DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The rejection of claims 53-63 and dependent claims 64-66 under 35 USC 112(b) is withdrawn in view of the amendment to claims 59-63 stating the product is administered and the cancellation of claims 56-59. Note claims 67-69 remain rejected below.
The rejection of claims 53-60 and dependent claims 64-66 under 35 USC 112(a), written description, is withdrawn in view of the cancellation of claims 53-58 and upon further consideration of claims 67 and 68, which recite only doses without frequency, and claim 69, which recites frequency without dose. As a result, claims 67-69 do not have the constraints that, for example, claims 59 and 60 do which limit both the dose and frequency of administration. Claims 59 and 60 remain rejected below.
The rejection of claim(s) 52, 56-58 and 62 under 35 U.S.C. 102(a)(1) as being anticipated by US Patent 8,524,672 B2 is withdrawn in view of the limitation of the claims to ianalumab and cancellation of claims.
The rejection of claim(s) 52-55, 70 and 71 under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials.gov Study NCT03400176, version 5, (https://clinicaltrials.gov/study/NCT03400176?term=NCT03400176&rank=1&tab=history&a=5#version-content-panel, 09/21/2018) and in light of Applicant’s admission in the specification in [0055] and Table 1 and US 2018/0251564 A1 (‘564, cited in the IDS filed 5/9/23) is withdrawn in view of the limitation of the claims requiring ianalumab and treatment of diffuse large B-cell lymphoma (DLBCL) and cancellation of claims 70 and 71.
The rejection of claim(s) 52-55 and 70-71 under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrial.gov Study NCT021137889 (https://clinicaltrials.gov/study/NCT02137889?intr=mor6654%20OR%20VAY736%20OR%20ianalumab&rank=14&tab=table, 02/28/2018,) and in light of Applicant’s admission in the specification in [0055] and Table 1, and [0101] and US 2018/0251564 A1 (‘564, cited in the IDS filed 5/9/23) is withdrawn in view of the limitation of the claims requiring ianalumab and treatment of diffuse large B-cell lymphoma and cancellation of claims 70 and 71.
The rejection of claim(s) 52-56, 62, 63 and 70 under 35 U.S.C. 102(a)(1) as being anticipated by US 2018/0251564 A1 (‘564, cited in the IDS filed 5/9/23) is withdrawn in view of the amendment requiring ianalumab administered in a dose of 3 or 9 mg/kg.
The rejection of claim(s) 53-58 and 70 under 35 U.S.C. 102(a)(1) as being anticipated by WO2010007082 (Heusser, cited in the IDS filed 1/18/2025) is moot in view of the cancellation of the claims. Note claims 52 and 61-63 are still rejected as anticipated by Heusser below.
The rejection of claim(s) 52-72 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2010007082 (Heusser, cited in the IDS filed 2/20/2025) as applied to claims 52-58, 61-63 and 70 above, and further in view of ClinicalTrial.gov Study NCT021137889 (https://clinicaltrials.gov/study/NCT02137889?intr=
mor6654%20OR%20VAY736%20OR%20ianalumab&rank=14&tab=table, 02/28/2018), Dömer et al. (Ann. Rheum. Dis. 78:641–647, Mar. 2019) and Revlimod Prescribing Information (https://www.accessdata.fda.gov/drugsatfda_
docs/label/2019/021880s057lbl.pdf, May 2019) and as admitted by Applicant in [0055] and Table 1, is withdrawn in view of the cancellation of claims 53-58 and amendment to independent claim wherein the subject being treated has specifically DLBCL. However, a new rejection appears below due to the amendment.
The provision rejection of claims 52-72 under 35 U.S.C. 101 as claiming the same invention as that of claims 49-69 of copending Application No. 18/019,467 (reference application) is withdrawn in view of the amendment limiting the copending claims to treating a subject having chronic lymphocytic leukemia (CLL) and the requirement for the subject to have a mutation conferring resistance to a BTK inhibitor and the requirement for the subject in the instant claims to having diffuse large B-cell lymphoma (DLBCL). However, a new provisional rejection appears below.
