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 the Claims/Application
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/26/2025 has been entered.
Claims 4, 6-16, 19, 21-30, 36-41 and 44 are canceled, claims 1-3, 5, 17-18, 20, 31, 42-43 and 45 are currently amended, claims 48-68 are new. Claims 1-3, 5, 17-18, 20, 31-35, 42-43, 45-68 are pending and herein under examination on the merits.
Priority
The instant application filed on 08/23/2022 claims priority to US Provisional Applications 63/236,035 filed on 08/23/2021, 63/297,908 filed on 01/10/2022, 63/319,500 filed on 03/14/2022 and 63/341,948 filed on 05/13/2022. The instant application will be examined with an effective filing date of 08/23/2021.
Withdrawn Rejections
Rejections Under 35 U.S.C § 112(b)
The applicant canceled claims 12 and 24, rendering the rejections under U.S.C § 112(b) moot.
Maintained/New Grounds for Rejection
Rejections Under U.S.C § 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.
The factual inquiries 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 non-obviousness.
Claims 1-3, 5, 17-18, 20, 31-35, 42-43, 45-68 are rejected under 35 U.S.C. 103 as being unpatentable over Treister AD, Lio PA. Long-term off-label dupilumab in pediatric atopic dermatitis: A case series. Pediatr Dermatol. 2019 Jan;36(1):85-88, and further in view of US 9,290,574 B2, WHO Child Growth Standards, Center for Disease Control and Prevention, Nov. 2008, US 2018/0078603 A1 and Siegfried et al. Use of dupilumab in pediatric atopic dermatitis: Access, dosing, and implications for managing severe atopic dermatitis. Pediatr Dermatol. 2019 Jan;36(1):172-176, herein further referred to as Treister, Kostic, WHO, Radin and Siegfried respectively.
Treister teaches the use dupilumab (an IL-4 inhibitor) for the treatment of moderate-to-severe atopic dermatitis (AD) in children under 18 years and weighing less than 40 kg (Treister Abstract). Treister further teaches a patient population whereby the patients have previously failed treatment from a topical AD medication such as (TCS) (Treister Tab. 1) and nonsteroidal systemic treatment (Treister pg. 87 col 1 Sec 4 para 1). Treister also teaches that all patients were encourage to continue topical treatment for AD (Treister pg. 86 Sec 2 para 2). Treister also teaches that 39% of patients who received dupilumab achieved the primary endpoint of IGA 0/1 after 16-week treatment duration (Treister pg. 87 col 1 Sec 4 para 1). Treister further discloses that in a clinical trial, children ages 6 months to 6 years where administered single-dose 3mg/kg with plans to increase to 6 mg/kg of dupilumab to weight (Treister pg. 87 Sec. 4 col. 2 para 1).
Treister does not specifically teach that 200 mg or 300 mg of dupilumab was administer subcutaneously Q4W to the specific patient population if ages ≥ 6 months to ≤ 6 years and weight (≥ 5 to ≤15 kg or ≥ 15 to ≤30 kg). Treister does not also teach that dupilumab is contained in a single-dose pre-filled syringe, pen delivery device or an autoinjector. Treister does not also specifically teach that administering dupilumab reduced the risk of a rescue treatment.
Kostic teaches that and IL-4 receptor inhibitor such as dupilumab can be subcutaneously administered with a pen delivery device that can be reusable or disposable (Kostic col 14 ln 26 -31) for the treatment of a pediatric patient with eosinophilic esophagitis (EoE, an IL-4 receptor related condition) (Kostic Col 1 ln 39-48), that also concurrently has atopic dermatitis (Kostic Col 2 ln 10-14), where the use of topical corticosteroid has failed (Kostic col 18 ln 60-67) and who is of ages including 6 months to 6 years (Kostic Col 5 ln 16-25). Kostic also teaches that the IL-4R inhibitor can be administered at different doses including 200 mg and 300 mg as a function to the patient’s body weight (for example it can be administered at a dose of about 0.0001 to about 100 mg/kg) at a frequency including every four weeks (Q4W) (Kostic col 6 ln 10-18) to effectuate the desired therapeutic effect (Kostic col 15 ln 32-57). Kostic further teaches that the use of rescue treatment (such as systemic or topical corticosteroid) during trials was only used when necessary if the patient need it (Kostic col 19 ln 6-12).
