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 1-9, 13, 14 and 17-21 are pending in the instant invention. According to the Listing of Claims, filed May 1, 2026, claims 1-9, 13, 14 and 17-21 were amended and claims 10-12, 15 and 16 were cancelled.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/EP2021/084448, filed December 6, 2021, which claims priority under 35 U.S.C. § 119(a-d) to: a) GB 2109583.1, filed July 2, 2021; and b) GB 2019702.6, filed December 14, 2020.
Status of Restrictions / Election of Species
PNG
media_image1.png
200
400
media_image1.png
Greyscale
The inventor’s or joint inventor’s affirmation of the following election, without traverse, in the reply filed on May 1, 2026, is acknowledged: a) Group I - claims 1-9, 13, 14 and 19-21; and b) substituted imidazo[1,2-b]pyridazine of formula (I) - p. 121, Example 17.
Similarly, the inventor or joint inventor should further note that the requirement was made FINAL in the Non-Final Rejection, mailed on February 2, 2026.
Likewise, the inventor or joint inventor should further note that claim 1 is directed to allowable substituted imidazo[1,2-b]pyridazines of the formula (I). Pursuant to the procedures set forth in MPEP § 821.04(b), (i) claim 17, directed to a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (ii) claim 18, directed to a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Next, the inventor or joint inventor should further note that since all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action, mailed on October 1, 2025, is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, the inventor or joint inventor is advised that if any claim presented in a continuation or divisional invention is anticipated by, or includes all the limitations of, a claim that is allowable in the present invention, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant invention.
Then, the inventor or joint inventor should further note that once the restriction requirement is withdrawn, the provisions of 35 U.S.C. § 121 are no longer applicable. {See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971); and MPEP § 804.01}.
Moreover, 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 February 2, 2026.
Also, 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 May 1, 2026.
Thus, a second Office action and prosecution on the merits of claims 1-9, 13, 14 and 17-22 is contained within.
New Claim Objections
Claim 1 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
A compound of formula (I):
PNG
media_image2.png
200
400
media_image2.png
Greyscale
(I)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
R1a represents H, F, Cl, CH3, CHF2, or CF3;
R1b represents H, F, Cl, CH3, CHF2, or CF3;
A represents formula (Aa), formula (Ab), formula (Ac), formula (Ad), or formula (Ae):
PNG
media_image3.png
200
400
media_image3.png
Greyscale
(Aa),
PNG
media_image4.png
200
400
media_image4.png
Greyscale
(Ab),
PNG
media_image5.png
200
400
media_image5.png
Greyscale
(Ac),
PNG
media_image6.png
200
400
media_image6.png
Greyscale
(Ad), or
PNG
media_image7.png
200
400
media_image7.png
Greyscale
(Ae),
wherein:
R2 represents OR2a, C3-9 cycloalkyl, C4-12 bicycloalkyl, C3-7 heterocycloalkyl, or C4-9 heterobicycloalkyl, wherein the C3-9 cycloalkyl, C4-12 bicycloalkyl, C3-7 heterocycloalkyl, or C4-9 heterobicycloalkyl is optionally substituted by one or more independently selected halogen substituents;
R2a represents C1-6 alkyl or C3-9 cycloalkyl;
wherein the C1-6 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2; and
wherein the C3-9 cycloalkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2;
R3 represents NR3aR3b or formula (Wa):
PNG
media_image8.png
200
400
media_image8.png
Greyscale
(Wa);
R3a represents H or C1-6 alkyl;
