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 1-58 are pending in the instant invention. According to the Amendments to the Claims, filed March 28, 2024, claims 3, 5, 7-25, 29, 32, 33 and 35-57 were amended.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/US2022/077120, filed September 27, 2022, which claims priority under 35 U.S.C. § 119(a-d) to International Application No. PCT/CN2021/121548, filed September 29, 2021.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on May 7, 2026, is acknowledged: a) Group I - claims 1-3, 8-27, 32-43 and 47-55; and b) substituted urea of Formula (I) - p. 132, Example 6, shown to the right below, and hereafter referred to as 1-(cyclopropylmethyl)-N-((6-methyl-5-(pyrazolo[1,5-a]pyridin-5-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-1H-pyrazole-4-sulfonamide, where n = 0; at N1, R1 = -CH2R11, wherein R11 = -cyclopropyl; ring Q = -pyrazol-1,4-diyl; R1 = -H; A = -CH2-; R3 = -CH3; R4 = -H; R5 = -H; R6 = -H; X1 = N; X2 = N; X3 = C; X4 = C; and X5 = C. Claims 1-3, 8, 9, 14, 27, 32, 33, 35, 38-42, 47, 48, 51, 52 and 55 read on the elected species. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
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Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Likewise, the inventor or joint inventor should further note that the elected species, shown to the right, was found to be free of the prior art. Thus, the examiner has expanded the forthcoming prosecution to include all claims relevant to the genus of Group I, for a first Office action and prosecution on the merits.
Moreover, the inventor or joint inventor should further note that claims 2, 4-7, 28-31, 44-46 and 56-58 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1, 3, 8-27, 32-43 and 47-55 is contained within.
Specification Objection - Disclosure
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the inventor’s or joint inventor’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility invention should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase Not Applicable should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR
DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A
COMPACT DISC.
(f) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art (including information disclosed under 37 CFR 1.97
and 1.98).
(g) BRIEF SUMMARY OF THE INVENTION.
(h) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(i) DETAILED DESCRIPTION OF THE INVENTION.
(j) CLAIM OR CLAIMS (commencing on a separate sheet).
(k) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(l) SEQUENCE LISTING (See MPEP § 2424 and 37 CFR 1.821-1.825).
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(b) above and 37 CFR 1.77(c). Revisions should particularly include and/or address: a) section headings (b-i), where applicable; and b) bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Abstract
The inventor or joint inventor is reminded of the proper content of an abstract of the disclosure.
With regard particularly to chemical patents, for compounds or compositions, the general nature of the compound or composition should be given as well as the use thereof, e.g., The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics. Exemplification of a species could be illustrative of members of the class. For processes, the reactions, reagents and process conditions should be stated, generally illustrated by a single example, unless variations are necessary. See MPEP § 608.01(b), Section B.
The abstract of the disclosure is objected to because it fails to exemplify any members or formulae illustrative of its class. Correction is required. See MPEP § 608.01(b).
The examiner suggests incorporating the structure of Formula (I) into the abstract, to overcome this objection.
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:
A compound of Formula (I):
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(I)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof,
wherein:
ring Q is C3-7 cycloalkyl, 5- or 6-membered heterocyclyl, or 5- or 6-membered heteroaryl;
R1 is H, C1-4 alkyl, C1-4 haloalkyl, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, or 4- to 6-membered heterocyclyl;
wherein the C1-4 alkyl, C1-4 haloalkyl, or OC1-4 alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl; and
wherein the OC3-7 cycloalkyl, C3-7 cycloalkyl, or 4- to 6-membered heterocyclyl is optionally substituted with one, two, or three independently selected R11 substituents;
each R2 is independently H, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)NRaRb, NRaRb, OH, OC1-4 alkyl, C3-7 cycloalkyl, or 4- to 6-membered heterocyclyl;
wherein each C1-4 alkyl, C1-4 haloalkyl, and OC1-4 alkyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl; and
wherein each C3-7 cycloalkyl and 4- to 6-membered heterocyclyl is optionally and independently substituted with one, two, or three independently selected R11 substituents;
n is 0, 1, or 2;
A is -CH2- or -O-;
R3 is H, halogen, CN, C1-4 alkyl, or C1-4 haloalkyl;
R4 is H, halogen, CN, C1-4 alkyl, or C1-4 haloalkyl;
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is:
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, or
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;
R5 is H, halogen, CN, C1-4 alkyl, or C1-4 haloalkyl;
R6 is H, halogen, CN, C1-4 alkyl, or C1-4 haloalkyl;
R7 is H or C1-4 alkyl;
each R11 is independently halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, or 4- to 6-membered heterocyclyl;
each Ra is independently H, C1-4 alkyl, or C3-5 cycloalkyl; and
each Rb is independently H, C1-4 alkyl, or C3-5 cycloalkyl; or
each Ra and Rb, taken together with the nitrogen atom to which they are attached, independently forms a saturated or unsaturated 3- to 7-membered heterocyclyl;
wherein each 3- to 7-membered heterocyclyl optionally and independently contains one or two additional heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S; and
wherein 3- to 7-membered heterocyclyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of C1-4 alkyl, CH2-phenyl, and phenyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein
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is:
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, or
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.
