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
Claim Status
Restriction Requirement sent on Claims 1-14 & 16-18;
Upon amendment entry, Claims 3-4, 6-7, 14-15, and 17-18 are cancelled.
Upon amendment entry, Claim 16 is withdrawn.
Claims 1-2, 5, 8-13 are now pending investigation.
Priority Status
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant claims NO foreign priority; the effective filing date is 02/04/2019.
Information Disclosure Statement
No IDS(s) were filed with this application.
Drawings
The drawings submitted on 08/03/2021 are accepted and acknowledged.
Response to Restriction Election
In response to the Restriction Requirement received 10/01/2024:
Examiner acknowledges Applicant’s clarification for Formula II and use of dotted lines or dots is for indicating resonance structures.
Applicant has elected: Group I, claim(s) 1-14 & 18, drawn to the method Nav1.5 voltage-gated channels.
The election was made without traverse.
Group II: Claims 16 drawn to a pharmaceutical composition of Formula I or Formula II, is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions.
Further, Applicant elected claims 1 and 13 to recite N-(1H-benzimidazol-2-yl)-4-methyl-2-pyrrol-1-yl-thiazole-5-carboxamide.
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Claims 1-2, 5, and 8-13 read on the elected species.
The elected specie was not identified in the art.
The elected specie would be allowable if an independent claim were drafted to the elected specie alone.
In addition, Examiner extended her search to the full scope of Claims 1-2, 5, 8-9 as per MPEP 802.03 (see rejections below).
No art was identified.
Claims 1-2, 5, and 8-9 has allowable subject matter.
The rejections below read on the Claims 10-13 (see 102 rejections below).
Claim Objections
Claim 13 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 10-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MX van Bemmelen, et. al in “Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination” (pub’d 08/06/2004; hereinafter “van Bemmelen”).
With respect to Claim 10-12, van Bemmelen teaches a method for treating a cardiovascular disease (pg. 284, col. 1, para. 1) since “the pivotal role of Nav 1.5 has been exemplified by the finding more than 30 genetic variants linked to cardiac phenotypes such as congenital and drug-acquired long QT syndromes, Brugada syndrome (BrS), conduction disorders, and sudden infant death syndrome.”
Since Long QT syndrome refers to an issue with the heart's electrical system taking longer than normal to recharge between heartbeats, van Bemmelen continues teaching in the article that:
the ubiquitin-protein ligase Nedd4-2 (a compound), expressed in cardiac cells, binds to the PY-motif of the cardiac sodium channels (meaning this motif acts as a recognition site for the Nedd4-2 protein, which can tag the sodium channel for degradation by adding ubiquitin molecules - leading to reduced sodium current in the cell);
Nedd4-2 ubiquitinates and likely downregulates (which defined by Merriam-Webster is the process of reducing or suppressing a response to stimulus”) Nav1.5 at the cell membrane; and
ubiquitinated fractions of Nav1.5 are found in heart (pg. 288, Discussion para. 1).”
This reads on the claim because “Nav1.5, the cardiac isoform of the voltage-gated Na+ channel, is critical to heart excitability and conduction” (abstract, pg. 284, col. 1, para. 1).
Thus according to the second statement of van Bemmelen above, the method of treating the subject (pg. 285, Materials and Methods; Human Nav1.5 cDNA, and human Nedd4–1 (KIAA0093) and Nedd4-2 (KIAA0439) cDNAs and cell lines), used an expression of cardiac cells. These cells are important because “Nav 1.5 is the pore-forming α-subunit of the predominant Na+ channel found in the heart.”
Claim(s) 10-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by M. de Lera Ruiz, et. al titled “Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications” (pub’d 09.24/2015; hereinafter “Ruiz”).
With respect to Claim(s) 10-12, Ruiz teaches “voltage-gated ion channels (VGICs) are transmembrane proteins that play important roles in the electrical signaling of cells. The activity of VGICs is regulated by the membrane potential of a cell, and open channels allow the movement of ions along an electrochemical gradient across cellular membranes.
Ruiz continues teaching: (Claim 10) A method of treating a cardiovascular disease (pg. 7101, col. 1, cont’d para. 1; Altered cardiac action potentials lead to ventricular arrhythmias and in extreme cases to Brugada syndrome, in which fibrillation may lead to death) comprising administering a compound that inhibits the inactivation of a Nav1.5 voltage-gated sodium channel to a subject in need thereof (pg. 7096, col. 1, full para. 3 and figure below) or comprising inhibiting the inactivation of a Nav1.5 voltage-gated sodium channel (pg. 7100-7101, col. 2, cardiovascular disease - Brugada syndrome) in a subject in need thereof.
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With respect to Claims 11 and 12, Ruiz teaches through the prior art, several examples of cardiovascular disease, background and examples on different Nav channels – the actions, as well as benzimidazoles for the use in aiding a patient suffering from dysfunction of the physiology of their sodium channels with its effects.
As seen in the Figure 2 (pg. 7097, see above) the following: (Claim 11): wherein the cardiovascular disease is Brugada Syndrome, and atrial fibrillation (pg. 7097, Figure 2).
(Claim 12): The method of claim 10, wherein the subject is a human (pg. 7097, Figure 2).
Conclusions
Claim(s) 10-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Josmalen M. Ramos-Lewis whose telephone number is (571)272-0084. The examiner can normally be reached M-F 9:00-5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached on (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Josmalen M. Ramos-Lewis, Ph.D.
Patent Examiner
Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights