DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of species of small molecular in the reply filed on 12/16/2025 is acknowledged because there is lacks of a prior art only teaches using cardiomyocyte to screen an agent to inhibit the SARS-Cov-2 virus.
The argument has been respectfully considered. However, it is not found persuasive because different species of the testing compounds are structural different agents. Claims 1-23 with elected species of a small molecular are considered.
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 1-5, 7, 14 and 17-18 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Sharma et al. (Cell Reports Medicine, published on July 21, 2020, pages 1-7 plus e1-e2).
The rejection claims are drawn to method comprising: incubating one or more test agents with cardiomyocytes in the presence of SARS-CoV-2 virus; and identifying any of the one or more test agents that reduce myofibrillar disruption, sarcomeric fragmentation, nuclear staining, enucleation, cardiac troponin solute levels, or a combination thereof in the cardiomyocytes compared to a control assay comprising with cardiomyocytes in the presence of SARS-CoV-2 virus without the test agent(s). wherein the SARS-CoV-2 virus is present at a multiplicity of infection of one or more SARS-CoV-2 virion particle per about 1000 cardiomyocyte cells; or of two or more SARS-CoV-2 virion particles per about 1000 cardiomyocyte cells; or of three or more SARS-CoV-2 virion particles per about 1000 cardiomyocyte cells; or of five or more SARS-CoV-2 virion particles per about 1000 cardiomyocyte cells; or of ten or more SAIRS-CoV-2 virion particles per about 1000 cardiomyocyte cells, wherein the SARS-CoV-2 virion particles infect cardiomyocytes, but do not infect cardiac fibroblasts, endothelial cells, or stem cells, wherein the cardiomyocytes are generated from induced pluripotent stem cells, i.e. the differentiated pluripotent cell into the cardiomyocytes rather than non-differentiated pluripotent stem cells. The cardiomyocytes cell line are from a subject without a cardiac condition or a cardiac disease and further the cell line generated comprises to identify one or more test agents that reduce cardiomyocyte enucleation compared to the control assay, wherein one or more of the test agents is a small molecule, an antibody, a nucleic acid, a carbohydrate, a protein, or a combination thereof.
Sharma et al teach coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well initially understood. They teach how to establishes a platform for understanding the mechanisms of cardiac-specific infection by SARS-CoV-2 in vitro and could potentially be employed to develop antiviral compounds. (Abstract).
In detail, They utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. By using hiPSC-CMs, they have found that SARS-Cov-2 replicate in this cell line and causes cytopathic effect, hereby inducing hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. They have established SARS-CoV-2 infection in hiPSC-CMs in vitro, and tested the small molecule line anti-AACE2 antibody to block the SARS-CoV-2 infection (See Fig. 1). In fact, Sharma et al. demonstrate that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are susceptible to SARS-CoV-2 infection. This hiPSC control line (02iCTR) was generated by the Cedars-Sinai Medical Center iPSC Core from peripheral blood mononuclear cells and shown to be fully pluripotent. The hiPSCs were differentiated into CMs using an established monolayer differentiation protocol utilizing small molecule modulators of Wnt signaling. Differentiated hiPSC-CMs were metabolically purified by depriving cells of glucose, as previously demonstrated that the purified hiPSC-CMs expressed standard cardiac sarcomeric markers cardiac troponin T (cTnT) and α-actinin (Figure 1A).
Regarding claim 2, the cite reference teach that Purified hiPSC-CMs were replated into 96-well plates at 100,000 cells per well and allowed to regain contractility before being subjected to SARS-CoV-2 infection. The SARS-CoV-2 was obtained from the Biodefense and Emerging Infections (BEI) Resources of the National Institute of Allergy and Infectious Diseases (NIAID) and tittered on Vero-E6 cells (see STAR Methods). A viral dose response and time course were conducted on hiPSC-CMs, and a multiplicity of infection (MOI) of 0.01 (equivalent to 1 virus particle /100 cell, or 10 virus particles per 1000 cells) was chosen for all experiments unless otherwise specified (Figure S1). This meets the limitation of claim 2 as the claim read on at least one M O I. Moreover, the hiPSC-MCs is not plus ones.
