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 .
Claim Status
Claim listing filed on November 11, 2025 is pending. Claims 2-5, 7-27, 30-37, 40-73, 75-92, 94-103, 105-106, and 108-131 are canceled. Claims 1, 6, 28-29, 38-39, 74, 93, 104, and 107 are amended. Claims 132-151 are new. Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are examined upon their merits.
Information Disclosure Statement
The information disclosure statement (IDS) filed on November 11, 2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. The IDS has been considered with the exception of the lined-through references (see attached) that do not have legible copies.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claims 2, 37, 43, 47, 59, 73, 91, 98, 101, and 118 have rendered all previous rejections directed to these claims moot.
The specification objections of record are withdrawn in view of Applicant’s amendments.
The sequence compliance objections of record are withdrawn in view of Applicant’s remarks filed 11/11/2025. Specifically, Applicant draws attention to the substitute specification filed on 11/22/2022 that has the appropriate SEQ ID NOs listed in Tables 1-4.
Claim Objections (New, necessitated by amendment)
Claim 151 is objected to because of the following informalities: “12-to 17 years old” should recite “12 to 17 years old” without the hyphen after “12.” Appropriate correction is required.
Applicant is advised that should claim 134 be found allowable, claim 135 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 102 (Modified, necessitated by amendment)
Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 138-149 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019.
The teachings of Kolkhir as they apply to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 138-149 are of record in the non-final action filed 06/11/2025. Amended Claims 1, 28, and 104 recite wherein the anti-IL-4R antibody comprises a heavy chain sequence comprising SEQ ID NO: 9 and a light chain sequence comprising SEQ ID NO: 10. SEQ ID NOs: 9 and 10 are the heavy and light chain sequences of the antibody dupilumab (defined in specification paragraphs [00422]-[00423]). It is of record that Kolkhir teaches a clinical trial evaluating the safety and efficacy of dupilumab in CSU patients with a loading dose of 600 mg and secondary treatments of 300 mg every 2 weeks (page 8, paragraph 2).
Amended Claims 1, 28, and 104 recite wherein the subject is naïve to treatment with an IgE antagonist. Kolkhir teaches a randomized Phase 2a clinical trial (NCT03749135) wherein dupilumab is administered to CSU patients ages 18-75 who remained symptomatic despite H1 antihistamine treatment (Table 1 and introduction paragraph 3). Clinicaltrials.gov defines that in NCT03749135, patients were recruited who remained symptomatic despite use of H1 antihistamine but who had not received anti-IgE therapy such as omalizumab (Inclusion Criteria and Exclusion Criteria). Therefore, Kolkhir’s teachings regarding clinical trial NCT03749135 read on the instant claim limitations.
As of record in the non-final filed 06/11/2025, claim limitations directed to patient response to treatment (ISS7, UAS7, and HSS7 in Claims 1, 28, 38-39, 74, 93, 104, 138-148) are inherent properties of the methodological treatment steps (MPEP § 2112.02.I). Because Kolkhir anticipates the method steps comprising administering dupilumab to CSU patients that are resistant to H1 antihistamine treatment and naïve to IgE antagonist treatment, the resulting treatment effects (i.e. patient responses) are inherently anticipated.
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive.
Applicant argues that Kolkhir fails to describe any quantitative results regarding using dupilumab to successfully achieve a decrease in ISS7 and/or UAS7 at week 24, specifically a decrease from baseline of at least 8 points at week 24 of treatment in ISS7 and/or a decrease from baseline of at least 15 points at week 24 of treatment in UAS7. As stated in the rejection above and of record in the non-final filed 06/11/2025, quantitative results of patient response to treatment are inherent properties of the method steps (see MPEP § 2112 for examples of inherent properties). A decrease in ISS7 and/or UAS7 does not alter the fundamental steps of the method of treatment claimed. Instead, a decrease in ISS7 and/or UAS7 is the result of administering dupilumab to CSU patients. Thus, prior art that anticipates administering dupilumab to CSU patients inherently anticipates the resulting treatment responses. Applicant’s arguments have been considered but are not persuasive, and Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 138-149 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kolkhir as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019.
Claim Rejections - 35 USC § 103 (Modified, necessitated by amendment)
Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are rejected under 35 U.S.C. 103 as being unpatentable over Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 in view of Siegfried et al. Pediatr Dermatol. Jan. 2019 (of record).
