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 .
Status of Application, Amendments and/or Claims
The amendment of 27 February 2026 has been entered in full. Claims 32, 35-37, 39, 46-48, 50, 51, , and 57 are amended. Claims 1-31, 33-35, 38, 39, 43, 44, 49, 55, 56, and 58-94 are cancelled.
Claims 32, 36, 37, 40-42, 45-48, 50-54, and 57 are under consideration in the instant application.
Withdrawn Objections and/or Rejections
1. The Sequence Listing Requirement deficiency set forth at pages 2-4 of the previous Office Action of 01 December 2025 is withdrawn in view of Applicant’s amendment to the instant specification (27 February 2026).
2. The objections to the specification as set forth at pages 4-5 of the previous Office Action of 01 December 2025 are withdrawn in view of the amended specification (27 February 2026).
3. The objection to claim 50 as set forth at page 5 of the previous Office Action of 01 December 2025 is withdrawn in view of the amended claim (27 February 2026).
4. The rejections of claims 36, 37, 46-48, 51-53, and 57 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth at pages 5-7 of the previous Office Action of 01 December 2025 are withdrawn in view of the amended claims (27 February 2026).
5. The rejection of claims 32, 35-37, 39-42, 45-48, 50-54, and 57 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as set forth at pages 7-12 of the previous Office Action of 01 December 2025 is withdrawn in view of the amended and cancelled claims (27 February 2026).
6. The rejection of claims 32, 35-37, 39-42, 54, and 57 under 35 U.S.C. 102(a)(1) as being anticipated by Bardroff et al. (WO 2014/037899 or U.S. Patent 9,376,489) as set forth at pages 12-17 of the previous Office Action of 01 December 2025 is withdrawn in view of the amended and cancelled claims (27 February 2026). Specifically, Bardroff et al. do not teach treating atopic dermatitis, as required by the amended claims.
7. The rejection of claims 35 and 39 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2014/037899 or U.S. Patent 9,376,489) as set forth at pages 17-21 of the previous Office Action of 01 December 2025 is withdrawn in view of the cancellation of these claims (27 February 2026). Please see rejection under 35 U.S.C. 103, below.
New Claim Objections
8. Claim 36, 45, 46, 50, 51, 52, and 53 are objected to because of the following informalities:
8a. In claim 36, line 4, the phrase “with a KD of” is duplicative and should be deleted.
8b. Claims 45, 46, 50, 51, 52, and 53 are 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.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
9. Claims 32, 36, 37, 40-42, 47, 48, 54, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Nakanishi et al. (JP 2006/199614 (cited on the IDS of 25 August 2023); citations below refer to the English translation document) 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. The basis for this rejection is set forth for claims 32, 35-37, 39-42, 47, 48, 54, and 57 at pages 17-21 of the previous Office Action of 01 December 2025 and is reiterated herein below for convenience.
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. disclose a method for the treatment of atopic dermatitis by administering an anti-IL-18 neutralizing antibody, meeting the limitations of instant claim 32 (page 5, [0015-0016]; 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. do not teach an antagonistic IL-18 antibody that specifically binds IL-18 and does not bind the IL-18 BP complex. Nakanishi et al. do not disclose any characteristics or amino acid sequences of such antibody. Nakanishi et al. do not teach that the anti-IL-18 antibody is administered subcutaneously or intravenously.
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 atopic dermatitis comprising administering an anti-IL-18 neutralizing antibody, as taught by Nakanishi et al., by 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 that modification because (i) the development of therapeutic molecules for targets, such as IL-18, which are regulated by natural inhibitors can be challenging; (ii) 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 (iii) 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.
(i) At the bottom of page 9 of the Response of 27 February 2026, Applicant argues that Nakanishi et al. (‘614) discloses the use of a rabbit polyclonal antibody in a mouse model of atopic dermatitis and that this neutralizing antibody suppresses development of atopic dermatitis. Applicant asserts that such an antibody (rabbit-derived and polyclonal) would not be suitable for therapeutic purposes in a human and it would take more than routine experimentation by a person skilled in the art to generate an IL-18 antibody according to claim 32 in view of the disclosure of Nakanishi et al.
Applicant’s arguments have been fully considered but are not found to be persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As discussed in the previous Office Action of 01 December 2025, 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. disclose a method for the treatment of atopic dermatitis by administering an anti-IL-18 neutralizing antibody, meeting the limitations of instant claim 32 (page 5, [0015-0016]; 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]).
