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
The present application claims priority to the application, 63/357,859 with effective filing date of 1 July 2022.
Claim Status
This Office Action is in response to Applicant’s Response to Restriction Requirement filed, 22 January 2026. Applicant’s election without traverse of Group I (claims 1-17) in the reply filed on 22 January 2026 is acknowledged.
Claims 21 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group (Group II: claims 21 and 22)(, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 22 January 2026.
Claims 1-17 are pending.
Information Disclosure Statement
The Information Disclosure Statements filed on 4 April 2024 and 22 January 2026 and the references cited therein have been considered, unless indicated otherwise.
The reference, wherein a copy was not provided, are lined through. This reference is WO 2009/062285.
Claim Rejections - 35 USC § 112
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.
1. Claims 8-15 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 in view of Bekerman (U.S. Patent Publication No. 2021/0188815, published 24 Jun 2021) and Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018).
Claim 8 recites a pharmaceutically acceptable salt which is substantially isolated. However, “substantially isolated” is unclear, because isolation of a small molecule is binary, wherein the small molecule is either isolated or not. The specification does not describe or define what the term “substantially isolated” means, and it is not a term known in the art. See MPEP § 2173.05(b)(III)(D).
Claims 9-11 recite a composition, wherein the compound or pharmaceutically acceptable salt thereof is present in the composition in an amount of greater than about 25% (claim 9), 50% (claim 10), or 75% (claim 11) by weight or greater than about 95% purity. However, “greater than about” is ambiguous in view of the closest prior art, Bekerman (U.S. Patent Publication No. 2021/0188815, published 24 Jun 2021). Bekerman teaches methods of administrating compounds of a significantly similar structure:
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, for preventing HIV in a subject and thus compositions thereof (abstract). Bekerman further teaches that the HIV/AIDs pandemic has claimed the lives of millions of people and that millions more are affected ([0003]). Further, Bekerman specifies that new and effective means for preventing HIV infection are needed, because there are only two medications being explored for pre-exposure prophylaxis ([0003]). Additionally, Bekerman teaches compositions where the compound is greater than 25% by weight, 50% by weight, and 75% by weight ([0160]). In the current record, there is nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of amount in terms of weight percent is covered by the term "about." Thus, the limitation of “greater than about” in claims 9-11 leads to uncertainty. See MPEP § 2173.05(b)(III)(A).
Claim 15 recites a preparation, wherein the compound or pharmaceutically acceptable salt thereof is present in greater than about 95% purity. However, “greater than about” is relative in view of the closest prior art, Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018). Brizgys teaches compounds for treatment of HIV (abstract). Brizgys specifically teaches the compounds:
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(column 117, lines 25-35; column 118, lines 35-45; column 118, lines 55-65; column 142, lines 5-15; column 148, lines 5-15). Further, Brizgys teaches that the stereoisomer is at least 98% pure, which significantly overlaps with claimed range (greater than about 95% purity; column 18, lines 39-42 and 47-50). In the current record, there is nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of purity is covered by the term "about." Thus, the limitation of “greater than about” in claim 15 leads to uncertainty. See MPEP § 2173.05(b)(III)(A).
Claims 12-14 recite a composition, wherein the compound or pharmaceutically acceptable salt thereof is present in the composition in an amount of less than about 25% (claim 12), 10% (claim 13), or 1% (claim 14) by weight. However, “less than about” is relative in view of the closest prior art, Bekerman (U.S. Patent Publication No. 2021/0188815, published 24 Jun 2021). Bekerman teaches methods of administrating compounds of a significantly similar structure:
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, for preventing HIV in a subject and thus compositions thereof (abstract). Bekerman further teaches that the HIV/AIDs pandemic has claimed the lives of millions of people and that millions more are affected ([0003]). Further, Bekerman specifies that new and effective means for preventing HIV infection are needed, because there are only two medications being explored for pre-exposure prophylaxis ([0003]). Regarding claim 12, Bekerman teaches compositions where the compound is where the excipient is present in an amount that is greater than about 70%, which corresponds to 30% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound), which corresponds to a composition wherein the compound is in an amount less than 25% weight ([0257]). Regarding claim 13, Bekerman teaches compositions where the excipient is present in an amount that is greater than about 90%, which corresponds to 10% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound), which corresponds to a composition wherein the compound is in an amount less than 10% by weight ([0257]). Regarding claim 14, Bekerman teaches compositions where the excipient is present in an amount that is greater than about 95%, which corresponds to about 5% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound), which corresponds to a composition wherein the compound is in an amount less than 5% ([0257]). Because of the lack of clarity on the endpoints of “less than about,” it can reasonably be inferred that 5% is about 1%. In the current record, there is nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of amount is covered by the term "about." Thus, the limitation of “less than about” in claims 9-11 leads to uncertainty. See MPEP § 2173.05(b)(III)(A).