While Kostic is silent on the baseline weights of ≥ 5 to ≤15 kg and ≥ 15 to ≤30 kg, WHO teaches that infants and children aged 0-2 years have an expected weight of about 2.5 to 15.5 kg.
Radin teaches that dupilumab (the IL-4R antagonist) composition can be contained in a standard needle and syringe as well as a pen delivery device or autoinjector (US’603 pg. 10-11 para 0072-0073). Radin also teaches that the IL-4R inhibitor (dupilumab) can be administered in combination with a topical therapy such as topical corticosteroid (US’603 pg. 2 para 0009)
Siegfried teaches that dupilumab is available as a single use, prefilled syringe (Siegfried pg. 173 Sec 2.2 para 3). Siegfried also teaches that smaller children of ages 7, 10 and 11 weighing 27 to 35 kg where administered half the dose administered to older and bigger children (Siegfried pg. 173 Sec 2.2 para 2) and that Treister and Lio chose to treat their pediatric patients with either a full adult dose or an estimated half dose. Siegfried also illustrates in Table 2 a reduction in dosing regimen as the children become younger and smaller (Siegfried pg. 174 Tab 2).
Therefore, it would have been obvious before the effective filing date for a person with ordinary skill in the art to modify the teachings of Treister in view of Kostic, WHO, Radin and Siegfried with a reasonable degree of predictable success to administer 200 or 300 mg subcutaneously Q4W through a single-dose pen delivery device or autoinjector to infants within the claimed age and weight having severe-to-moderate AD that are not being adequately treated by topical AD medication so that they can achieve an IGA score of 0 or 1 within 16 weeks of treatment. It is knows in the art that EoE and AD are both IL-4R related disease and therefore, using a similar treatment regimen for the claimed aged population that targets the same IL-4R would have being obvious to an ordinary skilled artisan in view of the teachings of Treister and Kostic. As indicated by Kostic and Siegfried, the dosage administered to a patient is based on their weight and age and indicated by Siegfried smaller and younger patients received lesser dose and further as indicated by Kostic the dosage can be administer at about 0.0001 to about 100 mg/kg. Therefore, a skilled artisan would have been able to perform a routine optimization based on the references to obtain a treatment outcome where an AD-associated parameter such as IGA for the claimed patient population would be 0 or 1 and where the treatment may reduce the patients risk for requiring a rescue treatment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 17-18, 31-35, 42-43, 45-62, and 64-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9, 11, 13, and 15-24 of U.S. Patent No. US12090201B2 in view of Kostic, WHO, Radin and Siegfried, herein referred to as Bansal.
Bansal teaches all the using IL-4 (dupilumab) (Bansal claim 19) for treating moderate-severe AD in children between 6 and less than 12 years old who cannot be adequately treated with a topical AD medication (Bansal claim 6) and is inadequately responding to treatment with TCS (Bansal claim 7), wherein dupilumab is subcutaneously administered at 300 mg Q4W, or at 200 mg Q2W or at 300 mg Q2W depending on the weight of the child (Bansal claims 1-5) and dupilumab is administered in combination with TCS (Bansal claim 11). Bansal further teaches that the improvement in baseline AD associated parameters after 16 weeks of treatment is achieved including a reduction in IGA score of 0 or 1 (Bansal claim 15). Bansal also teaches that dupilumab can be contained in as a single dose pre-filled syringe, an autoinjector or in a pen delivery device. Bansal also teaches that dupilumab comprises the claimed sequences as below.
Bansal does not teach the use of dupilumab in a subject ≥ 6 months to ≤ 6 years and of weight between ≥ 5 to ≤15 kg or ≥ 15 to ≤30 kg.