The hiPSC-CMs were infected with SARS-CoV-2 for 72 h in all experiments unless otherwise specified, with a mock treatment without virus serving as a control condition. Plaque formation assays conducted from supernatant harvested after hiPSC-CM infection confirmed active SARS-CoV-2 infection (Figure S1D). Cells from both infected and mock conditions were stained for cardiac marker cTnT and SARS-CoV-2 viral capsid “spike” protein (Figure 1B). The infected hiPSC-CMs stained positively for spike protein, suggesting that SARS-CoV-2 can establish active infection in hiPSC-CMs. They teach that pre-treatment of infected hiPSC-CMs with an ACE2 antibody significantly diminished viral protein expression and plaque forming unit production, suggesting that ACE2 is critical for SARS-CoV-2 internalization in hiPSC-CMs (Figure S1). SARS-CoV-2 Infection of hiPSC-CMs Causes Apoptosis and Cessation of Beating. However, SARS-CoV-2 induced a cytopathic effect on hiPSC-CMs, mock and infected hiPSC-CMs were stained for the apoptosis marker cleaved caspase-3, as well as for the double-stranded RNA (dsRNA) intermediate unique to positive sense RNA virus infection (Figure 1C). The dsRNA and spike protein stains represent two independent assays for visualizing SARS-CoV-2 viral uptake and genome replication in hiPSC-CMs. A proportion of infected cells were positive for dsRNA and also stained positive for cleaved caspase-3, indicating that hiPSC-CMs were undergoing virus-induced apoptosis. Pre-treatment of infected hiPSC-CMs with an ACE2 antibody significantly reduced cleaved caspase-3 expression and blunted apoptosis (Figure S1). Notably, the SARS-CoV-2 spike protein localized at perinuclear regions in hiPSC-CMs (Figure 1D). They concluded that these hiPSC-CMs are susceptible to ACE2-mediated SARS-CoV-2 infection and downstream detrimental cytopathic effects, the SARS-CoV-2 may be able to replicate in distinct perinuclear locations within hiPSC-CMs by co-opting cellular organelles for viral protein translation, and the SARS-CoV-2 infection significantly reduces functional contractility in hiPSC-CMs. They concluded that hiPSC-CMs model can be used from elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform including the screening the anti-SARS-CoV2 agent . (See entail document, particularly the sections of RESULTS, DISCUSSION and the last 4 pages of RESOURCE AVAILBILITY , EXPERIMENTAL MODLE AND SUBJECT DETAILS METHOD DETIALS.
Moreover, it is worth to note that the stem cells in the disclosed prior art are considered from a subject without any cardiac condition or disease for meeting the limitation of claims 7-8. The inhibition of the SARS-CoV-2 infection by using the anti- ACE2 antibody , hereby reducing the apoptotic effects caused by the SARS-CoV-2 infection inherently , which meets the limitations cited in claims 15 and 19 inherently because claims 15 and 19 are directed to all apoptotic pathology in cardiomyocytes caused by SARS-CoV-2 infection inherently.
Hence the cited reference teaches that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.
To this context, the cited reference meets the limitations of claims 1-5, 7-8, 14-15 and 17-18 explicitly and/or inherently.
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.
Claim(s) 1-9, 13-15 and 17-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. US 2017 /0058263A1 , Chen et al.(Cardiovascular Research, Volume 116, Issue 6, 1 May 2020, Pages 1097–1100 ), Sharma et al. (Cell Reports Medicine, published on July 21, 2020, pages 1-7 plus e1-e2), Ren et al. DNA AND CELL BIOLOGY, 2005, Vol. 24, Number 8, pp. 496-502) and Bittman et al. (J. Clin. Med. Res. Published in April , 2020, Vol. 12 (5), pp. 320-322).
