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 I, comprising claims 1-3, 65, 70, and 86-87 is acknowledged. Claims 6-8, 21, 41-42, 72, 77-81, and 83-84 are withdrawn from further consideration as being directed towards nonelected inventions. Claims 1-3, 6-8, 21, 41-42, 65, 70, 72, 77-81, 83-84 and 86-87 are pending. Claims 1-3, 65, 70, and 86-87 are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements filed on April 16th 2025 and March 23rd 2023 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 Interpretation
Claims 3, 86, and 87 each recite the phrase “a peak at approximately…” Applicant does not define the term “approximately” in the specification. The term will thereby be interpreted within the standards of the art of crystallography, as “± 0.2 degrees 2Θ.” For example, the phrase, “a peak at approximately 7.25 degrees 2Θ” will be interpreted as “a peak at approximately 7.25 ± 0.2 degrees 2Θ.”
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 1-3 and their dependent claims 65 and 70 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 107 and 108 are insufficient to describe the complete crystal form.
Claims 1-3 are directed to a crystalline form omadacycline (generically) or comprising one at least one XRPD peaks at any of 7.25, 7.37, 10.33, 12.58, 12.81, 14.75, 16.44, 17.86, 19.32, 19.44, 19.62, 22.19, or 23.38 ± 0.2 degrees 2Θ. While the combination of these peaks are sufficient to characterize applicant’s crystal structure, at least the six major peaks at 7.25, 7.37, 12.58, 12.81, 16.44, and 17.86 would be considered necessary to identify this crystal structure. Applicant’s written description is therefore inadequate to support claims 1-3, 65, and 70 as written. Applicant will be considered only to be in possession of the crystal structure of the compound having at least the peaks at 7.25, 7.37, 12.58, 12.81, 16.44, and 17.86 ± 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.
Claims 1, 2, 65, and 70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Coulter (U.S. Patent No. 9,255,068, effectively filed on May 12th 2011).
Claims 1 and 2 are directed to a crystalline form of freebase of omadacyline, represented by the formula:
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Coulter describes a crystalline free base of the same compound (Coulter, col. 23, Table 5), and thereby anticipates claims 1 and 2.
Claim 65 is directed towards a pharmaceutical composition comprising the crystalline form of claim 1. Coulter teaches such a composition (Coulter, col. 15-16), anticipating claim 65.
Claim 70 requires that the pharmaceutical composition of claim 65 is in a tablet form. Coulter teaches such a tablet form (Coulter, col. 14), anticipating claim 70.
Allowable Subject Matter
Claims 86 and 87 are free of the art.
Applicant has developed a crystalline polymorph of the freebase form of the broad-spectrum tetracycline antibiotic, omadacycline:
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Applicant’s crystalline form is not found in the art. Freebase crystalline forms of the compound are generally described in applicant’s patents, U.S. Patent No. 9,255,068 and U.S. Patent No. 8,383,610. However, in neither case are particular XRPD peaks of the crystalline form described, nor is the freebase form claimed.
Claims 86 and 87 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
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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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629