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 .
DETAILED ACTION
Claims 1-2, 4-18 and 20-29 are pending and are consideration in the instant office action.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 4/13/2026 are acknowledged. Claims 1 and 8 are amended , claim 3 is cancelled and new claims 21-29 are added. Claims under consideration in the instant office action are claims 1-2, 4-18 and 20-29..
Applicants' arguments, filed 4/113/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
In the interest of compact prosecution, Applicants were contacted on 5/26/2026 with a proposal of an examiner’s amendment to move this application forward. They requested that the examiner send out an action. See the attached interview summary for details.
Claim Rejections - 35 USC § 103
New grounds of rejection necessitated by the amendment and arguments filed on 4/13/2026
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-2, 4-18 and 20-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Mainolfi et al (WO 2020/113233, priority date 11/30/2018, referenced in IDS) as evidenced by Brunner et al (Scientific reports, 7:8707, 2017, pages 1-12 in view of Thijs et al. (J. Clin. Med 2015, 4, pages 479-487), (references already of record)
Instant claims are drawn to a method of treating hidradenitis suppurativa patient and/or atopic dermatitis in a patient having an elevated level of an inflammatory biomarker, comprising administering to the patient a therapeutically effective amount of an IRAK4 degrader, further comprising measuring an inflammatory biomarker level in a sample of a patient (Claim 1) . method of treating hidradenitis suppurativa patient and/or atopic dermatitis in a patient having a reduced level of an inflammatory biomarker after a treatment with an IRAK4 degrader, comprising administering to the patient a therapeutically effective amount of an IRAK4 degrader (Claim 4) and method of treating hidradenitis suppurativa patient and/or atopic dermatitis in a patient, comprising administering to a patient a therapeutically effective amount of an IRAK4 degrader, measuring an inflammatory biomarker level in a sample of a patient after a treatment with an IRAK4 degrader, selecting a patient having a reduced level of an inflammatory biomarker after a treatment with an IRAK4 degrader, and administering to the patient a therapeutically effective amount of an IRAK4 .degrader (Claim 7), The claims are drawn to the elected compounds the following IRAK degrader.
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Mainolfi et al. discloses the instantly claimed compounds as IRAK4 degrader 2 shown below ( See compound I-561 (page 539, table 1) and its synthesis (example 48)
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They disclose that these compounds are effective as degraders of IRAK kinases [00715] and are useful in the treatment of atopic dermatitis [00723]. They disclose administration to the patient through oral, topical, ophthalmic method [00698].
It is noted that Mainolfi et al. does not disclose that the patient has elevated level of an inflammatory biomarker. However, these conditions are highly inflammatory in nature and is inherently characterized by elevated levels of inflammatory biomarkers. This is evidenced by Brunner et al. who discloses that Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, associated with allergic manifestations (e.g. asthma, food allergies, seasonal allergies and other inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease8, and systemic lupus erythematosus (page 1, 1stpara). They further disclose that blood of severe AD patients showed significantly increased T-cell activation and increases in serum cytokines that correlated with clinical severity. These markers are largely associated with Th1 (IFN-γ, CXCL9, TNF-β, lymphotoxin-α), but also Th17 (CCL20) (page 6. Para 2) . They disclose large set of markers exclusively upregulated in AD included Th1 (CXCL10, CXCL11), Th2 (IL-13, CCL13, CCL17, CCL11, IL-10), Th17/Th22 (S100A12) and Th1/Th17/Th22 (IL-12/IL-23p40) associated products in serum of AD patients (page 6, para 2). They further disclose that AD, , was characterized by significant upregulation of several additional Th1 (CXCL10, CXCL11), Th2 (IL-13, CCL13, CCL17, CCL11, IL-10), Th17/Th22 (S100A12) and Th1/Th17/Th22 (IL-12/ IL-23p40) associated products, as well as a broad array of proteins involved in the development and activation of
T-cells (CD40L, IL-7, CCL25, IL2RB, IL15RA, CD6, RANKL, TNFRSF9/CD137) and dendritic cells/DC (CD40, FLT3 ligand) (Fig. 1d). Mediators involved in atherosclerosis (CX3CL1/fractalkine, CCL8, M-CSF, CXCL5, CCL4, HGF), tissue remodeling (MMP-12, MMP-1, MMP-10) and angiogenesis (VEGF-A) were also increased in AD. The growth factor TGF-α, the NF-κB-activator IKBKG/NEMO, molecules mediating chemotaxis of
T-cells/B-cells/eosinophils (CCL28) and neutrophils (CXCL5, CXCL6), as well as the soluble cytokine receptors IL-10RB and IL-18R1 were also higher in AD (page 2, Para 4). As such evidentiary documentation explicitly discloses that atopic dermatitis as a highly inflammatory disorder characterized by the increase in several different biomarkers. As such the atopic dermatitis patients being treated by the IRAK4 degraders in Mainolfi et al. would therefor inherently have increased levels of several inflammatory markers. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is also noted that, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430,433 (CCPA 1977).