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 of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is a 5-membered heteroaryl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is furanyl, thiophenyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, or triazolyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is:
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, or
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q together with R1 is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q together with R1 is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 16 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q together with R1 is:
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.
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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is a 6-membered heteroaryl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 18 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl.
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 of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is:
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, or
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.
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 of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q together with R1 is:
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.
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 of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is C3-7 cycloalkyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 22 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is cyclobutyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 23 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q is 5- or 6-membered heterocyclyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 24 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 23, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein the 5- or 6-membered heterocyclyl contains one or two heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S.
Appropriate correction is required. See MPEP § 2173.02.
Claim 25 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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein ring Q together with R1 is:
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.
Appropriate correction is required. See MPEP § 2173.02.
Claim 26 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is of Formula (Ia):
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(Ia)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 27 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is of Formula (Ib):
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(Ib)
or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 32 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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is C1-4 alkyl, C1-4 haloalkyl, NRaRb, OC1-4 alkyl, O(cyclopropyl), O(cyclobutyl), cyclopropyl, cyclobutyl, or 4- to 6-membered heterocyclyl:
wherein the C1-4 alkyl, C1-4 haloalkyl, or OC1-4 alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl; and
wherein the O(cyclopropyl), O(cyclobutyl), cyclopropyl, cyclobutyl, or 4- to 6-membered heterocyclyl is optionally substituted with one, two, or three independently selected R11 substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 33 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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is C1-4 alkyl, NRaRb, OC1-4 alkyl, OC3-5 cycloalkyl, C3-5 cycloalkyl, or 4- to 6-membered heterocyclyl;
wherein the C1-4 alkyl, or OC1-4 alkyl is optionally substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl; and
wherein the OC3-5 cycloalkyl, C3-5 cycloalkyl, or 4- to 6-membered heterocyclyl is optionally substituted with one, two, or three independently selected R11 substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 34 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 33, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein:
(a) OC3-5 cycloalkyl is O(cyclopropyl) or O(cyclobutyl); and
(b) C3-5 cycloalkyl is cyclopropyl or cyclobutyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 35 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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is CH3, wherein the CH3 is optionally substituted with one substituent selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 36 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is cyclopropyl, wherein the cyclopropyl is optionally substituted with one R11 substituent.
Appropriate correction is required. See MPEP § 2173.02.
Claim 37 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 is cyclobutyl, wherein the cyclobutyl is optionally substituted with one R11 substituent.
Appropriate correction is required. See MPEP § 2173.02.
Claim 38 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 compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein each R2 is independently H, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, NRaRb, OH, OC1-4 alkyl, C3-5 cycloalkyl, or 4- to 6-membered heterocyclyl;
wherein each C1-4 alkyl, C1-4 haloalkyl, and OC1-4 alkyl is optionally and independently substituted with one, two, or three substituents independently selected from the group consisting of halogen, CN, C(O)NRaRb, C(O)NHC(O)Ra, C(O)ORa, NRaRb, NRbC(O)Ra, OH, OC1-4 alkyl, OC(O)Ra, OC3-7 cycloalkyl, C3-7 cycloalkyl, and 4- to 6-membered heterocyclyl; and
wherein each C3-5 cycloalkyl and 4- to 6-membered heterocyclyl is optionally and independently substituted with one, two, or three independently selected R11 substituents.
Appropriate correction is required. See MPEP § 2173.02.