Although Nakanishi et al. do not teach (i) an antagonistic IL-18 antibody that specifically binds IL-18 and does not bind the IL-18 BP complex; (ii) any characteristics or amino acid sequences of such antibody; or (iii) that the anti-IL-18 antibody is administered subcutaneously or intravenously, such deficiencies are taught by Bardroff et al. Specifically, 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. 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.
(ii) At the bottom of page 9 of the Response, Applicant states that WO 2004/097019 describes the isolation of two anti-IL18 scFvs using phage display: h18-40 and h18-108. Applicant indicates that the effect of these scFv fragments on IFNγ production from human marrow mononuclear KG-1 cells stimulated by IL-18 is set out in Example 1, which shows that no inhibitory activity was found in the control scFv and the h18-40 scFv and activity was only found with the h18-108scFv ([0149]). Applicant argues that not all anti-human IL-18 binders are effective in reducing production of IFNγ. Applicant contends that this study demonstrates that not all anti-IL18 antibody fragments that bind to IL18 could be effective for treating diseases associated with overproduction of IL18.
Applicant’s arguments have been fully considered but are not found to be persuasive. First, Applicant cites WO 2004/097019, which is entirely in Japanese (other than the abstract) and has not been made of record in this application. Without official submission of this reference and its translation, the Examiner is unable to independently evaluate and draw conclusions about the information contained therein. Second, even if the reference and its translation had been submitted, it is not clear of its importance or relevance to the instant rejection at hand. The WO 2004/097019 was not utilized by the Examiner in the rejection of the claims under 35 U.S.C. 103.
Lastly, the claims are rejected under 35 U.S.C. 103 as being unpatentable over a combination of Nakanishi et al. and Bardroff et al. The IL-18 antagonist antibody of the instant claims (that does not bind the IL-18/IL-18 binding protein complex) is clearly taught by Bardroff et al. (page 3, lines 13-15; page 4, lines 8-12, 23-27; page 30, lines 20-31 through page 31, lines 1-4; see also Table 3 at pages 118-119). Bardroff et al. also 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. disclose that their IL-18 antagonistic binding molecule inhibits Th1 modulation, (page 1, lines 27-28; page 30, lines 27-28).
The person of ordinary skill in the art would have been motivated to modify the method of treating atopic dermatitis comprising administering an anti-IL-18 neutralizing antibody, as taught by Nakanishi et al., by administering the antagonistic anti-IL-18 antibody of Bardroff et al. because (i) the development of therapeutic molecules for targets, such as IL-18, which are regulated by natural inhibitors can be challenging; (ii) 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 (iii) 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).
(iii) At the middle of page 10 of the Response, Applicant submits that Bardroff et al. (‘899) describes the generation of anti-IL-18 antibodies by phage display. Applicant argues that it must follow from the disclosure of WO 2004/097019, that the skilled person would have no reasonable expectation of success to generate a binder to IL-18 that is efficacious, let alone to generate a human therapeutic antibody to IL-18 that could be used to treat atopic dermatitis. Applicant asserts that the specification of Bardroff et al. does not even mention that the antibody disclosed therein could be used to treat atopic dermatitis and there is no teaching or suggestion in Bardroff et al. that would lead the skilled person towards testing the antibody of Bardroff et al. in, for example, an animal model of atopic dermatitis, let alone to consider testing this antibody in a full clinical study for treating atopic dermatitis. As such, the claims as amended should not be considered obvious.
Applicant’s arguments have been fully considered but are not found to be persuasive. As discussed above, Applicant cites WO 2004/097019, which is entirely in Japanese (other than the abstract) and has not been made of record in this application. Without official submission of this reference and its translation, the Examiner is unable to independently evaluate and draw conclusions about the information contained therein. Second, even if the reference and its translation had been submitted, it is not clear of its importance or relevance to the instant rejection. The WO 2004/097019 was not utilized by the Examiner in the rejection of the claims under 35 U.S.C. 103.
Again, in response to applicant's continued arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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. disclose a method for the treatment of atopic dermatitis by administering an anti-IL-18 neutralizing antibody, meeting the limitations of instant claim 32 (page 5, [0015-0016]; 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]).
Although Nakanishi et al. do not teach (i) an antagonistic IL-18 antibody that specifically binds IL-18 and does not bind the IL-18 BP complex; (ii) any characteristics or amino acid sequences of such antibody; or (iii) that the anti-IL-18 antibody is administered subcutaneously or intravenously, such deficiencies are taught by Bardroff et al. Specifically, 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 8-12, 23-27; page 30, lines 20-31 through page 31, lines 1-4; see also Table 3 at pages 118-119). 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. also teach that their IL-18 antagonistic binding molecule inhibits Th1 modulation, (page 1, lines 27-28; page 30, lines 27-28).
