DETAILED ACTION
All rejections and objections not listed below have been withdrawn.
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
Acknowledgment is made of applicant’s claim for priority. The certified copy has been filed in parent Application No. 62/952,032, filed on 12/20/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/20/2022, 12/01/2022, 12/13/2023, 08/26/2024, 07/11/2025, 10/17/2025 and 10/28/2024 are being considered by the examiner.
The information disclosure statement filed 06/24/2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the foreign patent documents were not provided. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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.
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.
Claim(s) 1, 4-6, 8, 10, 19-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang (Huang et al., WO2019173082A1, 9/12/2019, previously provided) in view of Jong (Jong et al., “WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage”, Cancers 2019, 11, 1743, 11/7/2019, previously provided) further in view of Pinchman (Pinchman et al., WO2019139899A1, 7/18/2019, previously provided) further in view of Dancey (Dancey et al., Strategies for optimizing combinations of molecularly targeted anticancer agents, NATURE REVIEWS | DRUG DISCOVERY, VOLUME 5 | AUGUST 2006) .
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The reference Huang teaches the compounds of instant compound (A) (figure 1, reference claim 1).
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Figure 1: Huang Reference Claim 1 Formula (1)
The reference Huang also teaches compounds of the instant claim 2 (Figure 2, reference claim 122).
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Figure 2: Huang Reference Claim 122 Compounds
The reference Huang also teaches compounds of the instant claims 3 and 12-19 (Figure 3, reference claim 123).
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Figure 3: Huang Reference Claim 123 Compounds
The reference Huang also teaches “Use of an effective amount of a compound of any one of Claims 1-123, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of Claim 124 in the manufacture of a medicament for ameliorating or treating a cancer, wherein the cancer is selected from a brain cancer, a cervicocerebral cancer, an esophageal cancer, a thyroid cancer, a small cell cancer, a non-small cell cancer, a breast cancer, a lung cancer , a stomach cancer, a gallbladder/bile duct cancer, a liver cancer, a pancreatic cancer, a colon cancer, a rectal cancer, an ovarian cancer, a choriocarcinoma, an uterus body cancer, an uterocervical cancer, a renal pelvis/ureter cancer, a bladder cancer, a prostate cancer, a penis cancer, a testicular cancer, a fetal cancer, Wilms' cancer, a skin cancer, malignant melanoma, a neuroblastoma, an osteosarcoma, an Ewing's tumor, a soft part sarcoma, an acute leukemia, a chronic lymphatic leukemia, a chronic myelocytic leukemia, polycythemia vera, a malignant lymphoma, multiple myeloma, a Hodgkin's lymphoma, and a non-Hodgkin’s lymphoma” (reference claim 125) and “The present application relates to compounds that are WEE1 inhibitors and methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer”[0002]. This helps to teach claims 1-21.
The reference Huang teaches “The pharmaceutical compositions described herein can be administered to a human patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or carriers, diluents, excipients or combinations thereof. Proper formulation is dependent upon the route of administration chosen. Techniques for formulation and administration of the compounds described herein are known to those skilled in the art”[0127]. This helps to teach claims 23-27.
The reference Huang does not teach the combination of Compound (A) with any Bcl-2 inhibitors (all claims), the specific routes of administration (claims 23-27) or some of the specific cancers (claims 5, 10, 21, 22).
The reference Jong teaches “Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i) or S63845 (MCL-li) enhanced sensitivity in a cell-specific manner. In addition, we demonstrate that both G2/M cell cycle arrest and DNA damage induction put a similar stress on DLBCL cells, thereby enhancing anti-apoptotic dependency. Therefore, genotoxic or cell cycle disrupting agents combined with specific anti-apoptotic inhibitors may be very effective in genomic unstable cancers such as DLBCL and therefore warrants further clinical evaluation” (abstract) and “Indeed, blocking of WEE1 activity with AZD1775 results in apoptosis in solid cancers [11], lymphoma [4], and leukaemia [12,13]” (page 1). The reference Jong also teaches “In genomically unstable cancers such as DLBCL, WEE1 is highly expressed and a relevant target for therapy. Since the WEE1 inhibitor AZD1775 is indeed effective in inducing apoptosis we investigated if it could alter anti-apoptotic dependency and increase sensitivity to BH3 mimetic drugs in DLBCL cell lines and patient material. Our findings demonstrate that (1) AZD1775 induces cell death through apoptosis; (2) AZD1775-mediated inhibition of WEE1 alters the anti-apoptotic dependency in DLBCL; (3) combination of AZD1775 with cell-specific anti-apoptotic inhibitors (such as venetoclax) leads to enhanced potency; (4) both DNA damage and G2/M arrest induced by WEEl inhibition independently enhances dependency on anti-apoptotic proteins” (page 8). Additionally, the reference teaches “In conclusion, we demonstrate that treatment of cells with WEEl inhibitor AZD1775 can enhance the dependency on anti-apoptotic proteins and enhanced sensitivity to BH3 mimetic drugs. In addition, we showed that DNA damage and cell cycle arrest independently induce similar changes in the anti-apoptotic dependency. Therefore, we predict that other DNA damage-inducing of cell cycle arresting agents will synergize with BH3 mimetic drugs”(Conclusion). This helps to teach claims 1-20.
