Status of Claims/Rejections
The previous rejections over Beck et al. and Martin are withdrawn. The current amendments apply more congruently to Graham, as will be discussed in the new grounds of rejection below. The new grounds of rejection are under 35 USC 102(A)(1) and non-statutory double patenting, in view of Graham et al.
Claim Rejections 35 USC 102(A)(1)
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, 29 and 48-62 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Graham et al. (US2014/0072583 A1).
Graham teaches the dosing regimens for treating atopic dermatitis with the antibody or that specifically binds IL-4R, which comprises three heavy chain complementarity determining region (HCDR) sequences comprising SEQ ID NOs: 148, 150, 152, respectively, and three light chain complementarity determining (LCDR) sequences comprising SEQ ID NOs: 156, 158 and 160, respectively, which are part of a full human anti-hIL-4R antibody [0224, Table 1, see example 1]. Graham specifically teaches methods to treat AD in patients resistant, non-responsive or inadequately responsive to treatment with a topical corticosteroid (TCS) or a calcineurin inhibitor [0109]. Graham also teaches that "resistant, non-responsive or inadequately responsive to a TCS or a calcineurin inhibitor" refers to subjects or patients with AD who have been treated with a TCS or a calcineurin inhibitor and wherein the TCS/calcineurin inhibitor does not have a therapeutic effect. Graham teaches full human antibodies, where the term “antibody,” refers to immunoglobulin molecules comprising four polypeptide chains, two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, as well as multimers thereof (e.g., IgM), each heavy chain comprises a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region, where the heavy chain constant region comprises three domains, CH1, CH2 and CH3 and each light chain comprises a light chain variable region (LCVR or VL) and a light chain constant region. The light chain constant region comprises one domain (CL1). The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDRs), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 [0169]. Graham teaches that anti-IL-4R antibody may be identical to the human germline sequences, and that conventional therapeutic agents include systemic and topical corticosteroids (TCS), calcineurin inhibitors, anti-histamines, oral immunosuppressants, and glucocorticoids, systemic immunosuppressants such as methotrexate, cyclosporine, and azathioprine, but that these conventional treatments have numerous and considerable adverse side effects including diabetes, hypertension, osteoporosis, myelosuppression, nephrotoxicity, hepatotoxicity, leucopenia, an increased risk of microbial infections, dyspigmentation, acneiform eruptions and risks associated with systemic absorption including skin malignancies and lymphomas [0147].
Graham also teaches methods of treating AD comprising administering to a subject a pharmaceutical composition comprising an IL-4R antagonist at a dosing frequency of about four times a week, twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every eight weeks, once every twelve weeks, or less frequently, so long as a therapeutic response is achieved [0212-0213]. Graham further teaches methods comprising administering to a subject a pharmaceutical composition comprising an IL-4R antagonist at a dosing frequency of about four times a week, twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every eight weeks, once every twelve weeks, or less frequently so long as a therapeutic response is achieved [0214]. In certain embodiments administration of a pharmaceutical comprising an anti-IL-4R antibody, once a week dosing at about 75 mg, 150mg, or 300mg [0214]. Additionally, other therapeutics can be administered at the same time, such as another IL-4R antagonist, an IL-1 antagonist (including, e.g., an IL-1 antagonist as set forth in U.S. Pat. No. 6,927,044), an IL-6 antagonist, an IL-6R antagonist (including, e.g., an anti-IL-6R antibody as set forth in U.S. Pat. No. 7,582,298), an IL-13 antagonist, a TNF antagonist, an IL-8 antagonist, an IL-9 antagonist, an IL-17 antagonist, an IL-5 antagonist, an IgE antagonist, a CD48 antagonist, an IL-31 antagonist, antibiotics, topical corticosteroids, tacrolimus, pimecrolimus, cyclosporine, azathioprine, methotrexate, cromolyn sodium, proteinase inhibitors, or combinations thereof [0210]. The following table shows the dosing regimen of this mAb1 composition for patients with AD:
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390
420
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[0394].