R3b represents C1-6 alkyl, C1-6 alkylene-C3-7 cycloalkyl, C1-6 alkylene-C3-7 heterocycloalkyl, C1-6 alkylene-aryl, C1-6 alkylene-heteroaryl, C3-7 cycloalkyl, C4-12 bicycloalkyl, C3-7 heterocycloalkyl, aryl, or heteroaryl;
wherein any C1-6 alkyl or C1-6 alkylene is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, OCF2CH3, OCHFCH2F, OCH2CHF2, OCHFCHF2, OCF2CH2F, OCH2CF3, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2; and
wherein any C3-7 cycloalkyl, C4-12 bicycloalkyl, C3-7 heterocycloalkyl, aryl, or heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, OCF2CH3, OCHFCH2F, OCH2CHF2, OCHFCHF2, OCF2CH2F, OCH2CF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2;
(i) W represents the residue of a saturated monocyclic ring;
wherein the monocyclic ring contains 3, 4, 5, or 6 C atoms, 1 N heteroatom, and optionally 1, 2, or 3 additional heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S;
wherein the monocyclic ring contains no more than 1 O heteroatom or 1 S heteroatom; and
wherein the monocyclic ring is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-6 alkyl, CF3, C1-6 alkyl-C(O)OH, C1-6 alkyl-C(O)OC2-6 alkyl, C1-6 aminoalkyl, C1-6 alkyl-N(C1-6 alkyl)2, C1-6 hydroxyalkyl, C1-6 alkyl-OC1-6 alkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, and S(O)2C1-6 alkyl;
(ii) W represents the residue of a saturated bicyclic ring system;
wherein the bicyclic ring system contains 4, 5, 6, 7, 8, 9, or 10 C atoms, 1 N heteroatom, and optionally 1, 2, or 3 additional heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S;
wherein the bicyclic ring system contains no more than 1 O heteroatom or 1 S heteroatom; and
wherein the bicyclic ring system is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-6 alkyl, CF3, C1-6 alkyl-C(O)OH, C1-6 alkyl-C(O)OC2-6 alkyl, C1-6 aminoalkyl, C1-6 alkyl-N(C1-6 alkyl)2, C1-6 hydroxyalkyl, C1-6 alkyl-OC1-6 alkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, and S(O)2C1-6 alkyl;
(iii) W represents the residue of a saturated spirocyclic ring system;
wherein the spirocyclic ring system contains 5, 6, 7, 8, 9, or 10 C atoms, 1 N heteroatom, and optionally 1, 2, or 3 additional heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S;
wherein the spirocyclic ring system contains no more than 1 O heteroatom or 1 S heteroatom; and
wherein the spirocyclic ring system is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-6 alkyl, CF3, C1-6 alkyl-C(O)OH, C1-6 alkyl-C(O)OC2-6 alkyl, C1-6 aminoalkyl, C1-6 alkyl-N(C1-6 alkyl)2, C1-6 hydroxyalkyl, C1-6 alkyl-OC1-6 alkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, and S(O)2C1-6 alkyl; and
each asterisk (*) independently represents the point of attachment to the remainder of the molecule;
R4a represents H, F, C1-6 alkyl, or OH, wherein the C1-6 alkyl is optionally substituted by one or more independently selected from the group consisting of halogen, CN, NO2, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, OCF2CH3, OCHFCH2F, OCH2CHF2, OCHFCHF2, OCF2CH2F, OCH2CF3, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2;
R4b represents H, F, C1-6 alkyl, or OH, wherein the C1-6 alkyl is optionally substituted by one or more independently selected from the group consisting of halogen, CN, NO2, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, OCF2CH3, OCHFCH2F, OCH2CHF2, OCHFCHF2, OCF2CH2F, OCH2CF3, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2; or
R4a and R4b, taken together with the carbon atom to which they are both attached, represent a C3-9 cycloalkylene or C3-7 heterocycloalkylene, wherein the C3-9 cycloalkylene or C3-7 heterocycloalkylene is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, C1-6 alkyl, CF3, CF2CH3, CHFCH2F, CH2CHF2, CHFCHF2, CF2CH2F, CH2CF3, C(O)C2-6 alkyl, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, =O, SC1-6 alkyl, S(O)C1-6 alkyl, and S(O)2C1-6 alkyl;
Y represents -CR5aR5b-, -NR7-, -O-, -S-, -S(O)-, -S(NR8)(O)-, or -S(O)2-;