The reference Pinchman teaches “The present application relates to compounds that are Bcl-2 inhibitors and methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer and tumors, and viral infections such as infection with the human immunodeficiency virus (HIV)” [0002] and “A method for inhibiting the activity of Bcl-2 in a subject comprising providing an effective amount of a compound of any one of Claims 1-81, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of Claim 82 to the subject having a cancer or a tumor, wherein the cancer or the tumor is selected from a bladder cancer, a brain cancer, a breast cancer, a bone marrow cancer, a cervical cancer, a colorectal cancer, an esophageal cancer, a hepatocellular cancer, a lymphoblastic leukemia, a follicular lymphoma, a lymphoid malignancy of T-cell or B-cell origin, a melanoma, a myelogenous leukemia, a Hodgkin’s lymphoma, a Non-Hodgkin’s lymphoma, a head and neck cancer (including oral cancer), an ovarian cancer, a non-small cell lung cancer, a chronic lymphocytic leukemia, a myeloma, a prostate cancer, a small cell lung cancer, a spleen cancer, a polycythemia vera, a thyroid cancer, an endometrial cancer, a stomach cancer, a gallbladder cancer, a bile duct cancer, a testicular cancer, a neuroblastoma, an osteosarcoma, an Ewings’s tumor and a Wilm’s tumor” (reference claim 87). The reference Pinchman also teaches venetoclax and navitoclax as Bcl inhibitors (reference figure 2). This helps to teach claims 1-22.
The reference Dancey teaches “Strategies for optimizing combinations of molecularly targeted
anticancer agents” (title) and “The possible reasons for the failure of certain targeted agents in combination with standard cytotoxic therapies can be related to any of three factors: first, the nature of the effects of the agents, individually or in combination; second, the presence/functionality of the target; and third, the biological context of the target or other cellular factors that might alter the effect of agents on their target or the biological consequences of target modulation in the patient population selected for the clinical trial. The agent might have poor pharmacological properties that result in its failure to interact effectively with the target. There might be antagonism between the agents when administered together. For example, the latter might occur if the first agent induced G1 arrest in tumour cells whereas the additional agent is active only in S or M phases of the cell cycle. Such an unfavourable interaction has been reported from non-clinical studies for the combination of tamoxifen and chemotherapy in breast cancer, and clinical studies evaluating concurrent versus sequential administration of certain combination agents seem to demonstrate the superiority of the latter schedule17–19.”(page 651). The reference Dancey also teaches “In addition to the above considerations related to specific models, experimental conditions and individual agents, experiments assessing combinations must also be designed to determine optimal concentration/exposures and sequencing of agents. Preclinical studies of combinations require the generation of accurate dose–response curves for the agents tested, both alone and in combination. Therefore both the dynamic range of the assay and accurate assessment of the endpoint of interest is crucial41”(page 655) and “Second, laboratory studies can also provide information on optimal treatment sequences. For example, recent laboratory studies have suggested that the EGFR inhibitor gefitinib might be more effective in combination with standard cytotoxic agents given as a highdose ‘pulse’ prior to cytotoxic agent compared with continuous, concurrent administration55; this novel schedule is now being tested in a clinical trial”(page 656). This helps to teach claims 23-27.