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 .
DETAILED ACTION
Claims 2-7, 9-11, 14-18, 20-22, 26-33, 36-39, 41-44, 47-48, 51-60, 63-64 and 66 are cancelled.
Claims 1, 8, 12-13, 19, 23-25, 34-35, 40, 45-46, 49-50, 61-62 and 65 are pending and under examination herein.
Priority
This application, filed on 2/16/2024, is a 371 of PCT/US2022/036011 filed on 7/11/2022, which claims benefit of 63/234,287 filed on 8/18/2021. The effective filling date of the current application is August 18, 2021.
Claim Objections
Claims 19 and 62 are objected to because of the following informalities:
Claim 19 recites “the three-dimensional tissue relative to the support over the period of time the measurement of the strain” in lines 3-4, which is ungrammatical and appears to be missing the word “or” between “time” and “the”. It is suggested that the limitation be amended to recite “the three-dimensional tissue relative to the support over the period of time or the measurement of the strain”.
Claim 62 recites “wherein a difference between the first helical angle and the second helical angle falls is less than 90°” in the last two lines, which is ungrammatical. It is suggested that the word “falls” is deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claims 1, 8, 12, 19, 23-25 and 61 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by MacQueen et al. (“A tissue-engineered scale model of the heart ventricle”, Nature Biomedical Engineering, 2018, Vol. 2, pp.930-941).
Regarding claim 1, MacQueen teaches fabricating ellipsoidal thin-walled chambers composed of a nanofibrous synthetic-natural polymer-protein blend and seeded them with neonatal rat ventricular myocytes (NRVMs) or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) (p.930, 2nd column last paragraph – p.931 1st column top paragraph). MacQueen teaches the nanofiber ventricle chamber production strategy based on pull-spinning fibers on a rotating ellipsoidal collector ensured roughly circumferential fiber alignment (p.931, 1st column – ventricle scaffold). MacQueen teaches the fibers have a helical angle with respect to the longitudinal axis of the cavity in Fig. 1c. MacQueen teaches the fibers are of micron scale in Fig. 2.
MacQueen teaches the resulting tissue-engineered ventricle chambers were sutured to tubing or bioreactor components through which catheter sensors were introduced and stable contraction of both NRVM and hiPSC-CM ventricles permitted time-dependent pressure and volume measurements (p.931, 1st column top paragraph).
MacQueen teaches sheets of nanofibrous material using the same pull-spinning conditions as for ventricle chamber production were produced for biaxial tensile testing; subjected to four biaxial preconditioning cycles were run and the strain-strain curves were calculated using original dimensions of the nanofibrous samples (p.938, 1st column – Mechanical testing).
Regarding claim 8, MacQueen teaches optical mapping experiments to monitor calcium propagation using a modified tandem-lens macroscope equipped with a high-speed camera (p.939, 1st column – optical mapping experiments). MacQueen teaches a point stimulator was located at 0.5-1.0mm from the apex of the ventricle with a motorized xy-micromanipulator (p.939, 1st column – optical mapping experiments). MacQueen teaches imaging tissue-engineered ventricles from above using 5ms exposure and a 2.5 s recording time (p.939, 1st column – optical mapping experiments).
Regarding claim 12, MacQueen teaches a ventricle assembly affixed at the top (i.e. first end) and a pointed end opposite the first end that is affixed (p.935, Fig. 4a).
Regarding claim 19, MacQueen teaches electrical field and point stimulation was applied using two platinum electrodes with 20mm and 1mm spacing respectively (p.939, 1st column – optical mapping experiments). MacQueen teaches the point stimulator was located at 0.5–1.0 mm from the apex of the ventricle with a motorized xy-micromanipulator (Zaber Technologies); electrical pulses were generated with 12 V amplitude and 10 ms duration using a pulse generator (MyoPacer Cell Stimulator, IonOptix); and pacing frequency was 1 Hz for NRVM ventricles and 3 Hz for hiPSC-CM ventricles (p.939, 1st column – optical mapping experiments).