R5a represents H, F, CH3, CHF2, or CF3;
R5b represents H, F, CH3, or OH; or
R5a and R5b, taken together with the carbon atom to which they are both attached, represent cyclopropylene;
R7 represents H, C1-6 alkyl, C(O)R7a, C(O)OR7a, S(O)2R7b, C3-9 cycloalkyl, or C3-7 heterocycloalkyl, wherein the C1-6 alkyl, C3-9 cycloalkyl, or C3-7 heterocycloalkyl is optionally substituted by one or more F substituents;
R7a represents C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by one or more F substituents;
R7b represents C1-6 alkyl;
R8 represents C1-6 alkyl;
Z represents heteroaryl, wherein the heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CHF2, CF2CH3, CHFCH2F, CH2CHF2, C1-6 trifluoroalkyl, CH2-cyclopropyl, CH2-difluorocyclopropyl, C1-6 aminoalkyl, C1-6 (dialkylamino)alkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, OCF2CH3, OCHFCH2F, OCH2CHF2, OCHFCHF2, OCF2CH2F, OCH2CF3, -OCH2O-, -OCF2O-, =O, O(phenyl), SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, S(O)2N(C1-6 alkyl)2, cyclopropyl, difluorocyclopropyl, difluorocyclobutyl, fluorobicyclo[1.1.1]pentanyl, cyanobicyclo[1.1.1]pentanyl, spiro[2.2]pentanyl, and methylspiro[2.2]pentanyl; and
the asterisk (*) represents the point of attachment to the remainder of the molecule;
E represents formula (Ea), formula (Eb), formula (Ec), formula (Ed), or formula (Ee):
PNG
media_image9.png
200
400
media_image9.png
Greyscale
(Ea),
PNG
media_image10.png
200
400
media_image10.png
Greyscale
(Eb),
PNG
media_image11.png
200
400
media_image11.png
Greyscale
(Ec),
PNG
media_image12.png
200
400
media_image12.png
Greyscale
(Ed), or
PNG
media_image13.png
200
400
media_image13.png
Greyscale
(Ee),
wherein the asterisk (*) represents the point of attachment to the remainder of the molecule;
R6 represents C1-6 alkyl, C1-6 alkylene-C3-9 cycloalkyl, C1-6 alkylene-C3-7 heterocycloalkyl, C1-6 alkylene-aryl, C1-6 alkylene-heteroaryl, NR6bR6c, OR6a, C3-9 cycloalkyl, C3-7 heterocycloalkyl, aryl, or heteroaryl, wherein the C1-6 alkyl, C1-6 alkylene-C3-9 cycloalkyl, C1-6 alkylene-C3-7 heterocycloalkyl, C1-6 alkylene-aryl, C1-6 alkylene-heteroaryl, C3-9 cycloalkyl, C3-7 heterocycloalkyl, aryl, or heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C1-6 aminoalkyl, C1-6 alkyl-NHC(O)C2-6 alkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, S(O)2N(C1-6 alkyl)2, cyclopropyl, pyrrolidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, phenyl, and fluorophenyl;
R6a represents C1-6 alkyl, C3-9 cycloalkyl, or C3-7 heterocycloalkyl;
wherein the C1-6 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, SC1-6 alkyl, S(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2; and
wherein the C3-9 cycloalkyl or C3-7 heterocycloalkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, and S(O)2N(C1-6 alkyl)2;
R6b represents H or C1-6 alkyl; and
R6c represents H or C1-6 alkyl; or
R6b and R6c, taken together with the nitrogen atom to which they are both attached, represent azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, homopiperidin-1-yl, isoxazolidin-2-yl, oxazolidin-3-yl, isothiazolidin-2-yl, thiazolidin-3-yl, piperazin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, homopiperazin-1-yl, or homomorpholin-4-yl, wherein the azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, homopiperidin-1-yl, isoxazolidin-2-yl, oxazolidin-3-yl, isothiazolidin-2-yl, thiazolidin-3-yl, piperazin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, homopiperazin-1-yl, or homomorpholin-4-yl is optionally substituted by one or more substituents independently selected from the group consisting of CN, C1-6 alkyl, C1-6 aminoalkyl, C1-6 alkyl-NHC(O)C2-6 alkyl, C1-6 hydroxyalkyl, C(O)C2-6 alkyl, C(O)NH2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, OH, =O, and S(O)2C1-6 alkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R6 represents heteroaryl, wherein the heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C1-6 aminoalkyl, C1-6 alkyl-NHC(O)C2-6 alkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, S(O)2N(C1-6 alkyl)2, cyclopropyl, pyrrolidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, phenyl, and fluorophenyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 1, wherein the compound is represented by formula (IIA-1):
