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 .
Priority
The instant application is a 371 National Stage Entry of PCT/JP2020/030017 filed on August 5, 2020 which claims priority to foreign application PCT/JP2019/030980 filed on August 6, 2019.
Information Disclosure Statement
The information disclosure statements filed on June 27, 2025 and September 11, 2025 have been considered.
Status of Claims
Acknowledgement is made of cancelled (1-20), and new (21-24) claims filed on September 2, 2025. Claims 21-24 are pending in instant application.
Response to Arguments
Applicant’s arguments filed September 2, 2025 have been considered but are not convincing. A new grounds of rejection has been made due to the claim amendments.
Regarding Konstantinopoulos, Applicant argues Konstantinopoulos does not teach the instantly claimed components or dosing (see Remarks at p. 5). In the new rejections, Konstantinopoulos is relied upon to teach combining a PARP inhibitor and HSP90 inhibitor was known in the art to synergistically treat cancer, but the components and dosing regimen are taught by the references Ohkubo et. al.1, NIH2, and WO 2019/133697 A13.
The provisional double patenting rejection over Application No. 17/055,446 has been withdrawn, and a new double patenting rejection over Patent No. 12,414,940 B2 has been issued.
Claim Interpretation
Regarding all claims, 3-Ethyl-4-(3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)benzamide is understood to be CAS Registry No. 1260533-36-5, also known as pimitespib and TAS-116, and is well-known in the art to be an HSP90 inhibitor as shown by Ohkubo et. al.4, Suzuki et. al.5, and Lee et. al.6
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 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ohkubo et. al.7, NIH8, WO 2019/133697 A19, and Konstantinopoulos et. al.10 as evidenced by Reagan-Shaw et. al.11
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding 200 mg of niraparib daily and treating cancer, WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
Regarding 80 mg of pimitespib 5 days a week and treating cancer, NIH teaches administering dosage of pimitespib i) daily ii) every other day or iii) 5 days on/2 days off in 21-day cycles (reading on instant three week dosing period) (see NIH at Brief Summary) for treating solid tumors, neoplasms, HER2 positive metastatic breast cancer, non-small cell lung cancer (see id). Ohkubo teaches administering pimitespib in 3.6-14 mg/kg in rats for lung cancer (see Ohkubo at p. 16 left col. ¶2 and at Abstract). Reagan-Shaw explains these dosages convert to 35-136 mg for an average 60 kg adult (see Reagan-Shaw at p. 660 Figure 1). Ohkubo emphasizes HSP90 inhibitors are known to have toxic effects (see Ohkubo at p. 14 right col. ¶2 and p. 20 left col. ¶2). Ohkubo pursued further toxicity and efficacy tests with 116 mg (12 mg/kg rat) dosaging of pimitespib (see Ohkubo at p. 17 right col ¶2-3). NIH teaches examining dose escalation, safety, tolerability, and efficacy of pimitespib in subjects with solid tumors (see NIH at Brief Summary).
The prior art differs from the instant claims as follows, while the prior art teaches dosaging of the instant components, the prior art does not specify i) a combination of pimitespib and niraparib ii) 80 mg of pimitespib or iii) separate or concurrent administration.
However,
Regarding a combination, Ohkubo teaches pimitespib has a low drug–drug interaction potential that might allow combination administration with other drugs (see Ohkubo at p. 22 right col. lines 1-3). Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
Regarding dosaging, Ohkubo states “one approach to balancing the efficacy and toxicity of antitumor agents is optimization of the dosing schedule” (see Ohkubo at p. 20 right col. ¶2).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a combination, per MPEP § 2144.06(I), "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It would have been obvious to combine niraparib and pimitespib to treat cancer because both are known in the art to treat cancer, even more specifically both are taught to treat breast cancer and lung cancer (as taught by WO’697 and NIH), and pimitespib is known to be viable for combinatorial treatments (as taught by Ohkubo).
