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 .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
The Information Disclosure Statement (IDS) filed 5 October 2023 has been entered. Applicant’s submission of a substitute specification in both marked-up and clean formats in compliance with 37 C.F.R. 1.52, 1.121(b)(3), and 1.125, filed 27 August 2025, is acknowledged. Applicant’s amendment of the claims filed 12 December 2025 has been entered.
Election/Restriction
In the response received on 12 December 2025, Applicant elected, with traverse, the species of: A-c) wherein the patient has treatment-refractory SLE; B-a) wherein anifrolumab or the functional variant thereof is administered intravenously; and C) wherein the patient has received prior treatment with azathioprine.
Applicant traverses the requirement for a species election set forth in Group A and argues that independent claim 17 has been amended to recite “A method of treating SLE in a patient thereof, … wherein the patient has treatment-refractory SLE”, and previous independent claims 20 and 22 have been amended to depend from claim 17.
Applicant’s arguments have been fully considered. In view of the claim amendment, the requirement for a species election set forth in Group A is withdrawn.
Claims 1-16, 18-19 and 37-54 are cancelled. Claims 55-56 have been added. Claims 17, 20-36 and 55-56 are pending and under examination to the extent they read on the elected species: B-a) wherein anifrolumab or the functional variant thereof is administered intravenously; and C) wherein the patient has received prior treatment with azathioprine.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 17, 20, 22-24, 26-27 and 36 are objected to because of the following informalities:
Claims 17 and 26-27 use acronyms without first defining what they represent in the independent claims (e.g., “SLE”). While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym.
In claims 20 and 36, the term “the subject” should be “the patient”.
In claim 22, the phrase “wherein treatment” should be “wherein the treatment”.
In claim 23, the phrase “wherein the patient has previously received prior treatment …” should be “wherein the patient has received prior treatment …”.
In claim 24, the word “pre-treatment” should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 17 and 29 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 recites “a type I IFN receptor (IFNAR1) inhibitor”, and claim 29 recites “the type I IFN receptor inhibitor”. The type I IFN receptor consists of IFNAR1 and IFNAR2 chains. It is unclear whether the claims are limited to only IFNAR1 chain or the whole type I IFN receptor (IFNAR). The metes and bounds of the claims are unclear.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 33-35 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 33-35 recite “the functional variant thereof”. However, the previous claim 31 upon which claims 33-35 depend limits “wherein the method comprises administering about 300 mg to about 1000 mg of anifrolumab”. Claims 33-35 fail to further limit the subject matter of the claim upon which they depend.
Claim 35 recites “The method of claim 31, comprising administering anifrolumab … to the patient at a dose of 120 mg every week”. However, the previous claims upon which claim 35 depends recite “wherein the method comprises administering a fixed dose of anifrolumab” (claim 30), and “The method of claim 30, wherein the method comprises administering about 300 mg to about 1000 mg of anifrolumab” (claim 31). The dose of “120 mg every week” is outside the range of the fixed dose of “about 300 mg to about 1000 mg”. Therefore, claim 35 fails to further limit the subject matter of the claims upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17, 20-29, 33-36 and 55-56 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 17 recites a method of treating systemic lupus erythematosus (SLE) in a patient comprising administering to the patient a therapeutically effective amount of a type I IFN receptor (IFNAR1) inhibitor; and depending claims further limit wherein the type I IFN receptor inhibitor is anifrolumab or a functional variant thereof.
