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 .
Election/Restrictions
Claims 19, 41-42, 45, 48, 58, 103, 121, 130, 136, and 138 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species and group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 17 March 2026.
Claims 1, 2, 5, 41, 45, 48, 58, 98, 103, 121, 130, 132, 136, 138, and 141 have undergone amendments. Claims 19, 41-42, 45, 48, 58, 103, 121, 130, 136, and 138 remain withdrawn from consideration. Thus, Claims 1, 2, 5, 26-27, 98, 106, 132, and 141, submitted on 12 August 2026, represent all claims currently under consideration.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 12 August 2026, is acknowledged and has been considered.
Response to Arguments
The objection to Claim 1 is withdrawn. Applicant has amended the claim to recite a “3- to 6-membered saturated or unsaturated ring”.
The objection to Claim 5 is withdrawn. Applicant has amended Claim 5 to remove the comma.
The 35 U.S.C. § 112(a) rejection of Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 is withdrawn. Applicant has amended Claims 1, 132, 136, and 138 to remove “prodrug”.
The 35 U.S.C. § 112(b) rejection of Claims 1, 2, 5, 26, 27, 98, 106, and 141 is withdrawn. Applicant has amended the claim to recite “all available hydrogen atoms are optionally replaced with a fluorine atom”, obviating the indefiniteness.
The 35 U.S.C. § 112(b) rejection of Claims 1, 2, 5, 26, 27, 98, 106 and 141 is withdrawn. Applicant argues that the “and/or” clauses are not indefinite and does not cause a lack of clarity. After reading the claims in view of these arguments, the Examiner agrees and the rejection is withdrawn.
The 35 U.S.C. § 112(b) rejections of Claim 132 are each withdrawn. Applicant has amended the Claim to include the compounds which are cited in the table, and to remove compounds I-424 and I-465, which lack antecedent basis.
The 35 U.S.C. § 112(b) rejection of Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 is withdrawn. Applicant has amended the claim to remove the limitation of “and/or prodrug”.
The 35 U.S.C. § 112(d) rejections of Claim 132 is withdrawn. Applicant has amended Claim 132 to remove Compounds I424 and I465 which were more broad than claim 1.
The 35 U.S.C. § 103 rejection of Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 over Augeri in view of Meanwell is withdrawn. Applicant argues that the presently claimed compounds have been found to demonstrate significantly less inhibition of lymphocyte-specific protein tyrosine kinase (Lck). Applicant provides Table 2 to demonstrate the significantly greater specificity over HPK1 over Lck, and inhibition of this enzyme can result in broad immunosuppression. Applicant further investigated the selectivity for HPL1 over Lck of the presently claimed compounds compared to identical compounds which do not comprise fluorine at a position ortho to the N of the pyridine ring. Table 4 demonstrates that the insertion of this fluorine results in massive improvements in selectivity over HPK1 versus Lck. The Examiner finds these arguments to be persuasive.
The 35 U.S.C. § 103 rejection of Claims 1-2, 5, 26, 27, 98, 106, 132, and 141 over Gray in view of Meanwell is withdrawn for the reasons cited above.
The provisional non-statutory double patenting rejections of Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 over co-pending Application No. 18/288,222 in view of Thornber and over co-pending Application No. 18/288,219 in view of Thornber and Meanwell are each maintained. While they are the only rejections which remain, these co-pending applications share the same effective filing date as the examined application (30 April 2021).
Double Patenting- REJECTIONS MAINTAINED
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 25, 27, 132 and 141 of copending Application No. 18/288,222 (Amended Claims of 14 May 2024) (‘222) in view of Thornber (Chemical Society Reviews, Issue 4, 1979).
Determining the Scope and Contents of the Prior Art:
Claim 1 of ‘222 is directed to a compound of Formula (I) which has identical limitations to the compounds of the examined application, save for requiring that one of variable X4 or X5 is N with the other being CR3. Claim 25 is directed to the compound of Claim 1 wherein X4 is N and X5 is CR3. Claim 27 is directed to the compound of claim 1 wherein Cy1 is phenyl and is unsubstituted or is substituted with one or more R9, or is substituted with Z-Cy2 or is substituted with Z-Cy2 and one or more of R11. Claim 132 is directed to a compound of Claim 1 found in Table 1, such as I-1 . This table contains dozens of compounds which only differ from those claimed in the examined application by the central ring being pyrazine rather than pyridine. Claim 141 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable excipient.
