DETAILED ACTION
Status of Claims
The amendment submitted November 3, 2025 has been entered.
Claims 1-9 and 17-18 are pending and under consideration.
Claims 10-16 are cancelled by Applicant.
Claims 3-4 and 18 are withdrawn as explained below in the Election/Restriction section.
Claims 1-2, 5-9, and 17 are under consideration in the instant office action as explained below in the Election/Restriction section
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/CA2020/051755 filed December 18, 2020, which claims the benefit of priority to United States Provisional Application 62/949678 filed December 18, 2019.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-9 and 17, drawn to a method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula I in the reply filed on October 7, 2025 is acknowledged.
Applicant’s election without traverse of the compound of claim 2 (shown below) as a species of a compound of formula (I) and lymphoma as a species of cancer in the reply filed on October 7, 2025 likewise acknowledged.
The elected species reads on claims 1 where each Y is independently selected by N and CH, Z is a heteroaryl optionally substituted with one or more RA or R4 substituents, where R2 is L-aryl and L is C1 alkylene, and where W is N(R1)(R3), and wherein when R1 and R3 are attached to a nitrogen atom optionally they join together with the nitrogen atom to form a 6 membered ring, optionally substituted with one RA, where RA is NR1R3 and R1 and R3 are hydrogen. The elected species is also known as UM171 as per page 39, paragraph [00148].
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The elected species also reads on claims 2, 5, 6, 7, 8, 9, and 17.
Claims 3-4, 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 7, 2025.
Claims 1-2, 5-9, and 17 are under consideration and the subject of this Office Action.
Information Disclosure Statement
Four information disclosure statements (IDS) submitted on June 7, 2022; July 14, 2023; September 11, 2023 and February 28, 2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 1-2, 5-9, and 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Vas-Cath Inc. v. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the “written description” inquiry, is “whatever is now claimed” (See page 1117).
A review of the language of the claim indicates that these claims are drawn towards “A method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula (I)…or a prodrug thereof…with at least one cell expanding factor”
A description of the term "A method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula (I)…or a prodrug thereof…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”.
Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984).
Accordingly, claiming “A method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula (I)…or a prodrug thereof…” is not a description of “A method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula (I)…or a prodrug thereof.” Especially of concern are what prodrugs Applicant has contemplated or actually obtained possession of.
In Applicant’s originally filed specification, definitions for “prodrug” as found on page 37, paragraph [134] as “It may be convenient or desirable to prepare, purify, and/or handle the compound in the form of a prodrug. Thus, the term "prodrug", as used herein, pertains to a compound which, when metabolized (e.g., in vivo), yields the desired active compound. Typically, the prodrug is inactive, or less active than the desired active compound, but may provide advantageous handling, administration, or metabolic properties. Unless otherwise specified, a reference to a particular compound also includes prodrugs thereof.”
However, Applicant has failed to provide any specific examples or descriptions of which prodrugs Applicant has contemplated pertaining to the compounds disclosed.
As per MPEP 2163, 1, II, 3, i): “Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.
“In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
It is well-known in the art that prodrugs are not reasonably predictable.
Ettmayer notes that “The majority of all prodrug approaches face the challenge of identifying the optimal prodrug plus its activation system to enhance or prolong the concentration of the active principle at the site of action. Because of the complex situation of prodrug transport and processing, we recommend, especially for novel prodrug principles, that the first step should be to design and investigate different prodrug prototypes of high diversity (different attachment sites, linkers, promoieties, hydrolytic, oxidative, reductive activation, chemical vs enzymatic activation). The feasibility of these prototypes should subsequently be evaluated with appropriate in vivo pharmacokinetic experiments (Ettmayer, Peter, Gordon L. Amidon, Bernd Clement, and Bernard Testa. "Lessons learned from marketed and investigational prodrugs." Journal of medicinal chemistry 47, no. 10 (2004): 2393-2404).”
Consequently, a prodrug form of a compound of Formula (I) is not predictable and depends on multiple variables, further design and optimization.
Claim 9 is directed towards “the method of claim 1, wherein the compound degrades at least one of LSD1, RCOR1, HDAC2 and CoREST.”
