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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/02/2026 has been entered.
Status of Claims
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124-129 and 133 are pending.
Claims 1, 35, 99, 101, 106, 109, 110, 113, 117 and 129 have been amended by Applicant.
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124-129 and 133 are currently under examination in the instant Office Action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The U.S. effective filing date of all claims under examination is set at 04/24/2019 based on the provisional application 62/838,093 (filed 04/24/2019).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/02/2026 is being considered by the examiner.
Claim Objections - Withdrawn
The objection of claim 133 has been withdrawn because the claim has been amended.
Claim Rejections – Withdrawn
The rejection of claims 1, 2, 17, 35, 36, 109 and 125 under 35 USC § 112(b) or 35 USC § 112 (pre-AIA ), second paragraph has been withdrawn.
The rejection of claims 113, 123 and 129 under 35 USC § 112(b) or 35 USC § (pre-AIA ), second paragraph has been withdrawn.
The written description/new matter rejection of claim 133 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph has been withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103 (first)
Claims 1, 2, 17, 35, 125 and claim 133 are rejected under 35 U.S.C. 103 as being unpatentable over NCT02200770 (N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders; Record History 2018-04-05), Cree et al. (Multiple Sclerosis Journal 2016, Vol. 22(7) 862-872), Bradshaw and Kimbrough (Practical Neurology 2019: 76-89), Agius et al. (Multiple Sclerosis Journal 2019, Vol. 25(2) 235–245) and Patra et al. (Therapeutic Innovation & Regulatory Science 2016, Vol. 50(3) 375-384).
NCT02200770 teaches that the N-Momentum clinical trial is a clinical research study of inebilizumab in Neuromyelitis Optica Spectrum Disorders (NMOSD) (Title). They teach that the study compared the efficacy and safety of intravenous (IV) MEDI-551 in reducing the risk of an NMOSD attack in subjects with NMOSD (Brief Summary and Detailed Description). They teach that MEDI-551 is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen CD19 that would result in the depletion of B cells (Detailed Description). They teach that CD19 positive (CD19+) B-lineage plasmablasts are responsible for the production of autoantibodies against the AQP4 channel protein (Detailed Description). They also teach that the study included men and women 18 years or older with diagnoses of NMOSD that had been confirmed for NMOSD status using AQP4-IgG seropositivity (Inclusion Criteria). Thus, NCT02200770 teaches that intravenous administration of the antibody inebilizumab, also known as MEDI-511, was studied in a method for treating NMOSD in AQP4-IgG seropositive subjects in the N-Momentum study.
Of note, MEDI-551 is described in instant specification Paragraph [0032] (Pg. 6) as also being referred to as inebilizumab or VIB551 antibody, wherein VIB551 antibody comprises the amino acid sequence of VH as set forth in instant SEQ ID NO:1 and VL as set forth in instant SEQ ID NO:2 (Pg. 5 Paragraph [0024]). Therefore, MEDI-551 or inebilizumab as taught by NCT02200770 is an antibody also known as VIB551 that comprises the amino acid sequence of instant SEQ ID NO: 1 for the VH domain and instant SEQ ID NO: 2 for the VL domain as taught by instant specification.
NCT02200770 does not specifically teach the method comprising administering inebilizumab at a dose of 300 mg every 6 months, wherein after a first administration of inebilizumab on day 1, a 300 mg dose of inebilizumab is administered on day 15. They also do not specifically teach the administration is effective in reducing the risk of an NMOSD-related attack of the subject, wherein the reduction of the risk is between 60 and 85%. They further do not specifically teach the method wherein a corticosteroid is co-administered to the subject with the first 300 mg inebilizumab dose.
However, these deficiencies are made up in the teachings of Cree et al., Agius et al., Bradshaw and Kimbrough and Patra et al.
Cree et al. teaches that the N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo (Abstract). They teach that patients will receive MEDI-551 every 6 months until the study is terminated or until regulatory approval if successful (Pg. 866, Column, first, Paragraph, spanning).
Agius et al. teaches the administration of inebilizumab to adults with relapsing multiple sclerosis (MS) (Title and Abstract). They teach that inebilizumab was administered intravenously (IV) at two doses on days 1 and 15 and at 30, 100 or 600 mg (Abstract and Pg. 236 Column, second, Paragraph, third). They also teach the mean inebilizumab concentrations versus time upon IV administration of said three doses (Figure 3) as well as the median CD20 B-cell counts over time following inebilizumab administration (Figure 4). From Figure 3, it can be noted that upon the second dose of 30 mg, 100 mg and 600 mg IV administration, inebilizumab concentrations were at 30 µg/ml, 50 µg/ml and 300 µg/ml respectively and that over the course of up to 140 days the concentrations were below 0.1 µg/ml, at 0.1 µg/ml and at 2 µg/ml respectively. From Figure 4, it is noted that the dose of 30 mg IV inebilizumab administration provided complete depletion of CD20 B cells up to 16 weeks (112 days), while 100 mg IV administration provided the same up to 28 weeks (196 days) and 600 mg IV administration provided up to 36 weeks (252 days) of complete depletion of CD20 B cells.
Agius et al. also teaches that MRI outcomes by week 24 showed that the mean number of cumulative new lesions was 0.1 (standard deviation (SD) = 0.30) in the inebilizumab group versus 1.3 (SD = 1.38) in the placebo group (Pg. 240, Column, second, Paragraph, first; Figure 6). They further teach that the mean number of new or newly enlarging T2 lesions was 0.4 (SD = 0.94) in the inebilizumab group versus 2.4 (SD = 3.26) in the placebo group and the proportion of patients free of new inflammatory activity (i.e. no new Gd-enhancing lesions and no new or newly enlarging T2 lesions) was 75% in the inebilizumab group versus 43% in the placebo group (Pg. 240, Column, second, Paragraph, first). Further, they also teach that patients who received IV inebilizumab were administered IV methylprednisolone 100 mg to reduce risk of possible infusion reactions (Pg. 237, Column, first, Paragraph, spanning). It is well known in the art that methylprednisolone is a corticosteroid.
