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 .
Current Status of 18/549,778
This Office Action is responsive to the claims of 09/08/2023. Claims 9, 12-13, and 16-29 are pending in the application and have been considered on the merits.
Priority
The instant application is a national stage entry of PCT/CN2022/079924, international filing date 03/09/2022, which claims priority to Chinese patent application CN202110263595.X, filed 03/10/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/18/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because the figures are grainy and difficult to read. The axis labels of all figures are illegible as are the numbers within the correlation profiles of FIG 3. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: A method of treating glioma using Wee1 kinase inhibitor 6-(2,6-dichlorophenyl)-2-((3-fluoro-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one. This suggestion aligns the invention with the statutory category of invention and narrows the scope of the invention commensurate with the examples of the disclosure.
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 9, 12, and 16-22 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 a method of treating diffuse midline glioma, childhood diffuse pontine glioma, or midline glioma in an individual with a H3K27M mutation in the cancer cells, comprising administering an effective amount of 6-(2,6-dichlorophenyl)-2-((3-fluoro-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one, herein referenced as compound A, does not reasonably provide enablement for preventing any type of cancer bearing this mutation, nor does it provide enablement for treating cancers other than those listed above using any Wee1 inhibitor. 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.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating/preventing a cancer in an individual having a H3K27M mutation in the cancer cells by administering any Wee1 kinase inhibitor. Preventing cancer would require identifying patients who will acquire the disease before the disease occurs. This would require extensive and potentially open-ended clinical research on healthy subjects. The claims taken together with the specification imply that the method encompasses the treatment and prevention of any cancer bearing H3K27M mutations through the administration of any Wee1 kinase inhibitor. Thus, the scope of the claims is extremely broad.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the art is that no general procedure is art-recognized for determining which patient generally will suffer from cancer before the fact. The state of the art is that cancer is not preventable (Tomasetti, Cristian, and Bert Vogelstein. “Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.” Science (New York, N.Y.) vol. 347,6217 (2015): 78-81. doi:10.1126/science.1260825).
Currently, Wee1 kinase inhibitors (such as, adavosertib/AZD1775) are being developed across the field of oncology, but the evidence for their efficacy in treating H3K27M mutant diffuse midline glioma/DIPG remains limited. In children newly diagnosed with DIPG, AZD1775 was well tolerated, but did not improve overall survival in comparison to controls (see Mueller, Sabine et al. “Wee1 kinase inhibitor adavosertib with radiation in newly diagnosed diffuse intrinsic pontine glioma: A Children's Oncology Group phase I consortium study.” Neuro-oncology advances vol. 4,1 vdac073. 20 May. 2022, doi:10.1093/noajnl/vdac073). This highlights that while Wee1 inhibition is attractive as a replication-stress and DNA-damage checkpoint strategy, it remains uncertain who will benefit from these treatment strategies when predictive biomarkers and responder populations are still being identified (see Wang, Zizhuo et al. “An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.” Journal of cancer research and clinical oncology vol. 150,1 13. 17 Jan. 2024, doi:10.1007/s00432-023-05527-y; and Zhang, Chi et al. “Adavosertib and beyond: Biomarkers, drug combination and toxicity of WEE1 inhibitors.” Critical reviews in oncology/hematology vol. 193 (2024): 104233. doi:10.1016/j.critrevonc.2023.104233). These support the point that even in tumors closely linked to the mutation, response to Wee1 inhibition is not reliably predictable based on the current knowledge of Wee1 biology.
