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 .
DETAILED ACTION
This office action is in reply to the Response to Election/Restriction filed 09 July 2026 for application 18/613,180 filed 22 March 2024, with PRO 63/491,978 filed 24 March 2023. Claims 3-4, 6-8, 11-16, 19-20 and 28-30 are amended. Currently, claims 1-30 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 31 July 2024 was filed after the mailing date of the application on 22 March 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 09 July 2026 is acknowledged.
Applicant’s election of Example 56-2, (S)-2-(3-(1-(5,5-dimethylpyrrolidine-2-carbonyl)piperidine-4-carbonyl)-2-methyl-1H-pyrrolo[2,3-c]pyridine-1-yl)-5-fluoro-N,N-diisopropylbenzamide in the reply filed on 09 July 2026 is acknowledged.
Applicant’s election of leukemia in the reply filed on 09 July 2026 is acknowledged.
The elected species, per Applicant’s remarks, reads upon claims 1-9, 12-14 and 16-30. As such, claims 10-11, 15, and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. Election was made in the reply filed on 09 July 2026.
The elected species was found to be free of the prior art.
The search was expanded to the full scope of the claims.
Claims 1-9, 12-14 and 16-29 are allowable. Claims 10-11, 15, and 30, previously withdrawn from consideration as a result of a restriction requirement, requires all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions I and II and among species, as set forth in the Office action mailed on 09 April 2026, is hereby withdrawn and claim 30 hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or non-statutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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.
Claim 30 is 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.
A review of the rejected claim language indicates that these claims are drawn toward “a method of treating or preventing a Menin-mediated condition in a subject suffering from or susceptible to the Menin-mediated condition, the method comprising administering to the subject a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof”. A description of the term “a method of treating …” 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 Application/Control Number: 18/335,687 369, 372-73 (Fed. Cir. 1984).
In Applicant’s originally filed specification, Menin acts as a cofactor for MLL1, a histone methyltransferase which is a driver of leukemias including myeloid leukemias and acute lymphoid leukemias when multiple chromosomal translocations occur. The therapeutic strategy therefore targets the inhibition of Menin-MLL1 binding to attenuate disease progression. However, the Applicant only demonstrates application in terms of protein binding, human leukemia cell proliferation inhibition, hERG inhibition, muscarinic M2 receptor binding, microsome stability, hepatocyte stability, permeability, and a xenograft MLLr AML models, combination therapies with BCL2 inhibitor Venetoclax in cell and xenograft models and protein degradation assays. Applicant does not demonstrate that the product is capable of the claimed method of treatment of the various diseases of the claim limitations to the breadth and scope of which broadest reasonable interpretation requires. The biochemical, in vitro, in vivo, and pharmacokinetic data does not lead one to conclude that the Applicant was in possession of a method of treating or preventing all possible Menin-mediated conditions for all patients to the breadth and scope of which broadest reasonable interpretation requires. Dreijerink et al. (Twenty years of menin; emerging opportunities for restoration of transcriptional regulation in MEN1, Endocr. Relat. Cancer 2017, 24, 10, T135-T145) teach that menin-related diseases appear to be broad class of heterogenous diseases that does not have a general treatment or prevention, including leukemias and several different solid tumors (pg. 2). Menin also interacts with many different protein partners and genomic loci in context-dependent manners, implicating numerous cellular processes. It is therefore a broad field that encompasses numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. These factors undermine the concept that, regardless of the biochemical, in vitro, and in vivo data provided, are prophetic to the final therapeutic application of the invention to all the various diseases that menin-related conditions encompass. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather 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 structures, 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 predicable which are known to one of ordinary skill in the art, more evidence is required to show possession. One of skill in the art would not recognize from the disclosure that the applicant was in possession of a “method of treatment” for the diseases as claimed.