Kostic teaches that and IL-4 receptor inhibitor such as dupilumab can be subcutaneously administered with a pen delivery device that can be reusable or disposable (Kostic col 14 ln 26 -31) for the treatment of a pediatric patient with eosinophilic esophagitis (EoE, an IL-4 receptor related condition) (Kostic Col 1 ln 39-48), that also concurrently has atopic dermatitis (Kostic Col 2 ln 10-14), where the use of topical corticosteroid has failed (Kostic col 18 ln 60-67) and who is of ages including 6 months to 6 years (Kostic Col 5 ln 16-25). Kostic also teaches that the IL-4R inhibitor can be administered at different doses including 200 mg and 300 mg as a function to the patient’s body weight (for example it can be administered at a dose of about 0.0001 to about 100 mg/kg) at a frequency including every four weeks (Q4W) (Kostic col 6 ln 10-18) to effectuate the desired therapeutic effect (Kostic col 15 ln 32-57). Kostic further teaches that the use of rescue treatment (such as systemic or topical corticosteroid) during trials was only used when necessary if the patient need it (Kostic col 19 ln 6-12).
While Kostic is silent on the baseline weights of ≥ 5 to ≤15 kg and ≥ 15 to ≤30 kg, WHO teaches that infants and children aged 0-2 years have an expected weight of about 2.5 to 15.5 kg.
Radin teaches that dupilumab (the IL-4R antagonist) composition can be contained in a standard needle and syringe as well as a pen delivery device or autoinjector (US’603 pg. 10-11 para 0072-0073). Radin also teaches that the IL-4R inhibitor (dupilumab) can be administered in combination with a topical therapy such as topical corticosteroid (US’603 pg. 2 para 0009)
Siegfried teaches that dupilumab is available as a single use, prefilled syringe (Siegfried pg. 173 Sec 2.2 para 3). Siegfried also teaches that smaller children of ages 7, 10 and 11 weighing 27 to 35 kg where administered half the dose administered to older and bigger children (Siegfried pg. 173 Sec 2.2 para 2) and that Treister and Lio chose to treat their pediatric patients with either a full adult dose or an estimated half dose. Siegfried also illustrates in Table 2 a reduction in dosing regimen as the children become younger and smaller (Siegfried pg. 174 Tab 2).
Therefore, it would have been obvious before the effective filing date for a person with ordinary skill in the art to modify the teachings of Bansal in view of Kostic, WHO, Radin and Siegfried with a reasonable degree of predictable success to administer 200 or 300 mg subcutaneously Q4W through a single-dose pen delivery device or autoinjector to infants within the claimed age and weight having severe-to-moderate AD that are not being adequately treated by topical AD medication so that they can achieve an IGA score of 0 or 1 within 16 weeks of treatment. It is knows in the art that EoE and AD are both IL-4R related disease and therefore, using a similar treatment regimen for the claimed aged population that targets the same IL-4R would have being obvious to an ordinary skilled artisan in view of the teachings of Bansal and Kostic. As indicated by Kostic and Siegfried, the dosage administered to a patient is based on their weight and age and indicated by Siegfried smaller and younger patients received lesser dose and further as indicated by Kostic the dosage can be administer at about 0.0001 to about 100 mg/kg. Therefore, a skilled artisan would have been able to perform a routine optimization based on the references to obtain a treatment outcome where an AD-associated parameter such as IGA for the claimed patient population would be 0 or 1 and where the treatment may reduce the patients risk for requiring a rescue treatment.
Response to Arguments
Rejections Under U.S.C § 103
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive.
In the applicant remarks (pg. 13 para 2), the applicant asserts that Treister does not specifically teach the claims combination of weight bands, fixed doses, and Q4W dosing in patients aged ≥6 months to <6 years, and therefore a skilled artisan would not have being motivated to alter the dosing regimens of Treister for use in patients aged ≥6 months to <6 years. The applicant further asserts that a person of ordinary skill in the art would not have arrived at the claimed regimen without hindsight analysis of the disclosure of the instant applicant and that the examiner fails to account for the substantial effort, clinical judgement and scientific rigor required to develop a safe and effective dosing regimen for the claimed patient population (Remarks pg. 13 para. 3). Secondly, the applicant further argues that Kostic does not teach about Ad but relates to the treatment eosinophilic esophagitis (another IL4 receptor condition).Lastly, the applicant argues that WHO Child Growth merely provides a general weight and does not teach the specific weight-tier to whom dupilumab is administered at the claimed dosage and frequency (Remarks pg. 14 para 2).Regarding the applicant assertion that Treister does not teach all the element as claimed and therefore a skilled artisan would not have being motivated to alter the dosing regimen for use in the claimed patient population, the examiner would refer the applicant to MPEP 2145 IV, which particularly points out that arguments against individual reference used in an obviousness rejection is not sufficient to show non obviousness, because the test for obviousness is what the combined teachings of the references used would have suggested to an ordinary skilled artisan. The knowledge as presented by the examiner from the prior arts can be obvious to an ordinary artisan to reconstruct the claimed invention with a reasonable degree of predictable success because all the limitations of the claims are thought by the combination of prior art used for the rejection. Furthermore, there fact that, substantial effort, clinical judgement and scientific rigor is required to develop a safe dosage for the claimed population does not support that an ordinary skilled artisan would not have been motivated to develop the dosage regimen for the claimed population, the rationales to support a rejection under 35 U.S.C 103 are listed in MPEP 2141 (III).
