DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicant’s Amendments and Remarks, filed 11 September 2025, in the matter of Application N° 18/249,869. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim 5 has been canceled and its limitations incorporated into independent claim 1. This represents the only amendment made to the claims and it is supported by the originally-filed disclosure.
No claims have been added. No new matter has been added.
Thus, claims 1-4 and 6-16 now represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statement (IDS) filed 11 September 2025 is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 102
Applicant’s amendment to claim 1 as discussed above overcomes the previously raised anticipation rejection. Said rejection is withdrawn.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 12 June 2025 since the art that was previously cited continues to read on the amended and previously recited limitations.
Claim Rejections - 35 USC §103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 are 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.
Claims 1-4 and 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (US Pre-Grant Publication Nº 2020/0339585 A1) in view of Li et al. (WO 2020/173364 A1; machine translation attached and cited). [emphasis added to reflect canceled claim.
The limitations recited by amended claim 1 are directed to a tablet comprising polymorphically pure crystalline 2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(cyclopropylsulfonyl)azetidine-3-yl)acetonitrile (herein referred to as “Form II,” as defined by the instant specification). The tablet is recited as having an Acceptance Value of 5 or lower. Claim 2 recites that the tablet has an AV of 3.5 or lower, wherein the pure crystalline compound is in the form of particles having a particle size distribution characterized by d50 of 15-30 microns, a d90 of 50-80 microns, a dv90 of 80 microns or less, and a dv50 of 30 microns or less.
Regarding the recited property of “Acceptance Value,” the Examiner acknowledges that this is directed to the assessment of Content Uniformity as set forth by section <905> of the USP.
The Examiner additionally notes that this assessment does not appear to be tethered to any particular formulation discussed in the instant specification. However, per ¶[0098] and ¶[0205] of the instant specification, it appears that preferred tableting compounds comprise microcrystalline cellulose, pregelatinized starch, calcium phosphate dibasic dihydrate, povidone, magnesium stearate, and a coating. As such, where such a composition is disclosed in the art, it will be considered to anticipate the instantly claimed composition, whether an “Acceptance Value” is disclosed or not. MPEP §2112(I) states that “the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.”
Claim 8 recites a composition comprising particles of substantially polymorphically pure crystalline Form II, wherein the particles have the foregoing size distribution.
Claim 9 recites the XRPD pattern recited in claim 3. Claim 10 recites that the composition further comprises any combination of microcrystalline cellulose, pregelatinized starch, calcium phosphate dibasic dihydrate, povidone, magnesium stearate, and a coating. Claim 11 recites that the composition of claim 8 is an oral dosage form.
Claims 12 and 13 recite dosage amounts for the oral dosage forms of claim 11.
The teachings of Hu are presented above and disclose each and every limitation recited in the claims with the exception of the particle size distribution. Paragraph [0038] teaches that the compositions will be in particle form for analysis via XRPD and particles for the crystalline composition are taught and suggested by the foregoing method disclosed in ¶[0161] insomuch as the formation of the tablets occurs by compressing Form II and the disclosed excipients into a core which is then coated. However, specific particle sizes and distributions of particle sizes are not expressly disclosed.
Li bridges this gap disclosing oral pharmaceutical compositions of azetidine derivatives as the active agent, whereby the preparation process provides a formulation that is simple and stable and the API has good content and mixing uniformity (see e.g., Abstract). Claim 1 discloses preparing azetidine polymorph derivatives possessing the following core formula (I):
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,
wherein the method further discloses crushing the active ingredient to a particle size range comprising the following parameters:
Dv(90) is 1-500 microns, preferably 1-100 microns;
Dv(50) is 1-100 microns, preferably 1-20 microns.
Claim 7 discloses that one of the derivatives encompassed by the invention is compound 26 which has the following formula and reads directly on the instantly claimed compound:
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Li additionally discloses using the prepared particles and compressing them into tablets, preferably coated (see e.g., claim 8; ¶[0131]). Tableting excipients are also disclosed and include microcrystalline cellulose as a preferred filler and magnesium stearate as a preferred lubricant. See ¶[0124] and ¶[0126].
The reference also discloses administering the practiced compositions for the purposes of treating various disorders in mammals, such as non-human mammals (e.g., dogs). Disorders that are taught as being orally treated include atopic dermatitis (see e.g., claim 30; ¶[0159], ¶[0163]).
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment.
