DETAILED ACTION
Status of Claims
Receipt is acknowledged of the Applicants’ Amendments and Remarks, filed March 30, 2026
Claims 1-17 are pending and under consideration.
Claims 1, 6, 9, 13 are amended.
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
This application is a 371 National Phase Application of PCT/EP2021/073320 filed August, 24, 2021 which claims the benefit of priority to Indian Patent Application No. EP20192551.8, filed on August, 25, 2020.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d), and the certified copy has been filed.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
No additional information disclosure statements have been submitted.
WITHDRAWN OBJECTIONS
The examiner withdraws objections to claims 1, 9 and 13 based on amendments made by Applicant.
MAINTAINED/MODIFIED REJECTIONS
Claim Rejections - 35 USC § 112(a)
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 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01 (a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant.
A discussion of these factors they relate to the pending claims follows.
Breadth of Claims and The Nature of the Invention
Claims 1-17 are directed towards a method of treatment of cancer disease comprising administering BAY 2402234 also known as Orludodstat with a dosing schedule to a patient in need thereof (National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 134470179, Orludodstat. Retrieved December 17, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/Orludodstat).
On page 3, lines 14-34 and page 4, Applicant describes a wide range of heterogenous cancers varying in etiology, origin, treatment plan such as leukemias, brain cancers, solid tumors, reproductive cancers, and skin cancers.
It is well-known in the art that cancer is a broad class of heterogenous diseases for which there exists no general treatment. Hanahan explains that “there are more than 100 distinct types of cancer, and subtypes of tumors can be found within specific organs (Hanahan, Douglas, and Robert A. Weinberg. "The Hallmarks of Cancer." Cell 100, no. 1 (2000): 57-70).
Consequently, it is reasonable to conclude that the claims are broad with respect to the cancer disease.
Applicant has not directly defined treatment; however, Applicant mentions on page 18, lines 33-35 in embodiments with regards to dosing schedule “a method of treatment of cancer diseases comprising administering a specific amount of these compounds while using a days on 3 days off dosing schedule or 5 days on 2 days off dosing schedule and the respective schedule being optionally repeated one or more times as often as deemed necessary in order to control the disease, achieve its regression or cure the disease mentioned herein, whereby the specific amount depends on the patient condition and may vary from patient to patient but still within the amount ranges as disclosed herein.”
Consequently, it is reasonable to conclude that the claims are broad with respect to the purpose of “treatment,” and inclusive of curing disease.
Therefore, it reasonable to conclude the claims are broad with respect to cancer disease, patient population and treatment.
The state of the prior art
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05 (a).
It is well-known in the art that there is no sole pharmacological agent, including DHODH inhibitors capable of treating and/or curing all types of cancer diseases.
Although Orludodstat has shown promise for treating some types of cancers such as specific brain tumors such as IDH-mutant gliomas (Bar, Eli E., and Julie-Aurore Losman. "Exploiting genetic and environmental vulnerabilities to target DHODH in CNS tumors." Neuro-Oncology Advances 7, no. 1 (2025): vdaf149), and AML (Christian, Sven, Claudia Merz, Laura Evans, Stefan Gradl, Henrik Seidel, Anders Friberg, Ashley Eheim et al. "The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies." Leukemia 33, no. 10 (2019): 2403-2415), this does not mean that Orludodstat is capable of treating and/or curing all types of cancer diseases, particularly as a monotherapy.
By example only, Memorial Sloan Kettering Cancer Center teaches that “There are more than 125 different types of brain cancer. Most brain tumors fall into one of two categories: high grade (rapidly growing) or low grade (slow growing) (“Primary Brain Tumors,” Memorial Sloan Kettering Cancer Center, https://www.mskcc.org/cancer-care/types/brain-tumors-primary/types, Accessed: December 17, 2025).
As Schaff explains “Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation (Schaff, Lauren R., and Ingo K. Mellinghoff. "Glioblastoma and other primary brain malignancies in adults: a review." Jama 329, no. 7 (2023): 574-587).”