Therefore, the person of ordinary skill in the art would have been motivated to modify the method of treating atopic dermatitis comprising administering an anti-IL-18 neutralizing antibody, as taught by Nakanishi et al., by administering the antagonistic anti-IL-18 antibody of Bardroff et al. because (i) the development of therapeutic molecules for targets, such as IL-18, which are regulated by natural inhibitors can be challenging; (ii) 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 (iii) a therapeutic compound that binds both free and complexed IL-18 would be required in higher doses than one which selectively binds 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).
(iv) At the bottom of page 10 through page 11 of the Response of 27 February 2026, Applicant indicates that it has been demonstrated that the present invention provides an effective treatment of atopic dermatitis. For example, a randomized blinded and placebo controlled clinical study, described in Example 3 and corresponding to NCT04836858, has been carried out. Applicant points out that as reported at clinicaltrials.gov//study/NCT04836858?tab=results, the study consisted of up to 4 weeks screening period to assess participants eligibility, the baseline visit, 4-weekly administrations of CMK389 within the first 12 weeks of the 16-week treatment period, and an approximately 12 weeks follow up period which finished with the end of study visit (EoS). This was evaluated by assessing the Investigator Global assessment (IGA) response at week 16 using the Validated Investigator Global Assessment scale for Atopic Dermatitis, to determine the severity of atopic dermatitis signs and symptoms and clinical response to treatment. The IGA score reflected a participant's overall disease severity for the whole body based on a 5-point scale: clear, almost clear, mild, moderate, and severe disease. IGA response is defined as clear or almost clear and at least a 2 point-reduction from baseline at week 16. As can be observed from the table reproduced in the response, only participants treated with an antibody having the CDRs recited in claim 32 (CMK389) obtained an IGA response compared with pooled placebo. Applicant contends that in light of the disclosure of the prior art, the positive clinical results are surprising, and use of the antibody as claimed for the treatment of atopic dermatitis is clearly advantageous.
Applicant’s arguments have been fully considered but are not found to be persuasive. A Clinical Trial entry of NCT04836958 was previously made of record on the IDS of 25 August 2023. However, in the Response of 27 February 2026, Applicant seems to make reference to an updated results entry of Clinical Trial NCT04836858, which has not been made of record in this application. Without official submission of this reference, the Examiner is unable to independently evaluate and draw conclusions about the information contained therein.
Furthermore, even if the updated results entry of Clinical Trial NCT04836858 had been submitted, Applicant’s arguments would still not have been found to be persuasive. Although Applicant asserts that the results of a randomized blinded and placebo controlled clinical study, described in Example 3 and corresponding to NCT04836858, demonstrate efficacy of IL-18 antibody, CMK389, in patients with atopic dermatitis, these beneficial results would have been expected. First, 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 (page 5, [0015-0016]; page 11, [0082]) and indicate that there is 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). Second, 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 (page 3, lines 13-15; page 4, lines 8-12, 23-27; page 30, lines 20-31 through page 31, lines 1-4; see also Table 3 at pages 118-119). The IL-18 antagonistic binding molecule of Bardroff et al. comprises the same the amino acid sequences as recited in the claims of the instant application. Bardroff et al. also teach that their IL-18 antagonistic binding molecule inhibits Th1 modulation and is administered in a method of treating autoimmune diseases in a mammalian patient (page 1, lines 27-28; page 30, lines 27-28; page 100, lines 9-29 through page 101, lines 1-8, 26-31; page 102, lines 1-17).
Additionally, in view of the teachings of Nakanishi et al. and Bardroff et al., the teachings of the instant specification are not unexpected or unpredictable. In other words, upon reading the combined teachings of Nakanishi et al. and Bardroff et al., one of ordinary skill in the art would expect the IL-18 antagonistic binding molecule of Bardroff et al. to treat atopic dermatitis because Nakanishi et al. successfully treat atopic dermatitis by administering an anti-IL-18 neutralizing antibody to a Th1-type AD mouse model (page 5, [0015-0016]; page 6, [0025-0026]; page 11, [0082]; Figure 7) and Bardroff et al. disclose the generation of a binding molecule that (i) specifically binds IL-18, but does not bind the IL-18/IL-18 binding protein complex, and (ii) inhibits IL-18-induced interferon gamma production from KG-1 cells (page 3, lines 13-15; page 4, lines 23-27; page 30, lines 20-31 through page 31, lines 1-4; see also Table 3 at pages 118-119). Applicant is reminded that MPEP 716.02(c)(II) states that “expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” (In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1964); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989)).
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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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BEB
Art Unit 1647
19 May 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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