In addition or in the alternative per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. Combining a PARP inhibitor and HSP90 inhibitor is known in the art for treating cancer with synergy (as taught by Konstantinopoulos). Absent unexpected results, it would have been obvious to pick a PARP inhibitor known for treating a cancer such a breast cancer to use in combination with a HSP90 inhibitor known to treat breast cancer in order to treat breast cancer, administered concurrently or staggered, with a reasonable expectation of success because both components would be performing their art-recognized function separately as they would together (treating cancer), and the prior art teaches dosing routines for the components (as taught by Ohkubo and WO’697).
Regarding 80 mg of pimitespib, per MPEP § 2144.05(I), where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It would have been obvious to one skilled in the art to arrive at 80 mg dose of pimitespib in light of Ohkubo because Ohkubo teaches dosaging at 35-136 mg doses, further studying the 116 mg dose (which the Examiner notes is less than the 120 mg toxic dose mentioned by Applicant, see 9/2/25 Remarks at p. 9).
In addition or in the alternative, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Regarding staggered or concurrent administration, one skilled in the art would appreciate there are only two options when administering two components, either separately or together. The prior art even teaches optimization of dosing schedule is important for balancing efficacy and toxicity (as taught by Ohkubo) (see also MPEP § 2143(I)(G)).
Furthermore, it is well-within the ordinary skill in art to combine or optimize a dosage routine of known anti-cancer compounds for use in treating cancer. Furthermore, it is well-within the ordinary skill in art to incorporate an HSP90 inhibitor or PARP inhibitor in lieu of another HSP90 inhibitor or PARP inhibitor.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
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.
Provisional Non-Statutory Double Patenting Rejections
Claims 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8 of copending Application No. 19/031,62812 (reference application) in view of Ohkubo et. al.13, NIH14, WO 2019/133697 A115, and Konstantinopoulos et. al.16 as evidenced by Reagan-Shaw et. al.17
Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 21-24, App’628 claims a method of treating a tumor comprising administering a compound of Formula I and another antitumor agent in combination (App’628 claims 1 and 8) or administering a compound of Formula I to a cancer patient who has been administered other antitumor agents (App’628 claim 7). App’628 claims wherein the compound of Formula I is CAS# 1260533-36-5, known in the art as pimitespib (App’628 claim 3, also reads on App’628 claim 2). App’628 claims wherein administration is simultaneous or separate (App’628 claim 6).
The copending applications differ as follows: While instant application claims the second agent is the PARP inhibitor niraparib, App’628 does not specify wherein the second agent is niraparib, or specific dosing regimens.
However,
Regarding administering PARP inhibitors, A PARP inhibitor is not excluded from, and is in fact encompassed by, “other antitumor agent” as App’628 claims. WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
Regarding dosing of pimitespib, NIH teaches administering dosage of pimitespib i) daily ii) every other day or iii) 5 days on/2 days off in 21-day cycles (see NIH at Brief Summary) for treating solid tumors, neoplasms, HER2 positive metastatic breast cancer, non-small cell lung cancer (see id). Ohkubo teaches administering pimitespib in 3.6-14 mg/kg in rats for lung cancer (see Ohkubo at p. 16 left col. ¶2 and at Abstract). Reagan-Shaw explains these dosages convert to 35-136 mg for an average 60 kg adult (see Reagan-Shaw at p. 660 Figure 1). Ohkubo emphasizes HSP90 inhibitors are known to have toxic effects (see Ohkubo at p. 14 right col. ¶2 and p. 20 left col. ¶2). Ohkubo pursued further toxicity and efficacy tests with 116 mg (12 mg/kg rat) dosaging of pimitespib (see Ohkubo at p. 17 right col ¶2-3). NIH teaches examining dose escalation, safety, tolerability, and efficacy of pimitespib in subjects with solid tumors (see NIH at Brief Summary).
It would have been obvious to one skilled in the art to select a PARP inhibitor such as niraparib to use as the additional antitumor agent according to App’628 claims because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
In addition, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Accordingly, instant claims 21-24 are not patentably distinct over App’268 in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 18/873,21118 (reference application) in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims, App’211 claims a pharmaceutical composition for oral administration comprising CAS# 1260533-36-5, also known as pimitespib (see App’211 claim 8).
