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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/06/2025, were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Status of the Claims
Claims 234-257 are pending.
Applicants’ arguments filed on 11/06/2025, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Maintained Rejections:
Claim Rejections - 35 USC § 112-Maintained
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.
The rejection of claims 234-257 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, is maintained for the reasons of record set forth in the previous office action, of which said reasons are herein reiterated. 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. Claims 235-241 depend from claim 234 and are therefore, also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for reasons set forth below. Claims 243-249 depend from claim 242 and are therefore, also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for reasons set forth below. Claims 251-257 depend from claim 250 and are therefore, also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for reasons set forth below.
MPEP 2163 states:
“An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. ………… Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention.
Each of independent claims 234, 242 and 250 recites the limitation of a method of treating a patient having symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first Valsalva left ventricular outflow tract (VLVOT) gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
The specification (see, e.g., ¶s 414-415, Example 1 and Figure 4), states that, following initial 5 mg/day of mavacamten for 4 weeks (to oHCM patient with LVEF ≥ 55%), if:
a) LVEF < 50% at any clinic visit during first 4 weeks, treatment is interrupted and restarted after 4 weeks if LVEF ≥ 50%;
b) VLVOT is <20 mm Hg at week 4, then the mavacamten dose is 2.5 mg; and
c) VLVOT is ≥20 mm Hg at week 4, the dose is maintained at 5 mg.
However, a review of the instant specification and claims as originally filed, fails to provide any written support in such a way as to reasonably convey to one skilled in the art that the Applicants, at the time of the instant application, have possession of a method treating a patient having oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg from the patient.
MPEP §2163 states:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.” In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test of sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.” Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983))…Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991).”
Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112(pre-AIA ), first paragraph.
Response to Applicants’ Arguments/Remarks
The Applicants raised several arguments (see pages 2-3 of Remarks), alleging that the rejection of instant claims under 35 U.S.C. 112(pre-AIA ), first paragraph, is improper on the grounds that:
1) The specification allegedly provides clear support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient. Applicants cite ¶s 043, 111, 129, 130, 136, 216 and Figure 1 of the specification, in support of the Applicants’ allegations (see pages 2-3 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, a review of the instant specification (including ¶s 043, 111, 129, 130, 136 and 216, cited by the Applicants in support of the Applicants’ allegations), fails to reveal any support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient. Specifically:
¶ 043 relates to method for determining LVOT gradient, or another measure of LVOT obstruction. There is nothing in ¶ 043 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
¶ 111 relates to assessments that may comprise LVOT obstruction assessment (e.g., a Valsalva LVOT gradient) and/or LVEF assessment. There is nothing in ¶ 111 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
¶ 129 relates to disclosure of one or more assessments of the patient. There is nothing in ¶ 129 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
¶ 130 relates to assessments of the patient’s LVOT obstruction. There is nothing in ¶ 130 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
¶ 136 relates to how a first assessment is performed. There is nothing in ¶ 136 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
¶ 216 relates to a method in which a patient having symptomatic oHCM is administered 5 mg/day of mavacamten for a period of about 4 weeks, wherein subsequent treatment (administering 2.5 mg/day for about 4 weeks), is based on conditional limitation (when) of obtaining patient’s VLVOT measurement of < 20 mm Hg. There is nothing in ¶ 216 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
Figure 1 relates to a treatment protocols based on conditional limitations. There is nothing in Figure 1 which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
2) Applicants states:
“Moreover, while the claimed invention recites "obtaining" LVOT gradient measurements, the measurements are not "simply" obtained and then disregarded. The claims recite that the subsequent dose administered to the patient is based on the obtained measurement of LVOT gradient. For instance, claim 234 recites "administering to the patient for a second treatment period of about 4 weeks after the first treatment period a dose of 2.5 mg per day of mavacamten based on the first Valsalva LVOT gradient measurement of below 20 mmHg." (Emphasis added.) This is consistent with the description in paragraph [216] (discussed above) that describes the dose administered when VLVOT gradient is below 20 mmHg, and paragraph [129] (also discussed above) that describes that the obtained LVOT gradient is "used to guide the dose administered for the subsequent treatment period."” (see page 3 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, instant claim 234 only requires a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks (lines 3-4), and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg from the patient (lines 5-6). There are no conditional limitations (when, if, etc.), recited in instant claim 234.
Furthermore, Applicants’ reiteration of the previous arguments alleging that ¶ 216 of the specification provides support for the Applicants’ allegations have been fully considered but they are not found to be persuasive. This is because Applicants’ arguments have been addressed in the discussions above. The Examiner, therefore, applies the same response hereto.