In this example, all patients received 2 injections (a loading dose) on day 1, which is 600mg total for the loading dose, followed by injections of 2ml each, followed by weekly injections of 300mg for every 2 weeks (q2w), where the next dose of study drug was administered at week 2 and week 4, respectively [0395]. Graham further teaches that patients received a loading dose on day 1, consisting of a doubling of the nominal dose that was administered at subsequent visits, which allowed systemic concentrations of mAb1 to reach steady state and the targeted systemic concentration faster, potentially reducing the time to clinical benefit [0404]. This reference teaches that the study treatment was administered for 16 weeks so that systemic concentrations of functional mAb1 could stabilize for all dose-regimens [0404]. Graham also teaches that the NRS scores of the subjects improved, as summarized in the following table:
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710
562
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This reference meets the limitations of claims 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above). As to the inadvisable and non-responsive/inadequately responsive or intolerant limitations to systemic immunosuppressants, Graham teaches that “inadequate response represented failure to achieve and maintain remission or a low disease activity state,” (e.g., IGA 0=clear to 2=mild) despite treatment with topical corticosteroids of medium to high potency, applied daily for at least 28 days or for the maximum duration recommended by the product prescribing information, also considers important side effects or safety risks that outweigh the potential treatment benefits (e.g., hypersensitivity reactions, significant skin atrophy, systemic effects, etc., or imminence thereof), as assessed by the investigator or by patient's treating physician [0415]. As such, the inclusion criteria meets both the limitations of “inadvisable,” as well as the limitations of being previously treated with an immunosuppressant. The 16 week limitation is met because the loading dose is initial, and there are 15 more weeks in the regimen. As to the new limitation requiring the NRS score achieve a
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered additional agents including topical and systemic corticosteroids, and other immunosuppressant/immunomodulating agents substances [0147, 0416; see inclusion criteria for subjects]. Additionally, the study was designed to treat subjects for which the previous treatments were ineffective, which encompasses the entire patient class to which any systemic treatment was given or inadvisable. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS’s, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham also teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470].
As t claims 60-62, Graham teaches that the pharmaceutical compositions can be delivered subcutaneously or intravenously with a standard needle and syringe, a pen delivery device readily has applications in delivering a pharmaceutical composition that are reusable or disposable, including autoinjectors [0199-0200].
As such, the claims are anticipated by Graham et al.
Response to Arguments/Remarks
Applicant's arguments filed 11/04/25 have been fully considered but they are not persuasive. Applicants have argued that the amendments to the claims are not disclosed by Graham, rendering the specific combinations of the amendments which require the subject to have moderate to severe AD, for who a systemic immunosuppressant is unadvisable, or who was previously treated with an immunosuppressant. Graham teaches the latter limitation explicitly. The amendment to the dosage now requires it to be subcutaneously administered, with an initial dose of 600mg followed by 300mg every two weeks. Both of these limitations are taught by Graham, as discussed above. As to the he subject achieves a greater than or equal to 4-point improvement in Peak Pruritis Numerical rating scale from baseline at week 16, this is show by the above table, and also inherent to the method of delivering the same claimed composition to the same patient class, ass is supported by MPEP 2112, which states:
“[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Id.
As to the amendment requiring previous treatment with a systemic immunosuppressant, Graham teaches that same exact immunosuppressants administered prior to treatment and both teach treatment resistant human subjects. As to the “full human antibody” Graham teaches that the antibodies mAb1 are full human antibodies.
Therefore, the above new grounds of rejection meets the limitations of the amended and new claims 1, 29 and 48-62.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) 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).
Filing 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, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,167,004 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘004 are the following:
1. A method of treating atopic dermatitis (AD), the method comprising: administering to a subject having moderate-to-severe AD a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that specifically binds IL-4R, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:3, the HCDR2 comprises the amino acid sequence of SEQ ID NO:4, the HCDR3 comprises the amino acid sequence of SEQ ID NO:5, the LCDR1 comprises the amino acid sequence of SEQ ID NO:6, the LCDR2 comprises the amino acid sequence of SEQ ID NO:7, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:8; wherein the subject is non-responsive, inadequately responsive, or intolerant to treatment with a systemic immunosuppressant or wherein treatment with a systemic immunosuppressant is inadvisable.
2. The method of claim 1, wherein the systemic immunosuppressant is cyclosporine A (CSA).
3. The method of claim 2, wherein the subject is non-responsive, inadequately responsive, or intolerant to treatment with CSA.
4. The method of claim 2, wherein the subject has no prior exposure to CSA, and wherein treatment with CSA is inadvisable due to a condition selected from the group consisting of medical contraindications, hypersensitivity to CSA or excipients, use of a concomitant medication prohibited with CSA, increased susceptibility to CSA-induced renal damage, increased susceptibility to CSA-induced liver damage, and increased risk of serious infections.
5. The method of claim 1, wherein the subject has a concomitant disease or disorder selected from the group consisting of asthma, food allergy, seasonal allergy, house dust allergy, allergic rhinitis, and allergic conjunctivitis.
6. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:2.
7. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.
8. The method of claim 1, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.
9. The method of claim 1, wherein the IL-4R inhibitor is administered at a dose of about 50 mg to about 600 mg.
10. The method of claim 9, wherein the IL-4R inhibitor is administered at a dose of about 300 mg.
11. The method of claim 1, wherein the IL-4R inhibitor is administered at an initial dose followed by one or more secondary doses, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.
12. The method of claim 11, wherein the initial dose comprises about 600 mg of the IL-4R inhibitor, and each secondary dose comprises about 300 mg of the IL-4R inhibitor.
13. The method of claim 12, wherein each secondary dose is administered one week after the immediately preceding dose.
14. The method of claim 12, wherein each secondary dose is administered 2 weeks after the immediately preceding dose.
15. The method of claim 1, wherein the IL-4R inhibitor is administered subcutaneously
16. The method of claim 1, wherein the IL-4R inhibitor is contained in a syringe.
17. The method of claim 1, wherein the IL-4R inhibitor is contained in a pre-filled pen delivery device.
18. The method of claim 1, wherein the IL-4R inhibitor is contained in an autoinjector.
19. The method of claim 1, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent selected from the group consisting of a topical corticosteroid and a topical calcineurin inhibitor.
20. The method of claim 19, wherein the second therapeutic agent is a topical corticosteroid.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘004 is drawn to the same method of treating atopic dermatitis with the same peptide composition as instant claim 1.
The difference between the instant claims and the claims of ‘004 is that ‘004 does not teach treating atopic dermatitis flare ups, but teaches treating moderate to several AD itself, where the subject is non-responsive, inadequately responsive, or intolerant to treatment with a systemic immunosuppressant or where a systemic immunosuppressant is inadvisable. However, claim 1 of ‘004 still teaches a method of treating atopic dermatitis, which is the same patient class of instant claims 1, as it is drawn to treatment and prevention of flare ups in the same patient class of those with AD, and flare ups are the manifestation of the disease itself, making treatment of flare up and treatment of the disease inseparable when treated with the same composition.
The differences between the claims of 004 and the instant claims are rendered obvious by the teachings of Graham described supra.
Instant claims 29 and 50 are met because the same sequences are comprised in claims 6 and 7 of ‘004.
The remaining claims are rendered obvious by the teachings of Graham described supra.
This reference meets the limitations of claims 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant for AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above).
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered, additional agents including TCS’s and systemic corticosteroids [0416; see inclusion criteria]. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470]. Claims 60-62 are met because Graham teaches the same delivery methods.
As such, the claims are met by ‘004 and Graham et al.
As such, the instant application is obvious over the claims of ‘004.
Claims 1, 29 and 48-62are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,292,847 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘847 are drawn to the following:
1. A method for treating moderate-to-severe atopic dermatitis (AD) or improving an AD-associated parameter, the method comprising: administering an interleukin-4 receptor (IL-4R) inhibitor to a patient aged ≥12 years to <18 years with moderate-to-severe AD, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4Rα, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:3, the HCDR2 comprises the amino acid sequence of SEO ID NO. 4, the HCDR3 comprises the amino acid sequence of SEO ID NO:5, the LCDR1 comprises the amino acid sequence of SEO ID NO:6, the LCDR2 comprises the amino acid sequence of SEO ID NO:7, and the LCDR3 comprises the amino acid sequence of SEO ID NO. 8; wherein for a patient <60 kg in weight the IL-4R inhibitor is administered at (i) an initial dose of about 400 mg of the IL-4R inhibitor followed by one or more secondary doses of about 200 mg of the IL-4R inhibitor, wherein each secondary dose is administered two weeks after the immediately preceding dose; or for a patient ≥60 kg in weight the IL-4R inhibitor is administered at an initial dose of about 600 mg of the IL-4R inhibitor followed by one or more secondary doses of about 300 mg of the IL-4R inhibitor, wherein each secondary dose is administered two weeks after the immediately preceding dose.
