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 .
Priority
This application is a national stage entry of PCT/EP2020/066182 filed on 06/11/2020.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in INDIA on 06/12/2019.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in EP on 08/27/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Response to Amendment
No amendments to the claims were made by Applicant’s reply filed on October 15, 2025. Claims 5, 8, 9 and 11-29 are withdrawn. Claims 1-4, 6, 7 and 10 are currently presented for examination.
Response to Arguments
With respect to the rejection under 35 USC 112(b), Applicant argues formulas (A-1b) and (A-3b) are sub-formulas of (A) as defined in claim 1, and do not have a different structure and R1 is not in a different location on the cyclobutane ring. Applicant submits that the cyclobutane ring in formula (A) of claim 1 does not specify stereochemistry. As a consequence, (A-1a) and (A-3a) has R1 in the same position as in formulas (A-1b) and (A-3b), only with a different stereo-configuration. Those skilled in the art realize that the cyclobutane ring in any of formulas (A-1a), (A-3a), (A-1b) and (A-3b) can rotate about the spiro-fused carbon atom. When the cyclobutane rings in formulas (A-1a) and (A-3a) are rotated, for instance, 180 degrees, these cyclobutane rings would then have R1 in the same configuration as the cyclobutane rings in formulas (A-1b) and (A-3b), only in a different stereoconfiguration. These arguments are found persuasive, and thus the previous rejection under 35 USC 112(b) is hereby withdrawn.
Applicant's arguments filed October 15, 2025 with respect to the rejection under 35 USC 103 have been fully considered but they are not persuasive.
Applicant argues that no reason has been identified to select the Redlich compound as a lead compound. Applicant argues "In cases involving the patentability of a new chemical compound, prima facie obviousness under the third Graham factor generally turns on the structural similarities and differences between the claimed compound and the prior art compounds." Otsuka Pharma. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012). Applicant argues that obviousness requires selection of a "lead compound and determination of whether the prior art would have supplied a reason or motivation to modify that lead compound to make the claimed compound, with a reasonable expectation of success. Applicant argues that the claimed compounds contain functional groups that can be diversified to give access to compounds having activity against PRMT5 and the Examiner has not identified why the skilled person would have selected the compound of Redlich out of all the chemical compounds that were known when the instant patent application was filed and Applicant argues that Redlich is silent regarding any biological activity, in particular much less any biological activity with respect to PRMT5.
Applicant further argues that there is no reason to modify the Redlich compound to arrive at a compound as claimed. Applicant argues that an obviousness analysis, however, requires more than mere structural similarity or similar utility. Applicant argues that Patani does not cure the deficiencies of Redlich since to establish a prima facie case of obviousness based on a combination of elements in the prior art, the law requires a motivation to select the references and to combine them in the particular claimed manner to reach the claimed invention which must come from an analysis of the properties of the lead compound. Applicant argues that since Redlich is silent regarding any biological activity whatsoever, there is no basis for using the Redlich compound in a "lead compound" analysis and/or with Patani.
These arguments are found not persuasive because the rejected claims do not fall into the paradigm established by the lead compound analysis. In Takeda, the court applied the lead compound analysis to a claim to a specific compound, not a genus of compounds as in instant claim 1, finding that “in cases involving new chemical compounds, it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound.” Takeda Chemical Industries, Ltd. v. Alphapharm Pty., Ltd.,492 F.3d 1350, 1357 (Fed. Cir. 2007). That is, the Takeda court was not analyzing a claim drawn to thousands of compounds, like instant claim 1, but rather was analyzing a claim drawn to a compound with one specific chemical formula. Id. at 1353. Similarly, Otsuka also applied the lead compound analysis in the context of a claim to the specific compound, Ariprazole, and Daiichi to the specific compound Olmesartan, so neither decision was drawn to a genus claim of thousands of compounds as in the instant fact pattern. Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1284 (Fed. Cir. 2012); Daiichi Sankyo Co., Ltd. v. Matrix Labs., Ltd., 619 F.3d 1346 (Fed. Cir. 2010).