Bradshaw and Kimbrough teach that the results from the N-MOmentum trial reported that inebilizumab treatment of patients with NMOSD reduced the risk of relapse by 77% compared with treatment with placebo and that the primary and secondary endpoints of the trial were achieved (Pg. 83 Column, first, Paragraph third).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating NMOSD comprising administering inebilizumab intravenously to a subject in need of treatment for NMOSD wherein the subject is AQP4-IgG seropositive as taught by NCT02200770, combined with the administration schedule of inebilizumab of every 6 months as taught by Cree et al., and also combined with an inebilizumab dosing on day 1 and on day 15 for treating NMOSD as taught by Agius et al. for the treatment of MS, and further combined with the corticosteroid methylprednisolone that is co-administered with the first inebilizumab dose as taught by Agius et al. The motivation to use inebilizumab in the treatment of NMOSD stems from the teachings of Patra et al. which teaches that experience with rituximab suggested that B-cell depletion in NMO might reduce the occurrence of relapses (Pg. 377 Column second, second full paragraph) and that rituximab, a B-cell depleting monoclonal antibody was used off-label to treat NMOSD in several small case series (Pg. 377 Column, second, Paragraph, first). Further, Patra et al. also teaches that because both MEDI-551 and rituximab deplete B cells, it was postulated that their clinical effect may be similar, although MEDI-551 depletes a broader range of B cells and plasmablasts (Pg. 377 Column, second, Paragraph, first). The advantage of using inebilizumab/MEDI-511 for the treatment of NMOSD would be precisely due to its broader range of activity against B cells and plasmablasts causing depletion in the numbers of said cells. This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein inebilizumab is administered intravenously at doses of 300 mg on days 1 and 15, and continue with maintenance doses every 6 months after Day 1 or Day 15 for at least 1 year for treating NMOSD since it would have been obvious to optimize the dosage as taught by Agius et al. that inebilizumab was administered intravenously with doses on days 1 and 15 at 30, 100 or 600 mg for MS in a clinical trial (Abstract and Pg. 236 Column, second, Paragraph, third) and administered every 6 months to NMO patients until the study was terminated or until regulatory approval which could be for at least 1 year or more as taught by Cree et al. (Pg. 866, Column, first, Paragraph, spanning). Further, the teachings of Agius et al. corroborate the teachings of Patra et al. such that IV inebilizumab administered at doses of 100 mg and 300 mg was able to provide complete depletion of CD20 B cells up until around 28 weeks (196 days) after a dose on Day 1 and a second dose on Day 15. See MPEP 2144.05 II. A. Optimization Within Prior Art Conditions or Through Routine Experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). Also, "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
In addition, one of ordinary skill in the art would have been motivated to use said doses for the treatment of NMOSD by the combined method because of its safety profile in MS patients and effectiveness in reducing the number of new MRI lesions as taught by Agius et al. Further, the intravenous dosing schedule of inebilizumab taught by Agius et al., which is the same as the instant claims schedule on Day 1 and Day 15, was shown to rapidly deplete B cells (Pg. 241 Column, first, Paragraph, spanning), which is an effect of rituximab taught by Patra et al. as a factor contributing to the reduced occurrence of relapse with NMO (Pg. 377 Column second, second full paragraph).
With respect to instant claim 17, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating NMOSD because Bradshaw and Kimbrough teaches that in the N-MOmentum trial, inebilizumab treatment of NMOSD patients resulted in patients experiencing a reduced risk of NMOSD relapse by 77% (which is between the 60 and 85% recited in instant claim 17) compared with placebo (Pg. 83 Column, first, Paragraph third) and
With respect to instant claim 35, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the subject is co-administered IV methylprednisolone with an initial 300 mg inebilizumab dose to as taught by Agius et al. because Agius et al. teaches that patients who received IV inebilizumab were administered IV methylprednisolone 100 mg to reduce the risk of possible infusion reactions (Pg. 237, Column, first, Paragraph, spanning).
With respect to instant claim 125, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein inebilizumab is administered intravenously at doses of 300 mg every 6 months for at least 1 year for treating NMOSD because it would have been obvious to optimize the dosage as taught by Agius et al. to 300 mg and administered every 6 months until the study was terminated or until regulatory approval which could be for at least 1 year or more as taught by Cree et al. (Pg. 866, Column, first, Paragraph, spanning).
Response to Arguments
In the Reply of 03/02/2026, Applicant maintained previously cited information which includes: the dosing schedule presently claimed is the dosing schedule of UPLIZNA (inebilizumab), which was the first drug approved for the treatment of NMOSD. Applicants further cited that the claims require a 300 mg dose of inebilizumab (UPLIZNA) administered every 6 months starting at Day 1, with a loading dose at week 2/day 15. Applicant cites that the Examiner does not point to a single teaching in Cree that teaches administration of MEDI-551 every 6 months starting from day 1; that Agius does not present any of the doses disclosed in Agius as effective for treating MS, much less an entirely different disease, NMOSD; that while Agius does disclose three IV doses, 30, 10 or 600 mg, none of these doses is the 300 mug dose recited in the present claims, and the Office does not provide a reason why one of ordinary skill in the art would have picked a 300 mg IV dose base on the disclosure of Agius, but instead alleges that arriving at such a dose is routine optimization; that the Office has only arrived at a 300 mg IV dose using the Applicant's claim as a roadmap which is impermissible hindsight reconstruction; that the dosing schedule in claim 1, which is the approved dosing schedule of inebilizumab comprises the week 2 (day 15) loading dose that is specifically timed to deplete the newly recirculated B-cells from peripheral organs/tissues that are released to replenish what was previously depleted systemically from the initial dose, and the every 6 month dose maintains deep B-cell depletion, based on B-cell repletion kinetics; that Examiner has not, for example, pointed to a single prior art reference that discloses 1) a 300 mg IV dose of inebilizumab, 2) every 6 month maintenance dosing starting from Day 1, or 3) a loading dose of inebilizumab on Day 15/week 2, such that not a single one of these claim elements is present in the cited references, and the Examiner has not provided findings of facts or reasons, based on the cited references, why one of ordinary skill in the art would have had a reason to select any one of these elements, much less this combination of elements.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 03/02/2026 have been carefully considered but are not deemed persuasive.