Per MPEP §804(II)(B)(1), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. App’211 discloses the utility of the oral administration of CAS# 1260533-36-5 is “useful as a prophylactic agent and/or therapeutic agent for cancer or the like based on a HSP90 inhibitory effect” (see App’211 at p. 2 lines 2-3).
The copending applications differ as follows: While instant application claims administration of a compound of Formula I with a second agent is a PARP inhibitor, App’211 does not specify further administering niraparib or a dosing regimen.
However,
Regarding administering PARP inhibitors, A PARP inhibitor is not excluded from the claims of App’211. Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
Regarding dosing of a PARP inhibitor, WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
Regarding dosing of pimitespib, NIH teaches administering dosage of pimitespib i) daily ii) every other day or iii) 5 days on/2 days off in 21-day cycles (see NIH at Brief Summary) for treating solid tumors, neoplasms, HER2 positive metastatic breast cancer, non-small cell lung cancer (see id). Ohkubo teaches administering pimitespib in 3.6-14 mg/kg in rats for lung cancer (see Ohkubo at p. 16 left col. ¶2 and at Abstract). Reagan-Shaw explains these dosages convert to 35-136 mg for an average 60 kg adult (see Reagan-Shaw at p. 660 Figure 1). Ohkubo emphasizes HSP90 inhibitors are known to have toxic effects (see Ohkubo at p. 14 right col. ¶2 and p. 20 left col. ¶2). Ohkubo pursued further toxicity and efficacy tests with 116 mg (12 mg/kg rat) dosaging of pimitespib (see Ohkubo at p. 17 right col ¶2-3). NIH teaches examining dose escalation, safety, tolerability, and efficacy of pimitespib in subjects with solid tumors (see NIH at Brief Summary).
It would have been obvious to one skilled in the art to additionally administer a PARP inhibitor to use with the invention of App’211 because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
In addition, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Accordingly, instant claims 21-24 are not patentably distinct relative to claim 8 of App’211 in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 19/031,77319 (reference application) in view of WO’697 and Konstantinopoulos. Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims, App’773 claims a method for treating a malignant tumor comprising administering CAS# 1260533-36-5 also known as pimitespib, at a dose of from 40 mg/body/day to 240 mg/body/day, including 80 to 200 mg/body/day for at least one day and then providing a withdrawal period of at least 2 days (App’773 claims 1-9), including administered for 5 consecutive days (App’773 claim 19) which reads on the instantly claimed five consecutive days on, two days off. App’773 specifies tumors in claims 10-12 such as breast camcer. App’773 claims the dosage regimen of independent claim 1 reduces adverse eye events step in claims 13-26.
The copending applications differ as follows: While instant application claims a dosing routine for pimitespib, App’773 does not specify further administering niraparib.
However,
Regarding administering PARP inhibitors, additionally administering a PARP inhibitor is not excluded from the claims of App’773. Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
Regarding dosing of a PARP inhibitor, WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
It would have been obvious to one skilled in the art to additionally administer a PARP inhibitor to use with the invention of App’773 because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for synergistically treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
Accordingly, instant claims 21-24 are not patentably distinct relative to claim 1-26 of App’773 in view of WO’697 and Konstantinopoulos.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 16/646,27020 (reference application) in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw. Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims, App’270 claims a method of treating a gastrointestinal stromal tumor involving indoleamine 2,3-dioxygenase expression comprising administering CAS# 1260533-36-5, also known as pimitespib (App’270 claim 16).
The copending applications differ as follows: While instant application claims a method of treating a tumor comprising administering CAS# 1260533-36-5, App’270 does not specify further administering a PARP inhibitor.
