DETAILED ACTION
NOTE: The examiner for this application has changed. The new examiner is Sean Aeder.
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 .
The Amendments and Remarks filed 10/1/25 in response to the Office Action of 5/8/25 are acknowledged and have been entered.
Claims 47-93 have been added by Applicant.
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are pending.
Claims 1, 7, 8, 20-25, 28-31, 38, and 42-44 have been amended by Applicant.
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections.
Objections and Rejections Withdrawn
All previous objections and rejections are withdrawn.
New Rejections
Claim Rejections - 35 USC § 103
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18; 8/8/23 IDS).
Bar-Or et al teaches a method of therapeutically treating subjects with relapsing forms of multiple sclerosis (RRMS) comprising administering the anti-CD20 antibody ofatumumab to the subjects (page e1805 and Figure 2, in particular). Bar-Or et al further teaches such subjects with RMS are RRMS patients (left column on page e1806, in particular). Bar-Or et al further teaches administering ofatumumab to a subject causes a reduction in the subject’s B cells (right column on page e1808). Bar-Or et al further teaches both subcutaneous and intravenous administration of ofatumumab results in reduction in new MRI lesion activity in patients with RMS or RRMS (left column on page e1806 and Table 1, in particular). Bar-Or et al further teaches RRMS patients subcutaneously administered ofatumumab include those that have baseline MRI scans with active lesions (Table 1, in particular) and that the administration of ofatumumab to subjects with RMS therapeutically decreases new T2 lesions and decreases new GdE T1 lesions measured by MRI scan (page e1807, paragraph spanning columns on page e1808, Figure 2, and Figure e-3, in particular). Bar-Or et al does not teach administering a premedication before ofatumumab. Subjects of Bar-Or et al have an EDSS score of 0 to 5.5 prior to administration of ofatumumab (left column on page e1806, in particular) and predictably include subjects that are not lactating, as only 67% of the subjects were female (Table 1, in particular). Bar-Or et al further teaches subcutaneous administration of 3, 30, or 60 mg ofatumumab every 12 weeks or 60 mg every 4 weeks, where lesion reductions v placebo was obtained for all cumulative ofatumumab doses ≥30 mg/12 wk (Results at page e1805, in particular). Bar-Or et al further teaches, over a 24-week period of treatment with ofatumumab, 9-22 % of patients relapsed -as compared to 25% of patients treated with placebo (right column on page e1808, in particular). Prior use of other disease-modifying therapies, including natalizumab, was permitted by the subjects treated by Bar-Or et al (paragraph spanning column on page e1806, in particular).
In particular regards to instant claims 30, 65, and 66, Bar-Or et al does not specifically teach the treatment method of Bar-Or et al of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of Bar-Or et al appears to be the same as claims 30, 65, and 66 as the method of Bar-Or et al administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
While prior use of other disease-modifying therapies (including natalizumab) was permitted by Bar-Or et al, Bar-Or et al does not specifically teach the RRMS subjects were actually previously treated with any other particular disease-modifying therapy. However, these deficiencies are made up in the teachings of Hu et al, Baroncini et al, Blinkenberg et al, Huggins et al, and Wallstrom et al.
Hu et al teaches ocrelizumab (humanized anti-CD20 antibody), rituximab (mouse chimeric anti-CD20 antibody), natalizumab, glatiramer acetate (a first line treatment), and fingolimod as treatments for RRMS (Table 1, in particular). Hu et al further teaches ocrelizumab has limited availability (right column on page 542, in particular) and adverse events and relapse occur with patients administered rituximab (left column on page 546, in particular). Hu et al further teaches adverse events of administered rituximab include infusion-related adverse events, infection, and hematological disorder (left column on page 545, in particular).
Baroncini et al teaches treating RRMS patients with natalizumab or fingolimod, wherein 80% of the natalizumab patients became relapse-free and 66% of fingolimod patients became relapse-free (Abstract, in particular).
Blinkenberg et al teaches RRMS patients can be therapeutically treated with rituximab (page 364, in particular), natalizumab (page 358, in particular), and daclizumab (pages 361-362, in particular). Blinkenberg et al further teaches daclizumab can result in severe side effects (right column on page 367, in particular). Blinkenberg et al further teaches rituximab, natalizumab, and daclizumab are intravenously administered (left column on page 364, left column on page 358, right column on page 361, in particular).
Huggins et al teaches fingolimod of Hu et al and Baroncini et al is administered to RRMS patients orally (left column on page 447, in particular). Huggins et al further discusses lack of tolerability of some RRMS medications (left column on page 447, in particular).
