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 .
Priority
This application filed on 06/29/2023, is a National Stage Application under 35 U.S.C. 371 of PCT/US2021/0065777, filed on 12/30/2021, which claims the benefit of U.S. Provisional Patent Application Number 63/133,160, filed on 12/31/2020.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 06/29/2023 and 11/20/2024, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
The preliminary amendment filed on 03/06/2026, that cancelled claims 3, 5-7, 9-11, 13-17, 19-23, 26, 29, 35-38, 40-43, 45-47, 49, 51-56 and 58-61, is acknowledged. Claims 1-2, 4, 8, 12, 18, 24-25, 27-28, 30-34, 39, 44, 48, 50, and 57 are pending.
Election/Restriction
Applicant’s response filed on 03/06/2026 to Restriction/Election Requirement filed on 11/07/2025, is acknowledged. Applicant elected without traverse Group I drawn to a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4-ylethoxy) phenyl] benzamide (Compound 1). Claims 1, 2, 4, 8, 12, 18, 24-25, 27-28, 30-34, 39, 44, and 50 read on the elected Group. Claims 48 and 57 of Group II and III are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse, a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Claims 1, 8, 12, 18, 24-25, 28, 30, 39, 44, and 50 read on the elected species.
Thus, claims 1-2, 4, 8, 12, 18, 24-25, 27-28, 30-34, 39, 44, 48, 50 and 57 are pending with claims 2, 4, 27, 31-34, 48 and 57 are withdrawn from further consideration, and claims 1, 8, 12, 18, 24-25, 28, 30, 39, 44, and 50 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for first therapeutically effective amount
Claim 1 recites “a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising: administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- yl-ethoxy)phenyl]benzamide (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof.”
Instant specification recites:
“… administering parenterally a formulation of 3-methoxy-N-[3-{2-methylpyrazol-3-yl)-4-(2-morpholin-4-ylethoxy)phenyl]benzamide (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, to the individual for a first period of time; and subsequently administering orally a formulation of Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, to the individual for a second period of time.” [page 2, line 31-35]. “In some embodiments, Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is administered parenterally in an amount equivalent to between about 10 mg and about 100 mg of Compound 1 free base.” [page 17, ln. 31-34].
It appears that the first therapeutically effective amount refers to the parenteral amount. While the instant specification recites that in some embodiment the amount is 10-100 mg, a preferred embodiment is not a definition and, therefore a first therapeutically effective amount is given its plain meaning as any therapeutic amount of Compound I administered parenterally.
Claim Rejections - 35 USC § 103
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.
35 USC § 103 over Stirn, Adams and Taylor
Claims 1, 8, 12, 24-25, 28, 30, 39 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892) in view of J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892).
Stirn teaches methods for treating a 5-HT2A mediated diseases and disorders in an individual by administering a pharmaceutical compositions prepared by formulating a therapeutically effective amount 3-methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate or solvate thereof, [0009]:
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Stirn teaches that the composition are parenteral dosage forms sterilized before filling and sealing an appropriate vial or ampoule. [0176], [0179], [0185].
Stirn teaches that the 5-HT2A mediated diseases and disorders include platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation. [0057], [0058], [0059]. Stirn specifically teaches methods of treating a condition associated with platelet aggregation comprising administering to a patient in need thereof a therapeutically effective amount of hydrate or solvate of the 5-HT2A modulator above. [0060].
Stirn teaches that the hydrate or solvate of the 5-HT2A modulator above inhibit platelet aggregation and uses in antiplatelet therapies (conditions related to platelet aggregation), wherein the modulator above used to help prevent myocardial infarction or stroke in patients who are at risk of developing obstructive blood clots (e.g., coronary thrombosis). [0100], [0108]. Stirn teaches that the hydrate or solvate of the 5-HT2A modulator above provide beneficial improvement in microcirculation to patients in need of antiplatelet therapy by antagonizing the vasoconstrictive products of the aggregating platelets, and reducing platelet aggregation in a patient in need thereof. [0111].