The rejection claims are drawn to method that are described supra, the additional rejection claims including the limitations of the target cardiomyocytes possibly comprising a mutation in the cells that can express other gene as the target for the treatment target or observation marker(s) such as a cardiomyocyte mutant generated in-vitro from the pluripotent stem cell, and the pluripotent stem cell is an induced pluripotent stem cell. The gene(s) can be expressed encoding a sarcomeric protein selected from cardiac troponin T (TNNT2), myosin heavy chain (MYH7), tropomyosin 1 (TPM1), myosin binding protein C (MYBPC3), 5′-AMP-activated protein kinase subunit gamma-2 (PRKAG2), troponin I type 3 (TNNI3), titin (UN) etc. wherein the metho for observation can be used not with simpler and more routine assay cited in claim 13 as well as the method for making the identified agent as a therapeutic agent to treat the SARS-CoV-2 infection in vivo in combination with other small molecular inhibitor selected from a serine protease inhibitor and/or cathepsin inhibitor in vivo cited in claims 19-23.
Sun et al . teach a method of an in vitro-generated cardiomyocyte which comprises three kinds of approaches : a. the in-vitro-generated cardiomyocyte is generated from a pluripotent stem cell or a reprogrammed cell in vitro; b. the in-vitro-generated cardiomyocyte comprises at least one mutation in a gene encoding a sarcomeric protein; and c. the in-vitro-generated cardiomyocyte displays a phenotype associated with hypertrophic cardiomyopathy. wherein the in-vitro-generated cardiomyocyte exhibits, relative to a normal cardiomyocyte, one or more phenotypes selected from the group consisting of: an electrophysiological phenotype, contractile arrhythmia, an increased intracellular calcium level, and an increased ratio of β-myosin expression to α-myosin expression; wherein the in-vitro-generated cardiomyocyte exhibits, relative to a normal cardiomyocyte, one or more phenotypes selected from the group consisting of: an electrophysiological phenotype, contractile arrhythmia, an increased intracellular calcium level, and an increased ratio of β-myosin expression to α-myosin expression. wherein the in-vitro-generated cardiomyocyte is generated from the pluripotent stem cell, and the pluripotent stem cell is an induced pluripotent stem cell. The gene(s) can be expressed encoding a sarcomeric protein selected from cardiac troponin T (TNNT2), myosin heavy chain (MYH7), tropomyosin 1 (TPM1), myosin binding protein C (MYBPC3), 5′-AMP-activated protein kinase subunit gamma-2 (PRKAG2), troponin I type 3 (TNNI3), titin (UN), myosin light chain 2 (MYL2), actin alpha cardiac muscle 1 (ACTC1), or cardiac LIM protein (CSRP3). Furthermore, the at least one mutations is selected from caveolin 3 (CAV3), galactosidase alpha (GLA), lysosomal-associated membrane protein 2 (LAMP2), mitochondrial transfer RNA glycine (MTTG), mitochondrial transfer RNA isoleucine (MTTI), mitochondrial transfer RNA lysine (MTTK), mitochondrial transfer RNA glutamine (MTTQ), myosin light chain 3 (MYL3), troponin C (TNNC1), Transthyretin (TTR), GATA4, or a combination thereof. And more preferably in MYH7. a MYH7 R663H mutation (Claims 33-35). By using these created cell lines they teach a method for testing an agent(s) Particularly the method comprises incubating one or more test compounds with cardiomyocytes in attempting to screen a candidate compound in vitro , wherein the cardiomyocytes comprises at least one mutation in a gene encoding a sarcomere protein and identifying any of the one or more at least one compounds that reduce myofibrillar disruption, scarcomeric fragmentation, in nuclear staining , enucleation, cardiac troponin solute levels , or a combination thereof in the cardiomyocytes assay compared to a control assay in vitro using the same type of cells without the test compound(s) (See paragraph [0049]). An representative immunostaining for cardiac troponin T and F-actin demonstrate an increases cellular size and multinucleation in HCM iPSC-CMs as compared to control iPCS-CMs. While the cited reference does not explicitly teach to test any compound with the assay system in the presence of SARS-CoV-2 with or without text compound, Sun et al. also disclosed method used for identification of any potential compound having an effect on hear because it was known that the myocadiac cells comprises ACE2. Su et al. also teach formulation an agent into a composition (paragraph 0102). Sun et al. do not teach that that ACE2 is related to the SARS-Cov-2 (See detail description examples). The cited reference does not teach precisely the cell numbers, inherently or implicitly the cells generated are in large populations to obviously read on claim 2. Regarding claim 9, Sun et al. teach that the cardiomyocytes comprises a mutation or genetic variation that leads or contributes to impartments in contractility in a subject (Paragraph [0048]),
Sun et al. do not teach that SATS-CVoV-2 using ACE2 to infect cardiomyocytes.
