DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The instant application is a continuation of application 17/230,175 (now US 12,071,402) filed 14 April 2021 which is a continuation of application 16/804,926 filed 28 February 2020 which is a continuation of application 13/917,730 filed 14 June 2013 which is a continuation-in-part of PCT/EP2012/050151 filed 5 January 2012. Acknowledgement is made of the Applicant’s claim of foreign priority to application EP11150431.2 filed 7 January 2011.
Examiner's Note
Applicant's amendments and arguments filed 3 September 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant's response, filed 3 September 2026, it is noted that claims 14-21 have been newly added. Support can be found throughout the specification and claims as originally filed.
Status of the Claims
Claims 14-21 are pending.
Claims 14-21 are rejected.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 14-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ciszewski et al. (WO 2010/080409 A1) in view of Ando et al. (Remington chapter 38, published 2005) in view of Esperester et al. (US 2004/0151769).
Ciszewski teaches a hemifumarate salt of (1-{4-[1-(4-cyclohexyl-3-trifluoromethylbenzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid) (compound 1) (abstract; page 2, compound 1 ).
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The compound is formulated in the crystalline form and provided as a pharmaceutical composition comprising the API above and a pharmaceutically acceptable adjuvant, diluent, or carrier (pg 21, ¶4). There are no basic compounds necessarily present in the composition of Ciszewski. Regarding the form of the drug, Ciszewski teaches that generally it is important to provide the drug in a substantially crystalline and stable form (pg 2, ¶1) and that the hemifumarate salt of compound 1 is just that (pg 4, ¶10). Moreover, Ciszewski teaches the degree of crystallinity as being greater than 20%, with greater than 80% being a preferred embodiment, as required in instant claim 9 (pg 4, ¶10). As for the formulation, Ciszewski discloses that a suitable solid dosage form for oral administration is a tablet (pg 23, ¶1) and that the concentration of active agent should be between 1-1000 mg (pg 28, ¶3). Said solid dosage form can be prepared with a coating or shell (pg 24, ¶2). Among the suitable excipients to be included in the composition of Ciszewski are certain silicates or talc, binders, and disintegrating agents (pg 23, ¶1).
Ciszewski does not teach the compound as having an X90 diameter as required in instant claims 17-18. Ciszewski does not teach including colloidal silica.
Ando teaches general guidelines on the preparation of active pharmaceutical ingredients (APIs) including particle-size effects (pgs 734-735). In particular, Ando discloses that for a drug particle, the particle size is inversely proportional to the dissolution rate resulting in smaller particle dissolving faster than larger ones (pg 735, ¶1-2).
Esperester teaches that colloidal silica can be used as a disintegrant [0055] (claim 9).
It would have been prima facie obvious to prepare the invention of Ciszewski as a coated tablet comprising Compound 1 (1-1000 mg) along with non-basic excipients such as binding agents or disintegrants. The salt form in Ciszewski is a hemifumarate. Thus, to form said salt, fumaric acid would have to be included in the composition along with Compound 1. Regarding claims 6-7, Ando's teachings that particle-size can be varied to achieve a desired dissolution profile establish the X90 diameter as a result-effective variable that can be adjusted to the desires of the inventor. The optimum or workable range of particle size can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). After preparing the composition as a tablet, as taught by Ciszewski, the skilled artisan would have found it obvious, as stated above, to adjust the particle diameter to arrive at the instant invention.
It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Consistent with this reasoning, it would have been obvious to have selected various combinations of excipients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Regarding the selection of disintegrating agent, colloidal silica is known in the prior art as being a disintegrant, thus it would have been obvious to select it for use in the invention of Ciszewski. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).
Regarding the concentration of active agent, the art teaches a broad range of from 1-1000 mg, which overlaps with the claimed range of from 0.25-4 mg. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). MPEP 2144.05 (I).
Claims 14-21 are accordingly rejected in view of the prior art.
Response to Arguments
Applicant's arguments filed 3 September 2026 have been fully considered but they are not persuasive. The Applicant argues, on pages 5-6 of their remarks, that they have discovered that tablets of the claimed active agent can be stabilized by avoiding basic excipients, such as magnesium stearate. The Applicant points to Example 5 in the specification wherein a coated composition comprising magnesium stearate exhibited 16% degradation over time whereas an uncoated composition with glyceryl behenate instead showed only 4% degradation. The Applicant argues that routine optimization is thus misplaced.
In response, the Applicant has presented only one single data point using a direct comparison of two different lubricating agents. They have not shown that universally all non-basic excipients would result in higher degradation. At best, the Applicant has shown a unique and possibly unexpected result relating only to the use of glyceryl behenate. As such, the claims are not commensurate in scope with the data presented. There is a fundamental requirement that must be met before secondary considerations can carry the day. "For objective evidence of secondary considerations to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention." Wyers v. Master Lock Co., 616 F.3d 1231, 1246 [95 USPQ2d 1525] (Fed. Cir. 2010) (quotation omitted). Where the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention. Takai Corp. v. Easton Enters., Inc., 632 F.3d 1358, 1369 [97 USPQ2d 1673] (Fed. Cir. 2011) ("If commercial success is due to an element in the prior art, no nexus exists."); Ormco Corp., 463 F.3d at 1312 ("[l]f the feature that creates the commercial success was known in the prior art, the success is not pertinent."); In re Woodruff, 919 F.2d 1575, 1578 [16 USPQ2d 1934] (Fed. Cir. 1990). Therefore, the data in Example 5 does not amount to unexpected results that are sufficient in overcoming the pending obviousness rejection, and the rejection based on routine optimization is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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