2. The method of claim 1, wherein prior to or at the start of treatment the patient has an attribute selected from the group consisting of: (i) the patient has a baseline Investigator's Global Assessment (IGA) score=4; (ii) the patient has a baseline IGA score ≥3; (iii) the patient has a baseline Eczema Area and Severity (EASI) score ≥16; (iv) the patient has a baseline Pruritus Numerical Rating Scale (NRS) average score ≥4; (v) the patient has a ≥10% body surface area (BSA) of AD involvement at baseline; (vi) the patient has been previously treated with a topical AD medication; and (vii) the patient has a concomitant disease or disorder selected from the group consisting of food allergy, asthma, seasonal allergy, allergic conjunctivitis, allergic rhinitis, chronic rhinosinusitis, nasal polyps, house dust allergy, hives, and eosinophilic esophagitis.
3. The method of claim 1, wherein the patient has moderate-to-severe AD that is not adequately controlled with topical AD therapy.
4. The method of claim 1, wherein the patient is a patient with moderate-to-severe AD for whom topical AD therapy is not advisable.
5. The method of claim 1, wherein the patient is <60 kg in weight, and wherein the IL-4R inhibitor is administered at an initial dose of 400 mg followed by one or more secondary doses of 200 mg, wherein each secondary dose is administered two weeks after the immediately preceding dose.
6. The method of claim 1, wherein the patient is ≥60 kg in weight, and wherein the IL-4R inhibitor is administered at an initial dose of 600 mg followed by one or more secondary doses of 300 mg, wherein each secondary dose is administered two weeks after the immediately preceding dose.
7. The method of claim 1, wherein the administration of the IL-4R inhibitor results in an improvement a selected from the group consisting of: (i) an improvement of ≥75% in Eczema Area and Severity (EASI-75) from baseline to Week 16 after administration of the first dose of the IL-4R inhibitor, (ii) an improvement of ≥90% in Eczema Area and Severity (EASI-90) from baseline to Week 16 after administration of the first dose of the IL-4R inhibitor (iii) a reduction of ≥4 points in Peak Pruritus Numeric Rating Scale (NRS) score from baseline to Week 16 after administration of the first dose of the IL-4R inhibitor; (iv) achieving an Investigators Global Assessment (IGA) score of 0 or 1 by Week 16 after administration of the first dose of the IL-4R inhibitor, and/or (v) a reduction of ≥2 points in IGA score by Week 16 after administration of the first dose of the IL-4R inhibitor.
8. The method of claim 1, wherein the IL-4R inhibitor is administered in combination with a second therapeutic agent selected from the group consisting of a topical corticosteroid, a topical calcineurin inhibitor, an anti-histamine, an emollient, an anti-bacterial therapeutic, and a therapeutic agent for obstructive airway disease.
9. The method of claim 8, wherein the IL-4R inhibitor is administered combinations with topical corticosteroid.
10. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.
11. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.
12. The method of claim 1, wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.
13. The method of claim 1, wherein the IL-4R inhibitor is administered subcutaneously.
14. The method of claim 13, wherein the IL-4R inhibitor is contained in a container selected from the group consisting of a glass vial, a syringe, a pre-filled syringe, an autoinjector and a microinfuser.
15. The method of claim 1, wherein the IL-4R inhibitor is contained in a pre-filled syringe.
16. The method of claim 15, wherein the pre-filled syringe is a single-dose pre-filled syringe.
17. The method of claim 1, wherein the IL-4R inhibitor is contained in an autoinjector.
18. The method of claim 14, wherein the IL-4R inhibitor is contained in a volume of 1.15 mL.
19. The method of claim 14, wherein the IL-4R inhibitor is contained in a volume of 2.25 mL.
20. The method of claim 17, wherein the autoinjector comprises a pre-filled syringe.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘847 is drawn to the same method of treating atopic dermatitis with the same peptide composition as instant claims 1 teach treating severe atopic dermatitis with the same exact method of administering a composition comprising SEQ ID NOs: 3-8 (Same IL-4 fragments disclosed in 8,337,839, 10,370,449, 11,167,400, all dupilumab/RENG668 references, etc.).
Graham in combination with ‘847 meets the limitations of claim 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant for AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above).