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.
2. Claims 1-8 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018, see IDS filed 17 Oct 2023) in view of Graupe (U.S. Patent No. 10,071,985, issued 11 Sept 2018, see IDS filed 17 Oct 2023).
Brizgys teaches compounds for treatment of HIV (abstract).
Brizgys specifically teaches the compounds:
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(column 117, lines 25-35; column 118, lines 35-45; column 118, lines 55-65; column 142, lines 5-15; column 148, lines 5-15). Further, the compounds of Brizgys have the same stereochemistry. Rotating around the α-methylene relative to the amide provides the cyclopropane in the up-position and the hydrogens bridging the cyclopropane and cyclopentane rings in the down-position (similar to the claimed compounds). Additionally, the stereochemistry at the methylene adjacent to the pyridine ring is (S) in both the claimed compounds and Brizgys (priority of substituents: (1) N of amide; (2) C of pyridine; (3) C of methylene); (4) H; resulting in assignment of (S)).
Brizgys fails to teach compounds having a trifluoromethyl on the indazole.
Graupe teaches compounds of a similar core scaffold in compound IIa:
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and compositions thereof (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to simply substitute the methyl of the compounds in Brizgys with the methylene-CF3 of Graupe to obtain a compound of Formula I:
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to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Brizgys teaches compounds of a substantially similar scaffold for treating Tetroviridae viral infections, such as infections cause by the HIV virus (abstract),
-Brizgys teaches that there is a pressing need to discover new antiretroviral agents that are active against emerging drug-resistant HIV variants (column 1, lines 31-33),
-Brizgys teaches SAR surrounding the cyclopenta[c]pyrazole, indazole, alkyne, and pyridine and describe activity in tables (columns 172-175),
-Graupe teaches the compound,
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, which are useful in the treatment of a Retroviridae viral infection, including an infection caused by HIV virus (abstract),
-Graupe teaches that there is a need for compounds that are potent and stable and exhibit improved pharmacokinetic and/or pharmacodynamic profiles for the treatment of Retroviridae viral infection, including an infection caused by HIV virus (column 7, lines 16-20),
-Graupe teaches that an area of interest in HIV therapies and treatments is extending the pharmacokinetic property of regimens provided to patients, which requires daily pill consumption for the rest of their lives (column 7, lines 21-27),
-Graupe teaches that it would be beneficial to have HIV therapies that require patients to take medication less than once a day (column 7, lines 27-30), and
-Graupe teaches novel compounds exhibiting improved potency, improved metabolic stability, and improved pharmacokinetic and/or pharmacodynamic profiles (column 7, lines 31-34).
As such, an artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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.
Regarding Formula II of claim 1, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the alkene:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding Formula III of claim 1, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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Regarding Formula IV of claim 1, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula IV:
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Regarding Formula V of claim 1, Graupe teaches
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(abstract). While Graupe does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of a significantly similar scaffold of compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, Graupe teaches a compound of Formula V:
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Regarding Formula VI of claim 1, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula VI:
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Regarding claim 2, Brizgys teaches the compound:
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(column 118, lines 35-45). Graupe teaches
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(abstract). An artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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Regarding claim 3, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding claim 4, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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Regarding claim 5, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula IV:
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Regarding claim 6, Graupe teaches
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(abstract). While Graupe does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of a significantly similar scaffold of compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, Graupe teaches a compound of Formula V:
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Regarding claim 7, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula VI:
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Regarding claim 8, Brizgys teaches that the compounds may be isolated substantially free of their enantiomeric or diastereomeric partners (column 17, lines 64-67).
