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 .
Election/Restrictions
Applicant’s election without traverse of the following species:
Compound 1 having the structure of:
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as the elected compound species of formula (I);
glioblastoma (brain cancer) as the elected cancer species; and
EGFR inhibitor as the elected second therapeutic agent species;
are maintained.
Claims 15 and 21 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected specie, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 21, 2024.
Response to Amendment
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on October 23, 2025, wherein claims 1, 11-12, 16 and 19 are amended; claims 2-10, 15, 17 and 21 are unchanged; claims 13-14, 18 and 20 are cancelled.
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-12, 15-17, 19 and 21 are pending. Claims 15 and 21 remain withdrawn.
Claims 1-12, 16-17, and 19 are under examination in accordance with the elected species.
Priority
The instant application 17/426,296 filed on July 28, 2021 is a 371 of PCT/US2020/015398 filed on January 28, 2020, which claims priority to, and the benefits of U.S. Provisional Application No. 62/798,220 filed on January 29, 2019.
Claim Interpretation
The claimed terms “treating” and “treat”, when construed in light of page 13, line 7-18 of the specification as shown below:
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, is taken to include inhibiting, reliving and preventing the disease, disorder, or condition .
Action Summary
Applicant’s amendment to the claims overcome each and every objection previously sets
forth in the Non-Final Office Action mailed on July 29, 2025.
Claims 1-14, 16-17, and 19-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating glioblastoma associated with CDK4 and/or CDK6 activity to the extent that treating does not include preventing, does not reasonably provide enablement for treating full scope of brain cancer or brain metastasis of another cancer and preventing the full scope of brain metastasis in a subject with another cancer are maintained, but revisited and modified in view of the claim amendments.
Claim 11 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention are withdrawn in view of the claim amendments.
Claims 1-14, 16-17, and 19-20 rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives are withdrawn in view of the claim amendments.
Claims 1-14, 16-17, and 19-20 rejected under 35 U.S.C. 103 as being unpatentable Greco et al. (WO 2016/014904 A1; cited in the previous Office Action mailed on June 14, 2024) in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371), as evidenced by Comşa et al. (Anticancer Res, 2015. Vol. 35(6): 3147-3154) are maintained, but revisited and modified in view of the claim amendments.
Claims 1-14, 16-17, 19-20 and 23-27 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 14-18, and 20-27 of U.S. Patent No. 9,878,994 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) are maintained, but revisited and modified in view of the claim amendments.
Claims 1-14, 16-17, and 19-20 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-12 and 16 of U.S. Patent No. 10,239,864 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) are maintained, but revisited and modified in view of the claim amendments.
Claims 1-14, 16-17, 19-20 and 23-27 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13-18 of U.S. Patent No. 11,352,341 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) are maintained, but revisited and modified in view of the claim amendments.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12, 16-17, and 19 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating glioblastoma associated with CDK4 and/or CDK6 activity to the extent that treating does not include preventing, does not reasonably provide enablement for treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer to the extent that treating includes preventing. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Attention is directed to in re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary. All of the Wands factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
Claim 1 recites “[a] method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer, comprising administering to the subject in need thereof, a therapeutically effective amount of a composition comprising a compound of formula (I)…or a pharmaceutically acceptable salt, solvate, or prodrug thereof; wherein the method treats glioblastoma associated with CDK4 and/or CDK6 activity in said subject with another cancer”.
Claim 12 recites “[a] method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer, comprising administering to the subject in need thereof, a therapeutically effective amount of a composition comprising a compound of formula:
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or a pharmaceutically acceptable salt, solvate, or prodrug thereof; wherein the method treats glioblastoma associated with CDK4 and/or CDK6 activity in said subject with another cancer”.
Claim 19 recites “[a] method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer, associated with CDK4 and/or CDK6 activity, comprising administering to the subject in need thereof a compound of the formula:
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or a pharmaceutically acceptable salt, solvate, or prodrug thereof; wherein the method treats glioblastoma associated with CDK4 and/or CDK6 activity in said subject with another cancer”.
The claimed term “treating” when construed in light of page 13, line 7-18 of the specification shown below:
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, is taken to include inhibiting, reliving and preventing the disease, disorder, or condition, in this case, glioblastoma.
Therefore, the breadth of the claims include a subject with glioblastoma and “another cancer” with the intent to inhibit or relieve said cancer(s), and a subject without glioblastoma but with another cancer with the intent to prevent.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
As discussed above, the claimed invention is drawn to a method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer the extent that the claimed term “treating” includes preventing.
