NON-FINAL REJECTION
This application is a 35 U.S.C. 371 (national stage) application of PCT/US2021/032094, filed May 12, 2021, which claims benefit of priority to Provisional Applications 63/161,828, filed Mar. 16, 2021; 63/160,325, filed Mar. 12, 2021; 63/089,419, filed Oct. 8, 2020; 63/040,832, filed Jun. 18, 2020; and 63/025,490, filed May 15, 2020.
Claims 1, 11, 16, 21, 24, 28, 30-31, and 55-66, as amended, 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 .
Priority
Applicant' s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on Nov. 11, 2022, Mar. 28, 2024, Jan. 14, 2025, Oct. 24, 2025, and Dec. 19, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered.
Election/Restrictions
Applicant’s election without traverse of azenosertib (a.k.a. ZN-c3) as the species of compound (A), having the structural formula,
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paclitaxel as the species of compound (B); and ovarian cancer as the disease or condition to be treated, in the reply filed on Dec. 19, 2025 is acknowledged. The elected species read on claims 1, 11, 21, 28, 55-60, and 66.
Claims 16, 24, 30, 31, and 61-65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on Dec. 19, 2025.
Claims 1, 11, 21, 28, 55-60, and 66 are currently pending and under consideration.
Claim Rejections - 35 USC § 112 - Indefiniteness
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 1, 11, 21, 28, 55-60, and 66 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01.
Specifically, claim 1 recites administering the claimed compounds to treat a disease or condition, without specifying any subject having the disease, or any patient population to whom the compounds are administered, rendering the claims indefinite. Suggested language to unambiguously define the claimed patient population could be, e.g., “a patient in need thereof,” i.e., human or mammalian patients having the claimed disease(s), which can be treated by administering the claimed compounds.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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, 11, 21, 28, 55-60, and 66 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Wang et al. (US Pub. 2022/0324868) in view of Ledermann et al. (Eur. J. Cancer 60, pp. 49-58, 2016) (both cited on the IDS dated 11/11/2022).
Wang et al. claim methods for treating or preventing cancer comprising administering to a patient a therapeutically effective amount of a combination comprising substance X and an anticancer drug, wherein substance X is a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof (claims 18 and 25).
Compounds of formula (I) of Wang et al. include compound I-16 (claim 11), shown side-by-side for comparison with the claimed compound:
Compound of claim 1 (azenosertib)
Compound I-16 of Wang et al.
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Wang et al. disclose that the cancer to be treated includes the elected disease, ovarian cancer (paras. [0522]-[0531]; [0550]-[0555]; [0569]), as recited by claims 1, 11, 21, and 66.
The compounds of Wang et al. are disclosed as inhibitors of WEE1 kinase, which regulates the phosphorylation state of cyclin-dependent kinase 1 (CDK1), thus playing an important role in regulating DNA damage checkpoints. WEE1 is a key gene in G2/M phase
block, and is overexpressed in some cancers. Since P53 mutation often exists in tumor cells, making the G1 checkpoint defective, the regulation of cell division cycle in P53-mutated cells depends on the G2/M checkpoint (paras. [0004]-[0005]).
In addition, Ledermann et al. disclose that around 70% of epithelial ovarian cancers (EOC) are high-grade serous adenocarcinomas, a defining feature of which is the presence of mutations within the tumor suppressor gene p53 (i.e., TP-53 mutated ovarian cancer). In addition, molecular analysis of high-grade serous ovarian cancer found that around half have aberrations in homologous recombination repair (HRR), a critical DNA damage response pathway. Several genetic lesions causing homologous recombination deficiency (HRD) include germline and somatic BRCA mutations as well as mutations of other genes (Introduction; Fig. 1).
Thus, Wang et al. and Ledermann et al. disclose, teach, and suggest that a majority of ovarian cancers are TP53-mutated ovarian cancers, as recited by claim 21; and/or are positive for homologous recombination deficiency (HRD), as recited by claim 28.
