DETAILED ACTION
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 of the Application
Claims 1, 13, 22, 27, 29 and 40-41 are pending as of the response filed 03/11/2026. Claims 2-12, 14-21, 23-26, 28 and 30-39 are cancelled. Claim 41 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 13, 22, 27, 29 and 40 are examined herein.
Applicant’s remarks regarding the priority benefit is acknowledged and was found to be persuasive. Accordingly, the effective filing date of instant claims 1, 13, 22, 27, 29 and 40 is 01/25/2019, the filing date of PCT/US19/15296, which has support for the subject matter of the instant claims.
The claim objections and objections to the specification of previous record are withdrawn in consideration of the claim/specification amendments in the response dated 03/11/2026.
The 35 U.S.C. § 112(b) rejection of previous record is rendered moot in view of the cancellation of claim 24.
The 35 U.S.C. § 112(d) rejection of previous record is partially rendered moot in view of the cancellation of claims 15, 17 and 24. The 35 U.S.C. § 112(d) rejection of previous record over claims 13 , 22 and 29 are withdrawn in consideration of the claim amendments.
The nonstatutory double patenting rejection of previous record is maintained and modified to reflect the claim amendments and correct inadvertent errors.
Applicant’s arguments have been fully considered and are addressed below.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 13, 22, 27, 29 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 13-15 and 18 of U.S. Patent No. 11,708,367 B2 in view of Wermuth (Molecular variations based in isosteric replacements, 1996).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a compound of Formula I’ with variables as defined in instant claim 1.
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The claims of the reference ‘367 patent are drawn to a compound of Formula I’ with variables as defined in claim 1 of the reference patent.
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The reference ‘367 patent teaches a species of compound in claim 7, 1-N-[4-[(6,7-dimethoxy-1,5-naphthyridin-4-yl)oxy]phenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, having the following structure (Col, 422, Lns. 31-33).
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The above compound of the ‘367 patent overlaps considerably in scope with compound 81 of instant claim 29, differing only in the phenyl versus pyridinyl group, as highlighted.
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Wermuth teaches the substitution of -CH= by -N= in aromatic rings has been one of the most successful applications in classical isosterism (Pg. 211, first paragraph). Wermuth teaches isosterism to be an important research tool in medicinal chemistry, the reason being that isosteres are often much more alike in their biological property than in their physical and chemical properties (Pg. 207, first full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘367 patent and Wermuth, to replace the -CH= in the phenyl ring with -N= as taught by Wermuth, to arrive at the instantly claimed compound (compound 81), with a reasonable expectation of success.
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
Further according to MPEP 2144.09 (I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).” In the instant case, the compounds of the instant invention are taught to regulate, and/or modulate Axl and Mer receptor tyrosine of kinase activity (Para. [0001] of instant specification) and the compounds of the reference ‘367 patent are taught to have the same utility, regulators, and/or modulators of Axl and Mer receptor tyrosine of kinase activity (Abstract; Col. 1, Lns. 10-21 of the ‘367 patent).
The variables Y, R18, R19, R11, R12, R13, R14, R15, X, n, m and p, of the reference ‘367 patent considerably overlap in scope with the instant claims. Therefore, claims 1-10, 13-15 and 18 of the reference ‘367 patent in view of Wermuth render obvious the compounds of instant claims 1, 13, 22, 27, 29 and 40.
The instant claims 1, 13, 22, 27, 29 and 40 and claims 1-10, 13-15 and 18 of the ‘367 patent are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Response to Arguments
Applicants argue on pages 18-20 of the response dated 03/11/2026, that “First, claim 1 of the present application has been amended to recite a narrow genus that closely tracks the compounds exemplified in the present application. The definitions of the variables in the amended claim differ substantially from those in the '367 Patent. There is no teaching or suggestion in the '367 Patent that would have motivated a person skilled in the art to modify the disclosed compounds to arrive at the compounds claimed by the Applicant.” Applicants argue “Second, the '367 Patent discloses numerous compounds and broad structural possibilities. It provides no teaching, preference, or technical reasoning that would have led a skilled person to single out Compound 139 as a starting point for further modification. In the absence of any articulated reason to select this particular compound from among the many disclosed possibilities, the rejection is based on impermissible hindsight reconstruction.” Applicants conclude that Wermuth does not provide a specific teaching, suggestion or motivation to make the specific phenyl-to-pyridyl substitution in the context of the ‘367 patent to arrive at the instantly claimed compounds.
