Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status
The present FINAL office action is in response to December 1, 2025 Amendment/ Request
for Reconsideration and corresponding documents.
Claims 1-22 and 25 are pending, amended and rejected, claims 23 and 23 cancelled in the above-identified application.
Priority
U.S. Pat. Appln. Ser. No.: 18/015,261, Filed: January 09, 2023 is a 371 Nat.’ l Stage Entry of WO 2022/007882A1 (i.e., PCT/CN2021/105180, Intern.’ l Filing Date: July 08, 2021, Intern.’ l Pub. Date: January 13, 2022), which claims foreign priority to CN 202110308656.X, Filed: March 23, 2021 and CN 202010658085.8, Filed: July 9, 2020.
WITHDRAWN REJECTIONS
Rejection of claims 23 and 24 under 35 USC § 101 is rendered moot due to cancellation of claims and now is WITHDRAWN
Rejection of claims 1-22 and 25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para., as being indefinite for failing to particularly point out and distinctly claim the subject matter is WITHDRAWN due to claim amendments.
WITHDRAWN IN PART AND MAINTAINED IN-PART REJECTIONS
[1] Rejection of claims 23 and 24 cancelled) under 35 U.S.C. 112(a):
are rendered moot due to cancellation of claims 23 and 24 and now Withdrawn.
[2] Rejection of claims 1-22 and 25 (i.e., claims 23 -24 cancelled) under 35 U.S.C. 112(a):
is maintained in part identified by outstanding rejectable subject matter from original rejection in bold text (i.e., further clarified and/or explanation provided, if necessary) for reasons below:
the specification, while being enabling for:
compounds of Formulas I’, I, II,II-1, III, or III-1, respectively, or pharmaceutically acceptable salts thereof (i.e., as recited in claims 1-22 and 25); and
a method for treating cancer, fibrotic diseases, metabolic diseases, myelodysplastic syndrome, respiratory diseases, cardiovascular diseases, autoimmune diseases, inflammation, dermatological diseases, nervous system diseases, or pain associated pathologic features with increased Autotaxin (ATX) expression, which comprises compounds of claim 1 or pharmaceutically acceptable salts thereof;
does not reasonably provide enablement for:
ALL method(s) treating ALL related disease(s) with ALL pathologic feature(s) of increased ATX expression, which comprises administrating an effective amount of the compound or the pharmaceutically acceptable salt, or ALL solvate(s) to a subject in need thereof (i.e., as recited in claim 25).
Applicants’ Arguments
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Examiner’s Response
In general, 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 the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
In particular, Examiner respectfully disagrees with the Applicants arguments.
upon further review, consideration, maintained and now clarified enablement rejection supra.
Without reiteration of the record, relevant sections of the originally set forth rejection are incorporated herein in its entirety (i.e., excerpts of which are included in discussion below)
In particular, claims 1-22 and 25 are rejected here for lack of enablement, because:
[1] with regard to the definition of the term 'solvates' in the rejected claims, none of the exemplified 29 specification examples (i.e., identified as solid final products and characterized only by 1HNMR data) are directed to solvates.
Based on the foregoing use of the term “solvates” lacks enabling disclosure, Applicants are requested to delete the term “solvates: to overcome this rejection. Thus, the claimed solvates would be operable here.
[2] with regard to claim 25, it is unclear how and what such a method would treat given:
no specific “related disease(s)” are defined leading to diverse associated pathologic features of increased ATX expression given diseases are not identified;
no working examples, in vivo data, or specific formulation details demonstrating the treatment of whatever is defined by the broad term “diseases”.
Without any data, the skilled artisan would have to engage in undue experimentation to determine which compounds within the broad genus are effective for the broad term disease, as the efficacy of these compounds across such disparate disease and pathologies is not predictable.
However, the instant specification sets forth these specific diseases associated with pathologic feature(s) of increased ATX expression linked via a common mechanism of action (i.e., identified as ATX-LPA Axis: these diseases are linked by the overproduction of lysophosphatidic acid (LPA), a potent signaling phospholipid) conventionally known in the art (since early 2000’s):
cancer, fibrotic diseases, metabolic diseases, myelodysplastic syndrome, respiratory diseases, cardiovascular diseases, autoimmune diseases, inflammation, dermatological diseases, nervous system diseases, or pain (see specification and cancelled claims 23 and 24); and
such that the art of ATX inhibitors is predictable, meaning in vitro potency directly translates to in vivo success across all listed diseases.
The compounds claimed are structurally similar enough that data on a few is representative of the whole genus (representative number).