However,
Regarding administering PARP inhibitors, additionally administering a PARP inhibitor is not excluded from the claims of App’270. Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
Regarding dosing of a PARP inhibitor, WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
Regarding dosing of pimitespib, NIH teaches administering dosage of pimitespib i) daily ii) every other day or iii) 5 days on/2 days off in 21-day cycles (see NIH at Brief Summary) for treating solid tumors, neoplasms, HER2 positive metastatic breast cancer, non-small cell lung cancer (see id). Ohkubo teaches administering pimitespib in 3.6-14 mg/kg in rats for lung cancer (see Ohkubo at p. 16 left col. ¶2 and at Abstract). Reagan-Shaw explains these dosages convert to 35-136 mg for an average 60 kg adult (see Reagan-Shaw at p. 660 Figure 1). Ohkubo emphasizes HSP90 inhibitors are known to have toxic effects (see Ohkubo at p. 14 right col. ¶2 and p. 20 left col. ¶2). Ohkubo pursued further toxicity and efficacy tests with 116 mg (12 mg/kg rat) dosaging of pimitespib (see Ohkubo at p. 17 right col ¶2-3). NIH teaches examining dose escalation, safety, tolerability, and efficacy of pimitespib in subjects with solid tumors (see NIH at Brief Summary).
It would have been obvious to one skilled in the art to additionally administer a PARP inhibitor to use with the invention of App’270 because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
In addition, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Accordingly, instant claims 21-24 are not patentably distinct relative to claim 16 of App’270 in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
NSDP Rejections
Claims 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent 12,414,940 B221 in view of in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw. Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims, US’940 claims a method for treating a malignant tumor comprising administering CAS# 1260533-36-5, at a dose of from 40 mg/body/day to 240 mg/body/day for at least one day and then providing a withdrawal period of at least 2 days (US’940 claims 1-9). US’940 further claims specific tumor types (US’940 claims 10-12) including breast cancer. US’940 claims the dosage regimen of independent claim 1 reduces adverse eye events step in claims 13-26.
The copending applications differ as follows: App’446 does not specify further administering niraparib.
However,
Regarding administering PARP inhibitors, additionally administering a PARP inhibitor is not excluded from the claims of US’940.
Regarding a combination of a compound of Formula I and a PARP inhibitor, Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
Regarding dosing of a PARP inhibitor niraparib, WO’697 teaches administering a dose of 200 mg of the PARP inhibitor niraparib daily (see WO’697 [00082] and [000102] and [000407] and claim 333). WO’697 teaches niraparib for treating cancers such as breast cancer, lung cancer, pancreatic cancer, or ovarian cancer (see WO’697 at [00054]-[00057]).
Regarding dosing of pimitespib, NIH teaches administering dosage of pimitespib i) daily ii) every other day or iii) 5 days on/2 days off in 21-day cycles (see NIH at Brief Summary) for treating solid tumors, neoplasms, HER2 positive metastatic breast cancer, non-small cell lung cancer (see id). Ohkubo teaches administering pimitespib in 3.6-14 mg/kg in rats for lung cancer (see Ohkubo at p. 16 left col. ¶2 and at Abstract). Reagan-Shaw explains these dosages convert to 35-136 mg for an average 60 kg adult (see Reagan-Shaw at p. 660 Figure 1). Ohkubo emphasizes HSP90 inhibitors are known to have toxic effects (see Ohkubo at p. 14 right col. ¶2 and p. 20 left col. ¶2). Ohkubo pursued further toxicity and efficacy tests with 116 mg (12 mg/kg rat) dosaging of pimitespib (see Ohkubo at p. 17 right col ¶2-3). NIH teaches examining dose escalation, safety, tolerability, and efficacy of pimitespib in subjects with solid tumors (see NIH at Brief Summary).
It would have been obvious to one skilled in the art to additionally administer a PARP inhibitor to use with the invention of App’446 because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
In addition, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Accordingly, instant claims 21-24 are not patentably distinct relative to claim 1-26 of US’940 in view of in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 12 of U.S. Patent 8,779,142 B222 in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw. Although the claims at issue are not identical, they are not patentably distinct from each other.
The applicable analysis for Nonstatutory Double Patenting is set forth in MPEP § 804(II), and specifically MPEP § 804(II)(B). MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis. The instant analysis is an obviousness analysis.
Claim interpretation: The claim interpretations set forth in the “claim interpretation” section above are hereby incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims, US’142 claims a pharmaceutical composition comprising CAS# 1260533-36-5 (US’142 claim 12).
