DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-18 and 21 are pending in the instant invention. According to the Amendments to the Claims, filed April 2, 2026, claims 1-14 and 16-18 were amended, claims 19 and 20 were cancelled and claim 21 was added.
Status of Priority
This invention is a Continuation (CON) of US Application No. 17/029,013, filed September 22, 2020 and now US 11,571,420, which is a Continuation (CON) of US Application No. 16/910,308, filed June 24, 2020 and now US 10,898,481, which is a Continuation (CON) of International Application No. PCT/CN2019/100996, filed August 16, 2019, which claims priority under 35 U.S.C. § 119(a-d) to International Application No. PCT/CN2016/101006, filed August 17, 2018.
Status of Restrictions / Election of Species
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The inventor’s or joint inventor’s affirmation of the following election, without traverse, in the reply filed on April 2, 2026, is acknowledged: a) Group I - claims 1-18 and 21; and b) substituted pyrazine of Formula (I) - p. 237, Example/Cmpd No. 151/152.
Similarly, the inventor or joint inventor should further note that the requirement was made FINAL in the Non-Final Rejection, mailed on October 3, 2025.
Likewise, the inventor or joint inventor should further note that the sections of U.S.C. Title 35 that formed the basis of prior rejections formulated, as well as any references supporting said rejections, that are not included with this Office action, may be found in the Non-Final Rejection, mailed on October 3, 2025.
Moreover, the inventor or joint inventor should further note that any rejections and/or objections of record not explicitly addressed herein below, are hereby withdrawn, in light of the inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed April 2, 2026.
Thus, a second Office action and prosecution on the merits of claims 1-18 and 21 is contained within.
New Claim Objections
Claim 1 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation(s):
1. A method for inhibiting adenosine receptor (AR) activity in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of at least one compound of Formula (I):
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Formula (I)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
ring A is morpholinyl, pyridinyl, pyridazinyl, pyridazin-3(2H)-onyl, pyrimidinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-a]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, or quinoxalinyl;
each R1 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
m is 0, 1, 2, 3, or 4;
ring B is oxetanyl, pyrrolidinyl, tetrahydrofuranyl, pyridin-2(1H)-onyl, morpholinyl, 2-oxa-6-azaspiro[3.4]octanyl, phenyl, pyrrolyl, furanyl, imidazolyl, oxazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridinyl, or 1H-indolyl;
each R2 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, and OC1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl and saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R5 substituents;
each R5 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
n is 0, 1, 2, 3, or 4;
X is NH2;
W is C1-12 alkylene or -C(O)-, wherein the C1-12 alkylene is optionally substituted by one or more substituents independently selected from the group consisting of OH and OC1-12 alkyl;
V is -NH-, -NHC1-12 alkylene-, -NHC(O)-, or pyrrolidin-1-yl;
wherein any -NH- is optionally substituted by one substituent selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
wherein the C1-12 alkylene of -NHC1-12 alkylene- is optionally substituted by one or more substituents independently selected from the group consisting of NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl; and
wherein the pyrrolidin-1-yl is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, and OC1-12 alkyl;
Y is halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, C(O)R3, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)C1-12 alkyl, OC(O)NH2, S(O)2R3, saturated or unsaturated 3- to 12-membered carbocyclyl, or saturated or unsaturated 3- to 12-membered heterocyclyl;
wherein the C1-12 alkyl, C1-12 haloalkyl, C1-12 cyanoalkyl, C1-12 hydroxyalkyl, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, or OC(O)C1-12 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 12-membered carbocyclyl or saturated or unsaturated 3- to 12-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents;
each R3 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl;
wherein each C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, and S(O)2C1-12 alkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each NHC3-12 cycloalkyl, NHC(O)NH2, OC(O)NH2, and OP(O)(OH)2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each saturated or unsaturated 3- to 10-membered carbocyclyl, or saturated or unsaturated 3- to 10-membered heterocyclyl is optionally and independently substituted by one or more independently selected R6 substituents; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents.