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Huang WEE1 inhibitors for treating cancer by combining them with the Bcl-2 inhibitors taught by Jong and Pinchman because both types of inhibitors are used for the same purpose of treating cancer. "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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). One of ordinary skill in the art would have a reasonable expectation of success that combining two cancer treating agents together would produce a third cancer treating composition and one would be motivated to do so because they would be used for the same purpose. Additionally, one would be motivated to combine a WEE1 inhibitor with a Bcl-2 inhibitor because Jong teaches such a combination can lead to enhanced potency. It would have also been obvious to modify these references with Dancey because Dancey just teaches different ways to administer cancer combination therapies and since the references of Huang, Jong and Pinchman all teach cancer treatment it would have been obvious with a reasonable expectation of success to optimize the administration route for one of ordinary skill in the art. One would be motivated to optimize to get the best treatment response. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
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, 4-6, 8, 10, 19-27 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4, 5, 6, 7, 9, 18, and 20 of copending Application No. 18/389,654, over claims 1-5 and 7-21 of copending Application No. 18/743,544, over claims 1, 3, 4, 5, 7 9-13, 15-17, 20 and 23 of copending Application No. 18/554,951, over claims 38-40 of copending Application No. 18/004,628, over claims 1, 2, 7-16, 21, 22 and 26-31 of copending Application No. 18/743,595, over claims 1 and 6-24 of copending Application No. 18/793,337, over claims 1-5 and 11, 16-18, 23, 25, 27-36 of copending Application No. 17/757,483, over claims 18-19, 21, 32, 35-36, 38, 42, 44-45, 52 of copending Application No. 18/001,234, over claims 1, 4-12, 16, 21, 24, 28, 30, 31, 36-42, 44, 46, 48, 52-54 of copending Application No. 17/998,561, over claims 1-12 of copending Application No. 18/634,055, over claims 1-19 of copending Application No. 18/648,164, over claims 41-58 of copending Application No. 18/743,564, over claims 12, 15-20, 30, 36, 41, 44-47, 51-52, 59-65 of copending Application No. 19/045,327, over claims 1-9 and 11-22 of copending Application No. 19/079,930, over claims 1-50 of copending Application No. 19/201,446, over claims 1-60 of copending Application No. 19/201,378 in view of Huang (Huang et al., WO2019173082A1, 9/12/2019, previously provided) in view of Jong (Jong et al., “WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage”, Cancers 2019, 11, 1743, 11/7/2019, previously provided) further in view of Pinchman (Pinchman et al., WO2019139899A1, 7/18/2019, previously provided) further in view of Dancey (Dancey et al., Strategies for optimizing combinations of molecularly targeted anticancer agents, NATURE REVIEWS | DRUG DISCOVERY, VOLUME 5 | AUGUST 2006).
Application ‘654 claims(reference claim 2 and 18):
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Application ‘544 claims(reference claim 1):
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Application ‘951 claims(reference claim 1):
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Application ‘628 claims (reference claim 39 and 1):
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Application ‘595 claims(reference claim 1):
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Applications ‘337,’483, ‘234, ‘561, ‘055, ‘164, ‘564, ‘327, ‘930, ‘446, ‘378 all claim the instant compound A and cancer treatment or teach cancer treatment in the specification as the utility. A compound claim can be used to reject a method claim if the utility is disclosed in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1385 (CAFC 2010). See also MPEP § 804(II)(B)(2)(a).
This helps to teach claims 1, 4-6, 8, 10, 19-27.
Additionally, the other stereocenter would have been obvious. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (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). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
Applications ‘654, ‘544, ‘951, ‘628, ‘595, ‘337,’493, ‘234, ‘561, ‘055, ‘164, ‘564, ‘327, ‘930, ‘446, ‘378 do not teach the combination of Compound (A) with any Bcl-2 inhibitors (all claims), the specific routes of administration (claims 23-27) or some of the specific cancers (claims 5, 10, 21, 22).
The reference Huang has been discussed supra.
The reference Jong has been discussed supra.
The reference Pinchman has been discussed supra.