Claim Rejections - 35 USC § 112(b)
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.
Claims 67-69 remain 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.
Claims 67-69 are dependent claims drawn to an additional agent that “is to be administered” at a listed dosage or frequency of dosage. The claims are indefinite because it is unclear if the method requires administration of the additional agent and/or requires the intention of future administration but that actual administration is not per se that of the dose or frequency claimed. The rejection could be obviated if appropriate by deleting “to be” in the phrase.
Applicant argues (p. 5 of REMARKS) that the claims have been amended to no longer recite “to be administered”. The rejection has been fully considered but is not persuasive. Even though these are dependent claims that depend from claim 63, which recites ianalumab is administered in combination with one or more additional agents, it is still unclear if the doses or frequency recited in claims 67-69 are applied to the method of claim 63 or may be used at some point in the future.
Claim Rejections - 35 USC § 112(a)
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 59 and 60 remain 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 for the reasons set forth in the previous Office action and as recast here to address only claims 59-60.
The claims are drawn to administration of an anti-BAFFR antibody. No route of administration is recited in these claims. However, claims require a particular range of or dosage of drug and frequency of administration. Claim 61 specifies the antibody administration is intravenous (IV). The specification is silent with respect to routes of administration except for intravenous administration of the anti-BAFFR (e.g., [0110], [0134] and [0142]; VAY736/ MOR6654/ ianalumab [0055]), which agrees with the prior art [e.g., ClinicalTrials.gov Study NCT021137889 (https://clinicaltrials.gov/study/NCT02137889?intr=mor6654%20OR%20VAY736%20OR%20ianalumab&rank=14&tab=table, 02/28/2018), teaching treatment of patients having relapsed or refractory CLL (chronic lymphocytic leukemia) by intravenous administration of antibody VAY736 (Brief and Official Title)].
The route of administration influences what is an effective dose for any particular therapeutic and treatment. The frequency of administration is also related to dose. Pitiot et al. (Antibodies, 11(3):56, 2022; cited in the PTO-892 mailed 9/3/2025) reviewed antibody literature published before April 1, 2022, to describe the state of the art of antibody (Ab) administration. Each route has its limitations. While the advantages of and advancements related to subcutaneous (SC) administration of antibodies are discussed, it is also stated that bioavailability of SC delivered antibodies is difficult to predict. “Advances in preclinical models would be necessary to investigate the fate of Abs at the SC injection site and their diffusion into the blood/lymphatic compartment…. Nevertheless, as no in vitro model is yet accurate enough, the pharmacokinetics of Abs still relies on in vivo studies…. ⁋Formulating Abs for the SC route remains challenging…” (p. 7/25, section 2.1.4) Pitiot et al. discusses (p. 7/25, section 2.2.1) that intramuscular (IM) injection is often used for vaccines but rarely considered for Abs. IM injection requires a more concentrated product than IV administration. While a small number of IM administered antibodies are in phase 3 clinical trials, none have yet been approved by the FDA and/or EMA (Table 3). As to pulmonary administration, it was determined (end of p. 12/25), “Abs administration through systemic routes led to a low bioavailability in the airway compartment [84,85]. This may limit the efficacy of Abs to treat respiratory diseases, if their target antigen primarily acts within the respiratory organ, while exposing the rest of the body to potential side effects [86].” Issues for administration by inhalation include (p. 13/25, first paragraph), “Abs aerosolization is generally difficult since they are highly sensitive to mechanical, thermal, and physical stresses occurring during aerosol generation.” Also, only a single antibody is being developed for nasal inhalation and is not yet approved (p. 13/25, last sentence). Pitiot et al. concludes for inhalation routes (p. 14/25, end of first paragraph), “However, groundwork is still necessary to optimize Abs design and formulation, inhalation devices, as well as improving our knowledge of the physical and biological