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered, additional agents including TCS’s and systemic corticosteroids [0416; see inclusion criteria]. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470]. Claims 60-62 are met because Graham teaches the same delivery methods. As such, the claims are met by this combination.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,603,408 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘408 are drawn to the following:
1. A method of reducing susceptibility to a skin infection in a subject with atopic dermatitis, the method comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of an Interleukin-4 Receptor (IL-4R) antagonist to the subject in need thereof for a period of at least 12 weeks, wherein at the start of treatment a sample of skin from the subject is positive for microbial colonization by a microbe selected from the group consisting of Staphylococcus aureus, Streptococcus spp., Pseudomonas aeruginosa, Bacteroides spp., Herpes simplex virus, molluscum contagiosum virus, coxsackievirus, vaccinia virus, Candida albicans,Microsporum spp., Trichophyton spp., Penicillium spp., Cladosporium spp., Alternaria spp., and Aspergillus spp.; wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, wherein the antibody or antigen binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) of a heavy chain variable region (HCVR) comprising SEQ ID NO: 1, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) of a light chain, variable region (LCVR) comprising SEQ ID NO: 2; wherein the IL-4R antagonist is administered at an initial dose followed by one or more secondary doses, wherein the initial dose comprises about 50 mg to about 600 mg of the IL-4R antagonist and each secondary dose comprises about 25 mg to about 400 mg of the IL-4R antagonist, and wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.
2. The method of claim 1, wherein at the start of treatment a sample of skin from the subject is positive for microbial colonization by Staphylococcus aureus.
3. The method of claim 1, wherein the subject has moderate-to-severe atopic dermatitis.
4. The method of claim 1, wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8.
5. The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises an HCVR that comprises SEQ ID NO: 1 and an LCVR that comprises SEQ ID NO: 2.
6. The method of claim 1, wherein the anti-IL-4R antibody is dupilumab or a bioequivalent thereof.
7. The method of claim 1, wherein the initial dose comprises about 600 mg of the IL-4R antagonist, and each secondary dose comprises about 300 mg of the IL-4R antagonist.
8. The method of claim 7, wherein each secondary dose is administered one week after the immediately preceding dose.
9. The method of claim 7, wherein each secondary dose is administered 2 weeks after the immediately preceding dose.
10. The method of claim 1, wherein the IL-4R antagonist is administered subcutaneously.
11. The method of claim 1, wherein the IL-4R antagonist is contained in a container selected from the group consisting of a syringe, a glass vial, a pre-filled pen delivery device, and an autoinjector.
12. The method of claim 11, wherein the IL-4R antagonist is contained in a syringe.
13. The method of claim 11, wherein the IL-4R antagonist is contained in a glass vial.
14. The method of claim 11, wherein the IL-4R antagonist is contained in a pre-filled pen delivery device.
15. The method of claim 11, wherein the IL-4R antagonist is contained in an autoinjector.
16. The method of claim 1, wherein a second therapeutic agent is administered to the subject before, after, or concurrent with the pharmaceutical composition.
17. The method of claim 16, wherein the second therapeutic agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, another IL-4R antagonist, an IgE inhibitor, a corticosteroid, a non-steroid anti-inflammatory drug (NSAID), and IFNγ.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘408 is drawn to the same method of treating atopic dermatitis with the same peptide composition as instant claims 1.
The combination of ‘408 and Graham meets the limitations of claim 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant for AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above).
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered, additional agents including TCS’s and systemic corticosteroids [0416; see inclusion criteria]. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470]. Claims 60-62 are met because Graham teaches the same delivery methods. As such, the claims are met by this combination.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,370,449 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘449 are drawn to the following:
1. A method for treating, preventing or ameliorating a skin infection comprising: a) selecting a patient with moderate-to-severe atopic dermatitis and having a microbial infection; and b) administering a pharmaceutical composition comprising a therapeutically effective amount of an interleukin-4 receptor (IL-4R) antagonist to the patient in need thereof, wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα; wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) of a heavy chain variable region (HCVR) comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a light chain variable region (LCVR) comprising SEQ ID NO: 2; and wherein the IL-4R antagonist is administered at a dose of 75-600 mg.
2. The method of claim 1, wherein the skin infection is a bacterial infection.
3. The method of claim 1, wherein the skin infection is a viral infection.
4. The method of claim 1, wherein the skin infection is selected from the group consisting of impetigo, cellulitis, infected dermatitis, eczema herpeticum, folliculitis, infected blister, mycosis, tinea versicolor, Staphylococcus aureus infection, and Streptococcus infection.
5. The method of claim 4, wherein the skin infection is Staphylococcus aureus infection.
6. The method of claim 1, wherein the pharmaceutical composition is administered subcutaneously.
7. The method of claim 6, wherein the IL-4R antagonist is administered at a dose of 300 mg.
8. The method of claim 1, wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8.
9. The method of claim 8, wherein the HCVR comprises SEQ ID NO: 1 and the LCVR comprises SEQ ID NO: 2.
10. The method of claim 1, wherein the anti-IL-4Rα antibody is dupilumab or a bioequivalent thereof.
11. The method of claim 1, wherein a second therapeutic agent is administered to the subject before, after, or concurrent with the pharmaceutical composition.
