Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant’s election without traverse of upper respiratory infection as the condition, influenza as the virus, and the virus targeted by the vaccine, Psoriasis/psoriatic arthritis as the autoimmune disease, methotrexate as the disease-modifying antirheumatic drug and the drug for psoriasis, a cytostatic as the immunosuppressive agent, Alzheimer as the disease in the geriatric patient, and a steroid as the premedication in the reply filed on June 26, 2025 is acknowledged.
Claims 3, 10, 12, 14-15, 17, 22-26, 28-30, 38-39 are canceled. Claims 1-2, 5-9, 11, 16, 19, 33-34 and 36-37 are amended. Claims 54-57 are newly added. Claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and new claims 54-57 are pending in this application. Upon reconsideration, the species election among different treatments for a pervious condition recited in claims 8-9,11, 13, 16, 18-19 and the species election for premedication recited in claim 35 are withdrawn because the subject matter can be found in the same prior art. Thus the subject matter to the extent of different treatments and premedication recited claims 8-9, 11, 13, 16, 18-19 and 35 is included and under examination in this office action. Election was made without traverse in the reply filed on June 26, 2025.
3. Claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and 54-57 are under examination with respect to upper respiratory infection, influenza, influenza vaccine, Psoriasis/psoriatic arthritis, methotrexate, a cytostatic, Alzheimer’s disease and a steroid in this office action.
Priority
4. 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, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, EP1919678.2 filed Sep 11, 2019, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The instant application claims a method of treating relapsing multiple sclerosis (RMS), comprising administering to a patient in need thereof an effective amount of ofatumumab and a vaccine including influenza vaccine, and wherein the patient has a history of at least one previous or ongoing condition other than MS, wherein the pervious or ongoing condition includes upper respiratory tract infection including influenza , which is not presented in EP1919678.2 filed Sep 11, 2019. The claimed method of treating RMS using a combination of ofatumumab with a vaccine including influenza vaccine in patients with a history of at least one previous or ongoing condition other than MS was only disclosed in EP2015885.2 filed Feb 21, 2020. Therefore, the priority for the claimed method in the instant application is Feb 21, 2020.
Information Disclosure Statement
5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
6. The disclosure is objected to because of the following informalities: The use of the term "Simulect" "Zenapax" (p. 24), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
7. Claim 7 is objected to because of the following informalities: there is a duplicate of “transient ischemic attack” in line 7 of the claim 7. Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and 54-57 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of alleviating relapsing multiple sclerosis comprising administering to a patient in need thereof an effective amount of ofatumumab and an influenza vaccine, does not reasonably provide enablement for a method of treating including curing or preventing relapsing multiple sclerosis by ofatumumab and a structurally and functionally undefined vaccine as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue’. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and 54-57 are drawn to a method of treating relapsing multiple sclerosis, comprising administering to a patient in need thereof an effective amount of ofatumumab and a vaccine, thereby treating or preventing multiple sclerosis.
The instant claims encompass a method of treating or preventing relapsing multiple sclerosis using a combination of ofatumumab with a structurally and functionally undefined vaccine. Claims 8-9 encompass undefined treatment to cure or abolish a previous undefined condition, wherein the treatment includes a glucocorticoid, a nonsteroidal anti-inflammatory drug (NSAID) and/or an immune-suppressing drug.
The claimed invention is based on findings that i) APLIOS clinical trial: a 12-week, open-label, Phase 2 bioequivalence study: administering to patients with MS ofatumumab 20 mg (0.4 mL) s.c. loading doses on Days 1, 7 and 14, and maintenance doses every 4 weeks from Week 4 results in a rapid and sustained depletion of both CD20+ B and CD20+ T cells in patients with relapsing MS (Example 1); ii) Phase 3 ASCLEPIOS I/II clinical trials, administering to MS patients 20mg of ofatumumab via sc injections every 4 weeks after an initial loading regimen of 20mg sc doses on Days 1, 7 and 14 results in no decrease of IgG levels at week 72 and thereafter and low incidence of infection (Example 2, figures 2-3); iii) in metaanalysis, Ofatumumab sustains and even increases IgG levels on the long term, whereas ocrelizumab may lead to a rather continuous reduction of IgG levels (Example 3); iv) treatment of a single dose of 50ug/mouse anti-CD20 antibody via i.v. or s.c. injections in mice wherein mice were vaccinated with pneuomococcal 13-valent conjugate vaccine Prevnar13 results in reduced levels of serum pneumococcal-specific IgG and IgM as compared to controls (Example 5). Applicant extrapolates the above findings to the claimed method of treating relapsing MS in a patient in need thereof, comprising administering to the patient Ofatumumab and a vaccine to treat or prevent relapsing MS.