PNG
media_image14.png
200
400
media_image14.png
Greyscale
(IIA-1)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
X represents CH or N; and
R16 represents CH3, CH2CH3, CH(CH3)2, or cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 1, wherein the compound is represented by formula (IIA-2):
PNG
media_image15.png
200
400
media_image15.png
Greyscale
(IIA-2)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
X represents CH or N; and
R16 represents CH3, CH2CH3, CH(CH3)2, or cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 1, wherein the compound is represented by formula (IIB-1):
PNG
media_image16.png
200
400
media_image16.png
Greyscale
(IIB-1)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
X represents CH or N; and
R16 represents CH3, CH2CH3, CH(CH3)2, or cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 1, wherein the compound is represented by formula (IIB-2):
PNG
media_image17.png
200
400
media_image17.png
Greyscale
(IIB-2)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
X represents CH or N; and
R16 represents CH3, CH2CH3, CH(CH3)2, or cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for clarity, the claim is dependent upon an objected base claim. Appropriate correction is required. See MPEP § 2173.02.
Claim 17 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:
A method for modulating interleukin 17 (IL-17) activity in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of a compound as claimed in claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 18 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 as claimed in claim 17, wherein the patient has an autoimmune disorder or an inflammatory disorder.
Appropriate correction is required. See MPEP § 2173.02.
Claim 19 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 2, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein A represents formula (Aa), formula (Ac), formula (Ad), or formula (Ae):
PNG
media_image3.png
200
400
media_image3.png
Greyscale
(Aa),
PNG
media_image5.png
200
400
media_image5.png
Greyscale
(Ac),
PNG
media_image6.png
200
400
media_image6.png
Greyscale
(Ad), or
PNG
media_image7.png
200
400
media_image7.png
Greyscale
(Ae).
Appropriate correction is required. See MPEP § 2173.02.
Claim 20 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 2, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R6 represents heteroaryl, wherein the heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C1-6 aminoalkyl, C1-6 alkyl-NHC(O)C2-6 alkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, S(O)2N(C1-6 alkyl)2, cyclopropyl, pyrrolidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, phenyl, and fluorophenyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 21 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound as claimed in claim 3, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R6 represents heteroaryl, wherein the heteroaryl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, CF3, C1-6 aminoalkyl, C1-6 alkyl-NHC(O)C2-6 alkyl, C1-6 hydroxyalkyl, C(O)H, C(O)C2-6 alkyl, C(O)NH2, C(O)NHC1-6 alkyl, C(O)N(C1-6 alkyl)2, C(O)OH, C(O)OC2-6 alkyl, NH2, NHC1-6 alkyl, NHC(O)C2-6 alkyl, NHC(O)OC2-6 alkyl, NHS(O)2C1-6 alkyl, N(C1-6 alkyl)2, OH, OC1-6 alkyl, OCHF2, OCF3, =O, SC1-6 alkyl, S(O)C1-6 alkyl, S(NC1-6 alkyl)(O)C1-6 alkyl, S(O)2C1-6 alkyl, S(O)2NH2, S(O)2NHC1-6 alkyl, S(O)2N(C1-6 alkyl)2, cyclopropyl, pyrrolidinyl, tetrahydropyranyl, piperazinyl, morpholinyl, phenyl, and fluorophenyl.