22. The method of claim 1, wherein the subject suffers from an adenosine receptor (AR)-associated disease selected from the group consisting of acute heart failure, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), asthma, breast cancer, cerebral ischemia, chronic heart failure, chronic obstructive pulmonary disease (COPD), cognitive impairment, depression, epilepsy, human immunodeficieny virus (HIV), non-small cell lung cancer (NSCLC), Parkinson disease, prostate cancer, renal cell carcinoma (RCC), and a stroke.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
m is 0, 1, or 2;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, CH2OH, CH(OHCH3, CH2CH2OH, NH2, NHCH3, N(CH3)2, NHCH2CH3, NHCH(CH3)2, OH, OCH3, OCH2CH3, OCHF2, or OCF3, wherein each C1-12 alkyl and C1-12 haloalkyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OC1-12 alkyl, and OC1-12 haloalkyl; and
n is 0, 1, or 2.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein:
W is -CH2- or -C(O)-; or
(i) W is -CH2-; and
V is -NHC(O)-; or
(ii) W is -C(O)-; and
V is -NH-, -NHC1-12 alkylene-, or pyrrolidin-1-yl;
wherein the -NH- is optionally substituted by one substituent selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, OH, and OC1-12 alkyl;
wherein the C1-12 alkylene of -NHC1-12 alkylene- is optionally substituted by one or more substituents independently selected from the group consisting of OH and OC1-12 alkyl; and
wherein the pyrrolidin-1-yl is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl, C1-12 hydroxyalkyl, OH, and OC1-12 alkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein Y is CN, C1-12 alkyl, C1-12 hydroxyalkyl, C(O)R3, NH2, NHC1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, S(O)2R3, cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentanyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolidin-2-onyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, pyridin-2(1H)-onyl, tetrahydropyranyl, pyridazin-3(2H)-onyl, piperazinyl, morpholinyl, 1,4-dioxanyl, phenyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl, wherein the cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentanyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolidin-2-onyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, pyridin-2(1H)-onyl, tetrahydropyranyl, pyridazin-3(2H)-onyl, piperazinyl, morpholinyl, 1,4-dioxanyl, phenyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl is optionally substituted by one or more independently selected R3 substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein each R3 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2NH2, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH2CH3, NHcyclobutyl, OH, OCH3, OCH2CH3, OCH(OH)CH3, OCH2CH2OH, PH2, P(O)(OH)3, S(O)2CH3, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl, pyranyl, piperazinyl, morpholinyl, 1,4-dioxanyl, bicyclo[1.1.1]pentanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3,8-diazabicyclo[3.2.1]octanyl, phenyl, furanyl, pyridinyl, or pyrazinyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2NH2, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH2CH3, OH, OCH3, OCH2CH3, PH2, P(O)(OH)3, and S(O)2CH3 is optionally and independently substituted by one or more substituents independently selected from the group consisting of F, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, NH2, NHCH3, N(CH3)2, OH, OCH3, OCH2CH3, S(O)2CH3, and cyclopropyl; and
wherein each NHcyclobutyl, cyclopropyl, cyclobutyl, cyclohexyl, azetidinyl, pyrrolidinyl, piperidinyl, pyranyl, piperazinyl, morpholinyl, 1,4-dioxanyl, bicyclo[1.1.1]pentanyl, 1,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 2,6-diazaspiro[3.4]octanyl, 2,5-diazabicyclo[2.2.1]heptanyl, 3,6-diazabicyclo[3.1.1]heptanyl, 3,8-diazabicyclo[3.2.1]octanyl, phenyl, furanyl, pyridinyl, and pyrazinyl is optionally and independently substituted by one or more substituents independently selected from the group consisting of F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, NH2, NHCH3, N(CH3)2, OH, OCH3, OCH2CH3, S(O)2CH3, and cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is independently substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia):
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Formula (Ia)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