The reference Dancey has been discussed supra.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified ‘654, ‘544, ‘951, ‘628, ‘595, ‘337,’483, ‘234, ‘561, ‘055, ‘164, ‘564, ‘327, ‘930, ‘446, ‘378 WEE1 inhibitors for treating cancer by combining them with the Bcl-2 inhibitors taught by Jong and Pinchman and Huang because the inhibitors are used for the same purpose of treating cancer. "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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). One of ordinary skill in the art would have a reasonable expectation of success that combining two cancer treating agents together would produce a third cancer treating composition and one would be motivated to do so because they would be used for the same purpose. Additionally, one would be motivated to combine a WEE1 inhibitor with a Bcl-2 inhibitor because Jong teaches such a combination can lead to enhanced potency. It would have also been obvious to modify these references with Dancey because Dancey just teaches different ways to administer cancer combination therapies and since the references of Huang, Jong and Pinchman and the patent applications all teach cancer treatment it would have been obvious with a reasonable expectation of success to optimize the administration route for one of ordinary skill in the art. One would be motivated to optimize to get the best treatment response. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4-6, 8, 10, 19-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-20 of U.S. Patent No. 11261192 B2 in view of in view of Huang (Huang et al., WO2019173082A1, 9/12/2019, previously provided) in view of Jong (Jong et al., “WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage”, Cancers 2019, 11, 1743, 11/7/2019, previously provided) further in view of Pinchman (Pinchman et al., WO2019139899A1, 7/18/2019, previously provided) further in view of Dancey (Dancey et al., Strategies for optimizing combinations of molecularly targeted anticancer agents, NATURE REVIEWS | DRUG DISCOVERY, VOLUME 5 | AUGUST 2006).
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Patent ‘192 claims(reference claims 17 and 19):
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This helps to teach claims 1, 4-6, 8, 10, 19-27.
Patent ‘192 claims does not teach the combination of Compound (A) with any Bcl-2 inhibitors (all claims), the specific routes of administration (claims 23-27) or some of the specific cancers (claims 5, 10, 21, 22).
The reference Huang has been discussed supra.
The reference Jong has been discussed supra.
The reference Pinchman has been discussed supra.
The reference Dancey has been discussed supra.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Patent ‘192 WEE1 inhibitors also taught by (Huang) for treating cancer by combining them with the Bcl-2 inhibitors (such as venetoclax) taught by Jong and Pinchman because both types of inhibitors are used for the same purpose of treating cancer. "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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). One of ordinary skill in the art would have a reasonable expectation of success that combining two cancer treating agents together would produce a third cancer treating composition and one would be motivated to do so because they would be used for the same purpose. Additionally, one would be motivated to combine a WEE1 inhibitor with a Bcl-2 inhibitor such as venetoclax because Jong teaches such a combination can lead to enhanced potency. It would have also been obvious to modify these references with Dancey because Dancey just teaches different ways to administer cancer combination therapies and since the references of Huang, Jong and Pinchman and the patent ‘192 all teach cancer treatment it would have been obvious with a reasonable expectation of success to optimize the administration route for one of ordinary skill in the art. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
Response to Arguments
Applicant's arguments filed 10/17/2025 have been fully considered but they are not persuasive.
Applicants argue that there is no reason to select compound A or B or the specific cancers. This argument was not found persuasive because all compounds claimed in Huang including the instant compound were considered as WEE1 inhibitors and/or for cancer treatment and so are doing no more in the instant application than one of ordinary skill in the art would reasonably expect. Additionally, the reference Jong makes it obvious to select venetoclax as it recommends its combination with a WEE1 inhibitor. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989).
However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Applicants argue that the combination of compound (A) and navitoclax has literature that teaches away from this combination. This argument is not persuasive because the reference Jong still makes it obvious to combine venetoclax with compound A. Additionally, most drugs have undesirable side effects and are still used in many cases and since Jong teaches BCL inhibitors as obvious combination with WEE1 inhibitors it is still obvious to combine the two. Additionally, the specific reference mention was not found, it is assumed that the reference cited is a typo and was assumed to be the IDS reference from Wilson et al., 2010, this reference indicates Navitoclax should be further studied not abandoned and it safety further evaluated. Even if this is not the desired reference it supports the obviousness of using Navitoclax because it indicates at a later date than 2001 that Navitoclax is still being studied for it use as a potential therapeutic.