Applicant's arguments have been fully considered but they are not persuasive.
While the instant claims may be narrower in scope for the corresponding variables in comparison to the reference ‘367 patent, they nevertheless, have considerable overlap in scope. For instance, see below.
Variable
Instant claims
Claims of the ‘367 patent
X
N or CH
N or CH
Y
O, S, SO, SO2, NH, and -N(C1-6 alkyl)-
O, S, SO, SO2, NH, and -N(C1-6 alkyl)-
A ring
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R18 and R19
OH, (C1-C6) alkoxy, (C1-C6) alkoxy-(C1-C6) alkoxy, 5 or 6 membered heterocycloalkyl-(C1-C6) alkoxy, (C1-C6) alkoxy-phenyl-, carbamoyl-(C1-C6) alkoxy, dialkylamino-(C1-C6) alkoxy, and dihydroxy-(C1-C6) alkoxy; or
R18 and R19 taken together with the atoms to which they are attached form a fused C3-7 cycloalkyl ring or a fused 4- to 10-membered heterocycloalkyl ring
The -ORa of ‘367 patent overlaps in scope/anticipates the R18 and R19 variables
H, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C6-C10) aryl, (C3-C10) cycloalkyl, 4-14 membered heterocycloalkyl, phenyl, 5-14 membered heteroaryl, -CN, -NO2, -ORa, -SRa, -C(O)Ra, -C(O)NRaRa, -C(O)ORa, -NHRa, -NRaRa, and -NRaC(O)Ra, wherein the (C1-C6) alkyl, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C6-C10) aryl, (C3-C10) cycloalkyl, 4-14 membered heterocycloalkyl, phenyl, and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, (C1-C6) alkyl, -CN, and -OH; or
R18 and R19 taken together with the atoms to which they are attached form a fused C3-7 cycloalkyl ring or a fused 4- to 10-membered heterocycloalkyl ring;
each Ra is independently selected from the group consisting of —H, (C1-C6) alkyl, (C3-C10) cycloalkyl, 4-14 membered heterocycloalkyl, and (4-14 membered heterocycloalkyl)-(C1-C4) alkylene-, wherein the (C1-C6) alkyl, (C3-C10) cycloalkyl, 4-14 membered heterocycloalkyl, and (4-14 membered heterocycloalkyl)-(C1-C4) alkylene- of Ra are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkoxy, and —C(O)O(C1-C4) alkyl
R11
-H
-H
R13
-H; halo; -OH; -CN; (C1-C6) alkyl; (C1-C6) haloalkyl; (C1-C6) alkoxy; -CONH2; -CONH(C1-C6)alkyl; -CON(C1-C6 alkyl)2; and (C3-C6) cycloalkyl; -NH2; -NH(C1-C6)alkyl; -N(C1-C6 alkyl)2
-H; halo; -OH; -CN; optionally substituted (C1-C6) alkyl; (C1-C6) alkoxy; (C1-C6) haloalkoxy; -NH2; -NH(C1-C6)alkyl; -N(C1-C6 alkyl)2; and (C3-C6) cycloalkyl
R15
-H
-H
n
1, 2, 3, or 4
1, 2, 3, or 4;
m
1, 2, 3, 4, or 5
1, 2, 3, 4, or 5
p
0
0, 1, 2, 3, or 4
Therefore, the compounds of the reference patent have close structural similarity to the instant compounds, differing only in the phenyl versus pyridinyl group. Further, as discussed in the nonstatutory double patenting rejection above, Wermuth teaches the substitution of -CH= by -N= in aromatic rings as one of the most successful applications in classical isosterism. Applicants are reminded that the rejection is based on an obviousness rationale and not anticipation. The motivation for making the -CH= by -N= change (i.e., phenyl to pyridinyl) comes from the Wermuth reference.
According to MPEP 2144 (I), “The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings)”.
Further, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Also, MPEP 2145 (X)(A), states that “However, there is no requirement that an "express, written motivation to combine must appear in prior art references before a finding of obviousness". In the instant case, the reference patent teaches closely structurally similar compounds having the same utility as the instant compounds and Wermuth provides motivation to make the phenyl to pyridinyl change (all taught in the prior art).