In response to applicant's argument (Remarks pg. 13 para. 3) that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).Also, concerning the specific weight range claimed in applicants remarks (pg. 13 para 3) is not thought by Triester, MPEP 2144.05(I) states that, a prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. Kostic teaches that children of ages including 6 months to 6 years (Kostic Col 5 ln 16-25) can be treated with dupilumab and WHO Chart shows the weight range for children who are with the claim age group.
Applicant argues that, a person with ordinary skill would not have arrived at the claimed weight -tier, dose variations (fixed- vs loading), dosing interval, dose amount and patient age from Treister teachings without hindsight analysis and that the rejection fails to account for the effort and clinical judgement and scientific rigor required to develop a safe and effective dosing regimen for the population as claimed (Remarks pg. 13 para. 3), and that Kostic does not teach a fixed dose Q4W regimen of 300 mg or 200 mg of dupilumab achieves or mainstains therapeutic efficacy in young children with AD. Given the teachings of Treister in view of Kostic, WHO, Radin and Siegfried a skilled artisan would have been able to determine the weight-tier, dose variations (fixed- vs loading), dosing interval, dose amount and patient age required to administer dupilumab safely. Looking at Kostic teachings, Kostic discloses that 200 mg or 300 mg of dupilumab can be administered safely to children between 6 months and less than 6 years old for the treatment of patients having EoE (an IL4R condition) and also having AD (Kostic Col 2 ln 10-14). Here, Kostic demonstrates that dupilumab can be administered to infants of the claimed age and weight safely, and therefore it would have been obvious for a skilled artisan to administer dupilumab in a similar dose and frequency as in Kostic to a subject with claimed age and weight. Its known in the art and by a skilled artisan that AD and EoE are both IL4 receptor conditions and that treating either condition with a IL4 inhibitor such as dupilumab can have a predictably level of success in treating other IL4 receptor conditions, See MPEP 2141.02(V). Furthermore, Siegfried also teaches that smaller children of ages 7, 10 and 11 weighing 27 to 35 kg where administered half the dose administered to older and bigger children (Siegfried pg. 173 Sec 2.2 para 2) and that Treister chose to treat their pediatric patients with either a full adult dose or an estimated half dose. Siegfried also illustrates in Table 2 a reduction in dosing regimen for younger and smaller children (Siegfried pg. 174 Tab 2). Regarding the WHO Child Growth Chart, it merely shows that children within the claimed age group are generally within the weight tier as claimed. Therefore, a skilled artisan would have been able to apply these teachings by reducing the doses for younger and less heavy subject through routine optimization in other to obtain an effective dose for the claimed patient population.
Further Treister teaches that teaches a subset of patients who were administered 300 mg of dupilumab biweekly achieved a primary endpoint of IGA of 0 or 1 after 16 weeks treatment duration, therefore it would have been obvious for a skilled artisan in view of Treister, Kostic and WHO Child Growth Chart to measure a treatment outcome such as IGA for the claimed patient weight and age according to the claimed dosing regimen after 16 week to observed the improvement of the AD-associated parameter as claimed.
Non-Statutory Double Patenting (NSDP)
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive. As indicated in the analysis of the 35 USC 103 rejections above and on the same basis, the previously rejected claims 1-35 and 42-47 are not patentably distinct from claims 1-24 of Bansal in view of Kostic, WHO, Radin and Siegfried.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMMANUEL LED YOUTCHOM PENDIE whose telephone number is (571)272-6313. The examiner can normally be reached Mon - Fri: 8AM - 5PM CST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanna Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMMANUEL LED YOUTCHOM PENDIE/ Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647