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.
(1) Method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) Method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I)
Claims 17 and 18 are rejected under 35 U.S.C. § 112(a) as failing to comply with the enablement requirement because the claims contain subject matter, particularly (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, 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:
PNG
media_image1.png
200
400
media_image1.png
Greyscale
(a) Breadth of the claims - the breadth of the claims includes (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), shown to the right below; and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), shown to the right, respectively;
(b) Nature of the invention - the nature of the invention is performance of (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), shown to the right above; and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), shown to the right above, respectively;
(c) State of the prior art - Nature Reviews: Drug Discovery 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 disorders for which the administration of a modulator of IL-17 function is indicated, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder {See In re Hokum, 226 USPQ 353 (ComrPats 1985)}. Moreover, WO 22/128584 illustrates the synthesis of substituted imidazo[1,2-b]-pyridazines of the formula (I), and/or methods of use thereof {Brace, et al. WO 22/128584, 2022};
(d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s (1) method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, 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., 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) (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively;
(g) Existence of working examples - the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited (1) method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively.
Similarly, according to the specification, substituted imidazo[1,2-b]pyridazines of the formula (I) are capable of treating a variety of disorders for which the administration of a modulator of IL-17 function is indicated, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder; however, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any disorders for which the administration of a modulator of IL-17 function is indicated, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder. There is insufficient disclosure to reasonably conclude that the (1) method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, as recited, would contribute to treatment of any disorders for which the administration of a modulator of IL-17 function is indicated, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder. Furthermore, the combination of the instant specification and Brace, et al. in WO 22/128584, respectively, lacks adequate credible evidence to support the assertion that (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, as recited, would contribute to the prophylaxis of any disorders for which the administration of a modulator of IL-17 function is indicated, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder, since the inventor or joint inventor has neither provided convincing data for any patient 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.
PNG
media_image18.png
200
400
media_image18.png
Greyscale
(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 imidazo[1,2-b]pyridazine of the formula (I), such as (S)-4-cyclopropyl-N-((4,4-difluorocyclohexyl)(7-(4-((1,1-difluoroethyl)carbamoyl)tetrahydro-2H-pyran-4-yl)imidazo[1,2-b]pyridazin-2-yl)-methyl)-1,2,5-oxadiazole-3-carboxamide, shown to the left above, possesses utility as a therapeutic agent, useful in (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively. 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 (1) method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I); and (2) method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I), respectively, wherein the disorder for which the administration of a modulator of IL-17 function is indicated, includes, but is not limited to, an inflammatory disorder and/or an autoimmune disorder, to any patient 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) (1) a method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo-[1,2-b]pyridazine of the formula (I); and (2) a method for the treatment and/or prevention of an inflammatory or autoimmune disorder, which comprises administering… a substituted imidazo-[1,2-b]pyridazine of the formula (I), respectively, 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.
Claim 17 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 17 is reach-through claim. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented. Similarly, the metes and bounds of the treatable disorders for which the administration of a modulator of IL-17 function is indicated are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. Likewise, the specification, on page 1, uses open language, such as including, to define treatable disorders for which the administration of a modulator of IL-17 function is indicated as an inflammatory disorder and/or an autoimmune disorder; however, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments, including, but not limited to, an inflammatory disorder and/or an autoimmune disorder. Consequently, the method for the treatment and/or prevention of disorders for which the administration of a modulator of IL-17 function is indicated, which comprises administering… a substituted imidazo[1,2-b]pyridazine of the formula (I) has been rendered indefinite by the use of the reach-through protocol.
The examiner suggests amending the claim, particularly as stated in the section above entitled New Claim Objections, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
The inventor’s or joint inventor’s arguments and/or the Listing of Claims, filed May 1, 2026, necessitated the new ground 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
Prosecution Insights