Regarding claims 23 and 24, MacQueen teaches measuring the contractile response of tissue-engineered ventricles to increasing concentrations of the β-adrenergic agonist, isoproterenol (a test compound), by exposing engineered tissues to concentrations of isoproterenol ranging from 1 x 10-10 M to 1 x 10-4 M by cumulative addition of 1.0 log doses every 2 minutes (p.939, 2nd column – β-adrenergic response of tissue engineered ventricles). MacQueen further teaches pressure and volume recordings from the last 30 s of each measurement were converted to the frequency domain by fast Fourier transform using Matlab and beat rates were estimated using Matlab’s ‘findpeaks’ function applied to pressure or volume fast Fourier transform data (p.939, 2nd column – β-adrenergic response of tissue engineered ventricles). MacQueen teaches that PV loops measured before and after isoproterenol exposure showed an isoproterenol-induced reduction in stroke work, concomitant with an increase in beat frequency (p.932, 2nd column last paragraph; Fig. 3b, 3c).
Regarding claim 25, MacQueen teaches a tissue-engineered model heart ventricle (title). MacQueen teaches tissue-engineered scale models of the human left ventricle, made of nanofibrous scaffolds that promote native-like anisotropic myocardial tissue genesis and chamber-level contractile function (abstract). MacQueen teaches visualizing the relationship between pressure and volume change during cardiac contraction cycles by plotting PV loops for both rat and human ventricles from PV catheter measurements (p.932, 1st column; Fig. 3b). MacQueen teaches measuring time-dependent intraventricular pressure (i.e. strain) and volume by catheterization, an established method for heart chamber performance evaluation (p.931, 2nd column – Intraventricular pressure and volume measurements; Fig. 3). MacQueen further teaches that measured differences in chamber pressure were ~50µmHg (rat or human) and the volume change was ~5µl (rat) or 1µl (human); thus ejection fractions were ~1% (rat) or ~0.2% (human) (p.932, 1st column last sentence to 2nd column top paragraph).
Regarding claim 61, MacQueen teaches a tissue-engineered model heart ventricle (title).
Claim Rejections - 35 USC § 103
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 13 is rejected under 35 U.S.C. 103 as being unpatentable over MacQueen et al. (“A tissue-engineered scale model of the heart ventricle”, Nature Biomedical Engineering, 2018, Vol. 2, pp.930-941) in view of Shin et al. (“Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures”, Nature Communications, 2017, Vol. 8, article 15807, 12 pages).
The teachings of MacQueen et al. are discussed above.
Regarding claim 13, MacQueen teaches that ventricles were incubated with 2µM Rhod-2 (Invitrogen) for 30 min at 37°C, rinsed, and incubated in dye-free media for an additional 15min at 37°C before recording (p.939, 1st column – optical mapping experiments; p.936, Fig. 5). MacQueen teaches that calcium propagation was monitored using a modified tandem-lens macroscope equipped with a high-speed camera (p.939, 1st column - optical mapping experiments).
MacQueen does not disclose fiducial markers.
However, Shin teaches multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures (title). Shin teaches biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) that exhibit high contrast for real-time imaging and also strong adhesive properties, and cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (abstract). Shin further teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and their strong adhesion to soft tissues (p.8, 2nd column, top paragraph). Shin further teaches that TSNs could be clearly visualized in actively moving tissues by CT and fluoroscopy, and micro-CT images showed that the locations of the TSN markers did not change over two weeks (p.8, 2nd column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute tantalum silica nanoparticles as a fiducial marker taught by Shin for the Rhod-2 dye solution taught by MacQueen. One of ordinary skill in the art would have been motivated to use a biocompatible nanoparticle that exhibits high contrast for real-time imaging in an application for an implantable heart scaffold to allow imaging over time. One of ordinary skill in the art would have found it beneficial to do so because Shin teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and remained in place for follow-up imaging.