Where the teachings of Hu appear to depart from the claimed invention is with regard to the particle size distribution as recited by claims 5, 8, 12, and 13. However, the teachings of Li bridge this gap disclosing that particles of active compound that are substantially insoluble (e.g., instantly claimed Form II per instant the Spec; ¶[0059]), may be crushed or milled to particle meeting the recited d50, d90, dv50, and dv90 ranges. Regarding the recited ranges, the Examiner acknowledges that two types of ranges are recited: d50 v. dv50, with the former being given a range with a definitive lower limit (e.g., 15-30 microns) and the latter not (e.g., ≤ 30 microns). With respect to the disclosure of Li, the Examiner submits that the teachings of both the preferred dv50 range of 1-20 microns and the preferred dv90 range of 1-100 microns reads on both sets of ranges. The disclosed dv50 range reads expressly on the recited dv50 range and overlaps the d50 range, while the disclosed range for dv90 encompasses both the recited d90 and dv90 ranges. MPEP §2144.05(I) states that “[i]n he case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” MPEP §2144.05(II)(A) additionally states that “[g]enerally, 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. ‘Where 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.’” MPEP §2144.05(II)(B) lastly states that “[i]n order to properly support a rejection on the basis that an invention is the result of ‘routine optimization,’ the examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail. The articulated rationale must include an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range.”
In the instant case, the Examiner has provided showings in the art of preparing the claimed active compound as a polymorph, if not as a substantially pure polymorphic crystalline form, whereby the resulting particles are compressed, with excipients, in to the final form of a coated tablet. Hu teaches and suggests by disclosure of compression into tablets that the compound is in particle form, but does not expressly disclose the recited range(s). Li discloses preparing polymorphic compounds such as the instantly claimed compound as well as crushing or milling it do particles that overlap and meet the claimed d50/d90 and dv50/dv90 ranges. Li additionally discloses that the claimed compositions achieve dissolution times ranging from 30-60 minutes, a property that is directly tied to the size(s) of the milled particles compressed into the tablet formulations, as is understood by persons of ordinary skill in the pharmaceutical arts. As such, the Examiner submits that said artisan would be motivated to modify the teachings of Hu to utilize the particle distribution practiced by Li in order to modify and achieve an improved dissolution profile for the instant compound from an oral tablet.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Response to Arguments
Applicant’s arguments with regard to the rejection of claims 1-4 and 6-16 under 35 USC 103(a) as being unpatentable over the combined teachings of Hu et al. and Li et al. have been fully considered but they are not persuasive.
Applicant’s remark states that “Li discloses 71 derivatives of formula 1 in claim 7” and “does not teach or suggest any suitable particle size or particle size distribution for [the] API.”
The Examiner, in response, disagrees and maintains the rejection for the reasons already presented above.
Applicant next asserts that “[a] skilled artisan would face an undue burden of experimentation and have no reasonable expectation of success to arrive at a suitable particle size and particle size distribution for [the] API as Li does not provide any guidance related to the suitable particle size and particle size distribution suitable for [the] API … specifically within a dosage form.”
Applicant next turns to the Specification [0083], as originally filed, and points to the observation that “it is problematic to uniformly distribute the small amount of the compound in unit dose forms” and that “[i]t has been surprisingly found that the present compound may be effectively dispersed within a unit dose form by … controlling the PSD [particle size distribution].”
At the outset, in response to Applicant’s arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Therein, the argument that Li discloses 71 derivatives of formula 1 is unpersuasive on its face since the disclosure of Hu discloses preparing the exact, pure crystalline compound as is instantly recited, down to the XRD peak pattern. Thus, what is at issue with Li is less the compound and more pointedly the particle size distribution. In view of the combined teachings, the Examiner respectfully maintains that the skilled artisan would not be burdened with arriving at the specific compound.
Regarding the particle size distribution, the Examiner notes that Li does teach and suggest dv(50) and dv(90) size ranges, and that those ranges both: (i) encompass the recited d50 and d90 ranges, and (ii) are encompassed by the disclosure of Li as being applied to all compounds produced therein.
Thus, as Li does teach and suggest the claimed pure crystalline compound as one of its embodiments, the Examiner respectfully maintains that the instantly claimed compound, and particle size distribution are taught and suggested by the combination of the references.
Applicant’s remarks appear to assert the content uniformity of the practiced dosage form is controlled by the recited particle size distribution. However, the Examiner respectfully submits that on consideration of the originally-filed disclosure, that no criticality appears to be shown for these distribution ranges, only that they are preferred.
Li, on the other hand, discloses ranges for dv(50) and dv(90), both of which encompass the recited ranges and are additionally considered to encompass the recited d50 and d90 size ranges. Li also provides disclosure that mixing uniformity or “content uniformity” is achieved for each of the dosages produced, stating that “the preparation method provided in this application is simple and stable, the API content and mixing uniformity of the intermediate materials in the preparation process are good, and the finished preparations obtained have fast dissolution and stable quality.”
Thus, absent a clear showing of evidence to the contrary, the combined teachings of the references continue to read on the amended composition and methods.
Lastly, in response to Applicant’s argument that the Examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant’s arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
All claims under consideration remain rejected; no claims are allowed.
Conclusion
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 extension fee 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615