DETAILED OFFICE 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 .
Priority
The present application U.S. Appln. Ser. No.: 18/019,400, Filed: February 2, 2023 is a 371 Nat.’l Stage Entry of WO 2022/031330A1 Appln. (i.e., PCT/US21/30192, Intern.’l Filing Date: April 30, 2021, Intern.’l Pub. Date: February 10, 2022), which claims priority from U.S. Prov. Appln. No. 63/115,312, Filed: November 18, 2020 and from U.S. Prov. Appln. No. 63/060,413, Filed: August 3, 2020.
Status
This is in response to the October 23, 2025 Amendment and Response to Non-Final Office Action and corresponding documents.
Claims 1, 29, 30, 34, 46, 104,186, 195, 257, 259, 263 and 267-278 are pending;
Claims 1, 29, 30, 34, 46, 104,186, 195, 257, 259 and 263 are currently amended;
Claims 267-268 are previously presented;
Claims 269-278 are new; and
Claims 2-28, 31-33, 35-45, 47-103, 105-185, 187-194, 196-256, 258, 260-262 and 264-266 are cancelled
in the above identified application.
Information Disclosure Statement
An Information Disclosure Statements (IDS) submitted on October 23, 2025 (1) is filed in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
RESPONSE TO OBJECTIONS AND REJECTIONS
Objections to the Drawings
Objections to drawings for failure to be in compliance with 37 CFR 1.121(d) for unreadable figures (i.e., blurry/faint grey images, drawing, graphs with illegible and unreadable descriptive text, legends and/or x-y axis coordinates on graphs) is WITHDRAWN as per newly submitted Replacement Sheets 1-10 (i.e., directed to Figures 1, 2, 3, 4, 5A, 5B, 5C, 6, 7, 8, 9A, 9B, 10A, 10B, 10C, and 11).
Rejection under 35 USC § 101
Cancellation of claim 249 has obviated the rejection under 35 USC § 101, which is WITHDRAWN (for claiming “an integer number” or “a number”, which unpatentable non-statutory matter without substantial credible utility for an indeterminate “number of the unit dosage forms” that “supplies the entire dose of claim 1” for treatment of an unidentified disease or disorder state)
Claim Rejections - 35 USC § 112
Rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para. for being indefinite and failure to particularly point out and distinctly claim the subject matter are now WITHDRAWN due to claim amendments, cancellations and/or persuasive arguments have overcome rejections of claims 1, 104, 186, 195, 257, 259 and 263 (i.e., claims 198,199, 201, 249 cancelled; claims 1, 104, 186 ,195, 259 and 263 amended; claim 257 by argument)
Claim Rejections - 35 USC § 112(a)
Rejection of claims 1, 29, 30, 34, 46, 104,186, 195, 257, 259, 263 and 267-268 (i.e., claims 67-71, 198-199, 249 are cancelled) under 35 U.S.C. 112(a) are now WITHDRAWN.
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MAINTAINED REJECTIONS WITH CLARIFICATIONS OR MODIFICATIONS
Non-Statutory Double Patenting
The following Non-Statutory or Provisional Non-Statutory Obviousness-Type Double Patenting rejection are MAINTAINED for reasons of record (i.e., with relevant excerpts) with clarification reasons for why dosing range of 50 mg to 500 mg recited in claim amendments are rendered obvious in light of :
[I] Non-Statutory Obviousness-Type Double Patenting
[A] Claims 1, 29-30, 34, 46 67-71 and 104 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-7,15-17, 23, 25,-29 of U.S. Pat. No. 12,178,821 B2, Issued: December 31, 2024 (i.e., corresp. to U.S Appln. Ser. No. 17/680,995, Filed: February 25, 2022 (“U.S. ‘162 Pat.”)) in view of:
July 18, 2019 Clinical Trial Investigating An IRAK4 Kinase Inhibitor For CA-4948 In Non-Hodgkin Lymphoma (NHL)
CA-4948 (Oral IRAK4 Inhibitor) in Hematologic Malignancies
CA-4948 in Non-Hodgkin Lymphoma (NHL)
KT-474 (IRAK4 Degrader) In Healthyl Volunteers and Autoimmune Disease
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-13 of U.S. ‘821 Pat. are directed to:
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which embraces the instant claimed invention (i.e., which is directed to methods of treatment, which comprises administering a Compound 1 as identified above in Present Invention Summary) Note that the instant U.S. ‘821 Pat. recite administration doses between 100-1000 mg (QD, BID etc.; i.e., see cols. 27, lines 17-67 to col, 28, lines 1-33).
However, the following 4 clinical trial references are pertinent to understanding how the ordinary artisan would as a matter of routine dosing optimization be able to arrive at effective dosing ranges (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally), which are relevant to all double patenting rejections [A] to [D] characterized as [I] Non-Statutory Obviousness-Type Double Patenting and [II] Provisional Non-Statutory Obviousness-Type Double Patenting.
