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 application 18/725,158 filed 28 June 2024, 371 of PCT/CN2022/143908 filed 30 December 2022, claiming priority from CN202210948453.1 filed 12 August 2022 and CN 20211650341.X filed 31 December 2021. Claim 5-7, 9, 11 and 18-22 are amended. Claims 10, 12 and 23 are canceled. Currently, claims 1-9, 11 and 13-22 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 28 June 2024, 06 August 2025, and 08 December 2025, was filed after the mailing date of the application on 28 June 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.
Specification
The disclosure is objected to because of the following informalities: images on pgs. 95, 97-98 and 101-142 are not well-resolved (i.e. too blurry).
Appropriate correction is required.
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 21 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 biochemical inhibition of recombinant Menin protein, inhibition of cell proliferation through Menin-MLL interaction, in vivo anti-tumor properties in mice, along with disclosed liver microsome stability, pharmacokinetic data in mice, rat, and beagle dog, additionally with CYP450 and hERG toxicity tests, does not reasonably provide enablement for treating cancer comprising administering the compound of claim 1… to a subject in need. 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 21 is directed to “a method of treating cancer… administering the compound of claim 1… to a subject in need”. While the Applicant discloses the potential application of the product in developing new therapies for MLL leukemia, it does not demonstrate applicability, to what is known to one of ordinary skill in the art, is an incredibly broad field encompassing numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, co-morbidities, etc. Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prevention. Hanahan et al. (The hallmarks of cancer, Cell 2000, 100, 1, 50-70) teaches that “there are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs (pg. 1). Not only are the diseases varied as different patient populations, 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 only performed in a mouse model, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is “a method of treating cancer” considering the possible breadth of what is a very 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 cancer. This is emphasized by Hanahan, characterizing cancer as a disease that is already “complex beyond measure” (pg. 1). 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 of cancer” 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 Hanahan, cancer is a complex and sophisticated disease. Conversely, the specification does not demonstrate a means to treat this disease in subjects in need to the requirement of broadest reasonable interpretation. Instead, the instant specification only provides biochemical, in vitro and in vivo results. 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 a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates binding to the target proteins, 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 (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) 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 21, 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, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. 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 1-20 and 22 are allowed.
Reasons For Allowance
The following is an examiner’s statement of reasons for allowance: the compounds of formula I, illustrated in claim 1, were found to be free of the prior art in a 100% embodiment.
The closest matches are described by Cacatian et al. (Inhibitors of the menin-MLL interaction, WO 2017/214367 A1, 2017; entered into the IDS on 28 June 2024) who describe compounds encompassed by formula I as illustrated below:
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301
325
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Greyscale
This is further exemplified by compound Example 64, the only pendant spiro compound listed:
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257
264
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Greyscale
No teaching was derived to further expand the pendant spiro moiety into carbocycles other than the acetal protecting group. Therefore, since the teachings of Cacatian fail to teach and/or fairly suggest the claim limitations, the claims invention is novel and non-obvious.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Summary
Claim 21 is rejected under 35 U.S.C. 112(a). Claims 1-20 and 22 are allowable.
Conclusion
Claim 21 is rejected. Claims 1-20 and 22 are allowable.
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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