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 .
DETAILED ACTION
Status of 18/797,587
Claims 1-16 are currently pending.
Priority
Instant application 18/797,587, filed 8/8/2024, claims priority as follows:
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Support for the instant claims is found in the provisional application.
Information Disclosure Statement
All references from the IDS submitted on 1/29/2025 have been considered unless marked with a strikethrough.
Objection to the Abstract
The abstract of the disclosure is objected to for insufficient length, as it is less than 50 words. The abstract should generally be within the range of 50 to 150 words in length, and chemical abstracts in particular should provide the structure of the compound of a formula thereof in addition to methods of use. See MPEP § 608.01. Appropriate correction is required.
Claim Objections
Claims 4 and 5 are objected to as they are dependent on a rejected base claim.
Claim 16 is objected to for a minor grammatical informality. Claim 16 recites, “methyl t-butyl”, but should recite “methyl t-butyl” in an effort to be consistent with claim 14, from which 16 depends. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 9, and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 8, 9, and 12 recite the term, “about”, in reference to the temperature of the reactions. The term “about” is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the scope of time durations is rendered indefinite by the term “about”. In the interest of compact prosecution, the term “about” is currently being interpreted mean ±10% of the subsequent value modified by the term.
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.
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.
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 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 1-3 and 6-12 are rejected under 35 U.S.C. 103 as being unpatentable over Enanta Pharmaceuticals, Inc. (WO 2018/152413 A1, cited in the IDS of 1/29/2025, herein after “Enanta”), and further in view of Maj (Maj, A., Kudelko, A., and Swiatkowski, M. Molecules. 2022, 27, 459). The Examiner recognizes the instant application shares the Applicant with the WO 2018/152413 document. However, the document qualifies as prior art under 35 U.S.C. 102(a)(1) as it is was published more than a year than the effective filing date of the instant application.
Determining the scope and contents of the prior art
The reference Enanta teaches processes and intermediates useful in the preparation of respiratory syncytial virus inhibitors, and teaches the synthesis of compound (I-a), which is also known as instant Compound (I) (abstract, title). Specifically, Enanta teaches the reaction of instant compound (A) with 1,1’-cabonyldiimidazole to instant compound B in Step 3 (page 28):
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the reaction of instant compound (B) with instant compound (W) to generate instant compound (C) in Step 4 (page 28):
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And finally the reaction of instant compound (C) to instant compound (I) in Step 5 (page 29):
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With p-toluenesulfonyl chloride as the dehydration reagent.
With respect to claims 2 and 3, the conversion of compound (C) to compound (I) is conducted in the presence of Et3N, a base (page 29).
Regarding claims 6-9, the reaction of Step 3 of Enanta is run in acetonitrile and the reaction temperature begins at 20±5°C and is cooled down to 0±3°C.
With respect to claims 10-13, Step 4 of Enanta is conducted in N-methyl-2-pyrrolidone (NMP) and the reaction temperature begins at 25±5°C, is heated to 45°C, and cooled to 15°C then 3°C.
The reference Maj teaches the cyclodehydration a N,N’-diacylhydrazine with phosphorous pentachloride to a 1,3,4-oxadiazole (page 3, Scheme 1):
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Ascertaining the differences between the prior art and the claims at issue
Enanta fails to teach the conversion of instant compound (C) to instant compound (I) by a dehydration agent selected from the group consisting of N,N-dimethylsulfamoyl chloride, methyl N-(trimethylammoniumsulfonyl)carbamate, phosphorous trichloride, and phosphorous pentachloride. The reference Maj fails to teach the synthesis of Compound (I).
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of processes of producing respiratory syncytial virus (RSV) inhibitors. An artisan possess the technical knowledge necessary to make adjustments to the processes to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said processes of producing RSV inhibitors and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (B), it would have been prima facie obvious for one of ordinary skill in the art to substitute the reagent p-toluenesulfonyl chloride of Enanta with the phosphorous pentachloride of Maj because both reagents are known in the art to perform the same reaction, the conversion of N,N’-diacylhydrazines to 1,3,4-oxadiazoles. A skilled artisan would be motivated to make the substitution to optimize reaction conditions and identify additional methods of making Compound (I). Further, one of ordinary skill would reasonably predict that the substitution would result in a successful synthesis in light of the teachings of Enanta and Maj.
With respect to claims 8, 9, 12, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the reaction temperatures recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the temperatures of the reactions to provide optimal yields and reaction efficiency. The temperature of the reaction is a result effective parameter that will affect the physical properties of the final reaction. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the temperatures disclosed by Enanta above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal reaction temperatures to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the reaction and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. See MPEP § 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Claims 1-3 and 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Enanta Pharmaceuticals, Inc. (WO 2018/152413 A1, cited in the IDS of 1/29/2025, herein after “Enanta”), in view of Maj (Maj, A., Kudelko, A., and Swiatkowski, M. Molecules. 2022, 27, 459), Not Voodoo (https://web.archive.org/web/20220314054449/https://www.chem.rochester.edu/notvoodoo/pages/how_to.php?page=purify_crystallization, published March 14th, 2022), and Skonieczny (Skonieczny, S. “Recrystallization” January 6th, 2008).
