DETAILED ACTION
After further consideration of the prior art, the finality of the previous Office action of 22 May 2026 is withdrawn.
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 .
Status of Application, Amendments and/or Claims
The amendment of 20 August 2026 has been entered in full. Claims 32, 36, 46, 50, 52, 53 are amended. Claims 1-31, 33-35, 38, 39, 43-45, 49, 55, 56, and 58-94 are cancelled.
Claims 32, 36, 37, 40-42, 46-48, 50-54, and 57 are under consideration in the instant application.
Withdrawn Objections and/or Rejections
1. The objections to claims 36, 45, 46, 50, 51, 52, and 53 as set forth at page 3 of the previous Office Action of 22 May 2026 are withdrawn in view of the amended and cancelled claims (20 August 2026).
2. The rejection of claims 32, 36, 37, 40-42, 47, 48, 54, and 57 under 35 U.S.C. 103 as being unpatentable over Nakanishi et al. (JP 2006/199614) and Bardroff et al. (WO 2014/037899 or U.S. Patent 9,376,489) as set forth at pages 4-17 of the previous Office Action of 22 May 2026 is withdrawn in view of the amended claims (20 August 2026). Specifically, Nakanishi et al. and Bardroff et al. do not teach a method of treating moderate-to-severe atopic dermatitis.
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.
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.
3. Claims 32, 36, 37, 40-42, 47, 48, 54, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Terada et al. (Proc Natl Acad Sci USA 103(23): 8816-8821, 2006; cited on the IDS of 02 February 2025), Nakanishi et al. (JP 2006/199614; cited on the IDS of 25 August 2023); citations below refer to the English translation document on the PTO-892 of 01 December 2025), Kou et al. (Arch Dermatol Res 304: 305-312, 2012), and Bardroff et al. (WO 2014/037899 (cited on the IDS of 25 August 2023) or U.S. Patent 9,376,489). It is noted that WO 2014/037899 and U.S. Patent 9,376,489 have the same disclosure. Thus, for brevity, relevant portions of WO 2014/037899 will be cited below.
Terada et al. teach the generation of an intrinsic atopic dermatitis (AD) mouse model by daily application of protein A from S. aureus (SpA), after destruction of the skin barrier with a subclinical dose of SDS, a detergent, meeting the limitations of instant claims 47 and 48 (“NC/Nga mice”; page 8816, column 2, 1st full paragraph). Terada et al. disclose that the mice developed moderate and severe AD and accumulated IL-18 in their circulation, meeting the limitations of instant claim 32 (abstract; Figures 1 and 3C; page 8817, column 1, paragraph under Figure 1). Terada et al. state that clinical studies have shown that IL-18 production levels closely parallel disease severity (page 8816, column 1, last sentence through the top of column 2). Terada et al. teach the administration of neutralizing anti-IL-18 antibody to the mouse model and indicate that the mice have reduced AD scores, with little epidermal hyperplasia; little infiltration with T cells, eosinophils, and neutrophils; and basal levels of mast cells and MHC class II, meeting the limitations of instant claim 32 (page 8819, column 2, 3rd full paragraph; Figure 7; page 8820, column 2, 6th full paragraph).
Terada et al. do not teach treating moderate to severe AD in a human subject. Terada et al. do not teach an antagonistic IL-18 antibody that specifically binds IL-18 and does not bind the IL-18 BP complex (or any characteristics or amino acid sequences of such antibody). Terada et al. do not teach that the anti-IL-18 antibody is administered subcutaneously or intravenously.
Nakanishi et al. teach that IL-18 is a main factor that induces dermatitis in Th1-type atopic dermatitis (AD) (page 4, [0011]). Nakanishi et al. also disclose a method for the treatment of atopic dermatitis by administering an anti-IL-18 neutralizing antibody to a subject, meeting the limitations of instant claim 32 (page 5, [0015-0016]; page 8, [0049]; page 11, [0082]). Nakanishi et al. teach no significant onset of AD after administration of an anti-IL-18 neutralizing antibody to a Th1-type AD mouse model (page 6, [0025-0026]; page 11, [0082]; Figure 7). Nakanishi et al. indicate that protein A from Staphylococcus aureus (SpA) is used to induce AD, meeting the limitations of instant claims 47 and 48 (page 9, [0063], [0067]). Nakanishi et al. disclose the anti-IL-18 antibody is administered every 5 days, every 7 days, meeting the limitations of instant claim 57 (page 11, [0082]). Nakanishi et al. teach that the subject is a human, meeting the limitations of instant claim 32 (page 8, [0051]).
Kou et al. echo the teachings of Terada et al. by disclosing that IL-18 levels are significantly associated with moderate and severe AD in adult human patients (page 306, column 2, 2nd full paragraph; page 31,, column 1, 2nd full paragraph; Figure 1A and 1B).
