be screened for efficacy in tissue engineered systems of the invention comprising cardiac cells affected with diseases including, but not limited to, congestive heart failure, coronary artery disease, myocardial infarction, myocardial ischemia, effects of atherosclerosis or hypertension, cardiomyopathy, cardiac arrhythmias, muscular dystrophy, muscle mass abnormalities, muscle degeneration, myasthenia gravis, infective myocarditis, drug- and toxin-induced muscle abnormalities, hypersensitivity myocarditis, autoimmune endocarditis, and congenital heart disease. Preferably, test agents will be assayed for their ability to accelerate cardiac regeneration or improve contractile properties. In general, efficacy can be indicated by detection of improved contractility, electromechanical conduction and/or association, susceptibility to electrical dysfunction, ventricular fibrillation (sudden death), ionotropy, chronotropy, and decreased leakage of enzymes (e.g., CPK and SGOT). In various embodiments, the devices of the invention can be utilized or coupled together, including, e.g., in series (i.e., in tandem), in parallel or combinations thereof … ¶ 0569-0570; Tissue strands could be electrically paced and responded to physiological agonists such as epinephrine (β-adrenergic stimulation) by increasing spontaneous beating frequency. FIG. 8d shows optical mapping of impulse propagation. ¶ 0627; The beating activities of the human cardiac tissue strands were recorded at 16.67 frames/second before treatment and 24 hr post-treatment by Olympus IX81 while the tissue strands were kept at 37° C. The beating activities of the human cardiac tissue strands were quantified by the image analysis method described by Sage et al28. In brief, the movements of one spot at the same location on the human cardiac tissue strand before and after the NO treatment were characterized. ¶ 0692; FIG. 43 shows example results from drug testing. Norepinephrine is a stress hormone acting in the fight-or-flight response, by directly increasing heart rate72. FIG. 43A shows a representative tissue beating pattern at a given concentration of drugs in comparison with the control. The addition of Norepinephrine at 10 μM resulted in significant increased beating frequency. E4301 works as a blocking agent for human Ikr cardiac ion channel, blockage of which can result in after-depolarization and dangerous arrhythmias56. E4301 addition at 100 nM resulted in prolonged relaxation and occasional after beat, which clearly represent the function of this agent. Isoproterenol is a non-selective beta-adrenergic agonist that increases cardiac output. High dosage can desensitize the tissue and cause reverse effect73. FIG. 43B showed a dose responsive trend of tissue contractile forces normalized to forces before drug addition. Tissue had positive inotropic action (increase in contractility) at 100 nM and 1 μM, and a slight negative inotropic effect (decrease in contractility) at 10 μM. ¶ 0768; the systems, devices and assemblies could be modified to include additional or fewer of such elements/components. For example, while any of the elements/components disclosed may be referenced as being singular, the embodiments disclosed herein could be modified to include a plurality of such elements/components. Selected features from one or more of the above-described embodiments may be combined to create alternative embodiments not explicitly described. ¶ 0913); and
(iii) a second detection device (e.g., Olympus MVX-10 microscope ¶ 0606+, confocal microscope (Olympus IX81) or an upright confocal microscope (Zeiss LSM 510) ¶ 0687, or SEM (Hitachi S-3400 N) ¶ 0688, transmission electron microscope (Hitachi H-7000) ¶ 0605; see also i.e., Liquid chromatography coupled with tandem mass spectrometric detection (LC/MS/MS) can be used as an analytical method to monitor early absorption, distribution, metabolism and elimination testing. ¶ 0547; Hybrid quadrupole-time-of-flight (Q-TOF) LC/MS/MS systems can also be used for the characterization of metabolite profiles. The configuration of Q-TOF results in high sensitivity in mass resolution and mass accuracy in a variety of scan modes. ¶ 0549; Liquid chromatography coupled with nuclear magnetic resonance spectroscopy (LC-NMR) provides a way of confirming absolute molecular configurations. A linear ion-trap mass spectrometer possesses significantly enhanced production-scanning capabilities, while retaining all of the scan functions of a triple quadrupole MS. The ultra-high resolution and sensitivity of Fourier transform ion-cyclotron resonance MS (FI-ICRMS) can be useful for the analysis and characterization of biological mixtures. Data processing and interpretation software packages also enable efficient identification and quantification of metabolites using the tissue-engineered devices of the present invention. ¶ 0550) capable of monitoring the inotropic effect of the test compound on the cardiac organoid in the organoid cartridge in response to treatment with the test compound (see ¶ 0050, 0052, 0054, 0491, 0692, 0700, 0727, 0750, 0919 for example, and (b) (ii) above).