According to Arsenijevic et al. (Cancers (Basel), 2023. Vol. 15(3): 968; cited in the previous Office Action mailed on 7/29/2025), the effects of CDK4/6 inhibitor monotherapy on cholangiocarcinoma (CCA) cell lines were reported in a limited number of studies with conflicting results. Arsenijevic et al. further teaches Sitthihumcharee et al. showed that in 11 of 15 CCA cell lines tested, exposure of cells to palbociclib leads to cell cycle arrest and senescence. It has been further shown that those cell sensitive to palbociclib express retinoblastoma (RB) protein, and that the loss of RB conferred palbociclib resistance. Arsenijevic et al. further teaches the sensitivity of CCA to CDK4/6 inhibition has been associated with the activated KRAS signature; however, in another study, no inhibitory effect of palbociclib was observed on the proliferation of several CCA cell lines (see e.g., p. 7, “CDK4/6 Inhibitor Monotherapy in Preclinical Models of CCA and PDAC” section, 1st-2nd paragraph). The cited reference demonstrates the state of the art with regard to administering a CDK4/6 inhibitor for preventing glioblastoma in a subject with another cancer, in this case, a subject with cholangiocarcinoma, is still underdeveloped due the unpredictability of cancer cell response.
According to Fassl et al. (Cancer Cell, 2020. Vol. 37(3): 265-267), several studies documented that co-administration of CDK4/6 inhibitors antagonized the therapeutic effects of various classes of chemotherapeutic compounds that act during DNA synthesis (doxorubicin, gemcitabine, methotrexate, and mercaptopurine) or during mitosis (taxanes) (see e.g., p. 265, right column, 1st paragraph). Fassl et al. further teaches administration of CDK4/6 inhibitors prior to taxanes inhibited tumor cell proliferation and mitigate the therapeutic effect of the latter (see e.g., p. 266, left column, 2nd paragraph). Each of these findings demonstrate the state of the art with regard to combining a CDK4/6 inhibitor with any second therapeutic agent for treating glioblastoma in a subject with another cancer is still underdeveloped, because CDK4/6 inhibitors can antagonize the therapeutic effects of various classes of chemotherapeutic compounds.
At the time the application was filed, the relative skill of those in the art tasked with identifying compounds exerting anti-cancer activity would have been high, as the ordinarily skilled artisan would have had an experience with screening techniques, such as target-based screening or phenotypic-based screening, as evidenced by Coussens et al. (Pharmacological reviews, 2017. Vol. 69, 4: 479–496).
Even though the claimed compound of formula (I) may play a role in treating glioblastoma associated with CDK4 and/or CDK6 activity by inhibiting CDK4/6, it is uncertain whether administering any therapeutically effective amount of a compound of formula (I) or a composition comprising any therapeutically effective amount of said compound can successfully treat glioblastoma in a subject with another cancer to the extent that treatment includes prevention for the reasons set forth herein. In addition, it is also uncertain whether administering any therapeutically effective amount of the claimed composition with any second therapeutic agent can successfully treat glioblastoma in a subject with another cancer to the extent that treatment includes prevention for the reasons set forth herein
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the claimed invention. In the present case, Example 1 of instant specification discloses MG-Luc intracranially implanted mice were treated with Compound 1, 100 mg/kg, PO, QD x 21 (Days 21-41) in Group 3; and said mice were treated with temozolomide, 6 mg/kg, PO, QD x 5 (Days 21-25) + Compound 1, 100 mg/kg, PO, QD x21 (Daus 21-41) in Group 5 (see e.g., Example 1A-1C, Group 3 and 5). Even though the efficacy data (In vivo Bioluminescence Imaging) of Group 5 is illustrated in Figure 2, the efficacy results for Group 3 has not been disclosed therein. Please note the MG-Luc intracranially implanted mice referred therein is an orthotopic U87MG-luc human glioblastoma xenograft model (see e.g., p. 13, line 19-21 of the specification). Please also note the Compound 1 of instant specification is a compound having the structure of:
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. It is noted that the biological activities of Compound 1 with respect to preventing glioblastoma in a subject with another cancer has not been disclosed. In addition, the specification only tested the Compound 1 against U87MG-luc human glioblastoma cell, and fails to disclose its activities against glioblastoma in a subject with another cancer as encompassed by the instant claims. Furthermore, the specification only combines Compound 1 with temozolomide, and that does not include any other species of second therapeutic agent. Thus, one of the relative skill in the art armed with screening techniques could not reasonably predict which subject species encompassed by the claims (embraced by the claimed term “ a subject with another cancer”) administered with any amount of the claimed compound of formula (I) or a composition comprising said compound with or without any second therapeutic agent would successfully prevent or treat glioblastoma based on the limited disclosure provided; therefore, it would require an undue experimentation as it is highly unpredictable that the administration of the claimed compound of formula (I), the claimed composition comprising said compound, and the claimed combination would, in fact, be usable across the full scope of treating glioblastoma in a subject with another cancer to the extent that treating includes preventing.
