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 .
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.
Claims 86 and 88 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2019/182925 A1 to Terrett et. al. (Terrett’925; cited on the ISR form) in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
Regarding claims 86 and 88, Terrett’925 teach oxadiazole compounds, their manufacture, pharmaceutical compositions containing them and their use as Transient Receptor Potential (TRP) cation channel antagonists. See page 1 paragraph 0002. In particular, Terrett’925 teach the isolated intermediate (3R,5RZ)-5-(4-fluorophenyl)-N'-hydroxytetrahydrofuran-3-carboximidamide of structure
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. See page 103 paragraph 0312. See claim 86 limitation where R1 = R2 = R3 = R4 = H and R5 = F.
However, Terrett’925 fails to teach a compound of structure
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with the circled H. See claim 86. Moreover, Terrett’925 fails to teach a compound of structure
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with the circled Cl. See claim 88.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Additionally, Meanwell teach that F, Cl, and Br are also classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute NH2 for a H with a reasonable expectation that compounds with either NH2 or H would have similar biological properties. Furthermore, Meanwell suggest the ability to substitute F for Cl with a reasonable expectation that compounds with either F or Cl would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify isolated intermediate (3R,5RZ)-5-(4-fluorophenyl)-N'-hydroxytetrahydrofuran-3-carboximidamide Terrett’925 in view of Meanwell, that is to substitute the NH2 group for an H atom. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both H and NH2 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties. Moreover, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify isolated intermediate (3R,5RZ)-5-(4-fluorophenyl)-N'-hydroxytetrahydrofuran-3-carboximidamide Terrett’925 in view of Meanwell, that is to substitute the NH2 group for an Cl atom. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both Cl and NH2 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Claims 87 and 89 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2019/182925 A1 to Terrett et. al. (Terrett’925; cited on the ISR form) in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Terrett’925 and Meanwell as they relate to claims 86 and 88, from which claims 87 and 89 depend, are given previously in this office action and are fully incorporated here.
However, Terrett’925 fails to teach a compound of where R5 = Cl. See claims 87 and 88.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Additionally, Meanwell teach that F, Cl, and Br are also classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute F for Cl with a reasonable expectation that compounds with either F or Cl would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify isolated intermediate (3R,5RZ)-5-(4-fluorophenyl)-N'-hydroxytetrahydrofuran-3-carboximidamide Terrett’925 in view of Meanwell, that is to substitute the F atom for an Cl atom. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both Cl and F are halogens and classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Discussion of the Prior Art
The closest prior art is International Publication Number WO 2019/182925 A1 to Terrett et. al. (Terrett’925; cited on the ISR form) that teach oxadiazole compounds, their manufacture, pharmaceutical compositions containing them and their use as Transient Receptor Potential (TRP) cation channel antagonists. See page 1 paragraph 0002. In particular, Terrett’925 teach the isolated intermediate (3R,5RZ)-5-(4-fluorophenyl)-N'-hydroxytetrahydrofuran-3-carboximidamide of structure
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. See page 103 paragraph 0312. In fact, Terrett’925 teach the synthetic scheme which starts with the 4‐chlorobenzaldehyde. See page 93 paragraph 0289.
However, the prior art of Terrett’925 fails to teach a process for preparing compound (3) of structure
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by forming a reaction mixture comprising CO, H2, a rhodium catalyst, a ligand, a solvent, and compound (2), and reacting the reaction mixture to form a reaction product mixture comprising compound (3), wherein: (i) compound (2) is of the structure
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. See claim 1. Moreover, Terrett’925 fails to teach a process for preparing the intermediates as recited in dependent claims 13, 17, 36 – 38, 48 – 49, 57 – 58, 64 – 65, 73 – 74, and 83. See claims 13, 17, 36 – 38, 48 – 49, 57 – 58, 64 – 65, 73 – 74, and 83. Furthermore, Terrett’925 fails to teach compound (3) of structure
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. See claims 84 – 85. Thus given that the process requires the starting material of compound (3) and given that Terrett’925 fails to teach compound (3), the process claims are free of the prior art. Hence claims 1, 13, 17, 36 – 38, 48 – 49, 57 – 58, 64 – 65, 73 – 74, and 83 – 85 are free of the prior art.
Conclusion
Claims 1, 13, 17, 36 – 38, 48 – 49, 57 – 58, 64 – 65, 73 – 74, and 83 – 85 are allowable. Claims 86 – 89 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
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