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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/27/2026 has been entered.
Status of Claims
Examined Herein: 1-22
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PRO 62/884,012 on 8/7/2019, PRO 62/942,516 on 12/2/2019, PRO 62/947,737 on 12/13/2019, PRO 62/961,514 on 1/15/2020, and PCT/US20/15225 on 1/27/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/1/2021, 4/2/2024, and 10/3/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 1/27/2020 are accepted.
Withdrawn Rejections
The rejection of claims 1-8, 10-20, and 22 under 35 U.S.C. 103 over Panescu and Sutermeister is hereby withdrawn in view of Applicant’s substantive amendment to claims 1 and 12.
The rejection of claims 1-22 under 35 U.S.C. 103 over Panescu, Sutermeister, and Morishita is hereby withdrawn in view of Applicant’s substantive amendment to claims 1 and 12.
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.
Claims 1-14 and 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Darvish (US 2002/0183682 A1, Published 12/15/2002).
With respect to claims 1 and 12, Darvish discloses a method of delivering an agent to a tissue of a subject and/or a method of treating a cardiac disorder, comprising:
a) delivering the agent to a segment of coronary vasculature (coronary artery) of the subject; and
b) targeting the agent to a target cardiac tissue by electroporating (an electrically based transport technique) the target cardiac tissue of the subject, wherein:
said electroporation is performed using a volage of 100-10,000 volts, including less than 400 volts. [Darvish, 0230, 0007-0010, 0012, 0015-0017, 0021, 0037, 0065, 0066, 0069, 0144, 0154, 0155, 0157, 0209-0212, 0230]
The limitation “thereby distributing the agent to the target coronary tissue” recites language that does not require a step to be performed. This limitation expresses the intended result of the positively recited step of electroporating the target coronary tissue and, as a result, does not limit the claim scope. MPEP 2111.04.
With respect to claims 3, 4, 16, and 17, Darvish discloses that the segment of the coronary vasculature is the coronary artery. [Darvish, 0144, 0230]
With respect to claims 5 and 18, Darvish discloses that electroporation is performed following delivery of the agent to the segment of the coronary vasculature of the subject. [Darvish, 0007, 0015, 0144, 0155, 0157, 0230]
With respect to claims 6 and 19, Darvish discloses that the electroporating may be performed by endocardial electroporation. [Darvish, 0160]
With respect to claim 7, Darvish discloses that the agent comprises a therapeutic agent for the treatment of a cardiac disorder in the subject. [Darvish, 0009, 0073-0101]
With respect to claims 8 and 20, Darvish discloses that the agent comprises a nucleotide, an oligonucleotide, a protein, a peptide, a small molecule, or a macromolecule. [Darvish, 0009, 0073-0101]
With respect to claims 9 and 21, Darvish discloses that the agent comprises DNA. [Darvish, 0009, 0073-0101]
With respect to claims 10 and 11, Darvish discloses that the agent is Esmolol or Adenosine. [Darvish, 0078] Both Esmolol and Adenosine are therapeutics for heart arrhythmia, including atrial fibrillation and ventricular tachycardia.
With respect to claim 14, Darvish discloses that the cardiac disorder is a heart arrhythmia. [Darvish, 0016, 0017, 0010]
Darvish does not explicitly disclose that the target cardiac tissue is coronary tissue or that the target coronary tissue is different from the segment of coronary vasculature.
However, with respect to claims 1, 2, 12, and 13, Darvish discloses that electroporation is an electrically based transport technique. [Darvish, 0015, 0155, 0157, 0158] Darvish further discloses that the inside of the heart’s ventricles is more accessible to electrically based transport techniques, and provides the fastest action potential conduction in the heart. Moreover, Darvish discloses that controlling the conduction velocity in this area provides an opportunity to affect the activation of large sections of the heart. [Darvish, 0167] Furthermore, Darvish discloses more explicitly that the electric field may be applied to a significant portion of the heart, for example to most of a ventricle. [Darvish, 0177]
Modifying the method disclosed by Darvish by selecting a heart ventricle (i.e., the left ventricle or the right ventricle) as the target cardiac tissue results in the method of claim 1, 2, 12, and 13, wherein the method comprises:
b) targeting the agent to a target coronary tissue (the left ventricle or the right ventricle) by electroporating the target coronary tissue of the subject, wherein:
the target coronary tissue (the left ventricle or the right ventricle) is different from the segment of coronary vasculature (coronary artery).