Regarding claim 1, Miklas et al. inherently teach a system comprising two screening stages, see the use of a variety of assays known in the art to detect the effect of a test agent in cardiac tissue engineered systems. For example, the devices of the invention can be utilized or coupled together, including, e.g., in series, in parallel or combinations thereof, see ¶ 0566-0570 for example. In the event that a system comprising a two separate stage screening system is not shown with sufficient specificity, then it would have been obvious to one having ordinary skill in the art to provide a system comprising a two screening stage system to monitor with different detection devices (e.g., Olympus MVX-10 microscope ¶ 0606+, confocal microscope (Olympus IX81) or an upright confocal microscope (Zeiss LSM 510) ¶ 0687, or SEM (Hitachi S-3400 N) ¶ 0688, transmission electron microscope (Hitachi H-7000) ¶ 0605; see also i.e., Liquid chromatography coupled with tandem mass spectrometric detection (LC/MS/MS) can be used as an analytical method to monitor early absorption, distribution, metabolism and elimination testing. ¶ 0547; Hybrid quadrupole-time-of-flight (Q-TOF) LC/MS/MS systems can also be used for the characterization of metabolite profiles. The configuration of Q-TOF results in high sensitivity in mass resolution and mass accuracy in a variety of scan modes. ¶ 0549; Liquid chromatography coupled with nuclear magnetic resonance spectroscopy (LC-NMR) provides a way of confirming absolute molecular configurations. A linear ion-trap mass spectrometer possesses significantly enhanced production-scanning capabilities, while retaining all of the scan functions of a triple quadrupole MS. The ultra-high resolution and sensitivity of Fourier transform ion-cyclotron resonance MS (FI-ICRMS) can be useful for the analysis and characterization of biological mixtures. Data processing and interpretation software packages also enable efficient identification and quantification of metabolites using the tissue-engineered devices of the present invention. ¶ 0550) capable of detecting movement of the biocompatible gel (see ¶ 0491, 0692, 0700, 0727, 0750, 0919 for example) for measuring the effect on contractility of tissues formed thereon resulting from exposure to a therapeutic agent or a toxin or a test agent (test compound) of interest, as disclosed by Miklas et al. (see ¶ 0050, 0052, 0054, 0491, 0692, 0700, 0727, 0750, 0919 for example, and (b) (ii) above).
With regard to limitations in claims 1, 21, 29, 32, 35 (e.g., “for detecting movement of the biocompatible gel in response to treatment with the test compound”, “for applying an electrical pacing stimulus to the biocompatible gel”, “where fluid may pass and pressure and/or volume data is recorded to measure contractile response of the three-dimensional cardiac organoid”, “for simultaneous monitoring of an inotropic effect of the test compound on the cardiac organoid in the organoid cartridge”, “for monitoring the inotropic effect of the test compound on the cardiac organoid in the organoid cartridge in response to treatment with the test compound”, “for delivery of a compound to the cardiomyocytes, tissue, or organoid”, etc.), these claim limitations are considered process or intended use limitations, which do not further delineate the structure of the claimed apparatus from that of the prior art. The cited prior art teaches all of the positively recited structure of the claimed apparatus. The Courts have held that a statement of intended use in an apparatus claim fails to distinguish over a prior art apparatus. See In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962). The Courts have held that the manner of operating an apparatus does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex Parte Masham, 2 USPQ2d 1647 (BPAI 1987). The Courts have held that apparatus claims must be structurally distinguishable from the prior art in terms of structure, not function. See In re Danley, 120 USPQ 528, 531 (CCPA 1959); and Hewlett-Packard Co. V. Bausch and Lomb, Inc., 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (see MPEP §§ 2114 and 2173.05(g)). Furthermore, "[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims." See In re Young, 75 F.2d *>996, 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)) (see MPEP § 2115).