Regarding claim 15, Brizgys teaches that the stereoisomer is at least 98% pure, which significantly overlaps with claimed range (greater than about 95% purity; column 18, lines 39-42 and 47-50). Further, the range of the claimed invention does not provide an unexpected result in view of Brizgys, who describes compounds for treating HIV (abstract). Thus, Brizgys teaches a compound having greater than about 95% purity.
Regarding claim 16, Brizgys teaches compositions of compounds with significantly similar structure (column 18, lines 16-26).
Regarding claim 17, Brizgys teaches compositions of compounds with significantly similar structure in combination with at least one additional therapeutic agent, such as an anti-HIV agent (column 166, lines 41-46).
3. Claims 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018, see IDS filed 17 Oct 2023) and Graupe (U.S. Patent No. 10,071,985, issued 11 Sept 2018, see IDS filed 17 Oct 2023) as applied to claim 1-8 and 15-17 above, and further in view of Bekerman (U.S. Patent Publication No. 2021/0188815, published 24 Jun 2021).
Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018, see IDS filed 17 Oct 2023) and Graupe (U.S. Patent No. 10,071,985, issued 11 Sept 2018, see IDS filed 17 Oct 2023) are applied as discussed in the 35 U.S.C. 103 rejection above.
Regarding claim 9, while the combination of Brizgys and Graupe teach compositions of a compounds of Formula I-VI, they differ from that of the instantly claimed invention in that they do not explicitly teach a composition, wherein the compound is present in the composition in an amount greater than 25% by weight.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to exemplify the compounds and compositions of Brizgys and Graupe with the compositions of Bekerman to arrive at the instantly claimed invention.
One of ordinary skill in the art would have been motivated to substitute the compositions of Brizgys with the compositions of Bekerman to generate a composition with a compound in an amount greater than 25% by weight, because Bekerman teaches methods of administrating compounds of a significantly similar structure:
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, for preventing HIV in a subject and thus compositions thereof (abstract). Bekerman further teaches that the HIV/AIDs pandemic has claimed the lives of millions of people and that millions more are affected ([0003]). Further, Bekerman specifies that new and effective means for preventing HIV infection are needed, because there are only two medications being explored for pre-exposure prophylaxis ([0003]). Additionally, Bekerman teaches compositions where the compound is greater than 25% by weight ([0160]). Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable.
As such, an artisan having ordinary skill in the art would have been motivated to make
such a selection, to predictably arrive at instant claim 9: a compound of Formulas I-VI, wherein the compound wherein the compound is present in the composition in an amount greater than 25% by weight.
Regarding claim 10, Bekerman teaches a composition, wherein the compound is present in the composition in an amount greater than 50% by weight ([0160]).
Regarding claim 11, Bekerman teaches a composition, wherein the compound is present in the composition in an amount greater than 75% by weight ([0160]).
Regarding claim 12, Bekerman teaches compositions where the excipient is present in an amount that is greater than about 70%, which corresponds to 30% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound; [0257]). Thus, the claimed invention significantly overlaps with that of Bekerman. Further, the range of the claimed invention does not provide an unexpected result in view of Bekerman, who describes compositions for preventing HIV (abstract; [0267]). Thus, Bekerman teaches a composition, wherein the compound is present in the composition in an amount less than 25% by weight.
Regarding claim 13, Bekerman teaches compositions where the excipient is present in an amount that is greater than about 90%, which corresponds to 10% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound; [0257]). Thus, the claimed invention significantly overlaps with that of Bekerman. Further, the range of the claimed invention does not provide an unexpected result in view of Bekerman, who describes compositions for preventing HIV (abstract; [0267]). Thus, Bekerman teaches a composition, wherein the compound is present in the composition in an amount less than 10% by weight.