1 In fact, a July 18, 2019 clinical trial investigating an IRAK4 kinase inhibitor for CA-4948 in Non-Hodgkin Lymphoma (NHL) is the earliest reference to demonstrate a dose range of 50-5000 mg for administration of IRAK4 inhibitors to humans for cancer treatment (i.e., which is before earliest priority date of the present invention); i.e., where
the trial assesses safety/efficacy data, pharmacokinetics, pharmacodynamics, and clinical activity of CA 4948, focusing its effectiveness in combination with other treatments like ibrutinib;
Moreover, it is conventionally known in the art as provided by representative clinical trial references defined infra, which collectively establish the human tested dose window for IRAK4 targeting agents with first reference cited below CA-4948 in NHL being the earliest reference demonstrating 50 mg up to 500 mg dosing range in humans, (i.e., clearly dependent compound, schedule, and patient cohort considerations (patient body weight, toxicity limitations, etc. were taken into consideration)
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(i.e., see attached 3 teaching references and Clinical Trial CA-4948 in NHL above herewith)
Also, the literature further suggests that it is within the skill of the ordinary artisan to adapt common dosing optimization strategies.
For example, the WO ‘077 Appln. is a reference that:
discloses treatment of cancer and disorders with IRAK-4 inhibitors which are substituted pyrazolopyrimidines; i.e., e.g.,
based on mouse model data and shows effectiveness of different, including lower doses defined by:
25, 50, and 150 mg/kg p.o. b.i.d. in a collagen antibody-induced arthritis model;
50 and 150 mg/kg p.o. for tumor reduction in TMD8 cancer xenograft models; (which are a type of B-cell lymphoma, a hematological disorder); and .
teaches a preclinical dosing regimens demonstrating efficacy at lower doses of 150 mg/kg or lower (i.e., as low as 25–150 mg/kg) validating that reducing a dose from 560 mg is obvious to one skilled in the art.
[B] Claims 1, 29-30, 34, 46, 67-71 and 186 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-7 of U.S. Pat. No. 10,758,518 B2, Issued: November 8, 2022 (i.e., corresp. to U.S Appln. Ser. No. 15/733,732, Filed: April 9, 2019 (“U.S. ‘518 Pat.”)).in view of:
July 18, 2019 Clinical Trial Investigating An IRAK4 Kinase Inhibitor For CA-4948 In Non-Hodgkin Lymphoma (NHL)
CA-4948 (Oral IRAK4 Inhibitor) in Hematologic Malignancies
CA-4948 in Non-Hodgkin Lymphoma (NHL)
KT-474 (IRAK4 Degrader) In Healthyl Volunteers and Autoimmune Disease
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-5 of U.S.‘518 Pat. are directed to:
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which embraces the instant claimed invention (i.e., which is directed to methods of treatment, which comprises administering a Compound 1 as identified above under Present Invention Summary. Note the instant U.S. ‘518 Pat. recite administration doses between 100-1000 mg (i.e., col. 35, lines 29-39) with potential unit doses administered 1 or more times daily (i.e., see col. 41, lines 44-51).
However, see discussion above under [A[ regarding the 4 clinical trial references are pertinent to understanding how the ordinary artisan would as a matter of routine dosing optimization be able to arrive at effective dosing ranges (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally), which are relevant to all double patenting rejections [A] to [D] characterized as [I] Non-Statutory Obviousness-Type Double Patenting and [II] Provisional Non-Statutory Obviousness-Type Double Patenting.
[II] Provisional Non-Statutory Obviousness-Type Double Patenting
[C] Claims 1, 29-30, 34, 46, 67-71 and 186 are rejected on the ground of provisional non-statutory obviousness-type double patenting as being unpatentable over claim 1, 7, 12, 16-25 (i.e., heterocyclyl defn. therein, inc. heteroaryl) , 30-85, 87, 112-156, 161-186, 187, 193, 231-237, 243-244 of U.S. Pat. Appln. No.: 18/037,697, Filed: May 18, 2023 (i.e., corresp. to U.S Appln. Pub. No. US 2023/0414582A1, Pub. Date: December 28, 2023 (“U.S. ‘582 Appln.”).in view of
July 18, 2019 Clinical Trial Investigating An IRAK4 Kinase Inhibitor For CA-4948 In Non-Hodgkin Lymphoma (NHL)
CA-4948 (Oral IRAK4 Inhibitor) in Hematologic Malignancies
CA-4948 in Non-Hodgkin Lymphoma (NHL)
KT-474 (IRAK4 Degrader) In Healthyl Volunteers and Autoimmune Disease
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1, 7,12,16-25, 30-85, 87, 112-156, 161-186, 187, 193, 231-237, 243-244 of U.S. ‘582 Appln. are directed to:
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,
corresponding compounds associated with genus of Formula (I), which encompasses:
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associated dosing quantities 25-500 mg (QD, BID etc.), specific diseases or disorders, 2nd drug administrations or therapies, mutations, associated signaling or response characteristics, etc.
which embraces the instant claimed invention (i.e., which is directed to methods of treatment, which comprises administering a Compound 1 and corresponding directed to listed claims) as identified above under Present Invention Summary.