The teachings of Kolkhir as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 as they apply to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 138-149 are outlined in the rejection above. Kolkhir teaches a need for new therapies in children who have antihistamine-resistant CSU (page 5, paragraphs 2 and 4). Kolkhir fails to teach administering dupilumab in the pediatric setting, specifically: wherein the subject is 12 to 17 years old and has a body weight greater than or equal to 30 kg and less than 60 kg and the anti-IL-4R antibody is administered at an initial dose of 400 mg followed by 200 mg every 2 weeks (Claims 132, 134-136, and 150); or wherein the subject is 12 to 17 years old and has a body weight of at least 60 kg and the anti-IL-4R antibody is administered at an initial dose of 600 mg followed by 300 mg every 2 weeks (Claims 133, 137, and 151).
Siegfried teaches the dosing of dupilumab in pediatric atopic dermatitis (title). Table 1 teaches dupilumab dosing strategies under investigation in clinical trials including patients 12 years old to less than 18 years old having a body weight greater than or equal to 30 kg and less than 60 kg and the initial dose is 400 mg and followed by 200 mg administered every 2 weeks. Table 1 further teaches administering an initial dose of 600 mg followed by 300 mg every 2 weeks in patients at least 12 years old and less than 18 years old who weigh at least 60 kg. Note, differences in concentration are considered routine optimization and do not generally support the patentability of subject matter encompassed by the prior art (MPEP § 2144.05.II.A). The MPEP states “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation” (§ 2144.05.II.A).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to adapt the method of treating CSU by administering dupilumab taught by Kolkhir to include pediatric patients at doses known to be safe and effective as taught by Siegfried. Kolkhir teaches a population of patients under the age of 18 that have H1 antihistamine-resistant CSU and require further treatment. Because Kolkhir teaches that CSU adults who are unresponsive to antihistamine therapy can be treated with dupilumab, it is obvious that pediatric CSU patients who are unresponsive to antihistamine therapy can also be treated with dupilumab, given that the doses are appropriate and safe for their lower body weights. Siegfried teaches the specific dupilumab dosing regiments that are safe and effective in pediatric patients for the treatment of atopic dermatitis, a disease closely related to CSU. One of ordinary skill would understand that dupilumab is an effective treatment for adults with CSU, and if dupilumab is known to be safe for pediatric treatment in another dermatology disease, then dupilumab would be a safe and effective treatment option for CSU pediatric patients as well. The motivation to treat adult and pediatric CSU patients with dupilumab is because “antihistamines and omalizumab are the only current licensed treatments, and additional and better treatments are needed” (Kolkhir page 11, paragraph 1).
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive.
Applicant argues that it would not be obvious to combine the teachings of the cited references, because atopic dermatitis and CSU are distinct disorders. While atopic dermatitis and CSU are distinct disorders, they are closely related because they are both chronic inflammatory skin conditions. Further, it was understood in the state of the art prior to filing that dupilumab could be administered to simultaneously treat atopic dermatitis and urticaria (Ferrucci et al. Clin Exp Dermatol 2019; of record in IDS; title and page 2, paragraph 3) which supports how the pathology and treatment of the two diseases are similar. Note, Ferrucci is referenced solely in reply to Applicant’s arguments and not as a new grounds of rejection.
Applicant argues that the results provided by the instant application which demonstrate that an antibody that inhibits IL-4 and IL-13 was efficacious in treating CSU was unexpected. However, Kolkhir teaches treating CSU with dupilumab which is an antibody that blocks the IL-4 receptor alpha subunit which stops IL-4 and IL-13 signaling. Therefore, the results of the instant application are not unexpected as they were anticipated by Kolkhir.
Applicant argues that Siegfried fails to cure the deficiencies of Kolkhir. Siegfried is silent regarding using dupilumab to successfully achieve a decrease in ISS7 and/or UAS7 at week 24, specifically a decrease from baseline of at least 8 points at week 24 of treatment in ISS7 and/or a decrease from baseline of at least 15 points at week 24 of treatment in UAS7. As stated in the 102(a)(1) rejection above and of record in the non-final filed 06/11/2025, quantitative results of patient response to treatment are inherent properties of the method steps (see MPEP § 2112 for examples of inherent properties). A decrease in ISS7 and/or UAS7 does not alter the fundamental steps of the method of treatment claimed. Instead, a decrease in ISS7 and/or UAS7 is the result of administering dupilumab to CSU patients. Thus, prior art that anticipates administering dupilumab to CSU patients inherently anticipates the resulting treatment responses.