Per MPEP §804(II)(B)(1), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. US’142 discloses utility of the pharmaceutical composition containing the same, particularly, a preventive and/or therapeutic agent for cancer, etc., based on HSP90 inhibitory activity (see US’142 at Field of the Invention).
The copending claims differ from the patented claims as follows: While instant application claims a method of treating a tumor comprising administering CAS# 1260533-36-5, US’142 does not claim further administering niraparib.
Regarding administering PARP inhibitors, A PARP inhibitor is not excluded from the claims of US’142. Konstantinopoulos teaches administering the PARP inhibitor Olaparib (CAS Registry No. 763113-22-0) in combination with the HSP90 inhibitor AT13387, also known as Onalespib (CAS Registry No. 912999-49-6), to synergistically treat ovarian cancer (see Konstantinopoulos at Abstract).
It would have been obvious to one skilled in the art to additionally administer a PARP inhibitor to use with the invention of US’142 because the prior art teaches a PARP inhibitor in combination with an HSP90 inhibitor for treating cancer (as taught by Konstantinopoulos) (see MPEP § 2143(I)(A)).
In addition, per MPEP § 2144.05(II), a prima facie case of obviousness exists for optimization within prior art conditions or through routine experimentation. Ohkubo teaches toxic effects of HSP90 inhibitors are well-known, and an artisan would readily appreciate the importance of optimizing pimitespib dosing to avoid toxic effects. Furthermore, NIH teaches Phase 1 clinical trials of pimitespib, the purpose of which is to identify the ideal safe and effective dose (see also MPEP § 2143(I)(G)).
Accordingly, instant claims 21-24 are not patentably distinct relative to claim 12 of US’142 in view of Ohkubo, NIH, WO’697, and Konstantinopoulos as evidenced by Reagan-Shaw.
Allowable Subject Matter
Absent unexpected results regarding the instantly claimed combination, the claims are obvious over the prior art as discussed above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Ohkubo et. al. "TAS-116, a Highly Selective Inhibitor of Heat Shock Protein 90a and b, Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models" Mol Cancer Ther 2015, 14, 1, 14-22. DOI: 10.1158/1535-7163.MCT-14-0219. Hereinafter Ohkubo. Cited in previous Office Action.
2 ClinicalTrials.gov, NCT02965885 A Study of TAS-116 in Patients With Solid Tumors. NIH,
https://clinicaltrials.gov/study/NCT02965885?tab=history&a=3#version-content-panel (accessed October 20, 2025). Published April 4, 2018. Hereinafter NIH.
3 Filed December 27, 2018. Published July 4, 2019. Hereinafter WO’697.
4 Ohkubo et. al. "TAS-116, a Highly Selective Inhibitor of Heat Shock Protein 90α and β, Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models" Molecular Cancer Therapeutics, 2015, 14, 1, 14-22. DOI: 10.1158/1535-7163.MCT-14-0219. Hereinafter Ohkubo.
5 Suzuki et. al. "TAS-116 Second-generation HSP90-α/β inhibitor Cancer Therapy" Drugs of the Future, 2018, 43, 1, 13-21. DOI: 10.1358/dof.2018.043.01.2746373. Abstract only. Hereinafter Suzuki.
6 Lee et. al. "TAS-116, a novel Hsp90 inhibitor, selectively enhances radiosensitivity of human cancer cells to X-rays and carbon ion radiation" Mol Cancer Ther 2017, 16, 1, 16-24. DOI: 10.1158/1535-7163.MCT-16-0573. Hereinafter Lee. Cited in previous Office Action.
7 Ohkubo et. al. "TAS-116, a Highly Selective Inhibitor of Heat Shock Protein 90a and b, Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models" Mol Cancer Ther 2015, 14, 1, 14-22. DOI: 10.1158/1535-7163.MCT-14-0219. Hereinafter Ohkubo. Cited in previous Office Action.
8 ClinicalTrials.gov, NCT02965885 A Study of TAS-116 in Patients With Solid Tumors. NIH,
https://clinicaltrials.gov/study/NCT02965885?tab=history&a=3#version-content-panel (accessed October 20, 2025). Published April 4, 2018. Hereinafter NIH.
