NON-FINAL REJECTION
This application, filed Jun. 20, 2024, is a continuation of PCT/CN2022/141016, filed Dec. 22, 2022, which claims foreign priority to International Applications PCT/CN2022/136234, filed Dec. 2, 2022 and PCT/CN2021/141005, filed Dec. 23, 2021.
Claims 1, 3-9, and 96-98, as amended, are pending.
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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Acknowledgment is made of applicant's claim to foreign priority under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Sep. 4, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Specifically, claim 7 recites the crystalline form of claim 1, having an XRPD pattern "substantially as shown in FIG. 1A."
Similarly, claim 9 recites the crystalline form of claim 1, having a DSC thermogram "substantially as shown in FIG. 1B."
However, the claims are to be complete in themselves. As recognized by MPEP § 2173.05(s), 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). Therefore, a claim which refers to an external figure or table renders the metes and bounds of the claim indefinite.
Claim Rejections - 35 U.S.C. § 112(a) – Scope of Enablement
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, 3, 8, and 96-98 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for certain crystalline forms of the claimed compound and pharmaceutically acceptable salts thereof, does not reasonably provide enablement for any and all crystalline forms of the claimed compound and salts 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 practice the invention commensurate in scope with these claims.
As recognized by MPEP § 2164.01(a), "there are several factors to consider 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." In re Wands, 8 USPQ2d 1400 (1988), sets out these factors, which include:
A. The Breadth of the Claims. Claim 1 encompasses any and all crystalline forms of N-(5-(2,2-dimethyl-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-4-((6-(methylsulfonyl)-4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)pyridin-2-yl)acetamide, as well as any and all crystalline forms of any pharmaceutically acceptable salt thereof. Thus, the scope of claim 1 extends well beyond the limited number of specific crystal forms exemplified: it encompasses every possible crystalline form – including any polymorph, solvate, or hydrate – of the free base compound, as well as every possible crystalline form of every pharmaceutically acceptable salt thereof. Thus, the scope of claim 1 is exceptionally broad.
B. The Nature of the Invention. The invention relates to crystalline forms of N-(5-(2,2-dimethyl-2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl)-4-((6-(methylsulfonyl)-4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)pyridin-2-yl)acetamide, and pharmaceutically acceptable salts thereof, as well as methods of administering the crystalline forms to treat any inflammatory or autoimmune disease.
C. The State of the Prior Art and the Level of Predictability in the Art. Active pharmaceutical ingredients can exist in a variety of distinct solid forms, including polymorphs, solvates, hydrates, salts, co-crystals, and amorphous solids. Each form displays unique physicochemical properties that can profoundly influence the compound's bioavailability, purification, stability, and other performance characteristics. Hence, it is critical to understand the relationship between the particular solid form of a compound and its functional properties.
For ionizable compounds, preparation of salt forms using pharmaceutically acceptable acids and bases is a common strategy to improve bioavailability. However, the preparation of other solid forms, such as polymorphs and solvates, is much less predictable. In order to obtain patent protection on these forms, some of which may have significantly different properties and relevance as development candidates, it is essential to prepare them, identify conditions for making them, and evaluate their properties as valuable new pharmaceutical materials. A large number of factors can influence crystal nucleation and growth during this process, including the composition of the crystallization medium and the processes used to generate super-saturation and promote crystallization (see, e.g., Morissette et al., cited on PTO-892).
Further, Vippagunta et al. (cited on PTO-892) disclose that "[t]he main challenge in managing the phenomenon of multiple solid forms of a drug is the inability to predict the number of forms that can be expected in a given case." While prediction of polymorphs is an active field of research, "no general method is currently available for the prediction or interpretation of the properties of complicated polymorphic or pseudopolymorphic systems" (sec. 2.5, pp. 11-12).
Thus, the existence and characteristics of additional crystalline forms cannot be reliably predicted from a limited number of known forms. Because the preparation and properties of crystalline forms is highly unpredictable, one of ordinary skill in the art cannot predict which additional forms may exist, or how to prepare them, without undue experimentation.
D. The Amount of Direction or Guidance and Presence of Working Examples. The specification provides preparation methods and characterization data for approximately 22 specific crystalline forms of the claimed compound and salts thereof. While these examples are well-characterized (XRPD, DSC, TGA, etc.), they represent only a small subset of all the crystalline forms encompassed by claim 1. The disclosure of the specification is limited to the specific conditions used to produce these exemplified forms; no general guidance or techniques are provided that would enable a skilled artisan to prepare or identify any crystalline form of the claimed compound or its salts.
E. The Quantity of Experimentation Needed and the Level of Skill in the Art. Given the limited number of working examples relative to the scope of the claims, and the unpredictability of crystalline form discovery and solid form behavior, a skilled artisan would be required to engage in undue experimentation to prepare crystalline forms beyond those exemplified. This would include, for example, broad salt and polymorph screening, solvent and anti-solvent selection, temperature and humidity cycling, and characterization studies, essentially repeating and expanding upon the experimental work performed by the applicants, without any assurance as to which additional forms (if any) might exist or how they might be prepared.
Thus, for the foregoing reasons, one of ordinary skill in the art could not practice the invention commensurate with the full scope of the claims without undue experimentation.
Claim Objections
Claims 4-6 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARA E. TOWNSLEY/Examiner, Art Unit 1629
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