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 .
Applicants' arguments, filed 10/31/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 presently being applied to the instant application.
Claim Rejections - 35 USC § 102/103--Previous
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1a) Claim(s) 1-5, 7, 11, 15-23 is/are rejected under 35 U.S.C. 102(a2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Cooper et al., (WO 2020/112939, cited in IDS).
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. 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]) and had a platelet count of 895 x 109/L at baseline (p. 19, para. [0093]).
Concerning claims 2-7, 11, 15-22, Cooper et al. does not delineate the essential thrombocytosis patient. Accordingly, the artisan would have been expected to administer Compound 1 to essential thrombocytosis patient, simply because they present with essential thrombocytosis. Patients designated as “high risk” for essential thrombocythemia, according to the instant specification, “possesses any one of the following characteristics: 1) are age 60 years or older; 2) have a platelet count of greater than 1500 x 109/L (at any point during the patient’s disease); 3) have a previous documented thrombosis (including transient ischemic attack (TIA), erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease-related; 4) have a previous hemorrhage related to ET; 5) have diabetes or hypertension requiring pharmacological therapy for greater than 60 months” [emphasis added](p. 5, para. [0021]).
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.).
The prior art is anticipatory insofar as it teaches administering the claimed compound to a patient with essential thrombocythemia (ET), including high risk patients. Assuming for the sake of argument that the teaching is insufficient to rise to the level of anticipation, it would have been obvious to administer the compound to ET patients in need thereof, since ET is a myeloproliferative disorder and the compound is useful for treating myeoloproliferative disorders.
1b) Claim(s) 24-25 is/are rejected under 35 U.S.C. 102(a2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Cooper et al., (WO 2020/112939, cited in IDS) 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.
Claim Rejections - 35 USC § 103--Previous
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.
Claim(s) 1-5, 7, 11, 15-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hall (WO 2015/195862) and further in view of Jiang et al., (Cancer Cell, 2018).
Hall teaches “a crystalline form of 2-((4S)-6-(4-chlorophenyl)-1-4H- benzo [c] isoxazolo [4,5-e] azepin-4-yl) acetamide, which is useful as an inhibitor of bromodomain-containing proteins” (Abstract). The compound is also described as “a novel hydrated (e.g., monohydrate) crystalline Form” (p. 2, para. [0007]), as per claims 24-25.
Hall teaches, “Provided compositions may be formulated such that a dosage of between 0.001-100 mg/kg body weight/day of the inhibitor can be administered to a patient receiving these compositions” (p. 9, para. [0046]), as per claim 23.
Hall does not teach high risk essential thrombocythemia (ET).
Jiang et al. teaches treating 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.
Accordingly, it would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to administer the claimed compound to ET patients since the claimed compound functions as a bromodomain inhibitor, and bromodomain inhibition has been linked to attenuation of disease states such as overproduction of platelets, which is a hallmark of ET. Patients with high risk ET, nevertheless present with ET, and thus would have included in the ET discussion of Jiang et al.
Nonstatutory Obvious-type 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 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, 11, 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). 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).
2) Claims 1-5, 7, 11, 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). 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).
Response to Arguments
i. Applicant argues, “Cooper does not disclose each and every element of the claims required under §102” (p. 6), insofar as “Cooper, however, does not disclose that patient 247 has ET, much less high-risk ET” (Id.).
The Examiner disagrees.
Again, as stated above, patients considered “high risk” for ET are age 60 and older and the prior art describes a study where several patients treated with the compound of the instant claim1, i.e., “Compound 1” of the prior art presented “At baseline, median age: 69 years” (p. 21, para. [00102]).
The prior art also teaches treating patients with abnormally high platelet counts “thrombocytemic”, i.e., above “450,000 platelets/µL” and “more than 600,000 platelets/µL” (see Cooper et al. at p. 12, para. [0064]) which is a hallmark of high risk essential thrombocythemia (ET). Note: 450,000 platelets/µL is equivalent to 450 x 109 platelets/L.
ii. Applicant argues treating myelofibrosis is not necessarily equal to treating essential thrombocythemia. Applicant describes data presented in a poster by the American Society of Clinical Oncology showing that the claimed compound was able to normalize platelet and white blood cell (WBC) counts as well as reduce spleen to normal size (see p. 7 of Response). Applicant postulates that these results “could not have been reasonably predicted from the teachings of Cooper.
The Examiner disagrees.
Cooper teaches, “Compound 1 increased hemoglobin levels, normalized platelet counts, and reduced spleen size” (p. 4, para. [0048]). The patient population of Cooper also includes those with abnormal white blood cell counts (p. 12, para. [0065]). Accordingly, the poster does not provide evidence of unexpected results insofar as the effects shown therein were known at the time of applicant’s filing.
iii. Applicant argues, “Nothing in Hall or Jiang support a conclusion that high-risk ET could be treated, much less with the clinical results obtained by Applicant” (p. 10).
ET may be characterized based on risk, but the patients still present with ET. Note that in the instant specification, the treatment for ET is the same as high-risk ET (see p. 2, para. [0007]).
ET disclosed in Jiang is a generalized designation. Patients with ET may be high or low risk yet present with similar symptoms, such as high platelet count. Thus, the patient population of Jiang et al. would have included high-risk patients.
iv. In regard to the Double Patenting rejections, Applicant argues that high-risk ET is distinct from myelofibrosis.
However, essential thrombocythemia is a chronic myeloproliferative disorder. Patients with high risk ET would have been reasonably expected to be part of that patient population. Nothing on record has been presented to show otherwise.
Conclusion
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb /WALTER E WEBB/Primary Examiner, Art Unit 1612