While Stirn teaches methods of using the claimed compound in treating condition closely related to microvascular obstruction i.e., condition associated with platelet aggregation, obstructive blood clots, etc., Stirn does not specifically teaches that the condition is microvascular obstruction.
Adams teaches the effectiveness of [3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl-)benzamide] (APD791) as 5-HT2A receptor antagonist [Abstract]:
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Adams teaches that APD791 is high-affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle. [Abstract]. Adams teaches that APD791 is a potent and selective 5-HT2A receptor antagonist, and the clinical evaluation of APD791 offers potential improvements over previously described 5-HT2A receptor antagonists. The combined inhibition of 5-HT-mediated thrombosis, vasoconstriction, and smooth muscle cell proliferation by APD791 provide unique benefits for the treatment of thrombotic disease. [page 103, col. 1, 2nd para.]. Adams teaches that APD791 was effectively inhibited human platelet aggregation, was shown to effectively block coronary thrombosis without increasing bleeding time, [page 102, col. 1, 2nd para. and col. 2, last para.].
Taylor teaches the use of a 5-HT2 receptor antagonist for attenuating microvascular constriction and protecting against microvascular constriction. [Abstract]. Taylor teaches that the administration of the 5-HT2 receptor antagonist significantly reduced the elevated distal microvascular resistance, ameliorating microvascular obstruction. Taylor teaches that the administration of the 5-HT2 receptor antagonist activated platelets and initiate vascular constriction and microvascular constriction. [page 87, col. 2, 2nd 3rd para.]. Taylor teaches that administration of 5-HT2 receptor antagonist treat microvascular obstruction and restore microvascular patency and microvascular flow, and improve reperfusion in acute myocardial infarction. [page 88, col. 1, last para.].
In view of the foregoing, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to treat or prevent microvascular obstruction by administering parenterally a parenteral formulation of Stirn and Adams 5-HT2A antagonist, APD791. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Stirn teaches the use of 5-HT2A antagonist, APD791 for treating platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, and specifically treating a condition associated with platelet aggregation; Stirn teaches that APD791 used as antiplatelet therapies for inhibiting, prevent obstructive blood clots and coronary thrombosis; Adams teaches that APD791 is high-affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle; inhibiting thrombosis, vasoconstriction, smooth muscle cell proliferation, effectively inhibited human platelet aggregation, and effectively block coronary thrombosis; and Taylor teaches studies on the effectiveness of 5-HT2 receptor antagonist for ameliorating and protecting against microvascular obstruction, and that administration of 5-HT2 receptor antagonist treat microvascular obstruction and restore microvascular patency and microvascular flow, and improve reperfusion in acute myocardial infarction. [page 88, col. 1, last para.]. Moreover, Adams teaches that APD791 is a potent and selective 5-HT2A receptor antagonist, and the clinical evaluation of APD791 offers improvements over previously described 5-HT2A receptor antagonists [page 102, col. 1, 2nd para. and col. 2, last para.], which motivate skilled artisan to substitute Taylor 5-HT2 receptor antagonist with APD791 to treat microvascular obstruction. Therefore, Stirn, Adams and Taylor provide the requisite motivation to one of ordinary skill in the art to utilize 5-HT2A receptor antagonist, APD791 in treating microvascular obstruction, and therefore meet each and every limitation of claim 1.
With regard to claim 24, Stirn teaches that the parenteral solution administered intravenously. [0178].
With regard to claim 25, Stirn teaches that the parenteral solution is administers by continuous infusion in unit dose form in ampoules, pre-filled syringes, or small volume infusion. [0193].
With regard to claim 39, Stirn teaches that the above compound is HCl salt, [0219, Example 1], [0016].