Claims 34-35, 40, 45-46, and 49-50 are rejected under 35 U.S.C. 103 as being unpatentable over MacQueen et al. (“A tissue-engineered scale model of the heart ventricle”, Nature Biomedical Engineering, 2018, Vol. 2, pp.930-941) in view of Shin et al. (“Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures”, Nature Communications, 2017, Vol. 8, article 15807, 12 pages) and Faludi et al. (“Left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves: An in vivo study using echocardiographic particle image velocimetry”, The Journal of Thoracic and Cardiovascular Surgery, 2010, Vol. 139, Issue 6, pp.1501-1510). The rejection of claims 49 and 50 is further evidenced by Cleveland Clinic (Isoproterenol injection, https://my.clevelandclinic.org/health/drugs/23877-isoproterenol-injection, accessed on April 24, 2026).
Regarding claim 34, MacQueen teaches fabricating ellipsoidal thin-walled chambers composed of a nanofibrous synthetic-natural polymer-protein blend and seeded them with neonatal rat ventricular myocytes (NRVMs) or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) (p.930, 2nd column last paragraph – p.931 1st column top paragraph). MacQueen teaches the nanofiber ventricle chamber production strategy based on pull-spinning fibers on a rotating ellipsoidal collector ensured roughly circumferential fiber alignment (p.931, 1st column – ventricle scaffold). MacQueen teaches the fibers have a helical angle with respect to the longitudinal axis of the cavity in Fig. 1c. MacQueen teaches the ventricle scaffolds were sterilized using UV radiation, incubated with fibronectin and then transferred cells to the scaffold and incubated for 90 min (p.938, 2nd column – ventricle seeding). MacQueen further teaches the ventricles were transferred to larger wells with media refreshed every 48h until use (p.938, 2nd column – ventricle seeding).
MacQueen teaches that ventricles were incubated with 2µM Rhod-2 (Invitrogen) for 30 min at 37°C, rinsed, and incubated in dye-free media for an additional 15min at 37°C before recording (p.939, 1st column – optical mapping experiments; p.936, Fig. 5). MacQueen teaches that calcium propagation was monitored using a modified tandem-lens macroscope equipped with a high-speed camera (p.939, 1st column - optical mapping experiments).
MacQueen teaches that ventricle scaffolds were sutured over a support ring wherein input and output channels of the intraventricular flow loop converged, and pressure supplied by an external source to the extraventricular flow loop drives assisted ventricle contraction and flow through the intraventricular flow loop (p.935, Fig. 4). MacQueen further teaches ventricle catheterization enabled pressure and volume measurements during assisted ventricle contraction
MacQueen does not teach particle imaging velocimetry on fiducial markers.
However, Shin teaches multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures (title). Shin teaches biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) that exhibit high contrast for real-time imaging and also strong adhesive properties, and cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (abstract). Shin further teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and their strong adhesion to soft tissues (p.8, 2nd column, top paragraph). Shin further teaches that TSNs could be clearly visualized in actively moving tissues by CT and fluoroscopy, and micro-CT images showed that the locations of the TSN markers did not change over two weeks (p.8, 2nd column, 2nd paragraph).
Faludi teaches left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves using echocardiographic particle image velocimetry (title). Faludi teaches collecting 2-dimensional grayscale images with high frame rate and repeated intravenous administration of a low dose of left heart contrast (p.1502, 2nd column – Echocardiographic Image Acquisition). Faludi teaches that images were acquired when cavity contrast distribution was homogeneous and single contrast bubbles could be distinguished (p. 1502, 2nd column – Echocardiographic Image Acquisition). Faludi further teaches that Echocardiographic loops were processed offline using a dedicated prototype software; at first the endocardial border was manually traced in one still frame and then automatically tracked by the software during the cardiac cycle (p.1502, 2nd column - Particle Image Velocimetry (PIV)). Faludi teaches that bubbles were assumed to move with blood flow, and thus tracking them allowed them to obtain regional flow information by means of PIV; maximal vortex area during diastole was given in percentages of the left ventricular area (p.1502, 2nd column – Particle Image Velocimetry – 1503 1st column top paragraph). Faludi teaches that it might be relevant to optimize intracavitary blood flow after valve replacement, particularly in dysfunctional ventricles (p.1508, 2nd column – Clinical Considerations 3rd paragraph). Faludi teaches that this new technique of echocardiographic PIV can contribute to a better understanding of hemodynamic consequences of heart valve surgery and thus to an optimization of such a therapy (p.1508, 2nd column – Clinical Considerations 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute tantalum silica nanoparticles, which are fiducial marker taught by Shin, for the Rhod-2 dye solution taught by MacQueen in the ventricle incubation step taught by MacQueen. One of ordinary skill in the art would have been motivated to use a biocompatible nanoparticle that exhibits high contrast for real-time imaging in an application for an implantable heart scaffold to allow imaging over time. One of ordinary skill in the art would have found it beneficial to do so because Shin teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and remained in place for follow-up imaging.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine particle imaging velocimetry taught by Faludi with the method of MacQueen to image the area including the opening of the cavity, because Faludi teaches that echocardiographic PIV can contribute to a better understanding of hemodynamic consequences of heart valve surgery. One of ordinary skill in the art would have found it beneficial to optimize intracavitary blood flow after valve replacement, particularly in dysfunctional ventricles, to improve patient therapy following heart valve surgery.
