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 .
Claims Status
Claims 1-46 are pending and are examined on the merits.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-9, 12-16, 26, 28, 34, 36-37, 39-40, and 42-43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as evidenced by the instant specification and ClinicalTrials.gov ID: NCT03345914 (Version 2020-08-13; https://clinicaltrials.gov/study/NCT03345914; PTO-892), herein “NCT03345914”.
Regarding Claims 1-2 and 14, Bawany teaches treatment of a 9-year-old patient (i.e. ≥1 year and < 12 years old; Pg. 1150, Col. 1, ¶2) having eosinophilic esophagitis (EoE; Pg. 1151, Col. 2, ¶1) via administration of anti-IL-4Rα antibody dupilumab wherein treatment of said patient resulted in objective improvement in all comorbid allergic conditions (Introduction).
Regarding the sequences recited in Claims 1 and 12-13, each claimed sequence is the same as those comprised within dupilumab as evidenced by ¶070 and Table 7 of the instant specification (Pg. 64; SEQ ID NOs: 1-10).
Regarding Claim 3, Bawany teaches the patient had 5 to 25 intraepithelial eosinophils per high-power field as measured by esophageal biopsies at 21, 24, and 26 cm (i.e. proximal, mid, and distal) (Pg. 1151, Col. 2, ¶1).
Regarding Claims 4-5, Bawany teaches the patient was previously treated with omeprazole (i.e. a proton pump inhibitor), which yielded “only limited histological improvement” (i.e. inadequately responsive) (Pg. 1151, Col. 2, ¶1).
Regarding Claims 6-7, Bawany teaches the patient had concomitant atopic dermatitis (Introduction).
Regarding Claims 8-9, 16, and 26, Bawany teaches at baseline the patient was receiving 100 mg/d cyclosporine, which was the equivalent of 3.2 mg/kg/d (Pg. 1150, last ¶). Accordingly, at baseline the patient taught by Bawany weighed approximately 31.25 kg.
Regarding Claims 15-16, 28, and 34, Bawany teaches the patient received 200 mg dupilumab every 2 weeks (Q2W) (Pg. 1151, first ¶).
Regarding Claims 36 and 42-43, Bawany teaches that the patient was enrolled in trial NCT03345914 (Pg. 1151, first ¶). As evidenced by NCT03345914, dupilumab was provided in a pre-filled syringe and administered subcutaneously (§ Intervention/Treatment).
Regarding Claims 37 and 39, the patient was administered omeprazole (a proton pump inhibitor) concomitant with the first 32 weeks of dupilumab treatment (Fig. 1; Pg. 1151, Col. 2, ¶1).
Regarding Claim 40, Bawany teaches the patient achieved a decrease in peak eosinophil when measured at 70 weeks of treatment (Fig. 2; Pg. 1151, Col. 2, ¶1).
Claims 1-4, 6-8, 10, 12-15, 34, and 37-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Journal of pediatric gastroenterology and nutrition, 75(2), 192-195.; IDS dated 08/05/2024), herein “Patel”, as evidenced by the instant specification
Regarding Claims 1-2 and 14, Patel teaches treatment of a 9-year-old patient (“Patient 3”) having eosinophilic esophagitis (EoE) (Pg. 194, Col. 2, last ¶) via administration of dupilumab (Pg. 195, ¶1).
Regarding Claims 1 and 12-13, dupilumab is an anti-IL-4R antibody comprising each of the instantly claimed sequence, as evidenced by the instant specification (see ¶070 and Table 7).
Regarding Claim 3, Patel teaches the patient had 35, 45, and 65 eos/hpf as measured by biopsy of the proximal, mid, and distal esophagus (Pg. 195, ¶1).
Regarding Claim 4, Patel teaches the patient had previously been treated with a PPI and swallowed fluticasone (Pg. 195, ¶1).
Regarding Claims 6-7, Patel teaches the patient had concomitant atopic dermatitis (AD) (Pg. 195, ¶1).
Regarding Claim 8, Patel teaches that the patient had gained 18 lb (~8kg) on therapy prior to administration of dupilumab, indicating the patient weighed at least greater than 5kg.
Regarding Claim 10, Patel teaches of another patient, age 7 (“Patient 1”) presenting with EoE and treated with dupilumab that had a baseline IgE level of 1801 kU/L (Pg. 193, § Results, ¶2).