(i) Z is a bond; and
Y is C(O)R3, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OC1-12 alkyl, OC1-12 haloalkyl, S(O)2R3, saturated or unsaturated 3- to 6-membered carbocyclyl, or saturated or unsaturated 3- to 6-membered heterocyclyl;
wherein the NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OC1-12 alkyl, or OC1-12 haloalkyl, is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 6-membered carbocyclyl or saturated or unsaturated 3- to 6-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents; or
(ii) Z is C1-12 alkylene; and
Y is halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 6-membered carbocyclyl, and saturated or unsaturated 3- to 6-membered heterocyclyl; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 7, wherein:
(i) Z is a bond; and
Y is cyclobutyl, wherein the cyclobutyl is substituted by one OC1-12 alkyl substituent and optionally further substituted by one or more OCH3 substituents; or
(ii) Z is -CH2CH2-; and
Y is OCH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia-i):
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Formula (Ia-i)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
R7 is H, C1-6 alkyl, C1-6 hydroxyalkyl, or OC1-6 alkyl;
ring Q is a saturated or unsaturated 3- to 6-membered carbocyclyl or a saturated or unsaturated 3- to 6-membered heterocyclyl;
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents; and
i is 0, 1, 2, 3, or 4.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ib):
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Formula (Ib)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCH2CH3, OCF3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
each R2 is independently halogen, C1-12 alkyl, C1-12 haloalkyl, NH2, or OH, wherein each C1-12 alkyl, C1-12 haloalkyl, NH2, and OH is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, OH, OC1-12 alkyl, and OC1-12 haloalkyl;
R7 is H, C1-6 alkyl, C1-6 hydroxyalkyl, or OC1-6 alkyl;
ring Q is a saturated or unsaturated 3- to 6-membered carbocyclyl or a saturated or unsaturated 3- to 6-membered heterocyclyl;
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents; and
i is 0, 1, 2, 3, or 4.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 10, wherein:
each R1 is independently F, Cl, CH3, CH2CH3, CH(CH3)2, CH2F, CHF2, CF3, CH(OH)CH3, CH2CH2OH, NH2, cyclopropyl, or oxetanyl;
m is 0, 1, or 2;
ring B is phenyl, furanyl, oxazolyl, or 2H-1,2,3-triazolyl;
each R2 is independently F or CH3;
n is 0 or 1;
ring Q is cyclopropyl, cyclobutyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, phenyl, pyrazolyl, thiazolyl, pyridinyl, or pyrimidinyl;
each R3 is independently F, Cl, Br, CN, CH3, CH2F, CHF2, CF3, CH2OH, CH2P(CH3)2, CH2CH3, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHCH(CH3)2, NHCH(OH)CH3, NHCH2CH2OH, N(CH3)2, OCH3, OCHF2, OCF3, OCH2C(O)NH2, OCH2CH3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OCH(OH)CH3, OCH2CH2OH, OCH(NHCH3)CH3, OCH2CH2NHCH3, OCH[N(CH3)2]CH3, OCH2CH2N(CH3)2, OCH(OCH3)CH3, OCH2CH2OCH3, azetidinyl, azetidinyl-N(CH3)2, pyrrolidinyl, morpholinyl, 5-methyl-2,5-diazaspiro[3.3]heptan-2-yl, 6-methyl-2,6-diazaspiro[3.4]octan-2-yl, 3-methyl-3,6-diazabicyclo[3.1.1]heptanyl, 3-methyl-3,8-diazabicyclo[3.2.1]octan-8-yl, 8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl, pyrazinyl, or N-methylpyrazinyl; and
i is 0, 1, 2, or 3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the compound is of Formula (Ia-ii):
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Formula (Ia-ii)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently F, Cl, Br, CN, C1-12 alkyl, CH2F, CHF2, CF3, CH2OH, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, NHC(O)NH2, N(CH3)2, OH, OCH3, OCF3, OCH2CH3, OCH2CF3, OCH2FCHF2, OCF2CH2F, OC(O)NH2, cyclopropyl, oxetanyl, tetrahydrofuranyl, or 1,1-dioxothietanyl;
wherein each C1-12 alkyl, CH2F, CHF2, CHFCH3, CH2CH2F, CHFCH2F, CF2CH3, CH2CHF2, CH2CF3, CHFCHF2, CF2CH2F, CH2OH, CH(OH)CH3, CH2CH2OH, C(O)NH2, NH2, NHCH3, NHCH2CH3, N(CH3)2, OH, OCH3, OCH2CH3, OCH2CF3, OCH2FCHF2, and OCF2CH2F is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents;
wherein each NHC(O)NH2 and OC(O)NH2 is optionally and independently substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, S(O)2C1-12 alkyl, and cycloalkyl, wherein each cycloalkyl substituent is optionally and independently substituted by one or more independently selected C1-12 alkyl substituents; and