Chen et al. teach that a novel coronavirus SARS-CoV-2 causes disease named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV2. Angiotensin-converting enzyme 2 (ACE2), is the key host cellular receptor of SARS-CoV-2, which is distributed in cellular distribution in human heart in addition to other organs too. . This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition due to the cardiac injury among severe patients infected by SARS-CoV-2. (Abstract and Fig. 1). Chen et al. do not teach using a cardiomyocytes model to screen and identify an agent that can block the SAR-CoV-2 infection vial ACE2 receptor.
Sharma et al teach a Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform. In particular, they teach using cardiomyocytes to examine mechanisms of SARS-CoV-2 infection using cell-derived cardiomyocytes using human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanism of cardiomyocytes-specific infection by SARS-CoV-2 via ACE2 . Further, Sharma et al. teach comprising adding a test agents (page 6, col. 1, paragraph 1-3). Pretreatment off infected hiPSC-CMs with an ACE2 antibody significant cleavage capspase-3 expression and blunted apoptosis (Fig. S1). While the reference does not teach precisely the cell numbers, inherently or implicitly the cells generated are in large populations to obviously read on claim 2. Sharma et al. do not teach using a regular staining method cited in claim 13 comprising Hoechst and/or Hematoxilin staining to observe the apoptotic effect caused by the SARS-Cov-2 infection.
Ren et al. teach that Apoptosis induced by a SARS-associated coronavirus can be observed in Vreo cells, which is replication-depended and involves Caspase. Such apoptotic pathological changes can be noticed by morphological and biological changes in SARS-CoV infected Vero cells (Fig. 1 a & b) even under light microscopy using fluorescent micrographs with CPE , wherein the cells were fixed and stained with Hoechst to see the chromatin condensation, internucleaosomal DNA cleavage as well as low-molecular-weight DNA fragmentation identified by a agarose gel electrophoresis (See Fig. 1 and its legend).
In addition to the antibody to ACE2 capable of blocking the SARS-CoV-2 infection, Bittman et al. al. teach several other small molecules so available to be used in the field of treatment of SARS-CoV-2, which include ACE2 entry blocker, serine protease inhibitor, transmembrane serine protease inhibitor 2 (TMPRSS2) or Comostat and Cathepsin L/B (CTSL/CTSB). Bittman et al. teach that so many different treatment options are already under clinical trials (See Table 1) for controlling the COVID-19 infection. They particularly teach that simultaneous treatment of the cells with camostat and a cathepsin inhibitor has efficiently prevented both cell access and multi-step growth of SARS-CoV-2 in human. This efficient inhibition could be attributed to the double blockade of access from the cell surface and through the endosomal pathway. Their observations suggest camostat as a candidate antiviral drug to prevent or suppress TMPRSS2 dependent infection by the SARS-CoV-2.
Therefore, it would have been obvious for any person with an ordinarily skilled in the art to be motivated by the cited prior arts in combination to test any one or more candidate agents potentially block the ACE2 receptor binding and using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without mutation told by Sun et al. with many conventional methods available in the art to screen and identify any potential small molecular inhibitor to block the SARS-CpV-2 binding to the hiPSC-CMs via ACE2 receptor and also capable of using is as an reagent in combination with other inhibitor selected from serine protease inhibitor, transmembrane serine protease inhibitor 2 (TMPRSS2) or Comostat and/or Cathepsin L/B (CTSL/CTSB) to block the SARS-CoV-2 infection in a double blockade of access from the cell surface as well as other endosomal pathway in vivo to obtain an reasonable expectation of greater success than using one type of inhibitor alone.
