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 .
Current Status of 17/620,314
This Office Action is responsive to the amended claims of October 1, 2025. Claims 1-3, 7-11, 14-17, 25, and 26 have been examined on the merits.
Priority
Acknowledgement is made of Applicants’ claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP19182954.8, filed on 06/27/2019.
The effective filing date is 06/27/2019.
Response to Arguments
The Examiner acknowledges receipt of Applicants’ claim amendment and Reply of October 1, 2025.
§103 Rejection of Claims 15-17
The Applicants contend that Li ‘919 does not teach the presently claimed purification process for compound (7), because Li ‘919 discloses formation and isolation of compound (F), equivalent to instant compound (7), without teaching a subsequent purification step. Applicants allege that Li ‘919’s purification employs protic solvents such as methanol, but does not disclose or suggest the specific solvent combination of acetone and ethanol recited in claim 15. According to Applicants, Li ‘919 provides no motivation to employ these particular solvents nor any indication that such a solvent system would afford improved purity. Applicants further assert that the claimed process unexpectedly affords compound (7) with significantly higher purity (99.9%, UPLC) compared to the reported purity of Li ‘919 (99.4%), and therefore the use of acetone and ethanol cannot be regarded as a routine modification. In view of these alleged differences and purportedly superior purity results, Applicants argue that the claimed purification would not have been predicted or expected from Li ‘919.
Applicants’ arguments have been fully considered but they are not persuasive. While Applicants assert that Li ‘919 merely isolates compound (F), Li ‘919’s disclosure of solvent-induced crystallization and recovery of (F) as a high-purity solid constitutes purification of the intermediate. The fact that the reference does not label these operations as “purification” is immaterial, as crystallization is a standard purification technique in the chemical arts. Further, Li ‘919 already teaches recovery of (F) at purities exceeding 99%. An incremental numerical increase to approximately 99.9% does not by itself demonstrate an unexpected result. Further, the prior art is not required to expressly list each individual solvent within a well-known class. Selecting alternative members of a known solvent class (polar protic, polar, aprotic, etc.) for recrystallization is considered routine optimization, and does not require specific suggestion in the reference. Applicants have not provided comparative experimental data demonstrating that the alleged purity increase is attributable to the specific acetone/ethanol solvent system under comparable reaction conditions to Li ‘919. In the absence of controlled comparative evidence isolating the claimed feature, attorney assertion of unexpected results is insufficient to rebut the prima facie case.
§103 Rejection of Claims 1-3 and 25
Applicants argue that the combined teachings of Furniss and Li ‘918 do not provide motivation for streaming an inert gas over the reaction mixture at the claimed rate and further contend that the Examiner has committed a legal error by asserting reliance on Aller. However, the rejection of claims 1-3 and 25 did not rely on Aller, and the arguments directed to Aller are therefore not responsive to the actual grounds of rejection and are not considered further. Moreover, in the previous Office Action, the Examiner expressly cited evidentiary reference Reinhardt which explained that inerting or streaming inert gas above a reaction mixture is a well-known technique used to suppress undesired side reactions and protect oxygen- and moisture-sensitive reagents, intermediates, and products. Applicants have not addressed or rebutted this evidence. Accordingly, the Examiner’s rationale remains unrebutted, and the arguments presented do not overcome the prima facie case of obviousness. The rejection is therefore maintained.
§103 Rejection of Claims 1 and 14
Applicants again assert that the cited references fail to suggest the claimed streaming step. However, the Examiner previously provided an evidentiary reference establishing that streaming or inerting is a well-known technique used to protect oxygen- and moisture-sensitive reactions and suppress undesired side reactions. As stated above, Applicants have not addressed or rebutted this evidence. The Examiner’s prior discussion of this point is incorporated herein by reference. Because Applicants have not provided substantive response to the evidence supporting the Examiner’s rationale, the arguments are non-responsive and are not persuasive. Accordingly, the rejection is maintained.
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 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.