Determining the scope and contents of the prior art
The references Enanta and Maj teach as disclosed above, and at least those teachings are incorporated herein.
The reference Not Voodoo teaches a method of recrystallization of compounds, where a compound is dissolved in “solvent b” followed by the addition of “solvent a”, and where upon slow evaporation of “solvent b”, “solvent a” replaces “solvent b”, and crystallization is induced, which helps teach claims 13 and 14.
Finally, the reference Skonieczny teaches recrystallization procedures and common solvent pairs, and includes the pair ethanol and acetone, which helps teach claims 14-16 (page 4, Table).
Ascertaining the differences between the prior art and the claims at issue
The references Enanta and Maj fail to teach as disclosed above, and at least those teachings are incorporated herein.
The reference Not Voodoo fails to teach the synthesis of compound (I) and the solvent systems for recrystallization of the product, whereas Skonieczny fails to teach the synthesis of compound (I) and the solvent replacement recrystallization procedure.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the process for producing RSV inhibitors. An artisan possess the technical knowledge necessary to make adjustments to the processes to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said processes for producing RSV inhibitors and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the process of producing compound (I) of Enanta and Maj with the recrystallization techniques and solvents of Not Voodoo and Skonieczny because recrystallization is a known technique in organic chemistry to purify compounds. A skilled artisan would be motivated before the effective filing date to combine the references to discover additional methods of purification of compound (I), and to optimize the yield of the synthesis of compound (I). A skilled artisan would have reasonably predicted that such a combination would result in a successful, improved process for producing compound (I) in light of the teachings of Enanta, Maj, Not Voodoo, and Skonieczny.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 11-14, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 6-12 of U.S. Patent No. 10,358,441 B2 (herein after the “’441 Patent”) in view of Enanta Pharmaceuticals, Inc. (WO 2018/152413 A1, cited in the IDS of 1/29/2025, herein after “Enanta”) and Maj (Maj, A., Kudelko, A., and Swiatkowski, M. Molecules. 2022, 27, 459).
The ’441 Patent recites a process for preparing the compound of formula (I):
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Which when A is a substituted heteroaryl, m is 0, and each n is 1, is the same compound as instant compound (I). Specifically, the claims of the ‘441 Patent recite the reaction of a compound of formula (X) with a compound of formula (III):
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Which when PG is H, A is a substituted heteroaryl, m is 0, each n is 1, and R5 is a heteroaryl, are the same as instant compounds (W) and (B), respectively, to generate a compound of formula (V):
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Which when the variables are the same as above, is the same as instant compound (C).
The claims of the ‘441 Patent fail to teach reacting compound (A) with 1,1’-carbonyldiimidazole to generate instant compound (B), defined as formula (III) in the ‘441 patent, and the specific dehydration agents N,N-dimethylsulfamoyl chloride, methyl N-(triethylammoniumsulfonyl)carbamate, phosphorous trichloride and phosphorous pentachloride. However, these deficiencies are remedied by the teachings of Enanta and Maj, as stated above. These references teach as disclosed above, and at least those teachings are incorporated herein.
Applying KSR prong (A), it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of the ‘441 Patent with Enanta and Maj in order to identify additional synthetic methods of preparing instant compound (I). A skilled artisan would be motivated to combine the teachings to optimize reaction conditions and discover additional methods and making compound (I), and would reasonably predict that the combination would result in a successful synthesis in light of the teachings of the ‘441 Patent, Enanta, and Maj.
Claims 1, 2, 6-7, 10-11, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10-12, and 17 of U.S. Patent No. 10,906,895 B2 (herein after the “’895 Patent”) in view of Enanta Pharmaceuticals, Inc. (WO 2018/152413 A1, cited in the IDS of 1/29/2025, herein after “Enanta”) and Maj (Maj, A., Kudelko, A., and Swiatkowski, M. Molecules. 2022, 27, 459).
The ’895 Patent teaches a process for preparing compound 1a:
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Which is the same as instant compound 1, by the reaction of a compound of formula (Xd):
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Where PG is hydrogen with a compound IV and an amine activating reagent:
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followed by a cyclizing reagent in the presence of an organic base.
The claims of the ‘895 Patent fail to teach the specific dehydration agents N,N-dimethylsulfamoyl chloride, methyl N-(triethylammoniumsulfonyl)carbamate, phosphorous trichloride and phosphorous pentachloride. However, these deficiencies are remedied by the teachings of Enanta and Maj, as stated above. These references teach as disclosed above, and at least those teachings are incorporated herein.
Applying KSR prong (A), it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of the ‘895 Patent with Enanta and Maj in order to identify additional synthetic methods of preparing instant compound (I). A skilled artisan would be motivated to combine the teachings to optimize reaction conditions and discover additional methods and making compound (I), and would reasonably predict that the combination would result in a successful synthesis in light of the teachings of the ‘895 Patent, Enanta, and Maj.
Conclusion
Claims 1-3 and 6-16 are rejected. Claims 4-5 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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