With respect to Applicant’s argument pertaining to biological activity with respect to PRMT5, unlike Takeda’s claim to an antidiabetic composition, Otsuka’s claim to a schizophrenia treating composition, or Daiichi’s claim to treatment of high blood pressure, the rejected claims of the instant application do not encompass any particular “pertinent properties” or functional requirements nor are the rejected claims directed to the treatment of any particular disease. Therefore, even the attempt to apply the lead compound analysis fails because the rejected claims lack one specific activity or function to serve as the target for optimization using a lead compound. See Takeda, 492 F.3d 1353; Otsuka, 678 F.3d at 1285; and Daiichi, 619 F.3d at 1347.
In the instant case, Redlich discloses compounds having the same core structure as a subgenus of compounds of formula (A) as claimed in instant claim 1, wherein Y is O, n is 1, R2 is O, R1 is hydrogen, R4 and R5 taken together are a diol protecting group. The only difference between the claimed compounds and the compound of Redlich et al. is a methyl group attached to the cyclobutane ring instead of a hydrogen.
However, it is maintained that a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. In view of the teachings of Patani, a substitution of a hydrogen for a methyl group would not have been expected to change the physical or chemical properties of the compound. Patani et al. teaches the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties (page 3148). Patani et al. teaches that classical bioisosteres include methyl groups as replacements for hydrogen (page 3152). Thus, in view of the teachings of Patani et al., the compound as claimed and the compound of the prior art are similar enough that one would expect similar properties since the only difference between the compounds is a methyl group instead of a hydrogen which are bioisosteres known to elicit similar biological activity. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement).
Thus substituting a hydrogen for methyl does not patentably distinguish the claimed compound over the compound of Redlich et al. absent an unexpected showing that an obvious bioisosteric replacement of hydrogen for methyl produces compounds with vastly different properties. The presumption of obviousness based on a reference disclosing structurally similar compounds may be overcome where there is evidence showing there is no reasonable expectation of similar properties in structurally similar compounds. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963).
With respect to Applicant’s argument that the compounds of Redlich fail to possess any utility and thus there is no motivation to modify the compounds, it is noted that Redlich et al. specifically teaches that the compounds are optically active cyclobutanones, which are preparatively valuable building blocks, and thus this means that they are useful in drug development (page 777). Therefore, since these compounds are useful in drug development, an ordinary skilled artisan would have been motivated to modify the compounds by procedures well-known in the art such as bioisosteric replacement with a reasonable expectation of producing new and more useful building blocks for drug development. Thus, it is maintained that a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991).
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).
Accordingly, for the reasons detailed above, the previous rejection under 35 USC 103 is hereby maintained and reproduced below. This action is FINAL.
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.
Claims 1-4, 6, 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Redlich et al. (Angew. Chem. lnt. Ed. Engl. 28 (1989) No. 6, pages 777-778 Provided on IDS dated 12/08/2022) in view of Patani et al. (Chemical Reviews, 1996, Vol. 96, No. 8, pages 3147-3176).
Claims 1-4, 6, 7 and 10 of the instant application claim a compound of formula (A) having the following structure:
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190
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such as
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wherein Bn is benzyl.
Redlich et al. discloses the following compound
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wherein R is CH2Ph, R1 is Me and R2 is H, or R1 is H and R2 is Me (page 778). Thus Redlich et al. discloses
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200
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.
The only difference between the claimed compound and the compound of Redlich et al. is the methyl group attached to the cyclobutane ring.
However, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and/or similar utilities. “An obviousness rejection based on similarity in chemical structure and/or function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties.” In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In the instant case, a substitution of a hydrogen for a methyl group would not have been expected to change the physical or chemical properties of the compound.
Patani et al. teaches the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties (page 3148). Patani et al. teaches that the bioisosteric rationale for the modification of lead compounds is traced back to the observation by Langmuir in 1919 regarding the similarities of various physicochemical properties of atoms, groups, radicals, and molecules (page 3148). Patani et al. teaches that classical bioisosteres include methyl groups as replacements for hydrogen (page 3152).
Thus, in view of the teachings of Patani et al., the compound as claimed and the compound of the prior art are similar enough that one would expect similar properties since the only difference between the compounds is a methyl group instead of a hydrogen which are bioisosteres known to elicit similar biological activity. Thus the cited claims of the instant application are rendered obvious over the cited prior art teachings.
Conclusion
Claims 1-4, 6, 7 and 10 are rejected. Claims 5, 8, 9 and 11-29 are withdrawn. 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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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