DETAILED ACTION
Claims 194-203 were pending; per Applicant’s reply on 3/30/2026 claims 194 and 198 have been amended, claims 200-202 have been canceled, and claims 204-207 are newly added.
Claims 194-199 and 203-207 are pending and the subject of the Office Action below.
Priority
The Instant application, filed 08/01/2025 is a Continuation of 19082967, filed 03/18/2025. 19082967 is a Continuation of 18827049, filed 09/06/2024, now abandoned. 18827049 is a Continuation of 18584159, filed 02/22/2024, now abandoned. 18584159 is a Continuation of 17842389, filed 06/16/2022, now abandoned and having 1 RCE-type filing therein. 17842389 is a Continuation of 17701863, filed 03/23/2022, now abandoned. 17701863 is a Continuation of 17472767, filed 09/13/2021, now abandoned. 17472767 is a Continuation of 17167523, filed 02/04/2021, now abandoned. 17167523 is a Continuation of 16913571, filed 06/26/2020, now abandoned. 16913571 is a Continuation of 16679917, filed 11/11/2019, now abandoned. 16679917 is a Continuation of 16364322, filed 03/26/2019, now abandoned. 16364322 is a Continuation of 16054414, filed 08/03/2018, now abandoned. 16054414 Claims Priority from Provisional Application 62671585, filed 05/15/2018. 16054414 Claims Priority from Provisional Application 62639922, filed 03/07/2018. 16054414 Claims Priority from Provisional Application 62584537, filed 11/10/2017. 16054414 Claims Priority from Provisional Application 62541591, filed 08/04/2017.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 3/30/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement is being considered by the Examiner.
Claim Rejections - 35 USC § 103
(NEW Rejection based on Amendment)
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 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 194-199 and 203-207 are rejected under 35 U.S.C. 103 as being unpatentable over Dearani et al. “Treating obstructive hypertrophic cardiomyopathy—what’s best, what’s next?” The Journal of Thoracic and Cardiovascular Surgery 2016 Volume 152, Number 4, 988-990; Business Press Release, “MyoKardia Announces Topline Clinical Data Supporting Advancement of MYK-461 to Phase 2 PIONEER-HCM Study in Symptomatic, Obstructive Hypertrophic Cardiomyopathy Patients,” July 11, 2016; NCT02842242 Clinical Trials July 22, 2016; and McCormack et al. “Is bigger better? An argument for very low starting doses,” CMAJ, January 11, 2011, 183(1).
Claim 194 is generally directed towards a method of treating obstructive hypertrophic cardiomyopathy (oHCM) in a subject in need thereof, the method comprising administering a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof to said subject, the method comprising administering to the subject 5 mg per day of Compound 1 or a pharmaceutically acceptable salt thereof for a first treatment period; and wherein the subject, having received 5 mg per day for the first treatment period, is monitored and has a left ventricular ejection fraction (LVEF) of greater than or equal to 55% and a left ventricular outflow tract (LVOT) gradient of greater than or equal to 30 mm Hg, the method further comprising administering 10 mg per day of Compound 1 or a pharmaceutically acceptable salt thereof for a second treatment period based on the LVEF greater than or equal to 55% and the LVOT gradient greater than or equal to 30 mmHg.
Dearani teaches the company MyoKardia (San Francisco, Calif) received Orphan Drug Designation from the Food and Drug Administration in April 2016 for MYK-461 and its indication for the treatment of symptomatic obstructive HCM (meeting the limitation of claimed indicated disease). Following receiving Orphan Drug Designation for MYK-461, the study design for the phase II trial was posted online.
Dearani teaches giving the required drug to the required patient population in a therapeutically effective amount, though is silent on the dose of the drug. Dearani doesn’t teach the dose of the drug required which is a dose titration form 5 mg to 10 mg over a period of time.
The dose of the drug is rendered obvious from the following reference explaining in the phase I results in conjunction with the MPEP 2144.05 “Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions.”
The Business Press Release states MK-461 showed a reduction in excess cardiac contractility in all HCM patients studied. Indicating the administration of the drug to the HCM patient. This also indicates a therapeutically effective dose was given by indication of the effect of the compound which achieved a reduction in excess cardiac contractility.
The Business Press Release states in repeat dosing of MK-461 was achieved safely up to 25 mg for 28 days (meeting the requirement of instant claim 198 to daily dosing). This teaches a dose up to 25 mg when given repeatedly. The press release states that efficacy was seen in a dose dependent manner. This reference also teaches that a modest reduction of cardiac contractility (e.g. 5 to 10% relative reduction as measured by left ventricular ejection fraction, or LVEF) has potential as a treatment for HCM patients.