Accordingly, to the extent that treating includes preventing, the method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer is not enabled by the instant specification. Accordingly, claims 2-11 and 16-17 are rejected based on their dependency on a rejected base claim. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Response to Arguments
Applicant's arguments filed on October 23, 2025 with respect to the rejection of claims 1-14, 16-17, and 19-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, have been fully considered but they are not persuasive for the reasons set forth below.
In the present case, Applicant amends independent claims 1, 12 and 19 from the recitation of “treating a brain cancer or brain metastasis of another cancer, or preventing metastasis in a subject with another cancer” to “treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer” in the preamble; and further amends the limitation of “wherein the method treats brain cancer or brain metastasis of another cancer, or preventing metastasis in a subject with another cancer” to the limitation of “wherein the method treats glioblastoma associated with CDK4 and/or CDK6 activity in said subject with another cancer”. The claim amendment changes the scope of the claims and that necessitated a modification of the rejection on the record.
In Summary, applicant argues the claim amendment overcomes the previous rejection.
In response, applicant’s argument is not found persuasive, because the claimed term “treating” still encompass preventing glioblastoma as the brain cancer associated with CDK4 and/or CDK6 activity in a subject with another cancer, and that is not enabled by the instant specification. Specifically, the state of the art with respect to administering a single CDK4/6 inhibitor for the full scope of “treating” glioblastoma in a subject with each and every species of “another cancer” is still underdeveloped, because the cell-based assay presented by Arsenijevic et al. demonstrated cholangiocarcinoma cell lines with the loss of retinoblastoma protein are resistant to CDK4/6 inhibitor palbociclib, and some studies showed it has no inhibitory effect against the proliferation of several CCA cell lines (see rejection above). In other words, the cited reference demonstrates a single CDK4/6 inhibitor does not treat “another cancer”; and therefore, the use of CDK4/6 inhibitor for preventing the full scope of glioblastoma in a subject with another cancer, including glioblastoma metastasis from cholangiocarcinoma as another cancer, is still underdeveloped due the unpredictability of cancer cell response.
Given that the amendments change the scope of the claims, the rejection on the record has been revisited and modified in view of the claim amendments for the reasons set forth herein.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12, 16-17, and 19 remain rejected under 35 U.S.C. 103 as being unpatentable Greco et al. (WO 2016/014904 A1) in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371), as evidenced by Comşa et al. (Anticancer Res, 2015. Vol. 35(6): 3147-3154).
Greco et al. teaches a method of treating a disease, disorder, or condition mediated through at least one of cyclin-dependent kinases (CDK), in particular CDK4, CDK6, or a combination thereof, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug thereof; or administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising the compound of formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and one or more pharmaceutically acceptable excipients, such as adjuvants, diluents, and/or carriers (see e.g., page 2, line 24 to page 3, line 9); wherein said disease or disorder is cancer selected from the group consisting of, inter alia, breast cancer and glioblastoma (see e.g., claims 15, 17 and 28; p. 3, line 10-17). Greco et al. further teaches the compound of formula (I), N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-amine, having the structure shown as follows:
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(see e.g., page 25, table 1, Example 1; referred to herein as “Compound 1”) is a CDK4/6 inhibitor with an IC50 value of <1.0 nM in both CDK4 and CDK6 assays; and an IC50 value of < 2 µM against MCF7 human tumor cells (see e.g., p. 30, line 20-21). Please note the Compound 1 of Greco et al. is the elected compound species of formula (I), which is a compound of instant formula (I):
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, wherein R1 is ethyl (i.e., reads on C1-C6 alkyl); R2 is isopropyl (i.e., reads on C1-C6 alkyl); R3 is methyl (i.e., reads on C1-C6 alkyl); R4 is hydrogen; and R5 is fluoro. Please further note the MCF7 human tumor cells taught by Greco et al. is a breast cancer cell line, as evidenced by Comşa et al. (see e.g., abstract). Greco et al. further teaches the compound may be administered to a subject in need thereof in combination with administration of a second therapeutic agent, and the second therapeutic agent is, inter alia, an epidermal growth factor receptor (EGFR) inhibitor (see e.g., page 7, line 20-26). Greco et al. further teaches the biochemical and MCF7 cell-based data for the three reported CDK4/6 inhibitors 32, 33 and 34 are shown below:
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(see e.g., Table 2).