With regards to the instant specific intravenously dosing schedule of inebilizumab on Day 1, Day 15 and at 6 month intervals from Day 1, Agius et al. teaches that administration of inebilizumab on Day 1 and Day 15 provided the benefit of rapid depletion of B cells in multiple sclerosis patients (Pg. 241 Column, first, Paragraph, spanning), in addition to complete B-cell depletion that is accompanied by highly favorable control of new lesion development with said inebilizumab dosing schedule when compared with placebo (Abstract). Moreover, depletion of B cells is an effect of rituximab taught by Patra et al. as a factor contributing to the reduced occurrence of relapse with NMO (Pg. 377 Column second, second full paragraph). Since the dosing schedule of inebilizumab taught by Agius et al. was successful in rapidly and completely depleting B cells for superior management of MS, the depletion of B cells based on the schedule of Agius et al. would likewise provide a reduction in the symptoms of NMOSD as suggested by the teachings of Patra et al. Further, Damschroder et al. teaches that the administration of inebilizumab for the treatment of B cell disorders can be provided in a loading dose and a maintenance that is administered 14 days apart (Column 142 Lines 49-53), and Cree et al. teaches that inebilizumab was administered every 6 months to patients until the study was terminated or until regulatory approval (Pg. 866, Column, first, Paragraph, spanning) and Bradshaw and Kimbrough teaches said study reduced the risk of relapse by 77% compared with treatment with placebo (Pg. 83 Column, first, Paragraph third).
With regards to the instant specific intravenous dose of 300 mg of inebilizumab, the teachings of Agius et al. showed that intravenous administration of inebilizumab at three doses of 30, 100 or 600 mg provided favorable outcomes for patients with MS that included dramatically lowering the number of new or newly enlarging lesions and nearly doubled the proportion of patients free of new inflammatory activity when compared with placebo (Pg. 240, Column, second, Paragraph, first; Figure 6). Arriving at a dose of 300 mg for the treatment of NMOSD would have been guided by the teachings of Agius et al. Figure 4 which showed that the dose of 100 mg IV inebilizumab was able to deplete CD20 B cells up to 28 weeks (196 days) while that of 600 mg depleted CD B cell counts up to 36 weeks (252 days). Since the dosing frequency of 6 months (180 days) after the first dose is intended as instantly claimed, selecting a dose between 100 mg and 600 mg would provide the certainty that B cell depletion would be sustained up until the 6 month time point so that patients would be in remission.
With regards to UPLIZNA (inebilizumab) being the first drug approved by the FDA for the treatment of NMOSD, FDA approval does not necessarily render a dosing schedule suggested from teachings in the prior art as non-obvious. As described above, the dosing schedule for treatment of multiple scleroses as taught by Agius et al. would indicate the same dosing schedule applied to the treatment of NMOSD would benefit management of said disease when using the dosing schedule of a first dose on Day 1 and a second dose on Day 15 to provide rapid and complete depletion of B-cells during this time frame. Further, additional maintenance doses every six months would predictably maintain depletion of B-cells by inebilizumab based on teachings of Cree et al., Agius et al. and Bradshaw and Kimbrough.
Claim Rejections - 35 USC § 103 (second)
Claim(s) 99, 101, 103-106 and 109 are rejected under 35 U.S.C. 103 as being unpatentable over Damschroder et al. (US8883992B2 Date Published 2014-11-11).
Damschroder et al. teaches anti-CD19 mouse monoclonal antibodies (Abstract). Damschroder et al. also teaches human, humanized, or chimeric anti-CD19 antibodies that bind to the human CD19 antigen, as well as compositions comprising said antibodies (Column 4 Lines 14-17). They teach that a monoclonal antibody or fragment that binds a human CD19 antigen comprising a VH (heavy chain variable region) and a VK (light chain variable region), wherein said VH comprises the amino acid sequence of SEQ ID NO: 106, and wherein said VK comprises the amino acid sequence of SEQ ID NO: 111 (Column 152 Lines, 51-52 and Column 153 Lines 32-35). They also teach methods for the treatment of B cell disorders or diseases in human subjects using the therapeutic anti-CD19 antibodies that bind to the human CD19 antigen (Column 1 Lines 35-46). They further teach said methods wherein the therapeutic anti-CD19 antibodies that bind to the human CD19 antigen are administered intravenously (Paragraph spanning columns 96-97, in particular).
Sequence alignment of SEQ ID NO: 106 (VH) and SEQ ID NO: 111 (VK) as taught by Damschroder et al. with instant SEQ ID NO: 1 (VH) and SEQ ID NO: 2 (VL) respectively showed that these amino acid sequences matched 100%. In addition, it is to be noted that the instant specification teaches that MEDI-551 is also referred to as inebilizumab or VIB551 antibody (Pg. 6 Paragraph [0032]), and that VIB551 antibody comprises the amino acid sequence of VH of SEQ ID NO:1 and VL of SEQ ID NO:2 (Pg. 5 Paragraph [0024]). Since SEQ ID NO: 106 (VH) and SEQ ID NO: 111 (VK) of Damschroder et al. are identical to SEQ ID NO: 1 (VH) and SEQ ID NO: 2 (VL) of instant claim, the antibody of Damschroder et al. is therefore the antibody “inebilizumab”.