wherein each cyclopropyl, oxetanyl, tetrahydrofuranyl, and 1,1-dioxothietanyl is optionally and independently substituted by one or more independently selected R4 substituents;
each R4 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, NH2, OH, OC1-12 alkyl, or OC1-12 haloalkyl;
(i) Z is a bond; and
Y is OC1-12 alkyl, saturated or unsaturated 3- to 6-membered carbocyclyl, or saturated or unsaturated 3- to 6-membered heterocyclyl;
wherein the OC1-12 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC1-12 hydroxyalkyl, NHC3-12 cycloalkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, OP(O)(OH)2, PH2, PH(C1-12 alkyl), P(C1-12 alkyl)2, P(O)(OH)3, P(O)(OH)2(OC1-12 alkyl), P(O)(OH)(OC1-12 alkyl)2, S(O)2C1-12 alkyl, saturated or unsaturated 3- to 10-membered carbocyclyl, and saturated or unsaturated 3- to 10-membered heterocyclyl; and
wherein the saturated or unsaturated 3- to 6-membered carbocyclyl or saturated or unsaturated 3- to 6-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents; or
(ii) Z is C1-12 alkylene; and
Y is H, OH, OC1-12 alkyl, saturated or unsaturated 3- to 6-membered carbocyclyl, and saturated or unsaturated 3- to 6-membered heterocyclyl, wherein the saturated or unsaturated 3- to 6-membered carbocyclyl or saturated or unsaturated 3- to 6-membered heterocyclyl is optionally substituted by one or more independently selected R3 substituents; and
each R6 is independently halogen, CN, C1-12 alkyl, C1-12 haloalkyl, C1-12 hydroxyalkyl, C(O)NH2, C(O)NHC1-12 alkyl, C(O)N(C1-12 alkyl)2, NH2, NHC1-12 alkyl, NHC(O)C1-12 alkyl, NHC(O)NH2, N(C1-12 alkyl)2, OH, OC1-12 alkyl, OC1-12 haloalkyl, OC(O)NH2, S(O)2C1-12 alkyl, or cycloalkyl, wherein each cycloalkyl is substituted by one or more independently selected C1-12 alkyl substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 12, wherein:
R1 is CH3; and
m is 1.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The method of claim 12, wherein:
(i) Z is a bond; and
Y is cyclobutyl, wherein the cyclobutyl is substituted by one OCH3 substituent; or
(ii) Z is -CH2CH2-; and
Y is OCH3; or
(iii) Z is -CH2-; and
Y is pyrrolidinyl, tetrahydrofuranyl, or phenyl, wherein the pyrrolidinyl, tetrahydrofuranyl, or phenyl is optionally substituted by one or more independently selected R3 substituents; and
each R3 is independently halogen or C1-12 alkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 is objected to because of the following informalities: a) for clarity and precision, and should be inserted before the last species; and b) for clarity and precision, , or a pharmaceutically acceptable salt thereof should be inserted prior to the period. Appropriate correction is required. See MPEP § 2173.02.
Claim 16 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
The method of claim 1, wherein the method further comprises:
(a) administering to the subject in need thereof at least one immunotherapeutic; or
(b) administering to the subject in need thereof at least one chemotherapeutic; or
(c) applying radiotherapy to the subject.
Appropriate correction is required. See MPEP § 2173.02.
Claim 17 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The method of claim 16, wherein the immunotherapeutic is selected from the group consisting of an anti-CCR2 antibody, an anti-CD39 antibody, an anti-CD73 antibody, an anti-CTLA-4 antibody, and an anti-PD-1/PD-L1 antibody, or a combination thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 18 is objected to because of the following informalities: for clarity and precision to, the existing recitation should be replaced with the following recitation:
The method of claim 16, wherein the chemotherapeutic is selected from the group consisting of docetaxel, doxorubicin, etoposide, mitoxantrone, paclitaxel, and a platinum-based chemotherapeutic, or a combination thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 21 is objected to because of the following informalities: for clarity and precision to, the existing recitation should be replaced with the following recitation(s):
The method of claim 18, wherein the platinum-based chemotherapeutic is cisplatin or oxaliplatin.
Appropriate correction is required. See MPEP § 2173.02.