Regarding Claims 15 and 34, Patel teaches the patient was administered 300 mg dupilumab every 2 weeks (Pg. 195, ¶1).
Regarding Claims 37-38, Patel teaches the patient received dupilumab in combination with dietary elimination (Pg. 195, ¶1).
Claims 1-2, 11-14, 36, and 42-44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials.gov ID: NCT04394351 (Version 2021-05-19; https://clinicaltrials.gov/study/NCT04394351?tab=history&a=9#version-content-panel; PTO-892), herein “NCT04394351”, as evidenced by the instant specification.
Regarding Claims 1-2 and 14, NCT04394351 teaches a method of treating pediatric patients aged 1-11 with eosinophilic esophagitis (EoE) via administration of dupilumab (Title; § Eligibility; § Arms and Interventions).
Regarding Claims 1 and 12-13, dupilumab is an anti-IL-4R antibody comprising each of the instantly claimed sequence, as evidenced by the instant specification (see ¶070 and Table 7).
Regarding Claim 11, NCT04394351 teaches for example body weight <5 kg or ≥60 kg at screening and active H. pylori as among the study’s exclusion criteria (§ Key Exclusion Criteria).
Regarding Claims 36 and 42-44, NCT04394351 teaches the dupilumab is administered subcutaneously and provided as a single use pre-filled syringe (§ Arms and Interventions).
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.
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 nonobviousness.
Claims 8-9, 19, 23, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov ID: NCT04394351 (Version 2021-05-19; https://clinicaltrials.gov/study/NCT04394351?tab=history&a=9#version-content-panel; PTO-892), herein “NCT04394351”.
The teachings of NCT04394351 are summarized above.
Regarding Claims 8-9, 19, 23, and 26 NCT04394351 teaches that patients weighing less than 5 kg or greater than 60 kg were excluded from the study (§ Key Exclusion Criteria).
NCT04394351 further teaches that the dupilumab is administered at a tiered dosing regimen based on body weight (§ Arms and Interventions)
Although NCT04394351 is silent on the particular weight ranges that were expressly included, it would have been obvious to one of ordinary skill in the art that the method of treating EoE in children according to NCT04394351 could include those weighing between 5 kg and 60 kg, including those from subgroups such as 5-15kg, 15-30kg, and 30-60kg. The skilled artisan would have been motivated to choose patients within these weight ranges – and there would have been a reasonable expectation of success – because NCT04394351 teaches that dosing is tiered based on body weight and that patients outside these ranges were excluded from the study.
Claims 29-31 and 44-46 are rejected under 35 U.S.C. 103 as being unpatentable over Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as evidenced by ClinicalTrials.gov ID: NCT03345914 (Version 2020-08-13; https://clinicaltrials.gov/study/NCT03345914; PTO-892), as applied to claims 1 and 42-43 above, and further in view of Bansal 2019 (US 2019/0345253 A1; IDS dated 10/04/2023), herein “Bansal”.
The teachings of Bawany are summarized above.
Regarding instant Claims 29-31, Bawany further teaches that the patient continued to be treated and received the same dose of dupilumab when the patient was >12 years old (Pg. 1151, ¶1; Fig. 1B).
However, Bawany does not teach patients weighing >60 kg nor a 300mg dose. This deficiency is cured by Bansal.
Bansal teaches patients with atopic dermatitis aged 12 or older and weighing 60 kg or more are treated with 300mg dupilumab every week or every two weeks (Bansal claims 41, 50-52, 62), whereas those weighing less than 60 kg are treated at 200mg (Bansal claim 49).
It would have been obvious to one of ordinary skill in the art to modify the method of treating EoE with dupilumab as taught by Bawany to include patients weighing greater than 60kg treated at a dose of 300 mg every week or every two weeks as taught by Bansal. The skilled artisan would have been motivated to do so because Bansal teaches that patients weighing more are administered a higher dose of antibody than those that weight less. There would have been a reasonable expectation of success because Bansal teaches that patients weighing more than 60kg are administered a 300mg dose QW or Q2W and Bawany teaches that dupilumab effectively treats both atopic dermatitis and concomitant EoE and that the dose administered when the patient was older than 12 years was the same dose as when the patient was younger than 12 years.
Additionally, regarding Claims 44-46, Bawany does not teach a single dose prefilled syringe, an autoinjector, or a pen delivery device. This deficiency is cured by Bansal.