Damschroder et al. teaches preparing anti-CD19 antibody compositions with physiologically acceptable carriers, excipients or stabilizers, wherein acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include amino acids such as histidine; and sugars such as trehalose (Column 92 Lines 22-26, 28-30, 40-41 and 44-45). They further teach that the product can be formulated for i.v. administration in 9.0 mg/mL sodium chloride, 0.7 mg/mL polysorbate 80, and sterile water for injection where the pH is adjusted to 6.5 (Column 94, Lines 54-60). They further teach formulated anti-CD19 antibody can be supplied in either 100 mg (10 mL) or 500 mg (50 mL) single use vials which is equivalent to 10 mg/ml vials (Column 94, Lines 51-54).
Damschroder et al. teaches that the dose of anti-CD19 antibody used is at least about 1 to 10, 5 to 15, 10 to 20, or 15 to 25 mg/kg of body weight of a patient; or the dose of anti-CD19 antibody used is at least about 1 to 20, 3 to 15, or 5 to 10 mg/kg of body weight of a patient; or the dose of anti-CD19 antibody used is at least about 5, 6, 7, 8, 9, or 10 mg/kg of body weight of a patient (Column 98 Lines 13-20). They also teach that antibody compositions can be administered at a dose lower than about 375 mg/m2 at intervals of approximately every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, or 200 days (Column 98 Lines 56-60). They further teach that a loading dose of an anti-CD19 antibody composition can be administered first followed by a maintenance dose until the B cell malignancy being treated progresses or followed by a defined treatment course (Column 100 Lines 7-10). Damschroder et al. also teaches that the loading dose is about 10, 11, 12, 13, 14, 15, 16, 17, or 18 mg/kg of patient body weight and the maintenance dose is at least about 5 to 10 mg/kg of patient body weight, and that the maintenance dose is administered at intervals of every 7, 10, 14 or 21 days (Column 142 Lines 49-53).
Damschroder et al. does not specifically teach a composition wherein the composition comprises 20 mM of the histidine/histidine hydrochloride; 70 mM of the NaCI; 106 mM of the trehalose dihydrate; and 0.01% (w/v) of the polysorbate 80; wherein the composition comprises a pH of 6. They further do not specifically teach a vial comprising 10 mL of the said composition.
They also do not specifically teach a method of treatment comprising administering the composition of instant claim 101, formulated for intravenous administration, to a subject in need thereof, wherein the composition is administered at a dose of 300 mg; or wherein after a first administration of inebilizumab on Day 1, a 300 mg inebilizumab is administered to the subject on Day 15.
However, these deficiencies are made up by the teachings of Damschroder et al.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to optimize the physiologically acceptable carriers for the antibody composition to arrive at a composition that comprises 10 mg/mL of the antibody, 20 mM of the histidine/histidine hydrochloride; 70 mM of the NaCI; 106 mM of the trehalose dihydrate; and 0.01% (w/v) of the polysorbate 80. See MPEP 2144.05 II. A. Optimization Within Prior Art Conditions or Through Routine Experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). Also, "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the treatment method as taught by Damschroder et al. wherein a composition comprising the antibody inebilizumab as taught by Damschroder et al. in a composition comprising optimized concentrations and components of physiologically acceptable carriers of sodium chloride, trehalose and polysorbate 80 as taught by Damschroder et al. comprised in 10 mL vials as taught by Damschroder et al., and pH adjusted to about 6 as optimized from the teachings of Damschroder et al. to be administered intravenously to subjects as taught by Damschroder et al. at the loading dose and at the interval between the loading and maintenance dose of inebilizumab as optimized from the teachings of Damschroder et al. since it would have been obvious to optimize these parameters as taught by Damschroder et al. and because Damschroder et al. teaches methods for the treatment of B cell disorders or diseases in human subjects using anti-CD19 antibody inebilizumab.
The motivation to make said composition comprising inebilizumab and said physiologically acceptable carriers at the claimed concentrations would be to have a stable and safe composition that can simplify administration to a subject in need of treatment at a dosage and dosing schedule that has been utilized as taught by Damschroder et al.
With respect to claims 99, 106 and 109, to arrive at an administered dose that is 300 mg of inebilizumab, this would translate to a dose of 3.33 mg/kg for an average male of 90kg or4 mg/kg for an average female of 75 kg. The range of 1 to 20 mg/kg as taught by Damschroder et al. in Column 98 Lines 13-20 encompasses the dosing range calculated here of 3.33-4 mg/kg for the average male and female subject to arrive at the claimed administered dose of 300 mg.
With respect to claim 109, to arrive at a dosing interval or frequency of administering inebilizumab on Day 1 and Day 15, Damschroder et al. teaches that administration at intervals of every 7, 10, 14 or 21 days (Column 142 Lines 49-53) encompasses the claimed schedule on Day 1 and on Day 15 when an interval of every 14 days is employed.
Response to Arguments
In the Reply of 03/02/2026, Applicant cites that Applicant respectfully disagrees with the rejection. Applicant cites that claim 99 has been amended and now recites that 300 mg of the antibody in the composition is administered and claim 102 has been amended to recite the precise components of the formulation. Applicant also cites that Damschroder does not teach a composition with inebilizumab comprising the recited components, the precise concentrations of the components, or the dose that is administered; that the Office has provided no findings of fact or reason why a person of ordinary skill in the art would arrive at the claimed formulation or a 300 mg IV dose with a reasonable expectation of success based on the disclosure of Damschroder; and that the Office has only arrived at the rejection using the Applicant's claim as a roadmap which is impermissible hindsight reconstruction.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 03/02/2026 have been carefully considered but are not deemed persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Further, Damschroder teaches each of the components recited in the instant claims and also potential concentrations and pH ranges of the inebilizumab composition for treatment of B cell disorders or diseases. It would be obvious, with an expectation of success, to try the various concentrations with each component, including recited concentrations, in order to determine which concentrations would result in the best stability and/or therapeutic efficacy for the instant treatment of NMOSD. See MPEP 2144.05. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997) (Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.")
In addition, the recitation of “wherein the composition is administered at a dose of 300 mg” in claim 99 is regarded as intended use of a composition/product and as such the “dose of 300 mg” does not provide further structural limitation to the composition and of which can be arrived at through optimization of the teachings of Damschroder et al.