New Claim Rejections - 35 U.S.C. § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. § 112:
(a) IN GENERAL. The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I)
Claims 1-18 and 21 are rejected under 35 U.S.C. § 112(a) as failing to comply with the enablement requirement because the claims contain subject matter, particularly a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use (perform) the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
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(a) Breadth of the claims - the breadth of the claims includes a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), shown to the right;
(b) Nature of the invention - the nature of the invention is performance of a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), shown to the right above;
(c) State of the prior art - Nature Reviews: Drug Discovery, as provided in the file and cited in the Non-Final Rejection, mailed on October 3, 2025, offers a snapshot of the state of the drug development art. Herein, drug development is stated to follow the widely accepted Ehrlich model which includes: (1) development of a broad synthetic organic chemistry program; (2) subsequent testing of compounds in an appropriate laboratory model for the disease to be treated; and (3) screening of compounds with low toxicity in prospective clinical trials (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205). Similarly, no single drug has been discovered that is effective in treating the myriad of adenosine receptor-associated diseases, including, but not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma {See In re Hokum, 226 USPQ 353 (ComrPats 1985)}. Moreover, US 11,028,058, as cited in the Non-Final Rejection, mailed on October 3, 2025, illustrates the synthesis of substituted pyrazines of the Formula (I), and/or methods of use thereof {Pham, et al. US 11,028,058, 2021};
(d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I) would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience;
(e) Level of predictability in the art - Synthetic organic chemistry is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 ¶3). Similarly, it is well established that [T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor {See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970)}.
Moreover, the following excerpt is taken from Hackam, et al., as provided in the file and cited in the Non-Final Rejection, mailed on October 3, 2025, with respect to the poor replication of animal research in human clinical trials {Hackam, et al. JAMA, 296(14), 2006, 1731-1732}:
Only about a third of highly cited animal research translated at the level of human randomized trials. This rate of translation is lower than the recently estimated 44% replication rate for highly cited human studies. Nevertheless, we believe these findings have important implications. First, patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease. Second, major opportunities for improving study design and methodological quality are available for preclinical research. Finally, poor replication of even high-quality animal studies should be expected by those who conduct clinical research.
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using (performing) a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I);
(g) Existence of working examples - the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I).
Similarly, according to the specification, substituted pyrazines of the Formula (I) are capable of treating a variety of adenosine receptor-associated diseases, including, but not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma; however, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any adenosine receptor-associated diseases, including, but not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma. There is insufficient disclosure to reasonably conclude that the method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), as recited, would contribute to treatment of any adenosine receptor-associated diseases, including, but not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma. Furthermore, the combination of the instant specification and Pham, et al. in US 11,028,058, as cited in the Non-Final Rejection, mailed on October 3, 2025, lacks adequate credible evidence to support the assertion that a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), as recited, would contribute to the prophylaxis of any adenosine receptor-associated diseases, including, but not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma, since the inventor or joint inventor has neither provided convincing data for any subject population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claims.
Within the specification, [A]t least one specific operative embodiment or example of the invention must be set forth. The example(s) and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP § 608.01(p) and MPEP § 2173.05.
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(h) Quantity of experimentation needed to make and/or use (perform) the invention based on the content of the disclosure - predicting whether a recited compound is in fact one that produces a desired physiological effect at a therapeutic concentration and with useful kinetics, is filled with experimental uncertainty, and without proper guidance, would involve a substantial amount of experimentation (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205-213). Furthermore, it is unclear, based on the guidance provided by the specification, whether a substituted pyrazine of the Formula (I), such as 3-amino-N-(3-methoxycyclobutyl)-6-(3-methylimidazo[1,2-a]pyridin-6-yl)-5-(oxazol-2-yl)-pyrazine-2-carboxamide, shown to the left above, possesses utility as a therapeutic agent, useful in a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I). Thus, one of ordinary skill in the art, at the time this invention was made, would have an unreasonable expectation of success and undue experimentation in transferring the in vitro and/or in vivo method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), wherein the adenosine receptor-associated disease, includes, but is not limited to, NSCLC, RCC, prostate cancer, breast cancer, Parkinson disease, epilepsy, cerebral ischemia and stroke, depression, cognitive impairment, HIV, adenosine deaminase-severe combined immunodeficiency (ADA-SCID), acute heart failure, chronic heart failure, chronic obstructive pulmonary disease (COPD), and/or asthma, to any subject population.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. {See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. (See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404). These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for making and/or using (performing) a method of treating an adenosine receptor-associated disease, wherein the method comprises administering… a substituted pyrazine of the Formula (I), is clearly justified.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
New Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claims 1, 2, 4-6, 16-18 and 21 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 1 recites the limitation, C1-12 alkylene, wherein the C1-12 alkylene is optionally substituted by one or more substituents independently selected from the group consisting of C1-12 alkyl or C1-12 alkyl-OH, with respect to W, where the limitation is implausible, resulting in an incomplete valence. Claims are unduly speculative where they define only a portion of a substituted pyrazine of the Formula (I) administered within the method of treating an adenosine receptor-associated disease. Consequently, since incomplete valences are not permitted in the structure of the substituted pyrazines of the Formula (I) administered within the method of treating an adenosine receptor-associated disease, an essential portion of the substituted pyrazines of the Formula (I) administered within the method of treating an adenosine receptor-associated disease is indefinite and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the substituted pyrazines of the Formula (I) administered within the method of treating an adenosine receptor-associated disease. {See Ex parte Pedlow and Miner, 90 USPQ 395 (Bd. Pat. App. & Int. 1951)}.