Wallstrom et al teaches methods of treating a subject with MS, including RRMS, by subcutaneously administering to the subject ofatumumab (last paragraph on page 8, in particular). Wallstrom et al further teaches methods of treating MS comprising subcutaneously administering a loading dose of ofatumumab followed by a maintenance regimen (Abstract, in particular). Wallstrom et al further teaches said method wherein the loading dose is preferably 20 mg ofatumumab administered on day 0, day 7, and day 14 prior to administering the first maintenance dose (same as “three once weekly”; see first paragraph on page 3, in particular). Wallstrom et al further teaches said method wherein the maintenance dose is preferably administering 20 mg of ofatumumab at week 4 and every four weeks thereafter (same as “monthly”; second full paragraph on page 3, in particular). Wallstrom et al further teaches the administered ofatumumab formulation preferably comprises 50 mg/mL ofatumumab and 50 mM sodium acetate, 51 mM sodium chloride, 1% arginine free base, 0.05 mM EDTA, 0.02% polysorbate 80, and adjusted to pH 5.5 (fourth and fifth full paragraph on page 15, in particular). Wallstrom et al further teaches the administered ofatumumab formulation is provided for subcutaneous administration, and administered, by a pre-filled syringe (sixth full paragraph on page 15 and claim 15, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat subjects with RRMS that have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
This is an example of 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.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11161909 B2 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the patent claims and the instant claims are drawn to treating a subject with MS (including RRMS) by subcutaneously administering ofatumumab. The instant claims differ from the patent claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with another disease-modifying therapy. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the patent method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, patent claims do not specifically teach the treatment method of the patent of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the patent appears to be the same as claims 30, 65, and 66 as the method of the patent administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12338290 B2 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the patent claims and the instant claims are drawn to treating a subject with MS (including RRMS) by subcutaneously administering ofatumumab. The instant claims differ from the patent claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with another disease-modifying therapy. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the patent method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, patent claims do not specifically teach the treatment method of the patent of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the patent appears to be the same as claims 30, 65, and 66 as the method of the patent administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12570754 B2 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the patent claims and the instant claims are drawn to treating a subject with MS (including RRMS) by subcutaneously administering ofatumumab. The instant claims differ from the patent claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with another disease-modifying therapy. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the patent method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, patent claims do not specifically teach the treatment method of the patent of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the patent appears to be the same as claims 30, 65, and 66 as the method of the patent administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 20, 27, 31-37, 40, 41, and 54-57 of copending Application No. 17/753635 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the copending claims and the instant claims are drawn to treating a subject with MS (including RRMS) by subcutaneously administering ofatumumab. The instant claims differ from the copending claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with another disease-modifying therapy. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the copending method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (with or without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, copending claims do not specifically teach the treatment method of the copending claims of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the copending claims appears to be the same as claims 30, 65, and 66 as the method of the copending claims administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
This is a provisional nonstatutory double patenting rejection.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-36 of copending Application No. 18/683858 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the copending claims and the instant claims are drawn to treating a subject with MS (including RRMS), including a subject that has been previously treated by an MS disease-modifying therapy other than ofatumumab (see copending claim 26), by subcutaneously administering ofatumumab. The instant claims differ from the copending claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with a disease-modifying therapy recited by the instant claims. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the copending method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (with or without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, copending claims do not specifically teach the treatment method of the copending claims of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the copending claims appears to be the same as claims 30, 65, and 66 as the method of the copending claims administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
This is a provisional nonstatutory double patenting rejection.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-45 of copending Application No. 18/286030 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the copending claims and the instant claims are drawn to treating a subject with MS (including RRMS) by subcutaneously administering ofatumumab. The instant claims differ from the copending claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with another disease-modifying therapy. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the copending method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (with or without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, copending claims do not specifically teach the treatment method of the copending claims of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the copending claims appears to be the same as claims 30, 65, and 66 as the method of the copending claims administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
This is a provisional nonstatutory double patenting rejection.
Double Patenting
Claims 1-11, 20-25, 28-32, 38, 42-44, and 47-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-75 of copending Application No. 19/221422 in view of Bar-Or et al (Neurology, 2018, 90(20):e1805-e1814) in view of Hu et al (Autoimmunity Reviews, 2019, 18: 542-548), Baroncini et al (Multiple Sclerosis Journal, 2016, 22(10): 1315-1326), Blinkenberg et al (CNS Drugs, 2017, 31: 357-371), Huggins et al (Current Opinion in Ophthamology, 2011, 22(6): 447-450), and Wallstrom et al (WO 2018/033841 A1; 2/22/18).