Applicant argues that there is no motivation to combine Siegfried and Kolkhir to arrive at the claims with a reasonable expectation of success, and the Office is performing an impermissible hindsight analysis using Applicant’s specification and claims as a guide. However, Applicant did not distinctly and specifically point out the supposed errors in the Examiner’s action (i.e. how the instant application was relied upon in the rejection as impermissible hindsight analysis) as is required in a complete response (MPEP § 714.02). Therefore, these arguments do not warrant a complete response and are not persuasive. The motivation to apply the dupilumab pediatric dosing regimens taught by Siegfried to the method of treating CSU taught by Kolkhir is because Kolkhir teaches that additional therapeutic options are needed for pediatric CSU patients who are resistant to antihistamine therapy (as stated above). There is a reasonable expectation of success that the pediatric dosing regimen for atopic dermatitis would be both safe and effective for CSU pediatric patients because atopic dermatitis and CSU are closely related skin diseases and dupilimab was already known to be effective in treating adult CSU patients (as stated above). Applicant’s arguments are not persuasive and the rejection is maintained.
Double Patenting (Modified, necessitated by amendment)
1. Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 34-35, 47-49, 53-54, 64-68, 80-82, 86-87, and 97-99 of U.S. Patent No. 11,964,016 in view of Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 and Siegfried et al. Pediatr Dermatol. Jan. 2019 (of record). Note, the rejection of record applied to Claims 1-2, 6, 28-29, 37-39, 43, 47, 59, 73-74, 91, 93, 98, 101, 104, 107, and 118 and now applies to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 due to Applicant’s amendments.
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims of ‘016 fail to disclose a method of treating CSU, administering the claimed antibody, and the decreases in ISS7 and UAS7. As of record in the non-final rejection filed 06/11/2025, the ‘016 patent teaches treating chronic urticaria (Claim 35) by administering dupilumab (Claim 53). Treating CSU instead of chronic urticaria is obvious over the ‘016 claims in view of Kolkhir (of record). Further, the decreases in ISS7 and UAS7 are inherent properties of the method steps (see MPEP § 2112).
2. Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 and 9-11 of U.S. Patent No. 10,392,439 in view of Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 and Siegfried et al. Pediatr Dermatol. Jan. 2019 (of record). Note, the rejection of record applied to Claims 1-2, 6, 28-29, 37-39, 43, 47, 59, 73-74, 91, 93, 98, 101, 104, 107, and 118 and now applies to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 due to Applicant’s amendments.
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims of ‘439 fail to disclose a method of treating CSU, administering the claimed antibody, and the decreases in ISS7 and UAS7. As of record in the non-final rejection filed 06/11/2025, the ‘439 patent teaches treating urticaria (Claim 6) by administering dupilumab (Claim 5). Treating CSU instead of urticaria is obvious over the ‘439 claims in view of Kolkhir (of record). Further, the decreases in ISS7 and UAS7 are inherent properties of the method steps (see MPEP § 2112).
3. Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 6, 8, 11-21, and 23-24 of U.S. Patent No. 10,676,530 in view of Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 and Siegfried et al. Pediatr Dermatol. Jan. 2019 (of record). Note, the rejection of record applied to Claims 1-2, 6, 28-29, 37-39, 43, 47, 59, 73-74, 91, 93, 98, 101, 104, 107, and 118 and now applies to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 due to Applicant’s amendments.
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims of ‘530 fail to disclose a method of treating CSU, administering the claimed antibody, and the decreases in ISS7 and UAS7. As of record in the non-final rejection filed 06/11/2025, the ‘530 patent teaches treating urticaria (Claim 8) by administering dupilumab (Claim 16). Treating CSU instead of urticaria is obvious over the ‘530 claims in view of Kolkhir (of record). Further, the decreases in ISS7 and UAS7 are inherent properties of the method steps (see MPEP § 2112).
4. Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2 and 4-12 of U.S. Patent No. 11,485, 788 in view of Kolkhir et al. Ann Allergy Asthma Immunol. Aug. 2019 (of record) as evidenced by NCT03749135 ClinicalTrials.gov Nov. 2019 and Siegfried et al. Pediatr Dermatol. Jan. 2019 (of record). Note, the rejection of record applied to Claims 1-2, 6, 28-29, 37-39, 43, 47, 59, 73-74, 91, 93, 98, 101, 104, 107, and 118 and now applies to Claims 1, 6, 28-29, 38-39, 74, 93, 104, 107, and 132-151 due to Applicant’s amendments.
Applicant's arguments filed November 11, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims of ‘788 fail to disclose a method of treating CSU, administering the claimed antibody, and the decreases in ISS7 and UAS7. As of record in the non-final rejection filed 06/11/2025, the ‘788 patent teaches treating urticaria (Claim 2) by administering dupilumab (Claim 5). Treating CSU instead of urticaria is obvious over the ‘788 claims in view of Kolkhir (of record). Further, the decreases in ISS7 and UAS7 are inherent properties of the method steps (see MPEP § 2112).
Conclusion
No claim is 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAH COOPER PATTERSON/Examiner, Art Unit 1675 /JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675