Thornber teaches the concept of bioisosterism, which is the concept wherein groups or molecules which have chemical and physical similarities produce broadly similar biological properties (Page 563). Table 1 (Page 564) lists the classical isosteres, and includes ring equivalents. Such ring equivalents include -CH=CH-, =CH-, =N-, and S. These atoms have similar electronic properties and as such, their replacement within a ring system is not expected to significantly alter the properties of that ring.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
‘222 does not teach that the central ring is pyridine, while Thornber does not teach compounds similar to those of the examined application.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The artisan would have extensive training in medicinal or pharmaceutical chemistry with experience in structure-activity relationship in designing compounds and testing how modifications such as replacement of C for N alter the biological properties of a compound.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
‘222 and Thornber are considered analogous to the claimed invention as all are involved in drug development and design. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘222 by replacing the central pyrazine ring with pyridine as Thornber teaches that =N- and =CH- function as ring equivalents, and thus the artisan would not expect the properties of these compounds to be significantly altered by performing this substitution as due to the close chemical structure (See MPEP § 2144.09 I). The artisan would expect these compounds to have similar properties, and would not expect there to be significant differences in activity by performing this substitution.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 5, 26, 27, 98, 106, 132, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 72, 129, and 130 of copending Application No. 18/288,219 (Amended Claims of 14 May 2024) (‘219) in view of Thornber (Chemical Society Reviews, Issue 4, 1979). and Meanwell (Journal of Medicinal Chemistry, 2018, 61, 5822-5880).
Determining the Scope and Contents of the Prior Art:
Claim 1 of ‘219 is directed towards a compound of Formula (I)
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246
291
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which has identical limitations to the compounds of the examined application, save for requiring that at least one of X4 and X5 is N. Claim 72 of ‘219 is directed towards a compound of Formula (II)
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271
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which has identical limitations to the compounds of the examined application, save for requiring that at least one of X9 and X10 is N. Claim 129 of ‘219 is directed towards a compound of Claim 72 selected from Table 1-A, such as II-1
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131
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. Claim 130 of ‘219 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier or diluent.
Meanwell teaches the use of fluorine and fluorinated motifs in drug development and their use as bioisosteres. The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. Fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule (Abstract). The use of bioisosteres is a common principle in drug design. Introduction of fluorine can increase the overall lipophilicity of a molecule (Page 5823). The replacement of hydrogen with fluorine can lead to resistance towards oxidative metabolism, and fluorination has developed into a popular approach to address the poor pharmacokinetic performance of drug-like compounds in vitro and in vivo (Page 5824). The judicious replacement of a hydrogen atom in aromatic and heteroaromatic rings by a fluorine atom can exert a significant impact on the properties of a molecule that are beneficial to both drug design and development. An early focus of the introduction of fluorine to aromatic rings was as a tactic to slow metabolism. Fluorine is also introduced in order to improve the membrane permeability of compounds, improving bioavailability. Introduction of fluorine ortho- to an NH influences conformation, which resulted in both improved binding to the protein target, as well as improved pharmacokinetics and solubility (Replacing Hydrogen by Fluorine in Aromatic Rings).
The teachings of Thornber is previously described and are fully incorporated into this rejection.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
‘219 does not teach that the central ring is pyridine, or the fluorination of the pyridine ring, while Meanwell and Thornber do not disclose compounds of the examined application.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The artisan would have extensive training in medicinal or pharmaceutical chemistry with experience in structure-activity relationship in designing compounds and testing how modifications such as replacement of C for N, or insertion of fluorine atoms alter the biological properties of a compound.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
‘219 does not teach that the central ring is pyridine, or the fluorination of the pyridine ring.
‘219, Thornber, and Meanwell are considered analogous to the claimed invention as all are involved in drug design and development. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘219 in view of the teachings of Thornber and Meanwell by replacing the central pyrazine ring with a pyridine ring which is fluorinated. Thornber teaches that =N- and =CH- function as ring equivalents, while Meanwell teaches that fluorination is commonly employed to enhance pharmacokinetic and pharmacodynamics. Fluorination as taught by Meanwell is prima facie obvious application of a known technique to a known product ready for improvement to yield predictable results (See MPEP § 2143 I (D)); the compounds of ‘219 are shown to be effective both in vitro and in vivo, and fluorination is a known method to improve pharmacokinetic and pharmacodynamic properties. Moreover, the artisan would not expect the properties of these compounds to be significantly altered by performing these modifications due to the close chemical structure (See MPEP § 2144.09 I). The artisan would expect these compounds to have similar properties, and would not expect there to be significant differences in activity by performing these changes.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1, 2, 5, 26-27, 98, 106, 132, and 141 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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