In which case, with respect to claims 2 and 13, the target coronary tissue is the left ventricle or the right ventricle of the subject.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Darvish by selecting the left ventricle or the right ventricle as the target cardiac tissue and have a reasonable expectation of success. Darvish discloses a method comprising delivering an agent to a coronary artery and transporting/targeting the agent to nearby cardiac tissue by electroporating the cardiac tissue. Darvish additionally discloses that that electroporation is an electrically based transport technique and identifies the inside of the heart’s ventricles as accessible to such techniques. Moreover, Darvish discloses that an electric field may be applied to a heart ventricle. Accordingly, the teachings of Darvish suggest that the heart’s ventricles, the left ventricle and the right ventricle, are cardiac tissue accessible to electroporation. Therefore, it is reasonable to expect that the left ventricle or the right ventricle may be selected as the electroporated cardiac tissue. One would have been motivated to do so because it is prima facie obvious to modify a reference when the rationale for doing so is expressly or impliedly contained in the prior art. MPEP 2144(I). In the present case, Darvish discloses that the fastest action potential conduction in the heart is near the surface of the inside of the ventricles. [Darvish, 0167] Controlling the conduction velocity in this area using a non-excitatory electric field, such as electroporation, provides an opportunity to affect the activation of large sections of the heart. [Darvish, 0015, 0163, 0167] Therefore, one would have been motivated to select the left ventricle or the right ventricle as the target cardiac tissue because doing so enables control of the conduction velocity in this area and provides an opportunity to affect the activation of large sections of the heart.
Claims 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Darvish, as applied to claims 1-14 and 16-21 above, and further in view of Radecke (US 2017/0049497 A1, Published 2/23/2017).
With respect to claim 12, Darvish discloses the teachings above.
Darvish does not specify that the treated cardiac arrhythmia is atrial fibrillation or ventricular tachycardia.
However, with respect to claim 15, Radecke discloses that cardiac arrhythmias, including ventricular tachycardia and atrial fibrillation, may be treated by electroporation. [Radecke, 0004]
Modifying the method disclosed by Darvish by treating ventricular tachycardia or atrial fibrillation in the subject results in the method of claim 15.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Darvish by treating ventricular tachycardia or atrial fibrillation in the subject and have a reasonable expectation of success. Darvish discloses a method for treating a cardiac arrhythmia comprising performing electroporation on a subject’s heart. Radecke discloses that electroporation may treat cardiac arrhythmias, including ventricular tachycardia and atrial fibrillation. Accordingly, the combined teachings of Darvish and Radecke reasonably suggest that the method comprising performing electroporation on a subject’s heart disclosed by Darvish may be effective in treating cardiac arrhythmias, including ventricular tachycardia and atrial fibrillation. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Radecke discloses that electroporation may be used to treat cardiac arrhythmias, including ventricular tachycardia and atrial fibrillation. [Radecke, 0004] Therefore, one would have been motivated by the expectation that modifying the method disclosed by Darvish by treating ventricular tachycardia or atrial fibrillation in the subject would extend treatment to additional types of cardiac arrhythmias.
Claims 1-3, 5-16, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Kassab (US 2018/0036514 A1, Published 2/8/2018), in view of Darvish.
With respect to claim 1 and 12, Kassab discloses a method of delivering an agent to a coronary tissue of a subject and/or treating a cardiac disorder in a subject, comprising:
a) delivering an agent/drug to a segment of coronary vasculature (the pericardial space) of the subject; and
b) targeting the agent/drug to a target coronary tissue, such as the atrium or ventricle, by electroporating the target coronary tissue of the subject, wherein:
the target coronary tissue is different from the segment of coronary vasculature. [Kassab, 0005, 0042, 0043, 0165, 0181, 0238, 0273-0275]
The limitation “thereby distributing the agent to the target coronary tissue” recites language that does not require a step to be performed. This limitation expresses the intended result of the positively recited step of electroporating the target coronary tissue and, as a result, does not limit the claim scope. MPEP 2111.04.