Greco et al. does not expressly teach treating the elected brain cancer, in this case, glioblastoma in a subject with another cancer.
Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4 and CDK6 kinase inhibitor has potential for treating primary central nervous system tumors such as glioblastoma and some peripheral tumors with high incidence of brain metastases (see e.g., abstract; p. 1367, right column, “Discussion” section, 1st paragraph). Raub et al. further teaches brain metastases can develop from a variety of different primary tumors, but the frequency is highest for lung, breast, and melanoma cancers (see e.g., p. 1360, right column, “Introduction” section). Raub et al. further teaches orally dosed abemaciclib significantly increased survival in a rat orthotopic glioblastoma U87MG xenograft model compared with vehicle-treated animals, and efficacy coincide with a dose-dependent increase in unbound plasma and brain exposures in excess of the CDK4 and CDK6 Ki values (see e.g., abstract; p. 1366, “Efficacy in a Brain Tumor Model” section). Raub et al. further teaches abemaciclib is a CDK4 and CDK6 inhibitor having the chemical structure of:
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; and said compound was previously shown to have in vitro and in vivo antitumor activity against subcutaneous human xenograft tumors of diverse histologic origin, including lung, breast and melanoma representing human cancers that frequently metastasize to the brain (see e.g., abstract; Table 1; p. 1366, “Efficacy in a Brain Tumor Model” section).
Even though Greco et al. does not expressly teach the treatment of glioblastoma in a subject with another cancer, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Greco et al. by selecting Compound 1 as the compound of formula (I) for treating glioblastoma in a subject with another cancer, as taught by Raub et al. One would have been motivated to do so, because Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4/6 kinase inhibitor has potential for treating glioblastoma and some peripheral tumors with high incidence of brain metastases, including breast cancer, by testing abemaciclib against glioblastoma cell line U87MG; and Greco et al. teaches Compound 1 is a CDK4/6 inhibitor useful for treating cancers mediated by CDK4 and/or CDK6, including glioblastoma and breast cancer, with an IC50 value of <1.0 nM in both CDK4 and CDK6 assays, and an IC50 value of < 2 µM against breast cancer cell line MCF7, which is the same as the CDK4/6 inhibitor 33 of Greco et al. Please note the CDK4/6 inhibitor 33 of Greco et al. is structurally equivalent to abemaciclib of Raub et al. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the Compound 1 of Greco et al. is a CDK4/6 inhibitor useful for treating glioblastoma and breast cancer, and therefore by administering said compound in a therapeutically effective amount would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “a composition comprising a compound of formula (I)” in claims 1 and 12, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the method as set forth above by substituting the compound 1 of Greco et al. with a pharmaceutical composition comprising said compound 1, as taught by Greco et al. One would have been motivated to do so, because Greco et al. teaches a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and one or more pharmaceutically acceptable excipients is also useful for treating cancer mediated by CDK4 and/or CDK6, including glioblastoma and breast cancer. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the pharmaceutical composition comprising Compound 1 of Greco et al. would have exerted the same or substantially similar CDK4/6 inhibiting effect as the Compound 1 alone, and therefore, administering said pharmaceutical composition in a therapeutically effective amount would successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “wherein the administering is in conjunction with administration to the subject of a second therapeutic agent” in claim 16, and “the second therapeutic agent is … an EGFR inhibitor” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method as set forth above to conjunctively administer an EGFR inhibitor as the second therapeutic agent as taught by Greco et al. One would have been motivated to do so, because Greco et al. teaches Compound 1 may be administered to a subject in need thereof in combination with administration of a second therapeutic agent, including EGFR inhibitor. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering an EGFR inhibitor in conjunction with the Compound 1 of Greco et al. in the method as set forth above would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on October 23, 2025 with respect to the rejection of claims 1-14, 16-17, and 19-20 under 35 U.S.C. 103 as being unpatentable Greco et al. (WO 2016/014904 A1) in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371), as evidenced by Comşa et al. (Anticancer Res, 2015. Vol. 35(6): 3147-3154) have been fully considered but they are not persuasive for the reasons set forth below.