barriers that may impair the therapeutic response to inhaled Abs.” For localized intratumoral injection, a small number of antibodies, including checkpoint inhibitor antibodies such as pembrolizumab are in phase 2 and 3 clinical trials (Table 7); however, preclinical studies showed that a significantly lower amount of Ab injected intratumorally compared to IV was effective (bottom of p. 14/25), which suggests an IV dosage would not be appropriate for intra-tumoral injection. “For now, clinical validation of intra-tumoral delivery of Abs is still in the preliminary stages. Further work is needed to optimize the dosage and the formulation according to the type and the stage of the tumor lesion.” (p. 15/25, second paragraph of 2.5.3) Oral administration of antibodies has challenges, including harsh pH conditions and presence of proteases, such that less than 20% of orally administered antibodies have been found to be immunologically active after passage through the gastrointestinal tract, requiring large amounts (p. 18/25, last paragraph, and p. 19/25, first paragraph). Topical administration of Abs has shown low skin penetration, thereby requiring a high dose (p. 19/25, last paragraph). Therefore, no route for these recited doses and also frequencies (claims 56-60) of anti-BAFFR antibody other than IV, as supported by both the instant specification and prior art, meets the requirements for written description under 35 USC 112(a).
Applicant argues (pp. 5-6 of REMARKS) that the requirement for written description is not the same as for approval by health authorities (FDA) to receive approval to market a therapeutic. Further, the claims have been amended to be more narrow and to require intravenous administration of ianalumab. Therefore, the skilled artisan would conclude the inventors were in possession of the claimed invention. The argument has been fully considered but is not persuasive. The scope of claims 59-60 has been narrowed only by the anti-BAFFR antibody being limited to ianalumab. The dose and frequency have not been changed. The specification does not support treatment of a B-cell malignancy, including DLBCL, at this dose and frequency when the administration route is anything other than intravenous (IV). The standard for establishing written description under 35 USC 112(a) is not ‘make and test’. The specification and/or prior art must provide sufficient support for the full breadth of the claims. There is no basis in the specification for treatment as claimed in claims 59-60 where the route is not by intravenous injection or infusion. Based on the prior art use of VAY73 (ianalumab) by intravenous administration and general knowledge of antibody efficacy by different administration routes as reviewed by the post-filing reference Pitiot et al. (see rejection), the skilled artisan would not have recognized that the inventors were in possession of the invention as it generically relates to adiminstration. The prior art as a whole supports only intravenous administration of ianalumab for treatment as exemplified by WO 2010/007082 (Example 3 of peripheral B cell depletion in cynomolgus monkeys; cited in the IDS filed 1/18/2025), ClinicalTrial.gov Study NCT030400176* [cited in the PTO-892 mailed 9/3//2023, which as reviewed by Rogers et al. (Clin. Canc. Res. 31:5145–58, 2025, attached) used ianalumab to treat patients with R CLL by intravenous administration (Abstract:Purpose and Patients and Methods sections)], and ClinicalTrial.gov Study NCT02137889 v.8 (cited in the PTO-892 mailed 9/3/2025, treatment of R CLL by intravenous ianalumab, see Official Title). Even use of ianalumab for treatment of a different disease, Sjögren’s syndrome, was administered by IV infusion (Dömer et al., Ann. Rheum. Dis. 78:641-647, 2019, cited in the PTO-892 mailed 9/3/2025, Abstract:Method). *N.b., NCT03400176 (see “Unique Protocol ID”) is study CVAY736Y2102 referred to in Example 2 of the instant specification. The specification states VAY736 was administered intravenously (section 2.1.5). There is no written description for other routes and the skilled artisan could not readily envision non-IV routes as meeting the limitations of the claims for treatment of DLBCL with the species of prescribed dose and administration frequency.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 52, 59 and 61-64 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2010007082 (Heusser, cited in the IDS filed 1/18/2025) in view of Applicant’s admission in paragraphs [0055] and [0107] and Table 1.