For the reasons made of record in the previous Office action and reiterated above, the rejections are maintained.
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 234-257 are rejected under 35 U.S.C. 103 as being unpatentable over Olivotto of record (Lancet, 2020), is maintained for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
By way of a background, Applicants disclosed their invention as a method for treating hypertrophic cardiomyopathy (HCM), with mavacamten (see, e.g., ¶s 001-003 and Figure 4 of the specification). The initial daily dose of mavacamten can be 5 mg, 10 mg, or 15 mg and second daily dose can be 2.5 mg, 5 mg, or 10 mg (see e.g., ¶s 123-1242 of the specification). A patient is diagnosed as having HCM if the measured left ventricular ejection fraction (LVEF) ≥ 55% (see Figure 4 of the specification).
HCM monitoring techniques include:
i) mavacamten blood plasma concentration (see, e.g., ¶ 041 of the specification) and/or non-invasive techniques such as echocardiography (see, e.g., ¶ 044 of the specification) for monitoring Valsalva left ventricular outflow tract (VLVOT, see, e.g., ¶ 158 of the specification), and LVEF (see, e.g., ¶ 158 of the specification); and
ii) New York Heart Association (NYHA) class II-III HCM symptoms (see, e.g., ¶ 062 of the specification).
The specification (see, e.g., ¶s 414-415, Example 1 and FIG 4), states that, following initial 5 mg/day of mavacamten for 4 weeks (to a patient with LVEF ≥ 55%), if:
a) LVEF < 50% at any clinic visit during first 4 weeks, treatment is interrupted and restarted after 4 weeks if LVEF ≥ 50%;
b) VLVOT is <20 mm Hg at week 4 (condition A), then the mavacamten dose is 2.5 mg, whereas, if VLVOT is ≥20 mm Hg at week 4 (not condition A), the dose is maintained at 5 mg.
c) VLVOT is <20 mm Hg at week 8 (condition B), the dose is 0 mg for patients receiving 2.5 mg in step i) or 2.5 mg for patients receiving 5 mg in step i), whereas, if VLVOT is ≥20 mm Hg at week 8 (not condition B), the dose is maintained at 5 mg.
Independent claim 234 recites:
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Independent claim 242 recites:
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Independent claim 250 recites:
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Similar to the Applicants’ invention, Olivotto teaches a method for treating patients suffering from oHCM, with 5 mg/day of mavacamten for 30 weeks (see abstract). A patient is diagnosed as having oHCM if the measured LVEF at least 55% (see page 761, left column ¶). Treatment is temporarily discontinued if LVEF < 50% and restarted if LVEF ≥ 50% (see “Supplementary Methods” section at page 3).
Patients were evaluated every 2 weeks or 4 weeks during the 30-week treatment period, wherein subsequent treatments are based on conditional limitations. Results from the monitoring are used to adjust daily dose and dosing of 2.5, 5, 10 and 15 mg were administered to achieve target LVOT of < 30 mm Hg (which encompasses the claimed < 20 mm Hg) and mavacamten plasma concentration of between 350 ng/mL and 700 ng/mL. Please see abstract, “Procedures” section on pages 761-762 and Figure 1.
Olivotto teaches monitoring techniques including:
i) echocardiography (a non-invasive technique, see discussions above), for monitoring VLVOT and LVEF (see abstract and Table 1);
ii) mavacamten blood plasma concentration (see abstract); and
iii) New York Heart Association (NYHA) class II-III HCM symptoms (see abstract).
The subsequent mavacamten doses based on conditional limitation of VLVOT, LVEF and NYHA class II-III HCM symptoms recited in claims 234-257, are result effective variables that would have been routinely determined and optimized in the pharmaceutical art (see discussions above). Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claim 238-239, 246-247 and 254-255, Olivotto teaches using echocardiography (a non-invasive technique), for monitoring VLVOT and LVEF (see discussions above).
Regarding claim 240, 248 and 256, Olivotto teaches NYHA class II-III symptoms (see discussions above).
Regarding claims 241, 249 and 257, the recitation of the limitation of the method of claims 234, 242 and 250 resulting in reduction in a risk of systolic dysfunction and/or heart failure in the patient, is not given any patentable weight because the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Olivotto discloses a method of claims 234, 242 and 250 (see discussions above), the method of Olivotto, must necessarily produce the same outcomes of recited in claims 241, 249 and 257. This is because the recited outcome is a natural process that flows from the subject and the administered mavacamten. Please see MPEP, 2111.04.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Response to Applicants’ Arguments/Remarks
The Applicants raised several arguments (see pages 4-11 of Remarks), alleging that the rejection of instant claims under 35 U.S.C. 103, is improper on the grounds that:
1) the background information regarding the Applicants’ invention (see discussions above), is incorrect in stating that a patient is diagnosed as having HCM if the measured LVEF≥ 55% (see page 4 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, Applicants’ specification (see Figure 4), states: “5 mg once daily, initiate only if LVEF≥ 55%”. It is noted that Applicants are not arguing that the specification (see Figure 4), did not state: “5 mg once daily, initiate only if LVEF≥ 55%”.