The Business Press Release states all 15 HCM patients in our single ascending dose study demonstrated reductions in excess cardiac contractility. Furthermore, we observed achievement of stable reductions in contractility following repeat dosing to steady state in healthy volunteers in the two highest-dose cohorts of our multiple ascending dose study, confirming proof of mechanism for multiple doses. As previously noted, the scientific literature and MyoKardia’s research suggest that an agent that produces a modest reduction of cardiac contractility (e.g. 5 percent to 10 percent relative reduction as measured by left ventricular ejection fraction, or LVEF) has potential as a treatment for HCM patients.
NCT02842242 (The Phase II Trial) first posted July 22, 2016 states they will treat patients with obstructive HCM (see Conditions Section). Inclusion Criteria Section: “Documented LVEF ≥ 55% at the Screening visit as determined by the investigator and the investigational site's echocardiography laboratory.” This reference also states the inclusion of patients with a “[r]esting LVOT gradient ≤ 30 mg Hg and post-exercise peak LVOT gradient ≥ 50 mm Hg,”meeting the limitations of instant claims 194 and 196.
Lastly. McCormack is brought in to show that an up-titration approach was known in the art. McCormack states, “The ‘start low, go slow’ approach when starting medications — which entails starting with the lowest available dose — is generally well accepted in the medical community, especially for elderly patients.” This already provided motivation to begin at a smaller dose and up-titrate to efficacy while maintain safety. McCormack, continues to provide an alternate model of starting even lower, then escalating to higher doses. The rationale is then outlined in the “Rationale” section, page 65. McCormack concludes, “[d]ose titration will likely improve tolerability, may improve adherence if side effects are reduced, and will reduce drug costs if a low or very low dose is found to be effective.”
The instant claims are a simply combination of known facts, to arrive at using a known drug, for a known indication, in a known dosing range to arrive at the predictable result of treating the indicated disease in the patient population described by the inclusion and exclusion criteria of the clinical trial prior art while personalizing the care of starting low and proceeding slowly to a higher dose. The claims are obvious as one would seek the combination of art being motivated by treating a known disease in a safe and effective manner.
Claim 195 requires the subject has not received a beta-blocker therapy for a period of at least two weeks prior to initiating treatment. The NCT02842242 ref states, Key Exclusion Part A, Ongoing therapy with beta blockers, calcium channel blockers, or disopyramide. Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
Claim 196 states said subject has at least a 30 mmHg pressure gradient across the subject's left ventricular outflow tract (LVOT), prior to initiating treatment; or the therapeutically effective amount is sufficient to lower a post-exercise peak gradient LVOT to less than or equal to 30 mmHg in said subject. The NCT02842242 ref states the inclusion of patients with a resting LVOT gradient ≤ 30 mg Hg and post-exercise peak LVOT gradient ≥ 50 mm Hg.
Claim 197 is directed to how much increase is seen in the patient’s pVO2. This is directed to the outcome, the efficacy of treatment. If the patient is given the efficacious dose, the patient’s pVO2 will increase. As such this result is addressed by the dose and patient population, which are both shown to be obvious. Therefore the result does not lend to patentability of the claims.
Claim 198 states Compound 1 is administered: orally; or once daily; optionally wherein said Compound 1 is administered daily for at least twelve weeks. Compound 1 is administered: orally; or once daily; optionally wherein said Compound 1 is administered daily for at least twelve weeks. The NCT02842242 ref states the study is 12 weeks.
Claim 199 states wherein said subject: has a body mass index (BMI) of 18 to 37 kg/m2 +/- 10% prior to treatment; or prior to treatment, has a post-exercise peak LVOT gradient of 50 mmHg or higher. The NCT02842242 ref states an inclusion criterion of a BMI of 18-37 kg/m2.
New claims 204-207 are directed to the intervals of treatment, the first period length and second period length of time. The treatments of each as either 1 week or 8 weeks. These claims are obvious as the dose and duration of treatment are known variables to be optimized. This is shown by the dose ranging study, and the data provided stating the effect was dose dependent. Given these facts, a doctor/cardiologist would monitor the patient and adjust the dose to effect while maintaining safety.
Response to Amendments: Applicant has amended the claims and therefore a new search was performed and new art was used to render the dose titration from 5 to 10 mg over a period of time. These amendments have been found obvious as the optimization of the dose and the duration of the periods of time are known variables that are optimized. This is alluded to in the art that shows a dose dependent response to the drug, and the dosing periods would be adjusted for continued effect as the disease is chronic (being genetic). The interview request in the reply, in case of final will not be afforded as this case is expedited. The time to setup an interview on this case would push the case into an unacceptable response time. As such, an interview can be set up, but not at this time. Moreover, an interview will not be productive given the new art has not been considered by Applicant.
Double Patenting
(NEW Rejection based on Amendment)
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 194-199 and 203-207 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 194-203 of copending Application No. 19/082,967 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both directed to treating the same disease with the same drug in the same dose.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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