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claims, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
Claims 10 and 11 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that a broad limitation together with a narrow limitation that falls within the broad limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c), MPEP § 2173.05(h), and/or Eli Lilly & Co. v. Teva Parenteral Meds., 845 F.3d 1357, 1371, 121 USPQ2d 1277, 1287 (Fed. Cir. 2017).
Similarly, the inventor or joint inventor should further note that claim 10 recites the broad limitation, hydroxypropyl, with respect to R1, and the claim also recites 2-hydroxypropyl, with respect to R1, which is the narrower statement of the limitation.
Likewise, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), pertaining to where broad language is followed by such as and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and consequently, not required, or (b) a required feature of the claim.
Next, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
Moreover, the inventor or joint inventor should further note that [C]laims which depend from indefinite claims are also indefinite. {See Ex parte Cordova, 10 USPQ 2d 1949, 1952 (PTO Bd. App. 1989)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
Claim 11 is further rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 11 recites the limitation, The method of claim 10, wherein… ring B is… pyrazolyl. There is insufficient antecedent basis, in claim 10, for this limitation, with respect to the substituted pyrazines of the Formula (Ib) administered within the method of treating an adenosine receptor-associated disease. According to claim 1, ring B is not recited as pyrazolyl, with respect to the substituted pyrazines of the Formula (I) administered within the method of treating an adenosine receptor-associated disease.
The examiner suggests amending the claim, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
Claim 13 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 13 recites the limitation, The method of claim 12, wherein ring A is azaindolizinyl, in line 1 of the claim. There is insufficient antecedent basis, in claim 12, for this limitation, with respect to the substituted pyrazines of the Formula (Ia-ii) administered within the method of treating an adenosine receptor-associated disease. According to claim 1, ring A is not recited as azaindolizinyl, with respect to the substituted pyrazines of the Formula (I) administered within the method of treating an adenosine receptor-associated disease.
The examiner suggests amending the claim, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
New Claim Rejections - Obviousness-type 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 obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined invention claim is not patentably distinct from the reference claims because the examined invention claim is either anticipated by, or would have been obvious over, the reference claims. {See 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969)}.
US Patent No. 11,571,420
Consequently, claims 1-18 and 21 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of US Patent No. 11,571,420. Although the conflicting claims are not identical, they are not patentably distinct from each other because claim 1 in US 11,571,420 recites substituted pyrazines of the Formula (I), where m = 1; n = 0; ring A = -imidazo[1,2-a]pyridinyl; ring B = -5-6 membered saturated or unsaturated hetero-cyclyl having 1, 2, or 3 heteroatoms selected from N or O; R1 = -C1-12 alkyl; X = -NH2; W = -C(O)-; V = -NH-; and Y = -3-12 membered saturated or unsaturated carbocyclyl, monosubstituted by R3, wherein R3 = -C1-12 alkoxyl, respectively, which are administered within the instantly recited method of treating an adenosine receptor-associated disease, comprising administering… a substituted pyrazine of the Formula (I), comprising administering… a substituted pyrazine of the Formula (I), where m = 1; n = 0; ring A = -imidazo[1,2-a]pyridinyl; ring B = -5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or O; R1 = -C1-12 alkyl; X = -NH2; W = -C(O)-; V = -NH-; and Y = -3-12 membered saturated or unsaturated carbocyclyl, monosubstituted by R3, wherein R3 = -C1-12 alkoxyl, respectively.