12. The method of claim 11, wherein the second therapeutic agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, another IL-4R antagonist, an IgE inhibitor, a corticosteroid, a non-steroid anti-inflammatory drug (NSAID), and IFNγ.
13. A method of reducing microbial colonization of skin comprising: a) selecting a patient with moderate-to-severe atopic dermatitis and having microbial colonization in the skin; and b) sequentially administering a pharmaceutical composition comprising a therapeutically effective amount of an IL-4R antagonist at an initial dose followed by one or more secondary doses to the patient in need thereof, wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα; wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) of a HCVR comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a LCVR comprising SEQ ID NO: 2; and wherein the initial dose and the one or more secondary doses of the IL-4R antagonist are 75-600 mg.
14. The method of claim 13, wherein the colonization is of a microbe selected from the group consisting of Staphylococcus aureus, Streptococcus spp., Pseudomonas aeruginosa, Bacteroides spp., molluscum contagiosum virus, Herpes simplex virus, coxsackievirus, vaccinia virus, Candida albicans, Microsporum spp., Trichophyton spp., Penicillium spp., Cladosporium spp., Alternaria spp., and Aspergillus spp.
15. The method of claim 14, wherein the microbe is Staphylococcus aureus (S. aureus).
16. The method of claim 15, wherein the S. aureus colonization is reduced by at least 20% from the baseline.
17. The method of claim 13, wherein the IL-4R antagonist is administered at an initial dose of 600 mg followed by one or more secondary doses, and wherein each secondary dose comprises 300 mg and is administered weekly or biweekly.
18. The method of claim 13, wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8.
19. The method of claim 13, wherein the anti-IL-4Rα antibody is dupilumab or a bioequivalent thereof.
20. The method of claim 13, wherein a second therapeutic agent is administered to the subject before, after, or concurrent with the pharmaceutical composition.
21. The method of claim 20, wherein the second therapeutic agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, another IL-4R antagonist, an IgE inhibitor, a corticosteroid, NSAID, and IFNγ.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1, 7-9, 13 17 and 18 of ‘449 are drawn to the same method patient with moderate-to-severe atopic dermatitis with 75-600mg of the same peptide composition (SEQ ID NOS: 2-8) at a dosage and time interval that anticipates instant claims 1. The combination of ‘847 and Graham meets the limitations of claim 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant for AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above).
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered, additional agents including TCS’s and systemic corticosteroids [0416; see inclusion criteria]. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470]. Claims 60-62 are met because Graham teaches the same delivery methods. As such, the claims are met by this combination.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 8,337,839 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘839 et al. are drawn to the following:
1. A method of treating atopic dermatitis, said method comprising administering to a patient in need thereof an antibody or antigen-binding fragment thereof which specifically binds to a human interleukin-4 receptor, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) comprising the three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) from SEQ ID NO:162, and a light chain variable region (LCVR) comprising the three light chain CDRs (LCDR1, LCDR2 and LCDR3) from SEQ ID NO:164.
2. The method of claim 1, wherein: (a) the HCDR1 comprises SEQ ID NO:148; (b) the HCDR2 comprises SEQ ID NO:150; (c) the HCDR3 comprises SEQ ID NO:152; (d) the LCDR1 comprises SEQ ID NO:156; (e) the LCDR2 comprises SEQ ID NO:158; and (f) the LCDR3 comprises SEQ ID NO:160.
3. The method of claim 2, wherein the HCVR comprises SEQ ID NO:162.
4. The method of claim 2, wherein the LCVR comprises SEQ ID NO:164.
5. The method of claim 2, wherein the HCVR comprises SEQ ID NO:162 and the LCVR comprises SEQ ID NO:164.
This meets the limitations of claim 1 by teaching the same method of administering the same peptide (SEQ ID NOs: 148, 150, 152, 156, 158 and 160) are the same as instantly claimed SEQ ID NOs: 3-8, all drawn to IL-4R.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘839 is drawn to the same method of treating atopic dermatitis with the same peptide composition as instant claims 1.