Bansal teaches IL-4R antibody dupilumab is administered subcutaneously and can be supplied and delivered in a variety of formats including a single dose prefilled syringe, an autoinjector, or a pen delivery device (¶0065-0066; Bansal claims 62, & 64-71).
It would have been obvious to substitute the dupilumab prefilled syringe taught by Bawany with any of the alternative delivery devices taught by Bansal, including a single dose prefilled syringe, an autoinjector, or a pen delivery device. The skilled artisan would have recognized that each of the devices described in Bawany would have been suitable to achieve the same outcome of subcutaneous dupilumab injection, and there would have been a reasonable expectation of success because Bansal teaches that pharmaceutical compositions comprising dupilumab can be used with each of said delivery devices.
Claims 17-18, 20-22, 24-25, 27, 32-33, 35, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as applied to Claims 1-9, 12-16, 26, 28, 34, 36-37, 39-40, and 42-43 above, and further in view of ClinicalTrials.gov ID: NCT04394351 (Version 2021-05-19; https://clinicaltrials.gov/study/NCT04394351?tab=history&a=9#version-content-panel; PTO-892), herein “NCT04394351”, as applied to Claims 1-2, 8-9, 11-14, 19, 23, and 26 above.
The teachings of Bawany and NCT04394351 are summarized above.
Claims 17-18, 20-22, 24-25, 27, 32-33, and 35 in general are drawn to a variety of particular doses and variations of said doses wherein subjects weighing more are administered a greater amount of the IL-4R antagonist (e.g. 300 mg QW for subjects >40kg; Claim 33), subjects weighing less are administered a lower amount of the IL-4R antagonist (e.g. 100 mg Q2W for subjects 5-15kg), and/or wherein more drug is administered less frequently or less drug administered more frequently (e.g. Claims 20-21; 100mg Q2W or 200mg Q3W).
Although Bawany teaches effective treatment of a pediatric patient with EoE with subcutaneous dupilumab at 200mg Q2W and NCT04394351 teaches that dupilumab dosing in of children aged 1-11 is tiered based on body weight, the prior art does not teach the particular doses and/or schedules recited in instant 17-18, 20-22, 24-25, 27, 32-33, and 35.
However, the courts have held “[w]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP §2144.05). Moreover, it is well settled that “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272,276, 205 USPQ2d 1843, 1847-48 (Fed. Cir. 1989).
In the instant case, the prior art teaches both a particular species of dose within the range of the instant claims (i.e. 200mg Q2W for a patient weighing ~31kg; as applied to instant Claims 16, 26, 28, and 34 above; See Bawany) and that dupilumab is administered in a weight-tiered dosing scheme (see NCT04394351). Accordingly, discovery of the “optimal” dose for each particular weight category through routine optimization is conventional and well within the purview of one of ordinary skill in the art, and the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
In addition, regarding instant Claim 41, NCT04394351 teaches that the primary outcome measure is the proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf following 16 weeks of treatment (§ Outcome Measures).
Although neither NCT04394351 nor Bawany report particular patient outcomes at the 16-week time point, such a result would have been inherent to the method of treating EoE in patients younger than 12 years of age according to Bawany and NCT04394351. There would have been a reasonable expectation of success because the prior art teaches treatment of the same disease (EoE) in the same patient population (children less than 12 years old) with the same therapeutic (dupilumab) administered at the same dose (e.g. 200mg Q2W), and because Bawany teaches a case study of an individual patient having achieved dramatic improvements in EoE symptoms following said 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 1-10, 12-16, 26, 28, 34, 36-40, 42-43, and 45-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-46 of U.S. Patent No. 9,290,574
Claims 1-20 of U.S. Patent No. 10,730,948
Claims 1-16 of U.S. Patent No. 11,421,036
Claims 1-27 of U.S. Patent No. 12,291,571
in view of Kostic et al. 2015 (US 2015/0017176 A1; IDS dated 10/04/2023), herein “Kostic”, and Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as evidenced by the instant specification and ClinicalTrials.gov ID: NCT03345914 (Version 2020-08-13; https://clinicaltrials.gov/study/NCT03345914; PTO-892), herein “NCT03345914”.
The claims of ‘574, ‘948, ‘036, and ‘571 are drawn to a method of treating eosinophilic esophagitis comprising administering an interleukin-4 receptor (IL-4R) inhibitor.
Regarding instant Claims 1 and 12-14, ‘574 claims 9-13, 24-28, and 41-45, ‘948 claims 17-20 are drawn to IL-4R inhibitor dupilumab and sequences thereof.