WO2010007082 (Heusser) teaches the anti-BAFFR antibody MOR06654 having the VH and VL sequence of SEQ ID NOs: 51 and 45, respectively, comprising HCDR1-3 of SEQ ID NO:3, 10, 17, and LCDR1-3 of SEQ ID NO:24, 31, 38 (p. 62, Table). The subject treated may be a human, such that antibody administration kills human B cells (p. 49, second and fourth paragraphs). Administration is intravenous in a dose of 3 mg/kg, and may be given once every two weeks (p. 46, last paragraph). It is used to treat a B-cell neoplasm, including diffuse large cell lymphoma (p. 51, first paragraph). The antibody can be administered in combination with another active agent, such as an immunomodulating agent, e.g., leflunomide (p. 51, second paragraph).
Applicant admits in [0055] that MOR6654 is disclosed in WO 2010/007082 and is also known as VAY726 or ianalumab ([0107]), having the sequences of Table 1, which is the same as that disclosed for MOR06654 of Heusser (WO 2010/007082)..
Applicant’s admission is not necessary for anticipation, but provided only to show the that the antibody of Heusser et al. is the same as ianalumab.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 52-72 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2010007082 (Heusser, cited in the IDS filed 2/20/2025) as applied to claims 52, 59 and 61-64 above, and further in view of Mondello et al. (The Oncologist, 21:1107-1112, 2016) and Rodig et al. (Human Pathol. 36:111-119, 2005, cited in the IDS filed 5/29/2025) and as admitted by Applicant in [0055] and Table 1.
WO2010007082 (Heusser) teaches the anti-BAFFR antibody MOR06654 having the variable heavy (VH) and variable light (VL) chain sequence of SEQ ID NOs: 51 and 45, respectively, comprising HCDR1-3 of SEQ ID NO:3, 10, 17, and LCDR1-3 of SEQ ID NO:24, 31, 38 (p. 62, Table). The subject treated may be a human, such that antibody administration kills human B cells (p. 49, second and fourth paragraphs). Administration is intravenous in a dose of 0.03 to 10 mg/kg, including 3 or 10 mg/kg, given once every two weeks or four weeks (p. 46, last paragraph). It is used to treat a B-cell neoplasm, including diffuse large cell lymphoma (p. 51, first paragraph). The antibody can be administered in combination with another active agent, such as an immunomodulating agent, e.g., leflunomide (p. 51, second paragraph). The pharmaceutical composition comprising the antibody can be administered with other therapeutic agents, such as a chemotherapeutic agent (p. 43, second paragraph). Intravenous administration to cynomolgus monkeys every 4 weeks at a dose of 20 mg/kg resulted in rapid B cell depletion, which was maintained or increased with subsequent doses (Example 3, pp. 67-68). The effect was reversible when treatment was stopped (Id.). Heusser does not teach a dosage exactly of 9 mg/kg or treatment with an immunomodulatory imide drug that is lenalidomide.
Mondello et al. teaches many patients with diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype, relapse or die. Early clinical trials have shown that lenalidomide is safe and effective for treating DLBCL (Abstract:Background, and p. 1107, col. 1, first sentence). “Lenalidomide can stimulate the innate immune system, potentiate the antitumor activity of rituximab, and inhibit angiogenesis [18, 19]. These effects can be explained by the ability to inhibit tumor necrosis factor-α, vascular endothelial growth factor, and NF-kB in cancer cells [19, 20].” (p. 1108, col. 1, second full paragraph). Mondello et al. did a retrospective study of 123 patients with relapsed/refractory DLBCL treated with lenalidomide (p. 1108, col. 1, fourth full paragraph). Patients received either 15 mg/day or 25 mg/day, with both doses leading to progression-free survival (PFS) and remission in a percentage of patients (p. 1109, col. 2, third paragraph).
