DETAILED ACTION
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
The present application is the U.S. National Stage Application, pursuant to 35 U.S.C.371, of PCT International Application No.PCT/IB2021/056154 filed July 8, 2021 which claims priority to U.S. Patent Application No. 63/051,976 filed on July 15, 2020.
Status of the Claims
Claims 1-4,7-9,12-14,17-21,26 and 28 are pending.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on January 10, 2023 (6 references) and February 23, 2023 (1 reference) has been received entered into the present application, in compliance with the provisions of 37CFR 1.97. Accordingly, the Information Disclosure Statement is 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 and 3 and their dependent claims 2, 7, 8, 9, 12-14, 17-21, 26 and 28 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.
One of ordinary skill in the art would recognize that a single compound, and indeed a single salt, can have multiple packing arrangements, causing distinct changes in the crystal structure, and even in the pharmacological properties of the substance. For example, see Atipamula (Atipamula et al., Cryst. Growth Des. 2012, 12, 5, 2147–2152), who describes the phenomena of different solid forms of active pharmaceutical ingredients (APIs):
“An important aspect of drug development is determining which specific solid form of an active pharmaceutical ingredient (API) should be selected for scale-up, formulation activities, and clinical trials. This process is a nontrivial exercise since an API can be polymorphic, meaning that it can exist in two or more crystal forms. Frequently, the crystal forms of an API exhibit low solubility, and it might be appropriate to use a more soluble amorphous form or a more soluble multicomponent form, such as a salt form — for ionizable APIs — or a cocrystal form for neutral APIs. Furthermore, APIs are typically amenable to formation of multiple component crystals such as solvates and hydrates. In short, as presented in Scheme 1, for most APIs, there are numerous possible solid forms that can be obtained and subsequently must be investigated and characterized as part of drug development. Each solid form of an API has distinct physicochemical properties, and finding the optimal solid form is important to intellectual property, processing, enabling drug delivery and is a key to obtaining regulatory approval.”
Atipamula, pg. 2148, (emphasis added).
Atipamula further describes the polymorphism of cocrystals and demonstrates how a single compound can have multiple packing arrangements, leading to different pharmacological properties:
“Polymorphism in cocrystals (different packing arrangements with the same composition, e.g. carbamazepine saccharin (Figure 3) defy the idea that cocrystal formers play the same role as that of an excipient. Rather, cocrystals are novel solid forms that can be patented and are known to modulate physicochemical properties such as solubility in either direction. This means that they could be applicable in either immediate-release or extended-release formulations unlike the “API-excipient complexes”.”
Atipamula, pg. 2150 (emphasis added).
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Atipamula, pg. 2151.
Noting the substantial effect that a given crystal form can have on a compound’s pharmacological properties, applicant’s crystal forms as described in claims 1 and 3, are insufficient to describe the complete crystal form.
Claims 1 and 3 are directed to a crystalline form of the compound of formula (I) identified as (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-( 4-methyl-7H-pyrrolo[2, 3-d] pyrimidin-7-yl)cyclopentane-1,2-diol identified below:
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Claims 1, and 3 are directed to the substantial of formula (I), comprising one PXRD peaks of any of peaks at about 5.6, 13.1, 15.3 and 19.6 ± 0.2 degrees 2Θ (as in claim 2) and wherein the crystalline form further comprises one PXRD peak at any of 5.6, 13.1, 15.3 and 19.6 ± 0.2 degrees 2Θ (claim 3). While the combination of these peaks are sufficient to characterize applicant’s crystal structure, at least the five major peaks at 5.6, 10.5, 13.1, 15.3 and 19.6 (+/- 0.2 degrees 2- theta) would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claims 1-3,7-9,12-14,17-21,26 and 28 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 5.6, 10.5, 13.1, 15.3 and 19.6 (+/- 0.2 degrees 2- theta).
Conclusion
Claims 1-3, 7-9, 12-14, 17-21,26 and 28 are rejected.
Claim 4 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL RANDALL GAUGER whose telephone number is (571)272-1325. The examiner can normally be reached M-F 7:30-5:00.
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/P.R.G./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629