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
Restriction and Status of the Claims
Applicant’s election without traverse of Group II, comprising claim 10, as well as the substantial amendments to the claims in the response filed on July 15th 2026 are acknowledged. Applicant has amended all of the claims to require the crystalline inupadenant hydrochloride of claim 10. The restriction requirement filed on April 17th 2026 is rendered moot and is thereby withdrawn. Claims 10-11, 16-17, and 256-259 are pending and are examined on their merits.
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, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements filed on April 29th 2025, April 3rd 2025, January 15th 2025, October 24th 2024, September 27th 2024, and July 5th 2024 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Rejections - 35 USC § 112(b)
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 16 and 17 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.
Claims 16 and 17 are indefinite for failing to further limit claim 11, upon which they depend. Claim 16 recites: “The crystalline inupadenant hydrochloride of claim 11, having an XRPD pattern comprising one or more peaks at about 8.9° and about 9.3° 2Θ.” Claim 17 recites: “The crystalline inupadenant hydrochloride of claim 16, further comprising a peak at about 14.5° 2Θ.”
Each of these claims are dependent on claim 11, which recites:
“The crystalline inupadentant hydrochloride of claim 10, wherein the crystalline inupadenant hydrochloride is Form 2 inupadenant hydrochloride.”
One of ordinary skill in the art would understand “Form 2 inupadenant hydrochloride,” to be a particular form with a particular packing arrangement of molecules. Said packing arrangement would necessarily have the properties of ‘Form 2 inupadenant hydrochloride,’ as defined in the specification. That is, the XRPD spectrum would be as shown below:
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As described above, the XRPD pattern for Form 2 inupadenant hydrochloride would necessarily have all of the above XRPD peaks. That is, the XRPD peaks at “about 8.9°, about 9.3°, and about 14.5°,” would necessarily already be present in the XRPD spectrum for Form 2 inupadenant hydrochloride.
Thereby, it is unclear how claim 16 (further limiting Form 2 inupadenant hydrochloride to require peaks at about 8.9° and about 9.3°) and claim 17 (further limiting Form 2 inupadenant hydrochloride to require a peak at about 14.5°) are further limiting to the crystalline form of claim 11 (which is necessarily described by an XRPD spectrum that contains all 3 peaks). As one of ordinary skill in the art could not reasonably determine how claims 16 and 17 further limit claim 11, claims 16 and 17 are indefinite.
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 10 and 256-259 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]
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]
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[Atipamula, pg. 2151]
Such polymorphism can cause significant variance in the physical properties of even a single substance. For example, see Anuar (Anuar et al., (2022) Crystallisation of organic materials from the solution phase: a molecular, synthonic and crystallographic perspective, Crystallography Reviews, 28:2-3, 97-215) who teaches the variance in melting points in several polymorphic compounds, and demonstrates that the melting point of a single compound can differ as much as 50° C by changing the packing arrangement of the compound:
“The wider and, more importantly, the industrial impact of polymorphism can be signified by the close relationship between the crystal structure and its physico-chemical properties. For example, polymorphs frequently exhibit different melting points by virtue of their different crystal structures, and such differences may have a significant impact on their solubility (and hence bioavailability) as well as on aspects related to their downstream processing, such as their drying, comminution and compaction behaviour where the heat is either applied or generated.”
[Anuar, pg. 112]
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[Anuar, pg. 112, Table 5]
Furthermore, it is unpredictable whether particular polymorphs will share aspects of their XRPD spectrum. See Wang (Wang et al., Polymorph transformation in paracetamol monitored by in-line NIR spectroscopy during a cooling crystallization process. Aaps Pharmscitech. 2011;12(2):764–770) below, who teaches XRPD patterns for 2 polymorphic forms of the common drug, paracetamol:
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[Wang, pg. 766, Figure 2]
It is shown that the two forms share a major defining peak, and little else. One of ordinary skill in the art therefore could not reasonably distinguish between the two polymorphic forms from the presence of a single peak. I.e., while the major peak is one of the defining features of the two polymorphs, additional peaks would be necessary in order to properly distinguish the two structures.
Noting the substantial effect that a given crystal form can have on a compound’s pharmacological properties, and the differing XRPD patterns between polymorphic forms, applicant’s crystal forms as described in claims 10 and 256-259 are insufficient to describe the complete crystal form.