9 Filed December 27, 2018. Published July 4, 2019. Hereinafter WO’697.
10 Konstantinopoulos et al. "In vivo synergism between PARP-inhibitor olaparib and HSP90-inhibitor AT13387 in high grade serous ovarian cancer patient derived xenografts." Journal of Clinical Oncology 2016, 34, 15, e17045-e17045. DOI:10.1200/JCO.2016.34.15_suppl.e17045. Cite No. AY in the IDS filed 3/18/22. Hereinafter Konstantinopoulos. Cited in previous Office Action.
11 Reagan-Shaw et. al. "Dose translation from animal to human studies revisited". FASEB J, 2008, 22, 3, 659-661. DOI: 10.1096/fj.07-9574LSF. Hereinafter Reagan-Shaw.
12 Filed January 18, 2025. A continuation of U.S. Patent Application 18/422,511, filed January 25, 2024, pending, which is a continuation of U.S. Patent Application 17/490,256 filed September 30, 2021, now issued as U. S. Patent 11,918,562, which is a division of U.S. Patent Application No. 16/877,959, filed May 19, 2020, now U.S. Patent 11,166,943, which is a division of U.S. Patent Application No. 15/493,479, filed April 21, 2017, now issued as US 10,849,886, which is a continuation of U.S. Patent Application No. 15/025,797, filed March 29, 2016, now issued as US 9,694,001, which is National Stage Entry of International Application No. PCT/JP2014/075846, filed September 29, 2014, and claims priority to Japanese Application No. 2013-205500, filed September 30, 2013. Hereinafter App’628.
13 Ohkubo et. al. "TAS-116, a Highly Selective Inhibitor of Heat
Shock Protein 90a and b, Demonstrates Potent Antitumor Activity and Minimal Ocular Toxicity in Preclinical Models" Mol Cancer Ther 2015, 14, 1, 14-22. DOI: 10.1158/1535-7163.MCT-14-0219. Hereinafter Ohkubo. Cited in previous Office Action.
14 ClinicalTrials.gov, NCT02965885 A Study of TAS-116 in Patients With Solid Tumors. NIH,
https://clinicaltrials.gov/study/NCT02965885?tab=history&a=3#version-content-panel (accessed October 20, 2025). Published April 4, 2018. Hereinafter NIH.
15 Filed December 27, 2018. Published July 4, 2019. Hereinafter WO’697.
16 Konstantinopoulos et al. "In vivo synergism between PARP-inhibitor olaparib and HSP90-inhibitor AT13387 in high grade serous ovarian cancer patient derived xenografts." Journal of Clinical Oncology 2016, 34, 15, e17045-e17045. DOI:10.1200/JCO.2016.34.15_suppl.e17045. Cite No. AY in the IDS filed 3/18/22. Hereinafter Konstantinopoulos. Cited in previous Office Action.
17 Reagan-Shaw et. al. "Dose translation from animal to human studies revisited". FASEB J, 2008, 22, 3, 659-661. DOI: 10.1096/fj.07-9574LSF. Hereinafter Reagan-Shaw.
18 Filed December 9, 2024. National Stage Entry of International Application No. PCT/JP2023/021536 filed June 9, 2023 which claims priority to foreign Application No. JP2022-094747 filed June 10, 2022. Hereinafter App’211.
19 Filed January 18, 2025 which is a continuation of Application No. 17/055,446 filed November 13, 2020 which is a National Stage Entry of International Application No. PCT/JP2019/019010 filed May 14, 2019 which claims priority to foreign Application No. PCT/JP2018/018593 filed May 14, 2018. Hereinafter App’773.
20 Filed March 11, 2020, which is a National Stage Entry of International Application No. PCT/JP2018/034092 filed September 14, 2018 which claims priority to foreign Application No. JP2017-178247. Hereinafter App’270.
21 Patented September 16, 2025. Hereinafter US’940.
22 Corresponding to Application No. 13/378,527 and PCT/JP2010/004466 filed July 9, 2010. Hereinafter US’142.