Applicant describes on page 27, paragraph [0095] that “As demonstrated herein, UM171 and its derivatives activate the CULLIN3- RING ubiquitin ligase complex (CRL3 complex described herein). The CRL3/KBTBD4 complex degrades RCOR1 which normally acts as the scaffolding protein for the RCOR1/LSD1 and HDAC2 complex, itself being dissociated in the presence of UM171.”
Applicant further explains that ““[00210] UM171 by activating the CRL3 complex as described herein degrades RCOR1 which normally acts as the scaffolding protein for the RCOR1/LSD1 and HDAC2 complex, itself being dissociated in the presence of UM171. Thus UM171 acts like a molecular glue degrader, as an anti-cancer agent resulting in inhibition of HDACs and LSD1.”
However, Applicant has only provided support for UM171 as a small molecule degrader, which does not encompass the full structural diversity and scope of compounds as recited in the method of claim 1.
As per MPEP 2163, I, A, “An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.”
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that inventor was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." Id.
Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the inventor was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021. Where the process has actually been used to produce the product, the written description requirement for a product-by-process claim is clearly satisfied; however, the requirement may not be satisfied where it is not clear that the acts set forth in the specification can be performed, or that the product is produced by that process. Furthermore, disclosure of a partial structure without additional characterization of the product may not be sufficient to evidence possession of the claimed invention. See, e.g., Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021 ("A gene is a chemical compound, albeit a complex one, and it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it. Conception does not occur unless one has a mental picture of the structure of the chemical, or is able to define it by its method of preparation, its physical or chemical properties, or whatever characteristics sufficiently distinguish it. It is not sufficient to define it solely by its principal biological property, e.g., encoding human erythropoietin, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. We hold that when an inventor is unable to envision the detailed constitution of a gene so as to distinguish it from other materials, as well as a method for obtaining it, conception has not been achieved until reduction to practice has occurred, i.e., until after the gene has been isolated." (citations omitted)). In such instances the alleged conception fails not merely because the field is unpredictable or because of the general uncertainty surrounding experimental sciences, but because the conception is incomplete due to factual uncertainty that undermines the specificity of the inventor’s idea of the invention. Burroughs Wellcome Co. v. Barr Labs. Inc., 40 F.3d 1223, 1229, 32 USPQ2d 1915, 1920 (Fed. Cir. 1994). Reduction to practice in effect provides the only evidence to corroborate conception (and therefore possession) of the invention. Id.”
The specification does not clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing.
Specifically, the specification must describe the claimed invention in a manner understandable to a person of ordinary skill in the art in a way that shows that the inventor actually invented the claimed invention at the time of filing. Id.; Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172. See MPEP 2163, I
Consequently, the specification does not clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is claimed.
Claims 1-2, 5-9, and 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 Nature of Invention
Claims 1-2, 5-8 are directed to “a method of treating cancer in a patient comprising the step of administering to said patient at least one compound of formula I”
Claim 9 is directed to “wherein the compound degrades at least one of LSD1, RCOR1, HDAC2 and CoREST.”
Claim 17 is directed to “wherein said cancer is a cancer based on a K27 mutation, EZH2 mutation or PRC2 mutation.”
Van den Bent teaches that H3 K27M-mutant diffuse glioma is a type of cancer based on a K27 mutation (van den Bent, M., Saratsis, A.M., Geurts, M. and Franceschi, E., 2024. H3 K27M-altered glioma and diffuse intrinsic pontine glioma: Semi-systematic review of treatment landscape and future directions. Neuro-oncology, 26(Supplement_2), pp.S110-S124).
Van den Bent teaches that “H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors.”
Van den Bent further teaches that “The presence of the H3 K27M mutation is associated with dismal survival, although the reported prognostic magnitude relative to gliomas without the H3 K27M mutation depends on many variables.38–43 Although the H3 K27M mutation was discovered in DIPG and is often thought to be a pediatric disease, young adult patients are also affected. Reports indicate up to 90% of pediatric DIPG cases are H3 K27M-mutant. Among adults with DMG, the H3 K27M mutation occurs in 15%–60% of cases. In a study of young adult and adult patients with thalamic tumors, the mutation was absent in all patients over the age of 50, whereas 91% of patients under the age of 50 (range, 17–46 years) were H3 K27M-mutant.”