In Summary, Applicant argues Greco et al. does not teach or suggest treating glioblastoma in a subject with another cancer. Applicant further argues the combination of Greco '904 and Raub et al. does not disclose or suggest use of the compound of Formula I in a method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer. Applicant further argues Raub et al. generally discloses that abemaciclib and palbociclib were effective CDK4 and CDK6 inhibitors, but does not disclose Formula I may be used in a method of treating glioblastoma associated with CDK4 and/or CDK6 activity in a subject with another cancer.
In response, Applicant’s argument is not found persuasive. The rejection on the record is form on the basis that one would have a reasonable expectation of success to arrive at the claimed invention by modify the method of Greco et al. for treating a subject with glioblastoma and another cancer in view of Raub et al. and that is a subject with another cancer. In this case, Greco et al. clearly teaches a compound having the structure of:
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(referred to herein as “Compound 1”) is a compound of formula (I) and a CDK4/6 inhibitor that is useful for treating cancer mediated through CDK4 and/or CDK6 including glioblastoma and breast cancer (see e.g., Example 1; claims 1, 15-18); and has activity against MCF7 cell (see e.g., page 31, line17-18), which is a breast cancer cell line as evidenced by Comşa et al. (see e.g., abstract). Raub et al. teaches CDK4/6 inhibitor abemaciclib, which is equivalent to compound 33 of Greco et al., significantly increased survival in a rat orthotopic glioblastoma U87MG xenograft model compared with vehicle-treated animals (see e.g., abstract; p. 1366, “Efficacy in a Brain Tumor Model” section); and further teaches CDK4/6 inhibitor has potential for treating glioblastoma and some peripheral tumors with high incidence of brain metastases, including breast cancer (see e.g., p. 1361, left column, line 21-24; p. 1367, right column, line 14-18). One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound 1 of Greco et al. taught to be useful for treating glioblastoma and breast cancer has very close structural similarities to abemaciclib of Raub et al., and therefore, said compound would reasonably expected to exert CDK4/6 inhibiting effect for treating glioblastoma and another cancer, such as breast cancer that has high incidence of brain metastases, in a subject by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Therefore, the rejection on the record has been revisited and modified in view of the amendments for the reasons set forth herein.
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 1-12, 16-17, and 19 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 14-18, and 20-27 of U.S. Patent No. 9,878,994 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371).
The claims of reference patent are drawn to a method of relieving, ameliorating, or modulating a disease, disorder, or condition mediated through activity of at least one CDK, including CDK4 and/or CDK6, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of formula (I) according to claim 1, a pharmaceutically acceptable salt, solvate, or prodrug thereof; wherein the disease or disorder is cancer selected from, inter alia, breast cancer, glioblastoma, and complications thereof (see claims 15-18 and 25-27); in combination with administering to said subject a second therapeutic agent (see claim 20); wherein said therapeutic agent is, inter alia, EGFR inhibitor (see claim 21); wherein the compound of claim 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof is selected from, inter alia, Compound No. 1 that has the structure of:
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(see e.g., claims 1 and 12). The claims of reference patent further teaches a pharmaceutical composition comprising the compound of claim 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and one or more pharmaceutically acceptable adjuvants, diluents, and/or carriers (see claim 14). The claims of reference patent further teaches ab effective amount of the compound of claim 1 can inhibit CDK4, CDK6, or a combination thereof; and inhibit cell proliferation (see claims 22-24).
The claims of reference patent does not expressly teach treating glioblastoma in a subject with another cancer.
Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4 and CDK6 kinase inhibitor has potential for treating primary central nervous system tumors such as glioblastoma and some peripheral tumors with high incidence of brain metastases (see e.g., abstract; p. 1367, right column, “Discussion” section, 1st paragraph). Raub et al. further teaches brain metastases can develop from a variety of different primary tumors, but the frequency is highest for lung, breast, and melanoma cancers (see e.g., p. 1360, right column, “Introduction” section). Raub et al. further teaches orally dosed abemaciclib significantly increased survival in a rat orthotopic glioblastoma U87MG xenograft model compared with vehicle-treated animals, and efficacy coincide with a dose-dependent increase in unbound plasma and brain exposures in excess of the CDK4 and CDK6 Ki values (see e.g., abstract; p. 1366, “Efficacy in a Brain Tumor Model” section). Raub et al. further teaches abemaciclib is a CDK4 and CDK6 inhibitor having the chemical structure of:
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; and said compound was previously shown to have in vitro and in vivo antitumor activity against subcutaneous human xenograft tumors of diverse histologic origin, including lung, breast and melanoma representing human cancers that frequently metastasize to the brain (see e.g., abstract; Table 1; p. 1366, “Efficacy in a Brain Tumor Model” section).
