DETAILED ACTION
This is an initial Office action for non-provisional application 18/570297 filed December 14, 2023, which is a 371 of PCT/US2022/0033728 filed June 16, 2022, which claims priority to a provisional of 63/211276 filed June 16, 2021.
Claims 1-28 are pending.
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 . 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.
Claim Objections
Claims 18-19 objected to because of the following informalities:
For clarity, claim 18 should recite “…wherein a severity of the symptom is determined by self-assessment.”
For clarity, claim 19 should recite “…wherein a severity of the symptom is determined by self-reporting.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20-22, 26 and 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 20-22 and 26, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 27, it is noted that the claim refers to BTK inhibitors or pharmaceutically acceptable salts thereof in Table 1 of the specification. See MPEP 2173.05(s). Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). In this case, Table 1 lists over 100 compounds that are BTK inhibitors but these could easily be listed and recited in claim 27. Thus, claim 27 is rejected under indefiniteness for not being complete in itself.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-14 and 20-27 are rejected under 35 U.S.C. 103 as being unpatentable over Rothbaum (W0 2019/224803; cited in PTO-892 herein) in view of Handy et al (US 2019/0381044; cited in IDS mailed 12/13/23).
Regarding claim 1, Rothbaum discloses therapeutic methods and pharmaceutical compositions for treating a myeloproliferative neoplasm (MPN) comprising the step of administering to a human in need thereof, therapeutically effective amounts of a MDM2 inhibitor, and a therapeutic agent selected from the group consisting of a JAK inhibitor, an IDH inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, an interferon, a P13K inhibitor, an AKT inhibitor, an mTOR inhibitor a nucleoside analog and combinations thereof (abstract, paragraph 0006, whole document). Rothbaum further discloses administering its therapeutic agents with a BTK inhibitor (paragraph 0249). Although Rothbaum suggests the use of BTK inhibitors, for MPN treatment, Rothbaum does not immediately envisage the administration of BTK inhibitors.
Handy et al teach methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment (abstract; whole document). More specifically, Handy et al teach these BTK inhibitors can be used to treat MPN (paragraph 0595). Handy et al exemplify the administration of the specific BTK inhibitor, ibrutinib (paragraph 0688) in dosages from 5 mg-2000 mg (paragraph 0648), which are similar amounts of BTK inhibitors disclosed in the instant specification (see paragraph 0085; Table 1).
Thus, it would have been obvious to an artisan of ordinary skill before the effective filing date to administer an effective amount of BTK inhibitor to treat human subjects with MPN. A skilled artisan would have been motivated to do so since Rothbaum suggests BTK inhibitors as additional therapeutic agents for MPN treatment and Handy et al provide further motivation for using BTK inhibitors to treat human subjects with MPN. With respect to the limitation directed to reducing or alleviating symptoms selected from the group consisting of night sweats, fatigue, pruritus, abdominal pain, pain under ribs, fullness, bone pain in human subjects with MPN, it should be noted that the reduction or alleviation of such symptoms would naturally result from administering the BTK inhibitors to a human subject with MPN within the combined teachings of Rothbaum and Handy et al. See MPEP 2112.02. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).
Regarding claim 2, Rothbaum teaches the MPN can be selected from primary myelofibrosis (paragraph 0074).
Regarding claim 3, Rothbaum teaches the MPN can be selected from post-polycythemia vera myelofibrosis (paragraph 0075).
Regarding claim 4, Rothbaum teaches the MPN can be selected from post-essential thrombocythemia myelofibrosis (paragraph 0075).
Regarding claim 5, Rothbaum teaches the MPN can be selected from chronic myelogenous leukemia (paragraph 0026).
Regarding claim 6, Rothbaum teaches the MPN can be selected from chronic neutrophilic leukemia (paragraph 0028).
Regarding claim 7, Rothbaum teaches the MPN can be selected from chronic eosinophilic leukemia (paragraph 0031).
Regarding claim 8, Rothbaum teaches the MPN can be selected from chronic myelogenous leukemia (paragraph 0026) with blast phase MPN (paragraph 0105).
Regarding claim 9, Rothbaum teaches the MPN can be selected from chronic myelomonocytic leukemia (paragraph 0032).
Regarding claim 10, Rothbaum is silent with respect to its human subjects suffering from splenomegaly, hepatomegaly or hepatosplenomegaly. However, Handy et al discuss the BTK inhibitor, ibrutinib, shows substantial antitumor activity and induces durable regressions of splenomegaly in most subjects (paragraph 0689). Therefore, it would have been obvious before the effective filing date of the claimed invention to administer the BTK inhibitors discussed in both Rothbaum and Handy et al to human subjects suffering from splenomegaly with a reasonable expectation of success since Handy et al suggest such inhibitors show substantial progress in treating splenomegaly.