Van den Bent further teaches that “Despite the prevalence of small molecules for a variety of cancers, few compounds are being evaluated in DIPG and H3 K27M-mutant-exclusive populations.”
In terms of PRC2, Wang teaches that “Polycomb repressive complex 2 (PRC2) is known to regulate gene expression and chromatin structure as it methylates H3K27, resulting in gene silencing. Studies have shown that PRC2 has dual functions in oncogenesis that allow it to function as both an oncogene and a tumor suppressor. Because of this, nuanced strategies are necessary to promote or inhibit PRC2 activity therapeutically (Wang, M.S., Sussman, J., Xu, J.A., Patel, R., Elghawy, O. and Rawla, P., 2024. Pharmacological advancements of PRC2 in cancer therapy: a narrative review. Life, 14(12), p.1645).”
“Within PRC2, EZH2 serves as the catalytic subunit that mediates PRC2’s identity as a histone methyltransferase.”
Therefore, Wang teaches the relationship between PRC2 and EZH2 and cancer, and the nuances required to promote or inhibit PRC2 activity based on its dual function as oncogene and tumor suppressor.
Wang further teaches “Amongst the core subunits, EZH2 has been of particular interest within the literature due to its contribution toward drug resistance, and its overexpression is linked with both oncogenic and tumor suppression effects [2]. For example, the overexpression of EZH2 is common within non-small-cell lung carcinoma (NSCLC) [13,14], colorectal cancer (CRC) associated with claudin-23 (CLDN23) and Runt-related transcription factor 3 (RUNX3) [15,16], aggressive forms of breast cancer [17,18,19,20], Ras signaling-based pancreatic cancer [21,22], and hormone-refractory prostate cancer [23,24].”
Eich teaches that “EZH2 is overexpressed in numerous tumor entities including melanoma, ovarian, breast, endometrial, bladder, renal cell, lung, and liver cancer, and is associated with aggressive disease, leading to its classification as an oncogene. In prostate cancer, EZH2 is significantly overexpressed in metastatic disease compared with localized cancer and benign prostatic tissue at both the transcript and protein levels. Furthermore, EZH2 plays a role in prostate cancer cell proliferation and depending on its phosphorylation status acts as a coactivator for transcription factors like the androgen receptor (Eich, M.L., Athar, M., Ferguson III, J.E. and Varambally, S., 2020. EZH2-targeted therapies in cancer: hype or a reality. Cancer research, 80(24), pp.5449-5458).”
Eich further teaches that “EZH2 inhibition alone may not be highly effective in certain tumors, however, and combination with other drugs and immunotherapies may prove beneficial in cancers that are not sensitive to EZH2 inhibition alone…. Although our ability to predict EZH2 sensitivity is improving, more work is required to develop highly predictive biomarkers for EZH2 therapeutic response. ”
Volkel teaches that “A large set of experimental data have established that EZH2 acts as a key player in tumorigenesis. However, the molecular mechanisms involved in EZH2 dysregulation in cancer appear to be diverse. EZH2 overexpression is mainly found in solid tumors and activating mutations are found in B-cell lymphomas while inactivating mutations are often identified in myelodysplastic syndromes and myeloproliferative neoplasms. Finally a missense mutation in the gene encoding histone H3.3 (H3F3A) inhibiting EZH2 activity is present at high frequencies in pediatric gliomas. Thus, EZH2 functions as an oncogene in solid tumors and lymphomas whereas it behaves like a tumor suppressor gene in myeloid disorders and in pediatric glioblastomas. The oncogenic role of EZH2 mainly depends on its ability to repress gene expression programs via H3K27 methylation and chromatin compaction. However, studies in certain cancers revealed that the oncogenic function of EZH2 could also result of its action as a PRC2-independent transcriptional activator. Then, EZH2 could be involved in cancer through multiple mechanisms and could be regulated by different pathways depending on cellular context and cancer type. A better understanding of the regulatory network involving EZH2 is consequently required for the development of novel anti-cancer therapeutic strategies (Völkel, P., Dupret, B., Le Bourhis, X. and Angrand, P.O., 2015. Diverse involvement of EZH2 in cancer epigenetics. American journal of translational research, 7(2), p.175).”
Consequently, Völkel demonstrates the unpredictability associated with EZH2, whose function shows high variability.