Even though the reference patent does not expressly teach the treatment of glioblastoma in a subject with another cancer, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference patent to selectively choose to administer Compound No. 1 of reference patent for treating glioblastoma in a subject with another cancer. One would have been motivated to do so, because Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4/6 kinase inhibitor has potential for treating glioblastoma and some peripheral tumors with high incidence of brain metastases, including breast cancer, by testing abemaciclib against glioblastoma cell line U87MG; and the reference patent teaches the compound of formula (I), including Compound No. 1 of reference patent, can treat breast cancer and glioblastoma as the cancer mediated through activity of CDKs by inhibiting CDK4 and/or CDK6. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the Compound No. 1 of reference patent is a CDK4/6 inhibitor useful for treating glioblastoma and breast cancer, and therefore by administering said compound in a therapeutically effective amount would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “a composition comprising a compound of formula (I)” in claims 1 and 12, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the method as set forth above by substituting the Compound No. 1 of reference patent with a pharmaceutical composition comprising said compound. One would have been motivated to do so, because the reference patent teaches a pharmaceutical composition comprising the compound of formula (I), or a pharmaceutically acceptable salt thereof. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the pharmaceutical composition comprising the Compound No. 1 of the reference patent would have exerted the same or substantially similar CDK4/6 inhibiting effect as the Compound No. 1 alone, and therefore, administering said pharmaceutical composition in a therapeutically effective amount would successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “wherein the administering is in conjunction with administration to the subject a second therapeutic agent” in claim 16, and “the second therapeutic agent is … an EGFR inhibitor” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method as set forth above to conjunctively administer an EGFR inhibitor taught by the reference patent. One would have been motivated to do so, because reference patent teaches an EGFR inhibitor can be combine with the compound of formula (I) to treat the same cancer species mediated through CDKs, including CDK4 and/or CDK6, including glioblastoma and breast cancer. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering administer an EGFR inhibitor in conjunction with the Compound No. 1 of the reference patent would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on October 23, 2025 with respect to the rejection of claims 1-14, 16-17, 19-20 and 23-27 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 14-18, and 20-27 of U.S. Patent No. 9,878,994 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) have been fully considered but they are not persuasive.
Applicant noted that appropriate action will be taken until the identification of allowable subject
matter. Given that applicant did not put forth any arguments against the nonstatutory double patenting
rejection noted above, the rejection has been revisited and modified in light of the claim amendments.
Claims 1-12, 16-17, and 19 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-12 and 16 of U.S. Patent No. 10,239,864 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371).
The claims of reference patent are drawn to a method of relieving, ameliorating, or modulating a disease, disorder, or condition mediated through activity of at least one CDK, including CDK4 and/or CDK6, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of formula (Ia) according to claim 1, a pharmaceutically acceptable salt or composition thereof; wherein the disease or disorder is cancer selected from, inter alia, breast cancer, glioblastoma, and complications thereof (see claims 8-11). The claims of reference patent further teaches the compound of formula (Ia)
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or pharmaceutically acceptable salt thereof, wherein: R1 is ethyl; R2 is isopropyl; R3 is methyl; R4 is hydrogen; and R5 is fluoro (see e.g., claims 1-3 and 12). Please note the compound of formula (Ia) as set forth in claim 12 of the reference patent, wherein R1 is ethyl, R4 is hydrogen, and R5 is fluoro, is the elected compound species of formula (I) instantly claimed. The claims of reference patent further teaches the compound of formula (Ia) or composition thereof is also useful for inhibiting a cyclin-dependent kinase (CDK) selected from the group consisting of CDK4 , CDK6, and a combination thereof.
The claims of reference patent does not expressly teach treating glioblastoma in a subject with another cancer.
Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4 and CDK6 kinase inhibitor has potential for treating primary central nervous system tumors such as glioblastoma and some peripheral tumors with high incidence of brain metastases (see e.g., abstract; p. 1367, right column, “Discussion” section, 1st paragraph). Raub et al. further teaches brain metastases can develop from a variety of different primary tumors, but the frequency is highest for lung, breast, and melanoma cancers (see e.g., p. 1360, right column, “Introduction” section). Raub et al. further teaches orally dosed abemaciclib significantly increased survival in a rat orthotopic glioblastoma U87MG xenograft model compared with vehicle-treated animals, and efficacy coincide with a dose-dependent increase in unbound plasma and brain exposures in excess of the CDK4 and CDK6 Ki values (see e.g., abstract; p. 1366, “Efficacy in a Brain Tumor Model” section). Raub et al. further teaches abemaciclib is a CDK4 and CDK6 inhibitor having the chemical structure of:
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; and said compound was previously shown to have in vitro and in vivo antitumor activity against subcutaneous human xenograft tumors of diverse histologic origin, including lung, breast and melanoma representing human cancers that frequently metastasize to the brain (see e.g., abstract; Table 1; p. 1366, “Efficacy in a Brain Tumor Model” section).
Even though the reference patent does not expressly teach the treatment of glioblastoma in a subject with another cancer, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference patent to selectively choose to administer compound of formula (Ia) as set forth in claim 12 for treating glioblastoma in a subject with another cancer. One would have been motivated to do so, because Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4/6 kinase inhibitor has potential for treating glioblastoma and some peripheral tumors with high incidence of brain metastases, including breast cancer, by testing abemaciclib against glioblastoma cell line U87MG; and the reference patent teaches the compound of formula (Ia), including the compound species of formula (Ia) as set forth in claim 12, can treat breast cancer and glioblastoma as the cancer mediated through activity of CDKs by inhibiting CDK4 and/or CDK6. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound of formula (Ia) as set forth in claim 12 of the reference patent is a CDK4/6 inhibitor useful for treating glioblastoma and breast cancer, and therefore by administering said compound in a therapeutically effective amount would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “a composition comprising a compound of formula (I)” in claims 1 and 12, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the method as set forth above by substituting the compound of formula (Ia) as set forth in claim 12 of reference patent with a pharmaceutical composition comprising said compound. One would have been motivated to do so, because the reference patent teaches composition comprising the compound of formula (I), or a pharmaceutically acceptable salt thereof can also treat cancer mediated by CDK4 and/or CDK6, including glioblastoma and breast cancer. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the composition comprising the compound of formula (Ia) as set forth in claim 12 of the reference patent would have exerted the same or substantially similar CDK4/6 inhibiting effect as the compound of formula (Ia) alone, and therefore, administering said composition in a therapeutically effective amount would successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “wherein the administering is in conjunction with administration to the subject a second therapeutic agent” in claim 16, and “the second therapeutic agent is … a different CDK inhibitor” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method as set forth above to conjunctively administer a different compound species of formula (Ia) taught by the reference patent as the second therapeutic agent. One would have been motivated to do so, because reference patent teaches other compound species of formula (Ia) that can treat the same cancer species mediated through CDKs, including CDK4 and/or CDK6, including glioblastoma and breast cancer. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering another compound species of formula (Ia) in conjunction with the compound of formula (Ia) as set forth in claim 12 would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway. Please note the other compound species of formula (Ia) of the reference patent renders obvious the “different CDK inhibitor” instantly claimed.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on October 23, 2025 with respect to the rejection of claims 1-14, 16-17, and 19-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-12 and 16 of U.S. Patent No. 10,239,864 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) have been fully considered but they are not persuasive.
Applicant noted that appropriate action will be taken until the identification of allowable subject matter. Given that applicant did not put forth any arguments against the nonstatutory double patenting rejection noted above, the rejection has been revisited and modified in light of the claim amendments.
Claims 1-12, 16-17, and 19 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13-18 of U.S. Patent No. 11,352,341 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371).
The claims of reference patent are drawn to a method of relieving, ameliorating, or modulating a disease, disorder, or condition mediated through activity of at least one CDK, including CDK4 and/or CDK6, the method comprising administering to a subject in need thereof a therapeutically effective amount of the compound of formula (I) as set forth in claim 1; wherein the disease or disorder is cancer selected from, inter alia, breast cancer and glioblastoma; in combination with administering to said subject a second therapeutic agent that is, inter alia, EGFR inhibitor (see claims 14-18). The claims of reference patent further teach the compound of formula (I)
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is selected from, inter alia, Example 16 having the structure of:
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(see claims 1 and 13). Please note said Example 16 is a prodrug of the compound of formula (I) according to page 9, line 13-26 of the specification to include compound of formula (I) having an acyl group at R1. The claims of reference patent further teach a pharmaceutical composition comprising the compound of claim 1 or pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable adjuvants, diluents, and/or carriers (see claim 14).