With regard to claim 28, Stirn teaches that amount of the above 5-HT2A modulator use in the treatment will vary based on the age and condition of the patient and tailored by physician to the patient conditions based on nature and severity of the illness to be treated, and will ultimately be at the discretion of the attendant physician or clinician, wherein the doses include about 0.001-500 mg, about 0.001-50 mg, and about 0.001-25 mg. In general, one skilled in the art understands how to extrapolate the dose depending on factors include the type, age, weight, sex, diet and medical condition of the patient, the severity of the disease, the route of administration, pharmacological considerations such as the activity, etc. [0182], [0183]. As provided in the MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005) (claimed alloy held obvious over prior art alloy that taught ranges of weight percentages overlapping, and in most instances completely encompassing, claimed ranges; furthermore, narrower ranges taught by reference overlapped all but one range in claimed invention). moreover, MPEP 2144.05.II.A explains: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).”
With regard to claims 8 and 12, Stirn teaches that 5-HT2A modulators i.e., the above compound, provide protection from ischemic injury during percutaneous coronary intervention including complications resulting therefrom, [0109]. Taylor teaches 5-HT2 receptor antagonist was administer prior surgery, wherein 5-HT2 receptor antagonism significantly lower pressure distal to the atherosclerotic lesion, resists distal microvascular and plaque rapture, systemic blood pressure following plaque rupture was reduced following the administration of 5-HT2 receptor antagonist, [page 86, col. 1, 2]. Taylor teaches that the administration of 5-HT2 receptor antagonist was protective. [page 87, col. 2, 1st, 2nd 3rd para.]. Taylor teaches that 5-HT2 receptor antagonism is useful therapeutic strategy to prevent thrombus mediated vasoconstriction due to rupture of atherosclerotic lesions. [page 88, col. 1, 1st para.] Blockade of 5-HT2 receptors markedly reduces 5-HT-induced vasoconstriction in human coronary arteries ex vivo, and also during coronary angioplasty (PCI). [page 87, col. 2, last para.]. Therefore, one of ordinary skill in the art would have been motivated to administer the potent 5-HT2A receptor antagonist, APD791 to a patient undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome immediately prior the PCI.
With regard to claim 30, one of ordinary skill in the art would have been motivated to administer 5-HT2A antagonist, APD791 over 1 minute infusion because Taylor teaches that HT2A antagonist was administered over 1minute bolus to treat and protect microvascular obstruction. [page 86, col. 1, last para.].
Claim 44 is met for the following reasons: the combination of Stirn, Adams and Taylor teach a method of treating microvascular obstruction by administering APD791 above parenterally. combination of Stirn, Adams and Taylor is silent on the adverse cardiac event but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting incidence of a major adverse cardiac event (MACE) is inherently reduced. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
35 USC § 103 over the combination of Stirn, Adams, Taylor in view of Clinical Procedures
Claims 18 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892) in view of J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892), further in view of Clinical Procedures for Safer Patient Care, 2017,
(web.archive.org/web/20170708215135/https://opentextbc.ca/clinicalskills/chapter/safe-injection-administration-and-preparing-medication-from-ampules-and-vials/).
The combination of Stirn, Adams, and Taylor teaches a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (compound 1).
Stirn teaches that amount of the above 5-HT2A modulator use in the treatment will vary based on the age and condition of the patient, and will ultimately be at the discretion of the attendant physician or clinician, wherein the doses include about 0.001-500 mg, about 0.001-50 mg, and about 0.001-25 mg, [0182]. The obviousness of the claimed amount of 5-75 mg of compound 1 is established above (claim 28). Stirn teaches that the composition is parenteral dosage forms sterilized before filling and sealing an appropriate vial or ampoule. [0176]. Stirn teaches that the parenteral administration (e.g. by injection, for example bolus injection or continuous infusion) presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers, [0193]. However, the combination of Stirn, Adams and Taylor do not teach that the parenteral formulation comprising from about 1-50 mg/mL.