The inventor or joint inventor should note that [T]he discovery of a previously unappreciated property of a prior art compound, or of a scientific explanation for the prior art’s functioning, does not render the old compound patentably new to the discoverer. {See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)}.
Similarly, the inventor or joint inventor should further note that [T]he claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. {See In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977); and In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)}.
Likewise, the inventor or joint inventor should note that [W]hen the claim recites using an old compound and the use is directed to a result or property of that compound, then the claim is anticipated. {See In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978); and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966)}.
Next, the inventor or joint inventor should further note that [P]roducts of identical chemical composition may not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties the inventor or joint inventor discloses and/or claims are necessarily present. {See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)}.
Moreover, the inventor or joint inventor should further note that [A] claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use. {See Sun Pharmaceuticals Industries Ltd. v. Eli Lilly and Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353, 1363, 86 USPQ2d 1001 (Fed. Cir. 2008); and Geneva
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349 F.3d 1373, 68 USPQ2d 1865, (Fed. Cir. 2003)}.
US Patent No. 10,898,481
At least claims 1-5, 7, 8, 12-14, 16-18 and 21 are further rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 of US Patent No. 10,898,481. Although the conflicting claims are not identical, they are not patentably distinct from each other because claim 1 in US 10,898,481 recites substituted pyrazines of the Formula (Ia-ii), where m = 1; ring A = -azaindolizinyl; R1 = -CH3; Z = -a bond-; and Y = -methoxy-cyclobutyl, respectively, which are administered within the instantly recited method of treating an adenosine receptor-associated disease, comprising administering… a substituted pyrazine of the Formula (I), comprising administering… a substituted pyrazine of the Formula (I), where m = 1; n = 0; ring A = -imidazo[1,2-a]pyridinyl; ring B = -5-6 membered saturated or unsaturated heterocyclyl having 1, 2, or 3 heteroatoms selected from N or O; R1 = -C1-12 alkyl; X = -NH2; W = -C(O)-; V = -NH-; and Y = -3-12 membered saturated or unsaturated carbocyclyl, monosubstituted by R3, wherein R3 = -C1-12 alkoxyl, respectively.
The inventor or joint inventor should note that [T]he discovery of a previously unappreciated property of a prior art compound, or of a scientific explanation for the prior art’s functioning, does not render the old compound patentably new to the discoverer. {See Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)}.
Similarly, the inventor or joint inventor should further note that [T]he claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. {See In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977); and In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)}.
Likewise, the inventor or joint inventor should note that [W]hen the claim recites using an old compound and the use is directed to a result or property of that compound, then the claim is anticipated. {See In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978); and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966)}.
Next, the inventor or joint inventor should further note that [P]roducts of identical chemical composition may not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties the inventor or joint inventor discloses and/or claims are necessarily present. {See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)}.
Then, the inventor or joint inventor should further note that [A] claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use. {See Sun Pharmaceuticals Industries Ltd. v. Eli Lilly and Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353, 1363, 86 USPQ2d 1001 (Fed. Cir. 2008); and Geneva
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349 F.3d 1373, 68 USPQ2d 1865, (Fed. Cir. 2003)}.
Moreover, the inventor or joint inventor should also note that [I]t is obvious to add a carrier or solvent to an unpatentable compound. {See Ex parte Douros and Vanderweff, 163 USPQ 667, (BPAI 1968)}.
Now, the inventor or joint inventor should further note that a timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 37 CFR 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground, provided the conflicting invention or patent either is shown to be commonly owned with this invention, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Furthermore, the inventor or joint inventor should also note that the USPTO internet Web site contains terminal disclaimer forms which may be used, and the inventor or joint inventor is encouraged to visit http://www.uspto.gov/forms/, where (i) the filing date of the invention will determine what form should be used, and (ii) a web-based eTerminal Disclaimer may be filled out completely online using web-screens, respectively.
Also, the inventor or joint inventor should further note that an eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission.
Finally, for more information about eTerminal Disclaimers, the inventor or joint inventor should refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Allowable Subject Matter
No claims are allowed.
Conclusion
The inventor’s or joint inventor’s arguments and/or the Amendments to the Claims, filed April 2, 2026, necessitated the new grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). The inventor or joint inventor is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The Examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The Examiner is also available on alternate Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624
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