It is clear from the above discussion that the teachings of the reference ‘367 patent can be combined with the teachings of Wermuth to arrive at the instant compounds, with a reasonable expectation of success. Moreover, the replacement of a -CH= by -N= in aromatic rings (i.e., phenyl ring with pyridinyl ring) is a highly common and recognized bioisosteric strategy used in the field of pharmaceutical research. Therefore, the combined teachings of the reference ‘397 patent and Wermuth render the instant compounds prima facie obvious.
Regarding, Applicant’s contention that that there is no teaching, preference, or technical reasoning that would have led a skilled person to single out Compound 139 as a starting point for further modification, the examiner would like to bring Applicant’s attention to MPEP 2144.08 (d) which states that “Consider the properties and utilities of the structurally similar prior art species or subgenus. It is the properties and utilities that provide real world motivation for a person of ordinary skill to make species structurally similar to those in the prior art. Dillon, 919 F.2d at 697, 16 USPQ2d at 1905; In re Stemniski, 444 F.2d 581, 586, 170 USPQ 343, 348 (CCPA 1971).” In the instant case, the compounds of the instant invention and the compounds of the reference ‘397 patent are taught to have the same utility, i.e., regulate, and/or modulate Axl and Mer receptor tyrosine of kinase activity.
Additionally, according to MPEP 2143(I)(B), Example 9, “The Federal Circuit in Eisai makes it clear that from the perspective of the law of obviousness, any known compound might possibly serve as a lead compound …Office personnel might also base an obviousness rejection on a known compound that pharmaceutical chemists would not select as a lead compound due to expense, handling issues, or other business considerations. However, there must be some reason for starting with that particular lead compound other than the mere fact that the "lead compound" exists”.
Therefore, given the fact that the instant compounds and compounds of the reference ‘397 patent serve the same function, any of the species of the genus taught by the reference patent may be selected as a lead compound. Applicants have not demonstrated that the claimed compounds exhibit properties that are unexpectedly better than that of the reference compounds. Therefore, the examiner asserts that the choice of the lead compound to arrive at the instantly claimed compounds, as outlined above is proper. The nonstatutory double patenting rejection is maintained in the absence of evidence to the contrary.
Allowable Subject Matter
Except for the nonstatutory double patenting rejection, all claims would be allowable.
The closest prior art of record is Aftab et al. (WO 2015/164869 A1, 29 October 2015, hereinafter Aftab). Aftab teaches compounds of Formula (I) or a pharmaceutically acceptable salt thereof (Abstract; Para. [0007]) that are inhibitors of receptor tyrosine kinases (Para. [0003]; Para. [0011]).
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Aftab teaches an exemplary compound, compound 1 (Para. [0009]).
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Compound 1 of Aftab overlaps the scope of instant Formula I’, wherein
X is CH;
p is 0;
n is 0;
m is 1, R12 is halo (fluoro);
R15 is -H.
Compound 1 of Aftab differs in the A ring being substituted phenyl versus the instantly claimed
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and the phenyl versus instant pyridinyl ring (highlighted above) attached to the linking “O” group. There are at least two changes in going from the compounds of Aftab to the instantly claimed compounds, rendering the instant compounds novel and non-obvious.
Miscellaneous
While maintaining the restriction requirement, the examiner would like to bring Applicant’s attention to the following: withdrawn claim 41 is directed broadly to “a method of treating a disease, disorder, or syndrome mediated at least in part by modulating in vivo activity of a protein kinase, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof”.
The examiner notes that all biological data provided in the instant specification, indicate the handful of tested compounds as inhibitors of tyrosine kinases, such as AXL, KDR, Mer, Met kinases (Paras. [000602]-[000613] of the instant specification). Therefore, the specification does not provide adequate 112(a) support by way of enablement for the entire scope of the method claim. The specification does not enable a method of treating any and all kinds of diseases or conditions mediated by modulating (i.e., activating or inhibiting) any and all kinases implicated in a diseased condition, comprising administering the compounds of the instant invention.
It is suggested that Applicants amend the method claim to be commensurate in scope with the support in the specification, directed to a method of treating a disease, disorder or syndrome responsive to the inhibition of tyrosine protein kinases, wherein the tyrosine protein kinase is AXL, KDR, Mer, Met.
Conclusion
Claims 1, 13, 22, 27, 29 and 40 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. 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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/PADMAJA S RAO/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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