Hence the claimed invention as a whole is prima facie obvious absence unexpected results.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 6, 9-11 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. In the instant case, Application as its was originally filed does not have possession for making any mutation of the cardiomyocytes, wherein the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to impairments in contractility, impairments in ability to relax, diastolic dysfunction, abnormal or improper functioning of the heart's valves, cardiomyopathies, angina pectoris, myocardial ischemia, infarction, hypertension, inadequate blood supply to heart muscle, amyloidosis, hemochromatosis, global hypertrophy, regional hypertrophy, abnormal communications between heart chambers, or a combination thereof or the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to an abnormally enlarged, thickened heart, an abnormally stiffened heart, or a combination thereof in a subject, or wherein the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to ischemic cardiomyopathy, coronary artery disease, non-ischemic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, infiltrative cardiomyopathy, congestive heart failure, myocardial infarction, cardiac ischemia, myocarditis, arrhythmia. or a combination thereof in a subject, or wherein the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to myocarditis, Duchenne muscular dystrophy or Emery Dreiffuss dilated cardiomyopathy in a subject.
The first paragraph of 35 U.S.C. requires that the specification shall contain a written description of the invention. This requirement has several objectives: 1). To clearly convey the information that an applicant has invented the subject matter which is claimed; 2). To put the public in possession of what the applicant claims as the invention; and 3). To promoter the progress of the useful arts by ensuring that patentee adequately describe their inventions in their patent specification in exchange for the right to exclude others from participating the invention for the duration of the patent term.
Therefore, to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably concluded that the inventor had possession of the claimed invention. The possession of claimed invention can be shown by describing the claimed invention with all of its limitation in the specification including drawing or description of an actual reduction to practice. The written description may arise in the following situations: a). The claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention; b). The claimed invention as a whole may not adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art; and c). The invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function etc.
In the instant case, the claimed invention has not been described with sufficient particularity about how the claimed mutation is made in any gene of the cardiomyocytes that does not contain any genetic mutation is made for making the cardiomyocytes capable of suffering or contributing to impairments in contractility, impairments in ability to relax, diastolic dysfunction, abnormal or improper functioning of the heart's valves, cardiomyopathies, angina pectoris, myocardial ischemia, infarction, hypertension, inadequate blood supply to heart muscle, amyloidosis, hemochromatosis, global hypertrophy, regional hypertrophy, abnormal communications between heart chambers, or a combination thereof, or the cardiomyocytes comprising a mutation or genetic variation that leads to or contributes to an abnormally enlarged, thickened heart, an abnormally stiffened heart, or a combination thereof , or the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to ischemic cardiomyopathy, coronary artery disease, non-ischemic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, infiltrative cardiomyopathy, congestive heart failure, myocardial infarction, cardiac ischemia, myocarditis, arrhythmia. or a combination thereof or the cardiomyocytes comprise a mutation or genetic variation that leads to or contributes to myocarditis, Duchenne muscular dystrophy or Emery Dreiffuss dilated cardiomyopathy.
The specification of current application only describe a method for making a mixed cultures of induced pluripotent stem cell derived cardiomyocytes (iPS-CMs), induced pluripotent stem cell derived endothelial cells (iPS-ECs), and induced pluripotent stem cell derived cardiac fibroblasts (iPS-CFs). The Mixed Cultures of CMs, CFs, and ECs were created by combining single cell suspensions of each cell types. The mixed suspension of the hiPSCs were used for testing a small molecule agent test , preferably an antibody to block the SARS-CoV-2 infection via blocking the ACE2 . However, the specification does not either describe any mutation in any population of CMs, CFs, and ECs made by Applicants prior to the current Application was originally filed, nor show any reduction of practice the claimed invention. Therefore, the claimed invention in the current application is a new matter and applicants do not have the possession of claimed invention.
Conclusion
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/ Primary Examiner, Art Unit 1671