Regarding claim 14, Bekerman teaches compositions where the excipient is present in an amount that is greater than about 95%, which corresponds to about 5% for the remaining parts of the composition, such as the active pharmaceutical ingredient (i.e. the compound; [0257]). Because of the lack of clarity on the endpoints of “less than about,” it can reasonably be inferred that 5% is about 1%. Thus, the claimed invention significantly overlaps with that of Bekerman. Further, the range of the claimed invention does not provide an unexpected result in view of Bekerman, who describes compositions for preventing HIV (abstract; [0267]). Thus, Bekerman teaches a composition, wherein the compound is present in the composition in an amount less than about 1% by weight.
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.
4. Claims 1 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 56 of copending Application No. 18/061,150 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U.S. Application No. 18/061,150 claims a compound,
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(claim 56).
Regarding claim 1, ‘150 teaches
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(claim 56 of ‘150).
Regarding claim 5, ‘150 teaches
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(claim 56 of ‘150). These specific compounds of ‘150 are identical to the compounds claimed/recited in the rejected claims of the instant application. Thus, claim 56 of ‘150 anticipates instant claims 1 and 5.
5. Claims 1-8 and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 88 of U.S. Patent Publication No. 2020/0038389 in view of Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018, see IDS filed 17 Oct 2023).
U.S. Patent Publication No. 2020/0038389 teaches a composition of
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(claim 88).
Regarding claim 1, ‘389 fails to teach a compound of Formulas I-VI.
Brizgys teaches compounds for treatment of HIV (abstract). Brizgys specifically teaches the compounds:
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,
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, and
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(column 117, lines 25-35; column 118, lines 35-45; column 118, lines 55-65; column 142, lines 5-15; column 148, lines 5-15). Further, the compounds of Brizgys have the same stereochemistry. Rotating around the α-methylene relative to the amide provides the cyclopropane in the up-position and the hydrogens bridging the cyclopropane and cyclopentane rings in the down-position (similar to the claimed compounds). Additionally, the stereochemistry at the methylene adjacent to the pyridine ring is (S) in both the claimed compounds and Brizgys (priority of substituents: (1) N of amide; (2) C of pyridine; (3) C of methylene); (4) H; resulting in assignment of (S)).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to simply substitute the methyl of the compounds in Brizgys with the methylene-CF3 of ‘389 to obtain a compound of Formula I:
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to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Brizgys teaches compounds of a substantially similar scaffold for treating Tetroviridae viral infections, such as infections cause by the HIV virus (abstract),
-Brizgys teaches that there is a pressing need to discover new antiretroviral agents that are active against emerging drug-resistant HIV variants (column 1, lines 31-33),
-Brizgys teaches SAR surrounding the cyclopenta[c]pyrazole, indazole, alkyne, and pyridine and describe activity in tables (columns 172-175),
-‘389 teaches the compound,
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, which are useful in the treatment of an HIV infection in heavily treatment-experienced patients with multidrug resistant HIV infection (abstract),
-‘389 teaches that there is a need for compounds capable of combatting resistance as a significant number of patients utilizing current combination treatments experience a loss of virologic, immunologic, or clinical benefit from their current regiments ([0005]),
-‘389 teaches that viruses develop broad multi-class antiretroviral drug resistance and that patients have limited options for alternative treatment regimens and are at risk of significant morbidity and mortality ([0005]), and
-‘389 teaches methods of administering compounds of significant structural similarity in heavily treatment-experienced patients ([0007]).
As such, an artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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.
Regarding Formula II of claim 1, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding Formula III of claim 1, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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.
Regarding Formula IV of claim 1, ‘389 teaches
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(claim 88). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘389 differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘389 teaches a compound of Formula IV:
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.
Regarding Formula V of claim 1, ‘389 teaches
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(claim 88). While ‘389 does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, ‘389 teaches a compound of Formula V:
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.