Applicant is not enabled for treating including curing or preventing relapsing multiple sclerosis by any given agent because there is no cure for multiple sclerosis. Baecher-Allan et al. teaches that multiple sclerosis is heterogeneous, multifactorial and is influenced by both genetic and environmental factors (see p. 742, abstract; Baecher-Allan et al., Neuron, 2018; 97:742-768). It is known that prevention of multiple sclerosis or relapsing multiple sclerosis has not been achieved because the causes of multiple sclerosis are complicated, and haven’t been deciphered, the methods to prevent multiple sclerosis will likely be complicated and not the same for every patient.
The specification teaches that treatment of patients who have relapsing multiple sclerosis and meet a number of criteria with ofatumumab reduced the number of relapses as compared to placebo, or other disease-modifying therapies. However, the specification fails to provide any guidance as to how to cure or prevent relapsing multiple sclerosis, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
The specification fails to provide sufficient guidance as to what other vaccines can be used together with the claimed ofatumumab without affecting immune response in the patient with relapsing MS, and what treatment without affecting ofatumumab can be used for curing or abolish a previous or ongoing condition recited in claims 8-9. The specification fails to teach that the recited glucocorticoid, a NSAID or an immune-suppressing drug recited in claims 8-9 can cure or abolish any condition. It is not unknown that the glucocorticoid, a NSAID or an immune-suppressing drug recited in claims 8-9 can cure or abolish any condition. It is unpredictable what glucocorticoid, a NSAID or an immune-suppressing drug can be used or whether they can cure or abolish an unknown condition. Thus, a skilled artisan cannot contemplate how to use the claimed invention, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the claimed invention as it pertains to a method for treating relapsing MS by administration of Ofatumumab and a vaccine to a patient in need thereof.
9. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
10. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4-6, 8-9, 11, 13, 16, 18-19, 31-37, 40-41 and 54-57 are rejected under 35 U.S.C. 103 as being unpatentable over Leppert et al. (US2018/0327505) in view of NCT02792231 (or COMB157G2302, Novartis Clinical trial protocol, published 2016-06-02) and Keyser et al. (J. Neurol. Sci., 1998; 159:51-53).
Claims 1-2, 4-6, 8-9, 11, 13, 16, 18-19, 31-37, 40-41 and 54-57 as amended are drawn to a method of treating relapsing multiple sclerosis (MS), comprising administering to a patient in need thereof an effective amount of ofatumumab and a vaccine including influenza vaccine, thereby treating or preventing multiple sclerosis.