However, see discussion above under [A[ regarding the 4 clinical trial references are pertinent to understanding how the ordinary artisan would as a matter of routine dosing optimization be able to arrive at effective dosing ranges (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally), which are relevant to all double patenting rejections [A] to [D] characterized as [I] Non-Statutory Obviousness-Type Double Patenting and [II] Provisional Non-Statutory Obviousness-Type Double Patenting.
[D] Claims 1, 29-30, 34, 46, 67-71 and 186 are rejected on the ground of provisional non-statutory obviousness-type double patenting as being unpatentable over claims 1-5 of U.S. Pat. Appln. No.: 18/953,879, Filed: November 20, 2024 (i.e., corresp. to U.S Appln. Pub. No. US 2025/0082644 A1, Pub. Date: March 13, 2025 (“U.S. ‘879 Appln.”) in view of:
July 18, 2019 Clinical Trial Investigating An IRAK4 Kinase Inhibitor For CA-4948 In Non-Hodgkin Lymphoma (NHL)
CA-4948 (Oral IRAK4 Inhibitor) in Hematologic Malignancies
CA-4948 in Non-Hodgkin Lymphoma (NHL)
KT-474 (IRAK4 Degrader) In Healthyl Volunteers and Autoimmune Disease
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 209-211 and 216-223 of U.S. ‘879 Appln. are directed to:
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which embraces the instant claimed invention (i.e., which is directed to methods of treatment, which comprises administering a Compound 1 as identified above under Note that paras [0153]-[0155] of the instant U.S. ‘879 Appln. (i.e., US ‘644 Pub.) recite administration doses between 100-1000 mg, QD or BID.
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However, see discussion above under [A[ regarding the 4 clinical trial references are pertinent to understanding how the ordinary artisan would as a matter of routine dosing optimization be able to arrive at effective dosing ranges (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally), which are relevant to all double patenting rejections [A] to [D] characterized as [I] Non-Statutory Obviousness-Type Double Patenting and [II] Provisional Non-Statutory Obviousness-Type Double Patenting.
With respect to:
[A] to [B] directed to [I] Non-Statutory Obviousness-Type Double Patenting; and
[C] to [D] directed tp [II] Provisional Non-Statutory Obviousness-Type Double Patenting
Pharmacological studies often show that effective doses are lower than the maximum tolerated dose, making optimization to a lower, still effective range (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally)
Based on the above, one of ordinary skill in the art would have had a reasonable expectation of success in developing claimed invention cancer treatment methods via incorporating teachings of each of the patents [A] to [D] discussed aouve . directed to cancer treatment methods (inc. hematological disorders and solid malignant tumors), comprised of administration of IRAK 4 inhibitor substituted indazole compounds or pharmaceutically acceptable salts or pharmaceutical compositions thereof (i.e., reads on claims of the present invention) with adaptation of the CA-4893 Clinical Trial Cancer Treatment Study, where an optimum 50–500 mg dosing range of IRAK inhibitors in humans with application of common art dosing optimization strategies.
One of ordinary skill in the art would have been motivated to deduce dosing modification, because there remains an unmet need for additional therapies for treatment of cancers and other diseases associated with IRAK4
Based on the foregoing, claimed invention is rendered obvious over the cited patents [A] to [B] and patent applications [C] and [D]. alone, in view of or in combination with the teachings of all the cited references.
NEW REJECTIONS
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.
Claims 1, 29-30, 34. 46, 67-71, 186 and 198 are rejected under 35 U.S.C. 103 as being unpatentable over:
WO 2019/089580 A1 to Curis, Inc. (Intern.’l Filing Date: October 20, 2018, Intern.’l Pub. Date: May 9, 2019; “WO ‘580 Appln.”),
alone, in view of or in combination with:
WO 2021/064077 Appln. to Bayer (Intern.’l Filing Date: October 1, 2020, Earliest Priority Date: October 1, 2019; “WO ‘077 Appln.”),
CA-4948 in NHL (July 19, 2019) Clinical Trial Investigating The Safety And Efficacy of Emavusertib, An IRAK4 Kinase Inhibitor, In Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL).
Austin Health et al. IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial. Nature Medicine 2023;29:3127–3136 (3) .
