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 .
Claim Objections
Claims 3 – 4, 6 – 9, 15 – 16, and 18 – 21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 (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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 27, and 31 – 32 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Regarding claim 1, 2, 27, and 31 – 32, Qian’641 teaches chemical entities that are bufalin derivatives and pharmaceutical compositions (abstract). Qian’641 teaches compounds of Formula I
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and pharmaceutically acceptable salts thereof (page 1 paragraph 005). More specifically, Qian’641 teaches compound I-e of structure
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(page 19 paragraph 080). Additionally, Qian’641 teaches that compounds of Formula I, that includes compound I-e, also include crystalline (claims 2) and amorphous forms of those compounds, including, for example, polymorphs, pseudopolymorphs, solvates (including hydrates), unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof (page 15 paragraph 053). Furthermore, Qian’641 teaches that pharmaceutically acceptable salt includes salts with an organic acid, such as maleate (claim 1) (page 16 paragraph 063).
Moreover, Qian’641 teaches that the disclosure includes pharmaceutical compositions comprising a pharmaceutically acceptable carrier (claim 27) and at least one chemical entity described here, which includes the crystalline form of compound I-e as the maleate salt (page 3 paragraph 008). Qian’641 also teaches that the disclosure includes a packaged pharmaceutical composition (claim 31) comprising a pharmaceutical composition described herein, that is including the crystalline form of compound I-e as the maleate salt and instructions for using the composition to treat a subject suffering from cancer (page 3 paragraph 009). Additionally, Qian’641 teaches a method of treating cancer (claims 32 – 33) in a subject which comprises administering to a subject in need thereof a therapeutically effective amount of at least one chemical entity described herein, which includes the crystalline form of compound I-e as the maleate salt (page 3 paragraph 010).
Regarding claim 1, while Qian’641 does not teach the specific embodiment of compound I – e as a maleate salt; Qian’641 teaches that pharmaceutically acceptable salt includes salts with an organic acid, such as maleate (claim 1) (page 16 paragraph 063). Thus it would have been within the purview of one of ordinary skill in the art to formulation any one of the compounds of Qian’641, which includes compound I – e, as a maleate pharmaceutical salt.
Regarding claim 2, while Qian’641 does not teach the specific embodiment of compound I – e as a crystalline maleate salt; Qian’641 teaches that pharmaceutically acceptable salt includes salts with an organic acid, such as maleate (claim 2) (page 16 paragraph 063). Moreover, Qian’641 teaches that compounds of Formula I, which includes compound I-e, also include crystalline (claims 2) and amorphous forms of those compounds (page 15 paragraph 053). Thus it would have been within the purview of one of ordinary skill in the art to formulation any one of the compounds of Qian’641, which includes compound I – e, as a crystalline maleate pharmaceutical salt.
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 1 – 2, 27, and 31 – 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 7 – 9 of U.S. Patent No. US 8334376 B2 to Qian (herein after Qian’376; cited on the IDS dated December 13th, 2023) in view of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Qian’376 recites a compound of Formula I
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or a pharmaceutically acceptable salt thereof (reference claim 1); wherein Z is NR10R11 (reference claim 4) and R10 and R11 are joined together to form a 5- to 7- membered heterocycloalkyl ring (reference claim 7). More specifically, Qian’376 recites a compound chosen from compounds I-a – I-f that is compound I-e
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(reference claim 8; instant claim 1). Additionally, Qian’376 recites a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of (reference) claim 1 and (reference) claim 8, or a pharmaceutically acceptable salt thereof (reference claim 9 and 11).
However, Qian’376 fails to recite compound I-e as the maleate salt (instant claim 1) or as a maleate salt crystalline form I or II (instant claims 2 – 3, and 15).
Nevertheless, the teaching of Qian’641 as it relates to the prior art rejections of instant claims 1 – 2, 27, and 31 – 33, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious to one of ordinary skill in the art to modify the invention of Qian’376 that is the make compound I-e in view of Qian’641 a maleate salt and crystalline maleate. One of ordinary skill in the art would have been motivated to make this modification to obtain effective dosages. One of ordinary skill in the art would have had a reasonable expectation of success because as taught by Qian’641 those skilled in the art will recognize various synthetic methodologies that may be used to prepare non-toxic pharmaceutically acceptable addition salts.