Leppert et al. (US2018/0327505) teaches a method of treating relapsing multiple sclerosis comprising administering to a patient in need thereof a combination of an anti-CD20 antibody and a vaccine, wherein the anti-CD20 antibody includes Ocrelizumab (i.e. humanized anti-CD20 monoclonal antibody) and the vaccine includes an influenza vaccine as in claim 6 (see para. [0555]-[0557]). Leppert teaches that the patient has a history of at least one previous or ongoing condition other than MS that includes upper respiratory infection including influenza as related to claims 2 and 4, and that the vaccine is administered to the patient during the anti-CD20 antibody therapy as related to claim 5 or before the anti-CD20 antibody therapy as related to claim 56 (see para. [0555]-[0557]). Leppert teaches that several disease modifying drugs in five classes are approved for treatment of relapsing MS including: i) interferon class: IFN-beta-1a (REBIF®, Extavia, AVONEX® and PLEGRIDY™ and IFN-beta-1b (BETASERON®);ii) glatiramer acetate (COPAXONE®) (a polypeptide); iii) natalizumab (TYSABRI®), alemtuzumab (LEMTRADA®) (both monoclonal antibodies); iv) dimethyl fumarate (TECFIDERA®) and fingolimod (GILENYA®) (both small molecules), and v) mitoxantrone (NOVANTRONE®) ( a cytotoxic agent); teriflunomide (AUBAGIO®) and other disease modification therapies including methotrexate, cyclophosphamide, azathioprine, and intravenous (IV) immunoglobulin (see para. [0005]). Leppert teaches that the patient followed a treatment including a glucocorticoid, a NSAID, and/or an immune-suppressing drug to alleviate a pervious condition before commencing the anti-CD20 antibody as in claims 8-9, and autoimmune disease including rheumatoid arthritis treated with a disease-modifying antirheumatic drug including methotrexate, hydroxycholorquine, sulfasalazine, leflunomide, a TNF-alpha inhibitor, abatacept, anakinra, rituximab and tocilizumab or psoriasis treated with methotrexate, ciclosporin, hydroxycarbamide, fumarates, retinoids, anti-TNF therapy, etanercept, ixekizumab, Ustekinumab, gueslkumab, efalizumab or alefacept recited in claims 11 and 13, hospitalization and/or surgery treated with an immunosuppressive agent including glucocorticoid, cytostatic, antibody and a drug acting on immunophilins recited in claim 16 and 18-19 (see para. [0116]; [0329]-[0330]; [0446]; [0464];[0255]; [0257]-[0258]; [0265]-[0268]), and premedication comprising acetaminophen, antihistamines and/or steroids recited in claim 35 (see para. [0115]-[0116]; [0329]-[0330]; [0446]; [0464];[0595];[0255]; [0257]-[0258]; [0265]-[0268]).
Leppert teaches that the relapsing MS is relapsing remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS) as recited in claim 31 (see para. [0117]-[0119]), a premedication including steroids is administered before or 30-60 min before the first administration of the anti-CD20 antibody as related to claims 34-36, or no premedication prior to the first administration of the anti-CD20 antibody as related to claim 37(see para. [0115]), the patient is neurologically stable within one month prior to the first administration as recited in claim 40 or has an EDSS score of 0-5.5 at screening, which is within or overlapping with the claimed EDSS of 1-4 prior to the first administration as recited in claim 41 (see para. [0471], the administration does not impair the vaccine’s prevention of a virus-associated disease or does not develop a virus-associated disease for at least a period of 12 moths or longer after the treatment as recited in claims 54-55 (see para. [0114]).
But Leppert does not teach that the anti-CD20 antibody is Ofatumumab as recited in instant claims, at a dose of 10-30mg every 4 weeks and/or subcutaneously in claim 27, or 20 mg ofatumumab at days 1, 7, 14 or at week 0, 1, and 2 as a loading dose in claim 31 or without a loading dose in claim 32 or 20mg Ofatumumab monthly as a maintenance dose in claim 57.
NCT02792231 teaches that Ofatumumab is a fully human anti-CD20 monoclonal antibody (Ab) as recited in instant claims, which is predicted to have low potential for immunogenicity and with very low incidence of anti-drug antibodies against Ofatumumab (p. 21). NCT02792231 teaches a method of treating relapsing multiple sclerosis comprising administering to a patient in need thereof an effective amount of an anti-CD20 IgG1 human monoclonal antibody, Ofatumumab, at 20mg by subcutaneous injection on Days 1, 7, 14, Week 4 and every 4 weeks as in claims 27, 31-32 (see p. 38; p. 41), wherein the patient has 1 relapse during the previous 1 year, or 2 relapses during the previous 2 years, or a positive gadolinium-enhancing MRI scan during the year prior to randomization, and a disability status at screening with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and is neurologically stable within 1 month prior to randomization (see p. 17-18; p.32). NCT02792231 teaches concomitant medication and premedication with acetaminophen and/or antihistamines (or equivalent) or steroids (methylprednisolone 100 mg iv or equivalent) is recommended and the premedication should be administered 30 to 60 minutes prior to administration of Ofatumumab (see p. 43).
Keyser et al. teach patients with relapsing MS are susceptible to acute respiratory infection including infection caused by influenza virus. The patients with relapsing MS have a greater risk of relapse after influenza infection and illness. Influenza vaccination on patients with relapsing MS provides benefits to avoid serious illness such as pneumonia in patients with relapsing MS (see abstract).