Claim Rejections - 35 USC § 103 (third)
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119, 120, 124, 125, 129 and 133 are rejected under 35 U.S.C. 103 as being unpatentable over NCT02200770 (N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders; Record History 2018-04-05), Cree et al. (Multiple Sclerosis Journal 2016, Vol. 22(7) 862-872), Bradshaw and Kimbrough (Practical Neurology 2019: 76-89), Agius et al. (Multiple Sclerosis Journal 2019, Vol. 25(2) 235–245) and Patra et al. (Therapeutic Innovation & Regulatory Science 2016, Vol. 50(3) 375-384) as applied to Claims 1, 2, 17, 35, 125 and 133 above and further in view of Damschroder et al. (US8883992B2 Date Published 2014-11-11) and Kleiter and Gold (Neurotherapeutics Vol 13, Issue 1, 2016, Pages 70-83).
The combined teachings of NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al. and Patra et al. already render obvious instant claims 1, 2, 17, 35, 125 and claim 133, as discussed in the first 103 rejection above.
NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al. and Patra et al. do not specifically teach a method of treating NMOSD comprising intravenously administering a composition that comprises: (a) 10 mg/ml of an antibody that comprises a variable heavy chain and a variable light chain that comprise instant SEQ ID NO: 1 and instant SEQ ID NO: 2 (the SEQ ID NOs of inebilizumab of the combined method); and (b) 20 mM of histidine/histidine hydrochloride, 70 mM of NaCI, 106 mM of trehalose dihydrate, and 0.01% (w/v) of polysorbate 80, wherein the antibody is administered at a dose of 300 mg, wherein the 300 mg is administered every 6 months, wherein after a first administration of the antibody on day 1, a 300 mg dose of the antibody is administered to the subject on day 15; wherein the administering is effective in reducing the risk of an NMOSD-related attack of the subject and/or reducing the number of MRI lesions.
They also do not specifically teach a method wherein a corticosteroid is tapered.
However, these deficiencies are made up in the teachings of Damschroder et al. and Kleiter and Gold.
The teachings of Damschroder et al. are discussed above in the second 103 rejection.
Kleiter and Gold teach pharmacological therapies used for prevention of attacks in NMOSD include oral prednisolone of up to 1 mg/kg/day at a usual dose of 15-30 mg/day (Pg. 73 Table 1). They also teach that steroid side effects can occur and as such prednisolone is tapered after 1 year of administration (Pg. 73 Table 1). They further teach that a small retrospective study of 9 patients with NMOSD reported that the median ARR decreased from 1.48 in untreated patients to 0.49 in corticosteroid-treated patients; doses >10 mg/day were associated with fewer attacks (Pg. 73 Column, first, Paragraph, spanning).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating NMOSD comprising administering inebilizumab as taught by NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al. and Patra et al. and combining the method of administering the antibody that is comprised in a composition comprising 10 mg/ml of inebilizumab in 10 mL vials as taught by Damschroder et al. and comprising amounts/concentrations of physiologically acceptable carriers and pH adjusted to 6 as optimized from the teachings of Damschroder et al. and administered at doses and schedule intervals as taught by the combined method and by Damschroder et al. because Damschroder et al. teaches said physiologically acceptable carriers are formulated with the anti-CD19 antibody of inebilizumab for the treatment of human B cell diseases and optimizing loading dose/schedule is possible from the combined teachings of NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al. and Damschroder et al. The motivation to generate and use said antibody composition would be to have a stable and safe antibody composition that can simplify administration to a subject in need of treatment for NMOSD, at a dosage and dosing schedule that has been observed to reduce risk of NMOSD-related attacks and reducing number of MRI lesions upon administration. This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the corticosteroid prednisolone (that is tapered after use of one year) is also administered for the prevention of NMOSD attacks as taught by Kleiter and Gold. The motivation would be to provide an additional strategy for the prevention of attacks from the severely damaging and disabling outcomes of the NMOSD disease (Kleiter and Gold Abstract) while the motivation for tapering corticosteroid dose would be to lower the side effects that accompany long term use.
Response to Arguments
In the Reply of 03/02/2026, Applicant states they respectfully disagree with the rejection. Applicant also cites that the deficiencies of Cree in view of NCT02200770, Patra, Agius and Bradshaw and Kimbrough are discussed above and that Damschroder and Kleiter and Gold do not make up for this deficiency, as they do not disclose the specific dosing schedule of inebilizumab OR the specific components of the claimed composition, much less at the specific concentrations of each component.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 03/02/2026 have been carefully considered but are not deemed persuasive. The Examiner maintains the same response as the ones made for the Arguments to the first and second 103 rejections found in this Office Action.
The Examiner further adds that Kleiter and Gold teach the same disease of NMOSD that is claimed in the instant application and that methods of preventing NMOSD attacks include administration of oral prednisolone which is a well-known corticosteroid that is generally well-tolerated for short courses and that gradual tapering enhances tolerability by allowing adrenal function recovery and providing lowered side effects.
Claim Rejections - 35 USC § 103 (Fourth)
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124, 125, 129 and 133 are rejected under 35 U.S.C. 103 as being unpatentable over NCT02200770 (N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders; Record History 2018-04-05), Cree et al. (Multiple Sclerosis Journal 2016, Vol. 22(7) 862-872), Bradshaw and Kimbrough (Practical Neurology 2019: 76-89), Agius et al. (Multiple Sclerosis Journal 2019, Vol. 25(2) 235–245), Patra et al. (Therapeutic Innovation & Regulatory Science 2016, Vol. 50(3) 375-384), Damschroder et al. (US8883992B2 Date Published 2014-11-11) and Kleiter and Gold (Neurotherapeutics Vol 13, Issue 1, 2016, Pages 70-83) as applied to Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119, 120, 124, 125, 129 and 133 above and further in view of Borisow et al. (Frontiers in Neurology Vol. 9 (2018): 888) and Williams (Respiratory Care Vol. 63 (6), 2018).