Claims 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Li ‘919 (CN 104803919A, found IDS filed 12/17/2021).
Determining the scope of the prior art:
Li ‘919 teaches a preparation method of an enzalutamide intermediate F, wherein R1 can be methyl ethyl, or isopropyl (Li ‘919 claim 1). Li ‘919 teaches a purification process for the compound F (equivalent to instant claim 15, Formula (7), see below) comprising contacting F with a protic solvent, such as an alcohol, and then contacting F with a polar solvent, reading on instant claims 15-17.
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Ascertaining the differences between the prior art and the claims at issue:
Li ‘919 does not explicitly teach the solvents acetone or ethanol and does not teach the claimed solvent ratios.
Resolving the level of ordinary skill in the pertinent art:
Those of relevant skill in the art are those with the level of skill of the inventors of the references cited to support the Examiner’s positions.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to use a protic solvent (specifically, an alcohol) in combination with a polar solvent in the purification of compound F, based on the success of such solvent systems disclosed in Li ‘919. Given the demonstrated effectiveness of these systems in achieving high-purity products, the artisan would reasonably expect that applying similar alternative solvent combinations would yield compound F in comparable purity. The screening of alternative solvent systems within the same general categories (protic and polar solvents) is a well-established and routine practice in the art (evidenced by 2.20 of Vogel’s Textbook of Practical Organic Chemistry). In view of the reference Li ‘919, the artisan would have been further motivated to explore related solvent combinations, anticipating that such screening would produce recrystallized products with similar purity. The claimed solvent ratios are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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). See MPEP § 2144.05(II)(A)).
Applicants contend that the use of acetone and ethanol leads to a product of higher purity (99.9%) compared to the 99.4% purity disclosed in the prior art reference. However, the application does not disclose the analytical methods used to determine the reported purity values. Without such disclosure, the reliability, accuracy, and reproducibility of these values cannot be assessed. As such, there is no evidence of criticality or unexpected results sufficient to overcome the prima facie case of obviousness. The mere numerical difference in reported purity, unsupported by validated methodology, lacks probative value and does not demonstrate that the claimed purification process provides a non-obvious improvement over the prior art.
Claims 1-3, 25, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Li ‘918 (CN 104803918, found in IDS submitted 12/17/2021) in view of Furniss (Arthur Israel Vogel, et al. Vogel’s Textbook of Practical Organic Chemistry. Fifth ed., Prentice Hall, 1989).
Determining the scope of the prior art:
Li ‘918 teaches a method for preparing enzalutamide (compound G, which is equivalent to instant claim 1’s formula (1)) comprising the following steps:
Reacting compound (A) (equivalent to instant claim 1’s formula (2)) with compound (B) (equivalent to instant claim 1’s formula (3)) to produce compound (C) (equivalent to instant claim 1’s formula (4)) (Page 3). R1 of each of the compounds A, B, and C, above is methyl (Page 3, [0031]). LG is a halogen leaving group such as I, Br, Cl, F, reading on instant claims 2 and 25 (Page 3, [0033]). Example 1 of LI ‘918 further specifies that this reaction takes place in the solvent system of DMF and water and that the reaction was conducted under nitrogen, reading on instant claims 1a and 3 (Page 5, [0058]).
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Esterification of (C) (equivalent to instant claim 1’s formula (4)) to produce (D) (equivalent to instant claim 14’s formula (5)) (Page 4).
Reaction of (D) (equivalent to instant claim 14’s formula (5)) with (E) (equivalent to instant claim 14’s formula (6)) to produce (F) (equivalent to instant claim 14’s formula (7)) (Page 4).
Aminolysis of the ester of (F) (equivalent to instant claim 14’s formula (7)) with suitable amine to form amide of (G) (equivalent to instant claim 1’s formula (1)) (Page 3).
Steps ii-iv above from LI ‘918 teach transforming (C) (equivalent to instant claim 1’s formula (4)) into (G) (equivalent to instant claim 1’s (1)), reading on instant claim 1 b).