Claims 1 – 2, 27, and 31 – 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, and 15 – 18 of U.S. Patent No. US 10912784 B2 to Qian (herein after Qian’784; cited on the IDS dated December 13th, 2023) in view of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Qian’784 recites a compound selected from the group consisting of: (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate or a pharmtuically acceptable salt thereof (reference claim 1 and 12). Moreover, Qian’784 recites a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound or pharmaceutically acceptable salt of (reference) claim 1 (reference claim 15). Furthermore, Qian’784 recites a method of treating cancer in a subject which comprises administering to a subject having said cancer a therapeutically effective amount of the compound or pharmaceutically effective amount of the compound or pharmaceutically acceptable salt of (reference) claim 1, where in the cancer is selected from the group consisting of colorectal cancer, liver cancer, lung cancer (reference claim 17), breast cancer (reference claim 18), prostate cancer, pancreatic cancer, brain cancer, and oral cancer (reference claim 16).
However, Qian’784 fails to recite (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate as the maleate salt (instant claim 1) or as a maleate salt crystalline form (instant claim 2).
Nevertheless, the teaching of Qian’641 as it relates to the prior art rejections of instant claims 1 – 2, 27, and 31 – 33, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious to one of ordinary skill in the art to modify the invention of Qian’784 that is the make (3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate in view of Qian’641 a maleate salt and crystalline maleate salt. One of ordinary skill in the art would have been motivated to make this modification to obtain effective dosages. One of ordinary skill in the art would have had a reasonable expectation of success because as taught by Qian’641 those skilled in the art will recognize various synthetic methodologies that may be used to prepare non-toxic pharmaceutically acceptable addition salts.
Claims 1 – 2, 27, and 31 – 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 12, and 17 – 18 of U.S. Patent No. US 10179141 B2 to Qian (herein after Qian’141; cited on the IDS dated December 13th, 2023) in view of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Qian’141 recites a method of treating cancer in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula II:
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or a pharmtuically acceptable salt there of wherein the subject is human (reference claim 2); wherein R1 and R2 are joined together to form a 5- to 7- membered heterocycloalkyl ring (reference claim 12); wherein the cancer is lung cancer (reference claim 17) or breast cancer (reference claim 18).
However, Qian’141 fails to recite a method wherein the compound is a compound of structure
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(instant claim 1).
Nevertheless, the only structural difference between the instant compound of structure
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and a compound of invention Qian’141 of structure
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is the inclusion of a methyl unit (-CH2-) between the piperazine ring and the carbonyl. Moreover, both the instant compound and the compound species of invention Qian’141 are useful in methods of treating cancer. Given that the only structural difference is the inclusion of a methyl unit (-CH2-) both the instant compound and the compound species of invention Qian’141 are structural homologs of each other. Therefore, compounds which are homologs, that is compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). (MPEP 2144.09(II)).
However, Qian’141 also fails to recite whether compounds of the disclosure as the maleate salt (instant claim 1) or as a maleate salt crystalline form (instant claim 2).
Nevertheless, the teaching of Qian’641 as it relates to the prior art rejections of instant claims 1 – 2, 27, and 31 – 33, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious to one of ordinary skill in the art to modify the invention of Qian’141 that is the take the structural homolog of a compound in view of Qian’641 to make the maleate salt and crystalline maleate salt. One of ordinary skill in the art would have been motivated to make this modification to obtain effective dosages. One of ordinary skill in the art would have had a reasonable expectation of success because as taught by Qian’641 those skilled in the art will recognize various synthetic methodologies that may be used to prepare non-toxic pharmaceutically acceptable addition salts.
Claims 1 – 2, 27, and 31 – 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9, 20, and 23 – 24 of U.S. Patent No. US 9814735 B2 Qian (herein after Qian’735; cited on the IDS dated December 13th, 2023) in view of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Qian’735 recites a method of treating cancer in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula I:
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or a pharmaceutically acceptable salt thereof (reference claim 1); wherein the subject is human (reference claim 2); wherein the cancer is lung cancer (reference claim 6), prostate cancer (reference claim 4), pancreatic cancer (reference claim 5), liver cancer (reference claim 7), colorectal cancer (reference claim 8), brain cancer (reference claim 9), breast cancer (reference claim 3); wherein Z is NR10R11 (reference claim 20) and R10 and R11 are joined together to form a 5- to 7- membered heterocycloalkyl ring (reference claim 23). More specifically, Qian’735 recites a compound chosen from compounds I-a – I-f that is compound I-e
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(reference claim 24; instant claim 1).
