DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 41-57 in the reply filed on March 13, 2026 is acknowledged. Claims 41-57 are examined on the merits in this action. Claims 1, 3, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 13, 2026.
Claim Objections
Claim 41 is objected to because of the following informalities: inconsistent line break after “fluoro,” in the penultimate line. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 41-57 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Claims 41-57 encompass methods of “treating cancer”. Applicant defines "treating" or "treatment" as “prevention, partial alleviation, or cure of a disease, disorder or condition” (Specification para.[017]). Claims 41, 56, and 57 encompass treating cancer, comprising administering…” any compound of formula (I), not limited to the sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate in claims 42 and 43.
In re Wands, 858 F.2d 731, 736-40, 8 USPQ2d 1400, 1403-07 (Fed. Cir. 1988), set forth eight factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." (MPEP § 2164.01)
a. The breadth of the claim: The rejected claims encompass methods of preventing or inhibiting cancer in a patient. “Prevent" implies that cancer as a disease, disorder or condition is completely absent in patients treated according to the methods claimed. Claims 41, 56, and 57 encompass treating, including preventing cancer, comprising administering…” any compound of formula (I), not limited to the sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate in claims 42 and 43.
b. Nature of the invention: The nature of the invention is methods of treating, including preventing or inhibiting, any and all cancer, by administration of any compound(s) having formula (I) in claim 41 or any salt thereof, or sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate.
c. The state of the prior art: Nawrocki (Nawrocki et al., Abstract, The Aurora Kinase Inhibitor MLN8237 Has Potent Anticancer Activity in CML and Ph+ ALL Models and Significantly Increases the Efficacy of Nilotinib, Blood, 112, p.3198 (16 November 2008)) reports MLN8237, also known as sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate, “potently inhibited the in vitro growth and survival” of human chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) cell lines and primary cells derived from CML and Ph+ ALL patients. Also “in vitro kinase assays demonstrated that MLN8237 effectively inhibits the activity of wildtype and drug-resistant mutant forms of BCR-ABL gene”. However prevention or inhibition of CML and Ph+ALL in susceptible individuals or those with a BCR-ABL gene have not been contemplated, let alone studied. In 2012 Cervantes (Cervantes et al., Phase I Pharmacokinetic/Pharmacodynamic Study of MLN8237, an Investigational, Oral, Selective Aurora A Kinase Inhibitor, in Patients with Advanced Solid Tumors (2012)) reported pharmacokinetic and pharmacodynamic data which support a Phase II recommended dose of 50 mg twice daily for 7 days in 21-day cycles in adults with advanced solid tumors. Prevention or inhibition of any and all cancer as the term would be generally understood as absence of cancerous cells, via prophylactic administration of MLN8327, however, was not contemplated even in this later study.
d. Level of one of ordinary skill in the art: the level of ordinary skill is high as trained physicians would practice treating, including preventing, a cancer, by administering a compound of formula (I), including sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate.
e. Level of predictability in the art: the level of predictability in preventing cancer is low as known etiology of cancer is limited (e.g., smoking and lung cancer), and susceptibility to cancerous pathology varies widely among individuals. Furthermore Formula (I) in claim 41 encompasses numerous compounds other than sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate in claims 42 and 43. None of the other compounds appear to have been studied to any extent in relation to cancer therapy or prevention.
f. Amount of direction provided by the inventor: Applicant does not disclose guidance or methods of how to specifically prevent or inhibit any and all cancer using any compound of Formula (I), including sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate in claims 42 and 43. The disclosure refers to prior art regarding Aurora kinase inhibition and potential for “prophylaxis and therapy of diseases…such as cancer” (para.0006, pre-grant publication US 2016/0199382). However the cited references, e.g., US 2008/0045501, is similarly lacking in guidance concerning preventing a cancer or using any of the compounds in Formula (I).
g. Existence of working examples: The disclosure does not include any animal models or in vitro data tending to support any clinical attainment of prevention or inhibition of any cancerous condition. The Examples in the disclosure relate to tablet preparation, i.e., wet granulation, milling, and so on, of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate alone.
h. Quantity or experimentation needed to make or use the invention based on the content of the disclosure: considering the state of the art as discussed by the references above, particularly regarding the unpredictability of preventing a cancer, wide variability among individuals, and the lack of guidance provided in the specification, the person of ordinary skill would have to engage in significant amount experimentation and ingenuity to practice the invention commensurate in the scope of the claims.