By example only, Schaff further explains that for PCNSL: “PCNSL is a rare hematologic malignancy confined to the brain, spinal cord, and leptomeningeal or vitreoretinal space. The annual incidence is 0.4 per 100 000, but incidence increases with age to 4 per 100 000 in patients older than 70 years. Immunodeficiency is a known risk factor, but PCNSL also affects immunocompetent patients. Presenting neurologic symptoms develop over the course of weeks to months and may be reversed with treatment. Unlike other brain tumors discussed in this review, PCNSL is highly sensitive to chemotherapy and radiation, and the goal of treatment is cure, although approximately 33% to 60% of patients will relapse.”
By example only, Schaff further explains that for Malignant Ependymomas: “Ependymomas are a heterogenous group of tumors arising from the ependymal lining of the brain. These tumors differ in their biology according to patient age, tumor location, histology, and molecular features. Because malignant ependymomas are rare, few clinical trials of therapies for malignant ependymomas exist. In addition, 9 distinct ependymoma subgroups were identified recently, and it is unclear whether current treatments apply across the 9 subgroups.”
Consequently, it is not reasonable to conclude DHODH inhibitors and more specifically, Orludodstat is capable of treating and/or curing brain cancer, particularly as a monotherapy.
As Zhou explains: “DHODH is a promising target in multiple malignancy therapies. When applying in specific genetic context, DHODH inhibitors might exert more targeted and meaningful effects on malignancy therapy. Recent studies have illustrated that DHODH inhibitors are more effective against malignancies with specific genetic context, such as melanomas carrying BRAF (V600E) mutation [89] and glioblastoma stem cells [25] and breast cancer with PTEN deletion [25, 29] and pancreatic cancer with KRAS mutation [63]. Therefore, the specific genetic context for DHODH inhibitor treatment needs to be further explored.
Meanwhile, combination of DHODH inhibitors with other anti-cancer drugs is a promising approach to achieving clinical benefits in various tumor therapies as DHODH inhibitors alone have limited therapeutic windows and may not achieve desired outcomes” (Zhou, Yue, Lei Tao, Xia Zhou, Zeping Zuo, Jin Gong, Xiaocong Liu, Yang Zhou et al. "DHODH and cancer: promising prospects to be explored." Cancer & metabolism 9, no. 1 (2021): 22).”
Consequently, Zhou explains that DHODH inhibitors are targeted therapies, and not general towards broad classes of cancer as claimed. Zhou also emphasizes the importance of combination therapies with DHODH inhibitors to be effective.
Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples and guidance would be required to practice the invention as disclosed for treating and curing all cancer diseases claimed.
The level of one of ordinary skill
The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP § 2141.03 (I)
The invention described pertains to medicine and pharmacology. One of ordinary skill would be a person with training in oncology, pharmacology, biochemistry or a related technical discipline.
The level of predictability in the art
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling.
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. See MPEP § 2164.03.
Consequently, technologies involving physiological activity as opposed to mechanical or electrical inventions are generally regarded as being unpredictable sciences.
As aforementioned, cancer is an unpredictable, complex and heterogenous disease. It is also well-known in the prior art that DHODH inhibitors alone are insufficient for treating and/or curing all cancer diseases and that many cancers are incurable and/or lack treatment options.
Based on these culminative factors, it is reasonable to conclude that predictability in the art is low.
Consequently, the applicant would need to provide more details, working examples and guidance in order for the claimed invention to be enabling based on the scope and nature of the claimed invention.
The amount of direction provided by the inventor and The existence of working examples
The applicants’ working examples are directed towards:
In vivo mice studies using AML THP1 cells, Mantle Cell Lymphoma Z138 cells, and colorectal cancer cells (Examples 1-3).
However, Applicant has failed to provide sufficient working examples covering the broad range of cancer disease claimed, and has failed to provide sufficient working examples supporting that BAY 2402234 can cure the cancer diseases claimed.
On this basis and points discussed earlier, the working examples are both not commensurate with the scope of protection sought and are not enabling. One ordinarily skilled in the art would be unable to simply translate the evidence provided by the applicant into methods for treating and/or curing all cancer diseases in all subjects using the compounds claimed without undue experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
As aforementioned, the quantity of experimentation depends on the prior art, the predictability of the art, and the direction provided by the inventor, which are factors that were already discussed.
In order for one ordinarily skilled in the art to practice the invention as disclosed, some attributes one would require, but are not limited to:
In vitro and/or in vivo studies to validate BAY 2402234 is effective in treating the broad ranges of cancers claimed, particularly as a monotherapy.