Regarding instant Claim 3, ‘574 claim 1, ‘036 claim 2, and ‘571 claims 1 and 19 are drawn to patients having ≥15 eos/hpf.
Regarding instant Claims 6-7, ‘574 claims 15 and 30, ‘948 claim 5, ‘571 claims 6-7 are drawn to treatment of a subject having concomitant atopic disease.
Regarding instant Claims 37-39, ‘574 claims 14, 29, 46, ‘948 claim 14, are drawn to additional therapeutics including a proton pump inhibitor or diet management.
Regarding instant Claim 36, ‘948 claim 9, ‘036 claims 1 and 7, and ‘571 claims 8 and 24 are drawn to the antibody administered subcutaneously.
Regarding instant Claims 42-43 and 45-46 ‘036 claims 15-16 and ‘571 claims 25-27 are drawn to the antibody contained in a syringe or pen delivery device.
The claims of ‘574, ‘948, ‘036, and ‘571 are not drawn to the instantly claimed patient population of subjects <12 years old. Kostic and Bawany render this limitation obvious.
Each of patents ‘574, ‘948, ‘036, and ‘571 comprise the same disclosure as published in Kostic et al. 2015 (US 2015/0017176 A1).
Regarding instant Claims 1 and 12-14, Kostic teaches a method of treating EoE comprising administering an IL-4R antibody (Abstract) wherein the antibody is dupilumab (Abstract; ¶0009).
Regarding instant Claims 1-2, Kostic teaches that “the methods herein may be used to treat EoE in children”, including those aged 3, 4, 5, 6 years, etc. (¶0029).
Regarding instant Claims 42-43 and 45-46, Kostic teaches the IL-4R antibody can be contained within a prefilled syringe or pen delivery device (¶0061). Regarding instant Claim 45, a pen device satisfies the limitation of “autoinjector” as evidenced by ¶094 of the instant specification.
Regarding Claims 1-2 and 14, Bawany teaches treatment of a 9-year-old patient (i.e. ≥1 year and < 12 years old; Pg. 1150, Col. 1, ¶2) having eosinophilic esophagitis (EoE; Pg. 1151, Col. 2, ¶1) via administration of anti-IL-4Rα antibody dupilumab wherein treatment of said patient resulted in objective improvement in all comorbid allergic conditions (Introduction).
Regarding the sequences recited in Claims 1 and 12-13, each claimed sequence is the same as those comprised within dupilumab as evidenced by ¶070 and Table 7 of the instant specification (Pg. 64; SEQ ID NOs: 1-10).
Regarding Claim 3, Bawany teaches the patient had 5 to 25 intraepithelial eosinophils per high-power field as measured by esophageal biopsies at 21, 24, and 26 cm (i.e. proximal, mid, and distal) (Pg. 1151, Col. 2, ¶1).
Regarding Claims 4-5, Bawany teaches the patient was previously treated with omeprazole (i.e. a proton pump inhibitor), which yielded “only limited histological improvement” (i.e. inadequately responsive) (Pg. 1151, Col. 2, ¶1).
Regarding Claims 6-7, Bawany teaches the patient had concomitant atopic dermatitis (Introduction).
Regarding Claims 8-9, 16, and 26, Bawany teaches at baseline the patient was receiving 100 mg/d cyclosporine, which was the equivalent of 3.2 mg/kg/d (Pg. 1150, last ¶). Accordingly, at baseline the patient taught by Bawany weighed approximately 31.25 kg.
Regarding Claims 15-16, 28, and 34, Bawany teaches the patient received 200 mg dupilumab every 2 weeks (Q2W) (Pg. 1151, first ¶).
Regarding Claims 36 and 42-43, Bawany teaches that the patient was enrolled in trial NCT03345914 (Pg. 1151, first ¶). As evidenced by NCT03345914, dupilumab was provided in a pre-filled syringe and administered subcutaneously (§ Intervention/Treatment).
Regarding Claims 37 and 39, the patient was administered omeprazole (a proton pump inhibitor) concomitant with the first 32 weeks of dupilumab treatment (Fig. 1; Pg. 1151, Col. 2, ¶1).
Regarding Claim 40, Bawany teaches the patient achieved a decrease in peak eosinophil when measured at 70 weeks of treatment (Fig. 2; Pg. 1151, Col. 2, ¶1).
