DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment, filed 02/27/2024, has been entered.
Claims 1-89 have been canceled.
Claims 90-118 have been added.
Claims 90-118 are pending and currently under examination as they read on a method for treating type I interferon (IFN)-mediated disease comprising subcutaneously administering a dose of 120 mg a human monoclonal anti-IFNAR1 antibody, anifrolumab.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 90-118 are rejected under 35 U.S.C. 103 as being unpatentable over Higgs et al. (US 20150158949 A1) in view of Werth et al. (Arthritis Rheumatol. 2020; 72(Suppl 10): Abstract 0985); Furie et al. (Lancet Rheumatol, 2019, 1:e208-e219) and DePaz et al. (US 20170051066 A1).
Higgs teaches methods of treating type I IFN-mediated diseases comprising administering a fixed dose of an antibody that modulates type I IFN activity, including MEDI-546 (anifrolumab), a human monoclonal antibody that specifically binds IFNAR1 (paragraph 0124). Higgs teaches administration of MEDI-546 by various routes, including subcutaneous administration, and further teaches administering fixed doses approximately every week (QW) (paragraphs 0119-0122). Higgs also teaches administration of MEDI-546 at doses including 100 mg and teaches treatment of type I IFN-mediated diseases including myositis, lupus nephritis, and scleroderma (paragraphs 0124, 0002).
Given that Higgs teaches the same antibody, MEDI-546/anifrolumab, the antibody necessarily possesses the same HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 amino acid sequences, as well as the corresponding heavy- and light-chain variable region and heavy- and light-chain sequences, recited in the claims.
Higgs further teaches determining a patient’s type I interferon gene signature and treatment of patients having an elevated/high IFN gene signature with MEDI-546. Higgs teaches that administration of the antibody suppresses the type I IFN gene signature at fixed doses and results in improvement of the type I IFN-mediated disease (paragraph 0203). Accordingly, Higgs teaches the IFNGS-high patient-selection and IFNGS suppression aspects recited in the claims.
Higgs does not expressly teach treating cutaneous lupus erythematosus. Werth et al., however, teach treatment of cutaneous lupus disease with anifrolumab and report that anifrolumab treatment produces an early and sustained reduction in cutaneous lupus disease activity as measured by CLASI (see entire document). It would have been obvious to one of ordinary skill in the art to administer the MEDI-546/anifrolumab treatment taught by Higgs to a patient having cutaneous lupus erythematosus, as taught by Werth, because Werth demonstrates that the same antibody provides therapeutic benefit against cutaneous lupus manifestations (see Conclusion). Thus, one of ordinary skill would have had a reasonable expectation of successfully treating cutaneous lupus erythematosus with MEDI-546.
Higgs does not expressly teach administering MEDI-546 at a dose of 120 mg. Higgs, however, teaches administration of MEDI-546 at a dose of 100 mg and teaches that the amount and frequency of MEDI-546 administration may be varied to achieve a desired pharmacokinetic, pharmacodynamic, and/or therapeutic response, including suppression of the type I IFN gene signature. Thus, the amount of MEDI-546 administered was recognized in the prior art as a result-effective variable.
It would have been obvious to one of ordinary skill in the art at the time of the invention to optimize the amount of MEDI-546 administered, including increasing the expressly taught 100 mg dose to 120 mg, to obtain a desired degree and/or duration of type I IFN inhibition and therapeutic response. Higgs already teaches both subcutaneous administration and approximately once-weekly administration; therefore, selection of a 120 mg dose for the taught SC QW regimen would have amounted to routine optimization of a known result-effective variable with a reasonable expectation of success.
The 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 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847–48 (Fed. Cir. 1989) (determination of suitable dosage amounts through routine experimentation supported obviousness).