The claims of reference patent do not expressly teach treating glioblastoma in a subject with another cancer.
Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4 and CDK6 kinase inhibitor has potential for treating primary central nervous system tumors such as glioblastoma and some peripheral tumors with high incidence of brain metastases (see e.g., abstract; p. 1367, right column, “Discussion” section, 1st paragraph). Raub et al. further teaches brain metastases can develop from a variety of different primary tumors, but the frequency is highest for lung, breast, and melanoma cancers (see e.g., p. 1360, right column, “Introduction” section). Raub et al. further teaches orally dosed abemaciclib significantly increased survival in a rat orthotopic glioblastoma U87MG xenograft model compared with vehicle-treated animals, and efficacy coincide with a dose-dependent increase in unbound plasma and brain exposures in excess of the CDK4 and CDK6 Ki values (see e.g., abstract; p. 1366, “Efficacy in a Brain Tumor Model” section). Raub et al. further teaches abemaciclib is a CDK4 and CDK6 inhibitor having the chemical structure of:
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; and said compound was previously shown to have in vitro and in vivo antitumor activity against subcutaneous human xenograft tumors of diverse histologic origin, including lung, breast and melanoma representing human cancers that frequently metastasize to the brain (see e.g., abstract; Table 1; p. 1366, “Efficacy in a Brain Tumor Model” section).
Even though the reference patent does not expressly teach the treatment of glioblastoma in a subject with another cancer, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference patent to selectively choose to administer Compound Example 16 of reference patent for treating glioblastoma in a subject with another cancer. One would have been motivated to do so, because Raub et al. teaches targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway using a potent CDK4/6 kinase inhibitor has potential for treating glioblastoma and some peripheral tumors with high incidence of brain metastases, including breast cancer, by testing abemaciclib against glioblastoma cell line U87MG; and the reference patent teaches the compound of formula (I), including Compound Example 16 of reference patent, can treat breast cancer and glioblastoma as the disease mediated through activity of CDK4 and/or CDK6. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the Compound Example 16 of reference patent is useful for treating glioblastoma and breast cancer as the disease mediated by CDK4 and/or CDK6, and therefore by administering said compound in a therapeutically effective amount would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “a composition comprising a compound of formula (I)” in claims 1 and 12, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the method as set forth above by substituting the Compound Example 16 of reference patent with a pharmaceutical composition comprising said compound. One would have been motivated to do so, because the reference patent teaches a pharmaceutical composition comprising the compound of formula (I), or a pharmaceutically acceptable salt thereof. One of ordinary skill in the art would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the pharmaceutical composition comprising the Compound Example 16 of the reference patent would have exerted the same or substantially similar effect on CDK4 and/or CDK6 as the Compound Example 16 alone, and therefore, administering said pharmaceutical composition in a therapeutically effective amount would successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Regarding “wherein the administering is in conjunction with administration to the subject a second therapeutic agent” in claim 16, and “the second therapeutic agent is … an EGFR inhibitor” in claim 17, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method as set forth above to conjunctively administer an EGFR inhibitor taught by the reference patent. One would have been motivated to do so, because reference patent teaches an EGFR inhibitor can be combine with the compound of formula (I) to treat the same cancer species mediated through CDK4 and/or CDK6, including glioblastoma and breast cancer. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by administering administer an EGFR inhibitor in conjunction with the Compound Example 16 of the reference patent would have successfully treat glioblastoma in a subject with another cancer by targeting the CDK4/CDK6-cyclin D1-Rb-p16/ink4a pathway.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on October 23, 2025 with respect to the rejection of claims 1-14, 16-17, 19-20 and 23-27 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13-18 of U.S. Patent No. 11,352,341 B2 in view of Raub et al. (Drug Metab Dispos, 2015. Vol. 43(9): 1360-1371) have been fully considered but they are not persuasive.
Applicant noted that appropriate action will be taken until the identification of allowable subject matter. Given that applicant did not put forth any arguments against the nonstatutory double patenting rejection noted above, the rejection has been revisited and modified in light of the claim amendments.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628