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 considered in the instant office action. Receipt and consideration of Applicants amended claim set and remarks/arguments filed on 9/1/2026 is acknowledged. Claims1, 4, 7 are amended and are under consideration in the instant office action.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/1/2026 has been entered.
Applicants' arguments, filed 9/1/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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, examiner contacted the applicants with a proposal for an examiner’s amendment, to narrow claim 1 with the specific IRAK4 degrader which is of formula Degrader 2 recited in instant claim 20. Applicants said they preferred to
Claim Objections
Claim 20 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-18 and 21-29 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treatment of hidradenitis suppurative in a patient having an elevated level of an inflammatory biomarker with IRAK4 degrader with Degrader 1 and Degrader 2 recited in instant claim 20 does not reasonably provide enablement for treatment of hidradenitis suppurative in a patient having an elevated level of an inflammatory biomarker with each and every IRK4 degrader known.
The present claims relate to the mechanism underlying the treatment of the claimed diseased with IRAK4 degrader. Even if the inhibition of the IRAK4 by the various IRAK4 degraders is indisputably a pharmacological effect, it cannot in itself be considered a therapeutic application, nor can it fully enable the treatment of a specified pathological conditions, in the present case the treatment hidradenitis suppurative with every known IRAK degrader. . Accordingly the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention and the Breadth of the claims:
The invention is 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. The claims are broad in that it is inclusive of each and every compound or agent which acts as IRAK4 degrader.
IRAK4 degraders known in the art are several include several compounds such as all the compounds disclosed by Cravatt et al. in US2020/0190105, Compounds disclosed by Gray et al. in US 2021/0230144, Compounds disclosed by Von Roemeling et al. in US 2023/0414582
Relative skill of those in the art
The relative skill of those in the art is high, usually a doctorate or a masters level graduate.
State of the prior art/Predictability or unpredictability of the art:
The state of the prior art is such that it involves screening both in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. which compounds treat which specific Id2 related disease). There is no predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
The present claims relate to the mechanism underlying the treatment of the claimed diseased with the compounds of the instant invention. Although the discovery of such a mechanism may be an important piece of scientific knowledge, it still needs to be turned into a practical application in the form of a specified actual treatment of the pathological conditions.
With regard to treatment of hidradenitis suppurativa (HS) , Hoffman et al. (Seminars in Cutaneous Medicine and Surgery, volume 36, 2017, pages 86-92 ) teaches that “Treatment of HS remains challenging, as there are insufficient options for effective treatment, and no definitive cure exists. The European guidelines recommend a treatment ladder based on Hurley staging.1 There are only a dozen or so randomized controlled trials for HS, recently reviewed in a Cochrane analysis.49 Considering this is such a prevalent and devastating disease, this represents a huge knowledge gap in our understanding of HS”. Sabbat et al. (www.thelancet.com, volu 405, 2025 pages 420-38) teaches that. Historically, treatment of hidradenitis suppurativa has mostly been unsuccessful and conducted reluctantly by many disciplines, remaining a challenge today and that management options include topical and systemic drug therapies, surgical interventions, adjuvant therapies (also considering concomitant diseases), and lifestyle Modifications (figure 4). The specific approach should be appropriate to the respective phase of the disease, with regards to treatment based on biomarker elevation, Sabbat et al teaches that several scientific groups now address this topic, leading to the discovery of unexpected pathomechanism with a new view of pathogenesis, and identification of new therapeutic targets. In line with these developments, numerous placebo-controlled clinical phase 2 trials investigating targets from innate immune reaction (e.g., IL-1α [bermekimab, NCT04988308], IL-1α or IL-1β lutikizumab, NCT05139602], neutrophil attracting chemokines CXCL1-3 and CXCL5-8 [eltrekibart, NCT06046729], LTB4 [LYS006, NCT03827798], and G-CSF receptor [CSL324]), T-cellular reaction (e.g., IL-23 p19 [guselkumab, NCT03628924;
risankizumab, NCT03926169]), humoral or B-cell reaction (e.g., CD40 [iscalimab, NCT03827798], BTK [LOU064, NCT03827798], BAFF receptor [ianalumab,
NCT03827798], and OX40L [amlitelimab, NCT06118099]), and different immune reactions simultaneously (e.g., TNF or OX40L [SAR442970, NCT05849922] and IRAK4
[SAR444656, NCT06028230]) have recently been completed or are underway. From some of these studies, we have learned that IL-23127,128 and IL-1α (NCT04988308)
do not play essential roles in pathogenesis. Other target candidates—eg, IL-17 and JAK1—however, have proven promising in phase 2 studies177,178 and are currently
investigated in placebo-controlled clinical phase 3 trials (figure 5) or are even approved for this condition (panel).
While the IRAK4 studies are underway, the overall biomarker based treatment of HS is still in its infancy and as such treatment of this complicated disease with each and every IRAK degrader known in the art is highly unpredictable.
.
Amount of guidance/Existence of working examples:
More importantly, there is working example present for just the two IRAK4 degraders, Degrader 1 and Degrader 2,
Both example 1 and Example 2 in the instant disclosure (pages 29-37) have studies which demonstrate the use of Degrader 1 and Degrader 2 in the potential treatment of HS. There are no other IRAK4 degraders tested and just these two agents do not adequately represent the vast groups of IRAK 4 degraders. Thus, the specification fails to provide clear and convincing evidence in sufficient support for using the claimed compounds in a method to treating HS with each and every IRAK 4 degraders available as recited in the instant claims. Thus, factors such as “sufficient working examples”, “the level of skill in the art”, and “predictability”, etc. have been demonstrated to be sufficiently lacking in the instant claimed methods. In view of the breadth of the claims, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate with the scope of the claims.
The quantity of experimentation necessary
Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. Therefore, in view of the Wands factors discussed above, to practice the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation to test which all the known IRAK degraders in the treatment of HS as encompasses in the instant claims, with no assurance of success. Thus, rejection of claims 1-2, 4-18 and 20-29 under 35 U.S.C. §112, first paragraph, is deemed proper.
Conclusion
Claims 1-2, 4-18 and 21-29 are rejected. Claim 20 is objected. No claims are allowed
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 am to 4 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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