The claims are broad and encompass the use of a genus of type I IFN receptor (IFNAR1) inhibitors, however, the specification fails to provide adequate written description and evidence of possession of these molecules. The specification defines the term of a "type I interferon receptor inhibitor" as referring to “a molecule that is antagonistic for the receptor of type I interferon ligands such as interferon-a and interferon-b. Such inhibitors, subsequent to administration to a patient, preferably provide a reduction in the expression of at least 1 (preferably at least 4) pharmacodynamic (PD) marker genes selected from the group consisting of IF16, RSAD2, IF144, IF144L, IF127, MX1, IFIT1, HERC5, ISG15, LAMP3, OAS3, OAS1, EPST1, IFIT3, LY6E, OAS2, PLSCR1, SIGLECI, USP18, RTP4, and DNAPTP6.” The specification does not adequately describe the structural characteristics of the genus of molecules as claimed, which encompass any molecules (e.g., proteins, nucleic acids, antibodies, small molecules, etc.) that directly or indirectly interact with and/or inhibit the type I IFN receptor. Tran et al. (Front. Cardiovasc. Med., 2024, Vol. 11:1357343) teaches the complex of interferon-related pathways and their regulations. Alteration in any of the signaling or regulatory components may affect the activity of the receptor. Clearly, Applicant does not show evidence of possession of the genus of type I IFN receptor (IFNAR1) inhibitors encompassed in the present claims.
Further, while the specification provides the antibody anifrolumab, which is a monoclonal antibody targeting IFNAR1 (the receptor for a, b, and w interferons), the specification does not provide adequate written description for the functional variants of anifrolumab. It is well-known in the art that for any single epitope, there could be numerous antibodies that have distinct antigen-binding site structures and the structures and properties of these antibodies are unpredictable. Such is evidenced by Goel et al. (J. Immunol., 2004, Vol. 173(12):7358- 7367), who made three antibodies that bind to the same 12-mer but have very different CDRs. Even up to date, the state of art still lacks the knowledge of predicting the structures of antibodies that bind to a given epitope, let alone those exhibiting particular property or activity. Given the highly diverse nature of antibodies, particularly in the CDRs, one cannot envision the structure of an antibody by knowing its binding characteristics. The specification fails to teach the structures or a reasonable correlation of structure and function for the claimed functional variant antibodies. A skilled artisan would not recognize that Applicant was in possession of the genus of the antibodies as claimed at the time the application was filed.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making of the claimed product, or any combination thereof. In this case, there is no sufficient teachings regarding the structural characteristics of the genus, nor the correlation of structure to function. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structures of the encompassed genus of molecules, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that is part of the invention and reference to a method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, except for anifrolumab or functional variants thereof that comprise the six CDRs of anifrolumab, the specification does not provide adequate description for the full scope of the claimed molecules.
Claim Rejections - 35 USC § 102
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.
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 17, 20-34, 36 and 55-56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Furie et al. (Arthritis Rheumatol., 2017, Vol. 69(2):376-386).
Furie teaches administering anifrolumab, a type I interferon (IFN) receptor antagonist, to treat patients with moderate-to-severe systemic lupus erythematosus (SLE), wherein the patients received intravenous anifrolumab at a dose of 300 mg or 1,000 mg, every 4 weeks for 48 weeks (see Abstract). Furie teaches that the patients had prior treatment with glucocorticoids (e.g., methotrexate), antimalarials and/or immunosuppressants (p. 379, Table 1). The patients of Furie, who had moderate-to-severe SLE despite prior treatment, meet the limitation as having treatment-refractory SLE. Furie teaches that the patients had low C3 and/or C4 complement at baseline (p. 379, Table 1), and a score of ≥6 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (p. 377, col. 2, 3rd paragraph under “PATIENTS AND METHODS”). Furie teaches that the patients had a CLASI score of ≥10 at baseline, and the treatment led to a ≥50% reduction in the CLASI score by at least week 12 of treatment, which was maintained by week 52 (p. 380, Table 2; p. 382, col. 2, last paragraph; and p. 383, Figure 3). Furie teaches that the efficacy of treatment is assessed by determining, e.g., response in BICLA (p. 380, Table 2). Furie teaches that the use of oral corticosteroids was spared or tapered during the treatment (p. 378, col. 1, 1st full paragraph).
Regarding claim 28, which recites “wherein the method has been demonstrated in a phase III clinical trial”, the claim does not have a patentable weight because there is no difference in the method taught by Furie and that claimed in the instant application.