Regarding claims 11-12, the combined teachings of Rothbaum and Handy et al teach its BTK inhibitors can be administered in combination with a JAK2 inhibitor (Rothbaum: paragraph 0084; Handy et: paragraph 0533) and Rothbaum teaches the JAK2 inhibitors can be selected from ruxolitinib and pacritinib (paragraph 0088).
Regarding claim 13, Rothbaum teaches the BTK inhibitor is administered in combination with a MDM2 inhibitor (paragraph 0001).
Regarding claim 14, Rothbaum teaches the MPN can be selected from a MPN is a JAK2-V617F myeloproliferative neoplasm (paragraph 0112).
Regarding claims 20-26 and the specific symptoms reduced or alleviated; it should be noted that the reduction or alleviation of such symptoms would naturally result from administering the BTK inhibitors to a human subject with MPN within the combined teachings of Rothbaum and Handy et al. See MPEP 2112.02. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).
Regarding claim 27, the combined teachings of Rothbaum and Handy exemplify the administration of the specific BTK inhibitor, ibrutinib (Handy: paragraph 0688), which is compound No. 2 in Table 1 of the specification.
Claims 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Rothbaum (W0 2019/224803; cited in PTO-892 herein) in view of Handy et al (US 2019/0381044; cited in IDS mailed 12/13/23) as applied to claims 1-14 and 20-27 above, and in further view of Scherber (Blood, July 14 2011, Volume 118, Number 2; cited in PTO-892 herein).
The disclosures of Rothbaum and Handy et al are discussed above and incorporated herein.
Regarding claim 15, the combined teachings of Rothbaum and Handy et al do not explicitly teach symptoms of its human subjects persist for at least one day prior to administration of the BTK inhibitor.
Scherber et al address the symptomatic burden in patients with myeloproliferative neoplasms and sought to validate assessments and surveys to assess symptoms of myelofibrosis (abstract). The surveys assess fatigue, early satiety, abdominal pain, abdominal discomfort, inactivity, cough, night sweats, pruritus, bone pain, fever, weight loss and quality of life (pg. 402, Methods). Scherber et al note that patients self-completed the assessments (pg. 402, first column, MPN-SAF validation) and noted how symptoms affected them over the last week.
Therefore, it would have been obvious to an artisan of ordinary skill before the effective filing date of the claimed invention that symptoms including night sweats, fatigue, bone pain, etc. would persist in patients with MPN for at least one 1 day prior to administration of therapeutic agents, like BTK inhibitors discussed in the combined teachings of Rothbaum and Handy et al. According to Scherber et al, such symptoms often exist for at least one week via assessments taken by patients with MPN and thus, a skilled artisan would have a reasonable expectation that treatment would not be initiated until symptoms are assessed and analyzed.
Regarding claims 16-17, Scherber et al teach symptoms are assessed for severity within its surveys (pg. 402, column 2, Symptomatic burden). Thus, it would have been obvious before the effective filing date of the claimed invention to assess the severity of symptoms of patients with MPN prior to and after treatment. A skilled artisan would have been motivated to do so in order to effectively treat and optimize dosages of BTK inhibitors administered.
Regarding claims 18-19, Scherber et al teach its patients with MPN self-complete its assessments and surveys (pg. 402, first column, MPN-SAF validation). It would have been obvious to conduct such self-assessments and surveys since patients’ analysis of symptoms is crucial in determining an effective treatment plan according to Scherber et al.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Rothbaum (W0 2019/224803; cited in PTO-892 herein) in view of Handy et al (US 2019/0381044; cited in IDS mailed 12/13/23) as applied to claims 1-14 and 20-27 above, and in further view of Hondous et al (WO 2012/170976; cited in PTO-892 herein).
The disclosures of Rothbaum and Handy et al are discussed above and incorporated herein.
Regarding claim 28, the combined teachings of Rothbaum and Handy et al do not teach the BTK inhibitor is 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one or a pharmaceutically acceptable salt thereof.
Hondous et al teach irreversible kinase inhibitors including, BTK inhibitors (abstract) in compositions used to treat hematologic malignancies, such as acute myelogenous leukemia (pg. 24, line 34). Such BTK inhibitors include 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one (see Compound A225, pg. 264).
Thus, it would have been obvious to an artisan of ordinary skill before the effective filing date to administer the BTK inhibitor, 1-(4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-4-fluoropiperidin-1-yl)prop-2-en-1-one, to treat human subjects with MPN in the combined teachings of Rothbaum and Handy et al. A skilled artisan would have been motivated to do so since Hondous et al suggest the BTK inhibitor is effective for treating MPN including chronic myelogenous leukemia.
Conclusion
Claims 1-28 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHAEL E BREDEFELD whose telephone number is (571)270-5237. The examiner can normally be reached 8:00-5:00 Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Alford Kindred can be reached at (571)272-4037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RACHAEL E BREDEFELD/Supervisory Patent Examiner, Art Unit 3786