Both the copending claims and the instant claims are drawn to treating a subject with MS (including RRMS), including a subject that has been previously treated by an MS disease-modifying therapy other than ofatumumab (see copending claim 48), by subcutaneously administering ofatumumab. The instant claims differ from the copending claims in that the instant claims recite the subject with MS (or RRMS) has been previously treated with a disease-modifying therapy recited by the instant claims. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising the copending method of therapeutically treating subjects with RRMS wherein the subjects have been previously treated for RRMS and are not responsive to previous treatment(s), that are intolerable to previous treatment(s), or that lack availability to previous treatment(s) by performing a combined method comprising the method of Bar-Or et al of (with or without pre-treating) subcutaneously administering ofatumumab as an alternative therapeutic method at a cumulative ofatumumab dose ≥30 mg/12 wk using the syringes, ofatumumab formulations, loading dose, and maintenance regimen of Wallstrom et al wherein the subjects are any subjects with RRMS previously treated (at any previous time points) with one or just any combination of RRMS treatments (such as ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and/or fingolimod administered as taught by cited references) but are no longer administered the previous treatment(s) due to being no longer responsive to the previous treatment(s) (such as are exhibiting relapse or rebound evidenced by just any type in increase of RRMS lesion(s) – indicative of “breakthrough” disease), due to being found to be intolerable to the treatment(s) (as a result of adverse events or severe side effects, such those described by Hu et al and Blinkenberg et al), or a previous treatment is no longer available because Hu et al, Baroncini et al, and/or Blinkenberg et al teach ocrelizumab, rituximab, natalizumab, daclizumab, glatiramer acetate, and fingolimod as treatments for RRMS that can have limited availability and/or not prevent relapse in some RRMS patients, the previously administered therapeutic can be intolerable to a subject, and the method of Bar-Or et al is taught to therapeutically decreases new T2 lesions and decrease new GdE T1 lesions measured by MRI scan in a study with RRMS patients by subcutaneously administering ofatumumab at a dose ≥30 mg/12 wk wherein the study permitted use of prior disease-modifying therapies (including natalizumab) other than ofatumumab (paragraph spanning column on page e1806, in particular), and Wallstrom et al teaches using pre-filled syringes comprising ofatumumab formulations that are subcutaneously administered to MS patients using a loading dose and maintenance regimen that is encompassed by a cumulative ofatumumab dose ≥30 mg/12 wk of Bar-Or et al. The combined method would predictably therapeutically decrease new T2 lesions, decrease new GdE T1 lesions as claimed, in some cases prevent recurrent disease activity as measured by relapse rate as claimed, as taught by Bar-Or et al following treatment of RRMS with ofatumumab (Fig 2 and right column on page e1808, in particular).
Further, while the cited references do not demonstrate the combined method performed with a population of RRMS subjects with recited pre-treatments results in relapse rates at recited percentages as compared to a year before with the recited pre-treatments or reduces B cells in the subjects, the claimed method appears to be the same as the combined method because the combined method administers the same reagents to the same subjects, ofatumumab is taught to prevent recurrent disease activity as measured by relapse rate as claimed, and ofatumumab is taught to reduce B cells as claimed following treatment with ofatumumab (right column on page e1808 of Bar-Or et al, in particular).
In particular regards to instant claim 9, the instant specification explicitly defines “neurologically stable” as: “A clinical state characterized by lack of change in mental status or level of consciousness.” See lines 24-25 on page 9 and lines 7-9 on page 19. Without providing a particular limitation of, as compared to what, there is a “lack of change in mental status or level of consciousness” –patients of the combined method are neurologically stable within one month prior to first administration of ofatumumab.
In particular regards to instant claims 31-32, subjects of the combined method that are non-responsive to the prior therapeutic(s) and exhibit relapse would predictably include those that have increased MSIS-29 score – a measure increased MS severity.
In particular regards to instant claims 30, 65, and 66, copending claims do not specifically teach the treatment method of the copending claims of administering ofatumumab to a patient having RRMS reduces the loss of thalamus volume relative to patients receiving another disease-modifying therapy other than ofatumumab. However, the method of the copending claims appears to be the same as claims 30, 65, and 66 as the method of the copending claims administers the same reagent recited by claims 30, 65, and 66 to the same subject of claims 30, 65, and 66.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
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