However, Qian’735 fails to recite compound I-e as the maleate salt (instant claim 1) or as a maleate salt crystalline form (instant claim 2).
Nevertheless, teaching of Qian’641 as it relates to the prior art rejections of instant claims 1 – 2, 27, and 31 – 33, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious to one of ordinary skill in the art to modify the invention of Qian’735 that is the take compound I-e in view of Qian’641 a maleate salt and crystalline maleate salt. One of ordinary skill in the art would have been motivated to make this modification to obtain effective dosages. One of ordinary skill in the art would have had a reasonable expectation of success because as taught by Qian’641 those skilled in the art will recognize various synthetic methodologies that may be used to prepare non-toxic pharmaceutically acceptable addition salts. Moreover, as taught by Carvalho Jr. et. al. the formulation of a crystalline salt had good yields.
Claims 1 – 2, 27, and 31 – 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 9 of U.S. Patent No. US 8993550 B2 to Qian (herein after Qian’550; cited on the IDS dated December 13th, 2023) in view of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023).
Qian’550 recites a compound of Formula II:
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or a pharmtuically acceptable salt; wherein R1 and R2 are joined together to form a 5- to 7- membered heterocycloalkyl ring (reference claim 4); and a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of (reference) claim 1 (reference claim 9).
However, Qian’550 fails to recite a method wherein the compound is a compound of structure
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(instant claim 1).
Nevertheless, the only structural difference between the instant compound of structure
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and a compound of invention Qian’550 of structure
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is the inclusion of a methyl unit (-CH2-) between the piperazine ring and the carbonyl. Moreover, both the instant compound and the compound species of invention Qian’550 are useful in methods of treating cancer. Given that the only structural difference is the inclusion of a methyl unit (-CH2-) both the instant compound and the compound species of invention Qian’550 are structural homologs of each other. Therefore, compounds which are homologs, that is compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). (MPEP 2144.09(II)).
However, Qian’550 fails to recite compound I-e as the maleate salt (instant claim 1) or as a maleate salt crystalline form I or II (instant claim 2).
Nevertheless, the teaching of Qian’641 as it relates to the prior art rejections of instant claims 1 – 2, 27, and 31 – 33, are given previously in this office action and are fully incorporated here.
Therefore it would have been obvious to one of ordinary skill in the art to modify the invention of Qian’550 that is the take the structural homolog of a compound in view of Qian’641 to make the maleate salt and crystalline maleate. One of ordinary skill in the art would have been motivated to make this modification to obtain effective dosages. One of ordinary skill in the art would have had a reasonable expectation of success because as taught by Qian’641 those skilled in the art will recognize various synthetic methodologies that may be used to prepare non-toxic pharmaceutically acceptable addition salts.
Discussion of the prior art
The closet prior art of International Publication Number WO 2011/085641 A1 to Qian (herein after Qian’641; cited on the IDS dated December 13th, 2023) teaches chemical entities that are bufalin derivatives and pharmaceutical compositions (abstract). Qian’641 teaches compounds of Formula I
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and pharmaceutically acceptable salts thereof (page 1 paragraph 005). More specifically, Qian’641 teaches compound I-e of structure
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(page 19 paragraph 080). Additionally, Qian’641 teaches that compounds of Formula I, that includes compound I-e, also include crystalline and amorphous forms of those compounds, including, for example, polymorphs, pseudopolymorphs, solvates (including hydrates), unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof (page 15 paragraph 053). Furthermore, Qian’641 teaches that pharmaceutically acceptable salt includes salts with an organic acid, such as maleate (page 16 paragraph 063).
However, the prior art of Qian’641 fails to teach a method of preparing crystalline form I (claim 42) and crystalline form II (claim 55). Moreover, while the state of the prior art teaches the generic recrystallization steps for generically forming an acid salt and precipitate; the prior art fails to teach a method specifically for preparing crystalline form I and crystalline form II as both forms are defined. Thus the prior art of Qian’641 fails to anticipate and render obvious the method of instant claims 42 and 55. Thus instant claims 42 and 55 are free of the prior art and are allowable.
Conclusion
Claims 1 – 2, 27, and 31 – 33 are rejected. Claims 3 – 4, 6 – 9, 15 – 16, and 18 – 21, are objected. Claims 42 and 55 are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627