In accordance with MPEP §2131.01, it is proper to rely upon a secondary reference for a rejection under 35 U.S.C. 102, provided that the additional reference is relied upon to demonstrate that a characteristic or property not disclosed by the primary reference is, in fact, inherent.
Mainolfi et al. does not disclose measuring inflammatory biomarkers in samples of patients with hidradenitis suppurativa patient and/or atopic dermatitis treated with their inventive IRAK 4 degraders, and further selecting a patient having reduced level of an inflammatory biomarker and further administering another dosage of the IRAK4 degrader to the same patient.
However, Thijs et al. discloses that frequently reported serum biomarkers for disease severity in AD include eosinophilic cationic protein (ECP) [11], IL-2R [12], and thymus and activation-regulated chemokine (TARC/CCL17) (page 481. Section 2.2). They teach that while blood is the commonly used fluid for biomarker measurements, dried blood spots and saliva are potential alternatives (page 482, section 3). They conclude that the application of biomarkers in AD offers great opportunities, both in daily clinical practice as well as for research purposes and offer reliable and objective outcome measures. They further teach that the heterogeneous character of the disease and lack of clinical stratifies makes AD highly suitable for a biomarker based stratification. A panel of biomarkers can assess multiple molecular entities, and will be more suitable for assessing disease severity in AD compared to an individual biomarker. Biomarker stratification will identify subgroups of patients that will respond to treatment and enable tailoring of drugs to the biological signature of individual patients, accelerating the translation of new medicine from bench to bedside and can revolutionize AD therapy. They conclude that the use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patient’s specific biological signature and also by providing tools for predicting and monitoring of therapeutic response( page 484 , section 4).
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Weiss and Thijs et al. to arrive at the instant claims. Treatment of Atopic dermatitis with IRAK4 inhibitors is already well known in the art as taught by Mainolfi et al, Use of biomarkers in atopic dermatitis for objective determination of the disease , severity , confirmation of clinical diagnosis and to predict response to treatment was also very well known in the art at the time of this application as taught by Thijs et al. As such an ordinarily skilled artisan would be motivated from to utilize the biomarker analysis to determine the efficacy of any type of treatment of atopic dermatitis which includes treatment with IRAK4 inhibitors taught by Mainolfi et al, absence of evidence to the contrary. It would be obvious to an ordinarily skilled artisan to determine the biomarker levels after treatment to access the efficacy of the drugs and if the elevated markers are reduced, indicating the efficacy of the treatment, it would be obvious to further treat the patient with the same agent which has just shown efficacy with a reasonable expectation of success, absence of evidence to the contrary.
Response to arguments filed on 04/13/2026
In light of the new grounds of rejection above, the arguments submitted on 4/13/2026 which was for the previously submitted rejection is moot.
Conclusion
Claims 1-2, 4-18 and 20-29 are rejected. No claims are allowed
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7.00 am to 4.00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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