[3] Previous discussion of Wands factors indicated sufficient Amount of Guidance and Working Examples in the specification that:
teach Autotaxin (ATX) inhibitor phenyl amino thiazole compounds of Formula (I’) or a pharmaceutically acceptable salt thereof:
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; or a pharmaceutically acceptable salt thereof
(i.e., variables as defined in amended claim 1); corresponding pharmaceutical compositions;
Compound Examples 1 to 29: Directed to compounds species, corresponding preparation methods; i.e., which are solid forms, non-solvated, characterized by 1H NMR data
Supported by Preliminary Pre-Clinical Working Examples, which includes in-vitro and in-vivo biological laboratory and animal testing (i.e., e.g., ATX activity/CYP450 Enzyme and Time/Herg inhibition assays, pK/pD rat blood data, invitro cellular data safety, comparative testing with art known Ziritaxestat (first-in-class autotaxin (ATX) inhibitor GLPG1690; CAS No.: 1628260-79-6)
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To overcome this rejection, Applicants are requested to make amendments to claim 25 to recite:
a method for treating cancer, fibrotic diseases, metabolic diseases, myelodysplastic syndrome, respiratory diseases, cardiovascular diseases, autoimmune diseases, inflammation, dermatological diseases, nervous system diseases, or pain associated pathologic features with increased Autotaxin (ATX) expression, which comprises compounds of claim 1 or pharmaceutically acceptable salts thereof; and
to amend claim 1 to delete the term “solvate” as discussed supra.
It is well established that “the 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Appropriate action is required accordingly in the instant application.
MAINTAINED REJECTIONS
Rejection of claims 1-15, 18, 21,22 and 23-25 are under 35 U.S.C. 102(a)(1) as being anticipated by WO 2019/228403 to Fronthera U.S. Pharmaceuticals (i.e., “WO ‘403 Appln.”, Intern.’l Filing Date: May 29, 2019; Intern.’l Pub. Date: December 5, 2019) is MAINTAINED for reasons below:
Applicants Arguments
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In particular. Applicants state in there December 1, 2025 Amendment that:
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Examiner Arguments
The Examiner respectfully disagrees with Applicants arguments, because Frontera discloses compound 72 reads on the amended genus of Formula (I) of the present invention as shown below
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Therefore, the above-identified reference anticipates the claimed invention.
Rejection of claims 1-15, 18, 21,22 and 23-25 under 35 U.S.C. 102(a)(1) as being
anticipated by
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is MAINTAINED.
Applicants Arguments
Applicants maintain that:
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Examiner Arguments
After review of the amended claims, the Examiner respectfully disagrees with Applicants arguments.
In summary:
amended claims 1-2, 4-6, 8-9, 14-15 and 21-22 are directed to compounds and pharmaceutical compositions/formulations of the claimed invention; and
Joncour discloses the ATX inhibitor, 2-ethyl-N-[4-(4-fluorophenyl)-2-thiazolyl]-N-methyl-6-(3-pyridinyl)-imidazo[1,2-a]pyridin-3-amine, i.e., compound 3 (found in Table 1 at p. 7373 and in experimental example, see col. 1, lines 15-24 at p. 7384) and pharmaceutical compositions/formulations there are descrived as compound examples therein diluted in pH buffer solutions, inc. those with solubility enhancers, other excipients and the like. i.e., see biochemical assay and rat pK/pD examples (1 mg/mL of 40). at page 7390
Formula (I) (inc. corresponding definitions as recited) in amended claim 1 of the present invention encompasses Joncour compound 3 (found in Table 1 at p. 7373). Among other variables, it is possible to derive R6=H based on definitions set forth in amended claim 1of the present invention as shown below:
Joncour Compound
Amended Claim 1
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RN 2113717-30-7 HCAPLUS
CN Imidazo[1,2-a]pyridin-3-amine, 2-ethyl-N-[4-(4-fluorophenyl)-2-thiazolyl]-N-methyl-6-(3-pyridinyl)- (CA INDEX NAME)
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A =
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R6 = -L1-L2-W (i.e., hydrogen)
L1 = L2 = chemical bond
W = unsubstituted as follows: hydrogen . . . “
B=
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X1 = X2 = X3 = CR5
X4 = N
R5 = R2 = H
R4= C1-C6 alkyl (i.e., CH2CH3)
R3 = C1-C6 alkyl (i.e., CH3)
R1 = halogen (i.e. fluorine)
n = 1
is anticipated by the previously cited compound taught in the Joncour reference as follows , when the variable phrase of amended claim 1 is substituted with the definitions recited therein:
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Therefore, the above-identified reference anticipates the claimed invention..
CONCLUSION
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/G.C.H./
Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627