The applicant also argues unexpected results for the specific combinations. This argument is not persuasive because an affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). "A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference." In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). As the new evidence is not cited from a previously published source and not from the application and not in a declaration or affidavit it is not persuasive. Additionally, the cells used in the examples of the description of the present application were MV4-11 cells (corresponding to acute myeloid leukemia) were, while MOLT-4 cells (acute lymphocytic leukemia) were used as supplementary experimental data, and the method for the supplementary experiment is not disclosed in the examples of the description. Furthermore, although the specific compounds and the specific disease involved in the supplementary experimental data are mentioned in the description of the present application, the claims also describes various cancers (not tested). It is known in the art that different tumors vary in the pathogenesis and treatment mechanism, leading to differences in the efficacy medicaments. Thus, those skilled in the art cannot expect that different combinations of different compounds can achieve the same therapeutic effects on different cancers. Thus, the therapeutic effect of the combination of Compound A and navitoclax on the MOLT-4 cells (acute lymphocytic leukemia) that demonstrated by the supplementary experimental data is not commensurate in scope with the claims. Moreover, regarding the cancers defined in claim 1, the description of the present application only discloses a lung cancer and human myeloid monocytic leukemia. Thus, those skilled in the art cannot expect that the claimed combination can achieve effects similar to those in the examples of the description across all tumors (acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia) mentioned in the claims. Additionally, the claims are also not commensurate in scope with the claims because they are for any combination of concentrations while the unexpected results are at a specific combinations tested.
Conclusory statements that results were "unexpected," unsupported by objective factual evidence, were considered but were not found to be of substantial evidentiary value. Although an affidavit or declaration which states only conclusions may have some probative value, such an affidavit or declaration may have little weight when considered in light of all the evidence of record in the application. In re Brandstadter, 484 F.2d 1395, 179 USPQ 286 (CCPA 1973). The objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988). In the instant case, Applicants have not provided any evidence the unexpected results would be achieved in the same manner at any concentrations/amounts administered. The argument that it would also work in other amounts is a conclusory statement not supported by objective factual evidence.
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F .2d 731,741,218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).
MPEP 716.02(d) states “The nonobviousness of a broader claimed range can be supported by evidence based on unexpected results from testing a narrower range if one of ordinary skill in the art would be able to determine a trend in the exemplified data which would allow the artisan to reasonably extend the probative value thereof. In re Kollman, 595 F.2d 48, 201 USPQ 193 (CCPA 1979) (Claims directed to mixtures of an herbicide known as "FENAC" with a diphenyl ether herbicide in certain relative proportions were rejected as prima facie obvious. Applicant presented evidence alleging unexpected results testing three species of diphenyl ether herbicides over limited relative proportion ranges. The court held that the limited number of species exemplified did not provide an adequate basis for concluding that similar results would be obtained for the other diphenyl ether herbicides within the scope of the generic claims. Claims 6-8 recited a FENAC:diphenyl ether ratio of 1:1 to 4:1 for the three specific ethers tested. For two of the claimed ethers, unexpected results were demonstrated over a ratio of 16:1 to 2:1, and the effectiveness increased as the ratio approached the untested region of the claimed range. The court held these tests were commensurate in scope with the claims and supported the nonobviousness thereof. However, for a third ether, data was only provided over the range of 1:1 to 2:1 where the effectiveness decreased to the "expected level" as it approached the untested region. This evidence was not sufficient to overcome the obviousness rejection.); In re Lindner, 457 F.2d 506, 509, 173 USPQ 356, 359 (CCPA 1972) (Evidence of nonobviousness consisted of comparing a single composition within the broad scope of the claims with the prior art. The court did not find the evidence sufficient to rebut the prima facie case of obviousness because there was "no adequate basis for reasonably concluding that the great number and variety of compositions included in the claims would behave in the same manner as the tested composition.").”
The “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support”.
Finally, the combination of a BCL-2 inhibitor and a WEE1 inhibitor having enhanced activity is not unexpected in view of Jong. The reference Jong teaches “ We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i) or S63845 (MCL-li) enhanced sensitivity in a cell-specific manner. ” (page 1).
Double Patenting
Since the applicant merely asks the examiner to withdraw the provisional double patenting rejections on several applications due to the filing dates no persuasive argument has been made since there are other remaining rejections.
The arguments made against individual double patenting rejections have been discussed above.
The applicant argues that application ‘483 does not disclose all the elements of the instant application however, this is not persuasive because the remaining elements can be found in the prior art cited.
Conclusion
Claims 1, 4-6, 8, 10, 19-27 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/A.A.S./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627