Long-term studies to confirm no recurrence of the cancers claimed for curative properties.
Development of a specific treatment regime including how to determine effective dosage, timing, monitoring plan and administration method based on the diverse cancers claimed.
Consequently, the examiner concludes that one ordinarily skilled in the art would require undue experimentation in order to practice invention based on the details provided and scope of invention defined in Claims 1-17.
Consequently, claims 1-17 remain rejected for lacking enablement with respect to methods for treating all the cancer diseases claimed.
Response to Arguments
The Remarks of March 30, 2026 have been fully considered but are not fully persuasive for the reasons below.
35 USC 112(a)
Applicant’s Arguments:
“However, breadth alone does not establish lack of enablement, and the Examiner has not met the burden required to establish that the present claims are not enabled. The relevant inquiry is not whether cancers are heterogeneous in the abstract, but whether a person of ordinary skill in the art, in view of the disclosure and the knowledge in the art, would have been required to engage in undue experimentation to practice the claimed method.”
Examiner’s Response:
The examiner agrees that breadth alone does not establish lack of enablement; however, respectfully disagrees that the Examiner has not met the burden.
The Examiner has provided a thorough comprehensive analysis using the Wands factor analysis as it the test of enablement as per MPEP 2164.01(a) which includes:
A) The breadth of the claims;
(B) The nature of the invention; [AltContent: rect]
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Consequently, Applicant’s assertion that only the breadth of the claims was considered is inaccurate.
Furthermore, as per MPEP 2164.04: “According to In re Bowen, 492 F.2d 859, 862-63, 181 USPQ 48, 51 (CCPA 1974), the minimal requirement is for the examiner to give reasons explaining the uncertainty of the enablement. This standard is applicable even when there is no evidence in the record of operability without undue experimentation beyond the disclosed embodiments. See also In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (citing In re Bundy, 642 F.2d 430, 433, 209 USPQ 48, 51 (CCPA 1981)).”
The Examiner has fulfilled these requirements as provided herein and the previous Office Action. Applicant has made no amendments to the claims changing the current scope of invention.
Moreover, the level of predictability, amount of direction, existence of working examples and quantity of experimentation required are also key factors. It is well-known in the art that there are numerous cancer diseases that are incurable, untreatable, and heterogeneity pertaining to cancer generally is well-known as a significant challenge and burden in developing effective treatment options for patients.
This does not even cover the challenges associated with treating broader categories of cancers such as breast cancer, colorectal cancer, and pediatric cancers of which many are plagued by tumor heterogeneity and/or are highly dynamic, leading to high unpredictability, common recurrence and relapse and requiring a high level of skill, direction and experimentation to develop an effective treatment plan.
In summary, yes, cancer being heterogenous is a significant factor in determining undue experimentation; however, the determination of lack of enablement of the claimed method is not just based on assessing breadth but based on the other factors as clearly outlined by the Examiner. It is not reasonable to suggest an ordinarily-skilled artisan would be able to use the DHODH inhibitor as claimed as a general treatment and cure for all cancer diseases for all patients without undue experimentation based on the lack of predictability within the art of oncology and multivariable optimization often required to arrive at a treatment plan for patients.
Applicant is reminded that as per MPEP 2164.05: “To overcome a prima facie case of lack of enablement, applicant must present argument and/or evidence that the disclosure would have enabled one of ordinary skill in the art to make and use the claimed invention at the time of filing. This does not preclude applicant from providing a declaration after the filing date which demonstrates that the claimed invention works. However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art at the time of filing. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must reasonably enable the full scope of the claimed invention. See Pac. Biosciences of Cal., Inc. v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021)”
Applicant’s showings are not commensurate with the scope of the claimed invention.
Although Applicant has provided in vivo data for mice studies using AML THP1 cells, Mantle Cell Lymphoma Z138 cells, and colorectal cancer cells (Examples 1-3), this does not mean they have covered the full diversity of cancer disease in human patients across the diverse demographics nor does it mean Applicant has developed treatments that are curative.
The Examiner invites Applicant to fully respond to the arguments raised by the Examiner, particularly with regards to monotherapy for DHODH inhibitors, evidence supporting curative properties for the methods ascribed and Zhou’s remarks pertaining the limited therapeutic window for DHODH inhibitors and genetic context. Additionally, the Examiner invites Applicant to submit evidence or arguments supporting enablement commensurate with the full scope of the claims. To date, Applicant has failed to provide such evidence.