Regarding claim 35, MacQueen teaches a tissue-engineered model heart ventricle (title). MacQueen further teaches measured differences in chamber pressure were ~50µmHg (rat or human) and the volume change was ~5µl (rat) or 1µl (human); thus ejection fractions were ~1% (rat) or ~0.2% (human) (p.932, 2nd column top paragraph).
Regarding claim 40, MacQueen teaches that ventricles were incubated with 2µM Rhod-2 (Invitrogen) for 30 min at 37°C (i.e. markers are suspended in the medium), rinsed, and incubated in dye-free media for an additional 15min at 37°C before recording (p.939, 1st column – optical mapping experiments; p.936, Fig. 5).
MacQueen does not disclose fiducial markers.
However, Shin teaches multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures (title). Shin teaches biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) that exhibit high contrast for real-time imaging and also strong adhesive properties, and cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (abstract). Shin further teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and their strong adhesion to soft tissues (p.8, 2nd column, top paragraph). Shin further teaches that TSNs could be clearly visualized in actively moving tissues by CT and fluoroscopy, and micro-CT images showed that the locations of the TSN markers did not change over two weeks (p.8, 2nd column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute tantalum silica nanoparticles as a fiducial marker taught by Shin for the Rhod-2 dye taught by MacQueen in solution in the ventricle incubation step taught by MacQueen. One of ordinary skill in the art would have been motivated to use a biocompatible nanoparticle that exhibits high contrast for real-time imaging in an application for an implantable heart scaffold to allow imaging over time. One of ordinary skill in the art would have found it beneficial to do so because Shin teaches that TSNs are ideal fiducial markers due to their detectability by various imaging modalities and remained in place for follow-up imaging.
Regarding claim 45, MacQueen teaches electrical field and point stimulation was applied using two platinum electrodes with 20mm and 1mm spacing respectively (p.939, 1st column – optical mapping experiments). MacQueen teaches the point stimulator was located at 0.5–1.0 mm from the apex of the ventricle with a motorized xy-micromanipulator (Zaber Technologies); electrical pulses were generated with 12 V amplitude and 10 ms duration using a pulse generator (MyoPacer Cell Stimulator, IonOptix); and pacing frequency was 1 Hz for NRVM ventricles and 3 Hz for hiPSC-CM ventricles (p.939, 1st column – optical mapping experiments).
Regarding claim 46, MacQueen teaches measuring the contractile response of tissue-engineered ventricles to increasing concentrations of the β-adrenergic agonist isoproterenol by exposing engineered tissues to concentrations of isoproterenol ranging from 1 x 10-10 M to 1 x 10-4 M by cumulative addition of 1.0 log doses every 2 minutes (p.939, 2nd column – β-adrenergic response of tissue engineered ventricles). MacQueen teaches that PV loops measured before and after isoproterenol exposure showed an isoproterenol-induced reduction in stroke work, concomitant with an increase in beat frequency (p.932, 2nd column last paragraph; Fig. 3b, 3c).