A person of ordinary skill in the art would have recognized that selecting and applying the known fully human anti-CD20 monoclonal antibody Ofatumumab, the benefit of influenza vaccine together with a therapeutic treatment of relapsing MS and the known technique disclosed by NCT02792231 and Keyser to the Leppert’s method would have yielded the predictable result of treating relapsing MS and resulted in an improved method because Ofatumumab is a fully human anti-CD20 monoclonal antibody with very low anti-drug antibodies, and has been used for treating relapsing multiple sclerosis as taught by NCT02792231 and a combination of influenza vaccine with a therapeutic treatment of MS provides benefits for treating relapsing MS as taught by Keyer.
Using the known fully human anti-CD20 monoclonal antibody Ofatumumab in the combination of an anti-CD20 antibody with a vaccine including an influenza vaccine used in the Leppert’s method would treat relapsing MS, and expand application of the Leppert’s method, and would increase patient’s satisfaction with treatment of relapsing MS using a combination of an anti-CD20 antibody with a vaccine including an influenza vaccine.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known fully human anti-CD20 monoclonal antibody Ofatumumab, the benefit of influenza vaccine together with a therapeutic treatment of relapsing MS and the known technique disclosed by NCT02792231 and Keyser to the Leppert’s method, and yield the predictable result of better treating relapsing MS.
Claim Rejections - 35 USC § 103
11. Claims 7 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Leppert et al. (US2018/0327505) in view of NCT02792231 (or COMB157G2302) and Keyser et al. (1998) as applied to claims 1-2, 4-6, 8-9, 11, 13, 16, 18-19, 31-37, 40-41 and 54-57 above, and further in view of Caprio et al. (J. Vasc. Med. Surg., 2016; 4:2. dx.doi.org/10.4172/2329-6925.1000259) and Luczynski et al. (Multiple Sclerosis and Related Disorders, 2019; 27:232-238; published online on Oct 26, 2018).
Leppert, NCT02792231 and Keyser are set forth above but fail to teach that the patient has a history of vascular disease, stroke or cerebrovascular conditions recited in claim 7 or is a geriatric patient suffering from Alzheimer’s disease recited in claims 20-21.
Caprio et al. teach that patients with multiple sclerosis MS have an increased risk for ischemic stroke; and patients with MS also have ischemic disease, arterial cerebral hypoperfusion, abnormalities of endothelial cells and impaired venous drainage (see abstract).
Luczynski et al. teach that multiple sclerosis (MS) coexists with age-related disease, Alzheimer’s disease, and patients with relapsing MS also have dementia or AD (see abstract).
A person of ordinary skill in the art would have recognized that selecting and applying the known patients with MS and having a previous or ongoing condition including a history of vascular disease, stroke or cerebrovascular conditions or having AD and the known technique disclosed by Caprio and Luczynski to the method of Leppert, NCT02792231 and Keyser would have yielded the predictable result of treating relapsing MS and resulted in an improved method because MS patents also develop vascular disease, stroke or cerebrovascular conditions or have AD as taught by Caprio and Luczynski.
Treating the MS patients with a history of a known previous or ongoing condition including a history of vascular disease, stroke or cerebrovascular conditions or having AD in the method of Leppert, NCT02792231 and Keyser would treat relapsing MS, and expand application of the method of Leppert, NCT02792231 and Keyser, and would increase patient’s satisfaction with treatment of relapsing MS using a combination of an anti-CD20 antibody with a vaccine including an influenza vaccine.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known patients with MS and having a previous or ongoing condition including a history of vascular disease, stroke or cerebrovascular conditions or having AD and the known technique disclosed by Caprio and Luczynski to the method of Leppert, NCT02792231 and Keyser, and yield the predictable result of treating relapsing MS.
Claim Rejections - 35 USC § 103
12. Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Leppert et al. (US2018/0327505) in view of NCT02792231 (or COMB157G2302) and Keyser (1998) as applied to claims 1-2, 4-6, 8-9, 11, 13, 16, 18-19, 31-37, 40-41 and 54-57 above, and further in view of Kuhle et al. (Multiple Sclerosis J., 2016; 22:1550-1559) and Plavina et al. (WO2020/061355, published Mar 26, 2020, priority Sep 20, 2018)..