Applicant’s Arguments:
Indeed, the very references cited by the Examiner recognize a common metabolic rationale for DHODH-directed treatment across multiple cancers. Bar explains that tumor cells are highly proliferative and require particularly high levels of pyrimidines. Even in CNS cancers (the focus of the Examiner's allegations), where cancer cells may bypass DHODH inhibition through salvage pathways, "[t]his restricted access to salvage pathways could create a therapeutic window where DHODH inhibition effectively targets tumor cells while minimizing systemic toxicity." See Bar at p. 2-3. Bar further reports that DHODH inhibitors have shown "potent anti-tumor activity in preclinical models of numerous tumor types," including acute myeloid leukemia, B-cell lymphoma, IDH mutant glioma, diffuse midline glioma, medulloblastoma, and glioblastoma. See Bar at p. 3. Zhou likewise explains "DHODH is a promising target in multiple malignancy therapies." See Zhou at p. 19. Even if Zhou states DHODH inhibitors are "more effective against malignancies with specific genetic context," that is comparative language, not exclusionary language. Zhou does not state that cancers lacking those genetic features are not treatable with DHODH inhibitors (instead providing that some cancers are "more" responsive to treatment). See Zhou at p. 19 (emphasis added). Thus, the Examiner's own references recognize a cross-cancer biological rationale for DHODH-directed therapy. There is simply no basis to contend that the present claims are not enabled due to the alleged "breadth" associated with the recited cancer diseases. Instead, the references cited discussing DHODH inhibition illustrate otherwise.
Examiner’s Response:
The Examiner respectfully disagrees. Even in the selectively cited quotes, Zhou explains “DHOH is a promising target” and that “[t]his restricted access to salvage pathways could create a therapeutic window;” however, promise and potential does not translate into whether the methods of treatment, as claimed, is capable of treating and/or curing all types of cancer in all patients.
In fact, Applicant has failed to address the concerns raised by the Examiner pertaining to DHODH as a target, predictability, issues with monotherapy for DHODH inhibitors and has failed to provide sufficient guidance for a person of ordinary skill in the art of oncology to practice the invention as claimed. Applicant has also failed to address the Examiner’s concerns pertaining CNS cancers, including the examples provided above (i.e.,: Ependymomas and PCNSL, by example only). It is well-known that aside from efficacy, pharmacokinetics and drug delivery considerations also play a critical role in predicting success of a treatment.
Applicant is reminded pertaining predictability that “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).”
DHODH inhibitors are nascent technology; therefore, for the reasons stated and supported by Zhou, more detail is required for how to use the invention.
Applicant is further reminded that “…in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”
Consequently, Applicant’s limited examples do not sufficiently provide an adequate basis to support their generic claims of treating and curing cancer disease.
Applicant’s Arguments:
The Examiner has the "initial burden setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled." See In re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993). The Examiner has not met that burden. Moreover, even if some experimentation were necessary (which Applicant does not concede), that does not render the claims non-enabled unless that experimentation were undue (which is not the case here). Even a considerable amount of experimentation does not negate enablement SO long as it is routine. See, e.g., PPG Indus., Inc. V. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996); In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Moreover, the fact that experimentation may be complex also does not necessarily make it undue, if the art typically engages in such experimentation (e.g., assaying the one recited compound to identify treatment efficacy). See MPEP § 2164.01. Here, the Examiner identifies at most the possibility that some further work might be performed for some cancers. That is not the legal standard. There is no basis to contend that any experimentation that may be required is undue.
Examiner’s Response:
As stated above, the Examiner respectfully disagrees and has set forth a proper case for lack of enablement using the Wands factor analysis as is standard.
As aforementioned, there are numerous types of cancer and cancer is a heterogenous disease. A person of ordinary skill in the art would face undue experimentation in developing treatment plans including ones that are curative across the broad range of possible cancers would not be routine. Applicant is reminded that the claims are directed towards treating a patient and towards a cancer disease, which is highly unpredictable and therefore would not be routine and enabled across the full scope of the claims (i.e: treating and curing all types of cancer dieases in all patients).