Claim 10 is directed to crystalline inupadenant hydrochloride. No further definition is given of the crystal form. The claim language therefore implies “any and all crystalline forms of inupadenant hydrochloride.” Applicant’s written description is inadequate to support claim 1 as written and applicant will only be considered to have possession of the crystalline forms fully characterized by XRPD peaks.
Claim 256 is directed to a crystalline form of inupadenant hydrochloride, comprising an XRPD peak at 8.9 ± 0.2 degrees 2Θ. At least the five major peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claim 256 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 ± 0.2 degrees 2Θ.
Claim 257 is directed to a crystalline form of inupadenant hydrochloride, comprising an XRPD peak at 9.3 ± 0.2 degrees 2Θ. At least the five major peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claim 257 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 ± 0.2 degrees 2Θ.
Claim 258 is directed to a crystalline form of inupadenant hydrochloride, comprising an XRPD peak at 8.9 ± 0.2 degrees 2Θ and at least one XRPD peak at 3.3, 6.5, 22.3, 23.9, 24.8, or 26.8 ± 0.2 degrees 2Θ. At least the five major peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claim 258 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 ± 0.2 degrees 2Θ.
Claim 259 is directed to a crystalline form of inupadenant hydrochloride, comprising an XRPD peak at 8.9 ± 0.2 degrees 2Θ and at least one XRPD peak at 26.8, 29.1, 29.3, or 32.9 ± 0.2 degrees 2Θ. At least the five major peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claim 259 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 8.9, 9.3, 24.9, 25.9, and 26.7 ± 0.2 degrees 2Θ.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 10 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crosignani (WO 2020/053263 A1 published on March 19th 2020).
Claim 10 is directed to a crystalline form of inupadenant hydrochloride:
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Crosignani explicitly teaches the hydrochloride salt of inupadenant (Corsignani, pg. 141, Table 2, Compound 8a HCl salt; Compound 8a is identified as having the same structure on page 32). Corsignani further teaches crystalline polymorphs (generally) of the compounds, and identifies inupadenant (referred to as compound 8a) as a preferred embodiment (Corsignani, pg. 54). One of ordinary skill in the art would thereby be able to at once envisage a crystal of the hydrochloride salt of inupadenant. See MPEP § 2131.02(III):
A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). In Kennametal, the challenged claim was to a cutting tool requiring a ruthenium binding agent with a physical vapor deposition (PVD) coating. The reference described all the elements of the claimed coated cutting tool but did not explicitly disclose the specific combination of ruthenium binding agent with a PVD coating. However, the reference disclosed that ruthenium was one of five specified binding agents and PVD was one of three suitable coating techniques. The Federal Circuit stated that the reference’s "express ‘contemplat[ion]’ of PVD coatings provided sufficient evidence that a reasonable mind could find that a person of skill in the art… would immediately envisage applying a PVD coating. Thus, substantial evidence supports the Board's conclusion that [the reference] effectively teaches 15 combinations, of which one anticipates pending claim 1. Though it is true that there is no evidence in [the reference] of ‘actual performance’ of combining the ruthenium binder and PVD coatings, this is not required." Kennametal, 780 F.3d at 1383, 114 USPQ2d at 1255 (citations omitted). See also Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 851 F.3d 1270, 1274, 122 USPQ2d 1116, 1120 (Fed. Cir. 2017) ("Kennametal does not stand for the proposition that a reference missing a limitation can anticipate a claim if a skilled artisan viewing the reference would "at once envisage" the missing limitation. Rather, Kennametal addresses whether the disclosure of a limited number of combination possibilities discloses one of the possible combinations.").
As one of ordinary skill in the art would be able to at once envisage a crystal of the hydrochloride salt of inupadenant from the teachings of Corsignani, Corsignani anticipates claim 10.
Allowable Subject Matter
Claims 11, 16-17, and 256-259 are free of the prior art.
Applicant has developed a novel crystal form of the hydrochloride salt of the Adenosine A2A receptor antagonist, inupadenant:
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The closest art is Crosignani (WO 2020/053263 A1), who teaches the hydrochloride salt of the compound, and crystal forms (generally). However, the cited document does not claim applicant’s crystal forms, and said forms would not be predictable from the prior art..
Claims 11 is 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.
Claims 16-17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey 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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/ANTHONY JOSEPH SEITZ/Examiner, Art Unit 1629
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