Regarding claims 2-6, 8-14, 16, 19-35, Miklas et al. teach:
2. The system according to claim 1, wherein the cardiomyocytes are human cardiomyocytes (see ¶ 0686 for example).
3. The system according to claim 2, wherein the human cardiomyocytes are human ventricular cardiomyocytes (see ¶ 0665 for example).
4. The system according to claim 2, wherein the human cardiomyocytes are at least one human pluripotent stem cell (¶ 0032, 0930+).
5. The system according to claim 1, wherein the cardiomyocytes are present at a concentration of at least 10.sup.6 cells/ml (¶ 0880, 0940).
6. The system according to claim 1, wherein the biocompatible gel comprises a basement membrane matrix gel (e.g., Matrigel ¶ 0594, 0636+).
8. The system according to claim 6, wherein the biocompatible gel further comprises collagen (¶ 0626, 0710+).
9. The system according to claim 8, wherein the collagen is type I human collagen (¶ 0626, 0710+).
10. The system according to claim 8, wherein the collagen is present at a concentration of at least 1 mg/ml (¶ 0599, 0940).
11. The system according to claim 1, wherein the biocompatible support apparatus comprises at least two vertical support members (see ¶ 0762, 0795, 0822, 0847, 0876, 0940 for example).
12. The system according to claim 11, wherein the vertical support members are made of polydimethylsiloxane (see ¶ 0110, 0761, 0822, 0876+ for example).
13. The system according to claim 11, wherein the biocompatible support apparatus comprises two vertical support members (see ¶ 0762, 0795, 0822, 0847, 0876, 0940 for example).
14. The system according to claim 13, wherein the two vertical support members are approximately circular in cross-section with a diameter of about 0.5 mm (¶ 0876).
16. The system according to claim 1, wherein the first and/or second detection device is a camera (see ¶ 0606 for example).
19. The system of claim 1 further comprising a second organoid that is a heart, a brain, a nerve, a liver, a kidney, an adrenal gland, a stomach, a pancreas, a gall bladder, a lung, a small intestine, a colon, a bladder, a prostate, a uterus, a tumor, an eye, skin, blood, or a vascular organoid (see i.e., In yet another embodiments of the fourth aspect, the present disclosure relates to methods of using the three-dimensional tissue systems, the devices, and/or the systems of the invention in various applications, including, but not limited to, (a) the testing of the efficacy and safety (including toxicity) of experimental pharmacologic agents (including, but not limited to, small molecule drugs, biologics, nucleic acid-based agents), (b) the defining of pharmacokinetics and/or pharmacodynamics of pharmacologic agents (including, but not limited to, small molecule drugs, biologics, nucleic acid-based agents), (c) characterizing the properties and therapeutic effects of pharmacologic agents (including, but not limited to, small molecule drugs, biologics, nucleic acid-based agents) on a subject, (d) screening of new pharmacologic agents, (e) providing implantable engineered tissues for use in regenerative medicine for treating damaged and/or diseased tissues, (e.g., use of the tissue constructs, devices, and/or systems of the disclosure to study cardiac disease states, including patients with electrical conduction defects (iPSC-CM)), and (f) personalized medicine. In certain embodiments of the fourth aspect, two or more bioreactor systems may be connected to one another such that they are functionally interactive. The two or more bioreactors systems joined together, e.g., end to end in series, may be formed of the same types of tissues or entirely different tissues. For example, a system is contemplated where a first bioreactor systems comprising cardiac tissue is joined in series with a hepatic second bioreactor system. This pair of systems can be further modified with one or more additional bioreactor systems joined further in series with the first two systems. In another example, a first bioreactor system comprising healthy cardiac tissue can be joined in series with a second bioreactor system comprising diseased cardiac tissue. In this way, one can test not only the effects of a drug, toxin, or otherwise test agent on a first bioreactor system comprising a first