The combined teachings of NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al., Patra et al, Damschroder et al. and Kleiter and Gold already render obvious instant claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119, 120, 124, 125, 129 and 133 as discussed in the third 103 rejection above.
They do not specifically teach a method of treating NMOSD in a subject in need thereof, wherein the corticosteroid is prednisone.
However, these deficiencies are made up in the teachings of Borisow et al. and Williams.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating NMOSD comprising administering inebilizumab and prednisolone as taught by NCT00200770, Cree et al., Bradshaw and Kimbrough, Agius et al. and Patra et al. and Kleiter and Gold and substituting the prednisolone as taught by Kleiter and Gold for prednisone as taught by Borisow et al. and Williams to provide prophylaxis treatment against an NMOSD attack as taught by Kleiter and Gold and to prevent NMOSD acute attacks as taught by Borisow et al. The motivation would be due to reasons such as lower cost, higher dose per unit dosage tablet and wider availability in certain regions for prednisone. This is an example of (B) Simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 03/02/2026, Applicant states they respectfully disagree with the rejection. Applicant also cites that the deficiencies of Cree in view of NCT02200770, Patra, Agius and Bradshaw and Kimbrough and Kleiter and Gold are discussed above and that Borisow and Williams do not make up for this deficiency, as they do not disclose the specific dosing schedule of inebilizumab OR the specific components of the claimed composition, much less at the specific concentrations of each component.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 03/02/2026 have been carefully considered but are not deemed persuasive. The Examiner maintains the same responses made in response to the Arguments to the first, second and third 103 rejections found in this Office Action.
The Examiner further adds that Borisow et al. teaches the same disease of NMOSD that is claimed in the instant application and that therapeutic options to prevent acute NMOSD attacks include administration of low dose oral prednisone. Further, the teachings of Williams support the use of oral prednisone as taught by Borisow et al. or oral prednisolone as taught by Kleiter and Gold in the management of NMOSD by teaching that prednisone is the prodrug of prednisolone which would provide the same pharmacological benefits of decreasing frequency of acute attacks.
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.
First NSDP: Application No. 18/147287
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124, 125, 129 and 133 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 60, 67, 68, 73-75, 80, 81 and 89 of copending Application No. 18/147287, in view of NCT02200770 (N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders; Record History 2018-04-05), Cree et al. (Multiple Sclerosis Journal 2016, Vol. 22(7) 862-872), Bradshaw and Kimbrough (Practical Neurology 2019: 76-89), Agius et al. (Multiple Sclerosis Journal 2019, Vol. 25(2) 235–245), Patra et al. (Therapeutic Innovation & Regulatory Science 2016, Vol. 50(3) 375-384), Damschroder et al. (US8883992B2 Date Published 2014-11-11), Kleiter and Gold (Neurotherapeutics Vol 13, Issue 1, 2016, Pages 70-83), Borisow et al. (Frontiers in Neurology Vol. 9 (2018): 888) and Williams (Respiratory Care Vol. 63 (6), 2018).
Although the claims at issue are not identical, both the instant claims and the copending claims are drawn to methods of treating NMOSD comprising administering inebilizumab to a subject in need of treatment, wherein inebilizumab is administered at a dose of 300 mg every 6 months, wherein the administration is effective in reducing or suppressing NMOSD-related attack of the subject, and wherein corticosteroid is co-administered.
Claims of copending Application No. 18/147287 do not specifically recite a method of treating NMOSD comprising intravenously administering inebilizumab wherein after a first administration of inebilizumab on day 1, a 300 mg dose of inebilizumab is administered to the subject on day 15, wherein the subject is AQP4-IgG seropositive, wherein the reduction of risk of NMOSD-related attack is between 60-85%, wherein the inebilizumab is administered at a dose of 300 rug every 6 months for at least 1 year.
Claims of copending Application No. 18/147287 also do not specifically recite a composition comprising an antibody comprising the amino acid sequences of instant SEQ ID NOs: 1 and 2 or comprising the antibody inebilizumab in combination with acceptable carriers as recited in instant claims at pH 6; or a method of treatment comprising administering said composition using the instant claim recited dosing schedule on Day 1 and Day 15.
Claims of copending Application No. 18/147287 further do not specifically recite a method of treating NMOSD comprising intravenously administering a composition comprising 10 mg/ml of an antibody comprising the amino acid sequences of instant SEQ ID NOs: 1 and 2 and in combination with acceptable carriers as recited in instant claims at pH 6, using the instant claim recited dosing schedule on Day 1 and Day 15, and then every 6 months from Day 1; or wherein the method of treating NMOSD comprises administering said composition and administration of corticosteroid that is tapered or that is prednisone; or wherein the subject is AQP4-IgG seropositive.
However, these deficiencies are made-up in the teachings of NCT02200770, Bradshaw and Kimbrough, Agius et al., Patra et al., Damschroder et al., Kleiter and Gold, Borisow et al. and Williams.
The combined method of NCT02200770, Bradshaw and Kimbrough, Patra et al., Agius et al., Damschroder et al., Kleiter and Gold, Borisow et al. and Williams is discussed above in the 103 rejections.
