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 of PCT/KR2022/003703, filed Mar. 16, 2022, and claims foreign priority to KR10-2021-0034296, filed Mar. 16, 2021 in the Republic of Korea.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 24, 2024; Oct. 16, 2024; Sept. 19, 2025; and Oct. 28, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Status
Claims 1-8 are currently pending and subject to examination.
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 1-8 fail to comply with the written description requirement:
Claims 1-8 are rejected under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement. The claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
The written description requirement is distinct from the enablement requirement; as was first pointed out by the court in In re Ruschig, 3 79 F .2d 990, 154 USPQ 118 (CCP A 1967), and clarified in Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 19 USPQ2d 1111 (Fed. Cir. 1991). The issue of whether the claimed subject matter is adequately supported/described by the specification, is a question of fact. Id. at 1563, 19 USPQ2d at 1116.
When considering whether the claimed subject matter complies with the written description requirement, Applicants' disclosure should be read in light of the knowledge possessed by those skilled in the art.
"[T]he disclosure in question must be read in light of the knowledge possessed by those skilled in the art, and that knowledge can be established by affidavits of fact composed by an expert, and by referencing to patents and publications available to the public ... "
In re Lange, 644 F.2d 856, 863, 209 USPQ 288, 294. See also, In re Alton, 76 F.3d 1168, 37 USPQ2d 1578 (Fed. Cir. 1996).
Applicants enjoy the presumption that their patent application is valid and all statements contained therein are accurate; it is the PTO's burden to demonstrate why any of Applicants claims should be rejected or why any of Applicant's statements should be doubted.
"it is incumbent upon the Patent Office, whenever a rejection ... is made, to explain why it doubts the truth or accuracy of any statement in a supporting disclosure and to back up assertions of its own with acceptable evidence or reasoning which is inconsistent with the contested statement. Otherwise, there would be no need for the applicant to go to the trouble and expense of supporting his presumptively accurate disclosure."
In re Marzocchi, 439 F.2d 220, 224, 169 USPQ 367, 370. If successful in presenting such evidence and argument, the burden then shifts to the Applicant to provide evidence that would convince one to the contrary.
The Invention in General
A component of Applicant’s invention is directed to crystal forms of a compound, N-(4-(1-(2-cyanoacetyl)-3-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-6-yl)cyclopropanecarboxamide, having the structure:
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(drawn by examiner) (herein “the compound” ). The compound is described as an inhibitor of JAK kinases which are regarded as potentially useful for the clinical treatment of autoimmune conditions and Alzheimer’s disease (background). The application discloses a single crystal form of the compound referred to as “form A” which is identified, distinguished, and characterized principally on the basis of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA).
The Claimed Invention
The claimed invention is directed to a crystalline form of the compound (claims 1-5) and a method of preparing the crystalline form of the compound (claims 6-8). The independent claims characterize the crystal form by three XRPD peaks. The dependent claims 2 and 3 only require one additional peak characterizing the form. Dependent claims 4 and 5 additionally require thermogravimetric analysis (TGA) or differential scanning calorimetry (DSC) data.
Claims 6-8 are directed to a method for preparing the crystal form of the compound comprising mixing the compound with an organic solvent, water or a mixture thereof and stirring the mixture to precipitate crystals.
The Supporting Disclosure
Applicants' supporting disclosure describes the chemical formula and structure of the compound (pg. 2-3). The drawings of the disclosure provide, inter alia, powder x-ray diffraction patterns, DSC curves, and TGA curves for the non-solvated anhydrous crystal form. Peaks of interest from the diffraction patterns are provided in Table 1. For example, the disclosure identifies eight x-ray diffraction peak positions characteristic of the crystal form (Table 1).
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Above: Table 1 (p. 9-10).
The disclosure also provides two example methods preparing the crystal form (Examples 1-2), from a sample of the compound of unspecified solid form. Example 1 involves suspending a compound of formula (II)
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(drawn by Examiner) in 100 mL of ethyl formate to obtain a suspension, stirring, and then centrifuging and vacuum drying to obtain a solid product (Example 1). Example 2 involves mixing the compound of formula (II) in acetonitrile to obtain a suspension and then centrifuging and vacuum drying to obtain a solid product (Example 2).
The State of the Art
A number of references establish that different polymorphs, or crystal forms, of the same compound may often have shared or highly similar XRD peaks, Raman peaks, and solid-state NMR peaks. These references further establish that, because of such peak overlap and similarity, a minimum number of peaks is required in order to definitively characterize a single polymorph and distinguish it from all others that may exist, including any that are known and any that have yet to be discovered.