Bardroff et al. teach a binding molecule that specifically binds IL-18, wherein the binding molecule does not bind the IL-18/IL-18 binding protein complex, meeting the limitations of instant claim 32 (page 3, lines 13-15; page 4, lines 23-27). Bardroff et al. disclose that the binding molecule is an isolated antibody or a fragment of an isolated antibody, meeting the limitations of instant claim 32 (page 3, lines 26-27). Bardroff et al. indicate that the binding molecule is an isolated fully human, humanized or chimeric antibody or fragment thereof, meeting the limitations of instant claim 32 (page 4, lines 10-12). Bardroff et al. teach that the binding molecule binds IL-18 with a KD of 0.5 to 20 pM, meeting the limitations of instant claim 36 (page 4, lines 8-9; pages 113-114, Table 2A, first column). Bardroff et al. state that the binding molecule inhibits IL-18-induced interferon gamma production from KG-1 cells with IC50 of 0.3-0.8 nM, meeting the limitations of instant claim 37 (page 30, lines 20-31 through page 31, lines 1-4; Table 2B, page 116, lines 16-22).
Bardroff et al. disclose a pharmaceutical composition comprising the IL-18 binding molecule and that such may be administered subcutaneously or intravenously, meeting the limitations of instant claim 54 (page 13, lines 24-25; page 93, lines 5-8). Bardroff et al. teach a method of treating autoimmune diseases by administering an IL-18 antagonistic binding molecule to a mammalian patient (page 100, lines 9-29 through page 101, lines 1-8, 26-31; page 102, lines 1-17). Bardroff et al. state that an exemplary treatment regime entails administration once per every two weeks or once a month or once every 3 to 6 months, also meeting the limitations of instant claim 57 (page 94, lines 27-28).
Bardroff et al. teach an IL-18 antagonist comprising heavy chain variable region HCR1, HCDR2, and HCDR3 amino acid sequences of SEQ ID NOs: 3, 9, and 5, respectively; and light chain variable region LCDR1, LCDR2, and LCDR3 amino acid sequences of SEQ ID NOs: 6, 7, and 8, meeting the limitations of instant claim 32 (page 36, Embodiment 10; page 37, Embodiment 13, 14). Bardroff et al. disclose the IL-18 antagonist comprises a heavy chain variable domain comprising SEQ ID NO: 14 and a light chain variable domain comprising SEQ ID NO: 16, meeting the limitations of instant claim 40 (page 6, lines 1-6; page 47, Embodiment 43; page 51, Embodiment 53). Bardroff et al. state that the antagonist comprises an N30K mutation in the heavy chain framework, meeting the limitations of instant claim 41 (page 6, lines 1-6; page 52, Embodiment 56). Bardroff et al. teach that the IL-18 antagonist comprises a heavy chain comprising SEQ ID NO: 43 and a light chain comprising SEQ ID NO: 45, meeting the limitations of instant claim 42 (page 6, lines 12-25; page 57, Embodiment 75).
It is noted that the amino acid sequences of SEQ ID NOs: 3, 9, 5, 6-8, 14, 16, 43, and 45 of Bardroff et al. are 100% identical to the amino acid sequences of SEQ ID NOs: 3, 9, 5, 6-8, 14, 16, 43, and 45 as recited in the claims of the instant application. See sequence alignments set forth in the previous Office Action of 01 December 2025.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the method of treating moderate to severe atopic dermatitis comprising administering an anti-IL-18 neutralizing antibody, as taught by Terada et al. by administering the antibody to humans as taught by Nakanishi et al. and Kou et al., as well as administering the antagonistic anti-IL-18 antibody (that does not bind the IL-18/IL-18 binding protein complex) of Bardroff et al. The person of ordinary skill in the art would have been motivated to make those modifications because (i) IL-18 levels are associated with atopic dermatitis clinical severity in humans; (ii) the development of therapeutic molecules for targets, such as IL-18, which are regulated by natural inhibitors can be challenging; (iii) the presence of an increased amount of systemic or local total IL-18 does not reflect the level of biologically active protein (IL-18 free of IL-18BP); and (iv) a therapeutic compound that binds both free and complexed IL-18 would be required in higher doses than one which can selectively bind only free IL-18, possibly leading to increased side effects or immunogenicity (Bardroff et al., page 2, lines 28-29; page 3, lines 1-4). The person of ordinary skill in the art reasonably would have expected success because the anti-IL-18 antibody of Bardroff et al. successfully neutralizes IL-18 and does not recognize the IL-18/IL-18 BP complex (pages 112-120). Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)).
Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
Conclusion
Claims 32, 36, 37, 40-42, 47, 48, 54, and 57 are rejected. Claims 46, 50-53 are allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Trzeciak et al. Clin Exp Dermatol 36: 728-732, 2011 (teach IL-18 is significantly higher in patients with severe AD as compared to those with milder disease; abstract; page 730, column 1, 1st paragraph; Figure 1B)
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BEB
Art Unit 1647
10 September 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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