Claim 39 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R3 is H, F, Cl, or CH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 40 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R4 is H, halogen, or CH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 41 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R5 is H or CH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 42 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R6 is H or CH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 43 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R7 is H or CH3.
Appropriate correction is required. See MPEP § 2173.02.
Claim 47 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein each R11 is independently halogen, CN, C1-4 alkyl, NRaRb, OH, OC1-4 alkyl, OC3-5 cycloalkyl, C3-5 cycloalkyl, or 4- to 6-membered heterocyclyl;
wherein each 4- to 6-membered heterocyclyl independently contains one or two heteroatoms or heteroatomic groups independently selected from the group consisting of N, NH, O, and S.
Appropriate correction is required. See MPEP § 2173.02.
Claim 48 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein each R11 is independently cyclopropyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 49 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein each R11 is independently cyclobutyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 50 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein each R11 is independently oxetanyl.
Appropriate correction is required. See MPEP § 2173.02.
Claim 51 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein n is 0.
Appropriate correction is required. See MPEP § 2173.02.
Claim 52 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is selected from the group consisting of:
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or a pharmaceutically acceptable salt or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 53 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, wherein the compound is selected from the group consisting of:
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or a pharmaceutically acceptable salt or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 54 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The compound of claim 1, or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is selected from the group consisting of:
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or a pharmaceutically acceptable salt or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 55 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.
Appropriate correction is required. See MPEP § 2173.02.
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.
Substituted ureas of the Formula (I)
Claims 1, 8-27, 32-43, 47-51 and 55 are rejected under 35 U.S.C. § 112(a) because the specification, while being enabling for substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are as presented herein in the section above entitled Claim Objections, does not reasonably provide enablement for substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections, as recited in claim 1, have not been adequately enabled in the specification to allow any person having ordinary skill in the art, at the time this invention was made, to make and/or use substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections
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 instant invention, are summarized as follows:
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(a) Breadth of the claims - the breadth of the claims includes substituted ureas of the Formula (I), shown to the right;
(b) Nature of the invention - the nature of the invention is evaluation of substituted ureas of the Formula (I), shown to the right, and the pharmacokinetic behavior of these substances as inhibitors of interleukin-1 (IL-1) activity;
(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). Moreover, WO 23/056264 provides a synthesis of the instantly recited substituted ureas of the Formula (I) {Zhang, et al. WO 23/056264, 2023};
(d) Level of one of ordinary skill in the art - the artisans synthesizing the inventor’s or joint inventor’s substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections, 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 unclear based on the combination of the instant specification and Zhang, et al. in WO 23/056264, respectively, whether the instantly recited substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections, are enabled. Moreover, the following excerpt is taken from Dörwald, which has relevance to the synthesis of isotopes of substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections {Dörwald, F. Zaragoza. Side Reactions in Organic Synthesis: A Guide to Successful Synthesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2005, Preface}:
Most non-chemists would probably be horrified if they were to learn how many attempted syntheses fail, and how inefficient research chemists are. The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why.
Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who has experienced for himself the many failures and frustrations which the development (sometimes even the repetition) of a synthesis usually implies will be able to appraise such work.
Chemists tend not to publish negative results, because these are, as opposed to positive results, never definite (and far too copious).
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections;
(g) Existence of working examples - the inventor or joint inventor has provided sufficient guidance to make and/or use substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are as presented herein in the section above entitled Claim Objections; however, the disclosure is insufficient to allow extrapolation of the limited examples to enable the instantly recited substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections. The specification lacks working examples of substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections.
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 or use 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). Similarly, the specification, as originally filed, including any references incorporated therein, fails to provide the necessary support required by 35 U.S.C. § 112(a) to enable the instantly recited substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections. Thus, it is unclear, based on the guidance provided by the specification, whether a substituted urea of the Formula (I), such as 1-{[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]sulfonyl}-3-(6-methyl-5-{[1,2,3]triazolo[1,5-a]pyridin-6-yl}-2,3-dihydro-1H-inden-4-yl)urea, shown to the left above, is either synthetically feasible or possesses utility as an inhibitor of interleukin-1 (IL-1) activity.
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 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 substituted ureas of the Formula (I), where the substituted ureas of the Formula (I) are not as presented herein in the section above entitled Claim Objections, is clearly justified.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
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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