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BenchChem. [Application Notes and Protocols for In Vivo Dosing and Administration of IRAK-1/4 Inhibitors in Mouse Models]. BenchChem, [2026]. [Online PDF]. Available at: [https://www.benchchem.com/product/b1672172#in-vivo-dosing-and administration-of-irak-1-4-inhibitors-in-mouse-models]
In general, the present invention relates to methods of treating diseases and disorders (i.e., inc. IRAK4 associated ones), which comprises administering a compound identified as Compound 1:
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; or
a pharmaceutically acceptable salts or corresponding pharmaceutical compositions thereof.
The WO ‘580 Appln. discloses and teaches:
[a] methods for treating cancers (inc. hematological disorders and solid malignant tumors), administering compounds therein as IRAK 4 inhibitors (i.e. substituted indazole compounds or pharmaceutically acceptable salts or pharmaceutical compositions thereof) (i.e., encompasses and reads on claims of the present invention) ;
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[b] compounds administered in the WO ‘580 Appln. inc. those of Formula (II) or pharmaceutically acceptable salt thereof therein:
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; and
specifically teaches Compound A (i.e., CA-4948) therein, which is identical to compound 1 of the present invention
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[c] WO ‘580 Appln teaches:
a broad dose ranges of 1-1000 mg therein, which encompasses dose ranges of 50-500 mg as taught by the claimed invention (i.e., reads on claims 34 and 46);
where there is NO evidence of unexpected or surprising properties or any criticality associated with the narrower sub-range (i.e., improved efficacy or reduced toxicity at the claimed sub-range)
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While broad dosing information is in the WO ‘580 Appln., Applicants assert that it does not specifically teach the dose range of 50-5000 mg for the administration of IRAK4 inhibitors to humans for cancer treatment as in the instant invention and claims.
In fact, a July 18, 2019 clinical trial investigating an IRAK4 kinase inhibitor for CA-4948 in Non-Hodgkin Lymphoma (NHL) is the earliest reference to demonstrate a dose range of 50-5000 mg for administration of IRAK4 inhibitors to humans for cancer treatment (i.e., which is before earliest priority date of the present invention); i.e., where
the trial assesses safety/efficacy data, pharmacokinetics, pharmacodynamics, and clinical activity of CA 4948, focusing its effectiveness in combination with other treatments like ibrutinib;
Moreover, it is conventionally known in the art as provided by representative references collectively establish the human tested dose window for IRAK4 targeting agents with first reference cited below CA-4948 in NHL being the earliest reference demonstrating 50 mg up to 500 mg dosing range in humans, (i.e., clearly dependent compound, schedule, and patient cohort considerations (patient body weight, toxicity limitations, etc. were taken into consideration)
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(i.e., see attached 3 teaching references and Clinical Trial CA-4948 in NHL above herewith)
Also, the literature further suggests that it is within the skill of the ordinary artisan to adapt common dosing optimization strategies.
For example, the WO ‘077 Appln. is a reference that:
discloses treatment of cancer and disorders with IRAK-4 inhibitors which are substituted pyrazolopyrimidines; i.e., e.g.,
based on mouse model data and shows effectiveness of different, including lower doses defined by:
25, 50, and 150 mg/kg p.o. b.i.d. in a collagen antibody-induced arthritis model;
50 and 150 mg/kg p.o. for tumor reduction in TMD8 cancer xenograft models; (which are a type of B-cell lymphoma, a hematological disorder); and .
teaches a preclinical dosing regimens demonstrating efficacy at lower doses of 150 mg/kg or lower (i.e., as low as 25–150 mg/kg) validating that reducing a dose from 560 mg is obvious to one skilled in the art.
Pharmacological studies often show that effective doses are lower than the maximum tolerated dose, making optimization to a lower, still effective range (like 50–500 mg) as a matter of routine optimization (i.e., see teaching Benchmark reference generally)
Based on the above, one of ordinary skill in the art would have had a reasonable expectation of success in developing claimed invention cancer treatment methods via incorporating teachings of the WO ‘580 Appln. directed to cancer treatment methods (inc. hematological disorders and solid malignant tumors), comprised of administration of IRAK 4 inhibitor substituted indazole compounds or pharmaceutically acceptable salts or pharmaceutical compositions thereof (i.e., reads on claims of the present invention) with adaptation of the CA-4893 Clinical Trial Cancer Treatment Study, where an optimum 50–500 mg dosing range of IRAK inhibitors in humans with application of common art dosing optimization strategies.
One of ordinary skill in the art would have been motivated to deduce dosing modification, because there remains an unmet need for additional therapies for treatment of cancers and other diseases associated with IRAK4
Based on the foregoing, claimed invention is rendered obvious over the WO ‘580 Appln. alone, in view of or in combination with the teachings of all the cited references.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689. The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, KORTNEY L. KLINKEL can be reached on 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.C.H./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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