Therefore, Furie anticipates the instant claims.
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.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Furie et al. (cited above), as applied to claims 17, 20-34, 36 and 55-56 above, and further in view of Higgs et al. (US 2015/0158949 A1, Pub. Date: Jun. 11, 2015).
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.
Furie teaches as set forth above. Furie, however, does not teach administering anifrolumab or the functional variant thereof at a dose of 120 mg every week (claim 35).
Higgs teaches a method of treating a type I IFN-mediated disease or disorder, such as systemic lupus erythematosus (SLE), in a patient comprising administering to the patient at least one intravenous or subcutaneous fixed dose of an anti-IFNAR antibody, such as MEDI-546 (anifrolumab) [0124]. Higgs teachs that MEDI-546 may be administered subcutaneously at a fixed dose of about 100 mg, and the doses can be administered approximately every week [0117-0119].
While Higgs does not teach administering anifrolumab at a dose of 120 mg every week, given that the level of skill in this art is very high, and that optimizing parameters such as the dose and administration frequency of a therapeutic agent is routine, modifying the dose of anifrolumab used by Furie in view of the teachings of Higgs to arrive at the claimed dose (e.g., 120 mg every week) would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, with a reasonable expectation of success, absent evidence of unexpected results. As was found in In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
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 17, 20-36 and 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
1) claims 1-5 and 10 of U.S. Patent No. 12,060,429; and
2) claims 1-4, 6-8 and 11 of U.S. Patent No. 12,410,254.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the ‘429 and ‘254 patents recite a method of treating systemic lupus erythematosus (SLE) in a patient comprising administering to the patient anifrolumab (a type I IFN receptor inhibitor). The claims of the ‘429 and ‘254 patents differ from the instant claims in that the instant claims recite wherein the patient has treatment-refractory SLE. Furie (cited above) teaches administering anifrolumab to treat patients with treatment-refractory moderate-to-severe SLE. It would have been prima facie obvious to one ordinary skill in the art to use the methods claimed in the ‘429 and ‘254 patents to treat a patient having treatment-refractory moderate-to-severe SLE. One of ordinary skill in the art would have been motivated to do so and have a reasonable expectation of success, because Furie teaches that the method claimed in the ‘429 and ‘254 patents was effective to treat a patient having moderate-to-severe and treatment-refractory SLE. Therefore, the claims of the ‘429 and ‘254 patents render the instant claims obvious in view of Furie.
Claims 17, 20-36 and 55-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
3) claims 65, 68-74 and 76 of copending Application No. 17/755,801;
4) claims 20-22 and 33-46 of copending Application No. 18/291,671;
5) claims 67-70 of copending Application No. 18/435,476;
6) claims 67-70 of copending Application No. 18/474,601;
7) claims 1, 46-51, 53, 55 and 57 of copending Application No. 18/559,907; and
8) claims 11-18, 20, 27-28, 34-40 and 53 of copending Application No. 18/698,343.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of each of the above cited copending applications recite a method of treating systemic lupus erythematosus (SLE) in a patient comprising administering to the patient anifrolumab (a type I IFN receptor inhibitor). The claims of each of the above cited copending applications differ from the instant claims in that the instant claims recite wherein the patient has treatment-refractory SLE. Furie (cited above) teaches administering anifrolumab to treat patients with treatment-refractory moderate-to-severe SLE. It would have been prima facie obvious to one ordinary skill in the art to use the methods claimed in the above cited copending applications to treat a patient having treatment-refractory moderate-to-severe SLE. One of ordinary skill in the art would have been motivated to do so and have a reasonable expectation of success, because Furie teaches that the methods claimed in the above cited copending applications were effective to treat a patient having moderate-to-severe and treatment-refractory SLE. Therefore, the claims of each of the above cited copending applications render the instant claims obvious in view of Furie.
This is a provisional nonstatutory double patenting rejection.
Conclusion
NO CLAIM IS ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674