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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-9 and 15-18 in the reply filed on 3/29/2025 is acknowledged.
Applicant’s election without traverse of:
Water-soluble polymers; namely, polyvinylpyrrolidone;
Tablets;
Ethanol,
in the reply filed on 3/29/2025 is acknowledged.
Claims 10-14, 19-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/29/2025.
Claims 5, 18 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/29/2025.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-4, 6-9, 15-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pfarr (EP 2 520 293 A1; 2012; IDS reference); in view of Huang et al. (“Fundamental aspects of solid dispersion technology for poorly soluble drugs”; 2014; Acta Phamaceutica Ainica B; (4(1): 18-25; IDS reference).
Pfarr teaches compounds of general formula (1) for use in the treatment of filariasis (abstract). Among the compounds taught, a most preferred compound is compound (9)
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1186
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shown at [0024], [0042]; this compound is commonly denoted corallopyronin A [0025].
Preferably, the composition comprises a compound according to the invention as an active ingredient, a pharmaceutically acceptable carrier and optionally other adjuvants [0046]. The pharmaceutical carrier can be, for example, a solid. Suitable carriers and adjuvants can be solid and correspond to the substances ordinarily employed in formulation technology for pharmaceutical formulations [0047]. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy [0048]. The pharmaceutical composition of the present invention can be presented as discrete unit suitable for oral administration such as, inter alia, Applicant elected tablets containing a predetermined amount of the active ingredient [0050]. Dosing to mice at 35 mg/kg/day for 28 days was found to be effective to deplete >99% of Wolbachia content of worms [0086]. At this level, Corallopyronin A was well tolerated by the mice and no toxic effects were visually apparent [0089].
While Pfarr teaches excipients/carriers commonly used in pharmaceutical preparations, Pfarr does not explicitly teach Applicant elected polyvinylpyrrolidone, or Applicant elected class of water-soluble polymer where the formulation comprises an amorphous solid dispersion of Corallopyronin A embedded in the water-soluble polymer.
Huang teaches the solid dispersion has become an established solubilization technology for poorly water-soluble drugs; a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction being the determining factor in its design and performance; in this review we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology (abstract).
It is estimated that most compounds undergoing development at the present time are subjected to dissolution problems; to meet this pharmaceutical challenge, various solubilization technologies have been developed including solid dispersions; With accelerated FDA-approved products in recent years, solid dispersion is now firmly established as a platform technology for the formulation of poorly-soluble drugs. Inspection of examples of FDA approved medicines that use solid dispersion technologies (Table 1), examples include several that utilize PVP or PVP/AS as the polymer. Huang establishes the desirability of employing water-soluble polymers as excipient/carrier, in a solid dispersion of drug/polymer which are shown to be amorphous (see Figure 1 (A)), including Applicant elected PVP as polymer. The skilled artisan, in desiring to formulate soluble API in a solid (e.g., tablet) form, would have found it obvious to utilize one of the polymers taught by Huang, including Applicant elected PVP, in the form of an amorphous solid dispersion, which the corallopyronin A embedded in the PVP, which is formed into the tablet form taught (tablets are clearly named in Table 1), giving the elected solid formulation of the claims.
Regarding amounts of corallopyronin A, API doses taught by Huang range from 1 to 375 mg per tablet or capsule, which renders obvious the weight% ranges of claims 3, 16 & 17. For instance, 150 mg API in a typical 500 mg tablet size would correspond to 30% corallopyronin A. Therefore, the claimed ranges are considered to be similar to and overlapping with the exemplary amounts of Huang. Amount ranges would also have been obvious as a result of routine optimization to achieve the purpose taught by Pfarr, and taking into account examples of Huang for amorphous solid dispersions in the tablet forms as a starting point, and as a result of identifying workable amounts per tablet.
As pointed out in MPEP 2144.05 II, generally differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Applicant argues:
Pfarr teaches embodiments encompassed by [0047]-[0050]; arguing that there is no teaching or suggestion in Pfarr of an amorphous solid dispersion of CoA; that there is also no teaching or suggestion of embedding CoA in a water-soluble polymer or loading it into porous silica.
Applicant further argues that the Examiner has not provided any factual evidence for using Huang, motivating to specifically choose to formulate an amorphous solid dispersion of CoA. This somehow corresponds to improperly speculate a problem of limited oral bioavailability being incorporated into Pfarr, when Pfarr does not “show solubility data for Corallopyronin A”
This is not persuasive. The rejection is based on a combination of Pfarr and Huang.
Huang clearly discusses that “it is estimated that most compounds undergoing development at the present time are subjected to dissolution problems (p. 19, 1st paragraph). The word “most” means “the majority of, or nearly all of”. It is not unreasonable to infer from this that corallopyronin A would fall into this low solubility characteristic, just from this teaching in Huang; i.e., the rejection does not require a teaching from Pfarr that corallopyronin A has low solubility.
Nonetheless, from the structure of this compound, the skilled artisan would have known this low solubility is characteristic, based on knowledge of the structure. Reviewing the SciFinder CAS Registry Number: 9315-32-5 record of Corallopyronin A, Chemical Predicted properties include:
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1285
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…
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1355
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…
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i.e., a mass intrinsic solubility of 0 g/L; and a molar intrinsic solubility of 2.7 x 10-6 mol/L.
These values are calculated from knowledge of the structure of this compound, which was known at least from Pfarr.
These solubility values correlate to, as suggested by Huang, low solubility. The teachings of formulation techniques taught by Huang, which include Applicant elected embedding corallopyronin A in Applicant elected polyvinylpyrrolidone, where the corallopyronin A is presented in an amorphous solid dispersion, are particularly relevant to this compound, and follow the suggestion, made by Huang, that most compounds under development are subjected to dissolution problems; to meet this pharmaceutical challenge, various solubilization technologies have been developed including solid dispersions. Amorphous drug-rich domains dispersed in the polymeric matrix are depicted in Figure 1 ©, which would have been obvious to formulate with amorphous solid dispersion of CoA.
Applicant further argues that amorphous drug embodiments of Huan amount to cherry-picking from possible alternatives, and are hindsight reconstruction. MPEP 2123 (I) indicates that patents are relevant as prior art for all they contain. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
Applicant further argues that PVP and PVP-VA use surprisingly increases stability. Examiner notes that improvement in stability is discussed by Huang (see, for instance, p. 22, 2nd paragraph). It doesn’t appear that PVP achieves an unexpected result. Furthermore, reliance on Krome et al. does not appear to have any relevance to the instant invention, as publication date is after the instant foreign EP priority application date.
Conclusion
No claims are allowed
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIMOTHY P THOMAS whose telephone number is (571)272-8994. The examiner can normally be reached M-Th 6:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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TIMOTHY P. THOMAS
Primary Examiner
Art Unit 1614
/TIMOTHY P THOMAS/Primary Examiner, Art Unit 1614