Regarding Formula VI of claim 1, ‘389 teaches
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(claim 88). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘389 differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘389 teaches a compound of Formula VI:
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.
Regarding claim 2, Brizgys teaches the compound:
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(column 118, lines 35-45). ‘389 teaches
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(claim 88). An artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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.
Regarding claim 3, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding claim 4, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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Regarding claim 5, ‘389 teaches
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(claim 88). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘389 differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘389 teaches a compound of Formula IV:
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Regarding claim 6, ‘389 teaches
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(claim 88). While ‘389 does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, ‘389 teaches a compound of Formula V:
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Regarding claim 7, ‘389 teaches
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(claim 88). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘389 differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘389 teaches a compound of Formula VI:
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.
Regarding claim 8, Brizgys teaches that the compounds may be isolated substantially free of their enantiomeric or diastereomeric partners (column 17, lines 64-67).
Regarding claim 15, Brizgys teaches that the stereoisomer is at least 98% pure, which significantly overlaps with claimed range (greater than about 95% purity; column 18, lines 39-42 and 47-50). Further, the range of the claimed invention does not provide an unexpected result in view of Brizgys, who describes compounds for treating HIV (abstract). Thus, Brizgys teaches a compound having greater than about 95% purity.
Regarding claim 16, Brizgys teaches compositions of compounds with significantly similar structure (column 18, lines 16-26).
Regarding claim 17, Brizgys teaches compositions of compounds with significantly similar structure in combination with at least one additional therapeutic agent, such as an anti-HIV agent (column 166, lines 41-46).
6. Claims 1-7 and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15-17 of U.S. Patent No. 9,951,043 in view of Graupe (U.S. Patent No. 10,071,985, issued 11 Sept 2018, see IDS filed 17 Oct 2023).
U.S. Patent No. 9,951,043 teaches the compounds:
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(claim 15). Further, the compounds of ‘043 have the same stereochemistry. Rotating around the α-methylene relative to the amide provides the cyclopropane in the up-position and the hydrogens bridging the cyclopropane and cyclopentane rings in the down-position (similar to the claimed compounds). Additionally, the stereochemistry at the methylene adjacent to the pyridine ring is (S) in both the claimed compounds and ‘043 (priority of substituents: (1) N of amide; (2) C of pyridine; (3) C of methylene); (4) H; resulting in assignment of (S)).
‘043 fails to teach compounds having a trifluoromethyl on the indazole.
Graupe teaches compounds of similar core scaffold in compound IIa:
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and compositions thereof (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to simply substitute the methyl of the compounds in ‘043 with the methylene-CF3 of Graupe to obtain a compound of Formula I:
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to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-‘043 teaches compounds of a substantially similar scaffold for treating Tetroviridae viral infections, such as infections cause by the HIV virus (abstract),
-‘043 teaches that there is a pressing need to discover new antiretroviral agents that are active against emerging drug-resistant HIV variants (column 1, lines 31-33),
-‘043 teaches SAR surrounding the cyclopenta[c]pyrazole, indazole, alkyne, and pyridine and describe activity in tables (columns 172-175),
-Graupe teaches the compound,
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, which are useful in the treatment of a Retroviridae viral infection, including an infection caused by HIV virus (abstract),
-Graupe teaches that there is a need for compounds that are potent and stable and exhibit improved pharmacokinetic and/or pharmacodynamic profiles for the treatment of Retroviridae viral infection, including an infection caused by HIV virus (column 7, lines 16-20),
-Graupe teaches that an area of interest in HIV therapies and treatments is extending the pharmacokinetic property of regimens provided to patients, which requires daily pill consumption for the rest of their lives (column 7, lines 21-27),
-Graupe teaches that it would be beneficial to have HIV therapies that require patients to take medication less than once a day (column 7, lines 27-30), and
-Graupe teaches novel compounds exhibiting improved potency, improved metabolic stability, and improved pharmacokinetic and/or pharmacodynamic profiles (column 7, lines 31-34).
As such, an artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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Regarding Formula II of claim 1, ‘043 teaches the compounds:
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(claim 15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, ‘043 teaches a compound of Formula II.