2) pages 6-7 of the previous Office action (background information regarding the Applicants’ invention), allegedly appear to be improperly importing subject matter from the specification into the claimed invention (see pages 4-5 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, the rejection of the instant claims began on page 7 of the previous Office action with verbatim recitation of independent claims 234 and 242. Applicants appear to have wrongly construed a brief summary of the Applicants’ invention pages 6-7 of the previous Office action (background information regarding the Applicants’ invention), as an improper importation of subject matter from the specification into the claimed invention.
3) Applicants state:
“Lastly, the Office Action appears to select portions of the specification out of context to mischaracterize the claimed invention. For example, the Office Action states that specification teaches mavacamten blood plasma concentration as a HCM monitoring technique. However, the specification highlights the negative attributes of such invasive techniques (see para. [044] of the specification, "Where a non-invasive technique (e.g., imaging technique, echocardiography) is used for determining LVOT gradient and LVEF, the need for other procedures, including invasive procedures, may be eliminated. For example, the need for determining blood plasma concentration (e.g., a "trough" measurement) may be eliminated"). And the claimed invention does not recite mavacamten blood plasma concentration as a monitoring technique” (see page 5 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, the recitation of “the need for determining blood plasma concentration (e.g., a "trough" measurement) may be eliminated")”, would be construed by a person skilled in the art as meaning HCM monitoring techniques include mavacamten blood plasma concentration. Furthermore, Applicants’ Example 2 (Regiment #1), includes mavacamten blood plasma concentration the HCM monitoring techniques (see, e.g., ¶ 016 of the specification).
4) the claimed dosing method is allegedly substantially different from dosing method of Olivotto because Olivotto describes results from EXPLORER-HCM Phase 3 clinical trial (Ho et al, Circulation: Heart Failure, 2020), which employed pharmacokinetics (mavacamten blood plasma concentration) and non-invasive technique (echocardiogram) for monitoring VLVOT and LVEF, whereas, the claimed only requires non-invasive technique for monitoring VLVOT and LVEF. Please see pages 6-7 of Remarks.
Response
Similar to the claimed invention, Olivotto teaches a method for treating oHCM with mavacamten at a starting dosage of 5 mg/day, wherein subsequent treatments are based on conditional limitations (when, if, etc.). Please see discussions above. Olivotto teaches use of echocardiogram among the list of evaluation tools (see abstract), known for assessing VLVOT (see discussions above). Olivotto teaches that monitoring techniques include: i) mavacamten blood plasma concentration; ii) VLVOT; iii) LVEF; and iv) NYHA class II-III symptoms. Please see summary on page 759 and Figure 1.
The mavacamten blood plasma concentration was designed for establishing the efficacy, tolerability and a safe mavacamten starting dose for all patients, which is 5 mg (see, e.g., Ho et al at page 62).
5) one skilled in the art would have allegedly had substantial doubts about the safety and effectiveness of the Olivotto/ EXPLORER-HCM dosing method. Applicants cite the 2020 AHA/ACC Guidelines for the Diagnosis and Treatment of Patients HCM, in support of the Applicants’ allegations (see page 7 of Remarks).
Response
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, Olivotto/ EXPLORER-HCM establishes a safe mavacamten starting dose for all patients, which is 5 mg (see discussions above) and provided conditions (when, if, etc.) for dosage adjustments (see discussions above).
6) the limitation of VLVOT, LVEF and NYHA class II-III HCM symptoms recited in claims 234-257, are not result effective variables because the claims do not recite conditional limitations (see pages 7-9 of Remarks).
Response
Similar to the Applicants’ invention, Olivotto teaches a method for treating oHCM with mavacamten at a starting dosage of 5 mg/day, wherein subsequent treatments are based on conditional limitations (when, if, etc.) VLVOT, LVEF and NYHA class II-III HCM symptoms (see discussions above). Therefore, the limitation of VLVOT, LVEF and NYHA class II-III HCM symptoms recited in claims 234-257, are result effective variables that would have been routinely determined and optimized in the pharmaceutical art.