Wang et al. disclose that suitable anticancer drugs to be administered in combination with compounds of formula (I) include the elected chemotherapeutic agent, paclitaxel (paras. [0540], [0560], [0574], [0594]), as recited by claims 1, 59, 60, and 66.
Wang et al. further disclose that the components in the combination can be used simultaneously or separately (e.g., sequentially). The components of the combination may be prepared as a single pharmaceutical composition for simultaneous use, or the components may be individually prepared as a single independent pharmaceutical composition (e.g., in kit form), which may be administered simultaneously or separately (e.g., sequentially) (paras. [0547]-[0548]), as recited by claims 55-58.
Wang et al. differs from the instant claims only in that compound I-16 bears a 7-methyl substituent rather than a 7-ethyl group.
However, as recognized by MPEP § 2144.09, homologous compounds which differ regularly by the successive addition of the same functional group (e.g., CH2) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
A homologous form of the prior art compound is unpatentable unless it possesses some unexpected advantage or property not possessed by the prior art compound.
“[N]ovel members of a homologous series of chemical compounds must possess some unobvious or unexpected beneficial properties not possessed by a homologous compound disclosed in the prior art.” We stated that novelty alone, without invention, is not sufficient to lend patentability to a claim. . . . [C]hemists understand that members of a homologous series of chemical compounds possess the same principal characteristics which vary gradually from member to member, and that knowing the chemical and physical properties of one of the members suggests the properties of the other members.” In re Norris, 179 F.2d 970, 84 USPQ 458 (CCPA 1950).
In addition, where a compound is disclosed to have a particular utility, one of ordinary skill in the art would have a reasonable expectation that modifying the compound by the interchange of hydrogen and alkyl would yield compounds having similar properties, and thus have been held to be obvious variants. See In re Wood, 582 F.2d 638, 199 USPQ 137 (CCPA, 1978). The interchange of an alkyl group and hydrogen, in and of itself, is obvious. See Ex Parte Bluestone, 135 USPQ 199 (B.P.A.I. 1961); In re Lincoln and Byrkit, 53 USPQ 40 (C.C.P.A. 1942); In re Druey and Schmidt, 138 USPQ 39 (C.C.P.A. 1963); In re Lohr and Spurlin, 137 USPQ 548 (C.C.P.A. 1963); In re Hoeksema, 158 USPQ 596 (C.C.P.A. 1968); In re Hoke, 195 USPQ 148 (C.C.P.A. 1977); Ex parte Fauque, 121 USPQ 425 (B.P.A.I. 1954); Ex parte Henkel, 130 USPQ 474, (B.P.A.I. 1960).
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.
1. Claims 1, 11, 21, 28, 55-60, and 66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 38-45 of copending Application No. 18/004,628 in view of Wang et al. (US Pub. 2022/0324868) and Ledermann et al. (Eur. J. Cancer 60, pp. 49-58, 2016) (both cited on the IDS dated 11/11/2022).
Reference claims 38-45 are drawn to methods of ameliorating or treating a malignant growth or tumor comprising administering an effective amount of a polymorphic form of azenosertib, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the malignant growth or tumor is due to a cancer selected from, inter alia, ovarian cancer, uterine cancer, or osteosarcoma, as recited by examined claim 1.
The reference claims differ from the examined claims in that they do not recite administering azenosertib in combination with a chemotherapeutic agent, e.g., paclitaxel; or specify that the cancer is a TP53-mutated cancer, or is positive for homologous recombination deficiency (HRD).
Wang et al. claim methods for treating or preventing cancer comprising administering to a patient a therapeutically effective amount of a combination comprising a compound of formula (I) and an anticancer drug (claims 18 and 25).
The compounds of formula (I) of Wang et al. are disclosed as WEE1 inhibitors, including, e.g., compound I-16, which differs from azenosertib, as recited by reference claim 1 and examined claim 1, by only one methyl group, as shown below:
Azenosertib
Compound I-16 of Wang et al.