Regarding claims 49 and 50, MacQueen teaches measuring the contractile response of tissue-engineered ventricles to increasing concentrations of the β-adrenergic agonist isoproterenol by exposing engineered tissues to concentrations of isoproterenol ranging from 1 x 10-10 M to 1 x 10-4 M by cumulative addition of 1.0 log doses every 2 minutes (p.939, 2nd column – β-adrenergic response of tissue engineered ventricles). MacQueen teaches that PV loops measured before and after isoproterenol exposure showed an isoproterenol-induced reduction in stroke work, concomitant with an increase in beat frequency (p.932, 2nd column last paragraph; Fig. 3b, 3c). As evidenced by Cleveland Clinic, isoproterenol is a medication that increases the strength of heart muscle to treat heart failure, which is a condition that occurs when the heart doesn’t pump very well (p.1, 1st paragraph).
MacQueen does not teach particle imaging velocimetry.
However, Faludi teaches left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves using echocardiographic particle image velocimetry (title). Faludi teaches collecting 2-dimensional grayscale images with high frame rate and repeated intravenous administration of a low dose of left heart contrast (p.1502, 2nd column – Echocardiographic Image Acquisition). Faludi teaches that images were acquired when cavity contrast distribution was homogeneous and single contrast bubbles could be distinguished (p. 1502, 2nd column – Echocardiographic Image Acquisition). Faludi further teaches that Echocardiographic loops were processed offline using a dedicated prototype software; at first the endocardial border was manually traced in one still frame and then automatically tracked by the software during the cardiac cycle (p.1502, 2nd column - Particle Image Velocimetry). Faludi teaches that bubbles were assumed to move with blood flow, and thus tracking them allowed them to obtain regional flow information by means of PIV; maximal vortex area during diastole was given in percentages of the left ventricular area (p.1502, 2nd column – Particle Image Velocimetry – 1503 1st column top paragraph). Faludi teaches that image loops of 3 cardiac cycles were digitally stored for subsequent offline analysis (p.1502, 2nd column – Echocardiographic Image Acquisition). Faludi teaches that it might be relevant to optimize intracavitary blood flow after valve replacement, particularly in dysfunctional ventricles (p.1508, 2nd column – Clinical Considerations 3rd paragraph). Faludi teaches that this new technique of echocardiographic PIV can contribute to a better understanding of hemodynamic consequences of heart valve surgery and thus to an optimization of such a therapy (p.1508, 2nd column – Clinical Considerations 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the use of particle imaging velocimetry taught by Faludi with the administration of β-adrenergic agonist isoproterenol taught by MacQueen to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to do so because Faludi teaches that regional flow information could be obtained by means of PIV. One of ordinary skill in the art would have found it beneficial to obtain regional flow information before and after administering β-adrenergic agonist isoproterenol to determine how flow information is affected by increasing concentrations of isoproterenol, because MacQueen teaches PV loops measured before and after isoproterenol exposure showed an isoproterenol-induced reduction in stroke work, concomitant with an increase in beat frequency.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over MacQueen et al. (“A tissue-engineered scale model of the heart ventricle”, Nature Biomedical Engineering, 2018, Vol. 2, pp.930-941) in view of Guner et al. (“A dual-phase scaffold produced by rotary jet spinning and electrospinning for tendon tissue engineering”, Biomedical Materials, 2020, Vol. 15, No.6, Article 065014, 20 pages).
The teachings of MacQueen et al. are discussed above.
Regarding claim 62, MacQueen teaches ventricle scaffolds were produced by pull spinning PCL/gelatin nanofibers onto ellipsoidal collection mandrels (p.938, 1st column – Ventricle scaffold fabrication). MacQueen teaches human left ventricle ellipsoidal shape and fibrous ECM inspired their use of circumferentially oriented nanofibers in scale-model ellipsoidal ventricle scaffolds (p.932, Fig. 1). MacQueen teaches that the myocardial ECM is fibrillar and anisotropic, ultimately forming a helicoid structure that optimizes ejection fraction during ventricular contraction (p.931, 1st column – Ventricle scaffold). MacQueen further teaches a nanofiber ventricle chamber production strategy based on pull-spinning fibers on a rotating ellipsoidal collector which ensures roughly circumferential fiber alignment (p.931, 1st column – Ventricle scaffold).