The combination of ‘847 and Graham meets the limitations of claim 1 because the same full monoclonal human antibody mAb1 is administered to the same patient class – those having moderate to severe AD, who are resistant to previous systemic or topical immunosuppressant for AD treatment. As such, the same drug is administered to the same class of patients for the same purpose of treating AD and preventing flare-ups. The composition of mAB1 is identical to the claimed peptide, which is the IL-4R antagonist of the instant claims that comprises SEQ ID NOs: 148 (instantly claimed SEQ ID NO: 3), 150 (SEQ ID NO: 4), 152 (SEQ ID NO: 5), 156 (SEQ ID NO: 6), 158 (SEQ ID NO: 7), and 160 (SEQ ID NO: 8). Additionally, Graham teaches that same dosing regimen (see table 26, as discussed above).
Claims 29 and 50 are met because mAb1 comprises SEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 9 and SEQ ID NO: 10 (See above full length sequences). Claims 48, 49, 51-59 are met because Graham teaches that the subjects were previously administered, additional agents including TCS’s and systemic corticosteroids [0416; see inclusion criteria]. This reference also teaches that the additional systemic immunosuppressants can be administered in combination with TCS, concurrently or with the pharmaceutical composition comprising the IL-4R antagonist full monoclonal human antibody, meaning that the additional therapeutic agent is administered to the subject in a separate dosage form within less than 5 minutes (before, after, or at the same time) of administration of the pharmaceutical composition comprising the IL-4R antagonist, or administered to the subject as a single combined dosage formulation comprising both the additional therapeutic agent and the IL-4R antagonist mAb1 [0006, 0209, 0416]. As to the potency of the TCS, there is no specified level of potency recited in the claims and Graham teaches various levels of potency TCS and calcineurin inhibitors [e.g., see 0460, 0470]. As such,
As such, the claims are met by the combination of ‘847 and Graham et al.
Claims 1, 29 and 48-62 are also rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10,370,449 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘449 teach the following:
1. A method for treating, preventing or ameliorating a skin infection comprising: a) selecting a patient with moderate-to-severe atopic dermatitis and having a microbial infection; and b) administering a pharmaceutical composition comprising a therapeutically effective amount of an interleukin-4 receptor (IL-4R) antagonist to the patient in need thereof, wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα; wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) of a heavy chain variable region (HCVR) comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a light chain variable region (LCVR) comprising SEQ ID NO: 2; and wherein the IL-4R antagonist is administered at a dose of 75-600 mg.
2. The method of claim 1, wherein the skin infection is a bacterial infection.
3. The method of claim 1, wherein the skin infection is a viral infection.
4. The method of claim 1, wherein the skin infection is selected from the group consisting of impetigo, cellulitis, infected dermatitis, eczema herpeticum, folliculitis, infected blister, mycosis, tinea versicolor, Staphylococcus aureus infection, and Streptococcus infection.
5. The method of claim 4, wherein the skin infection is Staphylococcus aureus infection.
6. The method of claim 1, wherein the pharmaceutical composition is administered subcutaneously.
7. The method of claim 6, wherein the IL-4R antagonist is administered at a dose of 300 mg.
8. The method of claim 1, wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8.
9. The method of claim 8, wherein the HCVR comprises SEQ ID NO: 1 and the LCVR comprises SEQ ID NO: 2.
10. The method of claim 1, wherein the anti-IL-4Rα antibody is dupilumab or a bioequivalent thereof.
11. The method of claim 1, wherein a second therapeutic agent is administered to the subject before, after, or concurrent with the pharmaceutical composition.
12. The method of claim 11, wherein the second therapeutic agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, another IL-4R antagonist, an IgE inhibitor, a corticosteroid, a non-steroid anti-inflammatory drug (NSAID), and IFNγ.
13. A method of reducing microbial colonization of skin comprising: a) selecting a patient with moderate-to-severe atopic dermatitis and having microbial colonization in the skin; and b) sequentially administering a pharmaceutical composition comprising a therapeutically effective amount of an IL-4R antagonist at an initial dose followed by one or more secondary doses to the patient in need thereof, wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα; wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) of a HCVR comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a LCVR comprising SEQ ID NO: 2; and wherein the initial dose and the one or more secondary doses of the IL-4R antagonist are 75-600 mg.
14. The method of claim 13, wherein the colonization is of a microbe selected from the group consisting of Staphylococcus aureus, Streptococcus spp., Pseudomonas aeruginosa, Bacteroides spp., molluscum contagiosum virus, Herpes simplex virus, coxsackievirus, vaccinia virus, Candida albicans, Microsporum spp., Trichophyton spp., Penicillium spp., Cladosporium spp., Alternaria spp., and Aspergillus spp.