Therefore, it would have been obvious to perform a method of treating NMOSD as recited by the copending claims of administering inebilizumab to a subject in need of treatment, wherein inebilizumab is administered at a dose of 300 mg every 6 months, wherein the administration is effective in reducing or suppressing NMOSD-related attack of the subject, and wherein corticosteroid is co-administered, and combine it with the combined methods of administering inebilizumab to subjects that are AQP4-IgG positive as taught by NCT00200770, at a dosing frequency of day 1 and day 15 as taught by Agius et al. The motivation to perform said combined method would be to effectively reduce symptoms of NMOSD because Bradshaw and Kimbrough teach that inebilizumab administration every 6 months to patients with NMOSD reduced the risk of relapse by 77% compared with treatment with placebo and because Agius et al. teaches that inebilizumab administration on Day 1 and Day 15 is safe and is efficacious in MS patients. A further motivation to use inebilizumab in the treatment of NMOSD stems from the teachings of Patra et al. which teaches that experience with rituximab suggested that B-cell depletion in NMO might reduce the occurrence of relapses (Pg. 377 Column second, second full paragraph) and that rituximab, a B-cell depleting monoclonal antibody was used off-label to treat NMOSD in several small case series (Pg. 377 Column, second, Paragraph, first). Further, Patra et al. also teaches that because both MEDI-551 and rituximab deplete B cells, it was postulated that their clinical effect may be similar, although MEDI-551 depletes a broader range of B cells and plasmablasts (Pg. 377 Column, second, Paragraph, first). The advantage of using inebilizumab/MEDI-511 for the treatment of NMOSD would be precisely due to its broader range of activity against B cells and plasmablasts causing depletion in the numbers of said cells.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein inebilizumab is administered intravenously at doses of 300 mg on days 1 and 15, and continue with maintenance doses every 6 months after Day 1 or Day 15 for at least 1 year for treating NMOSD since it would have been obvious to optimize the dosage as taught by Agius et al. that inebilizumab was administered intravenously with doses on days 1 and 15 at 30, 100 or 600 mg for MS in a clinical trial (Abstract and Pg. 236 Column, second, Paragraph, third) and administered every 6 months to NMO patients until the study was terminated or until regulatory approval which could be for at least 1 year or more as taught by Cree et al. (Pg. 866, Column, first, Paragraph, spanning).
Also, with regards to instant claims reciting the composition comprising the antibody and physiologically acceptable carriers (claims 99, 101, 103-106, 109-110, 113, 114, 116, 117 and 119-121), it would also have been obvious to optimize and arrive at a composition comprising inebilizumab antibody recited by the copending claims and comprising amounts of physiologically acceptable carriers as taught by Damschroder et al. formulated in 10 mL vials, pH adjusted to 6 and optimized to the instant claim concentrations for histidine, trehalose, sodium chloride and polysorbate 80 and used at doses and at dosing intervals as guided by the teachings of Damschroder et al. since Damschroder et al. teaches said physiologically acceptable carriers, are formulated in a composition with the anti-CD19 antibody that matches in amino acid sequence with instant SEQ ID NOs: 1 and 2 for the treatment of B cell related diseases. The motivation to generate and use said antibody composition would be to have a stable and safe antibody composition that can simplify administration to a subject in need of treatment for NMOSD, at a dosage and dosing schedule that has been observed to reduce risk of NMOSD-related attacks and reducing number of MRI lesions upon administration.
With respect to instant claim 109, it would also have been obvious to arrive at a method of treatment comprising a dosing frequency of administering inebilizumab on Day 1 and Day 15 because Damschroder et al. teaches that administration of inebilizumab at intervals of every 7, 10, 14 or 21 days (Column 142 Lines 49-53) encompasses the instant claimed schedule on Day 1 and on Day 15 when an interval of every 14 days is employed.
With regards to instant claim 120, it would have been obvious to perform said combined method wherein the dose of the corticosteroid is tapered as taught by Kleiter and Gold. The motivation for tapering the corticosteroid dose would be to lower the side effects that accompany long term use.
With regards to instant claim 121, it would have been obvious to perform said combined method wherein the corticosteroid prednisone is also administered as taught by Borisow et al. and Williams. The motivation to include prednisone as the corticosteroid would be due to reasons such as lower cost, higher dose per unit dosage tablet and wider availability in certain regions for prednisone.
With respect to instant claim 133, it would have been obvious to perform the combined method of administering inebilizumab every 6 months at a dose of 300 mg as recited by the copending claims, in combination with the dosing schedule of inebilizumab on Day 1 and Day 15 as taught by Agius et al., because copending claims and Bradshaw and Kimbrough teaches dosing of inebilizumab at 6 monthly intervals in patients with NMOSD, and further because Bradshaw and Kimbrough teaches that in the N-Momentum clinical trial, inebilizumab provided superior reduction of relapse risk compared to placebo. Therefore, the combined dosing schedules of the copending, Agius et al. and Bradshaw and Kimbrough make it obvious to administer the dose of inebilizumab every six months for the benefits that have been described above.
This is a provisional nonstatutory double patenting rejection.
Second NSDP: Application No. 18/303303
Claims 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124, 125, 129 and 133 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-75 of copending Application No. 18/303303 in view of Damschroder et al. (US8883992B2 Date Published 2014-11-11), Kleiter and Gold (Neurotherapeutics Vol 13, Issue 1, 2016, Pages 70-83), Borisow et al. (Frontiers in Neurology Vol. 9 (2018): 888) and Williams (Respiratory Care Vol. 63 (6), 2018).
Although the claims at issue are not identical, both the instant claims and the copending claims are drawn to methods of treating NMOSD comprising intravenously administering the antibody VIB551/inebilizumab to a subject in need of treatment, wherein after a first 300 mg administration of VIB551/inebilizumab on day 1, a 300 mg dose of VIB551/inebilizumab is administered to the subject on day 15, and then every 6 months from Day 1, wherein the subject is AQP4-IgG seropositive; wherein the administration is effective in reducing a) worsening of Kurtzke Expanded Disability Severity Scale (EDSS) in the subject; b) number of magnetic resonance imaging (MRI) lesions; c) number of new MRI lesions; d) worsening of modified Rankin Score; e) frequency of in-patient hospitalizations of the subject related to NMOSD; f) between 60 and 85% risk of an NMOSD-related attack of the subject ; g) optic neuritis; or h) severity of NMOSD-related attacks;, and wherein corticosteroid is co-administered with the first 300 mg inebilizumab dose.
It is noted that the antibody VIB551 of copending claims is the same antibody inebilizumab as recited in instant claims and also disclosed in the instant specification (Pg. 6 Paragraph [0032]). In addition, the SEQ ID NOs: 1 and 2 of copending claim matches exactly with instant SEQ ID NOs: 1 and 2 which are the VH and VL amino acid sequences of the identical antibodies.
