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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/19/2026 has been entered.
Applicants' arguments, filed 05/19/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 presently being applied to the instant application.
Claim Rejections - 35 USC § 103—New by Amendment
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.
1a) Claim(s) 1-5, 7, 15-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Solberg (Seminars in Oncology, 2002) in view of Cooper et al., (WO 2020/112939, cited in IDS).
Solberg teaches therapeutic options for essential thrombocythemia (Ti), where, “One approach is to assign the patient to a risk category from which treatment recommendations follow” (Abstract). “The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis” (Id.). One of the indicators for the disease consideration, and subsequent treatment, include patients “who have platelet counts > 1,500 x 109/L” (Id.).
Treatment options include observation, aspirin, hydroxyurea, anagrelide, IFN-α, Busulfan, and p32 (see p. 12, Table 2), but does not include 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide or a pharmaceutical salt thereof.
Cooper et al. teaches “the use of 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide, and pharmaceutically acceptable salts thereof, for treating myelofibrosis” (Compound 1; Abstract).
Cooper et al. is focused on treating “Myeloproliferative Disorders” (Ti), which is relevant to the instant claims insofar as essential thrombocythemia is a myeloproliferative disorder. As indicated above, myelofibrosis is a risk for patients with essential thrombocythemia. Thus, the patient population of those in need of treatment for myelofibrosis would have included patients with essential thrombocytosis.
Cooper et al. describes a treatment regimen wherein a “Patient 247” was “suspected” as having “essential thrombocytosis” (p. 19, para. [0092]). “Within 2 months on Compound 1 monotherapy, the patient’s severe headaches had resolved; their night sweats were less frequent; and a 37% reduction in symptoms was assessed by the Myeloproliferative Neoplasm Symptom (MNS) score” (p. 19-20, para. [0094]). It should be noted here the MNS score is used to evaluate the symptom burden in individuals with essential thrombocythemia (ET). Subject was previously administered “hydroxyrurea” (p. 19, para. [0092]), which is a typical treatment for patients with essential thrombocytosis, as taught by Solberg above, and had an excessive platelet count of 895 x 109/L at baseline (p. 19, para. [0093]), which is one of the hallmarks of essential thrombocythemia.
Concerning claims 2-5, 7, 15-22, the limitations recited therein are merely situations that identify the claimed patient population. One of the hallmarks of ET is excessive platelet count, as taught by Solberg. Since platelets are products of megakaryocytes, a bone marrow biopsy showing proliferation mainly of megakaryocytes lineage with increased numbers of enlarged, mature megakaryocytes . . ., as per claim 2, would have been expected. Diagnosis of disease, as per claims 3-5, 7, 15-22, included administration of hydroxyurea, prior to treatment would have been expected in view of Solberg.
The artisan would have been reasonably expected to administer Compound 1 to essential thrombocytosis patients, simply because they present with essential thrombocytosis, especially in view of the fact that a patient administered compound 1 had a 37% reduction in symptoms assessed by the Myeloproliferative Neoplasm Symptom (MNS) score, which is a test used to measure the severity of symptoms caused by blood cancers like essential thrombocythemia.
In the prior art, patients treated with “Compound 1” would have been considered “high risk”, as claimed, insofar as the patients of the prior art were older than 60 years of age, e.g., “Patient 245” was “a 66 year-old female” (p. 18, para. [0088]), “Patient 248” was “a 76 year-old male” (p. 20, para. [0094]), and patients were, “At baseline, median age: 69 years” (p. 21, para. [00102]).
The dosing regimen “for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated” (p. 14-15, para. [0079]). “For example, in monotherapies, Compound 1 may be administered at a dosage of 50 mg to 300 mg/day . . . “ (p. 15, Id.).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to administer the compound of Cooper et al., i.e. 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide, to patients having ET, i.e. patients having a platelet count greater than 1500 x109/L as taught by Solberg, since the compound of Cooper et al. is useful for treating myeloproliferative disorders and ET is a myeloproliferative disorder.
1b) Claim(s) 24-25 is/are rejected under 35 U.S.C. 103 as obvious over Solberg (Seminars in Oncology, 2002) in view of Cooper et al., (WO 2020/112939, cited in IDS), as applied to claim 1 above, as evidenced by Hall, (US 9,969,747).