Clinical Procedures for Safer Patient Care teaches parenteral medications and preparing medications from ampules and vials [Title]. Parenteral medications are supplied in sterile vials, ampules, and prefilled syringes. Ampules are glass containers in 1 ml to 10 ml sizes that hold a single dose of medication in liquid form. [page 9, last para.].
One of ordinary skill in the art would have been motivated to utilize the size of ampules taught by the Clinical Procedures of 1 ml or 10 ml for Stirn’s ampoule of compound 1 parenteral dosage forms, and therefore, Stirn’s amount of 50 mg in an ampoule would be equivalent to 1mg/ml (50 mg/10 ml), or 50 mg/ml (50 mg/ 1 ml). therefore, claims 18 and 50 are met.
Double Patenting
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.
Double Patenting Rejection over U.S. Patent No. 8980891B2
Claims 1, 8, 12, 24-25, 28, 30, 39, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 12-13 of U.S. Patent No. 8,980,891 B2 in view of B. Teegarden et al. (US PG PUB 2013/0237540A1, 09/12/2013, “Teegarden” cited in the IDS dated 06/29/2023), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims recite “A method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof; wherein the individual is undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS); wherein the parenteral formulation is a sterilized solution comprising from about 1-50 mg/mL of an adjusted free-base concentration of Compound 1; wherein the parenteral formulation is administered intravenously or by infusion; wherein the parenteral formulation is administered over a period of about 5 or about 1 minute or less; wherein Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is an HCI salt of Compound 1; wherein said method results in reduction in an incidence of a major adverse cardiac event (MACE).
U.S. Patent No. 8,980,891 B2 recites “3-Methoxy-N-[3-(2-methyl-2H-pyrazol-3-yl)-4-(2-morpholin-4-yl-ethoxy)-phenyl]-benzamide hydrate, pharmaceutical composition comprising the hydrate and pharmaceutically acceptable carrier, and a method of treating a 5HT2A-related disorder comprising administering to a patient having said disorder a therapeutically effective amount of the hydrate, wherein the 5HT2A-related disorder is selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation.
U.S. Patent No. 8,980,891 B2 does not recite that the condition associated with platelet aggregation is microvascular obstruction, or the composition is a parenteral composition.
Teegarden teaches methods for treating a 5-HT2A mediated disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of the compound below:
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Wherein the 5-HT2A mediated disorder is conditions associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation and reducing the risk of blood clot formation in an angioplasty or coronary bypass surgery individual [[0029]-[0033], claim 1]. Teegarden teaches that the compound is administer in Parenteral dosage forms may be prepared by dissolving the compound of the invention in a suitable liquid vehicle and filter sterilizing the solution before filling and sealing an appropriate vial or ampoule, administered intravenously or by infusion, [0528], [0532], [0539], [0547]. Teegarden teaches that the hydrate or solvate of the 5-HT2A modulator above provide beneficial improvement in microcirculation to patients in need of antiplatelet therapy by antagonizing the vasoconstrictive products of the aggregating platelets, and reducing platelet aggregation in a patient in need thereof. [0399]. Teegarden teaches that 5-HT2A modulators i.e., the above compound, provide protection from ischemic injury during percutaneous coronary intervention including complications resulting therefrom, [0397].
Adams and Taylor teach as discussed above, pages 6-7.