It would have been obvious to one of ordinary skill in the art to adapt the method of treating EoE according to the claims of ‘574, ‘948, ‘036, and ‘571 to treat children under the age of 12, as taught by Bawany and Kostic. There would have been a reasonable expectation of success because both the claims of ‘574 and the treatment method of both Bawany and Kostic encompass use of the same antibody (dupilumab), because Kostic teaches that the methods disclosed therein can be applied to children, and because Bawany teaches that treatment of a pediatric patient with dupilumab resulted in substantial improvements in EoE symptoms.
Further, regarding instant Claim 10, ‘574 claims 6, 21, and 31, ‘948 claims 4 and 8, and ‘571 claim 3 are drawn to the method wherein the patient has an elevated serum level of IgE.
In addition, Kostic teaches that the EoE patient population may be identified by elevated biomarker such as IgE and that IgE levels greater than 150kU/L are considered elevated (¶0021, 0023).
Although Kostic does not teach the particular baseline IgE level of at least 400 IU/L, it would have been obvious that the method claims of ‘574, ‘948, ‘036, and ‘571 in view of Kostic and Bawany could further be used to treat patients with very high IgE levels at baseline (> 400 IU/L). There would have been a reasonable expectation of success because Kostic teaches that patients in need of treatment can be identified by elevated IgE levels.
Claims 11, 17-25, 27, 32-33, 35, 41, 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-46 of U.S. Patent No. 9,290,574
Claims 1-20 of U.S. Patent No. 10,730,948
Claims 1-16 of U.S. Patent No. 11,421,036
Claims 1-27 of U.S. Patent No. 12,291,571
in view of Kostic et al. 2015 (US 2015/0017176 A1; IDS dated 10/04/2023), herein “Kostic”, and Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as evidenced by the instant specification and ClinicalTrials.gov ID: NCT03345914 (Version 2020-08-13; https://clinicaltrials.gov/study/NCT03345914; PTO-892), herein “NCT03345914, as applied to claims 1-10, 12-16, 26, 28, 34, 36-40, 42-43, and 45-46 above, and further in view of ClinicalTrials.gov ID: NCT04394351 (Version 2021-05-19; https://clinicaltrials.gov/study/NCT04394351?tab=history&a=9#version-content-panel; PTO-892), herein “NCT04394351”.
The claims of ‘574, ‘948, ‘036, and ‘571 and the teachings of Bawany and Kostic are summarized above. The claims of ‘574, ‘948, ‘036, and ‘571 in view of the teachings of Bawany and Kostic are not drawn to the exclusion criteria of instant Claim 11, the particular patient weights and doses recited in the instant claims, the specific outcomes of instant Claim 41, nor a single dose prefilled syringe of instant Claim 44. These limitations are rendered obvious by NCT04394351.
NCT04394351 teaches a method of treating pediatric patients aged 1-11 with eosinophilic esophagitis (EoE) via administration of dupilumab (Title; § Eligibility; § Arms and Interventions).
Regarding instant Claim 11, NCT04394351 teaches for example body weight <5 kg at screening and active H. pylori as among the study’s exclusion criteria (§ Key Exclusion Criteria).
Regarding instant Claim 44, NCT04394351 teaches the dupilumab is administered subcutaneously and provided as a single use pre-filled syringe (§ Arms and Interventions).
It would have been obvious to one of ordinary skill in the art the method of treating EoE in children with dupilumab according to claims of ‘574, ‘948, ‘036, and ‘571 in view of Bawany and Kostic could further encompass the exclusion criteria and prefilled syringe of NCT04394351. There would have been a reasonable expectation of success because NCT04394351 encompasses treatment of the same patient population (EoE in children under 12 years old) taught by Bawany and Kostic with the same therapeutic (dupilumab) encompassed by the claims of ‘574, ‘948, ‘036, and ‘571.
Regarding instant Claims 17-25, 27, 32-33, 35, NCT04394351 further teaches that the dupilumab is administered at a tiered dosing regimen based on body weight (§ Arms and Interventions)
Instant Claims 17-25, 27, 32-33, 35 in general are drawn to a variety of particular doses and variations of said doses wherein subjects weighing more are administered a greater amount of the IL-4R antagonist (e.g. 300 mg QW for subjects >40kg; Claim 33), subjects weighing less are administered a lower amount of the IL-4R antagonist (e.g. 100 mg Q2W for subjects 5-15kg), and/or wherein more drug is administered less frequently or less drug administered more frequently (e.g. Claims 20-21; 100mg Q2W or 200mg Q3W).