On page 35, paragraph [00125], Applicant defines subject as "subject" or "patient" is intended to mean humans and non-human mammals such as primates, cats, dogs, swine, cattle, sheep, goats, horses, rabbits, rats, mice and the like.”
Applicant has not explicitly provided a definition for treating cancer, nor has Applicant provided a definition for cancer. Consequently,
Consequently, as per MPEP 2111, “the pending claims must be "given their broadest reasonable interpretation consistent with the specification."
As per MPEP 2111.01, I: “Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art.”
Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prevention. 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 patient population, cancer, and aim of treating.
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).
To the best knowledge of the examiner, there is no general pharmaceutical agent capable of treating all types of cancer.
Particularly, UM171 is not known to be a general treatment for cancer.
Even with considering solely the cancers of claim 17 “wherein said cancer is a cancer based on a K27 mutation, EZH2 mutation or PRC2 mutation,” a broad and heterogenous of cancer types based on etiology, origin, treatment options are present.
Applicant has provided no support suggesting UM171 is capable of treating such broad range aside from the leukemias tested.
In particular, Applicant has provided no support suggesting UM171 can be used in pediatric patients or has the required properties for treating brain cancers such as H3 K27M-mutant diffuse glioma, a cancer with poor prognosis whose patient population is predominantly pediatric, which currently has no effective chemotherapeutic options as aforementioned.
The role of EZH2 and PRC2 mutation is also highly variable. As aforementioned, for EZH2, the regulatory network is complex and is still not well-understood. PRC2 is known to have dual functions and can either suppress or promote tumors; therefore, also is highly variable and unpredictable. Applicant has provided no guidance or support demonstrating the nuances of the compounds claimed to actually being effective in treating cancer based on a K27 mutation, EZH2 mutation or PRC2 mutation.
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
(D) 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, veterinary medicine and pharmacology. One of ordinary skill would be a person with training in oncology, pharmacology, biochemistry or a related technical discipline.
(E) 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, including the cancers as recited in claim 17 associated with specific mutations based on the evidence provided above.
Based on these culminative factors, it is reasonable to conclude that predictability in the art is extremely 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 existence of working examples
The applicants’ working examples are directed towards:
Chemistry examples for synthesis of compounds (pages 41-56).
In vitro testing for instant compounds for AML3.
Whole Genome CRISPR/Cas9 Screen and methodology for UM171 of OCI-AML5 or OCI-AML1 cell lines.
PK assays for bioavailability for oral and intravenous delivery in mice for UM681 and UM729).
Western Blot and Flow cytometry-based analysis for H3K27 acetylation in response to UM171 (Fig.3(B)).
Western Blot analysis for KBTBD4 knockdown (Fig. 3 (D)).
Antineoplastic effects of UM171 and UM681 on cancerous cell lines specific to leukemias (AML, APL, etc.)(Table 1, page 25) (in vitro, IC50 data)
Antineoplastic effect of UM171 on cell proliferation from AML patients (Table 2, page 26, IC50 data).
However, there are no examples supporting the method can be used to treat all types of cancers, including the cancers as claimed in claim 17 directed to specific mutations. All examples are focused on leukemias. Additionally, despite the diverse range of compounds recited in claim 1, the working examples are directed towards only 2-3 key compounds. There is no additional data provided suggesting the data can be extrapolated from leukemias towards treating the broad range of heterogenous cancers and patient populations claimed, including brain cancers and pediatric patients.
It is also known that there are significant challenges translating in vitro studies to all biological subjects in a clinical setting and that not all in vitro studies can be directly translated to the clinical setting depending on the cancer type. Therefore, it is also not reasonable to suggest Applicant’s invention can be used to treat cancer including the specific cancers in all subjects.
On this basis and the prior discussion, the working examples are both not commensurate with the scope of protection sought and are not enabling. One ordinarily skilled in the art would unable to simply translate the evidence provided by the applicant to treat the cancers in the subjects as claimed using the broad range of 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:
Data supporting the broad and diverse class of compounds claimed is effective in treating the broad and heterogenous class of cancers claimed, including brain cancers.
Treatment regimen, dosing schedules, and guidance based on patient populations such as pediatric patients for the diverse cancers claimed, particularly as nuances are important for the cancers associated with specific mutations as per claim 17.