Applicant’s Arguments:
Contrary to the Examiner's allegations, a person of ordinary skill in the art would have understood that the recited treatment schedules for DHODH inhibition were expected to extend across multiple cancer types (particularly in view of the Examples of the originally filed specification). For example, WO 2018/077923 teaches that DHODH "is considered an attractive drug target for cancer," and that "preclinical studies indicate that DHODH inhibitors may be useful for the treatment of haematological cancer indications, for the treatment of solid tumors (e.g., neuroblastoma, melanoma, colon, breast and lung tumors)." See WO 2018/077923 at p. 2-3. WO 2018/077923 also provides DHODH inhibition data for N-(2-chloro-6-fluorophenyl)-4-[4-ethyl-3- (hydroxymethyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-5-fluoro-2-([(2S)-1,1,1-tifluoropropan benzamide as Example 189 (IC50 = 6.00 X 10⁻⁹ M), and reports DHODH inhibitory activity for other compounds within the described scaffold, including Example 1 (IC50 = 4.43 X 10-⁸ M), Example 106 (IC50 = 1.31 X 10⁻⁸ M), and Example 121 (IC50 = 4.17 X 10-9 M) in Table 3. Examples 1, 106, and 121 are shown to have broad cancer-panel activity (two of which have a lower activity in the DHODH assay). See Tables 3, 6 and 7. A person of ordinary skill in the art would have understood that DHODH inhibitors (particularly those in the scaffold of WO 2018/077923) were reasonably expected to have broad anti-cancer utility, although no relevant treatment windows such as that claimed, had yet been identified.
Examiner’s Response:
Applicant themselves acknowledge no relevant treatment windows have been identified.
The same arguments pertaining to lack of enablement commensurate with the scope of the claims stands as set forth above.
Applicant’s Arguments:
The present application provides the claimed schedule-specific teaching and representative in vivo data in AML, mantle cell lymphoma, and colorectal cancer, together with treatment- monitoring guidance, including that treatment effect may be "readily controlled by measurement of DHO in a blood sample," "readily controlled by measuring the count ratio of normal cells to differentiation arrested cells in a blood sample," and "readily controlled by non-invasive methods of imaging a solid tumor enabling measuring the size of the remaining tumor." See, e.g., claims 7-9. As explained in the originally filed specification, the recited treatments leverage the broad anti- cancer activity associated with DHODH inhibition (particularly for inhibitors of this scaffold). The originally filed specification explains that it has "surprisingly been found to establish comparable efficacy to daily BAY 2402234 dosing, while achieving similar or even higher weekly doses (comparing the total sum of doses given over a 7-day period independent of schedule) however also allowing off treatment days for potential side effect recovery." See p. 2, Ins. 20-25. In view of that prior-art backdrop and the present disclosure, there is no basis whatsoever to contend that the present claims are not enabled. Withdrawal is warranted.
Examiner’s Response:
As discussed previously, enablement must be commensurate with the scope of the claims. Although the instant invention may be enabled for some types of cancer, this does not mean it is enabled for all types of cancer diseases across all patient populations as claimed. Additionally, Applicant has failed address the challenges addressed by the Examiner’s pertaining genetic context, and that DHODH inhibitors as monotherapy is not effective as discussed by Zhou.
As per MPEP 2164.05, Applicant is reminded that “Once the examiner has weighed all the evidence and established a reasonable basis to question the enablement provided for the claimed invention, the burden falls on applicant to present persuasive arguments, supported by suitable proofs where necessary, that one skilled in the art would be able to make and use the claimed invention using the application as a guide. In re Brandstadter, 484 F.2d 1395, 1406-07, 179 USPQ 286, 294 (CCPA 1973). The evidence provided by applicant need not be absolute but merely convincing to one skilled in the art, based on a preponderance of the evidence standard.”
Applicant has failed to provide persuasive arguments supported by evidence supporting that the claimed invention is enabled. In the previous Office Action and reiterated in this Office Action, the examiner provided a detailed and thorough Wands factor analysis detailing the factors pertaining enablement as per MPEP 2164.01(a), and identifying key issues within Applicant’s disclosure pertaining enablement.
The examiner once more invites Applicant to present persuasive arguments and/or evidence to support their claims of an enabled disclosure.
For these reasons, the arguments by Applicant are not persuasive, and the claims remain rejected.
Conclusion
Claims 1-17 are pending and rejected.
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 CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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