In regard to the crystallin form of the claimed compound, Cooper et al. teaches, “Crystalline forms of Compound 1 are disclosed in U.S. 9,969,747, the entire contents of which are incorporated by reference herein” (p. 7, para. [0047]).
U.S. 9,969,747 to Hall teaches, “a novel hydrated (e.g., monohydrate) crystalline Form A” (col. 2, lines 26-38) of said compound “which has improved properties and displays advantages characteristics over the prior disclosed amorphous form” such as “improved relative humidity stability, ease of isolation, favorable pharmacokinetic parameters, and process reproducibility” (Id.).
Accordingly, it would have been within the scope of Cooper et al. to use the crystalline monohydrate forms of the claimed compound.
Technological Background
The prior art made of record and considered pertinent to applicant's disclosure Jiang et al., (Cancer Cell, 2018). Jiang et al. is pertinent for teaching a treatment for Myeloproliferative neoplasms (MPNs), which includes “polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)” (p. 3, 1st column). Further, “The identification of an activating point mutation, JAK2V617F, in 97% of patients with PV and 50% of patients with ET and MF provided the impetus for the rapid development of JAK kinase inhibitors” (Id. through 2nd column). Jiang et al. tested whether JQ1 “a BET bromodomain inhibitor, can attenuate MPN phenotype in MPLW515L and JAK2V617F mouse models” (p. 4, 2nd column).In summary, Juang et al. discovered that “BET inhibitors could prove to be useful in treating patients with MPNs and also provide insights into inflammation-dependent and -independent oncogenic transforming events in other cancer types” (p. 5, last paragraph). JQ1 alone was able to reduce platelets (p. 4, 2nd column), which would be beneficial in ET patients insofar as overproduction of platelets is a characterization of ET.
Nonstatutory Obvious-type Double Patenting—New by 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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
1) Claims 1-5, 7, 15-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,918,646 in view of Passamonti et al., (Haematologica 2008) and Solberg (Seminars in Oncology, 2002). The instant application and the ‘646 patent each claim administration of 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide to a patient. The ‘646 patent claims a broader patient population, i.e., patients with myelofibrosis, which would have included the instant claimed patient population, i.e., essential thrombocythemia, in view of Passamonti et al. teaching, “Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia” (Abstract). Solberg teaches, one of the indicators for essential thrombocythemia, and subsequent treatment, include patients “who have platelet counts > 1,500 x 109/L” (Id.).
2) Claims 1-5, 7, 15-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,070,464 in view of Passamonti et al., (Haematologica 2008) and Solberg (Seminars in Oncology, 2002). The instant application and the ‘464 patent each claim administration of 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide to a patient. The ‘464 patent claims a broader patient population, i.e., patients with myelofibrosis, which would have included the instant claimed patient population, i.e., essential thrombocythemia, in view of Passamonti et al. teaching, “Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia” (Abstract). Solberg teaches, one of the indicators for essential thrombocythemia, and subsequent treatment, include patients “who have platelet counts > 1,500 x 109/L” (Id.).
Response to Arguments
i) Applicant’s argument concerning anticipation, lack of a teaching of patients having platelet counts > 1,500 x 109/L, double patenting and Hall in view of Jiang et al. is moot in view of the new rejection above.
ii) Applicant argues, “to the extent a correlation between ET and MF is attempting to be made, it cannot be predicted that because the claimed compound was previously shown to be effective against MF, that similar clinical results would translate to treating ET in a subject having the claimed platelet count. There is no evidence for a reasonable expectation of success in this regard” (p. 7).
The Examiner disagrees.
Myelofibrosis (MF) is a disease that manifests in myeloproliferative disorders. Since patients with ET may develop MF, treating MF is one way treat ET. Again, a patient suspected of having ET, receiving applicant’s claimed compound, showed a 37% reduction in symptoms was assessed by the Myeloproliferative Neoplasm Symptom (MNS) score, which is a test to measure the severity of ET. Accordingly, it would have been obvious to administer the compound of Cooper to a patient with ET.
Conclusion
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
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Walter E. Webb
/WALTER E WEBB/Primary Examiner, Art Unit 1612
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