Regarding Formula III of claim 1, ‘043 teaches the compound:
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(claim 15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘043 differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘043 teaches a compound of Formula III:
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Regarding Formula IV of claim 1, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula IV:
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Regarding Formula V of claim 1, Graupe teaches
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(abstract). While Graupe does not teach the non-chlorinated indazole, ‘043 teaches the compound:
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(claim 15). Thus, ‘043 demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, Graupe teaches a compound of Formula V:
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Regarding Formula VI of claim 1, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula VI:
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Regarding claim 2, ‘043 teaches the compound:
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(claim 15). Graupe teaches
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(abstract). An artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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Regarding claim 3, ‘043 teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(claim 15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, ‘043 teaches a compound of Formula II.
Regarding claim 4, ‘043 teaches the compound:
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(claim 15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘043 differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘043 teaches a compound of Formula III:
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Regarding claim 5, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula IV:
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Regarding claim 6, Graupe teaches
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(abstract). While Graupe does not teach the non-chlorinated indazole, ‘043 teaches the compound:
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(claim 15). Thus, ‘043 demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, Graupe teaches a compound of Formula V:
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Regarding claim 7, Graupe teaches
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(abstract). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Graupe differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Graupe teaches a compound of Formula VI:
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.
Regarding claim 16, ‘043 teaches compositions of compounds with significantly similar structure (claim 16).
Regarding claim 17, ‘043 teaches compositions of compounds with significantly similar structure in combination with at least one additional therapeutic agent, such as an anti-HIV agent (claim 17).
7. Claims 1-8 and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 88 of U.S. Patent No. 10,071,985 in view of Brizgys (U.S. Patent No. 9,951,043, issued 24 Apr 2018, see IDS filed 17 Oct 2023).
U.S. Patent No. 10,071,985 teaches a compound of
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(claim 2).
Regarding claim 1, ‘985 fails to teach a compound of Formulas I-VI.
Brizgys teaches compounds for treatment of HIV (abstract). Brizgys specifically teaches the compounds:
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,
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,
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,
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, and
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(column 117, lines 25-35; column 118, lines 35-45; column 118, lines 55-65; column 142, lines 5-15; column 148, lines 5-15). Further, the compounds of Brizgys have the same stereochemistry. Rotating around the α-methylene relative to the amide provides the cyclopropane in the up-position and the hydrogens bridging the cyclopropane and cyclopentane rings in the down-position (similar to the claimed compounds). Additionally, the stereochemistry at the methylene adjacent to the pyridine ring is (S) in both the claimed compounds and Brizgys (priority of substituents: (1) N of amide; (2) C of pyridine; (3) C of methylene); (4) H; resulting in assignment of (S)).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to simply substitute the methyl of the compounds in Brizgys with the methylene-CF3 of ‘985 to obtain a compound of Formula I:
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to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Brizgys teaches compounds of a substantially similar scaffold for treating Tetroviridae viral infections, such as infections cause by the HIV virus (abstract),
-Brizgys teaches that there is a pressing need to discover new antiretroviral agents that are active against emerging drug-resistant HIV variants (column 1, lines 31-33),
-Brizgys teaches SAR surrounding the cyclopenta[c]pyrazole, indazole, alkyne, and pyridine and describe activity in tables (columns 172-175),
-‘985 teaches the compound,
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, which are useful in the treatment of a Retroviridae viral infection, including an infection caused by HIV virus (abstract),
-‘985 teaches that there is a need for compounds that are potent and stable and exhibit improved pharmacokinetic and/or pharmacodynamic profiles for the treatment of Retroviridae viral infection, including an infection caused by HIV virus (column 7, lines 16-20),
-‘985 teaches that an area of interest in HIV therapies and treatments is extending the pharmacokinetic property of regimens provided to patients, which requires daily pill consumption for the rest of their lives (column 7, lines 21-27),
-‘985 teaches that it would be beneficial to have HIV therapies that require patients to take medication less than once a day (column 7, lines 27-30), and
-‘985 teaches novel compounds exhibiting improved potency, improved metabolic stability, and improved pharmacokinetic and/or pharmacodynamic profiles (column 7, lines 31-34).