With respect to claims 2 and 13, Kassab defines the target tissue as the atrium (i.e., right atrium and/or left atrium) or the ventricle (i.e., right ventricle and/or left ventricle). [Kassab, 0126, 0165, 0238]
With respect to claims 3 and 16, Kassab discloses that the segment of coronary vasculature is the pericardial space. [Kassab, 0005]
With respect to claims 5 and 18, Kassab discloses that electroporation is performed concurrently with delivering the agent and/or following delivery of the agent to the segment of the coronary vasculature. [Kassab, 0042, 0043, 0274, 0275] Moreover, Kassab discloses that the method should not be limited to the particular sequence of steps described. [Kassab, 0277]
With respect to claims 6 and 19, Kassab discloses that electroporating (or ablating) the target coronary tissue of the subject is performed by epicardial electroporation. [Kassab, 0173]
With respect to claim 7, Kassab discloses that the agent is a therapeutic agent (cardiac drug, gene cell treatment, or pharmacological agent) for the treatment of a cardiac disorder in the subject. [Kassab, 0005, 0181, 0182]
With respect to claims 8 and 20, Kassab discloses that the agent comprises a nucleotide, a protein, a peptide, a small molecule, or a macromolecule. [Kassab, 0005, 0182]
With respect to claims 9 and 21, Kassab discloses that the agent comprises DNA (gene cells). [Kassab, 0182]
With respect to claims 10 and 11, Kassab discloses that the cardiac disorder is a heart arrhythmia, atrial fibrillation. [Kassab, 0181]
With respect to claims 14 and 15, Kassab discloses that the cardiac disorder is a heart arrhythmia, atrial fibrillation. [Kassab, 0181]
With respect to claim 22, Kassab implicitly discloses that the subject is human. Specifically, Kassab discloses that the method is performed on mammalian tissue /a mammalian organ. [Kassab, 0024] Humans are mammals. Therefore, Kassab’s method encompasses a human subject. Additionally, the term “patient” ordinarily and customarily refers to a human.
Kassab does not disclose that the electroporation is performed using a voltage of less than 400 volts.
However, with respect to claim 1 and 12, Darvish discloses that electroporation (defined as a non-excitatory signal providing device) performed at voltages between 0.01 and 40 volts makes it easier to transport large molecules into the heart tissues. [Dravish, 0015, 0063, 0064, 0066] Darvish further discloses that electroporation performed at voltages between 100 and 10,000 volts is suggested by the art. [Darvish, 0069]
Modifying the method disclosed by Kassab by performing the electroporation using a voltage of 0.01 to 40 volts or 100 to 10,000 volts, including less than 400 volts, results in the method of claim 1 and 12.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Kassab by performing the electroporation using a voltage of 0.01 to 40 volts or 100 to 10,000 volts, including less than 400 volts, and have a reasonable expectation of success. Kassab discloses a method comprising delivering a substance to a segment of coronary vasculature and performing electroporation on a target coronary tissue to increase uptake of the substance by the tissue. Darvish discloses that the art suggests performing electroporation at voltages between 100 and 10,000 volts. Darvish additionally discloses that electroporation of the heart at voltages between 0.01 and 40 volts makes it easier to transport large molecules into heart tissue. Accordingly, the combined teachings of Kassab and Darvish suggest that the step of electroporating a target coronary tissue in the method disclosed by Kassab may be performed using a voltage of 0.01 to 40 volts or 100 to 10,000 volts. One would have been motivated to do so because it is prima facie obvious to combine references when the rationale for doing so may be reasoned from knowledge generally available to one of ordinary skill in the art and when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(I-II). In the present case, Darvish discloses that the art suggests electroporation performed at voltages between 100 and 10,000 volts. [Darvish, 0069] Moreover, Darvish discloses that electroporation performed at voltages between 0.01 and 40 volts makes it easier to transport large molecules into the heart tissues. [Darvish, 0015, 0064, 0066] Therefore, one would have been motivated to perform the electroporation step in the method disclosed by Kassab using a voltage of 0.01 to 40 volts because such voltages are generally utilized in the art. Moreover, one would have been motivated by the expectation that using a voltage of 0.01 to 40 volts would make it easier to transport molecules into the atrium or ventricle.
Response to Arguments
Applicant’s arguments, filed 7/8/20226, with respect to the pending claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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