Therefore, In view of the foregoing, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to treating or preventing microvascular obstruction by administering parenterally a parenteral formulation of U.S. Patent No. 8,980,891 B2, Teegarden and Adams 5-HT2A antagonist above (APD791). One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because U.S. Patent No. 8,980,891 B2 teaches the use of 5-HT2A antagonist above for treating platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, and specifically treating a condition associated with platelet aggregation; Teegarden teaches that 5-HT2A antagonist above formulated in a parenteral composition for treating condition associated with platelet aggregation and used as antiplatelet therapies for inhibiting, prevent obstructive blood clots and coronary thrombosis; Adams teaches that APD791 is high-affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle; inhibiting thrombosis, vasoconstriction, smooth muscle cell proliferation, effectively inhibited human platelet aggregation, and effectively block coronary thrombosis; and Taylor teaches studies on the effectiveness of 5-HT2 receptor antagonist for ameliorating and protecting against microvascular obstruction, and that administration of 5-HT2 receptor antagonist treat microvascular obstruction and restore microvascular patency and microvascular flow, and improve reperfusion in acute myocardial infarction. [page 88, col. 1, last para.]. Moreover, Adams teaches that APD791 is a potent and selective 5-HT2A receptor antagonist, and the clinical evaluation of APD791 offers improvements over previously described 5-HT2A receptor antagonists [page 102, col. 1, 2nd para. and col. 2, last para.], which motivate skilled artisan to substitute Taylor 5-HT2 receptor antagonist with APD791 to treat microvascular obstruction. Therefore, U.S. Patent No. 8,980,891 B2, Teegarden, Adams and Taylor provide the requisite motivation to one of ordinary skill in the art to utilize 5-HT2A receptor antagonist, APD791 in treating microvascular obstruction, and therefore meet each and every limitation of claim 1.
Claims 8, 12, 24-25, 28, 30, 39 and 44 are met over the same rationale discussed above, pages 8-10.
Claims 18 and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 12-13 of U.S. Patent No. 8,980,891 B2 in view of B. Teegarden et al. (US PG PUB 2013/0237540A1, 09/12/2013, “Teegarden” cited in the IDS dated 06/29/2023), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892), further in view of Clinical Procedures for Safer Patient Care, 2017,
(https://web.archive.org/web/20170708215135/https://opentextbc.ca/clinicalskills/chapter/safe-injection-administration-and-preparing-medication-from-ampules-and-vials/).
The combination of U.S. Patent No. 8,980,891 B2, Teegarden, Adams and Taylor teaches a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (compound 1). However, the combination of Stirn, Adams and Taylor do not teach that the parenteral formulation comprising from about 1-50 mg/mL.
Clinical Procedures for Safer Patient Care teaches as discussed above, page 11.
The obviousness rationale is similar to the obviousness rationale for the 103 Rejection above, page 11.
Double Patenting Rejection over U.S. Patent No. 9199940B2
Claims 1, 8, 12, 24-25, 28, 30, 39 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 18 of U.S. Patent No. 9,199,940 B2 in view of S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims recite “A method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof; wherein the individual is undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS); wherein the parenteral formulation is a sterilized solution comprising from about 1-50 mg/mL of an adjusted free-base concentration of Compound 1; wherein the parenteral formulation is administered intravenously or by infusion; wherein the parenteral formulation is administered over a period of about 5 or about 1 minute or less; wherein Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is an HCI salt of Compound 1; wherein said method results in reduction in an incidence of a major adverse cardiac event (MACE).
U.S. Patent No. 9,199,940 B2 recites “4-(2-(4-(3-methoxybenzamido)-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethyl)morpholin-4-ium chloride, and pharmaceutical composition comprising the hydrate and pharmaceutically acceptable carrier.
Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”. in the instant case, U.S. Patent No. 9,199,940 B2 specification recites “a method of treating a 5HT2A-related disorder comprising administering to a patient having said disorder a therapeutically effective amount of the hydrate, wherein the 5HT2A-related disorder is selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation.” [col. 6, 35-65].
U.S. Patent No. 9,199,940 B2 does not recite that the condition associated with platelet aggregation is microvascular obstruction, or the composition is a parenteral composition.
Stirn, Adams and Taylor teach as discussed above, pages 5-7.
The obviousness rationale is similar to the obviousness rationale of the 103 Rejection above, pages 7-8.
Claims 8, 12, 24-25, 28, 30, 39 and 44 are met over the same rationale discussed above, pages 8-10.