With respect to claims 98 and 99, the recited pharmacokinetic/plasma-concentration limitations are inherent properties resulting from administration of anifrolumab according to the claimed 120 mg SC QW regimen. As set forth above, the prior art renders obvious administration of the same antibody, by the same subcutaneous route, at the same 120 mg dose and once-weekly dosing frequency. Applicant’s own disclosure establishes that the recited pharmacokinetic properties are results produced by administration according to that regimen (see instant specification [0016]; Figure 8A).
Accordingly, performance of the otherwise obvious 120 mg SC QW method would necessarily produce the pharmacokinetic properties and plasma concentrations resulting from that regimen. Recitation or recognition of an inherent property or result of an otherwise obvious method does not render the method patentable.
Similarly, with respect to claim 107, Applicant’s disclosure establishes that administration according to the claimed 120 mg SC QW regimen provides the recited therapeutic effect relative to administration of 300 mg anifrolumab IV Q4W. Thus, once administration of 120 mg anifrolumab SC QW is rendered obvious for the reasons discussed above, the therapeutic effect recited in claim 107 is a result of performing that same treatment regimen rather than an additional manipulative step that distinguishes the claimed method.
Applicant’s disclosure is relied upon here not as prior art for establishing the obviousness of selecting the 120 mg SC QW regimen, but as evidence that the claimed pharmacokinetic and therapeutic results necessarily flow from performance of that regimen.
Higgs does not expressly teach the pharmaceutical formulation recited in claim 108. DePaz, however, teaches a pharmaceutical formulation comprising 150 mg/mL anifrolumab, 50 mM lysine HCl, 130 mM trehalose dihydrate, 0.05% polysorbate 80, and 25 mM histidine/histidine HCl, corresponding to the formulation recited in claim 108. DePaz teaches the formulation as a stable pharmaceutical formulation of the same anti-IFNAR1 antibody, anifrolumab/MEDI-546, suitable for parenteral administration (paragraph 0013).
It would have been obvious to one of ordinary skill in the art to administer the anifrolumab of Higgs using the pharmaceutical formulation taught by DePaz because DePaz expressly provides a formulation designed for pharmaceutical administration of the same antibody. One of ordinary skill therefore would have had both a reason to use the DePaz formulation in carrying out the Higgs treatment and a reasonable expectation of successfully doing so.
With respect to claims 110 and 115–116, Higgs further teaches that treatment with the type I IFN-modulating antibody may alleviate the need to co-administer a second therapeutic agent, expressly including a steroid, and may lessen the dosage of administration of the second agent (paragraph 147). Thus, Higgs expressly contemplates administering MEDI-546 in conjunction with corticosteroid therapy and subsequently reducing corticosteroid exposure.
Higgs does not expressly teach the particular prednisone-equivalent doses recited in claims 117–118. Furie et al., however, teach administration of anifrolumab in conjunction with corticosteroid therapy and teach tapering prednisone-equivalent corticosteroid treatment, including reduction from approximately 10 mg/day to 7.5 mg/day or less.
It would have been obvious to one of ordinary skill in the art to employ the prednisone dosing and tapering regimen taught by Furie in the method of Higgs because Higgs expressly teaches co-administration of steroids and reduction of the steroid dosage, while Furie teaches the particular prednisone-equivalent doses used during anifrolumab treatment. The combination would predictably reduce corticosteroid exposure while continuing anifrolumab treatment of the underlying type I IFN-mediated disease.
Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 90-118 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,493,570 in view of Higgs et al. (US 20150158949 A1); Werth et al. (Arthritis Rheumatol. 2020; 72(Suppl 10): Abstract 0985); Furie et al. (Lancet Rheumatol, 2019, 1:e208-e219) and DePaz et al. (US 20170051066 A1).
The patent claim discloses a method of treating SLE comprising administering a fixed dose of anifrolumab. Although the patent claims did not teach subcutaneous administration or the dosages of the present claims, given the teachings of Higgs, Werth, Furie and DePaz as discussed above, it would have been obvious to one of ordinary skill in the art to arrive at the claimed methods of the present claims for reasons stated above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
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/SHARON X WEN/Primary Examiner, Art Unit 1644
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