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Wang et al. disclose that the cancer to be treated includes ovarian cancer (paras. [0522]-[0531]; [0550]-[0555]; [0569]), as recited by examined claims 1, 11, 21, and 66.
The compounds of Wang et al. are disclosed as inhibitors of WEE1 kinase, which regulates the phosphorylation state of cyclin-dependent kinase 1 (CDK1), thus playing an important role in regulating DNA damage checkpoints. WEE1 is a key gene in G2/M phase
block, and is overexpressed in some cancers. Since P53 mutation often exists in tumor cells, making the G1 checkpoint defective, the regulation of cell division cycle in P53-mutated cells depends on the G2/M checkpoint (paras. [0004]-[0005]).
In addition, Ledermann et al. disclose that around 70% of epithelial ovarian cancers (EOC) are high-grade serous adenocarcinomas, a defining feature of which is the presence of mutations within the tumor suppressor gene p53 (i.e., TP-53 mutated ovarian cancer). In addition, molecular analysis of high-grade serous ovarian cancer found that around half have aberrations in homologous recombination repair (HRR), a critical DNA damage response pathway. Several genetic lesions causing homologous recombination deficiency (HRD) include germline and somatic BRCA mutations as well as mutations of other genes (Introduction; Fig. 1).
Thus, Wang et al. and Ledermann et al. disclose, teach, and suggest that a majority of ovarian cancers are TP53-mutated ovarian cancers, as recited by examined claim 21; and/or are positive for homologous recombination deficiency (HRD), as recited by examined claim 28.
Wang et al. disclose that suitable anticancer drugs to be administered in combination with compounds of formula (I) include, e.g., paclitaxel (paras. [0540], [0560], [0574], [0594]), as recited by examined claims 1, 59, 60, and 66.
Wang et al. further disclose that the components in the combination can be used simultaneously or separately (e.g., sequentially). The components of the combination may be prepared as a single pharmaceutical composition for simultaneous use, or the components may be individually prepared as a single independent pharmaceutical composition (e.g., in kit form), which may be administered simultaneously or separately (e.g., sequentially) (paras. [0547]-[0548]), as recited by examined claims 55-58.
Compound I-16 of Wang et al. differs from azenosertib only in that it bears a 7-methyl substituent rather than a 7-ethyl group.
However, it would have been predictable to one of ordinary skill in the art as of the filing date to modify the reference claims by administering azenosertib in combination with paclitaxel to treat ovarian cancer with a reasonable expectation of success, because Wang et al. disclose the treatment of ovarian cancer with compound I-16, a WEE1 inhibitor differing from azenosertib by only one methyl group, in combination with paclitaxel.
As recognized by MPEP §2144.06, “it 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.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
This is not a provisional nonstatutory double patenting rejection, because the copending claims have been allowed.
2. Claims 1, 11, 21, 28, 55-60, and 66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19-21, 26, and 27 of U.S. Patent No. 11/261,192 in view of Wang et al. (US Pub. 2022/0324868) and Ledermann et al. (Eur. J. Cancer 60, pp. 49-58, 2016) (both cited on the IDS dated 11/11/2022).
The reference claims are drawn to methods for ameliorating or treating a cancer comprising administering to a subject an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from, inter alia, ovarian cancer; and the compound of formula (I) as recited by reference claims 26-27 is identical to compound (A) as recited by examined claim 1 (azenosertib).
The reference claims differ from the examined claims in that they do not recite administering azenosertib in combination with a chemotherapeutic agent, e.g., paclitaxel; or specify that the cancer is a TP53-mutated cancer, or is positive for homologous recombination deficiency (HRD).
Wang et al. claim methods for treating or preventing cancer comprising administering to a patient a therapeutically effective amount of a combination comprising a compound of formula (I) and an anticancer drug (claims 18 and 25).