In conclusion, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with claims 41-57.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claim 41, 56, and 57 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by the Claiborne '102 publication (US 2005/0256102 published on November 17, 2005).
Claiborne '102 publication teaches the compounds of formula (Va) which substantially overlap formula (I) in claim 41, and administering the same to treat a cancer (title; abstract; paras.0003, 0007-23, 0229-35, 0281).
Claims 41, 42, 56, and 57 are rejected under 35 U.S.C. 102(e) as being anticipated by the Claiborne '246 patent (US 8026246 issued on September 27, 2011).
The applied reference has a common assignee with the instant application. Based upon the earlier effective U.S. filing date of the reference, it constitutes prior art under 35 U.S.C. 102(e). This rejection under 35 U.S.C. 102(e) might be overcome either by a showing under 37 CFR 1.132 that any invention disclosed but not claimed in the reference was derived from the inventor of this application and is thus not the invention "by another," or by an appropriate showing under 37 CFR 1.131.
The Claiborne '246 patent teaches the compounds of formula( I), including sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate in claims 42 and 43 (title; abstract; Examples 2-3 at col.28 ll.20-67; claims 1-4). The Claiborne '246 patent also teaches treating a cancer by administering the compounds (abstract; col.25 lines 37-46).
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.
Claims 41, 42, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-19 of U.S. Patent No. 9988384.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering to the patient having the cancer a compound of formula (I) in claim 41 including sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate. The difference is that the ‘384 patent claims administering a therapeutically effective amount, which anticipates the current claims.
Claims 41 and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11958855.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass methods of treating cancer, comprising administering to the patient having the cancer sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate. The differences are that the ‘855 patent claims treating lung cancer specifically and combination with another therapeutic agent, which anticipates the current claims.
Claims 41, 42, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12042499.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof to the patient having the cancer. The differences are that the ‘499 patent claims a combination with a platin in a regimen, which anticipates the current claims.
Claims 41 and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10213436.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass methods of treating cancer, comprising administering to the patient having the cancer 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof. The differences are that the ‘436 patent claims treating lung cancer and a regimen. Therefore it anticipates the current claims.
Claims 41 and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10335494.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass methods of treating cancer, comprising administering to the patient having the cancer 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof. The differences are that the ‘494 patent claims treating lymphoma and a regimen, which anticipates the current claims.
Claims 41, 42, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9629850.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof the patient having the cancer. The difference is that the ‘850 patent claims a combination with a MEK inhibitor, which anticipates the current claims.
Claims 41 and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 3 of U.S. Patent No. 10391100.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass methods of treating cancer, comprising administering to the patient having the cancer 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof. The difference is that the ‘100 patent claims treating lymphoma and a regimen, which anticipates the current claims.
Claims 41, 42, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9504693.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate to the patient having the cancer. The difference is that the ‘693 patent claims a liquid pharmaceutical composition, which anticipates the current claims.
Claims 41, 42, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 9724354 .
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a salt thereof to the patient having the cancer. The difference is that the ‘354 patent claims a combination with an mTORC1/2 inhibitor, and therefore anticipates the current claims.
Claims 41, 42, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 20 of U.S. Patent No. 8653064.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate to the patient having the cancer. The difference is that the ‘064 patent claims crystalline forms, and therefore anticipates the current claims.
Claims 41, 42, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10017513.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to methods of treating cancer, comprising administering sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoate to the patient having the cancer. The difference is that the ‘513 patent claims crystalline forms, which anticipates the current claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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