Rodig et al. teach that BAFF-R is a cell-surface receptor expressed in a majority of B-cell lymphoproliferative diseases, including a subset of diffuse large B-cell lymphomas (p. 1114, col. 1, second paragraph, p. 1115, col. 1, first paragraph). The expression profile of BAFF-R in normal and malignant cells “support the notion that signaling through BAFF-R can provide critical survival signals at several stages of B-cell differentiation and present BAFF-R as a candidate receptor mediating the survival of select subsets of lymphoproliferative disorders.” (p. 1115, col. 1, end of first paragraph). This includes BAFF-R expression in the majority of diffuse large B-cell lymphoma cases (78%; Table 1). It is suggested that BAFF-R could be a target for immunological therapy (p. 1118, col. 2, end of first full paragraph).
Applicant admits in [0055] that MOR6654 is disclosed in WO 2010/007082 and is also known as VAY726 or ianalumab ([0107]), having the sequences of Table 1, which is the same as that disclosed for MOR06654 of Heusser (WO 2010/007082).
It would have been obvious to the artisan of ordinary skill before the effective filing date of the instant invention to have administered anti-BAFFR antibody VAY736 at a dose of 3 mg/kg every two weeks or about 9 mg/kg every four weeks because these doses and administration frequencies are within the range taught by Heusser for depletion of B cells, including for B cell neoplasias, such as diffuse large B-cell lymphoma, which depletion would have been desirable if not necessary for treatment of B cell neoplasias. Further, determining the optimal dosage at a particular dosing frequency would have been obvious because “It is not inventive to discover the optimum or workable ranges by routine experimentation” In re Aller, 220, F.2d 4554, 456, (CCPA); see also In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). “Discovery of an optimum value of a result effective variable in a known process is ordinary within the skill of the art.” In re Boesch, 617 F. 2d 272, 276 (CCPA1980). It further would have been obvious where the subject was treated with an additional therapeutic besides ianalumab, such as lenalidomide because that immunomodulatory imide drug (IMiD) had been shown to be safe and effective in the treatment of DLBCL, including in a dose of 15-25 mg/day, as taught by Modello et al. Because Heusser showed that the anti-BAFFR antibody led to B-cell depletion and Modello showed effectiveness of lenalidomide in the treatment of DLBCL, which was identified by Rodig et al. as expressing BAFFR in most cases, there would have been a reasonable expectation of success.
Applicant’s arguments which pertain to the new rejection are address here:
Applicant argues (paragraph bridging p. 6-7) that there is “a high unmet medical need for patients with B cell malignancies”. This argument has been fully considered but is not persuasive. As stated in MPEP 716.04(I), “Establishing long-felt need requires objective evidence that an art recognized problem existed in the art for a long period of time without solution.” There were successful treatments of DLBCL prior to the disclosure of the instant invention, including treatment with other B-cell-depleting therapeutics such as CD19-targeting therapies and standard chemotherapy (e.g., Zhao et al., Ann, Hematol. 99:1681-1699, 2020, p. 1684, col. 1, second and third paragraph cited in the IDS filed 5/9/2023). Therefore, there were solutions for treatment of DLBCL.
Applicant argues (pp. 7-8) that ianalumab has a dual mechanism that depletes B cells and suppresses B cell hyperactivity, potentially allowing greater clinical efficacy than a therapeutic agent with only one of these activities. “[T]he present application provides sufficient secondary indicia, by way of unexpected results in safety and efficacy, to support rebuttal of the obviousness allegation direct to the presently claimed invention.” This argument has been fully considered but is not persuasive. The rejection relies in part on the teachings of WO 2010/007082 (Heusser), which discloses using the ianalumab, called MOR06654, to deplete B cells in a primate. Further, prior art clinical trials are of record (NCT021137889 and NCT 03400176) which used ianalumab for treatment of relapsed/refractory CLL, again supporting the reasonable expectation of treatment of a B-cell malignancy by administration of ianalumab. There is no evidence of unexpected results, regardless of whether ianalumab is a ‘better’ therapeutic than other previously used agents that deplete B cells and/or have been used to treat a B-cell neoplasm. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) MPEP § 716.2 It is not agreed that the properties differ from the prior art to such an extent to be considered unexpected.