7) the claimed dosing method has been described in a prestigious and high impart journal (Owens et al, J. Am Heart Assoc., 2024, 13:e033767). (Ho et al, Circulation: Heart Failure, 2020), which employed pharmacokinetics (mavacamten blood plasma concentration) and non-invasive technique (echocardiogram) for monitoring VLVOT and LVEF, whereas, the claimed only requires non-invasive technique for monitoring VLVOT and LVEF. Please see pages 6-7 of Remarks.
Response
There is nothing in Owens et al which provides support for a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first Valsalva left ventricular outflow tract (VLVOT) gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient.
Similar to Olivotto and/or Ho et al (see discussions above), Owens et al (seepages 4-5, under the title “TREATMENT INITIATION”), discloses treating patients with mavacamten at a starting dosage of 5 mg/day, wherein subsequent treatments are based on conditional limitations (when, if, etc.) VLVOT, LVEF and NYHA class II-III HCM symptoms.
8) Applicants have surprisingly and unexpectedly discovered that the claimed invention was found to provide safety and efficacy in the treatment of oHCM patients, regardless of CYP2C19 phenotypes and other patient attributes, thus allowing all patients to be treated according to the same scheme. Applicants cite Example 2 (Regimen #2), Tables 9-12, Figures 14A-D of the specification and US FDA approval of a mavacamten dosing scheme consistent with Example 2 (Regimen #2), in support of the Applicants’ allegations (see pages 10-11 of Remarks).
Response
Regarding the advantageous results alleged by the Applicants for rebutting the obviousness of claimed invention, please note that advantageous results alone are not sufficient for overcoming an obviousness. The results must be unexpected (emphasis added). For the establishment of unexpected results, a few notable principles are well settled. It is Applicants’ burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). The claims must be commensurate in the scope with any evidence of unexpected results (emphasis added). See MPEP 716.02 (d). Further, A DECLARATION UNDER 37 CFR 1.132 must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case if obviousness. See, MPEP 716.02 (e). In instant case, the alleged advantageous results are not unexpected, rather would have been reasonably expected for the following reasons.
Olivotto/ EXPLORER-HCM establishes a safe mavacamten starting dose for all patients, which is 5 mg (see discussions above) and provided conditions (when, if, etc.) for dosage adjustments (see discussions above).
Therefore, it would not have been a surprisingly and unexpectedly discovery that mavacamten at a starting dosage of 5 mg/day, is found to be for all patients, and wherein subsequent treatments are based on conditional limitations of the art (see discussions above), would achieve a safe and effective unified posology for oHCM patients, regardless of CYP2C19 phenotypes and other patient attributes, thus allowing all patients to be treated according to the same scheme.
Furthermore, the evidence of unexpected results is not commensurate in the scope with the claimed invention. This is because the claimed invention is drawn to a method of treating a patient having symptomatic oHCM with 5 mg/day of mavacamten for a period of about 4 weeks, and simply obtaining a first VLVOT gradient measurement of, for example, < 20 mm Hg (claim 234) from the patient, whereas, Example 2 (Regimen #2), relates to a method of treating a patient having symptomatic oHCM with a starting dosage of 5 mg/day of mavacamten, wherein subsequent treatments are based on conditional limitations (when, if, etc.) VLVOT, LVEF and NYHA class II-III HCM symptoms (see ¶s 651-655, Tables 9-12 and Figures 14A-D).
For the reasons made of record in the previous Office action and reiterated above, the rejections are maintained.
Non-Statutory Obviousness-Type Double Patenting-Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The provisional rejection of claims 234-257 on the ground of nonstatutory double patenting as being unpatentable over claims of the U.S. application Nos: i) 17/775,375; ii) 18/042,632; and iii) 18/160,393, is maintained for the reasons of record set forth in the previous Office action.
The rejection of claims 234-257 on the ground of nonstatutory double patenting as being unpatentable over claims of the U.S. patent Nos: i) 9,585,883; and ii) 9,181,200, is maintained for the reasons of record set forth in the previous Office action.
Response to Applicants’ Arguments/Remarks
The Applicants argue alleging that the instant claims are non-obvious over U.S. application Nos: i) 17/775,375; ii) 18/042,632; iii) 18/160,393; and U.S. patent Nos: i) 9,585,883; and ii) 9,181,200, for the reasons discussed with regard to the alleged non-obviousness of the claims over Olivotto (see page 23 of Remarks).
Response
Applicants’ arguments against the alleging non-obviousness of the instant claims over Olivotto have been addressed in the discussions above. The Examiner, therefor, applies the same response hereto.
For the reasons made of record in the previous Office action and reiterated above, the rejections are maintained.
Conclusion
No claim is allowable.
THIS ACTION IS MADE FINAL. 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.
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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629