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 .
Current Status
This action is responsive to the amended claims of 08/06/2025. Please note, a supplemental response was filed on 08/06/2025 in addition to the response of 07/21/2025. The submissions of the supplemental response are under examination. Claims 11-12, 14, 17-18, and 20 are pending. Claim 20 was newly added in the response of 07/21/2025.
Claims 14 and 20 have been examined on the merits.
Election/Restrictions
Recall Applicant’s election without traverse of Group II (pending claims 11-12, 14, 17-18, and 20), compound 47, and non-alcoholic steatohepatitis in the reply filed on 02/11/2025.
Applicant has canceled all Group I claims (claims 1-7). The restriction requirement of 12/11/2024 is made moot by this cancellation.
Recall, the combination of elected species was found free of the prior art, thus, the Markush search was expanded to compound 63 and non-small cell lung cancer. The amendments to the claims overcome the pending 102 rejection; however, the compound 63 is not found free of the prior art. The Markush search for the species of disease is now expanded to Parkinson’s disease. The Markush compound search is also expanded to include a compound of Formula 10:
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which is also disclosed in the same prior art reference as compound 63.
The combination election of compound 63 and Parkinson’s disease reads on claim 20. While compound 63 shares the core structure of the Formula 10 of instant claim 14, it differs at R7.
The combination election of the above compound of Formula 10 and Parkinson’s disease reads on claim 14.
Claims 11-12 and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/11/2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date remains 12/16/2020.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the reply and amendments of 07/21/2025 and the supplemental amendment of 08/06/2025, no new matter is found.
The objection to the specification is withdrawn since Applicant has amended the title to not recite “novel” and has provided higher resolution images.
The objections to the claims are modified below in response to the amendments. The resolution issues have not been fully rectified by Applicant’s amendments.
The 112b and 112d rejections of claims 17-18 are withdrawn since Applicant has amended claim 17 to be independent.
The 102 rejection of claims 17-18 as anticipated by HUANG is withdrawn since these claims no longer recite compound 63 in the method of treating cancer. Thus, the Markush search for the species of elected disease is expanded.
Claim Objections – Necessitated by Amendments
Claims 14 and 20 are objected to because of the following informalities. Appropriate correction is required.
Claim 14 recites
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; the phenyl moiety is of poor image resolution. Please improve the resolution to improve readability.
In claim 20, please replace the semicolon at the end of line 5 with a colon.
To expedite allowance, please note, claim 11 would be objected to, if not withdrawn, concerning:
lack of a comma after “Parkinson’s disease” Pg. 1 Line 5;
lack of a colon after “steatohepatitis” Pg. 1 Line 5;
the image resolution of Formulas 2, 3, 5, and 6 is poor making the numbering on R groups difficult to read (note, Formula 4 is of great resolution);
lack of commas between structures for each Chemical Formula 2-6 and lack of an “and” before Chemical Formula 6;
the image resolution of the phenyl moiety of R1 is poor; and
there is an extra space at the end of the second line within the definition of R4 on Pg. 3:
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.
New Rejections – Necessitated by Amendments
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over HUANG (WO 2018/102366, pub. 06/07/2018, provided in IDS of 06/15/2022) in view of POTASHKIN (Potashkin, J.A., et al., PLOS ONE, 2012, 7(8), pg. 1-13).
Determining the Scope and Contents of the Prior Art:
HUANG teaches compound I-41
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(Pg. 73 Example 41 & Pg. 103 claim 60 Line 15-16). Compound I-41 is the same compound as instant compound 63
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(see instant claim 20).
HUANG teaches the compounds of the disclosure are effective HPK1 inhibitors (Pg. 2 P5), wherein HPK1 is also known as MAP4K1 (Pg. 1 P4). HUANG teaches the IC50 of compound I-41 for HPK1 is less than 5 nM (Pg. 89 P277 & Pg. 90 Table). HUANG teaches a method of treating a HPK1-mediated disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 60, i.e., including compound I-41 (Pg. 103 claim 63).
POTASHKIN teaches MAP4K1 is a splice variant biomarker for Parkinson’s disease (Pg. 2 Left Col. end of P2) and accurately distinguishes Parkinson’s from atypical Parkinsonian disorders (Pg. 3 Right Col. P1); MAP4K1 is significantly upregulated in Parkinson’s disease versus the healthy control (Pg. 6 Figure 3 & Pg. 10 Table 2). POTASHKIN also teaches Parkinson’s is characterized by cell death in the substantia nigra and several biomarkers including MAP4K1 have been implicated in cell death (Pg. 8 Left Col. P2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
HUANG does not teach wherein the HPK1-mediated disease is Parkinson’s disease.
POTASHKIN does not teach a method of treating Parkinson’s disease with an HPK1 inhibitor.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HPK1-mediated diseases and possesses the technical knowledge necessary to make adjustments to the target disease to optimize/enhance the treatment outcomes for more patient populations. Said artisan has also reviewed the problems in the art regarding the role of HPK1/MAP4K1 in Parkinson’s disease and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references HUANG and POTASHKIN.