15. The method of claim 14, wherein the microbe is Staphylococcus aureus (S. aureus).
16. The method of claim 15, wherein the S. aureus colonization is reduced by at least 20% from the baseline.
17. The method of claim 13, wherein the IL-4R antagonist is administered at an initial dose of 600 mg followed by one or more secondary doses, and wherein each secondary dose comprises 300 mg and is administered weekly or biweekly.
18. The method of claim 13, wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8.
19. The method of claim 13, wherein the anti-IL-4Rα antibody is dupilumab or a bioequivalent thereof.
20. The method of claim 13, wherein a second therapeutic agent is administered to the subject before, after, or concurrent with the pharmaceutical composition.
21. The method of claim 20, wherein the second therapeutic agent is selected from the group consisting of an anti-bacterial agent, an anti-viral agent, an anti-fungal agent, another IL-4R antagonist, an IgE inhibitor, a corticosteroid, NSAID, and IFNγ.
The teachings of Graham et al. have been described supra.
These teachings render all claims to AD treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Claims 1, 29 and 48-62 are rejected under 35 U.S.C. 103 as being unpatentable over claims 1-5 of U.S. Patent No. 8,337,839 in view of Graham et al. (US2014/0072583 A1).
The claims of ‘839 teach the following:
1. A method of treating atopic dermatitis, said method comprising administering to a patient in need thereof an antibody or antigen-binding fragment thereof which specifically binds to a human interleukin-4 receptor, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) comprising the three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) from SEQ ID NO:162, and a light chain variable region (LCVR) comprising the three light chain CDRs (LCDR1, LCDR2 and LCDR3) from SEQ ID NO:164.
2. The method of claim 1, wherein: (a) the HCDR1 comprises SEQ ID NO:148; (b) the HCDR2 comprises SEQ ID NO:150; (c) the HCDR3 comprises SEQ ID NO:152; (d) the LCDR1 comprises SEQ ID NO:156; (e) the LCDR2 comprises SEQ ID NO:158; and (f) the LCDR3 comprises SEQ ID NO:160.
3. The method of claim 2, wherein the HCVR comprises SEQ ID NO:162.
4. The method of claim 2, wherein the LCVR comprises SEQ ID NO:164.
5. The method of claim 2, wherein the HCVR comprises SEQ ID NO:162 and the LCVR comprises SEQ ID NO:164.
The claims of ‘839 combined with the teachings of Graham et al. render all claims to AD treatment and prevention obvious when combined with applicants’ ‘839 teaching SEQ ID NOs: 2-8 for treating AD and in light of the obviousness of ranges discussed in MPEP 2144.05, as discussed above.
Provisional Double Patenting
The following are provisional double patenting rejections, which have been shortened for brevity, as the rejections are repetitive and rationale has been provided for all of the rejections of the instant claims over similar prior art work that teaches the same method.
Note that the claims of each provisional patent rejection are drawn to at least a method of treating atopic dermatitis with an anti-IL4R human antibody, which meets SEQ ID NOs: 3-8 for the reasons discussed above, and are all rendered obvious in view of Graham, via the same rationale as applied above to the above NSDP obviousness rejections.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application No. 18/499,679 in view of Graham et al. (US2014/0072583 A1).
The teachings of Graham et al. have been described supra.
These teachings render all claims to AD flare up treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application No. 17/821665 in view of Graham et al. (US2014/0072583 A1).
The teachings of Graham et al. have been described supra.
These teachings render all claims to AD flare up treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Claims 1-5, 8-15, 19-22 and 29-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1of U.S. Patent Application No. 17/687,051 in view of Graham et al. (US2014/0072583 A1).
The teachings of Graham et al. have been described supra.
The combination of these teachings render all claims to AD treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Claims 1-5, 8-15, 19-22 and 29-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent Application No. 17/907,070 in view of Graham et al. (US2014/0072583 A1).
The teachings of Graham et al. have been described supra.
These teachings render all claims to AD treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Claims 1, 29 and 48-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent Application No. 17/951,987 in view of Graham et al. (US2014/0072583 A1).
The teachings of Graham et al. have been described supra.
These teachings render all claims to AD treatment and prevention obvious when combined with applicants’ prior patents teaching SEQ ID NOs: 2-8 for treating AD.
Response to Arguments/Remarks
In light of the new grounds of rejection, applicants’ remarks regarding the ODP rejections are moot. The new grounds of rejection were applied, as described above. Any provisional rejections with later filing dates will be considered for withdrawal upon allowable subject matter being indicated. Currently, the rejections are upheld.
Conclusion
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.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654