Support that in vitro data can be extrapolated to clinical models, particularly for cancers where in vitro models are not known to translate well.
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 1-2, 5-9 and 17
Consequently, Claims 1-2, 5-9 and 17 are rejected for lacking enablement.
Claim Rejections - 35 USC § 112(b)
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.
Claim 5 is 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.
At claim 5, line 1, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Additionally, claim 5, line 2 contains references to tables. As per MPEP 2173.05(s), “where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 5-8 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kang et al (US-PGPUB 2019/0093081A1).
Regarding claims 1-2 and 5, Kang teaches methods for treating cancer in a patient comprising administering UM171.
Kang specifically teaches treating a subject having glioblastoma through administering UM171 as a stem cell mobilizing agent (claims 1-25) and paragraph [0220].
Regarding claims 6-7, Kang teaches “wherein said patient is a human or an animal,” and “wherein said animal is a mouse.”
Kang specifically teaches at paragraph [0046], “In some embodiments of the above aspects, the subject is a mammal. In some embodiments, the subject is a human.”
Example 5 of Kang at paragraph [0456] additionally teaches where the subject is a mouse, and where the treatment is delivered via IV meeting the limitations of claim 8.
Therefore, Claims 1-2, 5-8 are rejected as being anticipated by Kang.
Claims 1-2, 5-9 ,and 17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sauvageau et al (USPN 9,757,378 B2).
Regarding claims 1-2, and 5, Sauvageau teaches methods for treating cancer in a patient comprising administering UM171.
Sauvageau specifically teaches “In another aspect, the present invention provides a method for inhibiting or eliminating AML initiating cells in a subject, said method comprising administering to said subject an effective amount of a pharmaceutically acceptable agonist of the Aryl hydrocarbon Receptor (AhR).”
Therefore, Sauvageau teaches methods for treating AML in a subject.
The elected species UM171 and its pharmaceutically acceptable salt is taught as compounds 40 and 41 (column 27), which is an aryl hydrocarbon receptor defined on column 2, lines 20-30. Consequently, Sauvageau meets the limitations of claims 1-2 and 5.
Regarding claims 6-7, X teaches “wherein said patient is a human or an animal,” and “wherein said animal is a mouse.”
Example 5 of Sauvageau (column 71,lines 44-67) and Fig 4A teaches where the patient is a mouse.
Regarding claim 8, Sauvageau teaches “wherein said compound is formulated for an administration orally, intramuscularly, intravenously or subcutaneously.”
Specifically, “In the method for inhibiting or eliminating AML initiating cells, and/or for preventing or inhibiting MRD, in a subject of the present invention, the pharmaceutically acceptable AhR agonist may be formulated into a pharmaceutical composition.
Such compositions may be prepared in a manner well known in the pharmaceutical art. Supplementary active compounds can also be incorporated into the compositions. As used herein “pharmaceutically acceptable carrier” or “excipient” or “diluent” includes any and all solvents, buffers, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. The carrier can be suitable, for example, for intravenous, parenteral, subcutaneous, intramuscular, intracranial, intraorbital, ophthalmic, intraventricular, intracapsular, intraspinal, intrathecal, epidural, intracisternal, intraperitoneal, intranasal or pulmonary (e.g., aerosol) administration (see Remington: The Science and Practice of Pharmacy by Alfonso R. Gennaro, 2003, 21st edition, Mack Publishing Company)(column 54, lines 14-34).”
Additionally, Fig. 4A shoes where “AML cells from 6 primary human AML samples were injected untreated into the tail vein of sublethally irradiated NSG mice at 4 different doses (column 38, lines 1-11).”
Therefore, Claims 1-2, 5-8 are rejected as being anticipated by Sauvageau.
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Rossi et al (US-PGPUB 2019/0119642 A1) disclose methods and compositions relating to expanding, enriching, and/or maintaining a population of hematopoietic stem cells ex vivo containing UM171. Sauvageau No. 2 (USPN 10,647,718 B2) and Sauvageau No. 3 (USPN 9,409,906 B2) additionally report the use of UM171 and similar analogues in treating diseases involving hematopoietic stem cells.
Conclusion
Claims 1-2, 5-9, and 17 are under consideration and are rejected.
No claims are allowed.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622