MacQueen does not teach a first helical angle and a second helical angle, or wherein the difference between the first helical angle and the second helical angle is less than 90°.
Guner teaches dual-phase scaffolds formed from aligned poly(ε-caprolactone) (PCL) fibers produced by rotary jet spinning (RJS) and randomly oriented PCL or PCL/gelatin fibers produced by wet electrospinning (WES) systems (abstract). Guner teaches RFS allows the creation of highly oriented fibers which can support high tension loads, while mimicking the oriented structure of tendon and directing oriented tissue regeneration by guiding cells (p.2, 1st column 2nd paragraph). Guner teaches preparing a 3D dual-phase scaffold consisting of an aligned outer fiber mat and a randomly oriented fibrous inner mat produced by the RJS and WES systems (p.3, 1st column last paragraph and Figure 1). As pictured in Figure 1c, the two layers of fibers are oriented such that the angles between the first layer and second layer is less than 90°.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare scaffolds having layers of fibers with different orientations to each other, as taught by Guner, in the scaffold of MacQueen, because Guner teaches using RJS allows the creation of highly oriented fibers which can support high tension loads. One of ordinary skill in the art would have been motivated to use RJS to select specific nanofiber orientation to recreate native ventricular tissue architecture taught by MacQueen to create a more functional model cardiac chamber.
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over MacQueen et al. (“A tissue-engineered scale model of the heart ventricle”, Nature Biomedical Engineering, 2018, Vol. 2, pp.930-941) in view of ElectrospinTech (“Electroblowing (gas-assisted/gas jet electrospinning)”, published July 23, 2014, https://electrospintech.com/electroblowing.html accessed on April 24, 2026).
The teachings of MacQueen et al. are discussed above.
Regarding claim 65, MacQueen teaches a nanofiber ventricle chamber production strategy based on pull-spinning fibers on a rotating ellipsoidal collector, which ensures roughly circumferential fiber alignment (p.931, 1st column – Ventricle Scaffold; Fig. 1b, Fig 1c). MacQueen teaches using polycaprolactone (PCL) / gelatin nanofibers as the material because they are biocompatible and biodegradable, promote cell adhesion, provide sufficient structural integrity for ventricle culture and catheterization, and can be produced by a variety of nanofiber production systems that include electrospinning and force-spinning methods (p.931, 1st column – Ventricle scaffold).
MacQueen does not teach directing at least one flow of gas through a portion of the reservoir radially inward of the outer sidewall.
However, ElectrospinTech teaches basic electrospinning is based on application of charges to a solution under an electric field to produce fibers without any other external forces (p.1, 1st paragraph). ElectrospinTech teaches that a commonly used complimentary external force application is through the use of gas jet surrounding the electrospinning nozzle, which can produce small diameter fibers (p.1, 1st paragraph; Fig. 1). ElectrospinTech teaches that electroblowing is effective in reducing fiber diameter when used with conventional electrospinning setup, and can result in fiber diameters to below 100nm (p.1, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute rotary jet spinning fiber fabrication taught by ElectrospinTech for the pull-spinning fiber fabrication method taught by MacQueen, because ElectrospinTech teaches using air to guide the fibers into thin microfibers. Each of MacQueen and ElectrospinTech teach the use of well-known fiber fabrication methods for electrospinning polymer fibers. One of ordinary skill in the art would reasonably expect that replacing pull-spinning fiber fabrication methods with rotary jet spinning fiber fabrication methods would predictably result in the preparation of a tissue scaffold having a shape corresponding to at least a portion of a three-dimensional tissue scaffold, because MacQueen teaches a nanofiber ventricle chamber production strategy based on using a rotating ellipsoidal collector, and it was known in the art at the time of invention that different methods could be used to produce fibers for three-dimensional tissue scaffolds.
Conclusion
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/DEEPA MISHRA/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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