As such, an artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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Regarding Formula II of claim 1, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding Formula III of claim 1, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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Regarding Formula IV of claim 1, ‘985 teaches
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(claim 2). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘985 differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘985 teaches a compound of Formula IV:
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Regarding Formula V of claim 1, ‘985 teaches
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(claim 2). While ‘985 does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, ‘985 teaches a compound of Formula V:
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Regarding Formula VI of claim 1, ‘985 teaches
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(claim 2). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘985 differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘985 teaches a compound of Formula VI:
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Regarding claim 2, Brizgys teaches the compound:
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(column 118, lines 35-45). ‘985 teaches
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(claim 2). An artisan having ordinary skill in the art would have been motivated to substitute one known element (methyl) for another (methylene-trifluoromethyl) to predictably arrive at a compound of Formula (I):
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Regarding claim 3, Brizgys teaches the compounds:
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and
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, which incorporates the saturated tert-butyl and alkene, respectively, which suggests incorporation of the olefin:
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(column 142, lines 5-15; column 148, lines 5-15). Further, structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Deuel, 51 F.3d 1552, 1558, 34 USPQ2d 1210, 1214 (Fed. Cir. 1995). See MPEP § 2144.08(II)(A)(4)(c). As alkenes and alkanes are homologous, Brizgys teaches a compound of Formula II.
Regarding claim 4, Brizgys teaches the compound:
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(column 142, lines 5-15). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of Brizgys differs from a compound of Formula III in the change from t-butyl to isopropyl (changing a methyl to a hydrogen), a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, Brizgys teaches a compound of Formula III:
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Regarding claim 5, ‘985 teaches
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(claim 2). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘985 differs from a compound of Formula IV in the methyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘985 teaches a compound of Formula IV:
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Regarding claim 6, ‘985 teaches
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(claim 2). While ‘985 does not teach the non-chlorinated indazole, Brizgys teaches the compound:
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(column 118, lines 55-65). Thus, Brizgys demonstrated the motivation to make non-chlorinated derivatives of similar core scaffold compounds, and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. See MPEP § 2144.08(II)(A)(4)(c). Thus, ‘985 teaches a compound of Formula V:
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.
Regarding claim 7, ‘985 teaches
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(claim 2). Structural similarities have been found to support a prima facie case of obviousness. See, e.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457, 460, 195 USPQ 426, 429 (CCPA 1977) (adjacent homologs and structural isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970) (acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41 (CCPA 1963) (omission of methyl group from pyrazole ring). Generally, some teaching of a structural similarity will be necessary to suggest selection of the claimed species or subgenus. The closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein). See MPEP § 2144.08(II)(A)(4)(c). As the compound of ‘985 differs from a compound of Formula VI in the ethyl group on the sulfonamide, a person of ordinary skill in the art would expect the compounds to have similar properties and thus would contemplate making them to try and obtain compounds with improved properties. Thus, ‘985 teaches a compound of Formula VI:
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.
Regarding claim 8, Brizgys teaches that the compounds may be isolated substantially free of their enantiomeric or diastereomeric partners (column 17, lines 64-67).
Regarding claim 15, Brizgys teaches that the stereoisomer is at least 98% pure, which significantly overlaps with claimed range (greater than about 95% purity; column 18, lines 39-42 and 47-50). Further, the range of the claimed invention does not provide an unexpected result in view of Brizgys, who describes compounds for treating HIV (abstract). Thus, Brizgys teaches a compound having greater than about 95% purity.
Regarding claim 16, Brizgys teaches compositions of compounds with significantly similar structure (column 18, lines 16-26).
Regarding claim 17, Brizgys teaches compositions of compounds with significantly similar structure in combination with at least one additional therapeutic agent, such as an anti-HIV agent (column 166, lines 41-46).
Conclusion
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622