The compounds of formula (I) of Wang et al. are disclosed as WEE1 inhibitors, including, e.g., compound I-16, which differs from azenosertib, as recited by reference claim 1 and examined claim 1, by only one methyl group, as shown below:
Azenosertib
Compound I-16 of Wang et al.
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Wang et al. disclose that the cancer to be treated includes ovarian cancer (paras. [0522]-[0531]; [0550]-[0555]; [0569]), as recited by examined claims 1, 11, 21, and 66.
The compounds of Wang et al. are disclosed as inhibitors of WEE1 kinase, which regulates the phosphorylation state of cyclin-dependent kinase 1 (CDK1), thus playing an important role in regulating DNA damage checkpoints. WEE1 is a key gene in G2/M phase
block, and is overexpressed in some cancers. Since P53 mutation often exists in tumor cells, making the G1 checkpoint defective, the regulation of cell division cycle in P53-mutated cells depends on the G2/M checkpoint (paras. [0004]-[0005]).
In addition, Ledermann et al. disclose that around 70% of epithelial ovarian cancers (EOC) are high-grade serous adenocarcinomas, a defining feature of which is the presence of mutations within the tumor suppressor gene p53 (i.e., TP-53 mutated ovarian cancer). In addition, molecular analysis of high-grade serous ovarian cancer found that around half have aberrations in homologous recombination repair (HRR), a critical DNA damage response pathway. Several genetic lesions causing homologous recombination deficiency (HRD) include germline and somatic BRCA mutations as well as mutations of other genes (Introduction; Fig. 1).
Thus, Wang et al. and Ledermann et al. disclose, teach, and suggest that a majority of ovarian cancers are TP53-mutated ovarian cancers, as recited by examined claim 21; and/or are positive for homologous recombination deficiency (HRD), as recited by examined claim 28.
Wang et al. disclose that suitable anticancer drugs to be administered in combination with compounds of formula (I) include, e.g., paclitaxel (paras. [0540], [0560], [0574], [0594]), as recited by examined claims 1, 59, 60, and 66.
Wang et al. further disclose that the components in the combination can be used simultaneously or separately (e.g., sequentially). The components of the combination may be prepared as a single pharmaceutical composition for simultaneous use, or the components may be individually prepared as a single independent pharmaceutical composition (e.g., in kit form), which may be administered simultaneously or separately (e.g., sequentially) (paras. [0547]-[0548]), as recited by examined claims 55-58.
Compound I-16 of Wang et al. differs from azenosertib only in that it bears a 7-methyl substituent rather than a 7-ethyl group.
It would have been predictable to one of ordinary skill in the art as of the filing date to modify the reference claims by administering azenosertib in combination with paclitaxel to treat ovarian cancer with a reasonable expectation of success, because Wang et al. disclose the treatment of ovarian cancer with compound I-16, a WEE1 inhibitor differing from azenosertib by only one methyl group, in combination with paclitaxel.
As recognized by MPEP §2144.06, “it 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.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
3. Claims 1, 11, 55-60, and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 8, 9, 29-33, 37, 38, 42, 47, 49, 55, 57, and 58 of copending Application No. 19/201,378.
The reference claims are drawn to methods of treating cancer comprising administering to a subject in need thereof a daily dose of azenosertib, or a pharmaceutically acceptable salt thereof, at or greater than 350 mg, or an equivalent thereof, in accordance with an intermittent dosing cycle, further comprising administering a second therapeutic agent during the intermittent dosing cycle, wherein the second therapeutic agent, or a pharmaceutically acceptable salt thereof, is selected from, inter alia, paclitaxel, or a PARP inhibitor; and wherein the cancer is selected from, inter alia, ovarian cancer.
Thus, the reference claims read on and would anticipate the examined claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 9:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA ELIZABETH TOWNSLEY/Examiner, Art Unit 1629