Claims of copending Application No. 18/303303 do not specifically recite a composition comprising the antibody VIB551/inebilizumab in combination with acceptable carriers as recited in instant claims at pH 6; or a method of treatment comprising administering said composition; or a method of treating NMOSD comprising administering said composition; or wherein said method of treating NMOSD comprises administration of corticosteroid that is tapered or that is prednisone.
However, these deficiencies are made-up in the teachings of Damschroder et al., Kleiter and Gold, Borisow et al. and Williams.
The combined method of Damschroder et al., Kleiter and Gold, Borisow et al. and Williams is discussed above in the 103 rejections.
Therefore, it would have been obvious to perform a combined method of treating NMOSD by administering the antibody VIB551/inebilizumab as recited by the copending claims at the dosage of 300 mg and the dosing intervals of Day 1, Day 15 and every 6 months from Day 1, and further wherein the antibody is comprised in a composition that also comprises physiologically acceptable carriers based on the teachings of Damschroder et al. formulated in 10 mL vials, pH adjusted to 6 and optimized to the instant claims concentrations for histidine, trehalose, sodium chloride and polysorbate 80 since Damschroder et al. teaches said physiologically acceptable carriers are formulated in a composition with the anti-CD19 antibody inebilizumab for the treatment of B cell related diseases. The motivation to generate and use the said antibody composition would be to have a stable and safe antibody composition that can simplify administration to a subject in need of treatment for NMOSD, at a dosage and dosing schedule that has been observed to reduce risk of NMOSD-related attacks and reducing number of MRI lesions upon administration.
Further, it would have been obvious to perform the said combined method of treating NMOSD comprising administering the said antibody composition as optimized based on the teachings of Damschroder et al., and further including a tapered dose of corticosteroid as taught by Kleiter and Gold, and even further by including prednisone as the corticosteroid as taught by Borisow et al. and Williams. The motivation for tapering the corticosteroid dose would be to lower the side effects that accompany long term use. The motivation to include prednisone as the corticosteroid would be due to reasons such as lower cost, higher dose per unit dosage tablet and wider availability in certain regions for prednisone.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 03/02/2026, Applicant repeats the citation that none of the cited references disclose the specific dose or dosing schedule of inebilizumab or the specific components of the claimed composition, much less at the specific concentrations of each component. Applicant also submits that the present claims are patentably distinct over the claims of the '287 application.
Examiner’s Response: The amendments to the claims and the arguments found in the Reply of 03/02/2026 have been carefully considered but are not deemed persuasive. The Examiner maintains the same responses made in response to the Arguments to the first, second, third and fourth 103 rejections found in this Office Action.
New Objections
Claim Objections - New
Claims 99, 101, 103, 110, 116, 117, 119, 125, 129 and 133 are objected to because of the following informalities:
Claims 99, 101, 110, 117, 129 and 133 recite the phrase “an antibody that comprises a variable heavy chain and variable light chain”. The word “a” is missing before “variable light chain”. It is suggested that the claims be amended to recite “an antibody that comprises a variable heavy chain and a variable light chain”.
Claims 103, 116 and 119 recite the name of the antibody “Inebilizumab” in capital. It is suggested that this be changed to “inebilizumab” for consistency as recited in other claims.
Claims 110 appears to have a typographical error in the phrase “10 mg/ml of the antibody of an antibody”. The phrase “of the antibody” should be deleted so that the claim recites “10 mg/ml of an antibody”.
Claim 125 appear to contain an unnecessary word “the” before “inebilizumab.
New Rejections
Claim Rejections - 35 USC § 112 - New
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 1, 2, 17, 35, 99, 101, 103-106, 109, 110, 113, 114, 116, 117, 119-121, 124, 125 and 129 are 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 99 and 106 recite the phrase “wherein the composition is administered at a dose of 300 mg”. It is unclear what component in the composition the dose of 300 mg refers to since the composition comprises an antibody, histidine/histidine hydrochloride, NaCI, trehalose dihydrate, and polysorbate 80. The Examiner has taken this 300 mg dose to refer to the dose of the antibody based in the limitations in claim 1. Therefore, it is suggested that the claims be amended to recite the phrase “wherein the composition is administered at a dose of 300 mg of the antibody”. Claim 109 which depends on claim 106 is also rejected here.
Claims 101, 110 and 117 recites the phrase “20 mM of the histidine/histidine hydrochloride; 70 mM of the NaCI; 106 mM of the trehalose dihydrate; and 0.01% (w/v) of the polysorbate 80”. There is lack of antecedent basis for “the histidine/histidine hydrochloride”, “the NaCI”, “the trehalose dihydrate” and “the polysorbate 80” in the claims. It is suggested that the claims be amended to recite “20 mM of histidine/histidine hydrochloride; 70 mM of NaCI; 106 mM of trehalose dihydrate; and 0.01% (w/v) of polysorbate 80”. Dependent claims of claim 101, namely 103-106 and 109, dependent claims of claim 110, namely claims 113, 114, 116, and dependent claims of claim 117, namely 119-121 and 124 are also rejected here.
Claims 120 and 121 recite the phrase “the corticosteroid”. There is lack of antecedent basis for “the corticosteroid” in the claims.
Claim 126 is rejected for reciting “The method of claim 108, wherein….”. Claim 108 is cancelled. The metes-and-bounds of claim 126 are unclear because it is unclear which method claim126 is further limiting.
Claim 127-128 are rejected for reciting “The method of claim 112, wherein….”. Claim 112 is cancelled. The metes-and-bounds of claims 127-128 are unclear because it is unclear which method the claims are further limiting.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia (Tonya) Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 8.30a - 5.30p Eastern Time Zone.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YIE-CHIA LEE (TONYA)/
Examiner, Art Unit 1642 /SEAN E AEDER/Primary Examiner, Art Unit 1642
Prosecution Insights