Claims 18 and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 12-13 of U.S. Patent No. 9,199,940 B2 in view of S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892), further in view of Clinical Procedures for Safer Patient Care, 2017,
(web.archive.org/web/20170708215135/https://opentextbc.ca/clinicalskills/chapter/safe-injection-administration-and-preparing-medication-from-ampules-and-vials/).
The combination of U.S. Patent No. 9,199,940 B2, Stirn, Adams and Taylor teaches a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (compound 1). However, the combination of Stirn, Adams and Taylor do not teach that the parenteral formulation comprising from about 1-50 mg/mL.
Clinical Procedures for Safer Patient Care teaches as discussed above, page 11.
The obviousness rationale is similar to the obviousness rationale for the 103 Rejection above, page 11.
Double Patenting Rejection over U.S. Patent No. 9,783,502 B2
Claims 1, 8, 12, 24-25, 28, 30, 39 and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 7-8 of U.S. Patent No. 9,783,502 B2 in view of S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims recite “A method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising a first therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof; wherein the individual is undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS); wherein the parenteral formulation is a sterilized solution comprising from about 1-50 mg/mL of an adjusted free-base concentration of Compound 1; wherein the parenteral formulation is administered intravenously or by infusion; wherein the parenteral formulation is administered over a period of about 5 or about 1 minute or less; wherein Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is an HCI salt of Compound 1; wherein said method results in reduction in an incidence of a major adverse cardiac event (MACE).
U.S. Patent No. 9,783,502 B2 recites “A hydrochloride salt of a compound of Formula (I), and pharmaceutical composition comprising the salt and pharmaceutically acceptable carrier.
Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”. in the instant case, U.S. Patent No. 9,783,502 B2 specification recites “a method of treating a 5HT2A-related disorder comprising administering to a patient having said disorder a therapeutically effective amount of the hydrate, wherein the 5HT2A-related disorder is selected from a condition associated with platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation.” [col. 6, 57- col. 7, 21].
U.S. Patent No. 9,783,502 B2 does not recite that the condition associated with platelet aggregation is microvascular obstruction, or the composition is a parenteral composition.
Stirn, Adams and Taylor teach as discussed above, pages 5-7.
The obviousness rationale is similar to the obviousness rationale of the 103 Rejection above, pages 7-8.
Claims 8, 12, 24-25, 28, 30, 39 and 44 are met over the same rationale discussed above, pages 8-10.
Claims 18 and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 12-13 of U.S. Patent No. 9,783,502 B2 in view of S. Stirn et al. (US PG PUB 2012/0252813A1, 10/04/2012, “Stirn” cited in the PTO-892), J. Adams, et al. (The Journal of Pharmacology and Experimental Therapeutics, Volume 331, Issue 1, 2009, Pages 96-103, ISSN 0022-3565, “Adams” cited in the PTO-892) and A. Taylor, et al. European Journal of Pharmacology, Volume 486, Issue 1, 2004, Pages 85-89, ISSN 0014-2999, “Taylor” cited in the PTO-892), further in view of Clinical Procedures for Safer Patient Care, 2017,
(web.archive.org/web/20170708215135/https://opentextbc.ca/clinicalskills/chapter/safe-injection-administration-and-preparing-medication-from-ampules-and-vials/).
The combination of U.S. Patent No. 9,783,502 B2, Stirn, Adams and Taylor teaches a method of treating or preventing microvascular obstruction in an individual in need thereof, comprising administering parenterally to the individual a parenteral formulation comprising therapeutically effective amount of 3-methoxy-N-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4- ylethoxy)phenyl]benzamide (compound 1). However, the combination of Stirn, Adams and Taylor do not teach that the parenteral formulation comprising from about 1-50 mg/mL.
Clinical Procedures for Safer Patient Care teaches as discussed above, page 11.
The obviousness rationale is similar to the obviousness rationale for the 103 Rejection above, page 11.
Conclusion
Claims 1, 8, 12, 18, 24-25, 28, 30, 39, 44, and 50 are rejected. No claim is allowed.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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