For example, the non-patent publication, “Thermoanalytical and Crystallographic Methods.” Polymorphism in Pharmaceutical Solids, 2nd edition, Editor Brittain, Publ. Informa Healthcare USA, pgs. 318-346 (2009) by Bhattacharya et al. (hereinafter, “Bhattacharya”), states that
The United States Pharmacopeia contains a general chapter on XRD, which sets the criterion that identity is established if the scattering angles in the powder patterns of the sample and reference standard agree to within the calibrated precision of the diffractometer. It is noted that it is generally sufficient that the scattering angles of the ten strongest reflections obtained for an analyte agree to within either ± 0.10 or ± 0.20° 2 q , whichever is more appropriate for the diffractometer used.
-Bhattacharya, pg. 334, second full paragraph, (emphasis added)
As such, Bhattacharya teaches ten XRD peaks is a standard for identifying a polymorph and distinguishing it from other polymorphs. Bhattacharya notes that in select circumstances, as few as five XRD peaks have been utilized for polymorph identification (pg. 334, last paragraph), but ten is described as the standard, and no example is suggested in which a number of XRD peaks as few as three has been deemed sufficient to identify a solid polymorph and distinguish the polymorph from other forms of the same substance.
Bhattacharya also teaches that DSC profiles can be used to distinguish polymorphs, but shows that two different polymorphs can have peaks within about 10°C of each other. Figure 1 shows that Form III has a DSC peak at about 167-168°C while form II has a DSC peak at about 173°C :
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Bhattacharya, Fig. 1, p. 320.
Bhattacharya also teaches that thermogravimetric (TG) analysis can be used to aid in the identification and characterization of solvatomorphs, but is typically not used alone to identify pure polymorphs (Bhattacharya, p. 324-325).
An additional publication, “Preparation and Identification of Polymorphs and Solvatomorphs” by Harry G. Brittain (CRC Press, 2008, p. 185-228) (herein “Brittain”) explains that different polymorphs of than same compound can be obtained using different solvents or even highly similar solvents. For example:
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Brittain, p. 206.
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Brittain, p. 208.
Brittain teaches that the polymorphic form is also dependent on temperature. For example:
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Brittain, p. 214.
Summary of Written Description Rejection
In view of the findings described above, and assuming the presently disclosed peaks accurately and consistently characterize the species to which they are assigned, the only effect of claiming one of the presently disclosed polymorphs, while reciting a small number of identifying peaks (3-4), would be to broaden the claim in a manner that allows it to potentially encompass polymorphic species not disclosed and perhaps not yet discovered. However, because only one specific polymorph of the compound is disclosed, and in order to comply with the written description requirement, the claims should be sufficiently specific and detailed to encompass only the polymorph that is disclosed and to exclude any non-disclosed polymorphs, such as any polymorphs that are yet to be discovered.
While the Applicant also recites a mass reduction rate of 1.6% at 150°C by TGA (claim 4) and a DSC peak at 142.07 to 157.29 °C, these limitations do not serve to fully identify the claimed polymorph because TGA analysis can only aid in the identification of polymorphs, is typically used in conjunction with other identification techniques, and is more useful in distinguishing solvatomorphs, and the range for the DSC peak is so broad that it does not exclude other polymorphs.
Furthermore, regarding the method of preparing the polymorph (claims 6-7), the method only requires mixing the compound with water and/or an organic solvent and precipitating crystals, which could yield a variety of polymorphs given the solvent used and the reaction conditions such as temperature and incubation time. While claim 8 further limits the organic solvent, it still does not clearly limit the method to a method of preparing the disclosed polymorph because it nonetheless recites a variety of organic solvents, e.g. ethyl acetate, acetone, toluene, and ethanol, which have differing characteristics and may precipitate different polymorphs. The specification only illustrates two solvent systems (acetonitrile and ethyl formate).
For the aforementioned reasons, claims 1-8 fail to comply with the written description requirement.
Closest Prior Art
The closest prior art is Lee et al. (KR20190043437A, of record, IDS dated May 24, 2024, Cite No. 9). Lee discloses the compound of formula (II):
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having an unspecified solid form (Lee, Specification, p. 244, paragraph [1745], compound 304). Lee does not teach crystalline form A as disclosed in the instant application.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629