DETAILED ACTION
This action is in response to Applicant’s submission dated October 25, 2023, in which Applicant amended claim 3, canceled claims 4-12, and added new claims 13 to 23.
Information Disclosure Statement
The references contained in the IDS dated October 25, 2023 are made of record.
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 .
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 non-obviousness.
Determining the scope and contents of the prior art.
Claims 1-3 and 13-23 are rejected under 35 U.S.C. § 103 as being unpatentable over WO 2016/038500 in view of Mino R. Caira, Crystalline Polymorphism of Organic Compounds, Topics in Current Chemistry, Vol. 198, pp. 163-208, XP008166276, ISSN: 0340-1022 (1998) and WO 2020/232325.
WO 2016/038500 discloses the same XRPD pattern structure but in two different crystalline forms 1 and 4. The only issue and potential difference between what is taught in the reference and the present claims is that the instant claims are directed towards a new crystalline form of Tafamidis: 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid, characterized by an XRPD profile with peaks at 9.6, 13.5, 16.3, 18.2, 20.4 and 27.5 degrees 2θ. This crystalline form alpha as instantly claimed is said to be stable and does not spontaneously evolve to other polymorphic forms. This result is also achieved by polymorphic forms 1 and 4 of WO 2016/038500. Tafamidis, in view of WO 2016/038500, appears to be prone to give numerous different crystalline forms, including thermodynamically stable forms like forms 1 and 4 of WO 2016/038500.
Ascertaining the difference between the prior art and the claims at issue.
The biological activity of a compound depends primarily on its molecular structure. To reach its target it will at some point be in solution, e.g. in body fluids, where all differences among polymorphs disappear. The skilled polymorphism chemist would thus expect that all polymorphs of compound tafamidis possess the same activity, at least to a certain extent. From common general knowledge it is known that the systematic investigation of a compound determines whether it is prone to polymorphism is routine practice in the pharmaceutical industry. It is also known that most substances when investigated for a sufficiently long time will reveal more than one polymorph. See Mino, et al., Crystalline Polymorphism of Organic Compounds, Topics in Current Chemistry, Vol. 198, pp. 163-208, XP008166276, ISSN: 0340-1022 (1998), particularly the paragraph bridging pages 165-166. Furthermore, the methods to screen for polymorphs are well known in the art. The skilled polymorphism chemist investigating the therapeutic application of compound tafamidis would thus routinely screen for polymorphs thereof. If such routine work yields another polymorph, e.g. the present polymorph alpha, then its provision is an obvious solution of said routine experimentation.
Any skilled polymorphism chemist would be incentivized to look for further crystalline forms of tafamidis, so that by trial and error would arrive at the new crystalline form having a stability equivalent to forms 1 and 4 already known in the art from WO 2016/038500. The use of the solvent and anti-solvent technique for recrystallization is a method routinely used by the average skilled organic chemist. Furthermore, tafamidis is already known from WO 2020/232325 to dissolve in methyl-THF for recrystallization purpose. The selection of the solvent/antisolvent technique is merely one of several straightforward possibilities from which the skilled organic chemist would select, in accordance with the circumstances, without the exercise of skill, in order to discover new polymorphs. The particular selection of hexane and heptane as anti-solvent is, by using trial and error, within the technical grasp of the skilled organic chemist.
As far as we know, this crystalline form alpha is disclosed in the reference. Applicants have to show that the instant compounds are different from the reference, by providing evidence such as melting point, or other physical or chemical characteristics.
“Mere recitation of newly-discovered function or property, inherently possessed by things in prior art, does not cause claim drawn to those things to distinguish over prior art; Patent Office can require applicant to prove that subject matter shown to be in prior art does not possess characteristic relied on where it has reason to believe that functional limitation asserted to be critical for establishing novelty in claimed subject matter may be inherent characteristic of prior art; this burden of proof is applicable to product and process claims reasonably considered as possessing allegedly inherent characteristics.” In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding the claims reciting the x-ray diffraction - these properties are inherently present in reference compounds. This compound disclosed in the reference renders the claims of the instant application obvious to one skilled in the art. See instant Figures 6-11.
Resolving the level of skill in the art.
The Court has addressed this obviousness issue: “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 12 (2007). “When there is a design need or market pressure to solve a problem and there are finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, … the fact that a combination was obvious to try might show that it was obvious”. Id. at 17. That is exactly the case here. The scope of polymorphs is a very finite list and Applicant was not left to pick and choose from a generic disclosure which compound (only Tafamidis) should be tested against the claimed polymorph. The instant polymorphic form of the present claims thus is reasonably expected to share the same properties as that taught in the reference given the express equivalency teaching recited.
Considering objective evidence present in the application indicating obviousness or non-obviousness.
In the absence of any substantiated unexpected property of the claimed polymorph alpha, which is relevant in comparison with the closest related crystalline form 1 of compound tafamidis, then non-obviousness cannot be acknowledged for polymorph alpha and subject matter referring thereto.
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ERICH A LEESER whose telephone number is (571) 272-9932. The Examiner can normally be reached Monday through Friday from 10-6 PST, M-F. PST.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Mr. James Alstrum-Acevedo can be reached at (571) 272-5548. The fax number for the organization where this application is assigned is 571-273-8300.
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/ERICH A LEESER/Primary Examiner, Art Unit 1622
United States Patent and Trademark Office
Tel. No.: (571) 272-9932