tissue, but also the effect of the metabolized drug, toxin, or otherwise agent on the downstream second bioreactor system, e.g., hepatic tissue. ¶ 0424; In various embodiments, a plurality of Angiochip systems may be configured in series, whereby a first Angiochip is formed of one type of cell or tissue (e.g., cardiac) and a second “downstream” or “upstream” Angiochip is formed of a second type of cell or tissue (e.g., diseased cardiac, or hepatic). In this manner, the interaction of drugs may be tested in the context of multiple organ or tissue systems. For example, a test agent may be introduced into an Angiochip prepared from hepatic tissue, which may be linked downstream to a second Angiochip prepared from cardiac tissue. In this manner, the drug may first interact with the hepatic tissue, and any metabolic products resulting therefrom may flow downstream to the cardiac tissue Angiochip, thereby facilitating one to test the effect of the drug's metabolism on cardiac function. Thus, the invention contemplates a plurality of Angiochip devices arranged in a tandem (i.e., in series) manner for use in testing inter-organ drug interactions in the body. Any conceivable combination of tissues could be tested in tandem, for example, cardiac/hepatic or hepatic/cardiac. ¶ 0426; see also ¶ 0018, 0489 for example).
20. The system of claim 19 wherein the second organoid is a heart organoid (see ¶ 0424, 0426, 0171 for example).
21. The system of claim 1, wherein the second-stage screening apparatus further comprises an electrode (see ¶ 0020, 0025, 0029 for example).
22. The system of claim 1, wherein the second-stage screening apparatus further comprises a temperature control element, a light source, a module access port, or any combination thereof (see ¶ 0606 for example).
23. The system of claim 1 further comprising (i) a data processor in electronic communication with the first and/or second detection device, (ii) a temperature control element, (iii) a light source, and/or (iv) a module access port, or any combination thereof (see Fig. 48 & ¶ 0776 for example).
24. The system of claim 23 wherein the first and/or second detection device comprises a digital camera and/or a pressure transducer (¶ 0606).
25. The system of claim 1 wherein the cardiac tissue or the cardiac organoid is of human origin (see ¶ 0119 for example).
26. The system of claim 1 further comprising a monitor (see Fig. 48 for example).
27. The system of claim 1 comprising a plurality of organoid modules (see ¶ 0424, 0426, 0682 for example).
28. The system of claim 1 further comprising an interconnected fluid exchange network, wherein the network comprises a plurality of fluid lines, a plurality of valves, at least one pump, and at least one fluid tank (see ¶ 0020, 0109, 0526, 0608 for example).
29. The system of claim 28 further comprising a port (see i.e., In use, nutrients and growth factors, as well as test agents (e.g., drugs, proteins, toxins etc.) may be delivered to the tissue strand via the perfusable lumen which is integrated with a means for delivering such materials (e.g., a reservoir element connected to the luman (sic) via a tube or vessel). ¶ 0020, 0029+; see also e.g., inlet ¶ 0109) capable of introducing the test compound (¶ 0020, 0029).
30. The system of claim 28 wherein the interconnected fluid exchange network comprises fluid communication between at least two organoid cartridges (see ¶ 0133 for example).
31. The system of claim 28 wherein the interconnected fluid exchange network comprises media (see ¶ 0020 for example).
32. The system of claim 28 wherein the fluid exchange network is capable of providing automated media exchange (¶ 0547).
33. The system of claim 1 further comprising a gas pressure controller (e.g., external pressure source ¶ 0680).
34. The system of claim 33 wherein the gas pressure controller is capable of controlling the external pressure source (e.g., external pressure source ¶ 0680).
35. The system of claim 1 further comprising a drug perfusion apparatus for delivery of a compound to the cardiomyocytes, tissue, or organoid (e.g., drug reservoir ¶ 0680, 0020, 0029+).
Claim Rejections - 35 USC § 103
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Miklas et al. (US 2016/0282338).