Although Bawany teaches effective treatment of a pediatric patient with EoE with subcutaneous dupilumab at 200mg Q2W and NCT04394351 teaches that dupilumab dosing in of children aged 1-11 is tiered based on body weight, the prior art does not teach the particular doses and/or schedules recited in instant claims 17-25, 27, 32-33, 35.
However, the courts have held “[w]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP §2144.05). Moreover, it is well settled that “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272,276, 205 USPQ2d 1843, 1847-48 (Fed. Cir. 1989).
In the instant case, the prior art teaches both a particular species of dose within the range of the instant claims (i.e. 200mg Q2W for a patient weighing ~31kg; as applied to instant Claims 16, 26, 28, and 34 above; See Bawany) and that dupilumab is administered in a weight-tiered dosing scheme (see NCT04394351). Accordingly, discovery of the “optimal” dose for each particular weight category through routine optimization is conventional and well within the purview of one of ordinary skill in the art, and the courts, over a period of over 50 years, have consistently held that treatment (i.e. dosage and intervals) optimization is obvious.
In addition, regarding instant Claim 41, NCT04394351 teaches that the primary outcome measure is the proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf following 16 weeks of treatment (§ Outcome Measures).
Although neither NCT04394351 nor Bawany report particular patient outcomes at the 16-week time point, such a result would have been inherent to the method of treating EoE in patients younger than 12 years of age according to Bawany and NCT04394351. There would have been a reasonable expectation of success because the prior art teaches treatment of the same disease (EoE) in the same patient population (children less than 12 years old) with the same therapeutic (dupilumab) administered at the same dose (e.g. 200mg Q2W), and because Bawany teaches a case study of an individual patient having achieved dramatic improvements in EoE symptoms following said treatment.
Claims 29-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-46 of U.S. Patent No. 9,290,574
Claims 1-20 of U.S. Patent No. 10,730,948
Claims 1-16 of U.S. Patent No. 11,421,036
Claims 1-27 of U.S. Patent No. 12,291,571
in view of Kostic et al. 2015 (US 2015/0017176 A1; IDS dated 10/04/2023), herein “Kostic”, and Bawany et al. 2020 (JAAD case reports, 6(11), 1150-1152.; PTO-892), herein “Bawany”, as evidenced by the instant specification and ClinicalTrials.gov ID: NCT03345914 (Version 2020-08-13; https://clinicaltrials.gov/study/NCT03345914; PTO-892), herein “NCT03345914, as applied to claims 1-10, 12-16, 26, 28, 34, 36-40, 42-43, and 45-46 above, and further in view of Bansal 2019 (US 2019/0345253 A1; IDS dated 10/04/2023), herein “Bansal”.
The claims of ‘574, ‘948, ‘036, and ‘571 and the teachings of Kostic and Bawany are summarized above.
Regarding instant Claims 29-31, Bawany further teaches that the patient continued to be treated and received the same dose of dupilumab when the patient was >12 years old (Pg. 1151, ¶1; Fig. 1B).
The claims of ‘574, ‘948, ‘036, and ‘571 in view of Kostic and Bawany are not drawn to patients weighing >60 kg nor a 300mg dose. This deficiency is cured by Bansal.
Bansal teaches patients with atopic dermatitis aged 12 or older and weighing 60 kg or more are treated with 300mg dupilumab every week or every two weeks (Bansal claims 41, 50-52, 62), whereas those weighing less than 60 kg are treated at 200mg (Bansal claim 49).
It would have been obvious to one of ordinary skill in the art to modify the method of treating EoE with dupilumab in children as encompassed by the claims of ‘574, ‘948, ‘036, and ‘571 in view of Kostic and Bawany to include patients weighing greater than 60kg treated at a dose of 300 mg every week or every two weeks as taught by Bansal. The skilled artisan would have been motivated to do so because Bansal teaches that patients weighing more are administered a higher dose of antibody than those that weight less. There would have been a reasonable expectation of success because Bansal teaches that patients weighing more than 60kg are administered a 300mg dose QW or Q2W and Bawany teaches that dupilumab effectively treats both atopic dermatitis and concomitant EoE and that the dose administered when the patient was older than 12 years was the same dose as when the patient was younger than 12 years.
Conclusion
No claim is allowed.
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/BRYAN WILLIAM HECK/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643