For the other listed tumor types of the claims, the state of the art provides even less reason to assume predictable efficacy in treatment. Pilocytic astrocytoma is characterized in the literature as tumor primarily driven by MAPK pathway dysregulation (see Gregory, Timothy A et al. “Adult pilocytic astrocytoma in the molecular era: a comprehensive review.” CNS oncology vol. 10,1 (2021): CNS68. doi:10.2217/cns-2020-0027; and Hawkins, Cynthia et al. “BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma.” Clinical cancer research : an official journal of the American Association for Cancer Research vol. 17,14 (2011): 4790-8. doi:10.1158/1078-0432.CCR-11-0034). Supratentorial ependymoma is molecularly heterogeneous and includes distinct fusion-defined subgroups involving RELA or YAP1, reinforcing that even within the class of CNS tumor, biology can differ substantially across entities (see Pajtler, Kristian W et al. “Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups.” Cancer cell vol. 27,5 (2015): 728-43. doi:10.1016/j.ccell.2015.04.002; Torre, Matthew et al. “Characterization of molecular signatures of supratentorial ependymomas.” Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc vol. 33,1 (2020): 47-56. doi:10.1038/s41379-019-0329-2; and Pajtler, K.W., Wei, Y., Okonechnikov, K. et al. YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. Nat Commun 10, 3914 (2019). https://doi.org/10.1038/s41467-019-11884-5). Germ cell tumors are clinically and biologically distinct from gliomas are commonly treated with platinum-based chemotherapy, with BEP regimens described as the standard of care (see National Cancer Institute; Matei, Daniela et al. “Updates in the management of ovarian germ cell tumors.” American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting (2013): 10.1200/EdBook_AM.2013.33.e210. doi:10.14694/EdBook_AM.2013.33.e210; and Park, Meerim et al. “Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.” Cancers vol. 15,21 5290. 4 Nov. 2023, doi:10.3390/cancers15215290). Taken together, the literature supports that Wee1 inhibition is not established nor is it broadly effective across these tumor types. This underpins the fact that extrapolating Wee1 inhibitory efficacy across mutation or histology defined cancers remains unpredictable without tumor-specific evidence to the contrary (see Wang; and Zhang).
(5) The relative skill of those in the art:
The artisan is likely involved in the treatment of cancer and while they might be skilled in the treatment of cancer, their technical skill would be insufficient to overcome the art-recognition that cancer is not preventable.
Wee1 kinase inhibitors have demonstrated their efficacy in treating cancer. However, neither the specification nor the cited prior art provides evidence or support for using these compounds in the prevention of cancer. While the artisan would be aware that Wee1 kinase inhibitors have been investigated for the treatment of cancer, such general knowledge would not enable the identification of which Wee1 inhibitors, across the full scope of structurally and functionally diverse inhibitors encompassed by the claims, would be effective for treating cancers harboring H3K27M mutation without undue experimentation.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for a method of treating diffuse midline glioma, childhood diffuse pontine glioma, or midline glioma in an individual with a H3K27M mutation in the cancer cells, comprising administering an effective amount of compound A.
However, the specification does not provide a method of using any Wee1 kinase inhibitor for the treatment of any cancer bearing a H3K27M mutation in the full range of the recited cancer cells.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the lack of examples using other Wee1 kinase inhibitors for the treatment of all types of cancer and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 21 and 24 are 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.
Regarding claims 21 and 24, the phrase "preferably" renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
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 9, 12-13, and 16-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, and 17-18 of U.S. Patent No.10703759 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent discloses a method of treating Wee1 mediated cancers using the same compounds. The specific compounds listed in claim 5 overlap extensively with the claimed compounds of instant claims 19 and 28.These methods are not precluded from treating Wee1 mediated cancers bearing the H3K27M mutation of the instant claims and are therefore not patentably distinct from the claims of the patent.
Claims 9, 12-13, and 16-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 11 of U.S. Patent No.11345711 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent discloses a method of treating Wee1 mediated cancers using the same compounds. The specific compounds listed in claim 9 overlap extensively with the claimed compounds of instant claims 19 and 28. These methods are not precluded from treating Wee1 mediated cancers bearing the H3K27M mutation of the instant claims and are therefore not patentably distinct from the claims of the patent.
.Conclusion
No claims are allowed.
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625