Regarding claim 7, Matrigel (the basement membrane matrix gel) is generally known to have about 9-12 mg/ml, and Miklas teach the use of 10% (v/v) Matrigel (¶ 0880+), (i.e., at least about 0.5 mg/ml). In addition, Miklas et al. teach various Matrigel concentration for desired cell density (¶ 0746, 0880, 0890+). However, Miklas et al. do not explicitly teach: 7. The system according to claim 6, wherein the basement membrane matrix gel is present at a concentration of at least 0.5 mg/ml.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the basement membrane matrix gel (Matrigel) concentration of at least 0.5 mg/ml to adjust the cell density/concentration. As noted by the Court in KSR, “[w]hen a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one”, 550 U.S. at ___, 82 USPQ2d at 1396 (emphasis added), or solves a problem which is different from that which the applicant was trying to solve, may also be considered for the purposes of 35 U.S.C. 103. See MPEP 2141.
Response to Arguments
Applicant's arguments filed 09/30/2025 have been fully considered but they are not persuasive.
Applicant’s amendments and arguments have been considered and have been addressed within the above art rejection.
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., “[...] the AngioChip device of Miklas does not comprise cardiac tissue compacted around a balloon core to form a 3D cardiac organoid.”) 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). However, Miklas appears to teach the argued element, see i.e., FIG. 51(c) depicts the seeding of the AngioChip surface with a gel/cell preparation (2) followed by gel compaction (3) around and within the AngioChip. ¶ 0109 & Fig. 51C “(3) Gel Compaction”.
In response to applicant's argument that “Miklas does not teach or suggest [...] where fluid may pass and pressure and/or volume data is recorded to measure contractile response of the three-dimensional cardiac organoid. [...] Further, Miklas does not teach [...] for screening a test compound (1) on a cardiac tissue strip in a first apparatus, and (2) on a 3D cardiac organoid in a second apparatus”, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. The Courts have held that limitations regarding the contents, intended use or manner of operating an apparatus do not further limit the patentability of apparatus claims. The Courts have held that a statement of intended use in an apparatus claim fails to distinguish over a prior art apparatus. See In re Sinex, 309 F.2d 488,492, 135 USPQ 302, 305 (CCPA 1962). The Courts have held that the manner of operating an apparatus does not differentiate an apparatus claim from the prior art, if the prior art apparatus teaches all of the structural limitations of the claim. See Ex Parte Masham, 2 USPQ2d 1647 (BPAI 1987). The Courts have held that apparatus claims must be structurally distinguishable from the prior art in terms of structure, not function. See In re Danley, 120 USPQ 528, 531 (CCPA 1959); and Hewlett-Packard Co. V. Bausch and Lomb, Inc., 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (see MPEP §§ 2114 and 2173.05(g)). "Expressions relating the apparatus to contents thereof during an intended operation are of no significance in determining patentability of the apparatus claim." Ex parte Thibault, 164 USPQ 666,667 (Bd. App. 1969). Furthermore, "[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims." See In re Young, 75 F.2d *>996, 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)) (see MPEP § 2115). However, Miklas et al. teach: a bioreactor system for growing a tissue culture, e.g., a three-dimensional tissue strand, that is suitable for measuring contractile forces. ¶ 0021; The scaffold elements are preferably deflectable, deformable, bendable, or the like, which are further configured to allow the measurement of contractile forces exerted by the tissue strand on the scaffold elements. ¶ 0022; see also ¶ 0027, 0727 for example. In addition, Miklas appears to teach the use of a variety of assays known in the art to detect the effect of a test agent in cardiac tissue engineered systems. For example, the devices of the invention can be utilized or coupled together, including, e.g., in series, in parallel or combinations thereof, see ¶ 0566-0570 for example. Therefore, Miklas’s device is fully capable of the process and/or intended use limitations.
Applicant is encouraged to amend the claims to include additional structural elements of the system. Applicant is thanked for their thoughtful amendments to the claims.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 DEAN KWAK whose telephone number is (571)270-7072. The examiner can normally be reached M-TH, 4:30 am - 2:30 pm EST.
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/DEAN KWAK/Primary Examiner, Art Unit 1798
DEAN KWAK
Primary Examiner
Art Unit 1798