The artisan would be motivated to substitute one disease (HPK1-mediated diseases) with another (Parkinson’s disease) since the prior art establishes both diseases are characterized by the same biomarker, i.e., HPK1 also known as MAP4K1. The artisan would be motivated to treat Parkinson’s disease (PD) with the method of HUANG, i.e., administration of compound I-41, since POTASHKIN teaches PD is characterized by MAP4K1 (Pg. 2 Left Col. P2) and HUANG teaches the compound I-41 is a potent (IC50 >5nM) inhibitor of MAP4K1 (Pg. 89 P277 & Pg. 90 Table) useful in the treatment of MAP4K1 characterized diseases (Pg. 103 claim 63). The artisan would have an expectation of success in treating the PD since POTASHKIN teaches PD is characterized by upregulated MAP4K1 (Pg. 6 Figure 3 & Pg. 10 Table 2) and cell death wherein MAP4K1 plays a role in cell death (Pg. 8 Left Col. P2). Thus, by administering a potent inhibitor of MAP4K1 (compound I-41), the artisan would expect to inhibit the upregulated MAP4K1 and treat the PD.
Thus, claim 20 is made obvious by the combined references.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over HUANG (WO 2018/102366, pub. 06/07/2018, provided in IDS of 06/15/2022) in view of POTASHKIN (Potashkin, J.A., et al., PLOS ONE, 2012, 7(8), pg. 1-13).
Determining the Scope and Contents of the Prior Art:
HUANG teaches compound I-5
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(Pg. 60 Example 5 & Pg. 100 claim 60 last two lines). Compound I-5 reads on instant claim 14 wherein R1 is
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, X is Cl, R2 is H, R6 is C1 alkyl, n is 1, m is 1, and R7 is halogen (F).
HUANG teaches the compounds of the disclosure are effective HPK1 inhibitors (Pg. 2 P5), wherein HPK1 is also known as MAP4K1 (Pg. 1 P4). HUANG teaches the IC50 of compound I-5 for HPK1 is less than 5 nM (Pg. 89 P277 & Pg. 90 Table). HUANG teaches a method of treating a HPK1-mediated disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 60, i.e., including compound I-5 (Pg. 103 claim 63).
POTASHKIN teaches MAP4K1 is a splice variant biomarker for Parkinson’s disease (Pg. 2 Left Col. end of P2) and accurately distinguishes Parkinson’s from atypical Parkinsonian disorders (Pg. 3 Right Col. P1); MAP4K1 is significantly upregulated in Parkinson’s disease versus the healthy control (Pg. 6 Figure 3 & Pg. 10 Table 2). POTASHKIN also teaches Parkinson’s is characterized by cell death in the substantia nigra and several biomarkers including MAP4K1 have been implicated in cell death (Pg. 8 Left Col. P2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
HUANG does not teach wherein the HPK1-mediated disease is Parkinson’s disease.
POTASHKIN does not teach a method of treating Parkinson’s disease with an HPK1 inhibitor.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of HPK1-mediated diseases and possesses the technical knowledge necessary to make adjustments to the target disease to optimize/enhance the treatment outcomes for more patient populations. Said artisan has also reviewed the problems in the art regarding the role of HPK1/MAP4K1 in Parkinson’s disease and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references HUANG and POTASHKIN.
The artisan would be motivated to substitute one disease (HPK1-mediated diseases) with another (Parkinson’s disease) since the prior art establishes both diseases are characterized by the same biomarker, i.e., HPK1 also known as MAP4K1. The artisan would be motivated to treat Parkinson’s disease (PD) with the method of HUANG, i.e., administration of compound I-5, since POTASHKIN teaches PD is characterized by MAP4K1 (Pg. 2 Left Col. P2) and HUANG teaches the compound I-5 is a potent (IC50 >5nM) inhibitor of MAP4K1 (Pg. 89 P277 & Pg. 90 Table) useful in the treatment of MAP4K1 characterized diseases (Pg. 103 claim 63). The artisan would have an expectation of success in treating the PD since POTASHKIN teaches PD is characterized by upregulated MAP4K1 (Pg. 6 Figure 3 & Pg. 10 Table 2) and cell death wherein MAP4K1 plays a role in cell death (Pg. 8 Left Col. P2). Thus, by administering a potent inhibitor of MAP4K1 (compound I-5), the artisan would expect to inhibit the upregulated MAP4K1 and treat the PD.
Thus, claim 14 is made obvious by the combined references.
To expedite time to allowance, Applicant is encouraged to provide unexpected results commensurate in scope with the claims. See MPEP 716.02. Unexpected results commensurate in scope with the claims would prohibit the Examiner from making further 103 rejections similar to those above.
Conclusion
Claims 14 and 20 are rejected.
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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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625