Nonstatutory 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 52 and 59-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 49, 55-58, 60-62 of copending Application No. 18/019,467 (‘467) in view of Mondello et al. (The Oncologist, 21:1107-1112, 2016) and Rodig et al. (Human Pathol. 36:111-119, 2005, cited in the IDS filed 5/29/2025).
Both applications claim a method of treating a subject having a disease by administering ianalumab at a dose of 3 mg/kg or 9 mg/kg, including wherein 3 mg/kg is administered once every two weeks or 9 mg/kg once every four weeks (claims 49, 55-57 of ‘467 and instant claims 52, 59-60 and 62). The administration is intravenous (instant claim 61 and claim 58 of ‘467). The administration may comprise an additional agent(s), including wherein the ianalumab is in a pharmaceutical combination therewith (claims 60-62 of ‘467 and instant claims 63-68). The copending application does not claim wherein the disease is diffuse large B-cell lymphoma (DLBCL; instant independent claim 52), but instead is drawn to chronic lymphocytic leukemia (CLL, copending claim 49). The copending application does not claim wherein the subject is also treated with lenalidomide (instant claims 64-69).
Mondello et al. teaches many patients with diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype, relapse or die. Early clinical trials have shown that lenalidomide is safe and effective for treating DLBCL (Abstract:Background, and p. 1107, col. 1, first sentence). “Lenalidomide can stimulate the innate immune system, potentiate the antitumor activity of rituximab, and inhibit angiogenesis [18, 19]. These effects can be explained by the ability to inhibit tumor necrosis factor-α, vascular endothelial growth factor, and NF-kB in cancer cells [19, 20].” (p. 1108, col. 1, second full paragraph). Mondello et al. did a retrospective study of 123 patients with relapsed/refractory DLBCL treated with lenalidomide (p. 1108, col. 1, fourth full paragraph). Patients received either 15 mg/day or 25 mg/day, with both doses leading to progression-free survival (PFS) and remission in a percentage of patients (p. 1109, col. 2, third paragraph).
Rodig et al. teach that BAFF-R is a cell-surface receptor expressed in a majority B-cell lymphoproliferative diseases, including a subset of diffuse large B-cell lymphomas and most cases of chronic lymphocytic leukemia (p. 1114, col. 1, second paragraph, p. 1115, col. 1, first paragraph). The expression profile of BAFF-R in normal and malignant cells “support the notion that signaling through BAFF-R can provide critical survival signals at several stages of B-cell differentiation and present BAFF-R as a candidate receptor mediating the survival of select subsets of lymphoproliferative disorders.” (p. 1115, col. 1, end of first paragraph). This includes BAFF-R expression in all examined cases of chronic lymphocytic leukemia and most cases of diffuse large B-cell lymphoma (78%; Table 1). It is suggested that BAFF-R could be a target for immunological therapy (p. 1118, col. 2, end of first full paragraph).
It would have been obvious to have treated DLBCL with ianalumab because that is an anti-BAFFR antibody and Rodig et al. teaches that both B-cell lymphoproliferative disorders CLL and DLBCL express BAFF-R. One of ordinary skill in the art would have expected that a BAFF-R-targeted treatment of one could also be used for treatment of the other, including at the same doses and dosage frequencies. It further would have been obvious wherein the treatment of DLBCL also included the addition of lenalidomide because Mondello et al. showed it was effective and safe for that. It would have been obvious to use the doses and frequency taught to be safe and effective, i.e., 15 to 25 mg/day.
This is a provisional nonstatutory double patenting rejection.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US Patent 9,216,219 B2 (‘219, cited in the previous Office action under “Prior Art”) also is noted for teaching the anti-BAFFR antibody can be used to treat B-cell neoplasms, including diffuse large cell lymphoma (col. 10, lines 62-64).
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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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
February 27, 2026