Furniss teaches how to set up apparatuses and maintain inert atmospheres for chemical reactions. Inert atmospheres can be maintained by maintaining a constant positive pressure of the inert gas or through continuous flow of the inert gas through the apparatus (pg. 126), reading on instant claim 1.
Ascertaining the differences between the prior art and the claims at issue:
Li ‘918 does not explicitly teach streaming the inert gas above the reaction mixture nor does it teach the claimed range of flow rates of the streamed gas.
Furniss does not teach the claimed chemical reaction.
Resolving the level of ordinary skill in the pertinent art:
Those of relevant skill in the art are those with the level of skill of the inventors of the references cited to support the Examiner’s positions.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to modify the reaction conditions of Li ‘918 to incorporate a streamed flow of an inert gas over the reaction mixture based on the teachings of Furniss. The artisan would recognize inert gas streaming as an analogous and commonly used alternative to other blanketing methods, such as the use of sealed vessels or static gas atmospheres. Incorporating inert gas streaming would have been an obvious optimization expected to suppress undesired side reactions and protect moisture and/or oxygen-sensitive reagents, intermediates, and products (see evidentiary reference Reinhardt, which describes inerting practices known in the art).
Although Applicants assert that streaming nitrogen reduces reaction time, the claimed process achieves a shorter reaction time (2.5 hours) at the cost of a lower yield (74%) compared to the process of Li ‘918 (14 hours, 78.5%). This suggests a basic tradeoff between time and conversion, not an unexpected result. Rather than demonstrating a critical or surprising effect from the nitrogen streaming, the data indicates the reaction was simply stopped earlier, before full conversion was achieved. As such, there is no evidence that this modification yields a result beyond what would have been reasonably expected by the artisan applying known inerting techniques.
Claim 26 has been amended in the present response. However, the amendment does not place the claim in condition for allowance, and the claim remains rejected for the reasons previously stated.
Claims 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Li ‘918 and Furniss in view of Thennati (WO 2017081702 A2, found in IDS submitted 12/17/2021).
Determining the scope of the prior art:
Li ‘918 and Furniss teach claim 1, see above.
Thennati teaches a reaction of a compound of formula (II) (equivalent to instant claim 1’s formula (4)), wherein R is C1-C4 alkyl, with a compound of formula (III) (equivalent to instant claim 14’s formula (6)), producing a compound of formula (IV) (equivalent to the instant claim 14’s formula (7)), seen below (Page 8, lines 10-15, Page 11, claim 1). This process reads on claim 14d in the instant application.
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Ascertaining the differences between the prior art and the claims at issue:
Li ‘918 does no teach the direct reaction of the compound of formula (4) with the compound of formula (6) to provide the compound of formula (7) as detailed in instant claim 14d.
Furniss does not teach the claimed chemical reactions.
Thennati does not teach the streaming of and inert gas over the reaction.
Resolving the level of ordinary skill in the pertinent art:
Those of relevant skill in the art are those with the level of skill of the inventors of the references cited to support the Examiner’s positions.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to modify the reaction conditions of Li ‘918 and Furniss with the process taught by Thennati which describes the condensation of compound of formula II (equivalent to instant claim 1’s formula (4)) with a compound of formula III (equivalent to instant claim 14’s formula (6)) to form compound of formula IV (equivalent to instant claim 14’s formula (7)). A person of ordinary skill in the art would have recognized that applying the process disclosed by Thennati represents an improvement over the method described by Li ‘918, as it provides an alternative route for the synthesis of (7) wherein the alternative route reduces the number of steps required to synthesize compound (7). Alternative routes that streamline the synthetic process would have been expected to enhance the production of compound (7) by minimizing time and costs associated with additional steps, thereby providing a more efficient synthetic route with a reasonable expectation of success.
Conclusion
Claims 7-11 are allowable.
Claims 1-3, 14-17, and 25-26 are rejected.
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 CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625