Leppert, NCT02792231 and Keyser are set forth above but do not teach that ofatumumab is administered when serum neurofilament light chain (sNfL) concentration is 4-13 pg/ml recited in claim 27.
Kuhle et al. teach that sNfL is a biomarker to predict early relapsing MS, and the level of sNfL in healthy controls is 1.3pg/ml (0~5.3pg/ml), and the sNfL baseline level in MS is 9.0pg/ml (2.7-26.2pg/ml) and the sNfL follow-up level in MS is 10.4 pg/ml (2.5-14.5pg/ml) and after mean 3.6 year follow up, the baseline sNfL in MS is 9 pg/ml (3-20.3 pg/ml) and the follow-up is 9 pg/ml (5-12 pg/ml) (see p. 1552, table 1).
Plavina et al. (WO2020/061355) teach that the level of sNfL in MS patients can be used for prediction of relapsing MS because in MS patients with >16 pg/ml sNfL, 12.5% of the MS patients reached an EDSS score of > 3.5 within 5 years after sNfL was measured; in MS patients with 8-16 pg/ml sNfL, 7% of the MS patients reached an EDSS score of ≥ 3.5 within 5 years after sNfL was measured, and in MS patients with <8 pg/ml sNfL, only 3.3% of the MS patients reached an EDSS score of ≥ 3.5 within 5 years after sNfL was measured. In addition, the volume of T2 lesions in MS patients with <8 pg/ml sNfL at baseline is very low, the sNfL is 8-16 pg/ml at baseline, the volume ofT2 lesions 5 years and 10 years later increases, and the sNfL is > 16 pg/ml, the volume of T2 lesion is the largest 5 years and 10 years after baseline (para. [000135]-[000136]). Plavina also teaches that when patients had a level of sNfL between 1.14~10.26 pg/ml at baseline (i.e., 5 years prior to the EDSS assessment), only 3.8% of the patients had a EDSS score of ≥3.5 or higher five years later. When patients had a level of sNfL between 10.37-18.3 pg/ml at baseline, 8.3% of the patients had an EDSS score of≥ 3.5 ([000135].
A person of ordinary skill in the art would have recognized that selecting and applying the known levels of sNfL such as the level of 2.5-14.5pg/ml, 9pg/ml, 10.4pg/ml, <8 pg/ml or 8-16 pg/ml as an early indicator of relapsing MS and the known method of administering Ofatumumab when the level of sNfL in MS patients is within the range of sNfL that has a less chance to develop relapsing MS and the known technique disclosed by Kuhle and Plavina to the method of Leppert, NCT02792231 and Keyser would have yielded the predictable result of treating relapsing MS and resulted in a better and improved method because MS patients with a level of sNfL at 2.5-14.5pg/ml, 9pg/ml, 10.4pg/ml, <8 pg/ml or 8-16 pg/ml has a less chance to increase the EDSS score or the T2 lesion and develop relapsing MS. better chance to
Using and selecting the known levels of sNfL such as the level of 2.5-14.5pg/ml, 9pg/ml, 10.4pg/ml, <8 pg/ml or 8-16 pg/ml as an early indicator of relapsing MS and administering Ofatumumab to the MS patients when their level of sNfL is within the range of sNfL that has a less chance to develop relapsing MS in the method of Leppert, NCT02792231 and Keyser would provide a better treatment of relapsing MS, and expand application of the method of Leppert, NCT02792231 and Keyser, and would increase patient’s satisfaction with treatment of relapsing MS using a combination of an anti-CD20 antibody with a vaccine including an influenza vaccine because MS patients with the levels of sNfL at 2.5-14.5pg/ml, 9pg/ml, 10.4pg/ml, <8 pg/ml or 8-16 pg/ml in MS patients have a less chance to develop relapsing MS as taught by Kuhle and Plavina
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known levels of sNfL such as the level of 2.5-14.5pg/ml, 9pg/ml, 10.4pg/ml, <8 pg/ml or 8-16 pg/ml as an early indicator of relapsing MS and the known method of administering Ofatumumab when the level of sNfL in MS patients is within the range of sNfL that has a less chance to develop relapsing MS and the known technique disclosed by Kuhle and Plavina to the method of Leppert, NCT02792231 and Keyser, and yield the predictable result of treating relapsing MS.