Additionally, it is known that there are significant challenges translating biochemical, in vitro, and in vivo studies to a clinical setting, and that not all biochemical, in vitro, and in vivo studies can be directly translated to the clinical setting. Indeed, J. M. McKim (Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo resistance, Combo. Chem. & High Throughput Scr. 2010, 13, 188-206) emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical, cell, or animal models (introduction). As the specification discloses working examples performed biochemically, in vitro, and in vivo primarily focused on menin-mediated leukemia, one of skill in the art would not recognize that the Applicant was in possession of “a method of treatment” of the various diseases and conditions claimed in a laboratory or clinical setting.
Claim 30 is 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 protein binding, human leukemia cell proliferation inhibition, hERG inhibition, muscarinic M2 receptor binding, microsome stability, hepatocyte stability, permeability, and a xenograft MLLr AML models, combination therapies with BCL2 inhibitor Venetoclax in cell and xenograft models and protein degradation assays, does not reasonably provide enablement for treating or preventing all menin-mediated diseases in a patient in need thereof. 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.
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 as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) Nature of invention –
The Applicant’s claims are broad. Claim 30 is directed to “a method of treating or preventing menin-mediated condition in a subject suffering from or susceptible to the menin-mediate condition…”. While the Applicant discloses the potential application of the product in MLL-menin leukemias, it does not demonstrate applicability in a broad field encompassing numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. Not only are the diseases varied, the term patient is extremely broad as it includes not only humans but any creature of whom this treatment may be relevant for including mammals of which there are far too many examples to list here. As the specification discloses working examples focused on MLL-menin interaction, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is a “a method of treating or preventing menin-mediated condition” considering the possible breadth of what is a diverse genus that can arise from multiple factors and pathways.
(C) 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 of the Examiner’s knowledge, there is no general pharmacological agent and/or pharmaceutical composition containing pharmacological agents capable of ubiquitously treating all menin-related conditions and diseases. It is therefore reasonable to conclude that the current state of the art is highly unpredictable and extremely complex, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for treating cancer as claimed.
(D) The level of one of ordinary skill in the art –
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
These hurdles render application of “a method of treatment or prevention of menin-mediated conditions” to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E) Existence of working examples & (F) Amount of direction or guidance by the inventor –
As previously established by Dreijerink, menin-mediated conditions are varied and sophisticated. Conversely, the specification does not demonstrate a means to treat this disease in subjects in need thereof to the requirement of the broadest reasonable interpretation. Instead, the instant specification only provides working examples focused on MLL-menin interaction. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claim.
(G) Quantity of experimentation needed to make or use the invention –
Taken together, the prior art demonstrates that the diseases and conditions arise from multiple factors and etiologies. This covers the breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates working examples with a specific condition, it does not demonstrate how “a compound” would be able to matriculate into a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. Even if the compound was not being considered for human treatment, there are, established by J. M. McKim who emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical cell, or animal models (introduction), introducing numerous hurdles that must be overcome for use in the broad category of a patient which is not a guaranteed, linear progression. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claimed invention and the unpredictability in successful application as described by claim 30, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in treating the disease claimed. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, and the lack of guidance and working examples provided in the specification meeting the scope of the claim. Therefore, the specification is not representative of the instant claim and the specification is not fully enabled for the instant claim. In view of the above, one of ordinary skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
Claims 1-29 are allowable.
Reasons for Allowability
The following is a statement of reasons for the indication of allowable subject matter: the structure defined by formula I in claim 1 was not taught in the prior art in a 100% embodiment. The closest art is described by Cai et al. (Substituted phenyl-1H-pyrrolo[2,3-c]pyridine derivatives, WO 2022/253167 A1, 2022; entered into the IDS on 31 July 2024) who discloses the general structure (pg. 4):
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While incorporating several similar motifs, no specific disclosed examples read upon the instant claims.
Therefore, the prior art neither anticipates nor reasonably makes obvious the claimed subject matter and therefore, the claimed subject matter is deemed novel and unobvious over the prior art.
Summary
Claims 1-29 are allowable. Claim 30 is rejected under 35 U.S.C. 112(a).
Conclusion
Claims 1-29 are allowable. Claim 30 is rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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