Double Patenting
13. 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.
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Claims 1-2, 4-6, 8-9, 11, 13, 16, 18-19, 31-37, 40-41 and 54-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25, 28-32, 38, 42-44 and 47-93 of copending Application No. 17/753632, claims 34-63 of copending Application No. 17/995820, or claims 26-45 of copending Application No. 18/286,030 or claims 16-36 of copending Application No. 18/683858 in view of Leppert et al. (US2018/0327505), NCT02792231 (or COMB157G2302) and Keyser et al. (1998).
Instant claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and 54-57 claim a method of treating relapsing multiple sclerosis, comprising administering to a patient in need thereof an effective amount of ofatumumab and a vaccine.
Claims 1-25, 28-32, 38, 42-44 and 47-93 of Application No. 17/753632 (the ‘632 Application) claim a method of treating relapsing multiple sclerosis in a patient in need thereof, comprising administering ofatumumab to the patient wherein the patient has been treated with a disease-modifying therapy other than Ofatumumab.
Claims 34-63 of copending Application No. 17/995820 (the ‘820 Application), claims a method of treating multiple sclerosis using Ofatumumab, comprising optionally administering a B cell and/or T cell inhibitor, monitoring serum IgG level; administering ofatumumab as B cell and/or T cell serum if serum IgG level falls below a concentration of 900mg/dL.
Claims 26-45 of Application No. 18/286,030 (the ‘030 Application) claim a method of treating multiple sclerosis (MS) in a patient, comprising administering a therapeutically effect amount of Ofatumumab to the patient wherein the patient is of Asian race, wherein serum IgG levels are maintained in the range of 900-1400mg/dl during the treatment and patient has different conditions including infections and treatment is a long-term treatment form more than 2 years and the ofatumumab is administer at a dose of 20mg every 4 weeks or administering 20mg at weeks 0, 1 and 2 and MS includes relapsing MS, CIS, RRMS and SPMS, and a premedication is administered to the patient prior to the first dose of ofatumumab, and the premedication comprises acetaminophen, antihistamines and/or steroids.
Claims 16-36 of Application No. 18/683,858 (the ‘858 Application) claim a method of treating multiple sclerosis, comprising administering Ofatumumab to a patient having at most 40kg body weight and/or aged between 5 and <18 years, wherein the loading dose or maintenance dose of ofatumumab is a subcutaneous injection of 20mg ofatumumab, and the patient includes patients who have received an MS disease-modifying therapy other than ofatumumab, which includes ocrelizumab, rituximab, fingolimod, teriflunomide, interferon beta or glatiramer acetate.
While the claims of the ‘635, the ‘820, the ‘030 or the ‘858 Applications do not recite a vaccine administered together with Ofatumumab or 20mg or specific regimens, Leppert (US2018/0327505), NCT02792231 and Keyser teach these limitations and provide motivation and an expectation of success in administering a vaccine together with Ofatumumab at 20mg with specific frequencies for the reasons set forth above under the 103 rejections. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known fully human anti-CD20 monoclonal antibody Ofatumumab, the benefit of influenza vaccine together with an anti-CD20 antibody for treatment of relapsing MS and the known technique disclosed by NCT02792231 and Keyser to the method of the claims of the ‘635, the ‘820, the ‘030 or the ‘858 Applications, and yield the predictable result of better treating relapsing MS.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
14. NO CLAIM IS ALLOWED.
15. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
NCT02545868 (F. Hoffmann-La Roche Clinical trial protocol, published Nov 7, 2016) teaches a method of treating relapsing multiple sclerosis comprising administering to a patient in need thereof a combination of an anti-CD20 antibody and a vaccine, wherein the anti-CD20 antibody includes Ocrelizumab (i.e. humanized anti-CD20 monoclonal antibody) and the vaccine includes an influenza vaccine, and wherein the patient includes the patient has a history of a previous or ongoing condition treated with a therapeutic agent to alleviate the condition, wherein the condition includes upper respiratory infection cause by influenza virus, and wherein the patient has EDSS score of <4 (see p.2126; p. 2130; 2133-2134; p. 2140).
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Chang-Yu Wang
November 4, 2025
/CHANG-YU WANG/Primary Examiner, Art Unit 1675